BR112018012392B1 - 4-PHENYL PYRIDINE COMPOUNDS REPLACED AS NON-SYSTEMIC TGR5 AGONISTS - Google Patents

Abstract

The invention relates to a non-systemic TGR5 agonist useful in the treatment of chemotherapy-induced diarrhea, diabetes, Type II diabetes, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome , ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition, especially during small bowel syndrome, irritable bowel syndrome (IBS), and other diseases and disorders associated with TGR5, having the formula: (I'), where R1, R2, R2?, R3, R4X1X2X3X4, Q and n are described in this document.

Description

Related requests

[0001] This application claims the benefit and priority of provisional applications no. 62/269,804, filed on December 18, 2015; and 62/419,939, filed November 9, 2016, the contents of which are incorporated herein by reference in their entirety.

Field of Invention

[0002] The present invention is directed to TGR5 receptor modulators useful in the treatment of TGR5-mediated diseases or disorders. Specifically, the invention relates to compounds and compositions thereof, which activate the TGR5 receptor, methods of treating diseases or disorders associated with TGR5, including chemotherapy-induced diarrhea, diabetes, type II diabetes, gestational diabetes, reduced fasting glucose, reduced glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ulcerative colitis (UC), Crohn's disease (CD), disorders associated with parenteral nutrition, especially during short bowel syndrome and irritable bowel syndrome (IBS) and methods of synthesis of these compounds.

BASICS OF THE INVENTION

[0003] Diabetes mellitus is a growing threat to human health. For example, in the United States, current estimates state that approximately 16 million people suffer from diabetes mellitus. Type II diabetes accounts for approximately 90-95% of diabetes cases, killing approximately 193,000 US residents per year. Type II diabetes is the seventh leading cause of all deaths. In Western societies, type II diabetes currently affects 6% of the adult population, with a global frequency expected to grow by 6% per year. Although there are certain hereditary traits that may predispose individuals to developing type II diabetes, the driving force behind the current increase in the incidence of the disease is the increase in sedentary lifestyle, diet and obesity, now prevalent in developed countries. About 80% of diabetics with type II diabetes are significantly overweight. Additionally, an increasing number of young people are developing the disease. Type II diabetes is now internationally recognized as one of the main threats to human health in the 21st century.

[0004] Type II diabetes manifests itself as an inability to adequately regulate blood glucose levels and can be characterized by a defect in insulin secretion or insulin resistance. That is, those suffering from type II diabetes have too little insulin or cannot use insulin effectively. Insulin resistance refers to the inability of the body's tissues to respond to endogenous insulin appropriately. Insulin resistance develops due to several factors, including genetics, obesity, increasing age, and high blood sugar over long periods of time. Type II diabetes can develop at any age, but it usually becomes apparent during adulthood. However, the incidence of type II diabetes in children is increasing. In diabetics, glucose levels build up in the blood and urine, causing excessive urination, thirst, hunger, and problems with fat and protein metabolism. If left untreated, diabetes mellitus can cause potentially fatal complications, including blindness, kidney failure and heart disease.

[0005] Type II diabetes is currently treated at several levels. A first level of therapy is through diet and/or exercise, alone or in combination with therapeutic agents. These agents may include insulin or drugs that lower blood glucose levels. About 49% of people with type II diabetes require oral medications, about 40% require insulin injections or a combination of insulin injections and oral medications, and 10% follow diet and exercise alone.

[0006] Traditional therapies include: insulin secretagogues, such as sulfonylureas, which increase insulin production from pancreatic β cells; glucose-lowering effectors, such as metformin, which reduces glucose production in the liver; activators of peroxisome proliferator-activated receptor Y (PPARY), such as thiazolidinediones, which increase insulin action; and α-glucosidase inhibitors, which interfere with glucose production in the intestine. There are, however, deficiencies associated with currently available treatments. For example, sulfonylureas and insulin injections may be associated with episodes of hypoglycemia and weight gain. Additionally, patients often lose responsiveness to sulfonylureas over time. Metformin and α-glucosidase inhibitors often cause gastrointestinal problems, and PPARY agonists tend to cause weight gain and edema.

[0007] More recently, new agents have been introduced onto the market that prolong or mimic the effects of naturally secreted incretin hormones (Neumiller, J Am Farm Assoc. 49(suppl 1):S16-S29, 2009). Incretins are a group of gastrointestinal hormones that are released from specialized intestinal cells when nutrients, especially glucose, are detected in the intestine. The two most important incretin hormones are glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 (released from L cells), which stimulate insulin secretion from the pancreas in a glucose-dependent manner and suppress glucagon secretion. However, GLP-1 itself is impractical as a clinical treatment for diabetes since it has a very short half-life in vivo. To address this, incretin-based agents currently available or under regulatory review for the treatment of T2D are designed to achieve prolonged action of incretins. For example, dipeptidyl peptidase-4 inhibitors, such as sitagliptin, inhibit the normally rapid proteolytic breakdown of endogenous incretin hormones. There are also human-derived and synthetic incretin mimetics that are designed to be more stable and/or have a prolonged serum half-life compared to naturally secreted GLP-1s and include agents such as liraglutide and exenatide. In either approach, the goal is to provide a sustained response to incretins and thereby enhance glucose-dependent insulin secretion. It is the glucose dependence of the insulin response that provides incretin therapies with a low risk of hypoglycemia. Furthermore, GLP-1 may also delay gastric emptying and beneficially affect satiety and therefore weight loss (Neumiller 2009).

[0008] Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract that causes segments of the gastrointestinal tract to become inflamed and ulcerated. IBD generally takes one of two forms, (CD) and (UC), and is generally considered to result from a combination of factors (environmental, genetic, changes in the microbiota, and immune dysfunction). It is likely that all of these factors are necessary to some degree for clinical disease to be present. Ultimately, dysregulation of the host's immune system, which occurs in response to environmental stimuli or gut bacteria, leaves the host at risk of uncontrolled chronic inflammation reaching the gut. Gut health is compromised by reduced barrier function, which exacerbates the response to antigen load, creating a vicious circle of chronic inflammation and disease. The diversity of causal factors makes the disease very difficult to treat and many patients with IBD remain undertreated, resulting in a high proportion of surgical resections (especially in CD).

[0009] The worldwide incidence rate of UC varies greatly, from 0.5 to 24.5/100,000 people, while that of CD varies between 0.116/100,000 people, with a prevalence rate of IBD that reaches up to 396/100,000 people (cdc.gov). In a 2012 analysis, the highest reported prevalence values of IBD were in Europe (UC, 505 per 100,000 people; CD, 322 per 100,000 people) and North America (UC, 249 per 100,000 people; CD, 319 per 100,000 people ). Furthermore, there was evidence of increasing incidence over time. IBD is one of the most important gastrointestinal diseases in the US, requiring a lifetime of patient care. Annually in the United States, IBD is responsible for more than 700,000 doctor visits, 100,000 hospitalizations, and 119,000 patients considered disabled (cdc.gov). In the long term, up to 75% of patients with CD and 25% of those with UC will require surgery (Ref: http://www.cdc.gov/ibd/). IBD is more common in European Americans than in African Americans, and lower rates of IBD have been reported in Hispanics and Asians. CD can affect up to 700,000 Americans. Men and women are equally likely to be affected, and although the disease can occur at any age, it is most prevalent among teenagers and young adults between the ages of 15 and 35.

[0010] Treatment of IBD includes conservative measures, as well as surgical approaches, in those who do not respond to medical treatment. Therapeutic objectives are to improve the patient's quality of life, induce and maintain remission, prevent complications, restore nutritional deficits and modify the course of the disease. The main therapeutic categories for this disease are anti-inflammatory drugs, immunosuppressive therapy, biological agents, antibiotics and drugs for symptomatic relief. Recent advances in understanding the pathogenesis of IBD have resulted in numerous new developmentally targeted therapies. First-line treatment is usually mesalamine and derivatives. It is relatively safe and effective, with 30-50% of patients achieving long-term relief. Second-line therapy is steroid treatment, with 30% long-term effectiveness. After steroids, immune modulators (thiopurines, cyclosporine) are tried. Recently, TNF inhibitors have become more widely used in IBD. They present good healing and mucosal rescue, but have a high rate of complications and do not maintain long-term effectiveness. Last-line treatment in IBD is surgical removal of the diseased tissue. This is highly invasive and reduces the quality of life of these patients.

[0011] GLP-2 is of particular importance for gastrointestinal health. The peripheral actions of GLP-2 are largely restricted to the intestinal mucosa, where it acts as a trophic hormone. Most of its effects occur in the small intestine and, to a lesser extent, the large intestine. Chronic administration of GLP-2 to healthy rodents increases intestinal weight through increased crypt cell proliferation and decreased villus apoptosis, resulting in expansion of villus height and, less consistently, crypt depth. As stated above, the trophic effects of GLP-2 are most pronounced in the proximal small intestine and any changes in intestinal morphology quickly reverse after stopping treatment. GLP-2 treatment also increases the digestive and absorptive capacity of the intestine, as indicated by increased expression and activity of brush border and nutrient absorption enzymes, and improves barrier function through reduced permeability. The positive effects of GLP-2 treatment on intestinal growth and/or function have been demonstrated in rodent models of intestinal damage involving resection, colitis (IBD), chemotherapy-induced diarrhea, necrotizing pancreatitis, food allergy, psychological stress, and thermal injury and in patients with short bowel syndrome. Additional effects of GLP-2 in the intestine include stimulation of intestinal glucose transport; inhibition of gastrointestinal motility in rodent models [conflicting results in humans]; gastric emptying and acid secretion (GLP-2 infusion in healthy humans reduces stimulated gastric acid secretion but has no effect on basal acid secretion or volume).

[0012] Intestinal L cells, the source of GLP-1 and GLP-2, co-express TGR5 receptors. Activation of TGR5 with small molecule agonists or partial agonists therefore has the potential to be a treatment for chemotherapy-induced diarrhea, diabetes, type II diabetes, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance , hyperglycemia, obesity and metabolic syndrome, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition, especially during short bowel syndrome, and irritable bowel syndrome (IBS) and other disorders. For this reason, there remains a considerable need for potent non-systemic small molecule TGR5 agonists.

Summary of the Invention

[0013] A first aspect of the invention relates to compounds of Formula (I'): and pharmaceutically acceptable salts, hydrates, solvates, isotopes, prodrugs, stereoisomers and tautomers thereof, wherein: Q is C = (O), -CH2-, -NR5- or -O-; when Q is C = (O) then Q1 is -NR5'-, when Q is -NR5- or -O- then Q1 is -CH2-, or when Q is -CH2- then Q1 is -O(CH2)0- 1- or - NR5-; X1 is CR6 or N; X2 is CR7 or N; X3 is CR8 or N; X4 is CR9 or N; Y is CRb or N; Ra and Rb are each independently H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, or halogen; or R1 and Ra, together with the atoms to which they are attached, form a heterocycloalkyl ring; R1 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6haloalkoxy, halogen, -S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from halogen, (C1-C4) alkoxy, -OH, -NH2, -NH(C1-C4) alkyl and -N((C1-C4) alkyl)2; or R1 and Ra, together with the atoms to which they are attached, form a heterocycloalkyl ring; on adjacent atoms together with the carbon atoms to which they are attached form a heterocycloalkyl optionally substituted with one or more substituents selected from (C1C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy and halogen; R2 and R2' are each independently H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, or (C1-C6) haloalkoxy, or R2 and R2' together with the carbon atom to which they are attached they form (C3-C8) cycloalkyl or heterocycloalkyl; each R3 is independently, at each occurrence, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, halogen, -S (O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from halogen, ( C1-C4) alkoxy, -OH, -NH2, -NH (C1-C4) alkyl and - N ((C1-C4) alkyl)2; or R1 and R3 together with the carbon atoms to which they are attached form a heterocycloalkyl optionally substituted with one or more substituents selected from (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1 -C6) haloalkoxy and halogen; R4 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3C8) cycloalkyl , heterocycloalkyl, -OH, -NH2, CN, -S(O)m(C1-C6) alkyl, -NH(C1-C4) alkyl or -N((C1-C4) alkyl)2; C1-C6) alkyl, -C(O)NR10R11, -C(O)(C1-C6) alkyl, or -C(O)O(C1-C6) alkyl; C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S (O)o(C1-C6) alkyl, -NH (C1-C4) alkyl, or -N ((C1-C4) alkyl)2; , (C1-C8) alkenyl, (C1-C8alkynyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, (C3-C8) cycloalkenyl, heterocycloalkyl, OH, -NH2, -S(O)qNH2, -S(O)qOH, CN or (C1-C18) alkyl, where 0 to 7 methylene of the (C1-C18) alkyl is optionally substituted by a portion selected from the group consisting of -O-, NR13-, -(SO)q-, -C(O)-, -C(CH2)- or -C (NH)-, provided that when two methylenes in the alkyl are substituted, then two -O-, two -S(O)q- or two -NR13- and -O- and -NR13- are not contiguous, wherein the alkyl is optionally substituted by one or more R12 and wherein cycloalkyl and cycloalkenyl are optionally substituted by one or more R13; R10 and R11 are each independently H or (C1-C6) alkyl optionally substituted with one or more substituents independently selected from -NH2 and OH; R12 is D, -OH, halogen, -NH2, -NH (Ci-Cβ) alkyl, -N ((C1-C6) alkyl)2, -C (O) OH, -OC (O) (C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, (Cβ-C10) aryl, heteroaryl or R17, wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from -OH, -NH2, -NH (C1-Cβ) alkyl, -N((C1- Cβ) alkyl)2, halogen and R14; R13 is H, -OH, (C3-C8) cycloalkyl, heterocycloalkyl, (Cβ-C10) aryl, heteroaryl or (C1-C12) alkyl, wherein 0 to 7 methylene of the (C1-C12) alkyl is optionally substituted by a selected portion of the group consisting of -O-, -NR13-, -S(O)r-, -C(O)-, or -C(NH)-, provided that when two methylenes in the alkyl are substituted, then O and N, are not contiguous and wherein the alkyl is optionally substituted with one or more R15 and wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more substituents selected from -OH, -C(O)OH, - NH2, -NH(C1-Cβ) alkyl and - N((C1-Cβ) alkyl)2; R14 is (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl, -O-heterocycloalkyl, (C1-C12) alkyl or (C2-C12) alkenyl, wherein 0 to 7 methylene of (C1- C12) alkyl and (C2-C12) alkenyl are optionally substituted by a moiety selected from the group consisting of -O-, -NR13-, -S(O)r-, -C(O)- or -C(NH) -, provided that when two methylenes in the alkyl or alkenyl are substituted, then O and N are not contiguous and wherein the alkyl and alkenyl are optionally substituted by one or more R15 and the cycloalkyl and heterocycloalkyl are optionally substituted by one or more R1β ; or when R12 is cycloalkyl or heterocycloalkyl, two R14 together with the atom to which they are attached form C=(O); or when R12 is cycloalkyl or heterocycloalkyl, two R14 together with the atoms to which they are attached form a (C3-C8) cycloalkyl or heterocycloalkyl optionally substituted with one or more R13; or when R12 is cycloalkyl or heterocycloalkyl, two R14 together with the atom to which they are attached form a (C3-C8) spirocycloalkyl or a spiroheterocycloalkyl optionally substituted with one or more R13; or when R12 is cycloalkyl or heterocycloalkyl, two R14 together with the atom to which they are attached form a (C6-C10) aryl or heteroaryl optionally substituted with one or more R13; Ris is -OH, -NH2, -NH(Ci-Cβ) alkyl, -N((Ci-Cβ) alkyl)2, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the (C3-C8) cjcioalkyl and heterocalkyl are optionally substituted with one or more substituents selected from (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, — C(O)OH, -OH, -NH2, -NH (Ci- Cβ) alkyl, -N((Ci-Cβ) alkyl^e oxo; Riβ is -OH, -C(O)OH, -NH2, -NH(Ci-Cβ) alkyl, -N((Ci-Cβ) alkyl )2, (C1-Cβ) alkoxy, (C1-Cβ) hydroxyalkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl, -O-heterocycloalkyl, (Cβ-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from (Ci-Cβ) hydroxyalkyl, (Ci-Cβ) aminoalkyl, -C(O)OH, -OH, -NH2, -NH (C1-Cβ) alkyl, -N ((C1-Cβ) alkyl^e oxo; Ri7 is (C1-C18) alkyl or (C2-C18) alkenyl, where 0 to 8 methylene of (C1-C18) alkyl and The (C2-Ci8) alkenyl are optionally substituted by a portion selected from the group consisting of -O-, -NRi3-, -S(O)r-, -C(O)-, or -C(NH)-, provided that when two methylene in alkyl or alkenyl is substituted, then O and N are not contiguous and wherein the alkyl and alkenyl are optionally substituted by one or more Ri8; Ri8 is Ri9, (Cβ-Ci0) aryl, or heteroaryl optionally substituted with one or more R2i; Ri9 is (Ci-Ci8) alkyl in which 0 to 8 methylene of the (Ci-Ci8) alkyl is optionally substituted by a portion selected from the group consisting of -O-, -NRi3-, -S(O)r-, -C(O)- or -C(NH)-, provided that when two methylenes in the alkyl or alkenyl are substituted, then O and N are not contiguous and wherein the alkyl is optionally substituted with one or more R20 R20 is (C6 -C10) aryl or heteroaryl optionally substituted with one or more R21; R21 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, or halogen; or two R21 together when on adjacent atoms they form a cycloalkyl or heterocycloalkyl optionally substituted with one or more R22; R22 is -C(O)NH2, -C(O)NH(Ci-C6)alkyl, -C(O)N((Ci-C6)alkyl)2, -C(O)(C3-C7)cycloalkyl, or -C(O)heterocycloalkyl, wherein the cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents independently selected from -OH and CN; each m, o, p, qer is independently, in each occurrence, 0, i or 2; en is 0, i or 2.

[0014] Another aspect of the invention relates to a method of treating or preventing a disease or disorder associated with TGR5 modulation. The method comprises administering to a patient in need of treatment for diseases or disorders associated with TGR5 modulation an effective amount of a compound of Formula (I'), or a salt, hydrate, solvate, prodrug, stereoisomer, or tautomer respective.

[0015] Another aspect of the invention relates to a method of treating a disease or disorder associated with TGR5 activation. The method comprises administering to a patient in need of treatment for diseases or disorders associated with TGR5 activation an effective amount of a compound of Formula (I') or a salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0016] Another aspect of the invention relates to a method of treating chemotherapy-induced diarrhea. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0017] Another aspect of the invention relates to a method of treating type II Diabetes mellitus. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0018] Another aspect of the invention relates to a method for treating or preventing hyperphosphatemia. The method comprises administering to a patient in need thereof, comprising an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0019] Another aspect of the invention relates to a method for treating or preventing kidney disease. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0020] Another aspect of the invention relates to a method for reducing serum creatinine levels. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0021] Another aspect of the invention relates to a method for treating or preventing proteinuria. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a salt, hydrate, solvate , pharmaceutically acceptable prodrug, stereoisomer or tautomer thereof.

[0022] Another aspect of the invention relates to a method for delaying the time of renal replacement therapy (RTR). The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0023] Another aspect of the invention relates to a method for reducing FGF23 levels. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0024] Another aspect of the invention relates to a method for reducing the hyperphosphatemic effect of active vitamin D. The method comprises administering to a patient in need an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0025] Another aspect of the invention relates to a method for alleviating hyperparathyroidism. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0026] Another aspect of the invention relates to a method for reducing serum parathyroid hormone (PTH). The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0027] Another aspect of the invention relates to a method for improving endothelial dysfunction. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0028] Another aspect of the invention relates to a method for reducing vascular calcification. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0029] Another aspect of the invention relates to a method for reducing urinary phosphorus. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0030] Another aspect of the invention relates to a method for normalizing serum phosphorus levels. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0031] Another aspect of the invention relates to a method for reducing phosphate load in an elderly patient. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0032] Another aspect of the invention relates to a method for decreasing the absorption of phosphate in the diet. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0033] Another aspect of the invention relates to a method for reducing renal hypertrophy. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0034] Another aspect of the invention relates to a method for reducing heart hypertrophy. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0035] Another aspect of the invention relates to a method for treating and/or preventing a disorder related to the stomach and intestine. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0036] Another aspect of the invention relates to a method for treating and/or preventing a side effect of chemotherapy or radiation treatment. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0037] Another aspect of the present invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament for the treatment of a disease associated with TGR5 activation.

[0038] Another aspect of the present invention relates to the use of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in the treatment of a disease associated with activation of TGR5.

[0039] Another aspect of the invention relates to a prodrug of a compound of Formula (I') having a Formula (II'): wherein: P is -O, -CH2OC(O)(CI-C6) alkyl, or -CH2OC(O)NRs (Ci-C6) alkyl, wherein the alkyl is optionally substituted with -OC(O)(C1- C3) alkyl; and R is H or C1-6-alkyl; and where P is a cleavable group.

[0040] Another aspect of the invention relates to a prodrug of a compound of Formula (I') having a Formula (II): where: P is -O, -CH2OC(O)(CI-C6) alkyl, or -CH2OC(O)NRs (Ci- Cβ) alkyl, wherein the alkyl is optionally substituted with -OC(O)(C1- C3) alkyl; and R is H or C1-6-alkyl; and where P is a cleavable group.

[0041] The present invention further provides methods of treating a disease or disorder associated with TGR5 modulation, including, without limitation, chemotherapy-induced diarrhea, diabetes, type II diabetes, gestational diabetes, reduced fasting blood glucose, reduced glucose tolerance , insulin resistance, hyperglycemia, obesity, metabolic syndrome, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition, especially during irritable bowel syndrome (IBS), comprising administering to a patient suffering from at least one of said diseases or disorders a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[0042] The present invention provides TGR5 agonists that are therapeutic agents in the treatment of diseases such as chemotherapy-induced diarrhea, diabetes, type II diabetes, gestational diabetes, reduced fasting glucose, reduced glucose tolerance, insulin resistance, hyperglycemia , obesity, metabolic syndrome, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition, especially during short bowel syndrome, and irritable bowel syndrome (IBS) and other diseases associated with TGR5 modulation.

[0043] The present invention further provides compounds and compositions with an improved efficacy and safety profile over known TGR5 agonists. The present disclosure also provides agents with novel mechanisms of action in relation to the TGR5 receptor in the treatment of various types of diseases, including chemotherapy-induced diarrhea, diabetes, type II diabetes, gestational diabetes, reduced fasting glucose, reduced glucose tolerance, resistance insulin, hyperglycemia, obesity, metabolic syndrome, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition, especially during short bowel syndrome, and irritable bowel syndrome (IBS). Ultimately, the present invention provides the medical community with a new pharmacological strategy for treating TGR5-mediated diseases and disorders.

BRIEF DESCRIPTION OF FIGURES

[0044] FIG. 1 shows Fecal Form Score (FFS) in mice with 5-fluorouracil (5-FU)-induced diarrhea after treatment with Compound I-388 at 30 mg/kg, teduglutide at 0.4 mg/kg and a vehicle.

[0045] FIG. 2 shows the DAI score in a mouse inflammatory bowel disease model upon treatment when the mice were treated with sitagliptin at 3.6 g/L, compound I-389 at 30 mg/kg, a combination of sitagliptin at 3 .6 g/L and compound i-389 at 30 mg/kg and a vehicle.

[0046] FIG. 3 shows colon length in a mouse model of inflammatory bowel disease upon treatment when the mice were treated with sitagliptin at 3.6 g/L, Compound I-389 at 30 mg/kg, a combination of sitagliptin at 3.6 g/L, L and Compound I-389 at 30 mg/kg and a vehicle.

[0047] FIG. 4 shows the colon cytokine level of KC/Gro in a mouse intestinal inflammatory disease model upon treatment when the mice were treated with sitagliptin at 3.6 g/L, Compound I-389 at 30 mg/kg, a combination of sitagliptin at 3.6 g/L and Compound I-389 at 30 mg/kg and a vehicle.

[0048] FIG. 5 shows colon histology scoring in a mouse model of inflammatory bowel disease upon treatment when mice were treated with sitagliptin at 3.6 g/L, compound I-389 at 30 mg/kg, a combination of sitagliptin at 3.6 g/L and compound i-389 at 30 mg/kg and a vehicle.

[0049] FIG. 6 shows the amount of length of the small intestine. The dye coursed through mice treated with Compound I-389 at 30 mg/kg and vehicle.

[0050] FIG. 7 shows the weight of the small intestine in mice when treated with teduglutide at 0.5 mg/kg, sitagliptin at 3.6 g/L, Compound I-389 at 30 mg/kg, Compound I-389 at 100 mg/kg, a combination of Sitagliptin at 3.6 g/L and Compound I-389 at 30 mg/kg, a combination of Sitagliptin at 3.6 g/L and Compound I-389 at 100 mg/kg and a vehicle.

[0051] FIG. 8 shows colon weight in mice when treated with teduglutide at 0.5 mg/kg, sitagliptin at 3.6 g/L, Compound I-389 at 30 mg/kg, Compound I-389 at 100 mg/kg, a combination of sitagliptin at 3.6 g/L and Compound I-389 at 30 mg/kg, a combination of sitagliptin at 3.6 g/L and Compound I-389 at 100 mg/kg and a vehicle.

[0052] FIG. 9 shows jejunal crypt length in mice when treated with Teduglutide at 0.5 mg/kg, Sitagliptin at 3.6 g/L, Compound I-389 at 30 mg/kg, Compound I-389 at 100 mg/kg , a combination of Sitagliptin at 3.6 g/L and Compound I-389 at 30 mg/kg, a combination of Sitagliptin at 3.6 g/L and Compound I-389 at 100 mg/kg and a vehicle.

[0053] FIG. 10 shows the crypt length of the ileum villi in mice when treated with teduglutide at 0.5 mg/kg, sitagliptin at 3.6 g/L, Compound I-389 at 30 mg/kg, Compound I-389 at 100 mg /kg, a combination of Sitagliptin at 3.6 g/L and Compound I-389 at 30 mg/kg, a combination of Sitagliptin at 3.6 g/L and Compound I-389 at 100 mg/kg and a vehicle.

[0054] FIG. 11 shows colonic crypt depth in mice when treated with teduglutide at 0.5 mg/kg, sitagliptin at 3.6 g/L, Compound I-389 at 30 mg/kg, Compound I-389 at 100 mg/kg , a combination of sitagliptin at 3.6 g/L and Compound I-389 at 30 mg/kg, a combination of sitagliptin at 3.6 g/L and Compound I-389 at 100 mg/kg, and a vehicle.

[0055] FIG. 12 shows active GLP-1 in mice when treated with teduglutide at 0.5 mg/kg, sitagliptin at 3.6 g/L, Compound I-389 at 30 mg/kg, Compound I-389 at 100 mg/kg, a combination of sitagliptin at 3.6 g/L and Compound I-389 at 30 mg/kg, a combination of sitagliptin at 3.6 g/L and Compound I-389 at 100 mg/kg and a vehicle.

[0056] FIG. 13 shows total GLP-2 in mice when treated with teduglutide at 0.5 mg/kg, sitagliptin at 3.6 g/L, Compound I-389 at 30 mg/kg, Compound I-389 at 100 mg/kg, a combination of sitagliptin at 3.6 g/L and Compound I-389 at 30 mg/kg, a combination of sitagliptin at 3.6 g/L and Compound I-389 at 100 mg/kg and a vehicle.

[0057] FIG. 14 shows active GLP-1 in WD-fed mice when treated with liraglutide at 0.4 mg/kg, linagliptin at 10 mg/kg, Compound I-389 at 30 mg/kg, a combination of Linagliptin at 10 mg/kg and Compound I- 389 at 30 mg/kg, single vehicle and a WD vehicle.

[0058] FIG. 15 shows total GLP-1 in WD-fed mice when treated with Liraglutide at 0.4 mg/kg, Linagliptin at 10 mg/kg, Compound I-389 at 30 mg/kg, a combination of Linagliptin at 10 mg/kg and Compound I-389 at 30 mg/kg, single vehicle and WD vehicle.

Detailed Description of the Invention

[0059] The present invention relates to compounds and compositions that are capable of activating TGR5. The invention provides methods of treating, preventing or ameliorating a disease or disorder in which TGR5 plays a role by administering to a patient in need thereof a therapeutically effective amount of a compound of Formula (I'), or a salt, hydrate, solvate pharmaceutically acceptable, prodrug, stereoisomer or tautomer thereof. The methods of the present invention can be used in the treatment of a variety of TGR5-dependent diseases and disorders by activating the TGR5 receptor. Activation of TGR5 provides a new approach to treating, preventing, or ameliorating diseases including, but not limited to, chemotherapy-induced diarrhea, diabetes, type II diabetes, gestational diabetes, reduced fasting glucose, reduced glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition, especially during short bowel syndrome, and irritable bowel syndrome (IBS).

[0060] In a first aspect of the invention, the compounds of Formula (I') are described: and pharmaceutically acceptable salts, hydrates, solvates, isotopes, prodrugs, stereoisomers and tautomers thereof, wherein Q, Q1, Ra, R1, R2, R2', R3, R4, X1, X2, X3, X4, Y en are as described above.

[0061] Details of the invention are set out in the accompanying description below. Although methods and materials similar or equivalent to those described herein may be used in the practice or testing of the present invention, illustrative methods and materials are now described. Other features, objects and advantages of the invention will be apparent from the description and claims. In the specification and attached claims, singular forms also include the plural, unless the context clearly indicates otherwise. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one skilled in the art to which this invention belongs. All patents and publications cited in this specification are incorporated herein by reference in their entirety. Definitions

[0062] The articles “a” and “an” used in this disclosure to refer to one or more of one (that is, at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.

[0063] The term “and/or” is used in this disclosure to mean “and” or “or”, unless otherwise indicated.

[0064] The term “optionally substituted” is understood to mean that a certain chemical grouping (for example, an alkyl group) can (but does not necessarily need to) be linked to other substituents (for example, heteroatoms). For example, an alkyl group that is optionally substituted by being a fully saturated alkyl chain (i.e., a pure hydrocarbon). Alternatively, the same optionally substituted alkyl group may have substituents other than hydrogen. For example, at any point along the chain, the group may be attached to a halogen atom, a hydroxyl group, or any other substituent described herein. Therefore, the term “optionally substituted” means that a given chemical group has the potential to contain other functional groups, but does not necessarily have other functional groups. Suitable substituents used in the optional substitution of the described groups include, without limitation, halogen, oxo, -OH, -CN, -COOH, -CH2CN, -O-(C1-C6) alkyl, (C1-C6) alkyl, C1 alkoxy -C6, (C1-C6) haloalkyl, C1-C6 haloalkoxy, -O-(C2-C6) alkenyl, -O-(C2-C6) alkynyl, (C2-C6) alkenyl, (C2-C6) alkynyl, - OH, -OP(O)(OH)2, -OC(O)(C1-C6) alkyl, -C(O)(C1-C6) alkyl, -OC(O)O(C1-C6) alkyl, - NH2, -NH((C1-C6) alkyl), -N((C1-C6) alkyl)2, - NHC(O)(C1-C6) alkyl, -C(O)NH (C1-C6) alkyl, -S(O)2(C1-C6) alkyl, -S(O)NH(C1-C6) alkyl and S(O)N((C1-C6) alkyl)2. The substituents may themselves be optionally substituted. "Optionally substituted", as used herein, also refers to substituted or unsubstituted whose meaning is described below.

[0065] As used herein, the term "substituted" means that the specified group or moiety has one or more suitable substituents in which the substituents can bind to the specified group or moiety at one or more positions. For example, an aryl substituted with a cycloalkyl may indicate that the cycloalkyl attaches to an aryl atom by bonding or fusing with the aryl and sharing two or more common atoms.

[0066] As used herein, the term "unsubstituted" means that the specified group has no substituents.

[0067] As used herein, the term "TGR5 activation" means that a compound or group of compounds acts as an agonist or partial agonist of TGR5.

[0068] Unless specifically defined otherwise, the term “aryl” refers to cyclic and aromatic hydrocarbon groups that have 1 to 3 aromatic rings, including monocyclic or bicyclic groups such as phenyl, biphenyl or naphthyl. When they contain two aromatic rings (bicyclic, etc.), the aromatic rings of the aryl group can be joined at a single point (e.g., biphenyl) or fused (e.g., naphthyl). The aryl group may be optionally substituted by one or more substituents, for example, 1 to 5 substituents, at any point in the bond. Exemplary substituents include, but are not limited to -H, -halogen, -O-(C1-C6) alkyl, (C1-C6) alkyl, -O-(C2-C6) alkenyl, -O-(C2-C6) alkynyl, (C2-C6) alkenyl, (C2-C6) alkynyl, -OH, -OP(O)(OH)2, -OC(O)(C1-C6) alkyl, -C(O)(C1-C6) ) alkyl, -OC(O)O(C1-C6) alkyl, NH2, NH((C1-C6) alkyl), N((C1-C6) alkyl)2, -S(O)2-(C1-C6 ) alkyl, -S(O)NH(C1-C6) alkyl and S(O)N((C1-C6) alkyl)2. The substituents may themselves be optionally substituted. Furthermore, by containing two fused rings, the aryl groups defined herein may have an unsaturated or partially saturated ring fused to a fully saturated ring. Exemplary ring systems of these aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl, anthracenyl, phenalenyl, phenantrenyl, indanyl, indenyl, tetrahydronaphthalenyl, tetrahydrobenzoannulenyl and the like.

[0069] Unless specifically defined otherwise, the term “heteroaryl” means a monovalent monocyclic radical of 5 to 24 ring atoms or a polycyclic aromatic radical, containing one or more ring heteroatoms selected from N, O or S , the remaining ring atoms being C. As defined herein, heteroaryl also means a bicyclic heteroaromatic group in which the heteroatom is selected from N, O, or S. The aromatic radical is optionally independently substituted by one or more of substituents described in this document. Examples include, but are not limited to, furyl, thienyl, pyrrolyl, pyridyl, pyrazolyl, pyrimidinyl, imidazolyl, isoxazolyl, oxazolyl, oxadiazolyl, pyrazinyl, indolyl, thiophen-2-yl, quinolyl, benzopyranyl, isothiazolyl, thiazolyl, thiadiazol, indazol benzimidazolyl, thieno[3,2-b]thiophene, triazolyl, triazinyl, imidazo[1,2- b]pyrazolyl, furo[2,3-c]pyridinyl, imidazo[1,2-a]pyridinyl, indazolyl, pyrrol[ 2,3- c]pyridinyl, pyrrol[3,2-c]pyridinyl, pyrazol[3,4-c]pyridinyl, thieno[3,2-c]pyridinyl, thieno[2,3- c]pyridinyl, thieno[ 2,3-b]pyridinyl, benzothiazolyl, indolyl, indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, benzofuran, cromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazine, dihydrobenzoxanil, quinolinyl, isoquinolinyl, 1,6-naphthyridinyl, benzo[de]isoquinolinyl, pyrido[4,3-b][1,6]naphthyridinyl, thieno[2,3-b]pyrazinyl, quinazolinyl, tetrazol[1,5-a]pyridinyl,[1,2,4]triazol[4,3- a]pyridinyl, isoindolyl, pyrrol[2,3-b]pyridinyl, pyrrol[3,4-b]pyridinyl, pyrrol[3,2-b]pyridinyl, imidazo[5,4-b]pyridinyl, pyrrol[1, 2-a]pyrimidinyl, tetrahydro pyrrolo[1,2-a]pyrimidinyl, 3,4-dihydro-2H-1À2-pyrrolo[2,1-b]pyrimidine, dibenzo[b,d]thiophene, pyridin-2 -one, furo[3,2-c]pyridinyl, furo[2,3-c]pyridinyl, 1H-pyrido[3,4-b][1,4]thiazinyl, benzooxazolyl, benzoisoxazolyl, furo[2,3- b]pyridinyl, benzothiophenyl, 1,5-naphthyridinyl, furo[3,2- b]pyridine,[1,2,4]triazol[1,5-a]pyridinyl, benzo[1,2,3]triazolyl, imidazo [1,2- a]pyrimidinyl,[1,2,4]triazol[4,3-b]pyridazinyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5] oxadiazole, 1,3-dihydro-2H-benzo[d]imidazol-2-one, 3,4-dihydro-2H-pyrazol[1,5-b][1,2]oxazinyl, 4,5,6,7 -tetrahydropyrazol[1,5-a]pyridinyl, thiazol[5,4-d]thiazolyl, imidazo[2,1-b][1,3,4]thiadiazolyl, thieno[2,3-b]pyrrolyl, 3H-indolyl and derivatives thereof. Furthermore, by containing two fused rings, the aryl groups defined herein may have an unsaturated or partially saturated ring fused to a fully saturated ring. Exemplary ring systems of these heteroaryl groups include indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuran, cromanyl, thiocanromanyl, tetrahydroquinolinyl, dihydrobenzothiazine, 3,4-dihydro-1H-isoquinolinyl, 2,3-dihydrobenzofuran, indolinyl, indolyl and dihydrobenzoxanil.

[0070] Halogen or "halo" refers to fluorine, chlorine, bromine or iodine.

[0071] Alkyl refers to a straight or branched chain saturated hydrocarbon containing 1-12 carbon atoms. Examples of an alkyl group (C1-C6) include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl and isohexyl.

[0072] “Alkoxy” refers to a straight or branched chain saturated hydrocarbon containing 1-12 carbon atoms that contains an “O” terminal in the chain, that is, -O(alkyl). Examples of alkoxy groups include, without limitation, methoxy, ethoxy, propoxy, butoxy, t-butoxy or pentoxy groups.

[0073] “Alkenyl” refers to an unsaturated straight or branched chain hydrocarbon containing 2-12 carbon atoms. The “alkenyl” group contains at least one double bond in the chain. The double bond of an alkenyl group can be unconjugated or conjugated with another unsaturated group. Examples of alkenyl groups include ethenyl, propenyl, n-butenyl, iso-butenyl, pentenyl or hexenyl. An alkenyl group may be unsubstituted or substituted. Alkenyl, as defined herein, may be linear or branched.

[0074] “Alkynyl” refers to an unsaturated straight or branched chain hydrocarbon containing 2-12 carbon atoms. The “alkynyl” group contains at least one triple bond in the chain. Examples of alkenyl groups include ethynyl, propargyl, n-butynyl, iso-butynyl, pentynyl or hexinyl. An alkynyl group may be unsubstituted or substituted.

[0075] The term "alkylene" or "alkylenyl" refers to a divalent alkyl radical. Any of the above-mentioned monovalent alkyl groups can be an alkylene by abstracting a second hydrogen atom from the alkyl. As defined herein, alkylene can also be a C1-C6 alkylene. An alkylene can also be a C1-C4 alkylene. Typical alkylene groups include, but are not limited to, -CH2-, -CH(CH3)-, -C(CH3)2-, -CH2CH2-, -CH2CH(CH3)-, -CH2C(CH3)2-, - CH2CH2CH2-, -CH2CH2CH2CH2-, and the like.

[0076] The term "aminoalkyl", as used herein, refers to an alkyl group, as defined herein, that is substituted with one or more aminos. Examples of aminoalkyl groups include, but are not limited to, aminomethyl, diaminomethyl, aminoethyl, 1,2-aminoethyl, etc.

[0077] “Cycloalkyl” means monocyclic or polycyclic saturated carbon rings (e.g., fused, bridged or spiro rings) containing 3-18 carbon atoms (e.g., C3-C10). Examples of cycloalkyl groups include, without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptanyl, cyclooctanyl, norboranyl, norborenyl, bicyclo[2.2.2]octanyl or bicyclo[2.2.2]octenyl.

[0078] “Heterocyclyl” or “heterocycloalkyl” means monocyclic or polycyclic rings (for example, fused, bridged or spiro rings) containing carbon and heteroatoms taken from oxygen, nitrogen or sulfur and in which there are no delocalized π electrons (aromaticity) shared between the ring carbon or heteroatoms. The heterocycloalkyl may be a 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 membered ring. The heterocycloalkyl ring structure may be replaced by one or more substituents. The substituents may themselves be optionally substituted. Examples of heterocyclic rings include, but are not limited to, oxetanyl, azetadinyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, pyranyl, thiopyranil, tetrahydropyranyl, dioxalinyl, piperidinyl, morpholinyl, thiomorpholinyl, S -thiomorpholinyl oxide, thiomorpholinyl dioxide, piperazinil, azepinil, oxepinil, diazepinil, tropanil, oxazolidinonyl and homotropanil. In accordance with the present invention, 3- to 10-membered heterocyclyl refers to saturated or partially saturated non-aromatic ring structures containing between 3 and 10 atoms in which there is at least one heteroatom selected from the group N, O or S.

[0079] The term "hydroxyalkyl" denotes an alkyl group as defined above, wherein the alkyl group is replaced by one or more -OH groups. Examples of hydroxyalkyl groups include HO-CH2-, HO-CH2-CH2- and CH3-CH(OH)-.

[0080] The term "haloalkyl", as used herein, refers to an alkyl group, as defined herein, that is substituted with one or more halogens. Examples of haloalkyl groups include, but are not limited to, trifluoromethyl, difluoromethyl, pentafluoroethyl, trichloromethyl, etc.

[0081] The term "haloalkoxy", as used herein, refers to an alkoxy group, as defined herein, that is substituted with one or more halogens. Examples of haloalkyl groups include, but are not limited to, trifluoromethoxy, difluoromethoxy, pentafluoroethoxy, trichloromethoxy, etc.

[0082] The term "cyano", as used in this document, means a substituent having a carbon atom linked to a nitrogen atom by a triple bond, that is, C=N.

[0083] The term "amine" as used herein refers to amines of (R-NH2, R * H) primary, (R2-NH, R2 * H) secondary and (R3-N, R * H) tertiary. A substituted amine is intended to mean an amine in which at least one of the hydrogen atoms has been replaced by the substituent.

[0084] The term "amino", as used herein, means a substituent with at least one nitrogen atom. Specifically, NH2, -NH(alkyl) or alkylamino, -N(alkyl)2 or dialkylamino, amide, carbamide, urea and sulfamide are included in the term "amino".

[0085] The term "dialkylamino" as used in this document refers to an amino or NH2 group in which both hydrogens have been replaced by alkyl groups, as defined in this document above, that is, -N(alkyl)2. The alkyl groups in the amino group can be the same or different alkyl groups. Example alkylamino groups include, but are not limited to, dimethylamino (i.e., -N(CH3)2), diethylamino, dipropylamino, diiso-propylamino, di-n-butylamino, di-sec-butylamino, di-tert-butylamino, methyl(ethyl)amino, methyl(butylamino), etc.

[0086] "Spirocycloalkyl" or "spirocyclyl" denote carbogenic bicyclic ring systems with both rings linked through a single atom. The ring may be different in size and nature or identical in size and nature. Examples include spiropentane, spirohexane, spiroheptane, spirooctane, spirononane or spirodecane. One or both rings in a spirocycle can be fused to another carbocyclic, heterocyclic, aromatic, or heteroaromatic ring. One or more of the carbon atoms in the spirocycle may be replaced by a heteroatom (e.g., O, N, S, or P). (C3-C12) spirocycloalkyl is a spirocycle containing between 3 and 12 carbon atoms. One or more of the carbon atoms may be replaced by a heteroatom.

[0087] The term "spiroheterocycloalkyl" or "spiroheterocyclyl" means a spirocycle in which at least one of the rings is a heterocycle (for example, at least one of the rings is furanyl, morpholinyl or piperadinyl).

[0088] The term "solvate" refers to a complex of variable stoichiometry formed by a solute and solvent. Such solvents, for the purpose of the invention, may not interfere with the biological activity of the solute. Examples of suitable solvents include, but are not limited to, water, MeOH, EtOH and AcOH. Solvates in which water is the solvent molecule are typically referred to as hydrates. Hydrates include compositions with stoichiometric amounts of water, as well as compositions with varying amounts of water.

[0089] The term “isomer” refers to compounds that have the same composition and molecular weight, but differ in physical and/or chemical properties. The structural difference may be in constitution (geometric isomers) or in the ability to rotate the plane of polarized light (stereoisomers). With regard to stereoisomers, compounds of Formula (I') may have one or more asymmetric carbon atoms and may occur as racemates, racemic mixtures and individual enantiomers or diastomers.

[0090] The compounds of the invention, or their pharmaceutically acceptable salts, may contain one or more asymmetric centers and may thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that can be defined, in terms of absolute stereochemistry, as (R)- or (S)- or, as (D)- or (L)-, for amino acids. The present invention is intended to include all possible isomers, as well as their racemic and optically pure forms. The optically active isomers (+) and (-), (R)- and (S)-, or (D)- and (L)-, can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques, e.g. example, chromatography and fractional crystallization. Conventional techniques for the preparation/isolation of individual enantiomers include chiral synthesis from a suitable optically pure precursor or resolution of the racemate (or the racemate from a salt or derivative) using, for example, phase high-pressure liquid chromatography. chiral (HPLC). When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless otherwise specified, the compounds are intended to include both Z and E geometric isomers. Likewise, all tautomeric forms must also be included.

[0091] A "stereoisomer" refers to a compound consisting of the same atoms linked by the same bonds, but having different three-dimensional structures, which are not interchangeable. The present invention contemplates various stereoisomers and mixtures thereof and includes "enantiomers", which refer to two stereoisomers, the molecules of which are non-overlapping mirror images.

[0092] A "tautomer" refers to a change of protons from one atom of a molecule to another atom of the same molecule. The present disclosure includes tautomers of any of said compounds.

[0093] The chemical nomenclature protocol and structure diagrams used in this document are a modified form of the I.U.P.A.C nomenclature system. using the "IUPAC Naming Plugin" software (ChemAxon) and/or the Struct=Name Pro 11.0 program of ChemDraw software (CambridgeSoft). For the complex chemical names used in this document, a substituent group is designated before the group to which it attaches. For example, cyclopropylethyl comprises an ethyl backbone with a cyclopropyl substituent.

[0094] The disclosure also includes pharmaceutical compositions comprising an effective amount of a disclosed compound and a pharmaceutically acceptable carrier. Representative "pharmaceutically acceptable salts" include, for example, water-soluble and water-insoluble salts, such as acetate, amsonate (4,4-diaminostilbene-2,2-disulfonate), benzenesulfonate, benzonate, bicarbonate, bisulfate, bitartrate, borate, bromide , butyrate, calcium, calcium edetate, camsylate, carbonate, chlorine, citrate, clavulariate, dihydrochloride, edetate, edisylate, estolate, esylate, fumerate, fiunarate, gluceptate, gluconate, glutamate, glycolylarsanilate, hexafluorophosphate, hexylresorcinate, hydrabamino, hydrobromide, hydrochloride , hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, laurate, magnesium, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, mucate, napsilate, nitrate, N-methylglucamine ammonium salt, 3-hydroxy-2-naphthoate, oleate, oxalate, palmitate, pamoate (1,1-methene-bis-2-hydroxy-3-naphthoate, einbonate), pantothenate, phosphate/diphosphate, picrate, polygalacturonate, propionate, p-toluenesulfonate, salicylate, stearate, subacetate, succinate , sulfate, sulfosalicylate, suramate, tannate, tartrate, theoclate, tosylate, triethiodide and valerate salts.

[0095] A “patient” or “subject” is a mammal, e.g., a human, mouse, rat, guinea pig, dog, cat, horse, cow, pig, or non-human primate, such as a monkey, chimpanzee , baboon or reso.

[0096] An “effective amount” when used in connection with a compound is an effective amount to treat or prevent a disease in a subject as described herein.

[0097] The term “carrier”, as used in this disclosure, encompasses carrier, excipients and diluents and means a material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting a pharmaceutical agent from one organ, or portion of the body, to another organ, or portion of the body of a subject.

[0098] The term “treat”, with respect to a subject, refers to improving at least one symptom of the subject's disorder. Treating includes curing, improving, or at least partially alleviating the disorder.

[0099] The term “disorder” is used in this disclosure to mean, and is used interchangeably with, the terms disease, condition or disorder, unless otherwise indicated.

[00100] The term “administering”, “administering” or “administration” as used in this disclosure refers to directly administering a disclosed compound or pharmaceutically acceptable salt of the disclosed compound or composition to a subject or administering a prodrug derivative or analogue of the compound or pharmaceutically acceptable salt of the compound or composition to the subject that can form an equivalent amount of the active compound within the subject's body.

[00101] The compounds of the present invention can also be prepared as prodrugs, for example, pharmaceutically acceptable prodrugs. The terms "prodrug" and "prodrug" are used interchangeably herein and refer to any compound that releases a drug of active origin in vivo. Since prodrugs are known to improve numerous desirable qualities of pharmaceutical products (e.g., solubility, bioavailability, manufacturability, etc.), the compounds of the present invention can be administered in prodrug form. Thus, the present invention is intended to include prodrugs of the currently claimed compounds, methods of delivery thereof and compositions containing them. "Prodrugs" are intended to include any covalently linked carriers that release an active parent drug of the present invention in vivo when such prodrug is administered to an individual. The prodrugs of the present invention can be prepared by modifying the functional groups present in the compound in such a way that the modifications are cleaved, both by routine manipulation and in vivo, in the parent compound. Prodrugs include compounds of the present invention in which a hydroxy, amino, sulfhydryl, carboxy or carbonyl group is attached to any group that can be cleaved in vivo to form a free hydroxyl, free amino, free sulfhydryl, free carboxyl or carbonyl group. free, respectively.

[00102] Examples of prodrugs include, but are not limited to, esters (e.g., acetate, dialkylaminoacetates, formates, phosphates, sulfates, N-oxides and benzoate derivatives) and carbamates (e.g., N,N-dimethylaminocarbonyl ) of hydroxy functional groups, esters (e.g. ethyl esters, morpholinoethanol esters) of carboxyl functional groups, N-acyl derivatives (e.g. N-acetyl), N-Mannich bases, Schiff bases and enaminones of amino functional groups , oximes, acetals, ketals and enol esters of ketone and aldehyde functional groups in compounds of the invention and the like. See Bundegaard, H., Design of Prodrugs, pp. 1-92, Elesevier, New York-Oxford (1985).

[00103] The present invention relates to pharmaceutically acceptable compounds or salts, hydrates, solvates, prodrugs, stereoisomers or tautomers, capable of activating TGR5, which are useful for the treatment of diseases and disorders associated with the modulation of a receptor of TGR5. The invention further relates to compounds, or pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers or tautomers, which are useful for activating TGR5.

[00104] In one embodiment, compounds of Formula (I') have the structure of Formula (I) or (Ia'): and pharmaceutically acceptable salts, hydrates, solvates, isotopes, prodrugs, stereoisomers and tautomers thereof.

[00105] In one embodiment, compounds of Formula (I') have the structure of Formula (Ib') or (Ic'): and pharmaceutically acceptable salts, hydrates, solvates, isotopes, prodrugs, stereoisomers and tautomers thereof.

[00106] In another embodiment, the compounds of Formula (I') have the structure of Formula (Ia): and pharmaceutically acceptable salts, hydrates, solvates, isotopes, prodrugs, stereoisomers and tautomers thereof.

[00107] In another embodiment, compounds of Formula (I') have the structure of Formula (Ib): and pharmaceutically acceptable salts, hydrates, solvates, isotopes, prodrugs, stereoisomers and tautomers thereof.

[00108] In one embodiment, compounds of Formula (I') have the structure of Formula (Ic): and pharmaceutically acceptable salts, hydrates, solvates, isotopes, prodrugs, stereoisomers and tautomers thereof.

[00109] In another embodiment, compounds of Formula (I') have the structure of Formula (Id), Formula (Ie), Formula (If) or Formula (Ig): and pharmaceutically acceptable salts, hydrates, solvates, isotopes, prodrugs, stereoisomers and tautomers thereof.

[00110] In another embodiment, compounds of Formula (I') have the structure of Formula (Ih), Formula (Ij), Formula (Ik) or Formula (Im): and pharmaceutically acceptable salts, hydrates, solvates, isotopes, prodrugs, stereoisomers and tautomers thereof.

[00111] In another embodiment, compounds of Formula (I') have the structure of Formula (Io), Formula (Ip), Formula (Iq) or Formula (Ir): and pharmaceutically acceptable salts, hydrates, solvates, isotopes, prodrugs, stereoisomers and tautomers thereof.

[00112] In another embodiment, compounds of Formula (I') have the structure of Formula (Iu), Formula (Iv), Formula (Iw) or Formula (Ix): and pharmaceutically acceptable salts, hydrates, solvates, isotopes, prodrugs, stereoisomers and tautomers thereof.

[00113] In another embodiment, compounds of Formula (I') have the structure of Formula (Iy), Formula (Iz), Formula (Iaa) or Formula (Ibb): and pharmaceutically acceptable salts, hydrates, solvates, isotopes, prodrugs, stereoisomers and tautomers thereof.

[00114] In one embodiment, compounds of Formula (I') have the structure of Formula (Icc): and pharmaceutically acceptable salts, hydrates, solvates, isotopes, prodrugs, stereoisomers and tautomers thereof.

[00115] In one embodiment, the compound of Formula (I') is a prodrug with a formula (II') or (II): Where: P is -O, -CH2OC(O)(C1-C6) alkyl, or -CH2OC(O)NRs(C1-C6) alkyl, where the alkyl is optionally substituted with -OC(O)(C1C3) alkyl; and Rs is H or C1-C6-alkyl; and where P is a cleavable group.

[00116] In one embodiment, P is -O

[00117] In some embodiments of the above Formulas Q is -NR5- or -O-; Q1 is -CH2-; X1 is CR6 or N; X2 is CR7 or N; X3 is CR8 or N; X4 is CR9 or N; Y is CH; Ra is H; R1 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6haloalkoxy, halogen, -S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from halogen, (C1-C4) alkoxy, -OH, -NH2, -NH(C1-C4) alkyl and -N((C1-C4) alkyl)2; R2 is (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl or (C1- C6) haloalkoxy; R2' is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl or (C1-C6) haloalkoxy or R2 and R2', together with the carbon atom next to it; which they are linked form (C3-C8) cycloalkyl or heterocycloalkyl; each R3 is, independently, at each occurrence, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, halogen, -S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, or -O-heterocycloalkyl, wherein alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from halogen, (C1-C4) alkoxy, -OH, -NH2, -NH (C1-C4) alkyl and -N ((C1-C4) alkyl)2; R4 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8 ) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S(O)m(C1-C6) alkyl, -NH(C1-C4) alkyl or -N((C1-C4) alkyl)2; , (C1-C6) alkyl, -C(O)NR10R11, -C(O)(C1-C6) alkyl, or -C(O)O(C1-C6) alkyl; C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S(O)o(C1-C6)alkyl, -NH(C1-C4)alkyl, or -N((C1-C4)alkyl)2; independently H, (C1-C8) alkenyl, (C1-C8) alkynyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, (C3-C8) cycloalkenyl, heterocycloalkyl, OH, -NH2, -S(O)qNH2, -S(O)qOH, CN or (C1-C18) alkyl, where 0 to 7 methylene of the (C1-C18) alkyl is optionally substituted by a portion selected from the group consisting of -O-, NR13-, -(SO)q-, -C(O)-, -C(CH2) - or -C(NH)-, provided that when two methylenes in the alkyl are substituted, then two -O-, two -S(O)q- or two -NR13- and -O- and -NR13- are not contiguous , wherein the alkyl is optionally substituted by one or more R12 and wherein the cycloalkyl and cycloalkenyl are optionally substituted by one or more R13; R10 and R11 are each independently H or (C1-C6) alkyl optionally substituted with one or more substituents independently selected from -NH2 and OH; R12 is -OH, halogen, -NH2, -NH(C1-C6) alkyl, -N((C1-C6) alkyl)2, -C(O)OH, -OC(O)(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from -OH, -NH2, -NH(C1 -C6) alkyl, -N((C1-C6) alkyl)2, halogen and R14; R13 is H, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl, heteroaryl or (C1-C12) alkyl, wherein 0 to 7 methylene of the (C1-C12) alkyl is optionally substituted by a selected portion of the group consisting of -O-, -NR13-, -S(O)r-, -C (O) -, or -C (NH) -, provided that when two methylenes in the alkyl is substituted, then O and N, are not contiguous and wherein the alkyl is optionally substituted with one or more R15e wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more substituents selected from -OH, -C(O)OH, -NH2 , -NH(C1-C6) alkyl and -N((C1-C6) alkyl)2; R14 is (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, -O-heterocycloalkyl, (C1-C12) alkyl or (C2-C12) alkenyl, wherein 0 to 7 methylene of (C1- C12) alkyl and (C2-C12) alkenyl are optionally substituted by a moiety selected from the group consisting of -O-, -NR13-, -S(O)r-, -C(O)- or -C(NH) -, provided that when two methylenes in alkyl or alkenyl are substituted, then O and N are not contiguous and wherein the alkyl and alkenyl are optionally substituted by one or more R15 and the cycloalkyl and heterocycloalkyl are optionally substituted by one or more R16 ; or when R12 is cycloalkyl or heterocycloalkyl, two R14, together with the atom to which they are attached, form C=(O); or when R12 is cycloalkyl or heterocycloalkyl, two R14, together with the atoms to which they are attached, form a (C3-C8) cycloalkyl or heterocycloalkyl optionally substituted by one or more R13; or when R12 is cycloalkyl or heterocycloalkyl, two R14, together with the atom to which they are attached, form a (C3-C8) spirocycloalkyl or a spiroheterocycloalkyl optionally substituted by one or more R13; or when R12 is cycloalkyl or heterocycloalkyl, two R14, together with the atom to which they are attached, form a (C6-C10) aryl or heteroaryl optionally substituted by one or more OH or R13; Ris is -OH, -NH2, -NH (Ci-Cβ) alkyl, -N ((Ci-Cβ) alkyl)2, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted by one or more substituents selected from (Ci-Cβ) hydroxyalkyl, (Ci-Cβ) aminoalkyl, -C(O)OH, -OH, -NH2, -NH ( Ci-Cβ) alkyl, -N ((Ci-Cβ) alkyl)2e oxo; Riβ is -OH, -C(O)OH, -NH2, -NH(Ci-Cβ)alkyl, -N((Ci-Cβ)alkyl)2, (Ci-Cβ)alkoxy, (Ci-Cβ)hydroxyalkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, -O-heterocycloalkyl, (Cβ-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted with one or plus substituents selected from (Ci-Cβ) hydroxyalkyl, (Ci-Cβ) aminoalkyl, -C(O)OH, -OH, -NH2, -NH(Ci-Cβ)alkyl, -N((Ci-Cβ)alkyl) 2 and oxo; each m, o, p, q and r is, independently, in each occurrence, 0, i or 2; and n is 0, i or 2.

[00118] In some embodiments of the Formulas above: Q is -NR5- or -O-; Xi is CRβ or N; X2 is CR7 or N; X3 is CR8 or N; X4 is CR9 or N; R1 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6haloalkoxy, halogen, -S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from halogen, (C1-C4) alkoxy, -OH, -NH2, -NH(C1-C4) alkyl and -N((C1-C4) alkyl)2; R2 and R2' are each independently (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) ) haloalkyl, or (C1-C6) haloalkoxy; or R2 and R2', together with the carbon atom to which they are attached form (C3-C8) cycloalkyl or heterocycloalkyl; -C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, halogen, -S (O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from halogen, (C1-C4) alkoxy, -OH, -NH2 , -NH (C1-C4) alkyl and -N ((C1-C4) alkyl)2; R4 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8 ) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S(O)m(C1-C6) alkyl, -NH(C1-C4) alkyl or -N((C1-C4) alkyl)2; , (C1-C6) alkyl, -C(O)NR10R11, -C(O)(C1-C6) alkyl, or -C(O)O(C1-C6) alkyl; C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S(O)o(C1-C6)alkyl, -NH(C1-C4)alkyl, or -N((C1-C4)alkyl)2; independently H, (C1-C8) alkenyl, (C1-C8) alkynyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, (C3-C8) cycloalkenyl, heterocycloalkyl, OH, -NH2, -S(O)qNH2, -S(O)qOH, CN or (C1-C18) alkyl, where 0 to 7 methylene of the (C1-C18) alkyl is optionally substituted by a portion selected from the group consisting of -O-, NR13-, -(SO)q-, -C(O)-, -C(CH2) - or -C(NH)-, provided that when two methylenes in the alkyl are substituted, then two -O-, two -S(O)q- or two -NR13- and -O- and -NR13- are not contiguous , wherein the alkyl is optionally substituted by one or more R12 and wherein the cycloalkyl and cycloalkenyl are optionally substituted by one or more R13; R10 and R11 are each independently H or (C1-C6) alkyl optionally substituted with one or more substituents independently selected from -NH2 and OH; R12 is -OH, -NH2, -NH (C1-C6)alkyl, -N((C1-C6)alkyl)2, -C(O)OH, (C3-C8)cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from -OH, -NH2, -NH (C1-C6) alkyl, -N((C1-C6) alkyl )2 and R14; R13 is H, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl, heteroaryl or (C1-C12) alkyl, wherein 0 to 7 methylenes of the (C1-C12) alkyl are optionally substituted by a selected moiety from the group consisting of -O-, -NR13-, -S(O)r-, -C(O)- or -C(NH)-, provided that when any one of two methylenes in the alkyl is substituted, then O and N are not contiguous and wherein the alkyl is optionally substituted by one or more R15 and wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from -OH, -C(O)OH , -NH2, -NH(C1-C6) alkyl and -N <(C1-C6) alkyl)2; R14 is (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, -O-heterocycloalkyl, (C1-C12) alkyl or (C2-C12) alkenyl, wherein 0 to 7 methylene of (C1- C12) alkyl and (C2-C12) alkenyl are optionally substituted by a moiety selected from the group consisting of -O-, -NR13-, -S(O)r-, -C(O)- or -C(NH) -, provided that when two methylenes in alkyl or alkenyl are substituted, then O and N are not contiguous and wherein the alkyl and alkenyl are optionally substituted by one or more R15 and the cycloalkyl and heterocycloalkyl are optionally substituted by one or more R16 ; or when R12 is a cycloalkyl or a heterocycloalkyl, two R14, together with the atom to which they are attached, form C=(O); or two R14, together with the atoms to which they are attached, form a (C3-C8) cycloalkyl or heterocycloalkyl optionally substituted by one or more R13; or when R12 is a cycloalkyl or a heterocycloalkyl, two R14, together with the atom to which they are attached, form a (C3-C8) spirocycloalkyl or a spiroheterocycloalkyl optionally substituted by one or more R13; R15 is -OH, -NH2, -NH (C1-C6) alkyl, -N ((C1-C6) alkyl)2, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted by one or more substituents selected from (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, -C(O)OH, -OH, -NH2, -NH ( C1-C6) alkyl, -N ((C1-C6) alkyl)2e oxo; R16 is -OH, -C(O)OH, -NH2, -NH(C1-C6)alkyl, -N((C1C6)alkyl)2, (C1-C6)alkoxy, (C1-C6)hydroxyalkyl, (C3 -C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, -O-heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, -C(O)OH, -OH, -NH2, -NH(C1-C6)alkyl, -N((C1-C6)alkyl)2 and oxo; each m, o, p, q and r is, independently, in each occurrence, 0, 1 or 2; and n is 0, 1 or 2

[00119] In some embodiments of the Formulas above: Q is -NR5- or -O-; X1 is CR6 or N; X2 is CR7 or N; X3 is CR8 or N; X4 is CR9 or N; R1 is (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, halogen, -S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from halogen, (C1-C4) alkoxy, -OH, -NH2, -NH(C1-C4) alkyl and -N((C1-C4) alkyl)2; R2 and R2' are each independently (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, or (C1-C6) haloalkoxy; or R2 and R2', together with the carbon atom to which they are attached form (C3-C8) cycloalkyl or heterocycloalkyl; each R3 is, independently, at each occurrence, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, halogen, -S (O)p(C1-C6 ) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from halogen, (C1-C4) alkoxy, -OH, -NH2, -NH (C1-C4) alkyl and -N ((C1-C4) alkyl)2; R4 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8 ) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S(O)m(C1-C6) alkyl, -NH(C1-C4) alkyl or -N((C1-C4) alkyl)2; , (C1-C6) alkyl, -C(O)NR10R11, -C(O)(C1-C6) alkyl, or -C(O)O(C1-C6) alkyl; C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S(O)o(C1-C6)alkyl, -NH(C1-C4)alkyl, or -N((C1-C4)alkyl)2; independently H, (C1-C8) alkenyl, (C1-C8) alkynyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, (C3-C8) cycloalkenyl, heterocycloalkyl, -OH, -NH2, CN or (C1-C18) alkyl, wherein 0 to 7 methylene of the (C1-C18) alkyl is optionally substituted by a portion selected from the group consisting of -O-, -NR13-, -S(O)q-, -C (O) -, -C (CH2)- or -C (NH)-, provided that , when any one of two methylenes in the alkyl are substituted, two -O-, two -S(O)q- or two -NR13- and -O- and -NR13- are not contiguous, wherein the alkyl is optionally substituted by one or more R12 and wherein the cycloalkyl and cycloalkenyl are optionally substituted by one or more R13; R10 and R11 are each independently H or (C1-C6) alkyl optionally substituted with one or more substituents independently selected from -NH2 and OH; R12 is -OH, -NH2, -NH (C1-C6)alkyl, -N((C1-C6)alkyl)2, -C(O)OH, (C3-C8)cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from -OH, -NH2, -NH (Ci-Cβ) alkyl, -N((Ci-Cβ) alkyl )2 and R14; R13 is H, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl, heteroaryl or (C1-C12) alkyl, wherein 0 to 7 methylene of the (C1-C12) alkyl is optionally substituted by a selected portion of the group consisting of -O-, -NRi3-, -S(O)r-, -C(O)-, or -C(NH)-, provided that when two methylenes in the alkyl are substituted, then O and N, are not contiguous and wherein the alkyl is optionally substituted with one or more Ri5e wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more substituents selected from -OH, -C(O)OH, -NH2 , -NH(C1-Cβ) alkyl and -N((C1-Cβ) alkyl)2; R14 is (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, -O-heterocycloalkyl, (C1-C12) alkyl or (C2-C12) alkenyl, wherein 0 to 7 methylene of (Ci- Ci2) alkyl and (C2-Ci2) alkenyl are optionally substituted by a moiety selected from the group consisting of -O-, -NRi3-, -S(O)r-, -C(O)- or -C(NH) -, provided that when two methylenes in alkyl or alkenyl are substituted, then O and N are not contiguous and wherein the alkyl and alkenyl are optionally substituted by one or more Ri5 and the cycloalkyl and heterocycloalkyl are optionally substituted by one or more Riβ ; or when Ri2 is a cycloalkyl or a heterocycloalkyl, two Ri4, together with the atom to which they are attached, form C=(O); or two Ri4, together with the atoms to which they are bonded, form a (C3-C8) cycloalkyl or heterocycloalkyl optionally substituted by one or more Ri3; or when Ri2 is a cycloalkyl or a heterocycloalkyl, two Ri4, together with the atom to which they are attached, form a (C3-C8) spirocycloalkyl or a spiroheterocycloalkyl optionally substituted by one or more Ri3; R15 is -OH, -NH2, -NH (Ci-Cβ) alkyl, -N ((Ci-Cβ) alkyl)2, (C3-C8) cycloalkyl, heterocycloalkyl, (Cβ-Ci0) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted by one or more substituents selected from (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, -C(O)OH, -OH, -NH2, -NH ( Ci-Cβ) alkyl, -N ((Ci-Cβ) alkyl^e oxo; R16 is -OH, -C (O) OH, -NH2, -NH (Ci-Cβ) alkyl, -N ((Ci- Cβ ) alkyl)2, (C1-Cβ) alkoxy, (C1-Cβ) hydroxyalkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, -O-heterocycloalkyl, (Cβ-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from (C1-Cβ) hydroxyalkyl, (C1-Cβ) aminoalkyl, -C(O)OH, -OH, -NH2, -NH (Ci-Cβ) alkyl, -N ((Ci-Cβ) alkyl)2 and oxo; each m, o, p, q and r is, independently, in each occurrence, 0, i or 2; or 2.

[00120] In some embodiments of the Formulas above: Q is -NR5- or -O-; Ri is H, (Ci-Cβ) alkyl, (Ci-Cβ) alkoxy, (Ci-Cβ) haloalkyl, (Ci-Cβ) haloalkoxy, halogen, -S (O)p(Ci-Cβ) alkyl, (C3- C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted by one or more substituents selected from halogen, (C1-C4) alkoxy or -OH; R2 and R2' are each independently (C1-C4) alkyl; or R2 and R2', together with the carbon atom to which they are attached form (C3-C8) cycloalkyl or heterocycloalkyl; each R3 is independently, in each occurrence, halogen; R4 is H, (Ci-Cβ) alkyl, (Ci-Cβ) alkoxy, (Ci-Cβ) haloalkyl, (Ci-Cβ) haloalkoxy, (Ci-Cβ) hydroxyalkyl, (Ci-Cβ) aminoalkyl, halogen, (C3 -C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S(O)m(C1-Cβ) alkyl, -NH(C1-C4) alkyl or -N((C1-C4) alkyl)2; R5 is H, (C1-C6)alkyl, -C(O)NR10R11, -C(O)(C1-C6)alkyl, or -C(O)O(C1-C6)alkyl; each R6 and R9 is independently H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S (O)o(C1-C6) alkyl, -NH (C1-C4) alkyl, or -N ((C1-C4) alkyl)2; each R7 and R8 is independently H, (C1-C8) alkenyl, (C1-C8alkynyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1 -C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, (C3-C8) cycloalkenyl, heterocycloalkyl, -OH, -NH2, CN or (C1-C18) alkyl, where 0 to 7 methylene of (C1-C18 ) alkyl is optionally substituted by a portion selected from the group consisting of -O-, -NR13-, -S(O)q-, -C(O)-, -C(CH2)- or -C(NH)- , provided that when any of two methylenes in the alkyl are substituted, two -O-, two -S(O)q- or two -NR13- and -O- and -NR13- are not contiguous, wherein the alkyl is optionally substituted by one or more R12 and wherein the cycloalkyl and cycloalkenyl are optionally substituted by one or more R13 and R11 are each independently H or (C1-C6) alkyl optionally substituted with one or more substituents independently selected from - NH2 and OH; C6-C10) aryl or heteroaryl, wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from -OH, -NH2, -NH (C1-C6) alkyl, -N((C1 -C6) alkyl)2 and R14; R13 is H, -OH, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl, heteroaryl or (C1-C12) alkyl, wherein 0 to 7 methylene of the (C1-C12) alkyl is optionally substituted by a selected portion of the group consisting of -O-, -NR13-, -S(O)r-, -C(O)-, or -C(NH)-, provided that when two methylenes in the alkyl are substituted, then O and N, are not contiguous and wherein the alkyl is optionally substituted with one or more R15e wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more substituents selected from -OH, -C(O)OH , -NH2, -NH(C1-C6) alkyl and -N((C1-C6) alkyl)2; R14 is (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, -O-heterocycloalkyl, (C1-C12) alkyl or (C2-C12) alkenyl, wherein 0 to 7 methylene of (C1- C12) alkyl and (C2-C12) alkenyl are optionally substituted by a moiety selected from the group consisting of -O-, -NR13-, -S(O)r-, -C(O)- or -C(NH) -, provided that when two methylenes in alkyl or alkenyl are substituted, then O and N are not contiguous and wherein the alkyl and alkenyl are optionally substituted by one or more R15 and the cycloalkyl and heterocycloalkyl are optionally substituted by one or more R16 ; or when R12 is a cycloalkyl or a heterocycloalkyl, two R14, together with the atom to which they are attached, form C=(O); or two R14, together with the atoms to which they are attached, form a (C3-C8) cycloalkyl or heterocycloalkyl optionally substituted by one or more R13; or when R12 is a cycloalkyl or a heterocycloalkyl, two R14, together with the atom to which they are attached, form a (C3-C8) spirocycloalkyl or a spiroheterocycloalkyl optionally substituted by one or more R13; Ri5 is -OH, -NH2, -NH (Ci-Ce) alkyl, -N ((Ci-Ce) alkyl)2, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted by one or more substituents selected from (Ci-Cβ) hydroxyalkyl, (Ci-Cβ) aminoalkyl, -C(O)OH, -OH, -NH2, -NH ( Ci-Cβ) alkyl, -N ((Ci-Cβ) alkyl)2e oxo; Riβ is -OH, -C(O)OH, -NH2, -NH(Ci-Cβ)alkyl, -N((Ci-Cβ)alkyl)2, (Ci-Cβ)alkoxy, (Ci-Cβ)hydroxyalkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, -O-heterocycloalkyl, (Cβ-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted with one or plus substituents selected from (C1-C6) hydroxyalkyl, (C1-Cβ) aminoalkyl, -C(O)OH, -OH, -NH2, -NH(Ci-Cβ)alkyl, -N((C1-C6)alkyl) 2 and oxo; each m, o, p, q and r is, independently, in each occurrence, 0, i or 2; and n is 0 or i.

[00121] In some embodiments of the Formulas above: Q is -O-; Ri is H, (Ci-Cβ) alkyl, (Ci-Cβ) alkoxy, (Ci-Cβ) haloalkyl, (Ci-Cβ) haloalkoxy, halogen, -S (O)p(Ci-Cβ) alkyl, (C3- C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted by one or more substituents selected from halogen, (C1-C4) alkoxy or -OH; R2 and R2' are each independently (C1-C4) alkyl; or R2 and R2', together with the carbon atom to which they are attached form (C3-C8) cycloalkyl or heterocycloalkyl; each R3 is independently, in each occurrence, halogen; R4 is H, (Ci-Cβ) alkyl, (Ci-Cβ) alkoxy, (Ci-Cβ) haloalkyl, (Ci-Cβhaloalkoxy, (Ci-Cβ) hydroxyalkyl, (Ci-Cβ) aminoalkyl, halogen, (C3-C8 ) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S(O)m(Ci-Cβ) alkyl, -NH(Ci-C4) alkyl or -N((Ci-C4) alkyl)2; R9 is independently H, (Ci-Cβ) alkyl, (Ci-Cβ) alkoxy, (Ci-Cβ) haloalkyl, (Ci-Cβ) haloalkoxy, (Ci-Cβ) hydroxyalkyl, (Ci-Cβ) aminoalkyl, halogen , (C3-C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S (O)o(Ci-Cβ) alkyl, -NH (Ci-C4) alkyl or -N((Ci-C4) alkyl) 2; each R7 and R8 is independently H, (C1-C8) alkenyl, (C1-C8) alkynyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, (C3-C8) cycloalkenyl, heterocycloalkyl, -OH, -NH2, CN or (C1-C18) alkyl, wherein 0 to 7 methylene of the (C1-C18) alkyl is optionally substituted by a portion selected from the group consisting of -O-, -NR13-, -S(O)q-, -C(O)-, -C(CH2)- or -C (NH)-, provided that when any of two methylenes in the alkyl are substituted, two -O-, two -S (O)q- or two -NR13- and -O- and -NR13- are not contiguous, in wherein the alkyl is optionally substituted by one or more R12 and wherein the cycloalkyl and cycloalkenyl are optionally substituted by one or more R13; R10 and R11 are each independently H or (C1-C6) alkyl optionally substituted with one or more substituents independently selected from -NH2 and OH; R12 is -OH, -NH2, -NH (C1-C6)alkyl, -N((C1-C6)alkyl)2, -C(O)OH, (C3-C8)cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from -OH, -NH2, -NH (C1-C6) alkyl, -N((C1-C6) alkyl )2 and R14; R13 is H, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl, heteroaryl or (C1-C12) alkyl, wherein 0 to 7 methylene of the (C1-C12) alkyl is optionally substituted by a selected portion of the group consisting of -O-, -NR13-, -S(O)r-, -C (O) -, or -C (NH) -, provided that when two methylenes in the alkyl are substituted, then O and N, are not contiguous and wherein the alkyl is optionally substituted with one or more R15e wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more substituents selected from -OH, -C(O)OH, -NH2 , -NH(C1-C6) alkyl and -N((C1-C6) alkyl)2; R14 is (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, -O-heterocycloalkyl, (C1-C12) alkyl or (C2-C12) alkenyl, wherein 0 to 7 methylene of (C1- C12) alkyl and (C2-C12) alkenyl are optionally substituted by a moiety selected from the group consisting of -O-, -NR13-, -S(O)r-, -C(O)- or -C(NH) -, provided that when two methylenes in alkyl or alkenyl are substituted, then O and N are not contiguous and wherein the alkyl and alkenyl are optionally substituted by one or more R15 and the cycloalkyl and heterocycloalkyl are optionally substituted by one or more R16 ; or when R12 is a cycloalkyl or a heterocycloalkyl, two R14, together with the atom to which they are attached, form C=(O); or two R14, together with the atoms to which they are attached, form a (C3-C8) cycloalkyl or heterocycloalkyl optionally substituted by one or more R13; or when R12 is a cycloalkyl or a heterocycloalkyl, two R14, together with the atom to which they are attached, form a (C3-C8) spirocycloalkyl or a spiroheterocycloalkyl optionally substituted by one or more R13; Ris is -OH, -NH2, -NH (Ci-Cβ) alkyl, -N ((Ci-Cβ) alkyl)2, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted by one or more substituents selected from (Ci-Cβ) hydroxyalkyl, (Ci-Cβ) aminoalkyl, -C(O)OH, -OH, -NH2, -NH ( Ci-Cβ) alkyl, -N ((Ci-Cβ) alkyl)2e oxo; Riβ is -OH, -C(O)OH, -NH2, -NH(Ci-Cβ)alkyl, -N((Ci-Cβ)alkyl)2, (Ci-Cβ)alkoxy, (Ci-Cβ)hydroxyalkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, -O-heterocycloalkyl, (Cβ-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted with one or plus substituents selected from (Ci-Cβ) hydroxyalkyl, (Ci-Cβ) aminoalkyl, -C(O)OH, -OH, -NH2, -NH(Ci-Cβ)alkyl, -N((Ci-Cβ)alkyl) 2 and oxo; each m, o, p, q and r is, independently, in each occurrence, 0, i or 2; and n is 0 or i.

[00122] In some embodiments of the Formulas above, Q is -NR5-. In another embodiment, Q is -O-. In another embodiment, -O-, - N(CH3) -, -N(H)- or -N(C(O)NH2)-. In another embodiment, Q is -NH- or -O-.

[00123] In some embodiments of the Formulas above, X1 is CR6, X2 is CR7, X3 is CR8, and X4 is CR9. In another embodiment, X1 is N, X2 is CR7, X3 is CR8, and X4 is CR9. In yet another embodiment, X1 is CR6, X2 is N, X3 is CR8, and X4 is CR9. In another embodiment, X1 is CR6, X2 is CR7, X3 is N and X4 is CR9. In yet another embodiment, X1 is CR6, X2 is CR7, X3 is CR8 and X4 is N. In another embodiment, X1 is N, X2 is CR7, X3 is N and X4 is CR9. In yet another embodiment, X1 is N, X2 is CR7, X3 is CR8, and X4 is N. In another embodiment, X1 is CR6, X2 is N, X3 is CR8 and X4 is N.

[00124] In some embodiments of the Formulas above, R1 is H, (C1-C4) alkyl, (C1-C4) alkoxy, (C1-C4) haloalkyl, (C1-C4) haloalkoxy, halogen, -S(O)p (C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted by one or plus substituents selected from halogen, (C1-C4) alkoxy, -OH, -NH2, -NH(C1-C4) alkyl and -N((C1-C4) alkyl)2. In another embodiment, R1 is H, (C1-C4) alkyl, (C1-C4) alkoxy, (C1-C4) haloalkyl, (C1-C4) haloalkoxy, halogen, -S(O)p(C1-C6) alkyl , (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O- heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted by one or more substituents selected from halogen, (C1- C4) alkoxy and -OH. In yet another embodiment, R1 is H, -CH3, - CH2CH3, -CH (CH3)2, F, Cl, -OCH3, -OCH2CH3, -OCH(CH3)2, -OCH2CH(CH3)3, - OCF3, -OCH2CF3, -CH2OCH3, -SCH3, -SCH2CH3 or -SCH(CH3)2, each of which is optionally substituted by -OH. In another embodiment, R1 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -O-cyclopropyl, -O-cyclobutyl, -O-cyclopentyl or -O-cyclohexyl, where each is optionally substituted by -OH. In yet another embodiment, R1 is , where each is optionally substituted by –OH.

[00125] In some embodiments of the Formulas above, R2 is (C1-C4) alkyl, (C1-C4) alkoxy, (C1-C4) haloalkyl or (C1-C4) haloalkoxy. In another embodiment, R2 is (C1-C2) alkyl, (C1-C2) alkoxy, (C1-C2) haloalkyl or (C1-C2) haloalkoxy. In yet another embodiment, R2 is methyl, ethyl, methoxyl, ethoxyl, trifluoroalkyl or trifluoroalkoxyl. In another embodiment, R2 is methyl or ethyl. In yet another embodiment, R2 is methyl.

[00126] In some embodiments of the Formulas above, R2' is (C1-C4) alkyl, (C1-C4) alkoxy, (C1-C4) haloalkyl or (C1-C4) haloalkoxy. In another embodiment, R2' is (C1-C2) alkyl, (C1-C2) alkoxy, (C1-C2) haloalkyl or (C1-C2) haloalkoxy. In yet another embodiment, R2' is methyl, ethyl, methoxyl, ethoxyl, trifluoroalkyl or trifluoroalkoxyl. In another embodiment, R2' is methyl or ethyl. In yet another embodiment, R2' is methyl.

[00127] In another embodiment, R2 and R2', together with the carbon atom to which they are attached, form a (C3-C8) cycloalkyl or heterocycloalkyl ring. In yet another embodiment, R2 and R2', together with the carbon atom to which they are linked, form the cyclopropyl, cyclobutyl, cyclopentyl, oxetanyl or furanyl ring. In another embodiment, R2 and R2', together with the carbon atom to which they are attached, form a cyclopropyl or oxetanil ring.

[00128] In some embodiments of the Formulas above, R3 is (C1-C4) alkyl, (C1-C4) alkoxy, (C1-C4) haloalkyl, (C1-C4) haloalkoxy, halogen, -S(O)p(C1 -C4) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O-heterocycloalkyl, wherein alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted by one or more substituents selected from halogen, (C1-C4) alkoxy, -OH, -NH2, -NH(C1-C4) alkyl and - N((C1-C4) alkyl)2. In another embodiment, R3 is (C1-C4) alkyl, (C1-C4) alkoxy, (C1-C4) haloalkyl or (C1-C4) haloalkoxy, halogen, wherein the alkyl and alkoxy are optionally substituted by one or more substituents selected from (C1-C4) alkoxy, -OH, -NH2, -NH (C1-C4) alkyl and -N((C1-C4) alkyl)2. In yet another embodiment, R3 is halogen or (C1-C4) alkyl optionally substituted by one or more substituents selected from (C1-C4) alkoxy, -OH, -NH2, -NH (C1-C4) alkyl and -N( (C1-C4) alkyl)2. In another embodiment, R3 is halogen or (C1-C4) alkyl. In yet another embodiment, R3 is halogen.

[00129] In some embodiments of the Formulas above, R4 is H, (C1-C3) alkyl, (C1-C3) alkoxy, (C1-C3) haloalkyl, (C1-C3) haloalkoxy, (C1C3) hydroxyalkyl, (C1- C3) aminoalkyl, halogen, (C3-C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S(O)m(C1-C3) alkyl, -NH (C1-C3) alkyl or - N((C1 -C3) alkyl)2. In another embodiment, R4 is H, (C1-C3) alkyl, (C1-C3) alkoxy, (C1-C3) haloalkyl, (C1-C3) haloalkoxy, (C1-C3) hydroxyalkyl, (C1-C3) aminoalkyl, halogen, -OH, -NH2, CN, -S(O)o(C1-C3) alkyl, -NH (C1-C3) alkyl or -N((C1-C3) alkyl)2. In yet another embodiment, R4 is H, (C1-C3) alkyl, (C1-C3) haloalkyl, halogen or -S(O)o(C1-C3) alkyl. In another embodiment, R4 is H, methyl, ethyl, n-propyl, iso-propyl, trifluoromethyl, F, Cl or -S(O)2CH3.

[00130] In some embodiments of the Formulas above, R5 is H, (C1-C3) alkyl, -C (O) NR10R11, -C(O)(C1-C3) alkyl or -C(O)O(C1-C3 ) alkyl. In another embodiment, R5 is H, (C1-C3) alkyl or -C(O)NR10R11. In another embodiment, R5 is H, methyl, ethyl, n-propyl, iso-propyl or -C(O)NR10R11.

[00131] In some embodiments of the Formulas above, R6 is H, (C1-C3) alkyl, (C1-C3) alkoxy, (C1-C3) haloalkyl, (C1-C3) haloalkoxy, (C1C3) hydroxyalkyl, (C1- C3) aminoalkyl, halogen, (C3-C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S (O)o(C1-C3) alkyl, -NH (C1-C3) alkyl or - N((C1 -C3) alkyl)2. In another embodiment, R6 is H, (C1-C3) alkyl, (C1-C3) alkoxy, (C1-C3) haloalkyl, (C1-C3) haloalkoxy, (C1-C3) hydroxyalkyl, (C1-C3) aminoalkyl, halogen, -OH, -NH2, CN, -S(O)o(C1-C3) alkyl, -NH(C1-C3) alkyl or -N((C1-C3) alkyl)2. In yet another embodiment, R6 is H, (C1-C3) alkyl, (C1-C3) haloalkyl, halogen or -S(O)o(C1-C3) alkyl. In another embodiment, R6 is H, methyl, ethyl, n-propyl, iso-propyl, trifluoromethyl, F, Cl or -S(O)2CH3. In yet another embodiment, R6 is H.

[00132] In some embodiments of the Formulas above, R7 is H, (C1-C8) alkenyl, (C1-C8) alkynyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, ( C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, (C3-C8) cycloalkenyl, heterocycloalkyl, -OH, -NH2, CN or (C1-C18) alkyl, where from 0 to 7 of the (C1-C18) alkyl methylenes are optionally substituted by a portion selected from the group consisting of -O-, -NR13-, -S(O)q-, -C(O)-, -C(CH2 )- or -C(NH) -, provided that when two of the alkyl methylenes are substituted, then two -O-, two -S(O)q- or two -NR13- and -O- and -NR13- do not are contiguous, in which the alkyl is optionally substituted by one to eight R12 and in which the cycloalkyl and cycloalkenyl are optionally substituted by one to eight R13.

[00133] In some embodiments of the Formulas above, R8 is H, (C1-C8) alkenyl, (C1-C8) alkynyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, ( C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, (C3-C8) cycloalkenyl, heterocycloalkyl, -OH, -NH2, CN or (C1-C18) alkyl, where from 0 to 7 of the (C1-C18) alkyl methylenes are optionally substituted by a portion selected from the group consisting of -O-, -NR13-, -S(O)q-, -C(O)-, -C(CH2 )- or -C(NH)-, provided that when two of the alkyl methylenes are substituted, then two -O-, two -S(O)q- or two -NR13- and -O- and -NR13- do not are contiguous, in which the alkyl is optionally substituted by one to eight R12 and in which the cycloalkyl and cycloalkenyl are optionally substituted by one to eight R13.

[00134] In some embodiments of the Formulas above, R9 is H, (C1-C3) alkyl, (C1-C3) alkoxy, (C1-C3) haloalkyl, (C1-C3) haloalkoxy, (C1-C3) hydroxyalkyl, ( C1-C3) aminoalkyl, halogen, (C3-C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S (O)o(C1-C3) alkyl, -NH (C1-C3) alkyl or - N( (C1-C3) alkyl)2. In another embodiment, R9 is H, (C1-C3) alkyl, (C1-C3) alkoxy, (C1-C3) haloalkyl, (C1-C3) haloalkoxy, (C1-C3) hydroxyalkyl, (C1-C3) aminoalkyl, halogen, -OH, -NH2, CN, -S(O)o(C1-C3) alkyl, -NH(C1-C3) alkyl or -N((C1-C3) alkyl)2. In yet another embodiment, R9 is H, (C1-C3) alkyl, (C1-C3) haloalkyl, halogen or -S(O)o(C1-C3) alkyl. In another embodiment, R9 is H, methyl, ethyl, n-propyl, iso-propyl, trifluoromethyl, F, Cl or -S(O)2CH3. In yet another embodiment, R9 is H or Cl.

[00135] In some embodiments of the Formulas above, R10 is H or (C1-C6) alkyl optionally substituted by one or more OH. In another embodiment, R10 is H.

[00136] In some embodiments of the Formulas above, R11 is H or (C1-C6) alkyl optionally substituted by one or more OH. In another embodiment, R11 is H.

[00137] In some embodiments of the Formulas above, Ri2 is -OH, -NH2, -NH(Ci-Cβ) alkyl, -N((Ci-C6) alkyl)2, -C (O) OH, (C3-C8 ) cycloalkyl, heterocycloalkyl, (Cβ-Ci0) aryl or heteroaryl, wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted by one to six substituents selected from -OH, - NH2, -NH (C1-C6) alkyl, - N((C1-Cβ) alkyl)2 and Ri4.

[00138] In some embodiments of the Formulas above, Ri3 is H, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-Ci0) aryl, heteroaryl or (Ci-Ci2) alkyl, where from 0 to 7 of the methylenes of (Ci -Ci2) alkyl are optionally substituted by a portion selected from the group consisting of -O-, -NRi3-, -S(O)r-, -C(O)- or -C(NH)-, provided that when two of the methylenes of the alkyl is substituted, then O and N are not contiguous and wherein the alkyl is optionally substituted by one to eight Ri5 and wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted by one to eight substituents selected from -OH , -C(O)OH, -NH2, -NH(C1-Ce) alkyl and -N((C1-C6) alkyl)2.

[00139] In some embodiments of the Formulas above, Ri4 is (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl, -O- heterocycloalkyl, (C1-C12) alkyl or (C2-C12) alkenyl, wherein 0 to 7 of the methylenes of the (Ci-Ci2) alkyl and the (C2-Ci2) alkenyl are optionally substituted by a portion selected from the group consisting of -O-, -NRi3-, -S(O)r- , - C(O)- or -C(NH)-, provided that when two alkyl or alkenyl methylenes are substituted, then O and N are not contiguous and wherein the alkyl and alkenyl are optionally substituted by one to eight Ri5e cycloalkyl and heterocycloalkyl are optionally substituted by one to eight Ri6.

[00140] In some embodiments of the Formulas above, when Ri2 is cycloalkyl or heterocycloalkyl, two Ri4, together with the atom to which they are bonded, form C=(O). In another embodiment, two Ri4, together with the atoms to which they are bonded, form a (C3-C8) cycloalkyl or heterocycloalkyl optionally substituted by one or six Ri3. In yet another embodiment, when Ri2 is cycloalkyl or heterocycloalkyl, two Ri4, together with the atom to which they are attached, form a (C3-C8) spirocycloalkyl or a spiroheterocycloalkyl optionally substituted by one or six Ri3.

[00141] In some embodiments of the Formulas above, R15 is -OH, -NH2, -NH(CI-C6) alkyl, -N((CI-C6) alkyl)2, (Ce-Ce) cycloalkyl, heterocycloalkyl, (C6 -Ci0) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted by one to eight substituents selected from (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, -C (O) OH, -OH, -NH2, -NH(CI-C6) alkyl, -N((CI-C6) alkyl)2 and oxo.

[00142] In some embodiments of the Formulas above, R16 is -OH, -C(O)OH, -NH2, -NH (C1-C6) alkyl, -N((C1-C6) alkyl)2, (C1-C6) ) alkoxy, (C1-C6) hydroxyalkyl, (C3-Ce) cycloalkyl, heterocycloalkyl, -O- (C3-Ce) cycloalkyl, -O-heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the (C3-Ce ) cycloalkyl and heterocycloalkyl are optionally substituted by one to eight substituents selected from (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, - C(O)OH, -OH, -NH2, -NH(CI-C6) alkyl , -N((CI-C6) alkyl)2 and oxo.

[00143] In some embodiments of the above Formulas, m is 0 or 1. In yet another embodiment, m is 1 or 2. In another embodiment, m is 0. In yet another embodiment, m is 1. In another embodiment, m is 2.

[00144] In some embodiments of the Formulas above, o is 0 or 1. In yet another embodiment, o is 1 or 2. In another embodiment, o is 0. In yet another embodiment, o is 1. In another embodiment, o is 2.

[00145] In some embodiments of the above Formulas, p is 0 or 1. In yet another embodiment, p is 1 or 2. In another embodiment, p is 0. In yet another embodiment, p is 1. In another embodiment, p is 2.

[00146] In some embodiments of the above Formulas, q is 0 or 1. In yet another embodiment, q is 1 or 2. In yet another embodiment, q is 0. In yet another embodiment, q is 1. In yet another embodiment, q is two.

[00147] In some embodiments of the above Formulas, r is 0 or 1. In yet another embodiment, r is 1 or 2. In yet another embodiment, r is 0. In yet another embodiment, r is 1. In yet another embodiment, r is 2.

[00148] In some embodiments of the above Formulas, n is 0 or 1. In yet another embodiment, n is 1 or 2. In another embodiment, n is 0. In yet another embodiment, n is 1. In another embodiment, n is 2.

[00149] In some embodiments of the Formulas above, X1 is CR6 and R6 is H or halogen.

[00150] In some embodiments of the Formulas above, X2 is CR9 and R9 is H or halogen.

[00151] In some embodiments of the Formulas above, X2 is N.

[00152] In some embodiments of the Formulas above, X3 is CR7.

[00153] In some embodiments of the Formulas above, X4 is N.

[00154] In some embodiments of the Formulas above, X4 is CR8.

[00155] In some embodiments of the Formulas above, Q is -NH- or -O-.

[00156] In some embodiments of the Formulas above, Q is -NH- or -O- and Qi is -CH2-.

[00157] In some embodiments of the Formulas above, Q is C=(O) and Qi is -NR5-.

[00158] In some embodiments of the Formulas above, Q is CH2- and Qi is -O(CH2)o-i- or -NR5-.

[00159] In some embodiments of the Formulas above, Q is CH2- and Qi is -O(CH2)o-i-. In another embodiment, Q is CH2- and Qi is -O(CH2) -. In another embodiment, Q is CH2- and Qi is -O (CH2) -.

[00160] In some embodiments of the above Formulas, Q is CH2- and Qi is -NR5-.

[00161] In some embodiments of the Formulas above, R2 and R2', together with the carbon atom to which they are attached, form (C3-C8) cycloalkyl or heterocycloalkyl.

[00162] In some embodiments of the Formulas above, R2 is methyl.

[00163] In some embodiments of the Formulas above, R2' is methyl.

[00164] In some embodiments of the Formulas above, R3 is halogen.

[00165] In some embodiments of the Formulas above, Xi is CR6 and R6 is H or halogen.

[00166] In some embodiments of the Formulas above, X2 is CR9 and R9 is H or halogen.

[00167] In some embodiments of the Formulas above, X2 is N.

[00168] In some embodiments of the Formulas above, X3 is CR7.

[00169] In some embodiments of the Formulas above, X4 is N.

[00170] In some embodiments of the Formulas above, X4 is CR8.

[00171] In some embodiments of the Formulas above, n is 1.

[00172] In some embodiments of the Formulas above, n is 0.

[00173] In some embodiments of the Formulas above, R2 is H and R2' is H.

[00174] In some embodiments of the Formulas above, R2 is H and R2' is (C1-C6) alkyl.

[00175] In some embodiments of the Formulas above, R2 is H and R2' is methyl.

[00176] In some embodiments of the Formulas above, R2 is (C1-C6) alkyl and R2 ' is H.

[00177] In some embodiments of the Formulas above, R2 is methyl and R2' is H.

[00178] In some embodiments of the Formulas above, R2 is (C1-C6) alkyl and R2 ' is (C1-C6) alkyl.

[00179] In some embodiments of the Formulas above, R2 is (C1-C3) alkyl and R2 ' is (C1-C3) alkyl.

[00180] In some embodiments of the Formulas above, R2 is methyl and R2' is methyl.

[00181] In some embodiments of the Formulas above, Y is CRb. In another embodiment, Y is N. In another embodiment, Y is CH or N. In another embodiment, Y is CH. In another embodiment, Y is N.

[00182] In some embodiments of the Formulas above, Ra is H, (C1-C4) alkyl, (C1-C4) alkoxy, (C1-C4) haloalkyl, (C1-C4) haloalkoxy or halogen. In another embodiment, Ra is H, (C1-C4) alkyl or (C1-C4) alkoxy. In another embodiment, Ra is H, (C1-C3) alkyl or (C1-C3) alkoxy. In another embodiment, Ra is (C1-C3) alkyl or (C1-C3) alkoxy. In another embodiment, Ra is (C1-C3) alkyl. In another embodiment, Ra is H or (C1-C3) alkyl. In another embodiment, Ra is H.

[00183] In some embodiments of the Formulas above, Rb is H, (C1-C4) alkyl, (C1-C4) alkoxy, (C1-C4) haloalkyl, (C1-C4) haloalkoxy or halogen. In another embodiment, Rb is H, (C1-C4) alkyl or (C1-C4) alkoxy. In another embodiment, Rb is H, (C1-C3) alkyl or (C1-C3) alkoxy. In another embodiment, Rb is (C1-C3) alkyl or (C1-C3) alkoxy. In another embodiment, Rb is (C1-C3) alkoxy. In another embodiment, Rb is H or (C1-C3) alkoxy. In another embodiment, Rb is H.

[00184] In some embodiments of the Formulas above, R1 and Ra, together with the carbon atoms to which they are attached, form a heterocycloalkyl. In another embodiment, R1 and Ra, together with the carbon atoms to which they are attached, form a 5 to 7 membered heterocycloalkyl comprising 1 to 3 heteroatoms selected from N, O or S.

[00185] In some embodiments of the Formulas above, R1 and R3, together with the carbon atoms to which they are attached, form a heterocycloalkyl optionally substituted by one or more substituents selected from (C1-C6) alkyl, (C1-C6) alkoxy , (C1-C6) haloalkyl, (C1-C6) haloalkoxy and halogen. In another embodiment, R1 and R3, when found on the adjacent carbon atom, together with the carbon atoms to which they are bonded, form a heterocycloalkyl optionally substituted by one or more substituents selected from (C1-C6) alkyl, (C1 -C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy and halogen. In another embodiment, R1 and R3, when found on the adjacent carbon atom, together with the carbon atoms to which they are bonded, form a 5- to 7-membered heterocycloalkyl comprising 1 to 3 heteroatoms selected from N, O or S and optionally substituted by one or more substituents selected from (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy and halogen. In another embodiment, R1 and R3, when found on the adjacent carbon atom, together with the carbon atoms to which they are bonded, form a 5 to 7 membered heterocycloalkyl comprising 1 to 3 heteroatoms selected from N, O or S and optionally replaced by halogen.

[00186] In some embodiments of the Formulas above, Ri2 is D, -OH, halogen, -NH2, -NH (Ci-Cβ) alkyl, -N((Ci-Cβ) aiquji)2, -C (O) OH, -OC(O)(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl, heteroaryl or R17, wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from - OH, -NH2, -NH (Ci-Cβ) alkyl, -N((Ci-Cβ) aiquii)2, halogen and R14.

[00187] In some embodiments of the Formulas above, Ri3 is H, -OH, (C3-C8) cycloalkyl, heterocycloalkyl, (Cβ-Ci0) aryl, heteroaryl or (Ci-Ci2) alkyl, where from 0 to 7 of the methylenes of the (Ci-Ci2) alkyl are optionally substituted by a portion selected from the group consisting of -O-, -NRi3-, -S(O)r-, -C(O)- or -C(NH)-, provided that when two of the methylenes in the alkyl are substituted, then O and N are not contiguous and the alkyl is optionally substituted by one or more Ri5 and the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from -OH , -C (O) OH, -NH2, -NH(C1-Cβ) alkyl and -N((C1-Cβ) alkyl)2.

[00188] In some embodiments of the Formulas above, when Ri2 is cycloalkyl or heterocycloalkyl, two Ri4, together with the atom to which they are attached, form a (C6-C10) aryl or heteroaryl optionally substituted by one or more R13. In another embodiment, when R12 is cycloalkyl or heterocycloalkyl, two R14 together with the atom to which they are bonded, form one (C6-C10 aryl optionally substituted by one or more R13. In another embodiment, when R12 is cycloalkyl or heterocycloalkyl, two R14, together with the atom to which they are attached, form a 5 to 12 membered heteroaryl comprising 1 to 3 heteroatoms selected from N, O or S optionally substituted by one or more R13. In another embodiment, when R12 is cycloalkyl. or heterocycloalkyl, two R14, together with the atom to which they are attached, form a 5 to 7 membered heteroaryl comprising 1 to 3 heteroatoms selected from N, O or S optionally substituted by one or more R13. when R12 is cycloalkyl or heterocycloalkyl, two R14, together with the atom to which they are attached, form a 5- or 6-membered heteroaryl comprising 1 to 3 heteroatoms selected from N, O or S optionally substituted by one or more R13.

[00189] In some embodiments of the above formulas, R17 is (C1-C18) alkyl or (C2-C18) alkenyl, in which 0 to 8 methylene of the (C1-C18) alkyl and the (C2-C18) alkenyl are optionally substituted by a portion selected from the group consisting of -O-, -NR13-, -S(O)r-, -C(O)-, or -C(NH)-, provided that when two of the alkyl or alkenyl methylenes are substituted, then O and N are not contiguous and the alkyl and alkenyl are optionally substituted by one or more R18.

[00190] In some embodiments of the Formulas above, R18 is R19, (C6-C10) aryl or heteroaryl optionally substituted by one or more R21.

[00191] In some embodiments of the above formulas, R19 is (C1-C18) alkyl in which 0 to 8 methylene of the (C1-C18) alkyl is optionally substituted by a selected portion of the group consisting of -O-, -NR13 -, -S(O)r-, -C(O)- or -C(NH) -, provided that when two methylenes of the alkyl or alkenyl are substituted, then O and N are not contiguous and wherein the alkyl is optionally replaced by one or more R20

[00192] In some embodiments of the Formulas above, R20 is (C6-C10) aryl or heteroaryl optionally substituted by one or more R21.

[00193] In some embodiments of the above formulas, R21 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy or halogen; or two R21, together, when they are on adjacent atoms, form a cycloalkyl or heterocycloalkyl optionally substituted by one or more R22. In another embodiment, R21 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy or halogen; or two R21, together, when on adjacent atoms, form a 5 to 8 membered (C5-C8) cycloalkyl or heterocycloalkyl comprising 1 to 3 heteroatoms selected from O, N or S, in which the cycloalkyl or heterocycloalkyl is optionally substituted by one or more R22. In another embodiment, R21 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy or halogen. In another embodiment, two R21, together, when on adjacent atoms, form a (C5-C8) 5- to 8-membered cycloalkyl or heterocycloalkyl comprising 1 to 3 heteroatoms selected from O, N or S, in which the cycloalkyl or heterocycloalkyl are optionally replaced by one or more R22. In another embodiment, two R21, together, when on adjacent atoms, form a (C5C8) cycloalkyl optionally substituted by one or more R22. In another embodiment, two R21, together, when on adjacent atoms, form a 5 to 8 membered heterocycloalkyl comprising 1 to 3 heteroatoms selected from O, N or S, optionally substituted by one or more R22.

[00194] In some embodiments of the Formulas above, R22 is -C (O) NH2, -C(O)NH(Ci-Cβ) alkyl, -C(O)N((Ci-Cβ) aiquji)2, -C (O)(C3-C7) cycloalkyl or -C(O)heterocycloalkyl, wherein the cycloalkyl and heterocycloalkyl are optionally substituted by one or more substituents independently selected from -OH and CN. In another embodiment, R22 is -C(O)N((C1-Ce)alkyl)2, -C(O)(C3-Cy) cycloalkyl or -C(O)heterocycloalkyl, wherein cycloalkyl and heterocycloalkyl are optionally substituted by one or more substituents independently selected from -OH and CN. In another embodiment, R22 is a -C(O)heterocycloalkyl optionally substituted by one or more substituents independently selected from -OH and CN.

[00195] In some embodiments of the Formulas above, Q is - NR5- or -O-; Q1 is -CH2-; X1 is CR6 or N; X2 is CR7 or N; X3 is CR8 or N; X4 is CR9 or N; Y is CH; Ra is H; R1 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6haloalkoxy, halogen, -S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from halogen, (C1-C4) alkoxy, -OH, -NH2, -NH(C1-C4) alkyl and -N((C1-C4) alkyl)2; R2 and R2 ' are each independently (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) ) haloalkyl, or (C1-C6) haloalkoxy; or R2 and R2', together with the carbon atom to which they are attached form (C3-C8) cycloalkyl or heterocycloalkyl; -C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, halogen, -S (O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from halogen, (C1-C4) alkoxy, -OH, -NH2 , -NH (C1-C4) alkyl and -N ((C1-C4) alkyl)2; R4 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6)haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3 -C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S(O)m(C1-C6) alkyl, -NH(C1-C4) alkyl or -N((C1-C4) alkyl)2; R5 is H, (C1-C6)alkyl, -C(O)NR10R11, -C(O)(C1-C6)alkyl, or -C(O)O(C1-C6)alkyl; each R6 and R9 is independently H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S (O)o(C1-C6) alkyl, -NH (C1-C4) alkyl, or -N ((C1-C4) alkyl)2; each R7 and R8 is independently H, (C1-C8) alkenyl, (C1-C8)alkynyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, (C3-C8) cycloalkenyl, heterocycloalkyl, OH, -NH2, -S(O)qNH2, -S(O)qOH, CN or (C1-C18 ) alkyl, wherein 0 to 7 methylene of the (C1-C18) alkyl is optionally substituted by a portion selected from the group consisting of -O-, NR13-, -(SO)q-, -C(O)-, -C(CH2)- or -C(NH)-, provided that when two methylenes in the alkyl are substituted, then two -O-, two -S(O)q- or two -NR13- and -O- and - NR13- are non-contiguous, in which the alkyl is optionally substituted by one or more R12 and in which the cycloalkyl and cycloalkenyl are optionally substituted by one or more R13; R10 and R11 are each independently H or (C1-C6) alkyl optionally substituted with one or more substituents independently selected from -NH2 and OH; R12 is -OH, -NH2, -NH(Ci-Ce)alkyl, -N((Ci-Ce)alkyl)2, -C(O)OH, (C3-C8)cycloalkyl, heterocycloalkyl, (Cβ-C10) aryl, or heteroaryl, wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more substituents selected from -OH, -NH2, -NH (C1-Cβ) alkyl, -N ((C1-Cβ) alkyl) 2e R14; R13 is H, C3-C8) cycloalkyl, heterocycloalkyl, (Cβ-C10) aryl, heteroaryl or (C1-C12) alkyl, wherein 0 to 7 methylene of the (C1-C12) alkyl is optionally substituted by a selected portion of the group which consists of -O-, -NR13-, -S(O)r-, -C(O)-, or -C(NH)-, provided that when two methylenes in the alkyl is substituted, then O and N, not are contiguous and wherein the alkyl is optionally substituted with one or more R15 and wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more substituents selected from -OH, -C(O)OH, -NH2, -NH (C1-Cβ) alkyl and - N((C1-Cβ) alkyl)2; R14 is (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, -O-heterocycloalkyl, (C1-C12) alkyl or (C2-C12) alkenyl, wherein 0 to 7 methylene of (C1- C12) alkyl and (C2-C12) alkenyl are optionally substituted by a moiety selected from the group consisting of -O-, -NR13-, -S(O)r-, -C(O)- or -C(NH) -, provided that when two methylenes in the alkyl or alkenyl are substituted, then O and N are not contiguous and wherein the alkyl and alkenyl are optionally substituted by one or more R15 and the cycloalkyl and heterocycloalkyl are optionally substituted by one or more R1β ; or when R12 is cycloalkyl or heterocycloalkyl, two R14 together with the atom to which they are attached form C = (O); or when R12 is cycloalkyl or heterocycloalkyl, two R14 together with the atoms to which they are attached form a (C3-C8) cycloalkyl or heterocycloalkyl optionally substituted with one or more R13; or when R12 is cycloalkyl or heterocycloalkyl, two R14 together with the atom to which they are attached form a (C3-C8) spirocycloalkyl or a spiroheterocycloalkyl optionally substituted with one or more 13; Ris is -OH, -NH2, -NH (Ci-Cβ) alkyl, -N ((Ci-Cβ) alkyl)2, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted by one or more substituents selected from (Ci-Cβ) hydroxyalkyl, (Ci-Cβ) aminoalkyl, -C(O)OH, -OH, -NH2, -NH ( Ci-Cβ) alkyl, -N ((Ci-Cβ) aiquii^e oxo; Riβ is -OH, -C (O) OH, -NH2, -NH (Ci-Cβ) alkyl, -N ((Ci- Cβ ) alkyl)2, (C1-Cβ) alkoxy, (C1-Cβ) hydroxyalkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, -O-heterocycloalkyl, (Cβ-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from (C1-Cβ) hydroxyalkyl, (C1-Cβ) aminoalkyl, -C(O)OH, -OH, -NH2, -NH (Ci-Cβ) alkyl, -N ((Ci-Cβ) alkyl)2 and oxo; each m, o, p, q and r is, independently, in each occurrence, 0, i or 2; or 2.

[00196] In some embodiments of Formula (I'),

[00197] In some embodiments of the Formulas above, Q is O. In another embodiment, Q is O and X1 is CR6. In yet another embodiment, Q is O, X1 is CR6 and X2 is CR7. In another embodiment, Q is O, X1 is CR6, X2 is CR7 and X3 is CR8. In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8 and X4 is CR9. In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted by one to three -OH. In yet another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted by one to three -OH and R2 and R2' are each independently a (C1-C6) alkyl. In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted by one to three -OH, R2 and R2' are each independently (C1-C6) alkyl and R6 is H.

[00198] In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, halogen, -S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O-heterocycloalkyl, wherein alkyl, alkoxy, cycloalkyl and The heterocycloalkyl are optionally substituted by one to three -OH, R2 and R2' are each independently (C1-C6) alkyl, R6 is H and R9 is H or halogen. In yet another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, , - S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O-heterocycloalkyl, wherein alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted by one to three -OH, R2 and R2' are each independently (C1-C6) alkyl, R6 is H, R9 is H or halogen, and n is 0. In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O- heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted by one to three -OH , R2 and R2' are each independently (C1-C6) alkyl, R6 is H, R9 is H or halogen, n is 1 and R3 is halogen.

[00199] In some embodiments of the Formulas above, Q is O. In another embodiment, Q is O and X1 is CR6. In yet another embodiment, Q is O, X1 is CR6 and X2 is CR7. In another embodiment, Q is O, X1 is CR6, X2 is CR7 and X3 is CR8. In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8 and X4 is CR9. In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted by one to three -OH. In yet another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O-heterocycloalkyl, wherein alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted by one to three -OH and R2 and R2', together with the carbon atom to which they are attached, form (C3-C8) cycloalkyl or heterocycloalkyl. In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O-heterocycloalkyl, wherein alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted by one to three -OH, R2 and R2', together with the carbon atom to which they are attached, form (C3-C8) cycloalkyl or heterocycloalkyl and R6 is H.

[00200] In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, halogen, -S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O-heterocycloalkyl, wherein alkyl, alkoxy, cycloalkyl and The heterocycloalkyl are optionally substituted by one to three -OH, R2 and R2', together with the carbon atom to which they are attached, form (C3C8) cycloalkyl or heterocycloalkyl, R6 is H and R9 is H or halogen. In yet another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, , -S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O-heterocycloalkyl, wherein alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted by one to three -OH, R2 and R2', together with the carbon atom to which they are attached, form a (C3-C8) cycloalkyl or a heterocycloalkyl, R6 is H, R9 is H or halogen and n is 0. In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, halogen, -S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O-heterocycloalkyl, wherein alkyl, alkoxy, cycloalkyl and The heterocycloalkyl are optionally substituted by one to three -OH, R2 and R2', together with the carbon atom to which they are attached, form (C3-C8) cycloalkyl or heterocycloalkyl, R6 is H, R9 is H or halogen, n is 1 and R3 is halogen.

[00201] In some embodiments of the Formulas above, Q is O. In another embodiment, Q is O and X1 is CR6. In yet another embodiment, Q is O, X1 is CR6 and X2 is CR7. In another embodiment, Q is O, X1 is CR6, X2 is CR7 and X3 is CR8. In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8 and X4 is CR9. In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, replaced by one to three - OH. In yet another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, are optionally substituted by one to three -OH and R2 and R2' are each independently (C1-C6) alkyl. In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, substituted by one to three -OH and R2 and R2' are each independently a (C1-C6) alkyl and R6 is H.

[00202] In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, heterocycloalkyl are optionally substituted by one to three -OH, R2 and R2' are each independently (C1-C6) alkyl, R6 is H and R9 is H or halogen. In yet another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, are optionally substituted by one to three -OH, R2 and R2' are each independently (C1-C6) alkyl, R6 is H, R9 is H or halogen, and n is 0. In another embodiment, Q is O, is CR6, X2 is CR7, X3 is CR8, and R2' are each independently (C1-C6) alkyl, R6 is H, R9 is H or halogen, n is 1 and R3 is halogen.

[00203] In some embodiments of the Formulas above, Q is O. In another embodiment, Q is O and X1 is CR6. In yet another embodiment, Q is O, X1 is CR6 and X2 is CR7. In another embodiment, Q is O, X1 is CR6, X2 is CR7 and X3 is CR8. In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8 and X4 is CR9. In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, replaced by one to three - OH. In yet another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, are optionally substituted by one to three -OH and R2 and R2', together with the carbon atom to which they are attached, form (C3C8) cycloalkyl or heterocycloalkyl. In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, substituted by one to three -OH, R2 and R2', together with the carbon atom to which they are attached, form (C3-C8) cycloalkyl or heterocycloalkyl and R6 is H.

[00204] In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, heterocycloalkyl are optionally substituted by one to three -OH, R2 and R2', together with the carbon atom to which they are attached, form (C3-C8) cycloalkyl or heterocycloalkyl, R6 is H and R9 is H or halogen. In yet another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, are optionally substituted by one to three - OH, R2 and R2', together with the carbon atom to which they are attached, form the (C3-C8) cycloalkyl or heterocycloalkyl, R6 is H, R9 is H or halogen and n is 0. In another embodiment, Q is O, X1 is CR6, X2 is CR7, X3 is CR8, are optionally substituted by one to three - OH, R2 and R2', together with the carbon atom to which they are attached, form the (C3-C8) cycloalkyl or heterocycloalkyl, R6, R9 is H or halogen, n is 1 and R3 is halogen.

[00205] In an embodiment of Formula (I') or Formula (I): Q is -NR5- or -O-; X1 is CR6 or N; X2 is CR7 or N; X3 is CR8 or N; X4 is CR9 or N; R1 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6)haloalkoxy, halogen, -S(O)p(C1-C6) alkyl, (C3- C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl or -O-heterocycloalkyl, in which the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from halogen, (C1-C4) alkoxy, -OH, -NH2, -NH(C1-C4) alkyl and -N((C1-C4) alkyl)2; R2 and R2' are each independently (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, or (C1-C6) haloalkoxy; or R2 and R2', together with the carbon atom to which they are attached form (C3-C8) cycloalkyl or heterocycloalkyl; each R3 is, independently, at each occurrence, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, halogen, -S (O)p(C1-C6 ) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from halogen, (C1-C4) alkoxy, -OH, -NH2, -NH (C1-C4) alkyl and -N ((C1-C4) alkyl)2; R4 is H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6)haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3 -C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S(O)m(C1-C6) alkyl, -NH(C1-C4) alkyl, or -N((C1-C4) alkyl)2; R5 is H, (C1-C6)alkyl, -C(O)NR10R11, -C(O)(C1-C6)alkyl, or -C(O)O(C1-C6)alkyl; each R6 and R9 is independently H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S (O)o(C1-C6) alkyl, -NH (C1-C4) alkyl, or -N ((C1-C4) alkyl)2; each R7 and R8 is independently H, (C1-C8) alkenyl, (C1-C8)alkynyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, (C3-C8) cycloalkenyl, heterocycloalkyl, OH, -NH2, -S(O)qNH2, -S(O)qOH, CN or (C1-C18 ) alkyl, wherein 0 to 7 methylene of the (C1-C18) alkyl is optionally substituted by a portion selected from the group consisting of -O-, NR13-, -(SO)q-, -C(O)-, -C(CH2)- or -C(NH)-, provided that when two methylenes in the alkyl are substituted, then two -O-, two -S(O)q- or two -NR13- and -O- and - NR13- are non-contiguous, in which the alkyl is optionally substituted by one or more R12 and in which the cycloalkyl and cycloalkenyl are optionally substituted by one or more R13; R10 and R11 are each independently H or (C1-C6) alkyl optionally substituted with one or more substituents independently selected from -NH2 and OH; R12 is -OH, -NH2, -NH (Ci-Cβ) alkyl, -N((Ci-Cβ) alkyl)2, - C (O) OH, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from -OH, -NH2, -NH (Ci-Cβ) alkyl, -N((Ci-Cβ) alkyl )2 and R14; R13 is H, (C3-C8) cycloalkyl, heterocycloalkyl, (Cβ-C10) aryl, heteroaryl or (C1-C12) alkyl, wherein 0 to 7 methylenes of the (C1-C12) alkyl are optionally substituted by a selected moiety from the group consisting of -O-, -NRi3-, -S(O)r-, -C(O)- or -C(NH)-, provided that when any one of two methylenes in the alkyl is substituted, then O and N are not contiguous and wherein the alkyl is optionally substituted by one or more Ri5 and wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted by one or more substituents selected from -OH, -C(O)OH , -NH2, - NH(C1-Cβ) alkyl and -N ((C1-Cβ) alkyl^; R14 is (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, -O-heterocycloalkyl, (Ci-Ci2) alkyl or (C2-Ci2) alkenyl, wherein 0 to 7 methylene of the (Ci-Ci2) alkyl and (C2-Ci2) alkenyl are optionally substituted by a fraction selected from the group consisting of -O-, -NRi3-, -S(O)r-, -C(O)- or -C(NH)-, provided that when two methylenes in the alkyl or alkenyl are substituted, then O and N are not contiguous and in which the alkyl and alkenyl are optionally substituted by one or more Ri5 and cycloalkyl and heterocycloalkyl are optionally substituted by one or more Riβ; or when R12 is a cycloalkyl or a heterocycloalkyl, two R14, together with the atom to which they are attached, form C=(O); or two R14, together with the atoms to which they are attached, form a (C3-C8) cycloalkyl or heterocycloalkyl optionally substituted by one or more R13; or when R12 is a cycloalkyl or a heterocycloalkyl, two R14, together with the atom to which they are attached, form a (C3-C8) spirocycloalkyl or a spiroheterocycloalkyl optionally substituted by one or more R13; Ris is -OH, -NH2, -NH (Ci-Cβ) alkyl, -N ((Ci-Cβ) alkyl)2, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted by one or more substituents selected from (Ci-Cβ) hydroxyalkyl, (Ci-Cβ) aminoalkyl, -C(O)OH, -OH, -NH2, -NH ( Ci-Cβ) alkyl, -N ((Ci-Cβ) alkyl)2e oxo; Riβ is -OH, -C(O)OH, -NH2, -NH(Ci-Cβ)alkyl, -N((Ci-Cβ)alkyl)2, (Ci-Cβ)alkoxy, (Ci-Cβ)hydroxyalkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, -O-heterocycloalkyl, (Cβ-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted with one or plus substituents selected from (Ci-Cβ) hydroxyalkyl, (Ci-Cβ) aminoalkyl, -C(O)OH, -OH, -NH2, -NH(Ci-Cβ)alkyl, -N((Ci-Cβ)alkyl) 2 and oxo; each m, o, p, q and r is, independently, in each occurrence, 0, i or 2; and n is 0, i or 2.

[00206] Non-limiting illustrative compounds of the invention include: i-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-[(2,5-dichlorophenyl)methyl]cyclopropan-i-amine (I-i); N-[(2,5-dichlorophenyl)methyl]-i-{4-[2-(propan-2-yloxy)phenyl]pyridin-3-yl}cyclopropan-i-amine (I-2); i-[4-(2-cyclopropoxy-5-fluorophenyl)pyridin-3-yl]-N-[(2,5-dichlorophenyl)methyl]cyclopropanyl-amine (I-3); N-[(2,5-dichlorophenyl)methyl]-1-[4-(2-methoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I-4); 1-[4-(2-cyclobutoxyphenyl)pyridin-3-yl]-N-[(2,5-dichlorophenyl)methyl]cyclopropan-1-amine (I-5); N-[(2,5-dichlorophenyl)methyl]-1-[4-(2-methylphenyl)pyridin-3-yl]cyclopropan-1-amine (I-6); N-[(2,5-dichlorophenyl)methyl]-1-{4-[2-(methylsulfanyl)phenyl]pyridin-3-yl}cyclopropan-1-amine (I-7); N-[(2,5-dichlorophenyl)methyl]-1-{4-[2-(2,2,2-trifluoroethoxy)phenyl]pyridin-3-yl}cyclopropan-1-amine (I-8); N-[(2,5-dichlorophenyl)methyl]-1-[4-(2-ethylphenyl)pyridin-3-yl]cyclopropan-1-amine (I-9); 1-[4-(2-cyclopropylphenyl)pyridin-3-yl]-N-[(2,5-dichlorophenyl)methyl]cyclopropan-1-amine (I-10); N-[(2,5-dichlorophenyl)methyl]-1-{4-[2-(trifluoromethoxy)phenyl]pyridin-3-yl}cyclopropan-1-amine (I-11); N-[(2,5-dichlorophenyl)methyl]-1-{4-[2-(methoxymethyl)phenyl]pyridin-3-yl}cyclopropan-1-amine (I-12); 1-(4-{2-[(tert-butoxy)methyl]phenyl}pyridin-3-yl)-N-[(2,5-dichlorophenyl)methyl]cyclopropan-1-amine (I-13); N-[(2,5-dichlorophenyl)methyl]-1-(4-phenylpyridin-3-yl)cyclopropan-1-amine (I-14); N-[(2,5-dichlorophenyl)methyl]-1-[4-(2-ethoxy-4,5-difluorophenyl)pyridin-3-yl]cyclopropan-1-amine (I-15); 1-[4-(2-chlorophenyl)pyridin-3-yl]-N-[(2,5-dichlorophenyl)methyl]cyclopropan-1-amine (I-16); N-[(2,5-dichlorophenyl)methyl]-1-[4-(2-fluorophenyl)pyridin-3-yl]cyclopropan-1-amine (I-17); 1-[4-(2-cyclopropoxy-4-fluorophenyl)pyridin-3-yl]-N-[(2,5-dichlorophenyl)methyl]cyclopropan-1-amine (I-18); N-[(2,5-dichlorophenyl)methyl]-1-{4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropan-1-amine (I-19); 2-{2-[3-(1-{[(2,5-dichlorophenyl)methyl]amino}cyclopropyl)pyridin-4-yl]phenoxy}propan-1-ol (I-20); N-[(2,5-dichlorophenyl)methyl]-1-{4-[2-(oxolan-3-yloxy)phenyl]pyridin-3-yl}cyclopropan-1-amine (I-21); (3R,4R)-4-{2-[3-(1-{[(2,5-dichlorophenyl)methyl]amino}cyclopropyl)pyridin-4-yl]phenoxy}oxolan-3-ol (I-22) ; N-{[2-chloro-5-(methylsulfanyl)phenyl]methyl}-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I-23); 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-[(2,5-dimethylphenyl)methyl]cyclopropan-1-amine (I-24); 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-{[3-methyl-6-(methylsulfanyl)pyridin-2-yl]methyl}cyclopropan-1-amine (I-25); 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-[(2,3-dichlorophenyl)methyl]cyclopropan-1-amine (I-26); 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-[(trimethylpyrazin-2-yl)methyl]cyclopropan-1-amine (I-27); 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-[(2,5-dichlorophenyl)methyl]cyclopropan-1-amine (I-28); 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-[(4-methoxy-2,5-dimethylphenyl)methyl] cyclopropan-1-amine (I-29); N-{[5-chloro-2-(trifluoromethyl)phenyl]methyl}-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I-30); N-[(2-chloro-5-cyclopropylphenyl)methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I-31); N-{[2-chloro-5-(trifluoromethyl)phenyl]methyl}-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I-32); N-[(2-chloro-5-methylphenyl)methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I-33); N-[(5-chloro-2-methylpyridin-4-yl)methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I-34); N-[(3-chloro-6-methylpyridin-2-yl)methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I-35); N-[(3-chloro-5-fluoro-4-methoxy-2-methylphenyl)methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I-36); 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-{[2-methyl-5-(trifluoromethyl)phenyl]methyl} cyclopropan-1-amine (I-37); 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-{[4-methoxy-2-methyl-5-(propan-2-yl)phenyl]methyl}cyclopropan-1-amine (I- 38); 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-{[3-methyl-5-(methylsulfanyl)pyridin-2-yl]methyl}cyclopropan-1-amine (I-39); N-[(5-chloro-2-methylphenyl)methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I-40); 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-{[2-methyl-5-(methylsulfanyl)pyridin-4-yl]methyl}cyclopropan-1-amine (I-42); N-[(5-chloro-2-methanesulfonylphenyl)methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I-43); 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-[(3,5-dichlorophenyl)methyl]cyclopropan-1-amine (I-44); 3-{1-[(2,5-dichlorophenyl)methoxy]cyclopropyl}-4-(2-methoxyphenyl)pyridine (I-45); 4-(2-cyclopropoxyphenyl)-3-{1-[(2,5-dichlorophenyl)methoxy]cyclopropyl}pyridine (I-46); 4-(2-cyclopropoxyphenyl)-3-{1-[(2,3-dichlorophenyl)methoxy]cyclopropyl}pyridine (I-47); 4-(2-cyclopropoxyphenyl)-3-{1-[(2,4-dichlorophenyl)methoxy]cyclopropyl}pyridine (I-48); 4-(2-cyclobutoxyphenyl)-3-{1-[(2,5-dichlorophenyl)methoxy]cyclopropyl}pyridine (I-49); 3-{1-[(2,5-dichlorophenyl)methoxy]cyclopropyl}-4-(2-fluorophenyl)pyridine (I-50); 3-(1-{[5-chloro-2-(trifluoromethyl)phenyl]methoxy}cyclopropyl)-4-(2-cyclopropoxyphenyl) pyridine (I-51); 3-(1-{[2-chloro-5-(trifluoromethyl)phenyl]methoxy}cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridine (I-52); 3-{1-[(2-chloro-5-cyclopropylphenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)pyridine (I-53); 3-{1-[(2-chloro-5-methylphenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)pyridine (I-54); 3-{1-[(5-chloro-2-methylphenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)pyridine (I-55); 4-(2-cyclopropoxyphenyl)-3-{1-[(3,5-dichlorophenyl)methoxy]cyclopropyl}pyridine (I-56); 1-{1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}-1-[(2,5-dichlorophenyl)methyl]urea (I-57); 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-[(2,5-dichlorophenyl)methyl]-N-methylcyclopropan-1-amine (I-58); 4-(2-cyclopropoxyphenyl)-3-{3-[(2,5-dichlorophenyl)methoxy]oxetan-3-yl}pyridine (I-59); 1-(5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl)-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-60); 5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentanoic acid (I-61); 5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-62); 4-[(4-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}butyl)[(2S,3R) acid ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl]butanoic acid (I-63); 1-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl] butyl}-3-[(2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl]urea (I-64); 1-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]butyl}-3-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-65); (2R,3R,4R,5S)-6-({4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl }amino)hexane-1,2,3,4,5-pentol (I-66); N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl] butyl}-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]oxane-4-carboxamide (I-67); N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl] butyl}-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-68); N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}-2-methyl-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide (I-69); 3-(benzenesulfonyl)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide (I-70); N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}-2-hydroxy-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-71); N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}-2-methoxy-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-72); N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl] butyl}-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide (I-73); N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl] butyl}-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-74); N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}-3-methoxy-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide (I-75); 1-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}-3-(2-methoxyethyl)-1 -[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-76); (5S)-3-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}-5-[(1S ,2R,3R)-1,2,3,4-tetrahydroxy-butyl]-1,3-oxazolidin-2-one (I-77); (2S)-4-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}-2-[(1S ,2R,3R)-1,2,3,4-tetrahydroxy-butyl]-1,4-oxazepan-5-one (I-78); 1-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}-3-methyl-1-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-79); N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl] butyl}-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]formamide (I-80); (2R,3S,4R,5R)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide (I-81); (2S,3S,4R,5S)-N-(carbamoylmethyl)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl}-2,3,4,5,6-pentahydroxyhexanamide (I-82); (2R,3S,4R,5R)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5,6-pentahydroxy-N-(6-hydroxyhexyl)hexanamide (I-83); (2R,3S,4R,5R)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5,6-pentahydroxy-N-(2-sulfamoylethyl)hexanamide (I-84); (2S,3S,4R,5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl]hexanamide (I-85); 1-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}-1-[2-(2-hydroxyethoxy )ethyl]-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-86); 2-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamido}acetic acid (I-87); 2-(4-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]pentanoyl}piperazin-1-yl) acid acetic (I-88); 2-(4-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]pentanoyl}piperazin-1-yl)- N-methyl-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide (I-89); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-(2-{2-[2-(2- {5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]pentanamido}ethoxy)ethoxy]ethoxy}ethyl)pentanamide (I- 90); 2-[4-(2-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]pentanamido}ethyl)piperazin acid - 1-yl]acetic acid (I-91); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-1-{4-[(2S,3R,4S,5R )-2,3,4,5,6-pentahydroxyhexyl]piperazin-1-yl}pentan-1-one (I-92); (2S,3S,4R,5R,6S)-6-({5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl) acid phenyl]pentanamido}methyl)-3,4,5-trihydroxyoxane-2-carboxylic acid (I-93); 1-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]butyl}-3-ethyl-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-94); 1-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]butyl}-3-[(2S,3R, 4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-95); 1-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]butyl}-1-ethyl-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-96); 1-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]butyl}-1-(2-hydroxyethyl)- 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-97); 2-(4-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]pentanoyl}piperazin-1-yl)- N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-98); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-{2-[4-({[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}methyl)piperazin-1-yl]ethyl}pentanamide (I-99); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-{2-[4-({methyl[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}methyl)piperazin-1-yl]ethyl}pentanamide (I-100); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-{3-[4-(3-{5- [2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]pentanamido}propyl)piperazin-1-yl]propyl}pentanamide (I-101 ); 4-(2-carboxyethyl)-4-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]pentanamido}heptanedioic acid (I-102); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-1-{4-[(2S,3R,4R,5R )-2,3,5,6-tetrahydroxy-4- {[(2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl ]oxy}hexyl]piperazin-1-yl}pentan-1-one (I-103); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-{[(3R,4R,5S,6R)- 3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]methyl}pentanamide (I-104); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-(2-hydroxyethyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-105); acid (2R,3R,4S,5R)-2-[({4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)-2- methylphenyl]butyl}carbamoyl)amino]-3,4,5,6-tetrahydroxyhexanoic acid (I-106); 1-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]butyl}-3-(2-hydroxyethyl)- 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-107); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-ethyl-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-108); 3-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]butyl}-1-{[(2S,3R ,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]methyl}urea (I-109); acid (2S,3S,4R,5R,6S)-6-{[({4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy}methyl) -2-methylphenyl]butyl}carbamoyl)amino]methyl}-3,4,5-trihydroxy-oxane-2-carboxylic acid (I 110); 2-(2-{2-[({4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]butyl} acid carbamoyl)amino]acetamido}acetamido)acetic (I-111); (2S)-2-[(2S)-2-[(2S)-2-[({4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl acid ]cyclopropoxy}methyl)-2-methylphenyl]butyl}carbamoyl)amino]propanamido]propanamido]propanoic acid (I-112); (2S)-5-carbamimidamido-2-[({4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl] acid butyl}carbamoyl)amino]pentanoic acid (I-113); N-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]butyl}-4-[(2S,3R, 4S,5R)-2,3,4,5,6-pentahydroxyhexyl]piperazine-1-carboxamide (I-114); 1-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]butyl}-1-methyl-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-115); 1-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]butyl}-1-(2-methoxyethyl)- 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-116); 1-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]butyl}-1-[2-(2- hydroxyethoxy)ethyl]-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-117); 1-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]butyl}-1-(5-hydroxypentyl)- 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-118); (2R)-6-amino-2-[({4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)-2-methylphenyl] acid butyl}carbamoyl)amino]hexanoic acid (I-119); N-benzyl-5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2R,3S,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-120); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-methyl-N-(2-{[(2R, 3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}ethyl) pentanamide (I-121); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-(2,3-dihydroxypropyl)-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-122); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2R)-2-hydroxybutyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-123); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2R)-2-hydroxy-3-methoxypropyl ]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide (I-124); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2S)-2-hydroxy-3-methoxypropyl ]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide (I-125); N-benzyl-5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-126); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-(2-methoxyethyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-127); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]-N-(propan-2-yl)pentanamide (I-128); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]-N-propyl-pentanamide (I-129); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-(2-methanesulfonylethyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-130); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-(oxan-4-yl)-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-131); (2S,3S,4R,5S)-N-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)-2-methylphenyl]butyl }-2,3,4,5,6-pentahydroxy-N-methylhexanamide (I-132); 5-{2,5-dichloro-4-[({1-[4-(2-methoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-133); 5-{2,5-dichloro-4-[({1-[4-(2-methoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-134); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]pentanamide (I-135); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-methyl-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-136); 5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-137); 1-(4-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}butyl)-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-138); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-2-methyl-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-139); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N,2-dimethyl-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-140); 1-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl] butyl}-3-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-141); 5-{5-chloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-2-methylphenyl}-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-142); 5-{5-chloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-2-methylphenyl}-N-methyl-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-143); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-2,2-dimethyl-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-144); 5-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-145); 5-[5-Chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]-N-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-146); 1-(4-{4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-2,5-dimethylphenyl}butyl)-3-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-147); 5-{4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-2,5-dimethylphenyl}-N-[(2S,3R,4R,5R) -2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-148); 5-{4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-2,5-dimethylphenyl}-N-methyl-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-149); 1-{4-[4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2,5-dimethylphenyl]butyl}-3-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-150); 1-(4-{5-chloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-2-methylphenyl}butyl)-3-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-151); 2-{2-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl] ethoxy}-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide (I-152); (2R,3R,4S,5R)-2-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]pentanamido acid }-3,4,5,6-tetrahydroxyhexanoic acid (I-153); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2R,3R,4R,5S,6R) -2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]pentanamide (I-154); 2-{2-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]ethoxy}-N-methyl-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide (I-155); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2S,3R,4S,5R)-1 ,3,4,5,6-pentahydroxyhexan-2-yl]pentanamide (I-156); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]pentanoic acid (I-157); 1-(1-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]pentanoyl}piperidin-4-yl)- 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-158); 1-(1-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]pentanoyl}piperidin-4-yl)- 3-methyl-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-159); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2S,3R,4S,5R)-3 ,4,5,6-tetrahydroxy-1-(morpholin-4-yl)hexan-2-yl]pentanamide (I-160); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]hexanamide (I-161); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-methyl-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-162); 1-(5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl)-3-methyl-3- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-163); 2-{[(2S,3R,4S,5R)-2-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy}methyl acid )phenyl]pentanamido}-3,4,5,6-tetrahydroxyhexyl](methyl)amino}acetic acid (I-164); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2S,3R,4S,5R)-1 -(dimethylamino)-3,4,5,6-tetrahydroxyhexan-2-yl]pentanamide ( I-165); 4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]butan-1-amine (I-166); 1-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methylphenyl]butyl}-3-methyl-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-167); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N,N-bis(2-{[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}ethyl)pentanamide (I-168); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N,N-bis(2-{methyl[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}ethyl)pentanamide (I-169); 5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl] phenyl}-N,N-bis(2-{[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}ethyl) pentanamide (I-170); 5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl] phenyl}-N,N-bis(2-{methyl[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}ethyl) pentanamide (I-171); (2S,3S,4R,5S)-N-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)-2-methylphenyl]butyl }-2,3,4,5,6-pentahydroxyhexanamide (I-172); (2S,3S,4R,5S)-6-[(1-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl acid )phenyl]pentanoyl}piperidin-4-yl)amino]-2,3,4,5-tetrahydroxyhexanoic acid (I-173); 1-[4-(2,5-dichloro-4-{[(1-{4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropyl)amino]methyl}phenyl)butyl] -3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-174); 1-[4-(2,5-dichloro-4-{[(1-{4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropyl)amino]methyl}phenyl)butyl] -3-methyl-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-175); (2S,3S,4R,5S)-N-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)-2-methylphenyl]butyl }-2,3,4,5-tetrahydroxy-6-(morpholin-4-yl)hexanamide (I-176); 5-(2,5-dichloro-4-{[(1-{4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropyl)amino]methyl} phenyl)-N-methyl- N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-177); 3-(5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R) acid ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamido)propanoic (I-178); (2S,3S,4R,5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5-tetrahydroxy-6-(morpholin-4-yl)hexanamide (I-179); (2S,3S,4R,5S)-6-[(3-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl acid )phenyl]-N-methylpentanamido}propyl)amino]-2,3,4,5-tetrahydroxyhexanoic acid (I-180); N-{[(2R,3S,4S,5R,6R)-6-{[(1R,2R,3S,4R,6S)-4,6-diamino- 3-{[(2S,3R,4S,5S ,6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-2-hydroxycyclohexyl]oxy}-3,4,5-trihydroxyoxan-2-yl]methyl }-5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]pentanamide (I-181); 4-({4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl)butanoic acid (I-182); 3-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamido}propanoic (I-183); (2S,3S,4R,5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5,6-pentahydroxy-N-methylhexanamide (I-184); (2S,3S,4R,5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5,6-pentahydroxyhexanamide (I-185); 2-[({4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}[(2S,3R,4R) acid ,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl)methoxy]acetic acid (I-186); 3-({4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl)propanoic acid (I-187); 2-({2-[(carboxymethyl)[({4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy}methyl)phenyl]butyl acid }(methyl)carbamoyl)methyl]amino]ethyl}[({4-[2,5-dichloro-4- ({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl] butyl}(methyl)carbamoyl)methyl]amino)acetic acid (I-188); (2S,3S,4R,5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5-tetrahydroxy-N-methyl-6-(morpholin-4-yl)hexanamide (I-189); 1-(4-{5-chloro-2-methyl-4-[(1-{4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropoxy)methyl]phenyl}butyl)- 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-190); 1-(4-{5-chloro-2-methyl-4-[(1-{4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropoxy)methyl]phenyl}butyl)- 3-methyl-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-191); 5-{2,5-dichloro-4-[(1-{4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropoxy)methyl]phenyl}-N-methyl-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-192); 1-(4-{2,5-dichloro-4-[(1-{4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropoxy)methyl]phenyl}butyl)-3- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-193); 1-({4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}sulfamoyl)-3-methyl-3- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-194); 2-{[({4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}[(2S,3R, 4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]carbamoyl)methyl](methyl)amino}acetic acid (I-195); 4-({4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl)-3,3-dimethylbutanoic acid (I-196); 2-[({4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}[(2S,3R,4R) acid ,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl)amino]acetic acid (I-197); 3-[({4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}[(2S,3R,4R) acid ,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl)amino]propanoic acid (I-198); 4-[({4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}[(2S,3R,4R) acid ,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl)amino]butanoic acid (I-199); 2-({[(4-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl] phenyl}butyl)[(2S ,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]carbamoyl]methyl}(methyl)amino) acetic acid (I-200); 4-[(4-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}butyl)[(2S,3R) acid ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl]-3,3-dimethylbutanoic acid (I-201); N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}-2-methanesulfonyl-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-202); N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}-2-(dimethylamino)-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-203); 1-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}-1-methyl-3-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-204); (2S,3S,4R,5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl] butyl} -2,3,4,5,6-pentahydroxy-N-propylhexanamide (I-205); (2S,3S,4R,5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5,6-pentahydroxy-N-(2-methoxyethyl)hexanamide (I-206); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[2-(dimethylamino)ethyl]-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-207); N-(carbamoylmethyl)-5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy}methyl)phenyl]-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-208); (2S,3S,4R,5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -N-ethyl-2,3,4,5,6-pentahydroxyhexanamide (I-209); (2S,3S,4R,5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5,6-pentahydroxy-N-(propan-2-yl)hexanamide (I-210); (2S,3S,4R,5S)-N-(cyclopropylmethyl)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl}-2,3,4,5,6-pentahydroxyhexanamide (I-211); (2S,3S,4R,5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5,6-pentahydroxy-N-(3-methoxypropyl)hexanamide (I-212); (2S,3S,4R,5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5,6-pentahydroxy-N-(2-hydroxyethyl)hexanamide (I-213); (2S,3S,4R,5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5,6-pentahydroxy-N-[(2R)-2-hydroxypropyl]hexanamide (I-214); (2S,3S,4R,5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5,6-pentahydroxy-N-[(2S)-2-hydroxypropyl]hexanamide (I-215); (2S,3S,4R,5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide (I-216); (2S,3S,4R,5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]butyl} -2,3,4,5,6-pentahydroxy-N-(3-hydroxypropyl)hexanamide (I-217); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-(3-hydroxypropyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-218); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(methylcarbamoyl)methyl]-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-219); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-(3-methoxypropyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-220); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(dimethylcarbamoyl)methyl]-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-221); 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[2-(dimethylcarbamoyl)ethyl]-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-222); N-(2-carbamoylethyl)-5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy}methyl)phenyl]-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-223); (2S,3S,4R,5S)-N-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]pentyl} -2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl]hexanamide (I-224); 1-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]pentyl}-3-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-225); (2S,3S,4R,5S)-N-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]pentyl} -2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl)hexanamide (I-226); (2S,3S,4R,5S)-N-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]pentyl} -N-[2-(ethanesulfonyl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide (I-227); (2S,3S,4R,5S)-N-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]pentyl} -2,3,4,5,6-pentahydroxy-N-methylhexanamide (I-228); 5-[4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2,5-dimethylphenyl]-N-[(2S,3R,4R,5R)-2, 3,4,5,6-pentahydroxyhexyl]pentanamide (I-229); 5-[4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2,5-dimethylphenyl]-N-methyl-N-[(2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-230); 5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2S,3R,4R,5R)-2,3 ,4,5,6-pentahydroxyhexyl]pentanamide (I-231); 5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-methyl-N-[(2S,3R,4R,5R) -2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-232); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-233); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-234); 5-[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]-N-[(2S,3R,4R,5R)-2,3, 4,5,6-pentahydroxyhexyl]pentanamide (I-235); 5-[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]-N-methyl-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-236); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]pentanamide (I-237); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-methyl-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-238); 1-{4-[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]butyl}-3-[(2S,3R,4R,5R) -2,3,4,5,6-pentahydroxyhexyl]urea (I-239); 1-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}butyl)-3-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-240); 1-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}butyl)-3-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-241); N-{[5-(6-aminohexan-2-yl)-2-chlorophenyl]methyl}-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I-242); N-({5-[(2S)-6-aminohexan-2-yl]-2-chlorophenyl}methyl)-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I -243); N-({5-[(2R)-6-aminohexan-2-yl]-2-chlorophenyl}methyl)-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I -244); (5S)-5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl] hexan-1-amine (I-245); (5R)-5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl] hexan-1-amine (I-246); (5S)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}hexanoic acid (I-247); (5R)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}hexanoic acid (I-248); 6-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}heptanoic acid (I-249); N-({5-[(2S)-5-aminopentan-2-yl]-2-chlorophenyl}methyl)-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I -250); N-({5-[(2R)-5-aminopentan-2-yl]-2-chlorophenyl}methyl)-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I -251); N-{[5-(5-aminopentan-2-yl)-2-chlorophenyl]methyl}-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (I-252); (5S)-5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}hexanoic acid (I-253); (5R)-5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}hexanoic acid (I-254); 1-[(5S)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}hexyl]-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-255); 1-[(5R)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}hexyl]-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-256); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]hexanamide (I-257); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-methylhexanamide (I-258); N-benzyl-5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-259); 5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-260); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-(5-hydroxypentyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-261); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[2-(morpholine-4-sulfonyl)ethyl ]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] hexanamide (I-262); 1-[(5S)-5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyll]hexyl]-3-[(2S,3R ,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-263); 1-[(5R)-5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl] hexyl]-3-[(2S,3R ,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-264); 1-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl)-3-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-265); 1-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}hexyl)-3-[(2S,3R, 4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-266); 1-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}hexyl)-3-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-267); 1-(6-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}heptyl)-3-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-268); 1-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}hexyl)-1-methyl-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-269); 1-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenylly}hexyl)-1-[2-(2- hydroxyethoxy)ethyl]-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] urea (I-270); 1-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}pentyl)-3-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-271); 1-(5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}hexyl)-3-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-272); 1-[(5R)-5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyll]hexyl]-3-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-273); 1-[(5S)-5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyll]hexyl]-3-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-274); 1-{5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl] hexyl}-3-[(2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl]urea (I-275); 1-{5-[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl] hexyl}-3-[(2S,3R,4R,5R) -2,3,4,5,6-pentahydroxyhexyl]urea (I-276); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-oxoimidazolidin-1-yl)ethyl] hexanamide (I-277); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxyhexanamide (I-278); (2S,3S,4R,5S)-N-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyll}hexyl )-2,3,4,5,6-pentahydroxyhexanamide (I-279); (2S,3S,4R,5S)-N-(6-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}heptyl )-2,3,4,5,6-pentahydroxyhexanamide (I-280); (2S,3S,4R,5S)-N-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyll}hexyl )-2,3,4,5,6-pentahydroxy-N-methylhexanamide (I-281); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(2-methoxyethyl)hexanamide (I-282); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide (I-283); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(3-methoxypropyl)hexanamide (I-284); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide (I-285); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl]hexanamide (I-286); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(oxan-4-ylmethyl)hexanamide (I-287); (2S,3S,4R,5S)-N-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyll}hexyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl]hexanamide (I-288); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl)hexanamide (I-289); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-N-(4-acetamidobutyl)-2,3,4,5,6-pentahydroxyhexanamide (I-290); (2S,3S,4R,5S)-N-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyll}hexyl )-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl)hexanamide (I-291); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl)hexanamide (I-292); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-N-[2-(ethanesulfonyl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide (I-293); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-[3-(2-oxopyrrolidin-1-yl)propyl]hexanamide (I-294); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-N-(1,1-dioxo-1À6-thian-4-yl)-2,3,4,5,6-pentahydroxyhexanamide (I-295); (2S,3S,4R,5S)-N-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenylly}hexyl )-N-[2-(ethanesulfonyl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide (I-296); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(4-methanesulfonamidobutyl) hexanamide (I-297); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-N-[2-(1,1-dioxo-1À6,4-thiomorpholin-4-yl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide (I-298); (2S,3S,4R,5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}pentyl) -2,3,4,5,6-pentahydroxyhexanamide (I-299); (2S,3S,4R,5S)-N-(5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenylene}hexyl) -2,3,4,5,6-pentahydroxyhexanamide (I-300); (2S,3S,4R,5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}pentyl) -2,3,4,5,6-pentahydroxy-N-methylhexanamide (I-301); (2S,3S,4R,5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}pentyl) -2,3,4,5,6-pentahydroxy-N-(2-methoxyethyl)hexanamide (I-302); (2S,3S,4R,5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}pentyl) -2,3,4,5,6-pentahydroxy-N-(3-methoxypropyl)hexanamide (I-303); (2S,3S,4R,5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}pentyl) -2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide (I-304); (2S,3S,4R,5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}pentyl) -2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl)hexanamide (I-305); (2S,3S,4R,5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}pentyl) -N-(1,1-dioxo-1À6-tian-4-yl)-2,3,4,5,6-pentahydroxyhexanamide (I-306); (2S,3S,4R,5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}pentyl) -N-[2-(ethanesulfonyl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide (I-307); (2S,3S,4R,5S)-N-{5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyll]hexyl}-2 ,3,4,5,6-pentahydroxyhexanamide (I-308); (2S,3S,4R,5S)-N-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]pentyl}-2 ,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl)hexanamide (I-309); (2S,3S,4R,5S)-N-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]pentyl}-N -[2-(ethanesulfonyl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide (I-310); (2S,3S,4R,5S)-N-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]pentyl}-N -(1,1-dioxo-1À6-tian-4-yl)-2,3,4,5,6-pentahydroxyhexanamide (I-311); (2S,3S,4R,5S)-N-{5-[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]hexyl}-2, 3,4,5,6-pentahydroxyhexanamide (I 312); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R,4S,5R)- 1,3,4,5,6-pentahydroxyhexan-2-yl]hexanamide (I-313); (5S)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-314); (5R)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-315); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-316); 6-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]heptanamide (I-317); (2S,3S,4R,5S)-6-{[1-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino acid) methyl]phenyl}hexanoyl)piperidin-4-yl]amino}-2,3,4,5-tetrahydroxyhexanoic acid (I-318); 4-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}hexanoyl)-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]piperazine-1-carboxamide (I-319); 1-[1-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}hexanoyl)piperidin-4-yl] -3-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]urea (I-320); 2-[4-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}hexanoyl)piperazin-1-yl] -N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-321); 4-[2-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}hexanamido)ethyl]-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]piperazine-1-carboxamide (I-322); 1-{2-[4-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}hexanoyl)piperazin-1 -yl]ethyl}-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-323); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-{2-[4-({[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}methyl)piperazin-1-yl]ethyl}hexanamide (I-324); (5S)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-325); (5R)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-326); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-327); (6S)-6-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]heptanamide (I-328); (6R)-6-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]heptanamide (I-329); 6-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]heptanamide (I-330); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-(2-hydroxyethyl)-N-[(2R ,3S,4S,5S)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-331); N-(carbamoylmethyl)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-332); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-(2-methoxyethyl)-N-[(2R ,3S,4S,5S)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-333); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-(3-hydroxypropyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-334); N-(2-carbamoylethyl)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-335); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(methylcarbamoyl)methyl]-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-336); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[2-(dimethylamino)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-337); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-(3-methoxypropyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-338); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-(oxan-4-yl)-N-[ (2R,3S,4S,5S)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-339); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(dimethylcarbamoyl)methyl]-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-340); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-(3-hydroxy-2,2-dimethylpropyl) -N-[(2R,3S,4S,5S)- 2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-341); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[2-(2-hydroxyethoxy)ethyl]- N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-342); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2R,3S,4S,5S)- 2,3,4,5,6-pentahydroxyhexyl]-N-[(1s,4s)-4-hydroxycyclohexyl]hexanamide (I-343); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[2-(ethylcarbamoyl)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-344); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[2-(dimethylcarbamoyl)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-345); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-(2-methanesulfonylethyl)-N-[(2R ,3S,4S,5S)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-346); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-(3-methanesulfonylpropyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-347); 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[2-(dimethylsulfamoyl)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-348); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-ethylphenyl}-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]hexanamide (I-349); (5S)-5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-methyl-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-350); (5R)-5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-methyl-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-351); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-methyl-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-352); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]-N-(propan-2-yl)hexanamide (I-353); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]-N-propylhexamide (I-354); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(2-hydroxyethyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-355); N-(carbamoylmethyl)-5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-356); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(2-methoxyethyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-357); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(3-hydroxypropyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-358); N-(2-carbamoylethyl)-5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-359); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(methylcarbamoyl)methyl]-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-360); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[2-(dimethylamino)ethyl]-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-361); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(3-methoxypropyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-362); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(oxan-4-yl)-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-363); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(dimethylcarbamoyl)methyl]-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-364); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[2-(ethylcarbamoyl)ethyl]-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-365); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[2-(dimethylcarbamoyl)ethyl]-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-366); (5S)-5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(2-methanesulfonylethyl)-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] hexanamide (I-367); (5R)-5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(2-methanesulfonylethyl)-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] hexanamide (I-368); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(2-methanesulfonylethyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-369); 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(3-methanesulfonylpropyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-370); 2-[4-(5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}hexanoyl)piperazin-1-yl]- N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide (I-371); 4-[2-(5-{4-chloro-3-[(1-{1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} {[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino)methyl]phenyl}hexanamido)ethyl]-N-[(2S,3R,4R,5R)-2,3,4,5, 6-pentahydroxyhexyl]piperazine-1-carboxamide (I-372); 5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-ethyl-N-[(2S,3R,4R,5R) -2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-373); 5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-(2-hydroxyethyl)-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-374); 5-[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]-N-ethyl-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-375); 5-[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]-N-(2-hydroxyethyl)-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-376); N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl)-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-377); N-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}hexyl)-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-378); 5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-379); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}- 5-hydroxypentyl)-2,3,4,5,6-pentahydroxyhexanamide (I-380); (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pent -4-en-1-yl)-2,3,4,5,6-pentahydroxyhexanamide (I-381); (2S,3S,4R,5S)-N-[3-(1-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl] phenyl}cyclopropyl)propyl]-2,3,4,5,6-pentahydroxyhexanamide (I-382); 1-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pent-4-en-1-yl)- 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-383); 1-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-5-hydroxypentyl)-3-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-384); 1-[3-(1-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}cyclopropyl)propyl]-3-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-385); (2S,3S,4R,5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-5 -hydroxypentyl)-2,3,4,5,6-pentahydroxyhexamide (I-386); 1-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-5-hydroxypentyl)-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-387); (2S,3S,4R,5S)-N-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]butyl}- 2 ,3,4,5,6-pentahydroxyhexanamide (I-388); 1-{4-[N-methyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4S ,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-389); 1-{4-[N-ethyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-390); 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]-1-{4-[N-(propan-2-yl)4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}urea (I-391); 1-(4-{N-methyl2,4-dichloro-5-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]benzenesulfonamido}butyl)- 3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-392); 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N,N-dimethylbenzene-1-sulfonamide (I-393); 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N-methylbenzene-1-sulfonamide (I-394); 3-(1-{[2-chloro-5-(pyrrolidine-1-sulfonyl)phenyl]methoxy}cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridine (I-395); 3-(1-{[2-chloro-5-(piperidine-1-sulfonyl)phenyl]methoxy}cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridine (I-396); (2S,3R,4R,5R)-S-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-2,3,4, 5,6-pentahydroxyhexane-1-sulfonamido (I-397); (2S,3R,4R,5R)-S-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-2,3,4, 5,6-pentahydroxy-N-methylhexane-1-sulfonamido (I-398); N-[2-(2-aminoethoxy)ethyl]-4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzene-1-sulfonamide (I-399 ); N-[2-(2-aminoethoxy)ethyl]-4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N-methylbenzene-1-sulfonamide ( I-400); 1-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl]urea (I-401); 1-{4-[N-methyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-402); 1-(2-{2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]ethoxy}ethyl)-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-403); 1-(2-{2-[N-methyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]ethoxy}ethyl)-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-404); 1-{5-[N-methyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]pentyl}-3-[(2S,3R,4S ,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-405); 1-(2-{2-[N-methyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]ethoxy}ethyl)-3-[( 2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-406); 1-{4-[N-(2-methoxyethyl)4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]butyl}-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-407); 1-(2-{2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]ethoxy}ethyl)-3-[(2S, 3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-408); 1-{5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]pentyl}-3-[(2S,3R,4S,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-409); 1-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4S,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-410); 1-(2-{2-[N-ethyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]ethoxy}ethyl)-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-411); 1-{5-[N-(2-methoxyethyl)4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]pentyl}-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-412); 1-{5-[N-(2-methoxyethyl)4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]pentyl}-3-[( 2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-413); 1-{4-[N-(2-hydroxyethyl)4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]butyl}-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-414); 1-(2-{2-[N-ethyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]ethoxy}ethyl)-3-[( 2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-415); 1-{4-[N-(2-methoxyethyl)4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]butyl}-3-[( 2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-416); 1-(2-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperidin-4-yl}ethyl)-3- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-417); 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]-1-[(1r,4r)-4-[4-chloro-3-({1-[4 -(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]cyclohexyl]urea (I-418); 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]-1-[(1s,4s)-4-[4-chloro-3-({1-[4 -(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]cyclohexyl]urea (I-419); 1-({1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]pyrrolidin-3-yl}methyl)-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-420); 1-(2-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}ethyl)-3- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-421); 1-(4-{2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]ethyl}cyclohexyl)-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-422); 1-(3-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperazin-1-yl}propyl)-3- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-423); 1-({1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperidin-4-yl}methyl)-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-424); 1-(2-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperazin-1-yl}ethyl)-3- [(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]urea(I-425); 1-({1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperidin-3-yl}methyl)-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-426); 1-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}-3-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-427); 1-{7-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]-7-azaspiro[3. 5]nonan-2-yl}-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] urea (I-428); 1-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]pyrrolidin-3-yl}-3-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-429); 1-{2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]-2-azaspiro[3. 3]heptan-6-yl}-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] urea (I-430); 6-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-[(2S,3R,4R,5R)-2,3 ,4,5,6-pentahydroxyhexyl]hexanamide (I-431); 7-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-[(2S,3R,4R,5R)-2,3 ,4,5,6-pentahydroxyhexyl]heptanamide (I-432); 5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-[(2S,3R,4R,5R)-2,3 ,4,5,6-pentahydroxyhexyl]pentanamide (I-433); 3-[N-methyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]propanamide (I-434); (1R,5S,6S)-3-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]-3-azabicyclo[3. 1. 0]hexane-6-carboxamide (I-435); (1r,4r)-4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamidomethyl]-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]cyclohexane-1-carboxamide (I-436); 1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]-N-[(2S,3R,4R,5R)-2,3 ,4,5,6-pentahydroxyhexyl]piperidine-4-carboxamide (I-437); 2-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-438); 3-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-[(2S,3R,4R,5R)-2,3 ,4,5,6-pentahydroxyhexyl]cyclopentane-1-carboxamide (I-439); 2-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperazin-1-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-440); 2-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperidin-4-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-441); (1r,4r)-4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]cyclohexane-1-carboxamide (I-442); 3-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperazin-1-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide (I-443); 2-({1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperidin-4-yl}oxy)-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-444); 4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-[(2S,3R,4R,5R)-2,3 ,4,5,6-pentahydroxyhexyl]bicyclo[2. two. 2]octane-1-carboxamide (I-445); (2E)-3-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]prop-2-enamide (I-446); 2-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}-N-methyl-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide (I-447); 3-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide (I-448); 3-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperidin-4-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide (I-449); (2E)-3-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]pyrrolidin-3-yl}-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]prop-2-enamide (I-450); 3-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]pyrrolidin-3-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide (I-451); (2E)-4-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]but-2-enamide (I-452); 4-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-453); 2-({1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}oxy)-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-454); 2-({1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]pyrrolidin-3-yl}methoxy)-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide (I-455); 2-({1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}methoxy)-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide (I-456); (2S,3S,4R,5S)-N-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]butyl}- 2 ,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl) hexanamide (I-457); (2S,3S,4R,5S)-2,3,4,5,6-pentahydroxy-N-{4-[N-methyl4-chloro- 3-({1-[4-(2-cyclopropoxyphenyl)pyridin- 3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}hexanamide (I-458); (2S,3S,4R,5S)-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl)-N-{4-[N-methyl4-chloro-3-({1-[4 -(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}hexanamide (I-459); (2S,3S,4R,5S)-N-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]butyl}- 2 ,3,4,5,6-pentahydroxy-N-methylhexanamide (I-460); (2S,3S,4R,5S)-2,3,4,5,6-pentahydroxy-N-methyl-N-{4-[N-methyl4-chloro-3-({1-[4-(2- cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}hexanamide (I-461); (2S,3S,4R,5S)-N-(2-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonyl]piperidin -4-yl}ethyl)-2,3,4,5,6-pentahydroxyhexanamide (I-462); N-(4-aminobutyl)-4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)-N-ethylbenzene-1-sulfonamide (I-463); 1-(4-{N-methyl4-chloro-3-[(1-{4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropoxy)methyl]benzenesulfonamido}butyl)-3- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-464); 1-{4-[N-ethyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4S ,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-465); 1-{4-[N-methyl4-chloro-5-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-fluorobenzenesulfonamido]butyl}-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-466); 1-{4-[N-methyl2,4-dichloro-5-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]butyl}-3-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-467); 1-(4-{N-methyl3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-(trifluoromethyl)benzenesulfonamido}butyl)-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] urea (I-468); 1-{4-[N-methyl3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-(trifluoromethyl)benzenesulfonamido]butyl}-3-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] urea (I-469); 1-(4-{N-methyl3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-(trifluoromethyl)benzenesulfonamido}butyl)-3-[( 2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-470); 1-(4-{N-methyl4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]benzenesulfonamido}butyl)-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-471); 1-(4-{N-methyl4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]benzenesulfonamido}butyl)-3-[(2S, 3R,4S,5R)- 1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-472); 1-(4-{N-ethyl4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]benzenesulfonamido}butyl)-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-473); 1-(4-{N-methyl4-chloro-5-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-2-fluorobenzenesulfonamido}butyl)-3-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] urea (I-474); 1-(4-{N-methyl4-chloro-5-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-2-fluorobenzenesulfonamido}butyl)-3-[ (2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-475); 1-(4-{N-methyl2,4-dichloro-5-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]benzenesulfonamido}butyl)- 3-[( 2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-476); 1-(4-{N-methyl3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylbenzenesulfonamido}butyl)-3-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-477); 1-(4-{N-methyl3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylbenzenesulfonamido}butyl)-3-[(2S,3R ,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-478); 1-{4-[N-methyl3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylbenzenesulfonamido]butyl}-3-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-479); (2S)-5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-2-{[(2,3,4,5 ,6-pentahydroxyhexyl)carbamoyl]amino}pentanoic acid (I-480); (2R)-2-amino-6-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-ethylhexamide (I-481) ; (2R)-6-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-ethyl-2-({[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino)hexanamide (I-482); (2S)-2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-6-({[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino) hexanoic acid (I-483); (2S)-2-amino-6-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]hexanoic acid (I-484); (2S)-6-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-2-({[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino) hexanoic acid (I-485); (2S)-2-amino-6-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-ethylhexamide (I-486) ; (2S)-6-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-ethyl-2-({[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino)hexanamide (I-487); 1-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}pentyl)-3-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-488); (2S,3S,4R,5S)-N-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}pentyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide (I-489); 1-[2-(2-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}ethoxy)ethyl]-3-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-490); 1-(2-{2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfinyl]ethoxy}ethyl)-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-491); 1-(2-{2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]ethoxy}ethyl)-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-492); 1-{2-[2-({4-chloro-3-[(1-{4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropoxy)methyl]phenyl}sulfanyl)ethoxy ]ethyl}-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-493); 1-[5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)pentyl]-3-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-494); 5-({6-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-5-methylpyridin-2-yl}sulfanyl)-N-methyl-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-495); 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-{[5-methyl-2-(methylsulfanyl)pyrimidin-4-yl]methyl}cyclopropan-1-amine (I-496); 4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-ethylphenyl]sulfanyl}-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]butanamide (I-497); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]butanamide (I-498); N-[5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)pentyl]-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-499); N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl)-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-500); N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl)-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-501); N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)propyl]-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-502); N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)butyl]-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-503); N-[2-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)ethyl]-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-504); N-(2-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}ethyl)-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-505); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-methylhexanamide (I-506); (2S,3S,4R,5S)-N-[5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)pentyl]-2,3,4,5,6-pentahydroxy-N-methylhexanamide (I-507); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-methylhexanamide (I-508); (2S,3S,4R,5S)-N-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}pentyl )-2,3,4,5,6-pentahydroxy-N-methylhexanamide (I-509); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-methylhexanamide (I-510); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-methylhexanamide (I-511); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide (I-512); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide (I-513); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide (I-514); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-[3-(2-oxopyrrolidin-1-yl)propyl] hexanamide (I-515); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-(oxan-4-ylmethyl)hexanamide (I-516); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-oxoimidazolidin-1-yl)ethyl] hexanamide (I-517); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide (I-518); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide (I-519); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-[3-(2-oxopyrrolidin-1-yl)propyl] hexanamide (I-520); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-N-[2-(1,1-dioxo-1À6,4-thiomorpholin-4-yl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide (I-521); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-(oxan-4-ylmethyl)hexanamide (I-522); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl)hexanamide (I-523); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-N-[2-(1,1-dioxo-1À6,4-thiomorpholin-4-yl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide (I-524); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl) hexanamide (I-525); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide (I-526); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide (I-527); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide (I-528); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-[3-(2-oxopyrrolidin-1-yl)propyl]hexanamide (I-529); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-N-[2-(1,1-dioxo-1À6,4-thiomorpholin-4-yl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide (I-530); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-[2-(2-oxoimidazolidin-1-yl)ethyl]hexanamide (I-531); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl) hexanamide (I-532); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide (I-533); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide (I-534); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide (I-535); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(oxan-4-ylmethyl)hexanamide (I-536); (2S,3S,4R,5S)-N-(3-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}propyl) -2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl) hexanamide (I-537); (2S,3S,4R,5S)-N-(3-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}propyl) -2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide (I-538); (2S,3S,4R,5S)-N-(3-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}propyl) -2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide (I-539); (2S,3S,4R,5S)-N-(3-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}propyl) -2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide (I-540); (2S,3S,4R,5S)-N-(4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}butyl) -2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide (I-541); (2S,3S,4R,5S)-N-[2-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)ethyl]-2,3,4,5,6-pentahydroxy-N-methylhexanamide (I-542); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-oxoimidazolidin-1-yl)ethyl]hexanamide (I-543); (2S,3S,4R,5S)-N-[3-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )propyl]-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl) hexanamide (I-544); (2S,3S,4R,5S)-N-[3-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )propyl]-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide (I-545); (2S,3S,4R,5S)-N-[3-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )propyl]-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl) hexanamide (I-546); (2S,3S,4R,5S)-N-[3-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )propyl]-2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide (I-547); (2S,3S,4R,5S)-N-[4-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )butyl]-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl)hexamide (I-548); (2S,3S,4R,5S)-N-[4-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )butyl]-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide (I-549); (2S,3S,4R,5S)-N-[4-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )butyl]-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide (I-550); (2S,3S,4R,5S)-N-(4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}butyl) -2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl]hexanamide (I-551); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-N-(1,1-dioxo-1À6-tian-4-yl)-2,3,4,5,6-pentahydroxyhexanamide (I-552); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(oxan-4-ylmethyl)hexanamide (I-553); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-[3-(2-oxopyrrolidin-1-yl)propyl]hexanamide (I-554); (2S,3S,4R,5S)-N-(2-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}ethyl )-2,3,4,5,6-pentahydroxy-N-methylhexanamide (I-555); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-N-(1,1-dioxo-1À6-tian-4-yl)-2,3,4,5,6-pentahydroxyhexanamide (I-556); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-N-[2-(1,1-dioxo-1À6,4-thiomorpholin-4-yl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide (I-557); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl) hexanamide (I-558); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl)hexanamide (I-559); (2S,3S,4R,5S)-N-[4-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )butyl]-2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide (I-560); (2S,3S,4R,5S)-N-(4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}butyl) -2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl)hexanamide (I-561); (2S,3S,4R,5S)-N-(4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}butyl) -2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide (I-562); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-N-(2-acetamidoethyl)-2,3,4,5,6-pentahydroxyhexanamide (I-563); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-N-(2-acetamidoethyl)-2,3,4,5,6-pentahydroxyhexanamide (I-564); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide (I-565); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-N-(3-acetamidopropyl)-2,3,4,5,6-pentahydroxyhexanamide (I-566); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-N-(4-acetamidobutyl)-2,3,4,5,6-pentahydroxyhexanamide (I-567); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-N-(4-acetamidobutyl)-2,3,4,5,6-pentahydroxyhexanamide (I-568); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-N-(1,1-dioxo-1À6-tian-4-yl)-2,3,4,5,6-pentahydroxyhexanamide (I-569); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-(4-methanesulfonamidobutyl) hexanamide (I-570); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonamidoethyl) hexanamide (I-571); ethyl N-{2-[(2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropyl }amino)methyl]phenyl}sulfanyl)butyl]-2,3,4,5,6-pentahydroxyhexanamido]ethyl} carbamate (I-572); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-N-(3-acetamidopropyl)-2,3,4,5,6-pentahydroxyhexanamide (I-573); ethyl N-{3-[(2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropyl }amino)methyl]phenyl}sulfanyl)butyl]-2,3,4,5,6-pentahydroxyhexanamido]propyl} carbamate (I-574); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonamidoethyl) hexanamide (I-575); ethyl N-{2-[(2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy} methyl)phenyl]sulfanyl}butyl)-2,3,4,5,6-pentahydroxyhexanamido]ethyl} carbamate (I-576); (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonamidopropyl) hexanamide (I-577); ethyl N-{3-[(2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy} methyl)phenyl]sulfanyl}butyl)-2,3,4,5,6-pentahydroxyhexanamido]propyl} carbamate (I-578); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-N-(4-acetamidobutyl)-2,3,4,5,6-pentahydroxyhexanamide (I-579); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-(4-methanesulfonamidobutyl) hexanamide (I-580); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-N-(1,1-dioxo-1À6-tian-4-yl)-2,3,4,5,6-pentahydroxyhexanamide (I-581); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(4-methanesulfonamidobutyl) hexanamide (I-582); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl) hexanamide (I-583); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl) hexanamide (I-584); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonamidoethyl) hexanamide (I-585); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-N-(2-acetamidoethyl)-2,3,4,5,6-pentahydroxyhexanamide (I-586); ethyl N-{2-[(2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropyl }amino)methyl]phenyl}sulfanyl)propyl]-2,3,4,5,6-pentahydroxyhexamido]ethyl} carbamate (I-587); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonamidopropyl) hexanamide (I-588); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-N-(3-acetamidopropyl)-2,3,4,5,6-pentahydroxyhexanamide (I-589); ethyl N-{3-[(2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropyl }amino)methyl]phenyl}sulfanyl)propyl]-2,3,4,5,6-pentahydroxyhexamido]propyl} carbamate (I-590); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonamidopropyl) hexanamide (I-591); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonamidopropyl) hexanamide (I-592); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonamidoethyl) hexanamide (I-593); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-N-(3-acetamidopropyl)-2,3,4,5,6-pentahydroxyhexanamide (I-594); (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}propyl )-N-(2-acetamidoethyl)-2,3,4,5,6-pentahydroxyhexanamide (I-595); ethyl N-{3-[(2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy} methyl)phenyl]sulfanyl}propyl)-2,3,4,5,6-pentahydroxyhexamido]propyl}carbamate (I-596); ethyl N-{2-[(2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy} methyl)phenyl]sulfanyl}propyl)-2,3,4,5,6-pentahydroxyhexamido]ethyl}carbamate (I-597); (2S,3S,4R,5S)-N-[5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)pentyl]-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl]hexanamide (I-598); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(4-methanesulfonamidobutyl) hexanamide (I-599); (2S,3S,4R,5S)-N-[5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)pentyl]-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide (I-600); (2S,3S,4R,5S)-N-[5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)pentyl]-2,3,4,5,6-pentahydroxy-N-(5-hydroxypentyl)hexanamide (I-601); (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-N-(4-acetamidobutyl)-2,3,4,5,6-pentahydroxyhexanamide (I-602); (2S,3S,4R,5S)-N-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl)hexanamide (I-603); (2S,3S,4R,5S)-N-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}pentyl )-N-[2-(ethanesulfonyl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide (I-604); (2S,3S,4R,5S)-N-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide (I-605); (2S,3S,4R,5S)-N-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(5-hydroxypentyl)hexanamide (I-606); (2S,3S,4R,5S)-N-{5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfinyl]pentyl}-2 ,3,4,5,6-pentahydroxyhexanamide (I-607); (2S,3S,4R,5S)-N-{5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonyl]pentyl}-2 ,3,4,5,6-pentahydroxyhexanamide (I-608); (2S,3S,4R,5S)-N-(carbamoylmethyl)-N-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl )phenyl]sulfanyl}pentyl)-2,3,4,5,6-pentahydroxyhexanamide (I-609); (2S,3S,4R,5S)-N-(carbamoylmethyl)-N-[5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl}sulfanyl)pentyl]-2,3,4,5,6-pentahydroxyhexanamide (I-610); (2S,3S,4R,5S)-N-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}pentyl )-2,3,4,5,6-pentahydroxyhexanamide (I-611); 2-({2-[(carboxymethyl)({[2-(2-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy}methyl)phenyl] sulfanyl}ethoxy)ethyl]carbamoyl}methyl)amino]ethyl}({[2-(2-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}ethoxy)ethyl]carbamoyl}methyl)amino)acetic acid (I-612); (2R,3R,4R,5S)-6-[(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl} butyl)(2-methanesulfonylethyl)amino]hexane-1,2,3,4,5-pentol (I-613); (2R,3R,4R,5S)-6-[(3-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}propyl )(2-methanesulfonylethyl)amino]hexane-1,2,3,4,5-pentol (I-614); (2R,3R,4R,5S)-6-[(4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}butyl )(2-methanesulfonylethyl)amino]hexane-1,2,3,4,5-pentol (I-615); 3-(1-{[2-chloro-5-(methylsulfanyl)phenyl]methoxy}cyclopropyl)-4-(2-cyclopropoxyphenyl) pyridine (I-617); [4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-{[5-methyl-2-(methylsulfanyl)pyridin-4-yl]methyl} cyclopropan-1-amine (I-619); 4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-(propan-2-yl)phenyl]sulfanyl}-N-methyl-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-620); 1-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl)-3-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-621); 1-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)propyl]-3-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-622); 1-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)butyl]-3-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea I-623); (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-[2-(2-oxoimidazolidin-1-yl) ethyl]hexanamide (I-624); 1-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl)-3-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-625); 1-{2-[2-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)ethoxy]ethyl}- 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-626); 1-(4-{[(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}pentyl)carbamoyl]amino} butyl)-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-627); 1-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl)-3-[(2S,3R, 4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-628); 1-(4-{[(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl)carbamoyl]amino} butyl)-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] urea (I-629); 1-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}pentyl)-3-[(1r,4r) -4-({[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino) cyclohexyl]urea (I-630); 2-(4-{[(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}pentyl)carbamoyl]amino} piperidin-1-yl)-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-631); 1-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl)-3-[(1r,4r) -4-({[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino) cyclohexyl]urea (I-632); 2-(4-{[(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl)carbamoyl]amino} piperidin-1-yl)-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-633); 1-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}pentyl)-3-[(1s,4s) -4-({[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino) cyclohexyl]urea (I-634); 1-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl)-3-[(1s,4s) -4-({[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino) cyclohexyl]urea (I-635); 1-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}pentyl)-3-[(2S,3R, 4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-636); 1-[2-(2-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}ethoxy)ethyl]-3-[ (2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-637); 3-[2-(2-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}ethoxy)ethyl]-1-[ 4-({[2-(2-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}ethoxy)ethyl]carbamoyl} amino)butyl]urea (I-638); 1-{5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfinyl]pentyl}-3-[(2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl]urea (I-639); 1-{5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]pentyl}-3-[(2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl]urea (I-640); 1-(2-{2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]ethoxy}ethyl)-3-[(2S, 3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-641); 1-{5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfinyl]pentyl}-3-[(2S,3R,4S,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-642); 1-{5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]pentyl}-3-[(2S,3R,4S,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-643); 1-(2-{2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfinyl]ethoxy}ethyl)-3-[(2S, 3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-644); 5-({6-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-5-methylpyridin-2-yl}sulfanyl)-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-645); 4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]benzenesulfonyl}-N-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-646); 4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]benzenesulfinyl}-N-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-647); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-648); 4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-649); 4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)-N-methyl-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-650); 4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]butanamide (I-651); 4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}-N-methyl-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-652); 4-({6-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-5-methylpyridin-2-yl}sulfanyl)-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-653); 4-({6-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-5-methylpyridin-2-yl}sulfanyl)-N-methyl-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-654); 4-({4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-5-methylpyrimidin-2-yl}sulfanyl)-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-655); 4-({4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-5-methylpyrimidin-2-yl}sulfanyl)-N-methyl-N- [ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] butanamide (I-656); 5-{[6-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-5-methylpyridin-2-yl]sulfanyl}-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-657); 5-{[6-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-5-methylpyridin-2-yl]sulfanyl}-N-methyl-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-658); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-ethyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-659); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(2-hydroxyethyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-660); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(3-hydroxypropyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-661); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[2-(dimethylamino)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-662); N-(carbamoylmethyl)-4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-663); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(2-methoxyethyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-664); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(2-methanesulfonylethyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-665); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]-N-propylbutanamide (I-666); N-benzyl-4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-667); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]-N-(propan-2-yl)butanamide (I-668); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(oxan-4-yl)-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-669); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[(methylcarbamoyl)methyl]-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] butanamide (I-670); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[2-(dimethylcarbamoyl)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] butanamide (I-671); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[2-(ethylcarbamoyl)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] butanamide (I-672); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(3-methoxypropyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-673); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[(dimethylcarbamoyl)methyl]-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-674); N-(2-carbamoylethyl)-4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-675); 3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)-N-methyl-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide (I-676); 3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide (I-677); 5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)-N-methyl-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-678); 2-[1-({[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}methyl)cyclopropyl]-N-methyl-N -[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]acetamide (I-679); 4-[({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)methyl]-N-methyl-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]benzamide (I-680); 2-{1-[({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)methyl]cyclopropyl}-N- methyl-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-681); 5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-682); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[2-(2-hydroxyethoxy)ethyl]- N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] butanamide (I-683); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(5-hydroxypentyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-684); 4-({[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}methyl)-N-methyl-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]benzamide (I-685); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[2-(morpholino-4-sulfonyl)ethyl ]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] butanamide (I-686); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(3-hydroxy-2,2-dimethylpropyl) -N- [(2R,3S,4S,5S)-2,3,4,5,6-pentahydroxyhexyl] butanamide (I-687); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[(2R,3S,4S,5S)- 2,3,4,5,6-pentahydroxyhexyl]-N-[(1s,4s)-4-hydroxycyclohexyl] butanamide (I-688); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N,2-dimethyl-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-689); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-2-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-690); 4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-ethylphenyl]sulfanyl}-N-methyl-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-691); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(4-hydroxybutyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-692); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[2-(dimethylsulfamoyl)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] butanamide (I-693); 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[2-(methylsulfamoyl)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] butanamide (I-694); N-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}pentyl)-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide (I-695); 1-(4-{N-ethyl4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]benzenesulfonamido}butyl)-3-[(2S, 3R,4S,5R)- 1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-696); 3-{1-[(2-chloro-5-{methyl[4-({[(2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]carbamoyl} amino )butyl]sulfamoyl}phenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)pyridin-1-io-1-olate (I-697); 3-[1-({2-chloro-5-[(2S)-6-({[(2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]carbamoyl } amino)hexan-2-yl]phenyl}methoxy)cyclopropyl]-4-(2-cyclopropoxyphenyl)pyridin-1-io-1-olate (I-698); 3-{1-[(2-chloro-5-{ethyl[4-({[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino) butyl]sulfamoyl }phenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)pyridin-1-io-1-olate (I-699); 2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenol (I-700); 3-{1-[(2-chloro-5-{ethyl[4-({[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino) butyl]sulfamoyl }phenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)-1-{[(2,2-dimethylpropanoyl)oxy]methyl}pyridin-1-ion (I-701); 1-[({[2-(acetyloxy)ethyl](methyl)carbamoyl}oxy)methyl]-3-{1-[(2-chloro-5-{ethyl[4-({[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino)butyl]sulfamoyl}phenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)pyridin-1-io (I-702) 3- (1-{[2-chloro-5-(ethylsulfamoyl)phenyl]methoxy}cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridin-1-io-1-olate (I-703); 3-(1-{[2-chloro-5-(methylsulfamoyl)phenyl]methoxy}cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridin-1-io-1-olate (I-704); 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N,N-diethylbenzene-1-sulfonamide (I-705); 1,3-bis[(5S)-5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl) phenyl]hexyl]urea (I-706 ); 2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl) benzenesulfonamido]ethane-1-sulfonic acid (I-707); 3-{1-[(2-chloro-5-sulfamoylphenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)pyridin-1-io-1-olate (I-708); 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzene-1-sulfonamide (I-709); 1-{2-[2-({4-chloro-3-[(1-{4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropoxy)methyl]phenyl}sulfanyl)ethoxy ]ethyl}-3-[(2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-710); 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N-methyl-N-(propan-2-yl)benzene-1-sulfonamide (I- 711); 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N-(propan-2-yl)benzene-1-sulfonamide (I-712); 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N-methyl-N-propylbenzene-1-sulfonamide (I-713); 4-chloro-N-cyclopentyl-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N-methylbenzene-1-sulfonamide (I-714); 4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]-3,3-dimethylmorpholino (I-715); 3-{1-[(2-chloro-5-{[4-({[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino)butyl] (propan -2-yl)sulfamoyl}phenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)pyridin-1-io-1-olate (I-716); 3-[(2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]-1-{4-[N-(propan-2-yl)4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}urea (I-717); (2S,3S,4R,5S)-2,3,4,5,6-pentahydroxy-N-{4-[N-(propan-2-yl)4-chloro-3-({1-[4- (2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}hexanamide (I-718); N-tert-butyl-4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl) benzene-1-sulfonamide (I-719); 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N-(oxan-4-yl)benzene-1-sulfonamide (I-720); (2S)-S-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-1-hydroxypropane-2-sulfonamido (I-721) ; (2R)-S-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-1-hydroxypropane-2-sulfonamido (I-722) ; 2-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)-N-(2,5-dichlorobenzyl)propan-2-amine (I-723); 4-(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenethyl)-N-((2S,3R,4R,5R)-2,3 ,4,5,6-pentahydroxyhexyl)benzamide (I-724); 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N,N-dimethylbenzamide (I-725); 1-(5-(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenoxy)pentyl)-3-((2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl)urea (I-726); 3-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)benzyl)oxy)-N-((2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl)benzamide (I-727); 4-chloro-5-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-fluoro-N-isopropyl-N-(4-(3-((2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)ureido)butyl)benzenesulfonamide (I-728); N-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)sulfonyl)acetamide (I-729); 4-chloro-5-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-methoxy-N,N-dimethylbenzenesulfonamide (I-730); 4-chloro-5-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-hydroxy-N,N-dimethylbenzenesulfonamide (I-731); 1-(4-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)sulfonyl)-1,4-diazepan-1-yl) ethan-1-one (I-732); 6-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)sulfonyl)-2-methoxy-5,6,7,8-tetrahydro -1,6-naphthyridine (I-733); 6-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)sulfonyl)-5,6,7,8-tetrahydro-1,6 -naphthyridin-2-ol (I-734); 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-methyl-N-(4-(3-((2S,3R,4S,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl-1,1,2,2,3,3,4,4-d8)benzenesulfonamide (I-735); (2R,3S,4R,5S)-5-(3-(4-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N - methylphenyl)sulfonamido)butyl)ureido)hexane-1,2,3,4,6-pentail pentapropionate (I-738); 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-(methylthio)phenyl)pyridine (I-739); 4-(2-cyclopropoxyphenyl)-3-(2-((2,5-dichlorobenzyl)oxy)propan-2-yl)pyridine (I-740); 4-(2-cyclopropoxyphenyl)-3-(1-((2,5-dichlorobenzyl)oxy)cyclobutyl)pyridine (I-741); 4-(2-cyclopropoxyphenyl)-3-(1-((2,5-dichlorobenzyl)oxy)cyclopentyl)pyridine (I-742); 4-(2-cyclopropoxyphenyl)-3-(3-((2,5-dichlorobenzyl)oxy)tetrahydrofuran-3-yl)pyridine (I-743); 4-chloro-3-(((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropyl)amino)methyl)-N-isopropyl-N-(4-(3-((2S,3R, 4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl)benzenesulfonamide (I-744); 4-(2-cyclopropoxyphenyl)-3-(1-((2,5-dichlorobenzyl)oxy)ethyl)pyridine (I-745); 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclobutoxy)methyl)-N-isopropyl-N-(4-(3-((2S,3R,4S,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl)benzenesulfonamide (I-746); 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclobutoxy)methyl)-N-isopropyl-N-(4-(3-((2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl)ureido)butyl)benzenesulfonamide (I-747); 5-(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenethyl)-N-((2S,3R,4R,5R)-2,3 ,4,5,6-pentahydroxyhexyl)picolinamide (I-748); 4-chloro-3-(((3-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)tetrahydrofuran-3-yl)oxy)methyl)-N-isopropyl-N-(4-(3-(( 2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl)benzenesulfonamide (I-749); 4-chloro-3-(((3-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)tetrahydrofuran-3-yl)oxy)methyl)-N-isopropyl-N-(4-(3-(( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)ureido)butyl)benzenesulfonamide (I-750); 4-chloro-3-(((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropyl)amino)methyl)-N-isopropyl-N-(4-(3-((2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl)ureido)butyl)benzenesulfonamide (I-751); 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)ethoxy)methyl)- N-isopropyl-N-(4-(3-((2S,3R,4S,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl)benzenesulfonamide (I-752); 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)ethoxy)methyl)- N-isopropyl-N-(4-(3-((2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl)ureido)butyl)benzenesulfonamide (I-753); 4-chloro-3-(((2-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)propan-2-yl)amino)methyl)-N-isopropyl-N-(4-(3-(( 2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl)benzenesulfonamide (I-754); 1-(4-(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenoxy)butyl)-3-((2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl)urea (I-755); 3-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)benzyl)oxy)-N-((2S,3R,4S,5R)- 1,3,4,5,6-pentahydroxyhexan-2-yl)benzamide (I-756); 6-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)benzyl)oxy)-N-((2S,3R,4S,5R)- 1,3,4,5,6-pentahydroxyhexan-2-yl)nicotinamide (I-757); 2-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)benzyl)thio)-1-methyl-N-((2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl)-1H-imidazole-5-carboxamide (I-758); 2-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)benzyl)thio)-1-methyl-N-((2S,3R,4S ,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl)-1H-imidazol-5-carboxamide (I-759); 1-(5-(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenoxy)pentyl)-3-((2S,3R,4S,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl)urea (I-760); 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-isobutyl-N-(4-(3-((2S,3R,4S,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl)benzenesulfonamide (I-761) 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3- yl)cyclopropoxy)methyl)-N-isobutyl-N-(4-(3-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)ureido)butyl)benzenesulfonamide (I- 762); 4-chloro-5-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-fluoro-N-isopropyl-N-(4-(3-((2S,3R ,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl)benzenesulfonamide (I-763); 4-chloro-5-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-fluoro-N-isopropyl-N-(4-(3-((2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)ureido)butyl)benzenesulfonamide (I-764); 4-(2-chloro-6-methoxyphenyl)-3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)pyridine I-765); N-(4-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-methylphenyl)sulfonamido)butyl)acetamide (I-766) ; 4-(2-chlorophenyl)-3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)pyridine (I-768); 1-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)sulfonyl)-4-methyl-1,4-diazepane (I-769 ); 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-(thiazol-2-yl)benzenesulfonamide (I-770); 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-phenylbenzenesulfonamide (I-771); 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-(2,2,2-trifluoroethyl)benzenesulfonamide (I-772); 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(o-tolyl)pyridine (I-773); 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-methoxy-4-methylphenyl)pyridine I-774); 3-(1-((2-chloro-5-(N-(4-((2S,3S,4R,5S)-2,3,4,5,6-pentahydroxyhexanamido)butyl)sulfamoyl)benzyl)oxy) cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridine 1-oxide (I-775); 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-methyl-N-(4-(3-((2S,3R,4R,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl)benzenesulfonamide I-776); (1S,4S)-2-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)sulfonyl)-5-methyl-2,5 -diazabicyclo[2. two. 1]heptane (I-777); 4-(2-cyclopropoxyphenyl)-3-(1-((2,5-dichlorobenzyl)oxy)propyl)pyridine (I-779); 1-((1S,4S)-5-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)sulfonyl)-2,5- diazabicyclo[2. two. 1]heptan-2-yl)etan-1-one (I-780); 4-chloro-N-(1-(((S)-3-((S)-2-cyanopyrrolidine-1-carbonyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)oxy)-10, 21-dioxo-3,6,14,17-tetraoxa-9,11,20,22-tetraazahexacosan-26-yl)-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy )methyl)-N-methylbenzenesulfonamide (I-781); 4-chloro-N-(1-(((S)-3-((S)-2-cyanopyrrolidine-1-carbonyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)oxy)-10, 21,28,39-tetraoxo-3,6,14,17,32,35- hexaoxa-9,11,20,22,27,29,38,40-octaazatetratetracontan-44-yl)-3-((1 -(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-methylbenzenesulfonamide (I-782) 4-(2-cyclopropoxyphenyl)-3-(1-((2,5-dichlorobenzyl)oxy )cyclopropyl)pyridazine (I-783) 1-(4-(2-cyclopropoxyphenyl)pyridazin-3-yl)-N-(2,5-dichlorobenzyl)cyclopropan-1-amine (I-784); 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)-6-ethylpyridin-3-yl)cyclopropoxy)methyl)-N-methyl-N-(4-(3-((2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl)ureido)butyl)benzenesulfonamide I-785); 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)-6-ethylpyridin-3-yl)cyclopropoxy)methyl)-N-methyl-N-(4-(3-methyl-3-(( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)ureido)butyl)benzenesulfonamide (I-786); 4-(2-cyclopropoxyphenyl)-5-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-2-ethylpyridine (I-787); 1-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-5H-chromeno[3,4-c]pyridine (I-788); 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-5-ethoxy-4-phenylpyridine (I-789); 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-5-methoxy-4-phenylpyridine (I-790); 1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)-N-(2,5-dichlorophenyl)cyclopropane-1-carboxamide (I-791); 4-(2-cyclopropoxyphenyl)-3-(1-((2,5-dichlorophenoxy)methyl)cyclopropyl)pyridine (I-792); 6-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenoxy)methyl)-N-((2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl)nicotinamide (I-793); 4-(2-cyclopropoxyphenyl)-3-(1-(((2,5-dichlorobenzyl)oxy)methyl)cyclopropyl)pyridine (I-794); 4-(2-cyclopropoxyphenyl)-3-(((2,5-dichlorobenzyl)oxy)methyl)pyridine (I-795); 6-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)benzyl)oxy)-N-((2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl)nicotinamide (I-796); 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-methoxy-6-methylphenyl)pyridine (I-797); 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-methoxy-3-methylphenyl)pyridine (I-798); 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-methyl-N-(4-(3-((2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl)ureido)butyl)benzamide (I-799); 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-methoxy-5-(trifluoromethoxy)phenyl)pyridine (I-800); 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-methoxy-5-(trifluoromethyl)phenyl)pyridine (I-801) 4-(3-chloro-2-methoxyphenyl)- 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)pyridine (I-802); 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-phenylpyridine (I 803); 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-methoxy-5-methylphenyl)pyridine (I-804); 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2,2-difluorobenzo[d][1,3]dioxol-4-yl)pyridine (I-805); 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(3-methoxyphenyl)pyridine (I-806); 4-(3-chlorophenyl)-3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)pyridine (I-807); 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(4-methoxyphenyl)pyridine (I-808); 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-(methylsulfonyl)phenyl)pyridine (I-809); and 4-(4-chlorophenyl)-3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)pyridine (I-810).

[00207] In another embodiment, the compounds of the invention include: 3-(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl) benzene]sulfonamido]butyl)-1-[2-(2-[2-[([4-[([2-[2-(2-[[(4-[N-methyl[4-chloro-3- ([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamoyl]amino]ethoxy)ethoxy]ethyl]carbamoyl)amino]butyl]carbamoyl)amino]ethoxy ]ethoxy)ethyl]urea (I-736); 3-(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)-1-[2- (2-[2-[([2-[2-(2-[[(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl ]cyclopropoxy]methyl)benzene] sulfonamido]butyl)carbamoyl]amino]ethoxy)ethoxy]ethyl]carbamoyl)amino]ethoxy]ethoxy)ethyl]urea (I-737); N,N'-((carbonylbis(azanediyl))bis(butane-4,1-diyl))bis(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy )methyl)-N-methylbenzenesulfonamide)(I-767); N,N'-(piperazine-1,4-diylbis(propane-3,1-diyl))bis(5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin- 3-yl)cyclopropoxy)methyl)phenyl)pentanamide) (I-811); N,N'-(((oxybis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(5-(2,5-dichloro-4-(( 1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)pentanamide) (I-812); 2,2'-(1,18-bis(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)-5,14-dimethyl -6,13-dioxo-5,8,11,14-tetraazaoctadecane-8,11-diyl)diacetic acid (I-813); 1,1'-(butane-1,4-diyl)bis(3-(2-(2-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl) cyclopropoxy)methyl)phenyl)thio)ethoxy)ethyl)urea) (I-814); and 6-(carboxymethyl)-14-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)thio)-3-(2-( (2-(2-((4-chloro-3- ((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)thio)ethoxy)ethyl)amino)- 2-oxoethyl )-8-oxo-12-oxa-3,6,9-triazatetradecanoic acid (I-815).

[00208] In another embodiment of the invention, the compounds of Formula (I') are enantiomers. In some embodiments, the compounds are (S)-enantiomers. In other embodiments, the compounds are the (R) enantiomer. In still other embodiments, the compounds of Formula (I') may be (+) or (-) enantiomers.

[00209] It should be understood that all isomeric forms are included within the scope of the present invention, including mixtures thereof. If the compound contains a double bond, the substituent may be in the E or Z configuration. If the compound contains a disubstituted cycloalkyl, the cycloalkyl substituent may have a cis or trans configuration. All tautomeric forms must also be included.

[00210] The compounds of the invention and pharmaceutically acceptable salts, hydrates, solvates, stereoisomers and prodrugs can exist in their tautomeric form (for example, as an amide or imino ether). All such tautomeric forms are contemplated herein as part of the present invention.

[00211] The compounds of the invention may contain asymmetric or chiral centers and, therefore, exist in different stereoisomeric forms. It is intended that all stereoisomeric forms of the compounds of the invention, as well as mixtures thereof, including racemic mixtures, form part of the present invention. Furthermore, the present invention encompasses all geometric and positional isomers. For example, if a compound of the invention incorporates a double bond or a fused ring, the cis- and trans-forms, as well as mixtures, are encompassed within the scope of the invention. Each compound described herein includes all enantiomers that conform to the general structure of the compound. Compounds can be in a racemic or enantiomerically pure form, or any other form in terms of stereochemistry. Assay results may reflect data collected for the racemic form, the enantiomerically pure form, or any other form in terms of stereochemistry.

[00212] Diastereomeric mixtures can be separated into their individual diastereomers based on their physicochemical differences by methods well known to those skilled in the art, such as, for example, by chromatography and/or fractional crystallization. The enantiomers can be separated by converting the enantiomeric mixture to a diastereomeric mixture by reacting with an appropriate optically active compound (e.g., chiral auxiliary such as a chiral alcohol or an acid Mosher chloride), separating the diastereomers and converting (e.g., by hydrolyzing) the individual diastereomers to the corresponding pure enantiomers. Furthermore, some of the compounds of the invention may be atropisomers (e.g., substituted biaryls) and are considered to be part of this invention. Enantiomers can also be separated using a chiral HPLC column.

[00213] It is also possible that the compounds of the invention may exist in different tautomeric forms and all these forms are covered within the scope of the invention. Furthermore, for example, all keto-enol and imine-enamine forms of the compounds are included in this invention.

[00214] All stereoisomers (e.g., geometric isomers, optical isomers, and the like) of the present compounds (including those of the salts, solvates, esters, and prodrugs of the compounds, as well as the salts, solvates, and esters of the prodrugs) , such as those that may exist due to asymmetric carbons in various substituents, including enantiomeric forms (which may exist even in the absence of asymmetric carbons), rotary forms, atropisomers and diastereomeric forms, within the scope of this invention, as well as positional isomers ( such as, for example, 4-pyridyl and 3-pyridyl). For example, if a compound of Formula (I') incorporates a double bond or a fused ring, the cis- and trans- forms, as well as mixtures, fall within the scope of the invention. Furthermore, for example, all keto-enol and imine-enamine forms of the compounds are included in this invention.) Individual stereoisomers of the compounds of the invention may, for example, be substantially free of other isomers, or may be mixed, e.g. example, as racemates or with all other selected stereoisomers. The chiral centers of the present invention may have the S or R configuration as defined by the IUPAC 1974 Recommendations. The use of the terms "salt", "solvate", "ester", "prodrug" and the like are intended to apply also to the salt, solvate, ester and prodrug of enantiomers, stereoisomers, rotamers, tautomers, positional isomers, racemates or prodrugs of the compounds of the invention.

[00215] The compounds of Formula I can form salts that are also within the scope of this invention. Reference to a compound of the Formula comprised herein includes reference to salts thereof, unless otherwise indicated.

[00216] The present invention relates to compounds that are TGR5 modulators. In one embodiment, the compounds of the present invention are TGR5 agonists.

[00217] The invention is directed to compounds as described herein and pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers or tautomers, and pharmaceutical compositions comprising one or more compounds as described herein, or salts, hydrates, solvates, prodrugs, pharmaceutically acceptable stereoisomers, or tautomers thereof.

Method for Preparation of Compounds

[00218] The compounds of the present invention can be produced by a variety of methods, including standard chemistry. Suitable synthetic pathways are represented in the schemes below.

[00219] Compounds of Formula (I') can be prepared by methods known in the art of organic synthesis as determined in part by the following synthetic schemes. In the schemes described below, it is well understood that protecting groups for sensitive or reactive groups are used when necessary in accordance with general principles or chemistry. Protecting groups are manipulated according to standard methods of organic synthesis (T. W. Greene and P. G. M. Wuts, "Protective Groups in Organic Synthesis", third edition, Wiley, New York 1999). These groups are removed at a convenient stage in the synthesis of the compound using methods that are apparent to those skilled in the art. The selection processes, as well as the reaction conditions and the order of their execution, must be consistent with the preparation of compounds of Formula (I').

[00220] Those skilled in the art will recognize whether a stereocenter exists in the compounds of Formula (I'). Accordingly, the present invention includes both possible stereoisomers (unless specified in the synthesis) and includes not only racemic compounds, but also the individual enantiomers and/or diastereomers. When a compound is desired in a single enantiomer or diastereomer, it can be obtained by stereospecific synthesis or by resolution of the final product or any convenient intermediate. Resolution of the final product, an intermediate or raw material may be carried out by any suitable method known in the art. See, for example, "Stereochemistry of Organic Compounds" by E. L. Eliel, S. H. Wilen, and L. N. Mander (Wiley-interscience, 1994).

[00221] The compounds described in this document can be made from commercially available raw materials or synthesized using known organic, inorganic and/or enzymatic processes.

[00222] The compounds of the present invention can be prepared in a variety of ways known to one skilled in the art of organic synthesis. By way of example, the compounds of the present invention can be synthesized using the methods described below together with synthetic methods known in the art of organic chemistry or variations thereof as appreciated by those skilled in the art. Preferred methods include, but are not limited to, the methods described below. The compounds of the present invention can be synthesized following the steps described in the General Schemes. 1 to 5 that comprise different sequences of assembly intermediates B-1 to B-20. The starting materials are commercially available or made by procedures known in the literature reported or as illustrated. wherein Ra, R1, R2, R2', R3, R4X1-X4, Y and n are defined as in Formula (I').

[00223] The general way of preparing compounds of Formula (I') using intermediates B-1, B-2, B-3, B-4, B-4, B-5, B-6 and B-7 is described in General Scheme 1. Alkylation of nitrile B-1 using an alkyllithium or Grignard reagent in a solvent, i.e., tetrahydrofuran (THF) or diethyl ether, and optionally in the presence of a Lewis acid, i.e. , cerium(III) chloride or titanium(IV) isopropoxide provides amine B-2. Alternatively, alkylation of nitrile B-1 using an alkyl zinc or Grignard reagent in a solvent, i.e., tetrahydrofuran (THF), diethyl ether, or toluene, in the presence of boron trifluoride etherate and a Lewis acid, that is, titanium(IV) isopropoxide or bis(cyclopentadienyl)zirconium(IV) dichloride, gives amine B-2 in which R2 and R2' form a cyclopropane ring. Boc protection of the primary amine B-2 using known protection methods (i.e., treatment of B-2 with di-tert-butyl dicarbonate using a base, i.e., NaHCO3, in a solvent, i.e., water and/or tetra- hydrofuran (THF)) provides B-3 Arylation of B-3 with an aryl boronic acid or ester in the presence of a metal catalyst, i.e., palladium(II) acetate (Pd(OAc)2), tris(dibenzylideneacetone)dipalladium (Pd2(dba)3) etc., and a base, i.e. potassium carbonate (K2CO3), cesium carbonate (Cs2CO3), in a solvent, i.e. dichloromethane, toluene, etc., gives B-4.

[00224] Alkylation of B-4 with an aryl halide, aryl sulfonate or aryl sulfate in the presence of a base, that is, K2CO3, Cs2CO3, KOH or NaH, in a solvent, that is, acetonitrile or acetone and, optionally, at an elevated temperature, B-5. Alternatively, B-5 can be obtained by alkylation of B-4 with a phenol using a Mitsunobu reagent (i.e., diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD)) and triphenyl phosphine in a solvent, i.e., tetra -hydrofuran (THF), dichloromethane (DCM). Deprotection of B-4 in the presence of an acid, i.e. hydrochloric acid (HCl) and in a solvent, i.e. dioxane and/or tetrahydrofuran (THF) provides free amine B-6. Alkylation of B-6 with aryl halide or heteroaryl halide B-7 using a base, i.e., potassium carbonate (K2CO3) or cesium carbonate (Cs2CO3), in a solvent, i.e., N,N-dimethylformamide (DMF ) or tetrahydrofuran (THF) provides the desired compound of Formula (I'). wherein Ra, R1, R2, R2', R3, R4, X1-X4, Y and n are defined as in Formula (I').

[00225] Alternatively, compounds of Formula (I') can be obtained via reductive amination of amine B-6 using aldehyde B-7a in the presence of a reducing agent, i.e., sodium triacetoxyborohydride, sodium cyanoborohydride or sodium borohydride, in a solvent, namely tetrahydrofuran (THF). wherein Ra, R1, R2, R2', R3, R4, X1-X4, Y and n are defined as in Formula (I').

[00226] Alternatively, compounds of Formula (I') can be prepared using intermediates B-7, B-8, B-9, B-10, B-11, and B-12 as described in General Scheme 3. Esterification of B-8 using trimethylsilylmethyldiazene in a solvent, i.e., dichloromethane or methanol, yields B-9. Alternatively, B-9 can be obtained by treating B-8 with oxaloyl chloride in a solvent, i.e., methanol. Coupling of B-9 and aryl- or heteroarylboronic acid or ter of aryl- or heteroarylboronate B-10 in the presence of a metal catalyst, i.e. palladium(II) acetate (Pd(OAc)2), tris(dibenzylideneacetone) dipalladium (Pd2(dba)3) etc., and a base, i.e. potassium phosphate, in a solvent, i.e. 1,4-dioxane, THF and/or water, provides B-11. Alkylation of the B-11 ester using an alkyllithium or Grignard reagent in a solvent, i.e., tetrahydrofuran (THF) or diethyl ether, and optionally in the presence of a Lewis acid, i.e., cerium chloride ( III) or titanium isopropoxide (IV) provides alcohol B-12. For compounds in which R2 and R2' form a cyclopropane ring, intermediate B-11 is treated with a Grignard reagent and bis(cyclopentadienyl)zirconium(IV) dichloride in a solvent, i.e., tetrahydrofuran (THF), ether diethyl or toluene, to provide the desired product. Alkylation of B-12 with aryl halide or heteroaryl halide B-7 in the presence of a strong base, i.e., sodium hydride (NaH), potassium bis(trimethylsilyl) amide (KHMDS), or potassium tert-butoxide and in a solvent, i.e., N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP) or tetrahydrofuran (THF), provides the desired compound of Formula (I'). General Scheme 4 wherein Ra, R1, R2, R2', R3, R4X1-X4, ien are defined as in Formula (I').

[00227] The general way of preparing target molecules of Formula (I') using intermediates B-7, B-10, B-12, B-13, B-14 and B-15 is outlined in General Scheme 4. Coupling of B-12 and aryl- or heteroarylboronic acid or aryl- or heteroarylboronate B-10 in the presence of a metal catalyst, i.e. palladium(II) acetate (Pd(OAc)2),tris(dibenzylideneacetone)dipalladium (Pd2 (dba)3) etc., and a base, i.e. potassium phosphate, in a solvent, i.e. 1,4-dioxane, THF and/or water, provides B-11. Treatment of B-11 with an alkyllithium or alkylmagnesium halide (i.e., butyllithium bromide and isopropylmagnesium) followed by addition of ketone B-14 in a solvent, i.e., tetrahydrofuran (THF ) or diethyl ether, gives alcohol B-15 Alkylation of B-15 with aryl halide or heteroaryl halide B-7 in the presence of a strong base, i.e., sodium hydride (NaH), potassium bis(trimethylsilyl) amide ( KHMDS) or potassium tert-butoxide and in a solvent, i.e., N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP) or tetrahydrofuran (THF), provides the desired compound of Formula (I' ). wherein Ra, R1, R2, R2', R3, R4X1-X4, ien are defined as in Formula (I').

[00228] Alternatively, compounds of Formula (I') can be prepared using intermediates B-15, B-16, B-17, B-18, B-19, and B-20 as described in General Scheme 5. Treatment of sulfonylchloride B- 13 with amine B-17 in the presence of a base, i.e., pyridine, triethylamine or NaHCO3 and in a solvent, i.e., tetrahydrofuran (THF), dichloromethane (DCM) or water, gives sulfonyl,mide B- 18. Reduction of carboxylic acid B-18 using isobutyl chloroformate in the presence of a base, i.e., Nmethylmorpholine or trimethylamine, in a solvent, i.e., tetrahydrofuran (THF), followed by addition of sodium borohydride B-19 . Halomethylene B-20 is obtained by reacting B-19 with dibromotriphenylphosphorane in a solvent, namely acetonitrile. Alkylation of B-15 with aryl halide or heteroaryl halide B-20 in the presence of a strong base, i.e., sodium hydride (NaH), potassium bis(trimethylsilyl)amide (KHMDS), KHMDS, or potassium tert- butoxide and in a solvent, i.e., N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP) or tetrahydrofuran (THF), provides the desired compound of Formula (I').

[00229] A mixture of enantiomers, diastereomers, cis/trans isomers resulting from the process described above can be separated into its simple components by chiral salt technique, chromatography using normal phase, reverse phase or chiral column, depending on the nature of the separation.

[00230] It should be understood that in the above description and formula, the various groups Ra, R1, R2, R2', R3, R4X1-X4, i and n are defined as in Formula (I') and other variables are as defined above, except where otherwise indicated. Furthermore, for synthetic purposes, the compounds of General Schemes 1 to 5 are merely representative with radicals chosen to illustrate the general synthetic methodology of compounds of Formula (I') as defined herein.

Methods of Using the Compositions

[00231] Another aspect of the invention relates to a method of treating or preventing a disease or disorder associated with TGR5 modulation. The method comprises administering to a patient in need of treatment for diseases or disorders associated with TGR5 modulation an effective amount of compositions and compounds of Formula (I'), or a salt, hydrate, solvate, prodrug, stereoisomer, or tautomer of the same. In some embodiments, the disease or disorder associated with modulation of TGR5 activity is selected from chemotherapy-induced diarrhea, diabetes, Type II diabetes, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ischemia, myocardial infarction, retinopathy, vascular restenosis, hypercholesterolemia, hypertriglyceridemia, dyslipidemia or hyperlipidemia, lipid disorders such as low HDL cholesterol or high LDL cholesterol, arterial hypertension, angina pectoris, coronary artery disease, atherosclerosis, cardiac hypertrophy, hyperphosphatemia, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease (COPD), psoriasis, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition, especially during small bowel syndrome, irritable bowel syndrome (IBS), allergic diseases, fatty liver disease, non-alcoholic fatty liver disease (NAFLD), liver fibrosis, non-alcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), liver cirrhosis, primary biliary cirrhosis (PBC), renal fibrosis, anorexia nervosa, intestinal motility, bulimia nervosa and neurological disorders such as Alzheimer's disease, multiple sclerosis, schizophrenia and impaired cognition.

[00232] In another aspect, the present invention relates to a method of treating or preventing a disease or disorder associated with the activation of TGR5. The method comprises administering to a patient in need of treatment for diseases or disorders associated with TGR5 activation an effective amount of compositions and compounds of Formula (I'), or a salt, hydrate, solvate, prodrug, stereoisomer, or tautomer of the same. In some embodiments, the disease or disorder associated with activation of TGR5 activity is selected from chemotherapy-induced diarrhea, diabetes, Type II diabetes, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ischemia, myocardial infarction, retinopathy, vascular restenosis, hypercholesterolemia, hypertriglyceridemia, dyslipidemia or hyperlipidemia, lipid disorders such as low HDL cholesterol or high LDL cholesterol, arterial hypertension, angina pectoris, coronary artery disease, atherosclerosis, cardiac hypertrophy, hyperphosphatemia, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease (COPD), psoriasis, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition, especially during small bowel syndrome, irritable bowel syndrome (IBS), allergic diseases, fatty liver disease, non-alcoholic fatty liver disease (NAFLD), liver fibrosis, non-alcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), liver cirrhosis, primary biliary cirrhosis (PBC), renal fibrosis, anorexia nervosa, intestinal motility, bulimia nervosa and neurological disorders such as Alzheimer's disease, multiple sclerosis, schizophrenia and impaired cognition.

[00233] Another aspect of the invention relates to a method of treating or preventing chemotherapy-induced diarrhea in a patient in need. The method comprises administering to a patient in need of cancer treatment for chemotherapy-induced diarrhea an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer of the same.

[00234] In another aspect, the present invention relates to a method of treating or preventing Type II Diabetes mellitus. The method consists of administering to a patient in need of treatment for Type II Diabetes mellitus an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00235] Another aspect of the invention relates to a method for treating or preventing hyperphosphatemia. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof. In one embodiment, the hyperphosphatemia is postprandial hyperphosphatemia.

[00236] In another aspect, the present invention relates to a method for treating or preventing kidney disease. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof. In one embodiment, the kidney disease is chronic kidney disease (CKD) or end-stage renal disease (ESRD).

[00237] Another aspect of the invention relates to a method for reducing serum creatinine levels. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00238] In another aspect, the present invention relates to a method for treating or preventing proteinuria. The method comprises administering to a patient in need of cancer treatment for chemotherapy-induced diarrhea an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer of the same.

[00239] Another aspect of the invention relates to a method for delaying renal replacement therapy (RTR) time. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00240] In another aspect, the present invention relates to a method for reducing FGF23 levels. The method comprises administering to a patient in need of cancer treatment for chemotherapy-induced diarrhea an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer of the same.

[00241] Another aspect of the invention relates to a method for reducing the hyperphosphatemic effect of active vitamin D. The method comprises administering to a patient in need an effective amount of a compound of Formula (I') or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00242] In another aspect, the present invention relates to a method for alleviating hyperparathyroidism. The method comprises administering to a patient in need of cancer treatment for chemotherapy-induced diarrhea an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer of the same. In one incarnation, hyperparathyroidism is secondary hyperparathyroidism.

[00243] Another aspect of the invention relates to a method for reducing parathyroid hormone (Pt) in serum. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00244] In another aspect, the present invention relates to a method for improving endothelial dysfunction. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof. In one embodiment, endothelial dysfunction is induced by postprandial serum phosphorus.

[00245] Another aspect of the invention relates to a method for reducing vascular calcification. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof. In one embodiment, the calcification is intimately-localized vascular calcification.

[00246] In another aspect, the present invention relates to a method for reducing urinary phosphorus. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00247] Another aspect of the invention relates to a method for normalizing serum phosphorus levels. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00248] In another aspect, the present invention relates to a method for reducing phosphate load in an elderly patient. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00249] Another aspect of the invention relates to a method for decreasing the absorption of phosphate in the diet. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00250] In another aspect, the present invention relates to a method for reducing renal hypertrophy. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00251] Another aspect of the invention relates to a method for reducing heart hypertrophy. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00252] In another aspect, the present invention relates to a method for treating and/or preventing a disorder related to the stomach and intestine. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof. In one embodiment, the stomach and intestine related disorder is ulcers, digestion disorders, malabsorption syndromes, short bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, celiac disease (e.g., resulting from induced enteropathy). due to gluten or celiac disease), tropical sprue, hypogammaglobulinemic sprue, enteritis, regional enteritis (Crohn's disease), ulcerative colitis, damage to the small intestine, or short bowel syndrome. In another embodiment, the stomach and intestine-related disorder is radiation enteritis, infectious or post-infectious enteritis, bone marrow transplant-induced enteritis, or damage to the small intestine due to toxic substances, or other chemotherapeutic agents.

[00253] Another aspect of the invention relates to a method for treating and/or preventing a side effect of chemotherapy or radiation treatment. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof. In some embodiments, the secondary effect of chemotherapy is diarrhea, abdominal cramps, vomiting, or structural and functional damage to the intestinal epithelium resulting from chemotherapy treatment. In one embodiment, diarrhea is induced by an immune checkpoint inhibitor.

[00254] In another aspect, the present invention relates to the use of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in the treatment or prevention of a disease associated with TGR5 activation. In some embodiments, the disease or disorder associated with activation of TGR5 activity is selected from chemotherapy-induced diarrhea, diabetes, Type II diabetes, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ischemia, myocardial infarction, retinopathy, vascular restenosis, hypercholesterolemia, hypertriglyceridemia, dyslipidemia or hyperlipidemia, lipid disorders such as low HDL cholesterol or high LDL cholesterol, arterial hypertension, angina pectoris, coronary artery disease, atherosclerosis, cardiac hypertrophy, hyperphosphatemia, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease (COPD), psoriasis, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition, especially during small bowel syndrome, irritable bowel syndrome (IBS), allergic diseases, fatty liver disease, non-alcoholic fatty liver disease (NAFLD), liver fibrosis, non-alcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), liver cirrhosis, primary biliary cirrhosis (PBC), renal fibrosis, anorexia nervosa, intestinal motility, bulimia nervosa and neurological disorders such as Alzheimer's disease, multiple sclerosis, schizophrenia and impaired cognition.

[00255] In some embodiments, the disease or disorder associated with activation of TGR5 activity is selected from chemotherapy-induced diarrhea, diabetes, Type II diabetes, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance, hyperglycemia , obesity, metabolic syndrome, ischemia, myocardial infarction, retinopathy, vascular restenosis, hypercholesterolemia, hypertriglyceridemia, dyslipidemia or hyperlipidemia, lipid disorders such as low HDL cholesterol or high LDL cholesterol, arterial hypertension, angina pectoris, coronary artery disease, atherosclerosis, cardiac hypertrophy, hyperphosphatemia, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease (COPD), psoriasis, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition, especially during small bowel syndrome, irritable bowel syndrome (IBS), diseases allergic, fatty liver disease, non-alcoholic fatty liver disease (NAFLD), liver fibrosis, non-alcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), liver cirrhosis, primary biliary cirrhosis (PBC), renal fibrosis, anorexia nervosa, bulimia nervosa and neurological disorders such as Alzheimer's disease, multiple sclerosis, schizophrenia, impaired cognition, dysmotility, Parkinson's bowel (DIOS), cystic fibrosis bowel, intestinal motility and gastroparesis.

[00256] In another embodiment, the disease or disorder associated with activation of TGR5 activity is selected from intestinal motility, gastrointestinal motility disorder, irritable bowel syndrome, chronic constipation, chronic idiopathic constipation, chronic constipation occurring in cystic fibrosis, induced constipation by opioids, chronic intestinal, pseudo-obstruction, colonic pseudo-obstruction, ulcerative colitis, inflammatory bowel disease, gastrointestinal tract disorder is associated with chronic kidney disease (stage 4 or 5), calcium supplement-induced constipation, constipation associated with use of therapeutic agent, constipation associated with neuropathic disorder, post-surgical constipation (post-operative ileus), idiopathic constipation (functional constipation or slow constipation), constipation associated with neuropathic, metabolic or endocrine disorder, constipation due to the use of drugs selected from of analgesics (e.g. opioids) antihypertensive, anticonvulsants, antidepressants, antispasmodics and antipsychotics, gastric ulcers, infectious diarrhea, leaky gut syndrome, cystic fibrosis, gastrointestinal disease, microscopic colitis, necrotizing enterocolitis, atopy, food allergy, acute inflammation , chronic inflammation, obesity-induced metabolic diseases, chronic kidney disease, kidney disease, diabetic kidney disease, heart disease, heart failure, congestive heart failure, liver disease, cirrhosis, non-alcoholic steatohepatitis, non-alcoholic fatty liver disease, steatosis, cholangitis primary sclerosing disease, primary biliary cholangitis, portal hypertension, type 1 diabetes, celiac disease multiple sclerosis, ankylosing spondylitis, rheumatoid arthritis, lupus, alopecia areata, polymyalgia rheumatica, multiple sclerosis, fibromyalgia, chronic fatigue syndrome, Sjogren's syndrome, vitiligo, thyroiditis , vasculitis, Crohn's disease, ulcerative colitis, urticaria, Rainaud syndrome, schizophrenia, autism spectrum disorders, multiple sclerosis, hepatic encephalopathy, small intestinal bacterial overgrowth, and chronic alcoholism.

[00257] Another aspect of the invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament for treating or preventing chemotherapy-induced diarrhea in a patient in need. The compound is administered to a patient who requires treatment for chemotherapy-induced diarrhea.

[00258] In another aspect, the present invention relates to the use of a compound of formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in the treatment or prevention of Diabetes mellitus type II. The method consists of administering to a patient in need of treatment for Type II Diabetes mellitus an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00259] Another aspect of the present invention relates to the use of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in the treatment or prevention of hyperphosphatemia. The use comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof. In one embodiment, the hyperphosphatemia is postprandial hyperphosphatemia.

[00260] In another aspect, the present invention relates to the use of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in the treatment or prevention of a disease renal. The use comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof. In one embodiment, the kidney disease is chronic kidney disease (CKD) or end-stage renal disease (ESRD).

[00261] Another aspect of the present invention relates to the use of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in reducing serum creatinine levels. . The use comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00262] In another aspect, the present invention relates to the use of a compound of formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in the treatment or prevention of proteinuria. The use comprises administering to a patient in need of cancer treatment for chemotherapy-induced diarrhea an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer of the same.

[00263] Another aspect of the present invention relates to the use of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, to delay the time to replacement therapy renal function (RTT). The use comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00264] In another aspect, the present invention relates to the use of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in reducing creatinine levels of FGF23. The use comprises administering to a patient in need of cancer treatment for chemotherapy-induced diarrhea an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer of the same.

[00265] Another aspect of the invention relates to the use of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer, in reducing the hyperphosphatemic effect of active vitamin D. The use comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00266] In another aspect, the present invention relates to the use of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in the attenuation of hyperparathyroidism. The use comprises administering to a patient in need of cancer treatment for chemotherapy-induced diarrhea an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer of the same. In one incarnation, hyperparathyroidism is secondary hyperparathyroidism.

[00267] Another aspect of the present invention relates to the use of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in reducing serum parathyroid hormone. (Pt). The use comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00268] In another aspect, the present invention relates to the use of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in improving endothelial dysfunction. The use comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof. In one embodiment, endothelial dysfunction is induced by postprandial serum phosphorus.

[00269] Another aspect of the present invention relates to the use of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in reducing vascular calcification. The use comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof. In one embodiment, the calcification is intimately-localized vascular calcification.

[00270] In another aspect, the present invention relates to the use of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in reducing urinary phosphorus. The method comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00271] Another aspect of the present invention relates to the use of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, to normalize serum phosphorus levels. The use comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00272] In another aspect, the present invention relates to the use of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in reducing the phosphate load in an elderly patient. The use comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00273] Another aspect of the present invention relates to the use of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, to decrease the absorption of dietary phosphate. The use comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00274] In another aspect, the present invention relates to the use of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in reducing renal hypertrophy. The use comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00275] Another aspect of the present invention relates to the use of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in reducing heart hypertrophy. The use comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof.

[00276] In another aspect, the present invention relates to the use of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in the treatment or prevention of a disorder related to intestine and stomach. The use comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof. In one embodiment, the stomach and intestine related disorder is ulcers, digestion disorders, malabsorption syndromes, short bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, celiac disease (e.g., resulting from induced enteropathy). due to gluten or celiac disease), tropical sprue, hypogammaglobulinemic sprue, enteritis, regional enteritis (Crohn's disease), ulcerative colitis, damage to the small intestine, or short bowel syndrome. In another embodiment, the stomach and intestine-related disorder is radiation enteritis, infectious or post-infectious enteritis, bone marrow transplant-induced enteritis, or damage to the small intestine due to toxic substances, or other chemotherapeutic agents.

[00277] Another aspect of the present invention relates to the use of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, in the treatment or prevention of side effects of radiation or chemotherapy. The use comprises administering to a patient in need thereof an effective amount of a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof. In some embodiments, the secondary effect of chemotherapy is diarrhea, abdominal cramps, vomiting, or structural and functional damage to the intestinal epithelium resulting from chemotherapy treatment. In one embodiment, diarrhea is induced by an immune checkpoint inhibitor.

[00278] Another aspect of the invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament for treating or preventing hyperphosphatemia. The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof. In one embodiment, the hyperphosphatemia is postprandial hyperphosphatemia.

[00279] In another aspect, the present invention relates to a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament for the treatment of kidney disease. The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof. In one embodiment, the kidney disease is chronic kidney disease (CKD) or end-stage renal disease (ESRD).

[00280] Another aspect of the invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament to reduce levels of serum creatinine. The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof.

[00281] Another aspect of the invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament for treating or preventing proteinuria. The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need of treatment for chemotherapy-induced diarrhea.

[00282] Another aspect of the present invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament for delaying the time to renal replacement therapy (RTT). The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof.

[00283] In another aspect the present invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament to reduce FGF23 levels. The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof.

[00284] Another aspect of the invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament to reduce the effect hyperphosphatemic active vitamin D. The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof.

[00285] In another aspect, the present invention relates to a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament for the mitigate hyperparathyroidism. The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need of treatment for chemotherapy-induced diarrhea. In one incarnation, hyperparathyroidism is secondary hyperparathyroidism.

[00286] Another aspect of the invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament for reducing parathyroid (Pt). The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof.

[00287] In another aspect the present invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament to improve endothelial dysfunction. The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof. In one embodiment, endothelial dysfunction is induced by postprandial serum phosphorus.

[00288] Another aspect of the invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament for reducing vascular calcification . The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof. In one embodiment, the calcification is intimately-localized vascular calcification.

[00289] In another aspect the present invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament to reduce urinary phosphorus. The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof.

[00290] Another aspect of the invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament to normalize levels of serum phosphorus. The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof.

[00291] In another aspect the present invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament to reduce Phosphate load in an elderly patient. The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof.

[00292] Another aspect of the invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament for decreasing absorption of dietary phosphate. The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof.

[00293] In another aspect the present invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament to reduce renal hypertrophy. The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof.

[00294] Another aspect of the invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament for reducing cardiac hypertrophy . The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof.

[00295] In another aspect, the present invention relates to a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament for the treatment and/or prevention of a disorder related to the intestine and stomach. The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof. In one embodiment, the stomach and intestine related disorder is ulcers, digestion disorders, malabsorption syndromes, short bowel syndrome, cul-de-sac syndrome, inflammatory bowel disease, celiac disease (e.g., resulting from induced enteropathy). due to gluten or celiac disease), tropical sprue, hypogammaglobulinemic sprue, enteritis, regional enteritis (Crohn's disease), ulcerative colitis, damage to the small intestine, or short bowel syndrome. In another embodiment, the stomach and intestine-related disorder is radiation enteritis, infectious or post-infectious enteritis, bone marrow transplant-induced enteritis, or damage to the small intestine due to toxic substances, or other chemotherapeutic agents.

[00296] Another aspect of the invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament for treating and/ or prevent a side effect of chemotherapy or radioactive treatment. The compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, is administered in an effective amount to a patient in need thereof. In some embodiments, the secondary effect of chemotherapy is diarrhea, abdominal cramps, vomiting, or structural and functional damage to the intestinal epithelium resulting from chemotherapy treatment. In one embodiment, diarrhea is induced by an immune checkpoint inhibitor.

[00297] Another aspect of the present invention relates to a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof, for use in the manufacture of a medicament for the treatment or prevention of a disease associated with TGR5 activation. In some embodiments, the disease or disorder associated with activation of TGR5 activity is selected from chemotherapy-induced diarrhea, diabetes, Type II diabetes, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ischemia, myocardial infarction, retinopathy, vascular restenosis, hypercholesterolemia, hypertriglyceridemia, dyslipidemia or hyperlipidemia, lipid disorders such as low HDL cholesterol or high LDL cholesterol, arterial hypertension, angina pectoris, coronary artery disease, atherosclerosis, cardiac hypertrophy, hyperphosphatemia, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease (COPD), psoriasis, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition, especially during small bowel syndrome, irritable bowel syndrome (IBS), allergic diseases, fatty liver disease, non-alcoholic fatty liver disease (NAFLD), liver fibrosis, non-alcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), liver cirrhosis, primary biliary cirrhosis (PBC), renal fibrosis, anorexia nervosa, intestinal motility, bulimia nervosa and neurological disorders such as Alzheimer's disease, multiple sclerosis, schizophrenia and impaired cognition.

[00298] Another aspect of the invention is directed to pharmaceutical compositions comprising a compound of Formula (I'), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer or tautomer thereof and a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may include a further excipient, diluent or surfactant.

[00299] In some embodiments, methods for treating a disease or disorder associated with TGR5 modulation include chemotherapy-induced diarrhea, diabetes, Type II diabetes, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ischemia, myocardial infarction, retinopathy, vascular restenosis, hypercholesterolemia, hypertriglyceridemia, dyslipidemia or hyperlipidemia, lipid disorders such as low HDL cholesterol or high LDL cholesterol, arterial hypertension, angina pectoris, coronary artery disease, atherosclerosis, hypertrophy cardiac, hyperphosphatemia, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease (COPD), psoriasis, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition, especially during small bowel syndrome, irritable bowel syndrome (IBS), allergic diseases , fatty liver disease, non-alcoholic fatty liver disease (NAFLD), liver fibrosis, non-alcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), liver cirrhosis, primary biliary cirrhosis (PBC), renal fibrosis, anorexia nervosa, bulimia nervous and neurological disorders such as Alzheimer's disease, multiple sclerosis, schizophrenia, intestinal motility and impaired cognition comprises administering to a patient suffering from at least one of said diseases or disorder a compound of Formula (1'). In another embodiment, the disease or disorder associated with modulation of TGR5 activity is intestinal motility.

[00300] A therapeutic use of the compounds or compositions of the present invention that activate TGR5 is to provide treatments to patients or subjects suffering from one or more diseases or disorders selected from chemotherapy-induced diarrhea, diabetes, Type II diabetes, gestational diabetes, fasting glucose impaired, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ischemia, myocardial infarction, retinopathy, vascular restenosis, hypercholesterolemia, hypertriglyceridemia, dyslipidemia or hyperlipidemia, lipid disorders such as low HDL cholesterol or high LDL cholesterol, arterial hypertension, angina pectoris, coronary artery disease, atherosclerosis, cardiac hypertrophy, hyperphosphatemia, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease (COPD), psoriasis, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition, especially during the small intestine, irritable bowel syndrome (IBS), allergic diseases, fatty liver disease, non-alcoholic fatty liver disease (NAFLD), liver fibrosis, non-alcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), liver cirrhosis, cirrhosis primary biliary tract (PBC), renal fibrosis, anorexia nervosa, bulimia nervosa, and neurological disorders such as Alzheimer's disease, multiple sclerosis, schizophrenia, and impaired cognition.

[00301] The disclosed compounds of the invention can be administered in amounts effective to treat or prevent a disorder and/or prevent its development in subjects.

[00302] The compounds of the invention can be administered in therapeutically effective amounts in a combinational therapy with one or more therapeutic agents (pharmaceutical combinations) or modalities, for example, non-drug therapies. For example, synergistic effects may occur with other antidiabetic, antidiarrheal, anti-obesity or anti-inflammatory substances. When compounds of the invention are administered in conjunction with other therapies, dosages of the co-administered compounds will obviously vary depending on the type of co-drug used, the specific drug used, the condition being treated, and so on.

[00303] Combination therapy includes administering the subject compounds in additional combination with other biologically active ingredients (such as an anti-diabetes agent (i.e., a DPP-IV inhibitor, insulin, etc.), an antidiarrheal agent or an anti-obesity agent) and non-drug therapies (such as, but not limited to, surgery). For example, the compounds of the invention can be used in combination with other pharmaceutically active compounds, preferably compounds that are capable of enhancing the effect of the compounds of the invention. The compounds of the invention can be administered simultaneously (as a single preparation or separate preparation) or sequentially to another drug therapy or treatment modality. In general, a combination therapy involves the administration of two or more medications during a single cycle or course of therapy.

[00304] In some embodiments, the disclosure provides a pharmaceutical composition comprising any of the foregoing compounds (i.e., a compound of Formula (I')), a pharmaceutically acceptable carrier or adjuvant, and at least one additional biologically active agent. In some embodiments, the pharmaceutical composition comprises one or more additional biologically active agents. In some embodiments, at least one additional biologically active agent is selected from dipeptidyl peptidase 4 (DPP-4) inhibitors, biguanidines, sulfonylureas, α-glucosidates, thiazolidinediones, incretin mimetics, CB1 antagonists, VPAC2 agonists, activators of glucokinase, glucagon receptor antagonists, PEPCK inhibitors, SGLT1 inhibitors, SGLT2 inhibitors, IL-1 receptor antagonists, SIRT1 activators, SPPARMs or 11 βHSD1 inhibitors.

[00305] In other embodiments, at least one additional biologically active agent prolongs the TGR5-mediated GLP-1 or GLP-2 signal. In other embodiments, at least one additional biologically active agent is a DPP-4 inhibitor. In still other embodiments, the at least one additional biologically active agent is a DPP-4 inhibitor selected from sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin, gemigliptin, omarigliptin, ordutogliptin.

[00306] In other embodiments, at least one additional biologically active agent is selected from metformin or another biguanidine, glyburide or other sulfonylurea; acarbose or other α-glucosidase inhibitor; rosiglitazone or other thiazolidinedione and exenatide, liraglutide or other incretin mimic; mesalazine and its prodrugs Olsalazine, Sulfasalazine or Balsalazide; agents useful in the treatment of chemotherapy-induced diarrhea including, but not limited to, Loperamide, tincture of opium, Lomotil, Octreotide, Elsiglutide, Teduglutide or other GLP-2 mimetics; corticosteroids including, but not limited to, Cortisone, Prednisone, Hydrocortisone, Methylprednisolone or Budesonide; immunosuppressants including, but not limited to, Mercaptopurine, Azathioprine, Methotrexate, Cyclosporine or Tacrolimus; JAK kinase inhibitors including, but not limited to, Tofacitinib or Filgotinib; biological immunomodulators including, but not limited to, Infliximab, Adalimumab, Certolizumab or Natalizumab; FXR (Farnesoid X receptor) agonists including, but not limited to, obeticholic acid, INT-767, Px-104, or LJN-452; agents useful in the treatment of NASH (non-alcoholic steatohepatitis) including, but not limited to, eicosapentaenoic acid ethyl ester, cenicriviroc mesylate, aramcol, emricasan or tipelukast; and agents used to treat hyperphosphatemia including, but not limited to, Sevelamer, Tenapanor, sucroferric oxyhydroxide, ferric citrate, Bixalomer, Lanthane carbonate, calcium acetate, niacin, Fermagate or cholestylan.

[00307] Administration of the disclosed compounds can be carried out through any mode of administration for therapeutic agents. These modes include systemic or local administration, such as oral, nasal, parenteral, transdermal, subcutaneous, vaginal, buccal, rectal or topical administration methods.

[00308] Depending on the intended mode of administration, the disclosed compositions may be in solid, semi-solid or liquid dosage form, such as, for example, injectables, tablets, suppositories, pills, delayed-release capsules, elixirs, tinctures, emulsions, syrups, powders, liquids, suspensions or the like, sometimes in unit dosages and consistent with conventional pharmaceutical practices. Likewise, they can also be administered intravenously (bolus and infusion), intraperitoneal, subcutaneous or intramuscular, as well as all forms of use well known to those skilled in pharmaceutical techniques.

[00309] Illustrative pharmaceutical compositions are tablets and gelatin capsules comprising a compound of the Invention and a pharmaceutically acceptable carrier, such as a) a diluent, for example purified water, triglyceride oils, such as hydrogenated or partially hydrogenated vegetable oil, or mixtures thereof, corn oil, olive oil, sunflower oil, safflower oil, fish oils such as EPA or DHA, or their esters or triglycerides or mixtures thereof, omega-3 fatty acids or their derivatives, lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, sodium, saccharin, glucose and/or glycine; B) a lubricant, for example, silica, talc, stearic acid, its magnesium or calcium salt, sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and/or polyethylene glycol ; for tablets too; C) a binder, for example, magnesium and aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, magnesium carbonate, natural sugars such as glucose or beta-lactose, corn sweeteners, natural gums and synthetics, such as arachnid gum, tragacanth or sodium alginate, waxes and/or polyvinylpyrrolidone, if desired; D) a disintegrant, for example, starches, agar, methyl cellulose, bentonite, xanthan gum, algic acid or its sodium salt or effervescent mixtures; E) absorbent, coloring, flavoring and sweetener; F) an emulsifier or dispersing agent, such as Tween 80, Labrasol, HPMC, DOSS, caproil 909, labrafac, labrafil, peceol, transcutol, capmul MCM, capmul PG-12, captex 355, gelucire, vitamin E TGPS or other acceptable emulsifier; and/or g) an agent that enhances absorption of the compound such as cyclodextrin, hydroxypropylcyclodextrin, PEG400 and PEG200.

[00310] Liquids, particularly injectable compositions can, for example, be prepared by dissolving, dispersing, etc. For example, the disclosed compound is dissolved in or mixed with a pharmaceutically acceptable solvent such as, for example, water, saline, aqueous dextrose, glycerol, ethanol and the like, to thereby form an injectable isotonic solution or suspension. Proteins such as albumin, chylomicron particles or serum proteins can be used to solubilize the disclosed compounds.

[00311] The disclosed compounds can also be formulated as a suppository that can be prepared from fatty emulsions or suspensions; using polyalkylene glycols such as propylene glycol as the carrier.

[00312] Parenteral injectable administration is generally used for subcutaneous, intramuscular or intravenous injections and infusions. Injectables can be prepared in conventional forms, either as liquid solutions or suspensions or solid forms suitable for dissolution in liquid prior to injection.

[00313] Another aspect of the invention is directed to pharmaceutical compositions comprising a compound of Formula (I') and a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may include a further excipient, diluent or surfactant.

[00314] The dosage regimen using the disclosed compounds is selected according to a variety of factors including type, species, age, weight, sex and medical condition of the patient; the severity of the condition being treated; the route of administration; the patient's kidney or liver function; and the particular disclosed compound that was used. A physician or veterinarian skilled in the art can easily determine and prescribe the effective amount of drug required to prevent, counter or halt the progress of the condition.

[00315] Effective dosage amounts of the disclosed compounds, when used for the indicated effects, range from about 0.5 mg, to about 5000 mg of the disclosed compound as needed to treat the condition. Compositions for in vivo or in vitro use may contain about 0.5, 5, 20, 50, 75, 100, 150, 250, 500, 750, 1000, 1250, 2500, 3500 or 5000 mg of the disclosed compound, or of a range from one quantity to another quantity in the dose list. In one embodiment, the compositions are in the form of a tablet that can be scored.

Examples

[00316] The disclosure is further illustrated by the following examples and summary schemes, which should not be interpreted as limiting this disclosure, in scope or spirit, as to the specific procedures described in this document. It should be understood that the examples are provided to illustrate certain embodiments and that no limitation of the scope of this disclosure is hereby intended. It should also be understood that it is possible to have resources in several other modalities, modifications and equivalents thereof, which may suggest the same to those skilled in the art, without deviating from the spirit of the present disclosure and/or the scope of the attached claims.

Analytical Methods, Materials and Instrumentation

[00317] Unless otherwise indicated, reagents and solvents were used as received from commercial suppliers. Proton nuclear magnetic resonance (NMR) spectra were obtained with a Varian spectrometer at 400 MHz. Spectra are given in ppm (δ) and coupling constants, J, are reported in Hertz. Tetramethylsilane (TMS) or the solvent peak was used as an internal standard. Low-resolution, purity mass spectrometry data were measured using a Finnigan Surveyor thermo HPLC system with Surveyor photographic diode array (PDA) detection and an LCQ FleetTM thermo ion trap mass spectrometer. Column: Synergi 4 micron, hydro-RP80A, 30x2.0 mm, flow rate: 0.500 mL/min; Solvent A (water +0.1% formic acid), Solvent B (acetonitrile +0.1% formic acid); Gradient: 2% B at = 0 to 95% B at 3 min to 95% B at 3.3 min. Abbreviations used in the following examples and elsewhere in this document are:

[00318] To a 100 mL round bottom flask purged and maintained under an inert nitrogen atmosphere, charged with 4-chloropyridine-3-carbonitrile (997.5 mg, 7.20 mmol, 1.00 equiv), toluene ( 50 mL), (2-cyclopropoxyphenyl)boronic acid (1.2 g, 6.74 mmol, 0.95 equiv), Pd(OAc)2 (16.14 mg, 0.07 mmol, 0.01 equiv), K3PO4 (3.11 g, 14.65 mmol, 2.00 equiv) and butyldi-1-adamantylphosphine (358.5 mg, 0.144 mmol, 0.02 equiv). The resulting solution was stirred for 2 h at 100°C in an oil bath. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:5). This resulted in 1.6 g (94%) of 4-(2-cyclopropoxyphenyl)pyridine-3-carbonitrile (A-1a) as light yellow oil. Step 2. 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (A-1):

[00319] To a 250 mL 3-neck round-bottom flask purged and maintained under an inert nitrogen atmosphere, charged with 4-(2-cyclopropoxyphenyl)pyridine-3-carbonitrile (1.7 g, 7.20 mmol, 1.00 equiv) and ether (200 mL). This was followed by the addition of Ti(OiPr)4 (3.4 mL, 1.66 equiv) at -78°C. To this was added 3M EtMgBr (7.86 mL, 3.32 equiv) at -78°C. To the mixture was added BF3-Et2O (3.4 mL, 3.03 equiv). The resulting solution was stirred for 5 min at -78°C.oC in a solution of N2/EtOH. The resulting solution was allowed to react, with stirring, for a further 2 h at room temperature. The resulting solution was allowed to react, with stirring, for a further 1 h at room temperature. The f value of the solution was adjusted to 1-2 with 31M HCl. The resulting solution was extracted with 100 mL of ethyl acetate and the aqueous layers combined. Sodium hydroxide (1 mol/L) was used to adjust f to 10. The resulting solution was extracted with 100 mL ethyl acetate, and the organic layers combined and concentrated under vacuum. The residue was applied to a silica gel column with dichloromethane/methanol (10:1). This resulted in 580 mg (30%) of intermediate (A-1) as light yellow oil.

[00320] The above general method for the synthesis of Intermediate A1 in Example 1 can be used to prepare intermediates (Int.) A-2-A-18 in Table 1 below starting from 4-chloropyridine-3-carbonitrile and the appropriate boronate .Table 1: Example 2: Intermediate A-19 1-[4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl] cyclopropan-1-amine

[00321] To a 500 mL round bottom flask purged and maintained under an inert nitrogen atmosphere, charged with 4-chloropyridine-3-carbonitrile (5.75 g, 41.50 mmol, 1.00 equiv) and ether ( 150 mL). This was followed by addition of Ti(OiPr)4 (17.7 g, 1.50 equiv.) dropwise with stirring at -78oC in 30 min. To this was added EtMgBr (34.6 mL, 2.50 equiv, 3M in Et2O) dropwise with stirring at -78oC in 30 min and stirred for 2 h at room temperature. To the mixture was added BF3-Et2O (23.56 g, 4.00 equiv). The resulting solution was stirred for 2 h at room temperature. The reaction was then quenched by the addition of 1M hydrogen chloride. The f value of the solution was adjusted to 10 with sodium hydroxide (4 mol/L). The resulting solution was extracted with 3 x 80 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with dichloromethane/methanol (0-10%). The collected fractions were combined and concentrated under vacuum. This resulted in 2 g (29%) of Intermediate A-19a as yellow oil. Step 2. Tert-Butyl N-[1-(4-chloropyridin-3-yl)cyclopropyl]carbamate (A-19b):

[00322] To a 250 mL round bottom flask, charged with 1-(4-chloropyridin-3-yl)cyclopropan-1-amine (1.9 g, 11.27 mmol, 1.00 equiv), tetra- hydrofuran (30 mL), water (30 mL), sodium carbonate (4.78 g, 45.10 mmol, 4.00 equiv), Boc2O (3.688 g, 16.90 mmol, 1.50 equiv.). The resulting solution was stirred overnight at room temperature. The reaction was cooled by adding 50 mL of water. The resulting solution was extracted with 3x50 mL of ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0-30%). The collected fractions were combined and concentrated under vacuum. This resulted in 1.2 g (40%) of Intermediate A-19b as a light yellow solid. Step 3. Tert-Butyl N-[1-[4-(2-hydroxyphenyl)pyridin-3-yl]cyclopropyl]carbamate (A-19c):

[00323] To an 8 mL round bottom flask purged and maintained under an inert nitrogen atmosphere, charged with N-[1-(4-chloropyridin-3-yl)cyclopropyl] tert-butyl carbamate (100 mg, 0 .37 mmol, 1.00 equiv), (2-hydroxyphenyl)boronic acid (77 mg, 0.56 mmol, 1.50 equiv), K3PO4 (158 mg, 0.74 mmol, 2.00 equiv), Pd ( OAc)2 (4 mg, 0.02 mmol, 0.05 equiv), butyldi-1-adamantylphosphine (13 mg, 0.10 equiv) and toluene (1 mL). The resulting solution was stirred for 3 h at 100oC. The resulting mixture was concentrated under vacuum. The resulting solution was extracted with 3x30 mL of ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with dichloromethane/methanol (0-5%). The collected fractions were combined and concentrated under vacuum. This resulted in 30 mg (25%) of Intermediate A-19c as a light yellow solid. Step 4. Tert-Butyl N-(1-[4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl]cyclopropyl)carbamate (A-19d):

[00324] For a 25 mL round bottom flask, charged with tert-butyl N-[1-[4-(2-hydroxyphenyl)pyridin-3-yl]cyclopropyl]carbamate (50 mg, 0.15 mmol, 1.00 equiv), 3-iodooxethane (34 mg, 0.18 mmol, 1.20 equiv), potassium carbonate (42 mg, 0.30 mmol, 2.00 equiv), N,N-dimethylformamide (10 mL ). The resulting solution was stirred overnight at 90 oC in an oil bath. The reaction was cooled by adding 10 mL of water. The resulting solution was extracted with 3x20 mL of ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0-50%). The collected fractions were combined and concentrated under vacuum. This resulted in 50 mg (85%) of Intermediate A-19d as a light yellow oil. Step 5. 1-[4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl]cyclopropan-1-amine (A-19):

[00325] For a 25 mL round bottom flask, charged with tert-butyl N-(1-[4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl]cyclopropyl)carbamate (50 mg, 0.13 mmol, 1.00 equiv), dichloromethane (4 mL), trifluoroacetic acid (4 mL). The resulting solution was stirred for 1 h at room temperature. The resulting mixture was concentrated under vacuum. This resulted in 36 mg (crude) of Intermediate A-19 as a yellow oil.

[00326] Intermediates A-20, A-21 and A-22 shown in Table 2 below were prepared using the route shown above in Example 2 to make A-19. Alkylation of the phenol intermediate A19c with the halide, epoxide or other appropriate electrophilic reagent and removal of the Boc protecting group using the general synthetic method described above provides Intermediates A-20, A-21 and A-22. The substitution of appropriate reagents and conditions in Step 4 of Example 2 is generally known to those skilled in the art. Table 2: METHOD A:Example 3: 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-[(2,5-dichlorophenyl)methyl] cyclopropan-1-amine (I-1)

[00327] To a 50 mL round-bottom flask purged and maintained under an inert nitrogen atmosphere, charged with 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (200 mg, 0 .75 mmol, 1.00 equiv), dichloromethane (20 mL), 2,5-dichlorobenzaldehyde (183 mg, 1.05 mmol, 1.00 equiv), and NaBH(OAc)3 (1.34 g, 6.32 mmol, 6.00 equiv). The resulting solution was stirred overnight at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:5). This resulted in 100 mg (31%) of Compound I-1 as a light yellow solid. MS (ES, m/z): 425.05 [M+H]+; 1H NMR (400 MHz, CDCI3): δ ppm 8.63 (s, 1H), 8.54 - 8.52 (d, 1H), 7.43 - 7.34 (m, 2H), 7.26 - 7.20 (m, 2H), 7.14 - 7.03 (m , 4H), 3.67 - 3.59 (m, 3H), 2.12 (brs, 1H), 0.84 (s, 4H), 0.73 - 0.64 (m, 2H), 0.62 - 0.52 (m, 2H).

[00328] The compounds in Table 1, Compounds I-2 to I-40 and I-42 to I-44, were prepared using Method A described above in this document in Example 1 and methods generally known to those skilled in the art from commercial or known starting materials and amine intermediates A2-A22 from graphs 1 and 2 above. Table 1: Compounds I-1 to I-40 and I-42 to I-44 Example 4: 3-[1-[(2,5-dichlorophenyl)methoxy]cyclopropyl]-4-(2-methoxyphenyl)pyridine (I-45)

[00329] A 100 mL 3-neck round bottom flask was charged with 4-chloropyridine-3-carboxylic acid (1 g, 6.35 mmol, 1.00 equiv), dichloromethane (15 mL), methanol (6 mL). This was followed by the addition of 2.0 M TMS-diazomethane in Et2O (4.76 mL, 1.50 equiv.) dropwise with stirring at 0 °C. The resulting solution was stirred for 1 h at 0 °C. The resulting mixture was concentrated in vacuo. This resulted in 1.4 g of methyl 4-chloropyridine-3-carboxylate (Intermediate 45a) as white oil, which was used in the next experiment without further purification. Step 2. Methyl 4-(2-methoxyphenyl)pyridine-3-carboxylate (Intermediate 45b)

[00330] A 100 mL round bottom flask was charged with methyl 4-chloropyridine-3-carboxylate (900 mg, 5.25 mmol, 1.00 equiv), (2-methoxyphenyl)boronic acid (1.2 g , 7.90 mmol, 1.50 equiv), Pd (OAc)2 (11.7 mg, 0.05 mmol, 0.01 equiv), K3PO4 (2.22 g, 10.46 mmol, 2.00 equiv ), Butyl di-1-adamantylphosphine (37.5 mg, 0.02 equiv), toluene (50 mL). The resulting solution was stirred for 1.5 h at 100°C. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (14.6:100). This resulted in 0.2 g (16%) of methyl 4-(2-methoxyphenyl)pyridine-3-carboxylate (Intermediate 45b) as a yellow oil. Step 3. 1-[4-(2-methoxyphenyl)pyridin-3-yl]cyclopropan-1-ol (Intermediate 45c)

[00331] A 50 mL 3-neck round bottom flask, purged and maintained under an inert nitrogen atmosphere was charged with a solution of Cp.2ZrCl2 (1.20 g, 4.11 mmol, 2.00 equiv) in toluene (10 mL). This was followed by addition of bromo(ethyl)magnesium (2.74 mL, 4.00 equiv.) dropwise with stirring at 0oC. The mixture was stirred for 1 h at 0 degrees C. To this was added a solution of methyl 4-(2-methoxyphenyl)pyridine-3-carboxylate (500 mg, 2.06 mmol, 1.00 equiv) in toluene (5 mL) dropwise with stirring at 0oC. The resulting solution was stirred for 3 h at 0°C. The reaction was then cooled by adding 10 mL of NH4Cl (aq). The resulting solution was extracted with 3x30 mL of dichloromethane and the organic layers were combined and dried over sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with PE:EA (1:1). This resulted in 150 mg (30%) of 1-[4-(2-methoxyphenyl)pyridin-3-yl]cyclopropan-1-ol (Intermediate 45c) as light yellow oil. Step 4. 3-[1-[(2,5-dichlorophenyl)methoxy]cyclopropyl]-4-(2-methoxyphenyl)pyridine (I-45)

[00332] A 50 mL round bottom flask was charged with a solution of 1-[4-(2-methoxyphenyl)pyridin-3-yl]cyclopropan-1-ol (150 mg, 0.62 mmol, 1.00 equiv) in N,N-dimethylformamide (5 mL), 2-(bromomethyl)-1,4-dichlorobenzene (179 mg, 0.75 mmol, 1.20 equiv). This was followed by the addition of sodium hydride (37 mg, 1.54 mmol, 1.50 equiv) in several batches at 0 oC. The resulting solution was stirred for 2 h at 0°C. The resulting solution was diluted with 10 mL of ethyl acetate. The reaction was cooled by adding 10 mL of. The resulting solution was extracted with 3x30 mL of ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:5). This resulted in 121.5 mg (49%) of I-45 as a light yellow solid. MS (ES, m/z): 400 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 8.63 (s, 1H), 8.49 (d, J =5.1Hz, 1H), 7.38-7.44 (m, 1H), 7.19-7.30 (m, 4H), 6.97-7.02 (m, 3H), 4.35 (s, 2H), 3.51 (s, 3H), 1.03 (s, 4H).Example 5: 1-Cyclopropoxy-2-iodobenzene (IntermediateA-23)

[00333] A 2000 mL round bottom flask was charged with 2-iodophenol (50 g, 227.26 mmol, 1.00 equiv), DMA (750 mL), Cs2CO3 (185.1 g, 566.35 mmol, 2.49 equiv.), bromocyclopropane (55 g, 454.64 mmol, 2.00 equiv). The resulting solution was stirred for 3 h at 120oC. The resulting solution was diluted with 2000 mL of H2O. The resulting solution was extracted with 3 x 500 mL ethyl acetate, and the organic layers combined and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether. This resulted in 38 g (64%) of 1-cyclopropoxy-2-iodobenzene (A-23a) as an off-white oil. Step 2. (2-cyclopropoxyphenyl)boronic acid (Intermediate A-23b)

[00334] A 1000 mL 3-neck round bottom flask was purged and maintained under an inert nitrogen atmosphere and charged with 1-cyclopropoxy-2-iodobenzene (75 g, 288.38 mmol, 1.00 equiv), THF (600 mL). This was followed by the addition of butyllithium (138 mL) dropwise with stirring at -78 oC. The above mixture was stirred for 1 h at -78°C. To this was added trimethyl borate (61.2 g, 588.95 mmol, 2.04 equiv.) dropwise with stirring at -78°C. The above mixture was stirred for 1 h at -78°C. The resulting solution was stirred for 1 h at 15-25oC. The reaction was cooled by adding 150 mL of MeOH. The resulting mixture was concentrated under vacuum. The crude product was washed with hexane. Solids were collected by filtration. This resulted in 55 g of dimethyl (2-cyclopropoxyphenyl) (A-23b) boronate as a white solid. A 1000 mL round bottom flask was charged with dimethyl(2-cyclopropoxyphenyl)boronate (55 g, 266.9 mmol, 1.00 equiv), water (500 mL), Conc. HCl (30 mL). The resulting solution was stirred for 1 h at 15-25oC. The solids were collected by filtration and dried. This resulted in 41 g of (2-cyclopropoxyphenyl)boronic acid as a white solid. It was then purified by recrystallization from hexane (150-200 ml) and gave 35 g (68%) of product as a white solid. Step 2. Methyl 4-chloronicotinate hydrochloride (Intermediate A23c)

[00335] 4-Chloronicotinic acid (3.00 g, 19 mmol) was slurried in DCM (25 mL) and a solution of oxalyl chloride (4.1 mL, 6.1 g, 48 mmol) in DCM was added ( 25 mL) dropwise over 15 min. After addition, DMF was added (7 x 100μ aliquots over 1 hour). The slurry was stirred for 30 min after the last addition. The reaction mixture was cooled on ice and MeOH (15 mL) was slowly added. The resulting solution was stirred at 0 oC for 15 minutes and then at room temperature for another 30 minutes. Toluene (10 mL) was added and the solvents were removed under reduced pressure to give the crude product as a tan solid. The solid was triturated with 50% EtOAc/heptane (15 mL) and collected in a Buchner funnel. The solids were washed with 50% EtOAc/heptane (2 x 10 mL) and then dried under vacuum to give the HCl salt of the title compound. (A-23c) as a yellowish-brown powder (3.93 g, 99%). Step 3. Methyl 4-(2-cyclopropoxyphenyl)pyridine-3-carboxylate (Intermediate A23d)

[00336] A 250 mL 3-neck round bottom flask, purged and maintained under an inert nitrogen atmosphere, was charged with (2-cyclopropoxyphenyl)boronic acid (940 mg, 5.28 mmol, 1.10 equiv), K3PO4 (4.08 g, 19.2 mmol, 4.00 equiv), methyl 4-chloropyridine-3-carboxylate hydrochloride (1.0 g, 4.81 mmol, 1.00 equiv), Pd (OAc) 2 (22 mg, 0.10 mmol, 0.02 equiv), Xfos (138 mg, 0.29 mmol, 0.06 equiv), tetrahydrofuran (14 mL), water (0.35 mL, 4.00 equiv). The resulting solution was stirred for 1 h at 75 oC in an oil bath. The reaction was monitored by LCMS. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 40 mL of sodium bicarbonate (sat.). The resulting solution was extracted with 3 x 50 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1 x 50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (2.2 g) was purified by flash light preparative HPLC with the following conditions (CombiFlash-1): Column, silica gel; mobile phase, 0% ethyl acetate/petroleum ether increasing to 25.7% in 30 min; Detector, UV 254 nm. This resulted in 951 mg (73%) of methyl 4-(2-cyclopropoxyphenyl)pyridine-3-carboxylate (A-23d) as yellow oil. Step 4. 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-ol (Intermediate A-23)

[00337] A 500 mL three-neck round bottom flask was charged with a solution of Cp2ZrCl2 (14.77 g, 50.64 mmol, 2.10 equiv) in fresh distilled toluene (400 mL). The flask was evacuated and washed three times with N2. This was followed by adding EtMgBr (3M in ether) (33.7 mL, 101.3 mmol, 4.2 equiv.) dropwise with stirring at 0 oC in 20 min and stirring for 40 min. To this end, a solution of A-23d (6.5 g, 24.14 mmol, 1.00 equiv) in toluene (60 mL) was added dropwise with stirring at 0 oC in 20 min. The resulting solution was stirred overnight at room temperature. The reaction was then cooled by adding 50 mL of NH4Cl. Sat. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 300 mL of water. The resulting solution was extracted with 5x500 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2x500 mL of saturated brine. The mixture was dried over anhydrous sodium sulfate. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:3 to 1:1). The crude product was recrystallized from DCM/hexane in a ratio of 1:10. This resulted in 2.5 g (39%) of 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-ol (A-23) as a light yellow solid.Example 6: 1-( 4-(2-fluorophenyl)pyridin-3-yl)cyclopropan-1-ol (Intermediate A-24); 1-(4-(2-cyclobutoxyphenyl)pyridin-3-yl)cyclopropan-1-ol (Intermediate A-25); 1-(4-(2-(oxetan-3-yloxy)phenyl)pyridin-3-yl)cyclopropan-1-ol(Intermediate A-26)

[00338] Intermediates A24-A26 were prepared from commercial or known raw materials, according to the procedure used for the preparation of Intermediate 45c in example 4.

[00339] The compounds in Table 2 below, Compounds I-46 to I-56, were prepared from commercial or known starting materials, in accordance with the procedure used for the preparation of Compound I-45 in Example 4 and generally accepted methods. known to those skilled in the art. Table 2. Compounds I-46 to I-56. Example 7: 1-[1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]-1-[(2,5-dichloro-phenyl)methyl]urea (I-57)

[00340] A 50 mL round bottom flask charged with 1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]-N-[(2,5-dichlorophenyl)methyl]cyclopropan-1-amine (I-1 , 50 mg, 0.12 mmol, 1.00 equiv), DCM (10 mL) and chlorosulfonyl isocyanate (50 mg, 0.35 mmol, 3.00 equiv). This was followed by the addition of water (10 mL) after 2 h. The resulting solution was stirred for 3 h at room temperature. The resulting solution was extracted with 3 x 25 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by preparative HPLC with the following conditions: Column, Atlantis Prep T3 OBD column, 19 x 150 mm 5 m 10 nm; mobile phase, water with 10 mmol NH4HCO3 and MeCN (20.0% MeCN at 50.0% in 8 min); Detector, 254 nm. This resulted in 5.3 mg (10%) of I-57 as a white solid. MS (ES, m/z): 468 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 8.85 (s, 1H), 8.42 (d, J = 4.9 Hz, 1H), 7.60-7.47 (m, 2H), 7, 27 (d, J = 8.5 Hz, 1H), 7.22-7.12 (m, 3H), 7.10 (d, J = 5.0 Hz, 1H), 6.89 (d, J = 2.4 Hz, 1H), 3.87-3.74 (m, 3H), 1.81-1.22 (m, 2H), 1.11 (s, 1H), 0.99 (s, 1H), 0.78-0.69 (m, 2H), 0.64 (s, 2H). Example 8: 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-[(2 ,5-dichlorophenyl)methyl]-N-methylcyclopropan-1-amine (I-58)

[00341] A 50 mL round bottom flask was charged with 1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]-N-[(2,5-dichlorophenyl)methyl]cyclopropan-1-amine (100 mg, 0.24 mmol, 1.00 equiv), formalin (40%) (0.7 mL, 23.45 mmol, 10.00 equiv), methanol (20 mL), and AcOH (1 mg, 0.02 mmol , 0.10 equiv). This was followed by the addition of NaBH(OAc)3 (300 mg, 1.42 mmol, 6.00 equiv) in portions at 0 oC. The resulting solution was stirred for 3 h at room temperature. The reaction was cooled by adding 5 mL of water. The resulting solution was extracted with 4 x 60 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3 x 30 ml of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by preparative HPLC with the following conditions: Column, Gemini-NX C18, 21.2 x 150 mm 5; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (40.0% MeCN to 70.0% in 10 min); Detector, 254 nm. This resulted in 68.8 mg (67%) of Compound I-58 as a white solid. MS (ES, m/z): 439 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 8.66 (s, 1H), 8.42 (d, J = 5.1 Hz, 1H), 7.48-7.38 (m, 2H), 7, 36-7.25 (m, 2H), 7.26-7.17 (m, 2H), 7.13 (d, J = 5.2 Hz, 1H), 7.07-7.03 (m, 1H), 3.77 (tt, J = 6.0, 2.9 Hz, 1H), 3.51 (s, 2H), 1.98 (s, 3H), 1.04-0.94 (m , 4H), 0.81-0.71 (m, 2H), 0.55 (h, J = 2.8 Hz, 2H). Example 9: 4-(2-cyclopropoxyphenyl)-3-[3-[ (2,5-dichlorophenyl)methoxy]oxetan-3-yl]pyridine (I-59) Step 1. 3-bromo-4-(2-cyclopropoxyphenyl)pyridine (Intermediate 59a)

[00342] A 100 mL round bottom flask was purged and maintained under an inert nitrogen atmosphere, charged with 3-bromo-4-iodopyridine (568 mg, 2.00 mmol, 1.00 equiv), acid (2- cyclopropoxyphenyl)boronic acid (430 mg, 2.42 mmol, 2.00 equiv), sodium carbonate (640 mg, 6.04 mmol, 3.00 equiv), potassium hydroxide (112 mg, 2.00 mmol, 1, 00 equiv). The above compounds were dissolved in tetrahydrofuran (40 mL) and water (20 mL). This was followed by the addition of Pd(Pf3)4 (230 mg, 0.20 mmol, 0.10 equiv.) in portions with stirring at room temperature. The resulting solution was heated at reflux for 20 h. The resulting mixture was concentrated under vacuum. The resulting solution was extracted with 3 x 40 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2 x 100 ml of water and 1 x 100 ml of sat. sodium chloride. The mixture was dried over anhydrous sodium sulfate. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 500 mg (86%) of 3-bromo-4-(2-cyclopropoxyphenyl)pyridine (59a) as a brown oil. Step 2. 3-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]oxetan-3-ol (Intermediate 59b)

[00343] A 50 mL round bottom flask was purged and maintained under an inert nitrogen atmosphere, charged with 3-bromo-4-(2-cyclopropoxyphenyl)pyridine (59a, 290 mg, 1.00 mmol, 1.00 equiv), ether (30 ml). This was followed by the addition of n-BuLi (2.5 M in hexane) (0.8 mL, 2.00 equiv) dropwise with stirring at -78 oC. The resulting solution was stirred for 15 min at -78 oC. To this was added a solution of oxetan-3-one (144 mg, 2.00 mmol, 2.00 equiv) in tetrahydrofuran (1 mL) dropwise with stirring at -78°C. The resulting solution was allowed to react, with stirring, for a further 1 h at -78 oC. The resulting solution was allowed to react, with stirring, for a further 14 h at room temperature. The reaction was cooled by adding 20 mL of water. The resulting solution was extracted with 3 x 30 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1 x 50 ml of water and 1 x 50 ml of sat. sodium chloride. The mixture was dried over anhydrous sodium sulfate. The residue was applied to a silica gel column with ethyl acetate. This resulted in 160 mg (57%) of 3-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]oxetan-3-ol (59b) as a colorless oil. Step 3. 4-(2-cyclopropoxyphenyl)-3-[3-[(2,5-dichlorophenyl)methoxy]oxetan-3-yl]pyridine (I-59)

[00344] A 25 mL round bottom flask was charged with 3-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]oxetan-3-ol (100 mg, 0.35 mmol, 1.00 equiv), 2-(bromomethyl)-1,4-dichlorobenzene (169 mg, 0.70 mmol, 2.00 equiv), N,N-dimethylformamide (10 mL). Sodium hydride (60% in oil) (56 mg, 2.33 mmol, 4.00 equiv) was then added. The resulting solution was stirred for 1 h at room temperature. The reaction was cooled by adding 15 mL of water. The resulting solution was extracted with 3 x 30 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1 x 50 ml of water and 1 x 50 ml of sat. sodium chloride. The mixture was dried over anhydrous sodium sulfate. The residue was applied to a silica gel column with ethyl acetate/hexane (1:1). The crude product was purified by preparative HPLC with the following conditions: Column, Gemini-NX 5u C18 110A, AXIA Pack, 150 x 21.2 mm; mobile phase, water with 10 mmol NH4HCO3 and MeCN (66.0% MeCN to 86.0% in 8 min); Detector, 254 nm. This resulted in 58 mg (37%) of 59 as a white solid. MS (ES, m/z): 442 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ 0.30-0.55 (m, 2H), 0.60-0.80 (m, 2H), 3.68 (s, 1H), 4.15 -4.50 (m, 3H), 4.60-4.80 (m, 2H), 5.00-5.20 (m, 1H), 7.93-7.00 (m, 1H), 7 .10-7.21 (m, 1H), 7.35-7.70 (m, 6H), 8.70-8.90 (m, 1H), 8.93-9.12 (m, 1H) Example 9: (1-(4-(3-aminopropyl)-2,5-dichlorobenzylamino)cyclopropyl)(4-cyclopropyl-3,4-dihydroquinoxalin-1(2H)-yl)methanone (Intermediate B1)

[00345] A stirred solution at 0° C of 1,4-dichloro-2-methoxybenzene (25.0 g, 141.2 mmol, 1.00 equiv) and TiCl4 (30.9 mL) in dichloromethane (300 mL) dichloro(methoxy)methane (16.2 g, 140.9 mmol, 1.00 equiv) was added dropwise. The resulting reaction mixture was stirred for 2 h at 60 °C and then quenched by addition of water/ice. The f value of the solution was adjusted to 1.0 with concentrated HCl extracted with ethyl acetate (4 x 500 mL) and the combined organic layers washed with brine (2 x 500 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to provide 31.0 g (gross) of B1a as a yellow solid. Step 2. 2,5-Dichloro-4-hydroxybenzaldehyde (Intermediate B1b)

[00346] A solution of 2,5-dichloro-4-methoxybenzaldehyde (14.0 g, 68.3 mmol, 1.00 equiv), LiCl (11.6 g, 274 mmol, 4.00 equiv) in DMF ( 150 mL) under an inert nitrogen atmosphere was stirred overnight at 140 °C in an oil bath. The reaction mixture was then quenched by adding water/ice and the f value of the solution was adjusted to 1-2 with concentrated HCl. The resulting solution was extracted with ethyl acetate (3 x 400 mL) and the combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified using silica gel column chromatography with an ethyl acetate/petroleum ether (1:10-1:5) gradient to provide 10.0 g (77%) of B1b as a light yellow solid. (300Hz, DMSO-d6): δ 11.99(s, 1H), 10.08(s, 1H), 7.81(s, 1H), 7.09(s, 1H). Step 3. 2,5-dichloro-4-formylphenyl trifluoromethanesulfonate (Intermediate B1c)

[00347] A stirred solution at 0°C of 2,5-dichloro-4-hydroxybenzaldehyde (3.0 g, 15.71 mmol, 1.00 equiv) and triethylamine (3.2 g, 31.62 mmol, 2 .00 equiv) in dichloromethane (50 mL) was added to a solution of trifluoromethanesulfonic anhydride (6.8 g, 24.10 mmol, 1.50 equiv) in dichloromethane (10 mL) dropwise. The resulting reaction mixture was stirred for 30 min at room temperature and then washed with brine (2 x 30 mL). The organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by silica gel column chromatography with an ethyl acetate/petroleum ether (1:50-1:10) eluent gradient provided 3.0 g (59%) of B1c as a white solid. 1H-NMR (300Hz, DMSO-d6): 10.22(s, 1H), 8.14-8.15(m, 2H). Step 3. Tert-Butyl N-[5-(2,5-dichloro-4-formylphenyl)pent-4-yn-1-yl]carbamate (Intermediate B1d)

[00348] A 250 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with 2,5-dichloro-4-formylphenyl trifluoromethanesulfonate (1 g, 3.10 mmol, 1.00 equiv), N tert-butyl-(pent-4-yn-1-yl)carbamate (567 mg, 3.09 mmol, 1.00 equiv), N,N-dimethylformamide (80 mL), DIEA (1.2 g, 9 .29 mmol, 3.00 equiv), CuI (88 mg, 0.46 mmol, 0.15 equiv), Pd (Pf3)2Cl2 (326 mg, 0.46 mmol, 0.15 equiv). The resulting solution was stirred for 3 h at room temperature. The resulting mixture was washed with 3x80 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0-20%). The collected fractions were combined and concentrated under vacuum. This resulted in 800 mg (73%) of tert-butyl N-[5-(2,5-dichloro-4-formylphenyl)pent-4-yn-1-yl]carbamate (B1d) as a light yellow oil. Step 4. Tert-Butyl N-[5-(2,5-dichloro-4-formylphenyl)pentyl]carbamate (Intermediate B1)

[00349] A 100 mL round bottom flask was purged and maintained with an H2 atmosphere and charged with tert-butyl butylcarbamate (800 mg, 2.25 mmol, 1.00 equiv) 1.2 g). The resulting solution was stirred overnight at room temperature. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0-20%). The collected fractions were combined and concentrated under vacuum. This resulted in 320 mg (40%) of tert-butyl N-[5-(2,5-dichloro-4-formylphenyl)pentyl]carbamate (B1) as a light yellow oil.

[00350] Intermediates B2 to B8 (Table 2a) were prepared from commercial or known raw materials, according to the procedure used for the preparation of Intermediate B1 in Example 9 above. Table 2a: Intermediates B2, B3, B4, B5 , B5a, B6, B7 and B8 Example 10: 5-(5-(tert-butyldiphenylsilyloxy)pentan-2-yl)-2-chlorobenzaldehyde (Intermediate B9)

[00351] A 250 mL round bottom flask was charged with 5-bromo-2-chlorobenzaldehyde (5.0 g, 22.78 mmol, 1.00 equiv), 4,4,5,5-tetramethyl-2- (tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (6.41 g, 25.24 mmol, 1.10 equiv), dioxane (100 mL), KOAc (6, 75 g, 68.78 mmol, 3.00 equiv) and Pd(dppf)Cl2 (500 mg, 0.68 mmol, 0.03 equiv). The resulting solution was stirred overnight at 80°C. The reaction mixture was diluted with 300 mL of water. The resulting solution was extracted with 300 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (5.5 g) was purified by flash chromatography with the following conditions: Column, silica gel; mobile phase, ethyl acetate: petroleum ether = 100:0 increasing to ethyl acetate: petroleum ether = 95:5 within 30 min; Detector, UV 254 nm. This resulted in 3.6 g (59%) of 2-chloro-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (B9a) as a white solid.

[00352] A 1000 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with pent-4-yn-1-ol (15 g, 178.32 mmol, 1.00 equiv), imidazole (30 .4 g, 2.50 equiv), dichloromethane (600 mL). This was followed by addition of TBDPSCl (61.3 g, 1.25 equiv.) dropwise with stirring at 0 oC. The resulting solution was stirred for 1 h at room temperature. The reaction was then quenched by adding 200 mL of water. The resulting solution was extracted with 3 x 150 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 3 x 100 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with petroleum ether. This resulted in 58.7 g (raw) of B9b as a colorless oil. Step 3. tert-butyl[(4-iodopent-4-en-1-yl)oxy]diphenylsilane (Intermediate B9c)

[00353] A 500 mL 3-neck round-bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of Ni(dppp)Cl2 (1.01 g, 0.03 equiv) in tetrahydrofuran ( 62 mL). This was followed by addition of DIBAL-H (81 mL, 1.30 equiv., 1 mol/L in hexane) dropwise with stirring. To this end, tert-butyl (pent-4-yn-1-yloxy)diphenylsilane (B9b) (20 g, 62.01 mmol, 1.00 equiv) was added dropwise with stirring at 0 oC. The mixture was stirred for 2 h. To the mixture was added a solution of NIS (28 g, 124.46 mmol, 2.00 equiv) in tetrahydrofuran (186 mL) dropwise with stirring at 0°C. The resulting solution was stirred for 1 h at room temperature. The resulting solution was diluted with 250 mL of ether. The reaction was then quenched by the addition of 250 ml of saturated aqueous Rochelle salt. After stirring for 15 min, the resulting mixture was filtered through cotton. The resulting clear filtrate was extracted with 5 x 100 mL of ether and the organic layers combined. The resulting mixture was washed with 3 x 100 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with petroleum ether. This resulted in 23.8 g (77%) of B9c as a light yellow oil. Step 4. 5-[5-[(tert-butyldiphenylsilyl)oxy]pent-1-en-2-yl]-2-chlorobenzaldehyde (Intermediate B9d)

[00354] A 100 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with [(4-iodopent-4-en-1-yl)oxy] tert-butyl diphenylsilane (B9c) (5.2 g, 11.54 mmol, 1.00 equiv.), Pd(Pf3)4 (1.3 g, 1.12 mmol, 0.10 equiv.), K3PO4 (4.9 g, 23.08 mmol, 2, 00 equiv), 2-chloro-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (B9a) (3.1 g, 11.63 mmol, 1.00 equiv), dioxane/H2O ( 31/3.1 mL). The resulting solution was stirred for 4 h at 80°C in an oil bath. The reaction mixture was cooled. The resulting solution was diluted with 100 mL of H2O. The resulting solution was extracted with 4 x 80 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1 x 50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (5/100). This resulted in 3.7 g (64%) of B9d as a yellow oil. Step 5. 5-[5-[(tert-butyldiphenylsilyl)oxy]pentan-2-yl]-2-chlorobenzaldehyde (Intermediate B9)

[00355] A 100 mL round bottom flask purged and maintained in a hydrogen atmosphere was charged with 5-[5-[(tert-butyldiphenylsilyl)oxy]pent-1-en-2-yl]-2-chlorobenzaldehyde ( B9d, 600 mg, 1.30 mmol, 1.00 equiv), ethyl acetate (20 mL), Rh/C (600 mg). The resulting solution was stirred overnight at room temperature. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0:1-1:3). This resulted in 300 mg (50%) of B9 as a light yellow oil. Example 11: Ethyl 5-(4-chloro-3-formylphenyl)hexanoate (Intermediate B10)

[00356] A 250 mL round bottom flask was charged with 2-chloro-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (3.5 g, 13.13 mmol, 1.10 equiv), ethyl 5-[(trifluoromethane)sulfonyloxy]hex-5-enoate (3.5 g, 12.06 mmol, 1.00 equiv), K3PO4 (7.7 g, 36.27 mmol, 3.00 equiv ), Pd (pf3) 4 (1.4 g, 1.21 mmol, 0.10 equiv), dioxane (120 mL), water (20 mL). The resulting solution was stirred for 1 night at 80 oC in an oil bath. The reaction was cooled by adding 300 mL of water. The resulting solution was extracted with 300 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (4.5 mg) was purified by flash chromatography with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ethyl acetate: petroleum ether = 100:0 increasing to ethyl acetate: petroleum ether = 95:5 within 30 min; Detector, UV 254 nm. This resulted in 2.2 g (65%) of ethyl 5-(4-chloro-3-formylphenyl)hex-5-enoate (B10a) as light red oil. Step 2. Ethyl 5-(4-chloro-3-formylphenyl)hexanoate (Intermediate B10)

[00357] A 250 mL round bottom flask was charged with ethyl 5-(4-chloro-3-formylphenyl)hex-5-enoate (B10a) (2.2 g, 7.84 mmol, 1.00 equiv ), Rh/C (2.2 g, 21.36 mmol, 3.00 equiv), ethyl acetate (50 mL). The resulting solution was stirred for 5 h at 30 °C in an oil bath. The resulting solution was diluted with 100 mL of ethyl acetate. The solids were filtered. The resulting mixture was concentrated under vacuum. The crude product (2.5 mg) was purified by flash chromatography with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ethyl acetate:petroleum ether=100:0 increasing to ethyl acetate:petroleum ether=95:5 within 30 min; Detector, UV 254 nm. This resulted in 2.1 g (95%) of ethyl 5-(4-chloro-3-formylphenyl)hexanoate (B10) as colorless oil.Example 12: Methyl 5-(6-formyl-5-methylpyridin-2-yl )pentanoate (Intermediate B11)

[00358] A 250 mL (1 atm) round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with methyl 3-methylpyridine-2-carboxylate (8.0 g, 52.92 mmol, 1.00 equiv ), dichloromethane (100 mL), m-CPBA (27.3 g, 158.72 mmol, 3.00 equiv). The resulting solution was stirred overnight at 25°C in an oil bath. The resulting solution was diluted with 100 mL of DCM. The resulting mixture was washed with 1 x 100 ml of water and 1 x 100 ml of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with dichloromethane/methanol (20:1). This resulted in 6.0 g (68%) of product (B11a) as colorless oil. Step 2. Methyl 6-chloro-3-methylpyridine-2-carboxylate (Intermediate B11b)

[00359] A 250 mL (1 atm) round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with 2-(methoxycarbonyl)-3-methylpyridin-1-io-1-olate (1.5 g, 8.97 mmol, 1.00 equiv), phosphoroyl trichloride (60 mL). The resulting solution was stirred overnight at 60 oC in an oil bath. The resulting solution was diluted with 200 mL of DCM. The resulting mixture was washed with 1 x 100 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0%-25%). This resulted in 318 mg (19%) of methyl 6-chloro-3-methylpyridine-2-carboxylate (B11b) as a white solid. Step 3. (6-chloro-3-methylpyridin-2-yl)methanol (Intermediate B11c)

[00360] A 250 mL (1 atm) 3-neck round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with methyl 6-chloro-3-methylpyridine-2-carboxylate (1.86 g, 10 .02 mmol, 1.00 equiv), THF (100 mL). This was followed by the addition of DIBAL-H (40 ml, 4.00 equiv) at -78 oC. The resulting solution was stirred for 3 h at room temperature in an ethanol/liquid N2 bath. The resulting solution was diluted with 100 mL of ethyl acetate. The reaction was then quenched by the addition of 60 mL of C4H4KNaO6 diatomite. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0-50%). This resulted in 1.3 g (82%) of (6-chloro-3-methylpyridin-2-yl)methanol (B11c:) as colorless oil. Step 4. 2-[[(tert-butyldimethylsilyl)oxy]methyl]-6-chloro-3-methylpyridine (Intermediate B11d)

[00361] A 500 mL 3-neck round bottom flask was charged with (6-chloro-3-methylpyridin-2-yl)methanol (6.4 g, 40.61 mmol, 1.00 equiv), dichloromethane (300 mL), imidazole (4.2 g), TBDMSCl (7.6 g). The resulting solution was stirred for 2 h at 0°C in a salt/ice bath. The reaction was cooled by adding 30 mL of water. The resulting solution was extracted with 3 x 50 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 2x50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 10.4 g (94%) of 2-[[(tert-butyldimethylsilyl)oxy]methyl]-6-chloro-3-methylpyridine (B11d) as a brown solid. Step 5. Methyl 5-(6-[[(tert-butyldimethylsilyl)oxy]methyl]-5-methylpyridin-2-yl)pent-4-inoate (Intermediate B11e)

[00362] A 100 mL three-neck round-bottom flask, purged and maintained under an inert nitrogen atmosphere, was charged with Cs2CO3 (6.9 g, 21.18 mmol, 1.92 equiv), (A-tafosPdCl2 )2 (195 mg), 2-[[(tert-butyldimethylsilyl)oxy]methyl]-6-chloro-3-methylpyridine (3 g, 11.04 mmol, 1.00 equiv) in CH3CN (20 mL), methyl pent-4-inoate (3.5 g, 31.21 mmol, 2.83 equiv) in CH3CN (20 mL). The resulting solution was stirred overnight at 95oC in an oil bath. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1/100-10/100). This resulted in 1.1 g (29%) of methyl 5-(6-[[(tertbutyldimethylsilyl)oxy]methyl]-5-methylpyridin-2-yl)pent-4-noate (B11e) as brown oil. Step 6. Methyl 5-[6-(hydroxymethyl)-5-methylpyridin-2-yl]pent-4-inoate (Intermediate B11f)

[00363] To a 100 mL round bottom flask charged with methyl 5-(6-[[(tert-butyldimethylsilyl)oxy]methyl]-5-methylpyridin-2-yl)pent-4-inoate (1.5 g , 4.32 mmol, 1.00 equiv) in tetrahydrofuran (10 mL) was added dropwise to TBAF (6.5 mL, 1 M) with stirring. The resulting solution was stirred for 1 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1/100-20/100). This resulted in 600 mg (60%) of methyl 5-[6-(hydroxymethyl)-5-methylpyridin-2-yl]pent-4-inoate (B11f) as brown oil. Step 7. Methyl 5-[6-(hydroxymethyl)-5-methylpyridin-2-yl]pentanoate (Intermediate B11g)

[00364] A 100 mL round bottom flask loaded with methyl 5-[6-(hydroxymethyl)-5-methylpyridin-2-yl]pent-4-inoate (700 mg, 3.00 mmol, 1.00 equiv) , ethyl acetate (10 mL) and Rh/C (0.7 g) was purged and maintained with an H2 atmosphere. The resulting suspension was stirred for 2 h at 25 oC in an oil bath. The solids were filtered. The resulting mixture was concentrated under vacuum. This resulted in 0.6 g (84%) of methyl 5-[6-(hydroxymethyl)-5-methylpyridin-2-yl]pentanoate (B11g) as brown oil. Step 8. Methyl 5-(6-formyl-5-methylpyridin-2-yl)pentanoate (B11)

[00365] A 50 mL round bottom flask was charged with a solution of methyl 5-[6-(hydroxymethyl)-5-methylpyridin-2-yl]pentanoate (202 mg, 0.85 mmol, 1.00 equiv) in dichloromethane (5 mL), MnO2 (741.5 mg, 8.53 mmol, 10.02 equiv). The resulting solution was stirred overnight at 50 oC in an oil bath. The solids were filtered. The resulting mixture was concentrated under vacuum. This resulted in 180 mg (90%) of methyl 5-(6-formyl-5-methylpyridin-2-yl)pentanoate (B11) as light brown oil.Example 13: N-[4-[3-(bromomethyl)- tert-butyl 4-chlorophenyl]butyl]carbamate (Intermediate C1)

[00366] A 100 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with (2-chloro-5-iodophenyl) methanol (212 mg, 0.79 mmol, 1.00 equiv), N- tert-butyl (but-3-yn-1-yl)carbamate (160 mg, 0.95 mmol, 1.20 equiv), DIEA (0.39 mL, 3.00 equiv), CuI (15 mg, 0 .08 mmol, 0.10 equiv), dichloropalladium bis(triphenylphosphine) (55.5 mg, 0.08 mmol, 0.10 equiv) and N,N-dimethylformamide (8 mL). The resulting solution was stirred overnight at room temperature. The resulting solution was diluted with 20 mL of water. The resulting solution was extracted with 4 x 20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 5 x 100 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:3). This resulted in 220 mg (90%) of tert-butyl N-[4-[4-chloro-3-(hydroxymethyl)phenyl]but-3-yn-1-yl]carbamate (C1a) as a yellow oil. Step 2. Tert-Butyl N-[4-[4-chloro-3-(hydroxymethyl)phenyl]butyl]carbamate (Intermediate C1b)

[00367] A 100 mL round bottom flask, purged and maintained with a hydrogen atmosphere, was added N-[4-[4-chloro-3-(hydroxymethyl)phenyl]but-3-yn-1-yl] tert-butyl carbamate (350 mg, 1.13 mmol, 1.00 equiv), ethyl acetate (20 mL), Rh/C (350 mg). The resulting solution was stirred overnight at room temperature. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:3). This resulted in 300 mg (85%) of tert-butyl N-[4-[4-chloro-3-(hydroxymethyl)phenyl]butyl]carbamate (C1b) as a light yellow oil. Step 3. Tert-Butyl N-[4-[3-(bromomethyl)-4-chlorophenyl]butyl]carbamate (Intermediate C1)

[00368] A 100 mL round bottom flask was charged with tert-butyl N-[4-[4-chloro-3-(hydroxymethyl)phenyl]butyl]carbamate (300 mg, 0.96 mmol, 1.00 equiv), dichloromethane (10 mL), THF (10 mL), NBS (255 mg, 4.33 mmol, 1.50 equiv). This was followed by the addition of triphenylphosphane (375 mg, 1.43 mmol, 1.50 equiv) in several batches at 0-5 oC. The resulting solution was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:3). This resulted in 270 mg (75%) of tert-butyl N-[4-[3-(bromomethyl)-4-chlorophenyl]butyl]carbamate (C1) as a yellow oil.Example 14: N-[4-[4 tert-butyl -(bromomethyl)-5-chloro-2-methylphenyl]butyl]carbamate (Intermediate C2)

[00369] A 50 mL round bottom flask was charged with tert-butyl N-[4-(5-chloro-4-formyl-2-methylphenyl)butyl]carbamate (B4) (150 mg, 0.46 mmol , 1.00 equiv), methanol (15 mL) and NaBH4 (34.83 mg, 0.92 mmol, 2.00 equiv). The resulting solution was stirred at room temperature for 0.5 hours. The reaction mixture was cooled to 0°C with a water/ice bath. The reaction was cooled by adding 10 mL of water. The resulting solution was extracted with 3 x 20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2 x 20 ml of brine. The mixture was dried over anhydrous sodium sulfate. The solids were filtered and the resulting mixture was concentrated in vacuo. This resulted in 180 mg (crude) of tert-butyl N-[4-[5-chloro-4-(hydroxymethyl)-2-methylphenyl]butyl]carbamate (C2a) as a white oil. Step 2. Tert-Butyl N-[4-[4-(bromomethyl)-5-chloro-2-methylphenyl]butyl]carbamate (Intermediate C2)

[00370] A 100 mL round bottom flask was charged with tert-butyl N-[4-[5-chloro-4-(hydroxymethyl)-2-methylphenyl]butyl]carbamate (180 mg, 0.55 mmol, 1.00 equiv) and tetrahydrofuran/DCM (10/10 mL). This was followed by the addition of NBS (156.7 mg, 0.88 mmol, 1.60 equiv) in several batches at 0°C. This was followed by the addition of f3P (216.73 mg) in several batches at 0 oC. The resulting solution was stirred for 20 min at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 194 mg (90%) of tert-butyl N-[4-[4-(bromomethyl)-5-chloro-2-methylphenyl]butyl]carbamate (C2) as a white oil.

[00371] Intermediates C3 to C10 (Table 2b) were prepared from commercial or known starting materials according to the procedure used to synthesize Intermediate C1 in example 14. Table 2b. C ring bromides C3 toC10 Example 15: 1-(5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pentyl)-3-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea hydrochloride (I-60)

[00372] A 50 mL round bottom flask was charged with tert-butyl N-[5-(2,5-dichloro-4-formylphenyl)pentyl]carbamate (B2) (320 mg, 0.89 mmol, 1 .00 equiv), 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (A1) (236 mg, 0.89 mmol, 1.00 equiv), dichloromethane (10 mL), NaBH(OAc)3 (1.13 g, 6.00 equiv). The resulting solution was stirred overnight at room temperature. The reaction was cooled by adding 10 mL of water. The resulting solution was extracted with 3 x 20 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0-20%). The collected fractions were combined and concentrated under vacuum. This resulted in 280 mg (52%) of N-(5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl [tert-butyl pentyl]carbamate) (60a) as a light yellow oil. Step 2. N-[[4-(5-aminopentyl)-2,5-dichlorophenyl]methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (Intermediate 60b)

[00373] A 100 mL round bottom flask was charged with N-(5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino tert-butyl)methyl]phenyl]pentyl)carbamate (350 mg, 0.57 mmol, 1.00 equiv), dichloromethane (5 mL) and trifluoroacetic acid (5 mL). The resulting solution was stirred for 1 h at room temperature. The resulting mixture was concentrated under vacuum. The f value of the solution was adjusted to 10 with sodium hydroxide (1 mol/L). The resulting solution was extracted with 3 x 20 mL of ethyl acetate and the organic layers combined and dried in a reduced pressure oven and concentrated in vacuo. This resulted in 280 mg (96%) of N-[[4-(5-aminopentyl)-2,5-dichlorophenyl]methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1 -amine (60b) as a light yellow oil. Step 3. 1-(5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pentyl)-3-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea hydrochloride (I-60)

[00374] A 100 mL round bottom flask was charged with N-[[4-(5-aminopentyl)-2,5-dichlorophenyl]methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl ]cyclopropan-1-amine (130 mg, 0.25 mmol, 1.00 equiv), N,N-dimethylformamide (10 mL), DIEA (39 mg, 0.30 mmol, 1.20 equiv), DSC (78 mg, 1.20 equiv), the resulting solution was stirred for 1.5 h at 25°C. Then (2R,3R,4R,5S)-6-aminohexane-1,2,3,4,5-pentol (138.4 mg, 0.76 mmol, 3.00 equiv) was added. The resulting solution was stirred overnight at 25°C. The resulting solution was diluted with 50 mL of ethyl acetate. The resulting mixture was washed with 3x50 mL of brine. The crude product was purified by preparative HPLC with the following conditions: Column, Gemini-NX 5u C18 110A, AXIA Pack, 150 x 21.2 mm; mobile phase, water with NH4HCO310mM and MeCN (28.0% MeCN up to 54.0% in 8 min); Detector, 254 nm. The product was obtained and concentrated under vacuum. This resulted in 70.6 mg (37%) of -(5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl] phenyl]pentyl)-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea hydrochloride (I-60) as a white solid. MS (ES, m/z): 717 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 0.51 (s, 2H), 0.71 (d, J = 6.1 Hz, 2H), 1.26 - 1.67 (m, 10H), 2.70 (d, J = 7.3 Hz, 2H), 3.08-3.15 (m, 3H), 3.35 (dd, J = 14.0, 4.3 Hz, 1H), 3.53 - 3.80 (m, 6H), 3.80 - 3.92 (m, 1H), 4.26 (m, 2H), 7.17 - 7.50 (m, 3H), 7.59 (td, J = 7.1, 6.3, 1.7 Hz, 3H), 7.87 (s, 1H), 8.86 (dd, J = 23.4, 6.1 Hz, 1H), 9.33 (s, 1H) .Example 16: 5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pentanoic acid (I-61)

[00375] A 50 mL round bottom flask was charged with 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (A-1) (350 mg, 1.31 mmol, 1 .00 equiv), methyl 5-(2,5-dichloro-4-formylphenyl)pentanoate (B5) (416 mg, 1.44 mmol, 1.00 equiv). The above compound was dissolved in dichloromethane (25 mL). Acetic acid (1 drop, cat.) was added. This was followed by the addition of NaBH(OAc)3 (1.4 g, 6.61 mmol, 5.00 equiv) in portions at room temperature. The resulting solution was stirred for 16 h at room temperature. The reaction was cooled by adding 20 mL of water. The resulting solution was extracted with 2x mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1 x 100 ml of water and 1 x 100 ml of sat. sodium chloride. The mixture was dried over anhydrous sodium sulfate. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:3). This resulted in 535 mg (76%) of methyl 5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pentanoate (61a) as colorless oil. Step 2. 5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pentanoic acid (I-61)

[00376] A 50 mL round bottom flask was charged with methyl 5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl ]phenyl]pentanoate (61a, 535 mg, 0.99 mmol, 1.00 equiv), methanol (15 mL), water (15 mL). This was followed by the addition of LiOH.H2O (168 mg, 4.00 mmol, 4.00 equiv) in portions at room temperature. The resulting solution was stirred for 2 h at 50°C. The resulting solution was diluted with 20 mL of water. The f value of the solution was adjusted to 2-3 with con hydrogen chloride. The resulting solution was extracted with 3 x 50 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1 x 50 ml of water and 1 x 50 ml of sat. sodium chloride. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 500 mg (96%) of 5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pentanoic acid (I-61) as a light yellow oil. MS (ES, m/z): 525 [M+H]+ H-NMR (CD3OD, 400 M, ppm): 8.56 (s, 1H), 8.46 - 8.44 (d, 1H), 7.48 - 7.46 (d, 2H), 7.27 (s, 1H), 7.20 - 7.16 (m, 3H), 7.12 - 7.06 (m, 1H), 3.68 - 3.65 (m, 3H), 2.71 - 2.68 (m, 2H), 2.32 - 2.29 ( m, 2H), 1.63 - 1.29 (m, 4H), 0.89 - 0.81 (m, 4H), 0.68 (t, 2H), 0.50 (t, 2H).Example 17: 5-[2,5-dichloro-4 -[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]-N-[(2S,3R,4R,5R)-2,3,4,5, 6-pentahydroxyhexyl]pentanamide (I-62)

[00377] A 25 mL round bottom flask was charged with 5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl] phenyl]pentanoic acid (61) (260 mg, 0.49 mmol, 1.00 equiv), N,N-dimethylformamide (10 mL), DIEA (161 mg, 2.50 equiv). The resulting solution was stirred at room temperature for 10 min. This was followed by the addition of HATU (475 mg, 1.25 mmol, 2.50 equiv) in portions at room temperature. To this was added D-glucamine (181 mg, 2.00 equiv). The resulting solution was stirred for 16 h at room temperature. The reaction was cooled by adding 15 mL of water. The resulting solution was diluted with 30 mL of water. The resulting solution was extracted with 3 x 50 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1 x 100 mL of water and 1 x 100 mL of sat. of sodium chloride. The mixture was dried over anhydrous sodium sulfate. The crude product was purified by preparative HPLC with the following conditions: Column, XBridge C18 OBD Prepared Column, 5 μm, 19 mm X 250 mm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (38.0% MeCN to 61.0% in 8 min); Detector, 254 nm. This resulted in 170 mg (50%) of 5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]-N -[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]pentanamide (I-62) as a yellow solid. MS (ES, m/z): 717 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 0.35-0.48 (m, 2H), 0.620.75 (m, 2H), 1.00-1.25 (m, 4H), 1.40-1 .60 (m, 4H), 2.10 (s, 2H), 2.66 (s, 2H), 2.96-3.08 (m, 1H), 3.20-3.30 (m, 1H ), 3.35-3.65 (m, 6H), 3.78-3.85 (m, 1H), 3.91 (s, 2H), 7.14 (t, J = 7.2 Hz, 1H), 7.35-7.45 (m, 2H), 7.48-7.60 (m, 4H), 7.74 (t, J = 5.2 Hz, 1H), 8.70 (d , J = 4.8 Hz, 1H), 8.98 (s, 1H). Example 18: 4-[(4-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]butyl)[(2S ,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]carbamoyl]butanoic acid (I-63)

[00378] A 500 mL round bottom flask was charged with a solution of (NE)-N-[(4-[4-[(tert-butyldiphenylsilyl)oxy]butyl]-2,5-dichlorophenyl)methylidene]- 1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]cyclopropan-1-amine (5.8 g, 7.90 mmol, 1.00 equiv) in dichloromethane (200 mL), NaBH(OAc)3 ( 5.2 g, 24.54 mmol, 3.00 equiv). The resulting solution was stirred for 2 h at 30°C in an oil bath. The resulting solution was diluted with 800 mL of ethyl acetate. The resulting mixture was washed with 3x150 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0:100-50:50). This resulted in 4.7 g (81%) of N-[(4-[4-[(tert-butyldiphenylsilyl)oxy]butyl]-2,5-dichlorophenyl)methyl]-1-[4-(2-cyclopropoxyphenyl )pyridin-3-yl]cyclopropan-1-amine (63a) as light yellow oil. Step 2. 4-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]butan-1-ol (Intermediate 63b)

[00379] A 250 mL round bottom flask was charged with N-[(4-[4-[(tert-butyldiphenylsilyl)oxy]butyl]-2,5-dichlorophenyl)methyl]-1-[4-(2 -cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (63a) (4.0 g, 5.44 mmol, 1.00 equiv), tetrahydrofuran (100 mL), TBAF (2.8 g, 10 .71 mmol, 2.00 equiv). The resulting solution was stirred at room temperature for 1.5 h. The resulting solution was diluted with 500 mL of H2O. The resulting solution was extracted with 3 x 150 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (100:0-50:50). This resulted in 2.2 g (81%) of 4-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl] phenyl] butan-1-ol (63b) as an off-white solid. Step 3. 4-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]butanal (Intermediate 63c)

[00380] A 250 mL 3-neck round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of oxalyl chloride (486 mg, 3.83 mmol, 1.50 equiv) in dichloromethane (100 mL). This was followed by adding a solution of DMSO (684 mg, 8.75 mmol, 3.00 equiv) in dichloromethane (5 mL) dropwise with stirring at -78°C in 30 min. The mixture was stirred for 30 min at -78 oC. To this was added a solution of 4-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl] butan-1- ol (63b) (1.2 g, 2.41 mmol, 1.00 equiv) in dichloromethane (10 mL) dropwise with stirring at -78oC in 5 min. The mixture was stirred for 5 min at -78 oC. To the mixture, a solution of TEA (1.2 g, 11.86 mmol, 5.00 equiv) in dichloromethane (5 mL) was added dropwise with stirring at -78oC in 3 min. The mixture was stirred for 30 min at -78 oC. The resulting solution was stirred for 2 h at room temperature. The reaction was cooled by adding 600 mL of water. The resulting solution was extracted with 4 x 150 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 600 mg (50%) of 4-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]butanal ( 63c) as a light yellow oil. Step 4. (2R,3R,4R,5S)-6-[(4-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino )methyl]phenyl]butyl)amino]hexane- 1,2,3,4,5-pentol (Intermediate 63d)

[00381] A 50 mL flask was charged with 4-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]butanal (63c) (320 mg, 0.65 mmol, 1.00 equiv), methanol (6 mL), dichloromethane (2 mL). This was followed by the addition of (2R, 3R, 4R, 5S)-6-aminohexane-1,2,3,4,5-pentol (234 mg, 1.29 mmol, 1.20 eq). The mixture was stirred at r.t. for 30 min. To this was added NaBH(OAc)3 (274 mg, 1.29 mmol, 2.00 equiv). The resulting solution was stirred for 1 night at 30 oC in an oil bath. The resulting solution was diluted with 200 ml of ethyl acetate. The resulting mixture was washed with 2 x 50 ml of 0.5 M sodium hydroxide. The resulting mixture was washed with 2 x 50 ml of brine. The mixture was dried over sodium sulfate and concentrated in vacuo. This resulted in 400 mg (94%) of (2R,3R,4R,5S)-6-[(4-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin- 3-yl]cyclopropyl]amino)methyl]phenyl]butyl)amino]hexane-1,2,3,4,5-pentol (63d) as a pale yellow crude solid. Step 5. 4-[(4-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]butyl)[(2S ,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]carbamoyl]butanoic acid (I-63)

[00382] A 50 mL round bottom flask was charged with (2R,3R,4R,5S)-6-[(4-[2,5-dichloro-4-[([1-[4-(2- cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]butyl)amino]hexane-1,2,3,4,5-pentol (63d) (400 mg, 0.30 mmol, 1.00 equiv, 50%), DMSO (3 mL), oxane-2,6-dione (70 mg, 0.61 mmol, 1.00 equiv). The resulting solution was stirred for 2 h at 50 oC in an oil bath. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, Gemini-NX 5μ C18 110A, AXIA Packed, 150 x 21.2 mm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (30.0% MeCN to 80.0% in 10 min); Detector, UV 254 nm. This resulted in 30.9 mg (13%) of 4-[(4-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino) methyl]phenyl]butyl)[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl]butanoic acid (I-63) as a white solid. MS (ES, m/z): 774 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 8.55 (1H, s), 8.46 (1H, s), 7.46-7.46 (2H, m), 7.23 (1H, s), 7.20-7.16(3H, m), 7.11-7.09 (1H, m), 3.96 (1H, m), 3.76-3.46 (11H, m), 3, 34 -3.31 (1H, m), 2.89 -2.83 (2H, m), 2.73 -2.70 (4H, m), 2.32 -2.30 (2H, m), 1.90-1.89(2H, m), 1.65-1.57 (4H, m), 0.89 -0.81 (4H, m), 0.67 -0.65 (2H, d ), 0.43 (2H, d).Example 19: 1-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl ]phenyl]butyl)-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-64)

[00383] A 100 mL round bottom flask was charged with 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (101.1 mg, 0.38 mmol, 1.00 equiv ), tert-butyl N-[4-[3-(bromomethyl)-4-chlorophenyl]butyl]carbamate (143 mg, 0.38 mmol, 1.00 equiv), DIEA (0.19 mL, 3.00 equiv), acetonitrile (10 mL). The resulting solution was stirred overnight at 50 oC in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was extracted with 3 x 30 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3x80 mL of brine. The solid was dried in an oven at reduced pressure. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:3). This resulted in 180 mg (84%) of N-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]butyl ) tert-butyl carbamate (64a) as a yellow oil. Step 2. N-[[5-(4-aminobutyl)-2-chlorophenyl]methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (Intermediate 64b)

[00384] A 100 mL round bottom flask was charged with N-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl tert-butyl ]phenyl]butyl)carbamate (300 mg, 0.53 mmol, 1.00 equiv), dichloromethane (10 mL), trifluoroacetic acid (10 mL). The resulting solution was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 30 mL of ethyl acetate. The f value of the solution was adjusted to 8~9 with sodium hydroxide (1 mol/L). The resulting solution was extracted with 4 x 30 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 235 mg (95%) of N-[[5-(4-aminobutyl)-2-chlorophenyl]methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (64b) as a light yellow oil. Step 3. 1-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]butyl)-3-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-64)

[00385] A 50 mL round bottom flask was charged with N-[[5-(4-aminobutyl)-2-chlorophenyl]methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan -1-amine (235 mg, 0.51 mmol, 1.00 equiv), DSC (157 mg, 3.20 mmol, 0.20 equiv), N,N-dimethylformamide (10 mL), DIEA (0.1 mL, 1.20 eq). This was followed by the addition of (2R,3R,4R,5S)-6-aminohexane-1,2,3,4,5-pentol (276 mg, 1.52 mmol, 3.00 equiv) after 2 h. To this was added hydrogen chloride (1 mol/L) (0.15 mL). The resulting solution was stirred overnight at room temperature. The resulting solution was extracted with 5 x 50 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by preparative HPLC with the following conditions: Column, Gemini-NX 5μ C18 110A, AXIA Packed, 150 x 21.2 mm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (28.0% MeCN to 56.0% in 8 min); Detector, nm. After lyophilization, 10 drops of hydrogen chloride (1 mol/L) were added to the product in 50 ml of MeCN. After lyophilization, this resulted in 123.1 mg (36%) of 1-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino) methyl] phenyl]butyl)-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-64) as a white solid. MS (ES, m/z): 669 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 0.40 - 0.47 (m, 2H), 0.60 - 0.69 (m, 2H), 1.11 (s, 2H), 1.21 (s , 2H), 1.40 - 1.53 (m, 2H), 1.55 - 1.68 (m, 2H), 2.61 (t, J = 7.5 Hz, 2H), 3.07 - 3.21 (m, 3H), 3.32 - 3.42 (m, 1H), 3.57 - 3.81 (m, 7H), 4.06 (s, 2H), 7.11 - 7, 39 (m, 6H), 7.47 - 7.58 (m, 2H), 8.63 - 8.87 (m, 1H), 8.87 (s, 1H).Example 20: 1-[4- [5-chloro-4-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-methylphenyl]butyl]-3-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]urea (I-65)

[00386] A 100 mL round bottom flask was charged with tert-butyl N-[4-[4-(bromomethyl)-5-chloro-2-methylphenyl]butyl]carbamate (C5) (194 mg, 0. 50 mmol, 1.00 equiv), 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-ol (A23) (140 mg, 0.52 mmol, 1.05 equiv), N, N-dimethylformamide (13 mL). This was followed by the addition of sodium hydride (40 mg, 1.67 mmol, 3.36 equiv) in several batches at 0 oC. The resulting solution was stirred at room temperature for 0.5 h. The reaction mixture was cooled to 0°C with a water/ice bath. The resulting solution was diluted with 20 mL of ethyl acetate. The reaction was then cooled by adding 10 mL of NH4Cl. The resulting solution was extracted with 2 x 20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2 x 20 ml of brine. The mixture was dried over anhydrous sodium sulfate. The resulting mixture was concentrated under vacuum. This resulted in 143 mg (50%) of N-[4-[5-chloro-4-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-methylphenyl]butyl ] tert-butyl carbamate (65a) as a white solid. Step 2. 4-[5-chloro-4-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-methylphenyl]butan-1-amine (Intermediate 65b)

[00387] A 100 mL round bottom flask was charged with N-[4-[5-chloro-4-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2 tert-butyl-methylphenyl]butyl]carbamate (65a) (143 mg, 0.25 mmol, 1.00 equiv), TFA/DCM (8/10 mL). The resulting solution was stirred for 1.0 h at room temperature. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 20 mL of ethyl acetate. The f value of the solution was adjusted to 9 with sodium bicarbonate (100%). The resulting solution was extracted with 2 x 20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1 x 20 ml of brine. The mixture was dried over anhydrous sodium sulfate. The solids were filtered. The resulting mixture was concentrated under vacuum. This resulted in 120 mg (raw) of 4-[5-chloro-4-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-methylphenyl]butan-1- amine (65b) as a yellow oil. Step 3. 1-[4-[5-chloro-4-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-methylphenyl]butyl]-3-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-65)

[00388] A 100 mL round bottom flask was charged with 4-[5-chloro-4-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-methylphenyl] butan-1-amine (65b) (120 mg, 0.25 mmol, 1.00 equiv), N,N-dimethylformamide (10 mL), DIEA (0.054 mL), DSC (84.48 mg), the resulting solution was stirred for 1.0 h at room temperature. Then (2S,3S,4S,5R)-6-aminohexane-1,2,3,4,5-pentol (136.8 mg, 0.76 mmol, 3.00 equiv) was added. The resulting solution was stirred for an additional 12 h at room temperature. The solids were filtered. The resulting mixture was concentrated under vacuum. The crude product was purified by preparative HPLC with the following conditions: Column, Gemini-NX 5μ C18 110A, AXIA Packed, 150 x 21.2 mm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (30.0% MeCN to 54.0% in 10 min); Detector, 254 nm. This resulted in 50.2 mg (29%) of 1-[4-[5-chloro-4-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-methylphenyl ]butyl]-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-65) as a white solid. MS (ES, m/z): 684[M+H]+; 1H-NMR (400 MHz, CD3OD) δ 0.40 (s, 2H), 0.62 (d, J = 6.2 Hz, 2H), 0.91 (s, 3H), 0.99 (s, 2H), 1.53 (q, J = 7.1, 6.4 Hz, 4H), 2.21 (s, 3H), 2.57 (t, J = 7.3 Hz, 2H), 3, 15 (dt, J = 12.5, 6.2 Hz, 3H), 3.38 (dd, J = 13.9, 4.5 Hz, 1H), 3.49 - 3.81 (m, 7H) , 4.33 (s, 2H), 6.83 (s, 1H), 6.99 (td, J = 7.3, 1.4 Hz, 1H), 7.06 (s, 1H), 7, 22 (d, J = 5.0 Hz, 1H), 7.26 - 7.43 (m, 3H), 8.46 (d, J = 5.1 Hz, 1H), 8.64 (d, J = 0.7 Hz, 1H).Example 21: (2R,3R,4R,5S)-6-(4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin- 3-yl)cyclopropoxy)methyl)phenyl)butylamino)hexane-1,2,3,4,5-pentaol (I-66)

[00389] 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-ol (C9) (3.4 g, 12.72 mmol, 1.00 equiv), [4-[4- (bromomethyl)-2,5-dichlorophenyl]butoxy](tert-butyl)diphenylsilane (7.6 g, 13.81 mmol, 1.09 equiv) were dissolved in N,N-dimethylformamide (100 mL). This was followed by the addition of sodium hydride (60% in oil) (1.5 g, 62.50 mmol, 3.00 equiv) in portions at 0 °C. The resulting solution was stirred for 1 h at 0°C. The reaction was cooled by adding 100 mL of water. The resulting solution was extracted with 3 x 100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2 x 200 ml of water and 1 x 100 ml of sat. sodium chloride. The mixture was dried over anhydrous sodium sulfate. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:20-1:10). This resulted in 6.3 g (67%) of 3-[1-[(4-[4-[(tert-butyldiphenylsilyl)oxy]butyl]-2,5-dichlorophenyl)methoxy]cyclopropyl]-4-(2 -cyclopropoxyphenyl)pyridine (66a) as brown oil. Step 2. 4-[2,5-dichloro-4-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy] methyl) phenyl]butan-1-ol (Intermediate 66b)

[00390] 3-[1-[(4-[4-[(tert-butyldiphenylsilyl)oxy]butyl]-2,5-dichlorophenyl)methoxy]cyclopropyl]-4-(2-cyclopropoxyphenyl)pyridine (66a) (4 .6 g, 6.24 mmol, 1.00 equiv) was dissolved in tetrahydrofuran (20 mL). This was followed by addition of TBAF (1.0 M in tetrahydrofuran) (12.5 mL, 2.00 equiv.) dropwise with stirring at room temperature. The resulting solution was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 300 mL of ethyl acetate. The resulting mixture was washed with 2 x 100 ml of water and 1 x 100 ml of sat. sodium chloride. The mixture was dried over anhydrous sodium sulfate. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:4-1:1). This resulted in 2.8 g (90%) of 4-[2,5-dichloro-4-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]butan-1 -ol (66b) as a light yellow semisolid: MS (ES, m/z): 498.15 [M+H]+; 1H NMR (CDCl3, 300MHz, ppm): δ: 0.40-0.50 (m, 2H), 0.58-0.70 (m, 2H), 0.80-0.92 (m, 2H) , 0.93-1.02 (m, 2H), 1.55-1.75 (m, 4H), 2.68 (t, J = 7.2 Hz, 2H), 3.47-3.58 (m, 1H), 3.67 (t, J = 6.0 Hz, 2H), 4.34 (s, 2H), 6.95-7.07 (m, 2H), 7.10-7, 20 (m, 2H), 7.23-7.35 (m, 2H), 7.36-7.43 (m, 1H), 8.53 (d, J = 4.8 Hz, 1H), 8 .67 (s, 1H). Step 3. 4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)butanal (Intermediate 66c)

[00391] 4-[2,5-dichloro-4-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy] methyl)phenyl]butan-1-ol (66b) (996 mg, 2.00 mmol) was dissolved in dry dichloromethane (20 mL) under a nitrogen atmosphere. Dess-Martin Periodinane (1.017 g, 2.40 mmol) was added and the reaction mixture was stirred at room temperature for 30 minutes, at which time LCMS indicated complete conversion to the aldehyde. The crude mixture was diluted with dichloromethane and washed successively with 20 mL portions of 15% Na2S2O3, saturated NaHCO3 and brine. The resulting solution was dried over Na2SO4 and purified by flash chromatography (24 g SiO2 DCM to 25% EtOAc in DCM for 15 minutes) to give 939 mg of intermediate 66c (95%) as a clear oil. Step 4. (2R,3R,4R,5S)-6-(4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl )butylamino)hexane-1,2,3,4,5-pentaol (I-66):

[00392] 4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)butanal (66c) (939 mg, 1.90 mmol ) was dissolved in dichloromethane/methanol (1:1, 20 mL). D-Glucamine (377 mg, 2.08 mmol) was added and the mixture was stirred at room temperature for 15 minutes. NaBH(OAc)3 (483 mg, 2.28 mmol) was added and the reaction mixture was stirred at room temperature for an additional 1 hour, at which time LCMS indicated complete conversion. The crude mixture was diluted with dichloromethane and washed successively with 30 mL portions of saturated NaHCO3, water and brine. The resulting solution was dried over Na2SO4 to give 1.18 g of I-66 (95%) as free base. A portion of this material was purified by preparative HPLC (10 to 95% MeCN in H2O with 0.1% TFA) to give I-66 (19.5 mg) as the TFA salt. MS (ES, m/z): 661.30 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.37 (s, 1H), 8.23 (d, J = 4.4 Hz, 1H), 7.95 (s, 2H), 7.05 ( s, 2H), 6.99 (d, J = 8.4 Hz, 1H), 6.92 (d, J = 5.9 Hz, 2H), 6.70 - 6.57 (m, 2H), 5.40 (d, J = 1.0 Hz, 2H), 3.26 (dd, J = 22.0, 15.2 Hz, 11H), 3.08 (dd, J = 15.7, 10, 8Hz, 6H), 2.69 (s, 2H), 2.56 (s, 3H), 2.30 (s, 2H), 2.14 (s, 5H), 1.21 (s, 4H) , 0.61 (d, J = 10.8 Hz, 4H), 0.28 (d, J = 10.8 Hz, 4H), 0.28 (d, J = 5.9 Hz, 2H).

[00393] The following amino alcohols were prepared as the free base from 4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl) butanal using the same method described in Example 21 by replacing D-Glucamine with the amine described. Table 3. Intermediates G1-G5 Example 22: N-(4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)butyl)-N-((2S, 3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl)tetrahydro-2H-pyran-4-carboxamide (I-67)

[00394] (2R,3R,4R,5S)-6-(4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl )butylamino)hexane-1,2,3,4,5-pentaol (I-66) (30 mg, 0.044 mmol) in N,N-dimethylformamide (0.25 mL) was added tetrahydro-2H-pyran-4- carboxylic acid (8.6 mg, 0.066 mmol), DIEA at 8.5 mg, 0.066 mmol), and finally HATU (25.7 mg, 0.066 mmol). After stirring at room temperature for 17.5 hours, LCMS showed complete conversion to the product with some over-acylation. The crude mixture was diluted with MeCN (1 mL) and then H2O (3 mL). TFA was added until the solution was acidic and the resulting clear solution was purified by preparative HPLC (10 to 95% MeCN in H2 for 30 minutes). The product fractions were collected and neutralized with Amberlist A26 hydroxide resin to f 67. The resulting mixture was filtered and lyophilized to provide 9.0 mg of Compound I-67 (25%) as a TFA salt. MS (ES, m/z): 773.4 [M+H]+; 1H- NMR (400 MHz, DMSO-d6) δ 8.75 (s, 1H), 8.62 (d, J = 5.0 Hz, 1H), 7.44-7.31 (m, 4H), 7.29 (d, J = 7.2 Hz, 1H), 7.04-6.95 (m, 1H), 6.93 (s, 1H), 4.24 (s, 3H), 3.87 -3.76 (m, 4H), 3.76-3.68 (m, 5H), 3.22-3.10 (m, 2H), 3.04-2.91 (m, 2H), 2 .71-2.58 (m, 3H), 1.65-1.49 (m, 3H), 1.49-1.36 (m, 4H), 1.01 (d, J = 11.7 Hz , 4H),0.63 (d, J = 6.1 Hz, 2H), 0.32 (s, 2H).

[00395] The following compounds were prepared from I-66 according to the procedure described in Example 22 by replacing the described acid with tetrahydro-2H-pyran-4-carboxylic acid: Table 4. Compounds I-68 to I -74 Example 23: N-(4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)butyl)-3-methoxy-N- ((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)propanamide (I-75)

[00396] To a solution of (2R,3R,4R,5S)-6-(4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl)cyclopropoxy )methyl)phenyl)butylamino)hexane-1,2,3,4,5-pentaol (66) (41 mg, 0.061 mmol) in DCM (0.5 mL) was added TEA (9.3 mg, 0.09 mmol) followed by 3-methoxypropanoyl chloride (7.5 mg, 0.061 mmol). After 5 hours, additional 3-methoxypropanoyl chloride (15 mg, 0.12 mmol) was added. After another 16 hours, the starting material was consumed giving a mixture of over-acylated products. The reaction mixture was diluted with EtOAc (2 mL), washed with brine (2 mL) and dried over Na2SO4. The solvent was removed and the crude residue was diluted with a mixture of THF/MeOH (1.2 mL, 1:1). 1N NaOH (0.3 mL) was added and the mixture was stirred for 30 minutes, at which time only the desired product was observed. The solvent was removed and the reaction mixture was diluted with MeCN (1 mL) and H2O (3 mL) and acidified with TFA. Purification by preparative HPLC (10-90% over 30 minutes) gave 14.5 mg of I-75 as TFA salt. MS (ES, m/z): 747 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.76 (s, 1H), 8.63 (d, J = 5.8 Hz, 1H), 7.45 - 7.26 (m, 6H), 7.00 (t, J = 7.7 Hz, 1h), 6.94 (d, J = 5.6 Hz, 1H), 4.24 (s, 3H), 3.19 (s, 5H), 2.69 - 2.60 (m, 6H), 1.57 - 1.49 (m, 2H), 1.45 (s, 3H), 1.01 (d, J = 11.6 Hz, 4H) , 0.63 (d, J = 6.5 Hz, 2H), 0.33 (s, 2H).

[00397] The following compounds (Table 5) were prepared according to the procedure described in Example 23 of(2R,3R,4R,5S)-6-(4-(2,5-dichloro-4-((1- (4-(2-cyclopropoxy-phenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)butylamino)hexane-1,2,3,4,5-pentaol (I-66) replacing the described reagent with 4-chloride -methoxybutanoyl.Table 5.Compounds I-76 to I-77 Example 24: (S)-4-(4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)butyl)-2- ((1S,2R,3R)-1,2,3,4-tetrahydroxybutyl)-1,4-oxazepan-5-one (I-78)

[00398] (S)-4-(4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy) methyl)phenyl)butyl)-2- ((1S,2R,3R)-1,2,3,4- tetrahydroxybutyl)-1,4-oxazepan-5-one: A solution of (2R,3R,4R,5S)-6-(4- ( 2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)butylamino)hexane-1,2,3,4,5-pentaol (I- 66) (30 mg, 0.044 mmol) in DMF (0.25 mL) DIEA (8.5 mg, 0.066 mmol) was added followed by 3-(phenylsulfonyl)propanoic acid (9.3 mg, 0.044 mmol) and finally HATU (25.7 mg, 0.066 mmol). After 3.5 hours, product mixing and over-acylation were observed. The reaction mixture was diluted with MeOH (0.5 mL) and NaOMe (50, 25 wt% in MeOH) was added. After 30 minutes, LCMS showed complete conversion to the cyclized product. The solvent was removed and the crude residue was diluted with MeCN (1 ml) and H2O (3 ml) and acidified with TFA. Purification by preparative HPLC (10-90% over 30 minutes) gave 10.0 mg of I-78 as a TFA salt. MS (ES, m/z): 715.4 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.75 (s, 1H), 8.62 (d, J = 5.5 Hz, 1H), 7.47 - 7.31 (m, 4H), 7.29 (d, Ji= 7.2 Hz, 1H), 7.00 (t, J = 8.1 Hz, 1H), 6.94 (s, 1H), 4.24 (s, 2H), 2.69 - 2.60 (m, 4H), 1.56 - 1.38 (m, 4H), 1.00 (d, J = 11.0 Hz, 4H), 0.63 (d, J = 5.0 Hz, 2H), 0.33 (s, 2H). Example 25: 1-(4-(2,5-dichloro-4-((1-(4-(2- cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy) methyl)phenyl)butyl)-3-methyl-1- ((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)urea (I-79)

[00399] A suspension of (2R,3R,4R,5S)-6-(4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxy-phenyl)pyridin-3-yl) cyclopropoxy)methyl)phenyl)butylamino)hexane-1,2,3,4,5-pentaol (I-66) (182 mg, 0.275 mmol) in dry DMF (1.0 mL) under a N2 atmosphere was added TEA (42 mg, 0.415 mmol) and then 2,5-dioxopyrrolidin-1-yl methylcarbamate (47 mg, 0.275 mmol). After 18 hours, LCMS indicated complete conversion to the product. The crude reaction mixture was diluted with MeCN (1 mL) and H2O (3 mL) and acidified with TFA. Purification by preparative HPLC (10-95% over 30 minutes) gave 85 mg of 79 contaminated with 15% TFA ester byproduct. This mixture was dissolved in MeOH (1 mL) and NaOMe (20 L, 25 wt% in MeOH) was added. After 2 hours, only the product remained. Amberlite IR-120(H) resin (50 mg) was added and the mixture was stirred for 10 minutes. After filtration, the solvent was removed and lyophilization of MeCN/H2O (1:1, 2.0 mL) gave 64 mg of I-79 as a TFA salt. MS (ES, m/z): 718.12 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.85 (s, 1h), 8.72 (d, J = 5.6 Hz, 1H), 7.57 (d, J = 5.3 Hz, 1H), 7.44 (d, J = 8.7 Hz, 1H), 7.35 (dd, J = 16.2, 7.0 Hz, 3H), 7.03 (t, J = 7.3 Hz, 1H), 6.92 (s, 1H), 4.25 (s, 4H), 3.70 (s, 1H), 3.60 (d, J = 14.9 Hz, 2H), 3, 55 (s, 2H), 3.46 (s, 2H), 3.37 (dd, J = 10.9, 5.2 Hz, 1H), 3.32 - 3.06 (m, 5H), 2 .64 (s, 2H), 2.54 (s, 4H), 2.52 - 2.43 (m, 6H), 1.45 (s, 4H), 1.06 (d, J = 14.7 Hz, 4H), 0.64 (d, J = 5.9 Hz, 2H), 0.34 (s, 2H). Example 26: N-(4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)butyl)-N-((2S, 3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl)formamide (I-80)

[00400] Formic acid (51.1 mg, 1.11 mmol) and acetic anhydride (75 mg, 0.74 mmol) were stirred at 0 ° C for 10 minutes. A solution of (2R,3R,4R,5S)-6-(4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl )butylamino)hexane-1,2,3,4,5-pentaol (1-66, 49 mg, 0.074 mmol) in THF (0.2 mL) was added and the reaction mixture was allowed to warm to room temperature. After 2 hours, no starting material remained and LCMS showed a mixture of acylated and formylated product. EtOAc (5 mL) was added and the reaction mixture was washed with saturated NaHCO3 (2 x 5 mL), water (2 x 5 mL) and dried over Na2SO4. The solvent was removed and the crude residue was diluted with MeOH (0.5 mL). NaOMe (20 L, 25 wt% in MeOH) was added. After 15 minutes, LCMS showed only the desired product. The solvent was removed and the crude residue was diluted with MeCN (1 mL), H2O (3 mL) and acidified with TFA. This solution was purified by preparative HPLC (10-95% over 30 minutes). The product fractions were combined and neutralized with Amberlist A26 hydroxide resin to f 6-7. After filtration, lyophilization gave the desired compound (I-80, 10.5 mg) as a TFA salt. MS (ES, m/z): 689 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.64 (s, 1H), 8.50 (s, 1H), 8.04 - 8.00 (m, 1H), 7.91 (s, 1H ), 7.36 (d, J = 7.8 Hz, 2H), 7.31 (s, 1H), 7.23 (s, 1H), 7.13 (s, 1H), 6.95 (s , 2H), 4.56 - 4.9 (m, 3H), 4.21 (s, 2H), 3.55 (s, 9H), 2.99 (s, 2H), 2.98 (s, 3H), 2.62 (s, 5H), 1.45 (s, 5H), 0.93 (s, 4H), 0.59 (s, 2H), 0.30 (s, 2H). Example 26: (2R,3S,4R,5R)-N-(4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl )butyl)-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide (I-81)

[00401] A solution of G2 (284 mg, 0.50 mmol) in DMF (5 mL) was added (2S,3S,4S,5R,6S)-3,4,5,6-tetraacetoxytetrahydro-2H-pyran- 2-carboxylic acid (181 mg, 0.50 mmol) and DIEA at 97 mg, 0.75 mmol). HATU (285 mg, 0.75 mmol) was added and the reaction mixture was stirred for 16 hours. The crude solution was diluted with EtOAc (10 mL), washed with saturated NaHCO3 (5 mL) and brine (5 mL), and dried over Na2SO4. Purification by flash chromatography (12 g SiO2, DCM 5% MeOH in DCM for 15 minutes) provided 408 mg (89%) of Intermediate 81a as an oil. Step 2. (2S,3S,4R,5S)-N-(4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl )butyl)-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl) hexanamide (I-81)

[00402] 81a (408 mg, 0.44 mmol) was dissolved in MeOH (1 mL) and NaOMe solution (100μL, 25% by weight in MeOH) was added. After 90 minutes, no starting material remained. NaBH4 (92 mg, 2.5 mmol) was added. After another 30 minutes the reaction was complete and the solvent was removed. The crude residue was diluted with MeCN (9 mL) and water (9 mL) and acidified with TFA. After purification by preparative HPLC (10% to 60% MeCN in H2O with 0.1% TFA over 30 minutes), the combined product fractions were neutralized (f 6-7) with Amberlist A26 hydroxide resin. Filtration followed by lyophilization provided 26 mg of Compound I-81 (7%) as a white solid. MS (ES, m/z): 747 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.70 (s, 1H), 8.55 (s, 1H), 7.38 (d, J = 5.4 Hz, 2H), 7.33 ( d, J = 8.2 Hz, 1H), 7.30 - 7.20 (m, 3H), 7.11 (s, 1H), 6.98 (d, J = 8.8 Hz, 2H), 4.30 (d, J = 8.5 Hz, 1h), 4.24 (s, 3H), 2.65 (s, 3H), 1.49 (s, 7H), 1.38 (s, 2H ), 0.96 (s, 2H), 0.33 (s, 2H).

[00403] The following examples in Table 6 were made according to the procedure used in Example 26 from the appropriate starting amine in Table 3. Table 6. Compounds I-82 to I-85 Example 27: 1-(4-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)butyl)-1-(2-( 2-hydroxyethoxy)ethyl)-3-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)urea (I-86)

[00404] A solution of intermediate G4 (280 mg, 0.48 mmol) and TEA (63 mg, 0.624 mmol) in dichloromethane (4 mL) were added as a solution of (2R,3R,4R,5S)-6-isocyanate -hexane-1,2,3,4,5 - pentyl pentaacetate (260 mg, 0.624 mmol) in dichloromethane (1 mL). After 24 hours, additional TEA (63 mg, 0.624 mmol) and ((2R,3R,4R,5S)-6-isocyanatohexane-1,2,3,4,5-pentail pentaacetate (D10) (41 mg, 0.624 mmol) 1 mmol) in DCM (0.2 mL) was added. After a further 5 minutes, the reaction was complete. The crude mixture was diluted with dichloromethane (15 mL), washed with saturated NaHCO3 solution (15 mL), water (15 mL). mL) and brine (15 mL), and dried over Na2SO4. The solvent was removed to give crude Intermediate 86a as an oil which was used without further purification. -4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)butyl)-1-(2-(2-hydroxyethoxy)ethyl)-3-((2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)urea (I-86)

[00405] Crude intermediate 86a was diluted with MeOH (2 mL). NaOMe (50 L, 25 wt% in MeOH) was added and the reaction mixture was stirred for 1 hour. The solvent was removed, the crude residue was diluted with MeCN (4 mL) and water (4 mL), and the sample was acidified with TFA. After purification by preparative HPLC (30% to 95% MeCN in H2O with 0.1% TFA over 18 minutes), product fractions were combined and neutralized with Amberlist A26 hydroxide resin. Filtration and lyophilization gave 38.6 mg of Example I-86 (9%) as a trifluoroacetate salt. MS (ES, m/z): 792 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.66 (s, 1H), 8.52 (d, J = 4.9 Hz, 1H), 7.42 - 7.35 (m, 3H), 7.32 (d, J = 8.2 Hz, 1H), 7.25 (d, Ji = 6.0 Hz, 1H), 7.15 (d, J = 4.9 Hz, 1H), 7, 01 - 6.93 (m, 2H), 6.23 (s, 1H), 4.92 (d, J = 4.1 Hz, 1H, 4.58 (t, J = 5.4 Hz, 1H) , 4.44 (d, J = 5.6 Hz, 1H), 4.37 (d, J = 5.5 Hz, 1H), 4.31 (d, Ji = 6.0 Hz, 2H), 4 .23 (s, 2H, 3.57 (d, J = 5.6 Hz, 5H), 3.46 (dd, J = 13.9, 5.3 Hz, 6H), 3.40 (t, J = 5.1 Hz, 4H), 3.19 (s, 4H), 3.01 (d, J = 11.6 Hz, 2H, 2.64 (s, 2H), 1.46 (s, 4H) , 0.96 (s, 4H, 0.62 (d, J = 5.9 Hz, 2H), 0.32 (s, 2H).Example 28: 2-(5-(2,5-dichloro-4 -((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl )pentanamido)acetic acid (I-87)

[00406] A mixture of 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)pentanoic acid, 120b (50 mg, 0.095 mmol, 1.0 equiv), in DMF (0.4 mL) HOAt (15.5 mg, 0.114 mmol, 1.2 equiv) and EDC.HCl (20 mg, 0.104 mmol, 1.1 equiv) were added. The mixture was stirred at room temperature for 30 minutes. To the resulting mixture was added N,N-diisopropylethylamine (66.2μL, 0.38 mmol 4.0 equiv), followed by the addition of (9H-fluoren-9-yl)methyl 2-(((2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl)amino) acetate, D7 (75.7 mg, 0.142 mmol, 1.5 equiv). The resulting reaction mixture was stirred at room temperature over the weekend and purified by preparative HPLC to give 18.7 mg (23%) of the title compound TFA I-87 salt as a white solid. MS (ES, m/z): 747 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 8.88 (s, 1H), 8.72 (d, J = 5.7 Hz, 1H), 7.82 (d, J = 5.9 Hz, 1H) , 7.51 (t, J = 8.0 Hz, 1H), 7.43 - 7.34 (m, 2H), 7.27 (s, 1H), 7.09 (t, J = 7.6 Hz, 1H), 6.89 (s, 1H), 4.38 - 4.27 (m, 3H), 4.13 (s, 1H), 4.00 - 3.90 (m, 1H), 3 .81 - 3.74 (m, 2H), 3.73 - 3.58 (m, 5H), 3.58 - 3.43 (m, 2H), 2.76 - 2.67 (m, 2H) , 2.66 - 2.48 (m, 1H), 1.72 - 1.55 (m, 4H), 1.23 - 1.13 (m, 4H), 0.68 - 0.59 (m, 2H), 0.44 - 0.29 (m, 2H). Example 29: 2-(4-(5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin- 3-yl)cyclopropoxy)methyl)phenyl)pentanoyl)piperazin-1-yl)acetic acid (I-88)

[00407] A mixture of 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)pentanoic acid, 120b (80.6 mg N, 0.153 mmol, 1.0 equiv) and t-butyl 2-(piperazin-1-yl) acetate dihydrochloride (50.2 mg, 0.184 mmol, 1.2 equiv) in DMF (0.8 mL) were added. N-diisopropylethylamine (106.7μL, 0.612 mmol, 4.0 equiv) and HATU (69.8 mg, 0.184 mmol, 1.2 equiv). The mixture was then stirred at room temperature overnight. The resulting mixture was diluted with ethyl acetate, washed with H2O (2x) and brine (1x), dried and concentrated. The residue was column purified to give 98 mg (90%) of 88a as clear syrup. Step 2. 2-(4-(5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)pentanoyl)piperazin-1- il) acetic acid (I-88):

[00408] For t-butyl 2-(4-(5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)pentanoyl) piperazin-1-yl)acetate, 88a (122 mg, 0.172 mmol) was added 4.0 M HCl in dioxane (5 mL). The mixture was stirred at room temperature for 3 h and concentrated to give 138 mg of the crude dihydrochloride salt of the title compound as a yellow solid. The crude product (8 mg) was purified by preparative HPLC to give 5.4 mg (62%) of the title compound TFA I-88 salt as a white solid. MS (ES, m/z): 652 [M+H]+, 1H-NMR (400MHz, CD3OD) δ 8.90 (s, 1H), 8.73 (d, J = 5.8 Hz, 1H) , 7.81 (d, J = 5.8 Hz, 1H), 7.50 (t, J = 7.9 Hz, 1H), 7.43 - 7.36 (m, 2H), 7.26 ( s, 1H), 7.08 (t, J = 7.5 Hz, 1H), 6.90 (s, 1H), 4.34 (s, 2H), 4.09 (s, 2H), 3, 94 - 3.79 (m, 4H), 3.59 - 3.50 (m, 1H), 3.46 - 3.33 (m, 4H), 2.77 - 2.66 (m, 2H), 2.52 - 2.43 (m, 2H), 1.70 - 1.56 (m, 4H), 1.23 - 1.13 (m, 4H), 0.69 - 0.59 (m, 2H) ), 0.43 - 0.34 (m, 2H).Example 30: 2-(4-(5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3 -yl)cyclopropoxy)methyl)phenyl)pentanoyl)piperazin-1-yl)-N-methyl-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)acetamide (I -89)

[00409] A mixture of 2-(4-(5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl))pyridin-3-yl)cyclopropoxy)methyl)phenyl dihydrochloride salt )pentanoyl)piperazin-1-yl)acetic acid, crude example I-89 (60.7 mg, 0.0837 mmol, 1.0 equiv) and N-methyl-D-glucamine (19.6 mg, 0.100 mmol, 1.2 equiv) in DMF (0.4 mL) N,N-diisopropylethylamine (58.3, 0.335 mmol, 4.0 equiv) and HATU (38.2 mg, 0.100 mmol, 1.2 equiv) were added. The mixture was stirred at room temperature for 2 h and purified by preparative HPLC to give 61.4 mg (69%) of the title compound TFA I-89 salt as a white solid. MS (ES, m/z): 829 [M+H]+; 1H-NMR (400MHz, CD3OD) δ 8.86 (s, 1H), 8.70 (d, J = 5.7 Hz, 1H), 7.75 (d, J = 5.7 Hz, 1H), 7.52 - 7.46 (m, 1H), 7.41 - 7.35 (m, 2H), 7.26 (s, 1H), 7.07 (td, J = 7.5, 1.0 Hz, 1H), 6.91 (s, 1H), 4.48 (d, J = 15.8 Hz, 1H), 4.33 (s, 2H), 4.29 (d, J = 13.6 Hz, 1H), 4.02 (tt, J = 7.9, 4.0 Hz, 1H), 3.95 - 3.82 (m, 2H), 3.81 - 3.75 (m, 2H) , 3.73 (dd, J = 4.0, 2.2 Hz, 1H), 3.72 - 3.51 (m, 7H), 3.46 - 3.33 (m, 4H), 3.09 (s, 1H), 3.03 (s, 2H), 2.77 - 2.65 (m, 2H), 2.53 - 2.42 (m, 2H), 1.73 - 1.57 (m , 4H), 1.21 - 1.11 (m, 4H), 0.68 - 0.56 (m, 2H), 0.45 - 0.33 (m, 2H).Example 31: N,N' -(((oxybis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(5-(2,5-dichloro-4-((1-(4 -(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)pentanamide) (I-90)

[00410] A mixture of 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)pentanoic acid, 120b (31.2 mg , 0.0593 mmol, 2.0 equiv), and 2,2'-((oxybis(ethane-2,1-diyl))bis(oxy))diethanamine (5.7 mg, 0.030 mmol, 1.0 equiv ) in DMF (0.3 mL) N,N-diisopropylethylamine (31 μL, 0.178 mmol, 6.0 equiv) and HATU (24.7 mg, 0.0652 mmol, 2.2 equiv) were added. The mixture was stirred at room temperature for 2 h and purified by preparative HPLC to give 31.1 mg (36%) of the title compound I-90 as a white solid. MS (ES, m/z): 1207 [M+H]+; 1H-NMR (400MHz, CD3OD) δ 8.89 (s, 2H), 8.73 (d, J = 5.8 Hz, 2H), 7.82 (d, J = 5.9 Hz, 2H), 7.53 - 7.46 (m, 2H), 7.42 - 7.35 (m, 4H), 7.24 (s, 2H), 7.08 (td, J = 7.5, 1.0 Hz, 2H), 6.89 (s, 2H), 4.33 (s, 4H), 3.61 - 3.54 (m, 10H), 3.53 - 3.49 (m, 4H), 3 .34 (t, J = 5.5 Hz, 4H), 2.68 (t, J = 7.3 Hz, 4H), 2.22 (t, J = 7.0 Hz, 4H), 1.69 - 1.52 (m, 8H), 1.21 - 1.14 (m, 8H), 0.69 - 0.60 (m, 4H), 0.42 - 0.33 (m, 4H).Example 32: 2-(4-(2-(5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)pentanamido)ethyl) piperazin-1-yl)acetic acid (I-91)cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)pentanamido)ethyl)piperazine-1-carboxylate (Intermediate 91a)

[00411] A mixture of 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)pentanoic acid, 120b (101 mg, 0.192 mmol , 1.0 equiv) and t-butyl 4-(2-aminoethyl)piperazine-1-carboxylate (52.8 mg, 0.23 mmol, 1.2 equiv) in DMF (0.9 mL) were added N, N-diisopropylethylamine (100.3 L, 0.576 mmol, 3.0 equiv) and HATU (87.5 mg, 0.23 mmol, 1.2 equiv). The mixture was stirred at room temperature for 2 h. The resulting mixture was diluted with ethyl acetate, washed with H2O (2x) and brine (1x), dried and concentrated. The residue was column purified to give 135.5 mg (96%) of 91a as a white solid. Step 2. 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)-N-(2-(piperazin-1-yl )ethyl)pentanamide (Intermediate 91b)

[00412] To a t-butyl 4-(2-(5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl) cyclopropoxy)methyl)phenyl)pentanamido )ethyl)piperazine-1-carboxylate, 91a (135.5 mg, 0.184 mmol), 4.0 M HCl in dioxane (4 mL) was added. The mixture was stirred at room temperature for 30 minutes and concentrated to give 160 mg of the title compound in crude HCl salt (91b) as a yellow solid. Step 3. Intermediate 91c: t-butyl 2-(4-(2-(5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl )phenyl)pentanamido)ethyl)piperazin-1-yl)acetate (Intermediate 91c)

[00413] A mixture of 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)-N-(2-(piperazin- 1-yl)ethyl)pentanamide, crude 91b (0.191 mmol, 1.0 equiv), in THF (1.0 mL) trimethylamine (133μL, 0.955 mmol, 5 equiv) was added, followed by dropwise addition of 2 -t-butylbromoacetate (29.6 μL, 0.201 mmol, 1.05 equiv). The mixture was stirred at room temperature for 2 h. The resulting mixture was diluted with ethyl acetate, washed with H2O (2x) and brine (1x), dried and concentrated. The residue was column purified to give 130 mg (90%, 3 steps) of 91c. Step 4. 2-(4-(2-(5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)pentanamido)ethyl )piperazin- 1-yl)acetic acid (I-91)

[00414] For t-butyl 2-(4-(2-(5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl) cyclopropoxy)methyl)phenyl )pentanamido)ethyl)piperazin-1-yl)acetate, 91c (130 mg, 0.173 mmol), 4.0 M HCl in dioxane (4 mL) was added. The mixture was stirred at room temperature for 4 h and concentrated to give 146 mg of the HCl salt of the crude title compound as a yellow solid. The crude product (7 mg) was purified by preparative HPLC to give 3.6 mg (47%) of the title compound TFA salt (I-91) as a white solid. MS (ES, m/z): 695 [M+H]+; 1H-NMR (400MHz, CD3OD) δ 8.89 (s, 1H), 8.72 (d, J = 5.7 Hz, 1H), 7.80 (d, J = 5.8 Hz, 1H), 7.49 (t, J = 7.9 Hz, 1H), 7.39 (dd, J = 7.9, 6.5 Hz, 2H), 7.25 (s, 1H), 7.08 (t , J = 7.5 Hz, 1H), 6.90 (s, 1H), 4.33 (s, 2H), 3.60 - 3.53 (m, 1H), 3.53 - 3.46 ( m, 4H), 3.28 - 3.21 (m, 4H), 3.12 (t, J = 5.6 Hz, 2H), 3.08 - 2.96 (m, 4H), 2.70 (t, J = 6.9 Hz, 2H), 2.27 (t, J = 6.7 Hz, 2H), 1.70 - 1.54 (m, 4H), 1.24 - 1.13 ( m, 4H), 0.68 - 0.59 (m, 2H), 0.42 - 0.32 (m, 2H).Example 33: 5-(2,5-dichloro-4-((1-( 4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)-1-(4-((2S,3R,4S,5R)-2,3,4,5,6-pentahydroxyhexyl)piperazin- 1-yl)pentan-1-one (I-92 )

[00415] A mixture of galactose (241.8 mg, 1.342 mmol, 1.25 equiv) and tert-butyl piperazine-1-carboxylate (200 mg, 1.074 mmol, 1.00 equiv) in MeOH (11 mL) added HOAc (615μL, 10.74 mmol, 10.00 equiv) is added. The mixture was stirred at room temperature for 30 minutes and then NaCNBH3 (202.4 mg, 3.22 mmol, 3.00 equiv) was added. The resulting mixture was then stirred at room temperature overnight and concentrated. The residue was diluted with 10% MeOH in DCM, filtered and concentrated to give 0.76 g of crude product 92a as a white solid. Step 2. (2R,3S,4R,5S)-6-(piperazin-1-yl)hexane-1,2,3,4,5-pentaol (Intermediate 92b)

[00416] To t-butyl 4-((2S,3R,4S,5R)-2,3,4,5,6-pentahydroxyhexyl)piperazine-1-carboxylate, crude (92a,0.76 g), added se 4.0 M HCl in dioxane (5 mL). The mixture was stirred at room temperature for 2 h and concentrated. The residue was triturated with ether to give 0.616 g of the crude HCl salt 92b as a white solid. Step 3. 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)-1-(4-((2S,3R, 4S,5R)-2,3,4,5,6-pentahydroxyhexyl)piperazin-1-yl)pentan-1-one (I-92)

[00417] A mixture of 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)pentanoic acid, 120b (30 mg, 0.057 mmol, 1.0 equiv) and (2R,3S,4R,5S)-6-(piperazin-1-yl)hexane-1,2,3,4,5-pentaol, crude 92b (40.5 mg, 0.125 mmol, 2.2 equiv), in DMF (0.3 mL) N,N-diisopropylethylamine (79.4μL, 0.456 mmol, 8.0 equiv) and HATU (30.3 mg, 0.080 mmol, 1.4 equiv). The mixture was stirred at room temperature for 2 h and purified by preparative HPLC to give 25.2 mg (45%) of the title compound TFA salt (I-92) as a white solid. MS (ES, m/z): 758 [M+H]+; 1H-NMR (400MHz, CD3OD) δ 8.86 (s, 1H), 8.70 (d, J = 5.6 Hz, 1H), 7.75 (d, J = 5.3 Hz, 1H), 7.49 (t, J = 7.9 Hz, 1H), 7.42 - 7.35 (m, 2H), 7.27 (s, 1H), 7.08 (t, J = 7.5 Hz , 1H), 6.91 (s, 1H), 4.38 - 4.30 (m, 4H), 3.90 (t, J = 6.3 Hz, 1H), 3.69 - 3.63 ( m, 5H), 3.57 - 3.50 (m, 4H), 3.49 - 3.41 (m, 3H), 3.28 - 3.22 (m, 2H), 2.76 - 2, 68 (m, 2H), 2.52 - 2.44 (m, 2H), 1.69 - 1.59 (m, 4H), 1.19 - 1.11 (m, 4H), 0.68 - 0.58 (m, 2H), 0.42 - 0.34 (m, 2H).Example 34: (2S,3S,4R,5R,6S)-6-((5-(2,5-dichloro- 4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)pentanamido)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid (I- 93)

[00418] A mixture of (2R,3S,4R,5R,6S)-2-(hydroxymethyl)-6-(nitromethyl)tetrahydro-2H-pyran-3,4,5-triol (510 mg, 2.285 mmol) in MeOH (9.6 mL) and water (2.4 mL) were added to 10% Pd on carbon (350 mg) and purged with hydrogen gas. The mixture was stirred under hydrogen at room temperature overnight, filtered and concentrated to give 93a as a white solid. Step 2. Benzyl (((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)methyl)carbamate (Intermediate 93b)

[00419] A mixture of (2S,3R,4R,5S,6R)-2-(aminomethyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, 93a (2.285 mmol, 1, 0 equiv), in MeOH (9.6 mL) and water (2.4 mL) was added NaHCO3 (1.07 g, 12.74 mmol, 5.6 equiv) and benzyl chloroformate (1.73 mL, 12 .11 mmol, 5.3 equiv). The mixture was stirred at room temperature for 2 h and concentrated. The residue was diluted with water, washed with ether (2x) and lyophilized to give a white solid. The solid was taken up in 10% MeOH in DCM (30 mL), filtered and concentrated to give 700 mg (94%, 2 steps) of 93b as a white solid. Step 3. (2S,3S,4R,5R,6S)-6- ((((benzyloxy)carbonyl)amino)methyl)-3,4,5-trihydroxy-tetrahydro-2H-pyran-2-carboxylic acid (Intermediate 93c)

[00420] A mixture of benzyl (((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)methyl)carbamate, 93b ( 503.4 mg, 1.539 mmol, 1.0 equiv), in THF (18 mL) and sat. aq. (18 mL) TEMPO (48.1 mg, 0.308 mmol, 0.2 equiv) and KBr (54.9 mg, 0.462 mmol, 0.3 equiv) were added. The mixture was cooled to 0°C and bleach (5.5 mL) was added dropwise. The mixture was stirred at room temperature for 2 min and cooled to 0°C. More time (25 mg, 0.16 mmol, 0.1 equiv.) and bleach (3 mL) were added. The resulting mixture was stirred at room temperature for a further 1 h and extracted with ether (2x). The aqueous layer was acidified with 2M HCl to f 1-2, extracted with ethyl acetate (5x). The combined organic layers were washed with brine (1x), dried, concentrated and purified by preparative HPLC to give 241.6 mg (46%) of 93c. Step 4. (2S,3S,4R,5R,6S)-6-(aminomethyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid (Intermediate 93d)

[00421] A mixture of (2S,3S,4R,5R,6S)-6- ((((benzyloxy)carbonyl)amino)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid 93c (167 mg, 0.49 mmol), in MeOH (10 mL) added 10% Pd on carbon (35 mg) and purged with hydrogen. The mixture was stirred under hydrogen at room temperature for 3 h, filtered, washed with water (3x) and concentrated to give 102 mg (100%) of 93d as a white solid. Step 5. (2S,3S,4R,5R,6S)-6-((5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy) methyl)phenyl)pentanamido)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid (I-93)

[00422] A mixture of 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)pentanoic acid, 120b (50 mg, 0.095 mmol, 1.0 equiv), in DCM (0.7 mL) were added N,N'-N,N'- disuccinimidyl carbonate (36.5 mg, 0.142 mmol, 1.5 equiv) and trimethylamine (26. 5 L, 0.190 mmol, 2.0 equiv). The mixture was stirred at room temperature for 1 h, concentrated and column purified to give the acid N-succinimidyl ester. To the mixture of N-succinimidyl ester (0.095 mmol, 1.0 equiv) in DCM (1.1 mL) was added (2S,3S,4R,5R,6S)-6-(aminomethyl)-3,4,5- trihydroxytetrahydro-2H-pyran-2-carboxylic acid, 93d (29.5 mg, 0.142 mmol, 1.49 equiv) and trimethylamine (76.1μL, 0.546 mmol, 5.75 equiv). The mixture was stirred at room temperature overnight and purified by preparative HPLC to give 42.7 mg (54%) of the title compound TFA salt (I-93) as a white solid. MS (ES, m/z): 715 [M+H]+. 1H-NMR (400MHz, CD3OD) δ 8.88 (s, 1H), 8.72 (d, J = 5.9 Hz, 1H), 7.81 (d, J = 5.7 Hz, 1H), 7.51 (t, J = 7.9 Hz, 1H), 7.43 - 7.36 (m, 2H), 7.26 (s, 1H), 7.09 (t, J = 7.5 Hz , 1H), 6.90 (s, 1H), 4.34 (s, 2H), 3.76 (d, J = 9.6 Hz, 1H), 3.64 - 3.52 (m, 2H) , 3.49 - 3.33 (m, 4H), 3.14 (t, J = 8.7 Hz, 1H), 2.71 (t, J = 7.0 Hz, 2H), 2.26 ( t, J = 6.8 Hz, 2H), 1.70 - 1.54 (m, 4H), 1.24 - 1.12 (m, 4H), 0.70 - 0.60 (m, 2H) , 0.41 - 0.34 (m, 2H).Example 35: 3-(4-(5-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl )-2-methylphenyl)butyl)-1-ethyl-1-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)urea (I-94)

[00423] A mixture of 4-(5-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-methylphenyl)butan-1-amine, 65b ( 50 mg, 0.105 mmol, 1.0 equiv), in DMF (0.5 mL) was added disuccinimidyl N,N'-carbonate (32.2 mg, 0.126 mmol, 1.2 equiv). The mixture was stirred at room temperature for 1 h. Then (2R,3R,4R,5S)-6-(ethylamino)hexane-1,2,3,4,5-pentaol (43.9 mg, 0.210 mmol, 2.0 equiv) was added. The resulting mixture was stirred at 60°C overnight and purified by preparative HPLC to give 64.7 mg (75%) of the title compound (TFAI-94 salt) as a white solid. MS (ES, m/z): 712 [M+H]+. 1H-NMR (400MHz, CD3OD) δ 8.92 (s, 1H), 8.74 (d, J = 5.8 Hz, 1H), 7.87 (d, J = 5.9 Hz, 1H), 7.51 (t, J = 7.8 Hz, 1H), 7.44 (dd, J = 16.2, 8.0 Hz, 2H), 7.12 - 7.05 (m, 2H), 6 .77 (s, 1H), 4.38 (s, 2H), 3.94 - 3.87 (m, 1H), 3.80 - 3.74 (m, 1H), 3.73 - 3.55 (m, 6H), 3.42 (dd, J = 15.1, 4.5 Hz, 1H), 3.38 - 3.34 (m, 2H), 3.20 - 3.12 (m, 2H ), 2.62 - 2.53 (m, 2H), 2.21 (s, 3H), 1.63 - 1.48 (m, 4H), 1.21 - 1.01 (m, 7H), 0.70 - 0.62 (m, 2H), 0.44 - 0.36 (m, 2H).Example 36: 1-(4-(5-chloro-4-((1-(4-(2 -cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-methylphenyl)butyl)-3-((2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl) urea (I-95)

[00424] A mixture of glucosamine HCl salt (500 mg, 2.32 mmol, 1.0 equiv) in MeOH (10 mL) at 0 oC was added NaBH4 (395 mg, 10.44 mmol, 4.5 equiv. ) in portions.

[00425] A mixture of glucosamine HCl salt (500 mg, 2.32 mmol, 1.0 equiv) in MeOH (10 mL) at 0 oC was added NaBH4 (395 mg, 10.44 mmol, 4.5 equiv. ) in portions. The mixture was stirred at 0 - 10 oC for 3 h. To the mixture was added water (2.5 mL) and NaHCO3 (584.6 mg, 6.96 mmol, 3.0 equiv), followed by the dropwise addition of benzyl chloroformate (1.66 mL, 11.63 mmol, 5.0 equiv). The mixture was then stirred at room temperature overnight and concentrated. The residue was diluted with water and extracted with ether (2x). The aqueous layer was purified by preparative HPLC to give 258.3 mg (35%) of 95a as a white solid. Step 2. (2R, 3S, 4R, 5S) -5-aminohexane-1,2,3,4,6-pentaol (Intermediate 95b)

[00426] A mixture of (2S, 3R, 4S, 5R) -1,3,4,5,6-pentahydroxyhexan-2-yl) benzyl carbamate, 95a (258.3 mg, 0.82 mmol), in MeOH (10 mL) was added 10% Pd on carbon (40 mg) and purged with hydrogen. The mixture was stirred under hydrogen at room temperature for 1 h, filtered, washed with water (3x) and concentrated to give 150 mg (100%) of 95b as a brown sticky solid. Step 3. 1- (4- (5-chloro-4 - ((1- (4- (2-cyclopropoxyphenyl) pyridin-3- yl) cyclopropoxy) methyl) -2-methylphenyl) butyl) -3 - ((2S , 3R, 4S, 5R) - 1,3,4,5,6-pentahydroxyhexan-2-yl) urea (I-95):

[00427] A mixture of 4- (5-chloro-4 - ((1- (4- (2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) -2-methylphenyl) butan-1-amine,65b ( 28.2 mg, 0.059 mmol, 1.0 equiv), in DMF (0.3 mL) was added disuccinimidyl N,N'-carbonate (16.7 mg, 0.065 mmol, 1.1 equiv). The mixture was stirred at room temperature for 1 h. (2R, 3S, 4R, 5S)-5-aminohexane-1,2,3,4,6-pentaol, 95b (14 mg, 0.077 mmol, 1.3 equiv), was added. The mixture was stirred at 55 oC for 2 h. Then more 95b (6 mg, 0.033 mmol, 0.56 equiv) was added. The resulting mixture was stirred at 55°C overnight and purified by preparative HPLC to give 16.3 mg (35%) of the title compound (I-95) TFA salt as a white solid. MS (ES, m/z): 684 [M+H]+. 1H-NMR (400MHz, CD3OD) δ 8.88 (s, 1H), 8.73 - 8.67 (m, 1H), 7.85 - 7.77 (m, 1H), 7.53 - 7, 37 (m, 3H), 7.12 - 7.04 (m, 2H), 6.79 (s, 1H), 4.38 (s, 2H), 3.98 - 3.91 (m, 1H) , 3.88 - 3.81 (m, 1H), 3.81 - 3.73 (m, 1H), 3.72 - 3.52 (m, 6H), 3.22 - 3.09 (m, 2H), 2.62 - 2.52 (m, 2H), 2.21 (s, 3H), 1.63 - 1.44 (m, 4H), 1.20 - 1.11 (m, 2H) , 1.11 - 1.00 (m, 2H), 0.70 - 0.60 (m, 2H), 0.45 - 0.36 (m, 2H).Example 37: 1-(4-(5 -chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-methylphenyl)butyl)-1-ethyl-3-((2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl)urea (I-96)

[00428] A mixture of 4-(5-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-methylphenyl)butan-1-amine, 65b ( 200 mg, 0.419 mmol, 1.0 equiv), in DCM (0.5 mL) at 0 oC was added a solution of (Boc)2O (100.7 mg, 0.461 mmol, 1.1 equiv) in DCM (0 .5 mL) drop by drop. The mixture was stirred at room temperature overnight and cooled to 0°C. More (BocfeO (50 mg, 0.229 mmol, 0.55 equiv) and TEA (70μL, 0.50 mmol, 1.2 equiv) were added. The resulting mixture was stirred at room temperature for 1 h, concentrated, and column purified to give 200 mg (83%) of 96a as clear syrup. Step 2. (4-(5-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)- t-Butyl 2-methylphenyl)butyl)(ethyl)carbamate (Intermediate 96b)

[00429] A mixture of t-(4-(5-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)-cyclopropoxy)methyl)-2-methylphenyl)butyl)carbamate butyl, 96b (108.4 mg, 0.188 mmol, 1.0 equiv), in THF (0.44 mL) at 0 oC was added NaH (60% in mineral oil, 22.5 mg, 0.563 mmol, 3.0 equiv). The mixture was stirred at room temperature for 30 minutes, cooled to 0oC and then ethyl iodide (30.2μL, 0.376 mmol, 2.0 equiv) was added. The mixture was stirred at room temperature overnight, quenched with water and extracted with ethyl acetate. The organic layer was washed with brine (1x), dried, concentrated and column purified to give 47.4 (42%) of 96b as a yellow solid. Step 4. 4-(5-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-methylphenyl)-N-ethylbutan-1-amine (Intermediate 96c )

[00430] To (4-(5-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)-cyclopropoxy)methyl)-2-methylphenyl)butyl)(ethyl)carbamate of t -butyl, 96b (47.4 mg, 0.0783 mmol), 4.0 M HCl in dioxane (1 mL) was added. The mixture was stirred at room temperature for 30 minutes and concentrated to give the 96c HCl salt as a solid. Step 5. 1-(4-(5-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-methylphenyl)butyl)-1-ethyl-3 -((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)urea (I-96)

[00431] A mixture of 4-(5-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-methylphenyl)-N-ethylbutan-1-amine , crude 96c HCl salt (0.0783 mmol, 1.0 equiv), in DCM (0.5 mL), trimethylamine (32.8μL, 0.235 mmol, 3.0 equiv) was added, followed by dropwise addition drop of a solution of (2R, 3R, 4R, 5S) - 6-isocyanatohexane-1,2,3,4,5-pentanyl penta-acetate (D10) (35.9 mg, 0.0862 mmol, 1, 1 equiv) in DCM (0.5 mL). The mixture was stirred at room temperature for 1 h and column purified to give urea. A mixture of urea in MeOH (3 mL) was added (25% by weight in MeOH, 60μL). The mixture was stirred at room temperature for 5 minutes and purified by preparative HPLC. The HPLC fractions were combined, neutralized with the amberlyst® A26 hydroxide form to pH 6 and lyophilized to give 36.1 mg (65%) of the title compound. I-96 as a white solid. MS (ES, m/z): 712 [M+H]+. 1H-NMR (400MHz, CD3OD) δ 8.64 (d, J = 0.7 Hz, 1H), 8.46 (d, J = 5.1 Hz, 1H), 7.41 - 7.32 (m , 2H), 7.29 (dd, J = 7.5, 1.5 Hz, 1H), 7.22 (dd, J = 5.1, 0.6 Hz, 1H), 7.07 (s, 1H), 7.01 - 6.96 (m, 1H), 6.83 (s, 1H), 4.34 (s, 2H), 3.82 - 3.73 (m, 3H), 3.72 - 3.67 (m, 1H), 3.67 - 3.58 (m, 2H), 3.55 (tt, J = 6.0, 3.0 Hz, 1H), 3.43 (dd, J = 13.9, 5.1 Hz, 1H), 3.29 - 3.20 (m, 5H), 2.59 (t, J = 7.4 Hz, 2H), 2.21 (s, 3H) , 1.65 - 1.47 (m, 4H), 1.11 (t, J = 7.1 Hz, 3H), 1.02 - 0.86 (m, 4H), 0.65 - 0.56 (m, 2H), 0.43 - 0.36 (m, 2H).Example 38: 1- (4- (5-chloro-4 - ((1- (4- (2-cyclopropoxyphenyl) pyridin-3- il) cyclopropoxy) methyl) -2-methylphenyl) butyl) -1-(2-hydroxyethyl)-3 - ((2S, 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl) urea (I-97)

[00432] A mixture of 4-(5-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-methylphenyl)butan-1-amine, 65b( 50.3 mg, 0.105 mmol, 1.0 equiv), in acetonitrile (1.0 mL) were added 2-bromoethanol (8.2 μL, 0.116 mmol, 1.1 equiv) and trimethylamine (22μL, 0.158 mmol, 1 .5 equiv). The mixture was stirred at 60°C for 4 h, diluted with ethyl acetate, washed with brine (1x), dried and concentrated to give 47.9 mg (88%) of 97a as yellow syrup. Step 2. 1-(4-(5-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-methylphenyl)butyl)-1-(2- hydroxyethyl)-3-((2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl)urea (I-97)

[00433] I-97 was prepared according to the procedures described in Example 37. MS (ES, m/z): 728 [M+H]+. 1H NMR (400 MHz, CD3OD) δ 8.64 (s, 1H), 8.46 (d, J = 4.7 Hz, 1H), 7.42 - 7.32 (m, 2H), 7.29 (d, J = 7.5 Hz, 1H), 7.22 (d, J = 4.9 Hz, 1H), 7.07 (s, 1H), 6.99 (t, J = 7.3 Hz , 1H), 6.84 (s, 1H), 4.34 (s, 2H), 3.83 - 3.70 (m, 4H), 3.70 - 3.58 (m, 5H), 3, 58 - 3.52 (m, 1H), 3.42 (dd, J = 14.0, 4.8 Hz, 1H), 3.35 (t, J = 5.3 Hz, 2H), 3.29 - 3.19 (m, 2H), 2.59 (t, J = 7.4 Hz, 2H), 2.22 (s, 3H), 1.65 - 1.45 (m, 4H), 1, 04 - 0.88 (m, 4H), 0.67 - 0.58 (m, 2H), 0.44 - 0.36 (m, 2H).

[00434] Compounds I-98 to I-119 in Table 7 were prepared from known commercial starting materials in accordance with the methods described in Examples 30 to 38 for Compounds I-88 to I-97 and methods generally known to those of skill in the art. in the art. Table 7. Compounds I-98 to I-119

[00435] A solution of benzaldehyde (4.69 g, 44.15 mmol, 1.00 equiv) in MeOH (300 mL) d-glucamine (8.00 g, 44.15 mmol, 1.00 equiv) was added. ), The mixture was stirred at 15°C for 1 h, then heated to 65°C and stirred for 2 h. The mixture was cooled to 10°C, NaBH4 (3.34 g, 88.30 mmol, 2.00 equiv), the mixture was stirred at 10°C for 30 min, then water (30 mL) was added and continued. stirred for 30 min at 15°C. LCMS showed that the desired compound was detected. The mixture was concentrated. The residue was dissolved in EtOH, Amberlite IR-120 (H+) resin (10 g) was added and stirred for 15 min. The mixture was filtered, the filtrate was collected. 4N HCl/1,4-dioxane solution was added dropwise to the filtrate at 20°C until pH = 3. The precipitate was filtered and collected, then dried to give D1 (13.80 g, HCl salt) as a white solid.1H NMR: (400MHz, D2O, ppm): 7.44 (m, 5H), 4.27 (s, 2H), 4.01 (m, 1H), 3.74-3.71 ( m, 3H), 3.58-3.54 (m, 2H), 3.18-3.11 (m, 2H). Example 40: (2R, 3R, 4R, 5S) -6- (propylamino) hexane -1,2,3,4,5-pentaol (Intermediate D2)

[00436] A solution of propanal (2.00 g, 34.50 mmol, 1.25 equiv) in MeOH (200 mL) was added d-glucamine (5.00 g, 27.60 mmol, 1.00 equiv) The mixture was stirred at 15°C for 1 h, then heated to 65°C and stirred for 2 h. The mixture was concentrated under reduced pressure. The residue was dissolved in MeOH (200 mL), NaBH4 (2.09 g, 55.20 mmol, 2.00 equiv) was added at 10°C and stirred for 30 min. Then, water (20 mL) was added and stirring continued for 30 min. The mixture was concentrated. The residue was dissolved in EtOH; Amberlite IR-120 (H+) resin (8 g) was added and stirred for 15 min. Then the mixture was filtered, the filtrate was collected. 4N HCl/1,4-dioxane solution was added dropwise to the filtrate at 20°C until pH = 3. The precipitate was removed by filtration (2.3 g, most of the solid was inorganic salt). The filtrate was concentrated to about 80 mL, then EtOAc (160 mL) was added dropwise, a white precipitate formed. The second batch of precipitate was filtered and collected, then dried to D2 (4.20 g, 16.17 mmol, 58.59% yield, HCl salt) as a white solid. MS: (ES, m/z): 224 [M+H]. 1H NMR: (400MHz, D2O, ppm): 4.03-4.02 (m, 1H), 3.74-3.66 (m, 5H), 3.15-2.96 (m, 4H), 1.67-1.61 (m, 2H), 0.91-0.87 (m, 3H).Example 41: (2R,3R,4R,5S)-6-(2-methoxyethylamino)hexane- 1, 2,3,4,5-pentaol (Intermediate D3)

[00437] A solution of 2-methoxyethamine (2.29 g, 30.53 mmol, 1.10 equiv) in MeOH (200.00 mL) was added glucose (5.00 g, 27.75 mmol, 1.00 equiv), The mixture was stirred at 15°C for 1 h, then heated to 65°C and stirred for 2 h. NaBH4 (2.10 g, 55.50 mmol, 2.00 equiv) was added at 10°C and stirred for 30 min. Then, water (20 mL) was added and stirring continued for 30 min. The mixture was concentrated. The residue was dissolved in EtOH; Amberlite IR-120 (H+) (8 g) was added to the resin, the mixture was stirred for 15 min. Then the mixture was filtered, the filtrate was collected. 4N HCl/1,4-dioxane solution was added dropwise to the filtrate at 20°C until pH = 3. The precipitate was removed by filtration (about 2.2 g, most of the solid was inorganic salt ). The filtrate was concentrated to about 80 mL, then EtOAc (160 mL) was added dropwise, a white precipitate formed. The second batch of precipitate was filtered and collected, then dried to D3 (4.30 g, 15.59 mmol, 56.20% yield, HCl salt) as a white solid. MS: (ES, m/z): 240 [M+H]. 1H NMR: (400MHz, D2O, ppm): 4.02-4.01 (m, 1H), 3.73-3.72 (m, 2H), 3.69-3.62 (m, 3H), 3.55-3.55 (m, 2H), 3.30 (s, 3H), 3.22-3.22 (m, 3H), 3.07 (m, 1H).Example 42: (2R, 3R,4R,5S)-6-(2-(methylsulfonyl)ethylamino)hexane-1,2,3,4,5-pentaol (Intermediate D4)

[00438] To a mixture of d-glucamine (2.00 g, 11.04 mmol, 1.00 equiv) in MeOH (20 mL) was added 1-methylsulfonylethylene (1.17 g, 11.04 mmol, 1.00 equiv ) dropwise at 15° C. The reaction mixture was degassed and purged with N2 for 3 times, and then the mixture was stirred at 15°C for 16 h under N2 atmosphere. LC-MS showed that the reaction was complete. The reaction mixture was concentrated to about 10 mL and filtered. The filter cake was washed with MeOH (5 mL). D4 (2.20 g, 7.66 mmol, 69.35% yield) was obtained as a white solid. 1H NMR: (400MHz, D2O, ppm): 3.70-3.64 (m, 4H), 3.53-3.51 (m, 2H), 3.38-3.34 (m, 2H), 3.05-3.02 (m, 5H), 3.67-2.60 (m, 2H)Example 43:(2R, 3R, 4R, 5S) -6- (isopropylamino) hexane- 1,2,3 ,4,5-pentaol (Intermediate D5)

[00439] A solution of glucose (5.00 g, 27.75 mmol, 1.00 equiv) in MeOH (100 mL) was added to propan-2-amine (16.40 g, 277.50 mmol, 10.00 equiv). The mixture was stirred at 15°C for 1 h. Then the mixture was heated to 60°C and stirred at 60°C for 2 h. LC-MS showed that the starting material was converted into the intermediate. The solvent and excess propan-2-amine were removed under reduced pressure. The residue was dissolved in MeOH (100 mL), NaBH4 (1.57 g, 41.63 mmol, 1.50 equiv) was added to the mixture and the mixture was stirred at 15°C for 30 min. H2O (6 mL) was added to the mixture to quench the reaction. The solvent was removed under reduced pressure and the residue was dissolved in ethanol (60 ml). To the solution, Amberlite IR-120 Resin (H+) (12 g) was added and the mixture was stirred for 30 min. Then the mixture was filtered and the filtrate was adjusted to pH = 4 with a solution of HCl (4 mol/L) dioxane. The mixture was filtered and the solid was collected. The solid was dissolved in H2O (10 mL) and the solution was added to column A, which was filled with Amberlite IR-120 Resin (H +). The column was washed with H2O and 15% NH3 solution. The solution was concentrated under reduced pressure. D5 (700.00 mg, 3.07 mmol, 11.06% yield and 97.9% purity) was obtained as a light yellow solid. MS: (ES, m/z): 224.1 [M+H]. 1H NMR: (400MHz, D2O, ppm): 3.84 - 3.70 (m, 4H), 3.62-3.59 (m, 2H), 2.80 - 2.72 (m, 2H), 2.60 - 2.58 (m, 1H), 1.10 (d, J = 5.6 Hz, 6H). Example 44: (2R,3R,4R,5S)-6-(tetrahydro-2H -pyran-4-ylamino)hexane-1,2,3,4,5-pentaol (Intermediate D6)

[00440] Intermediate D6 (2R, 3R, 4R, 5S) -6- ((tetrahydro-2H-pyran-4-yl) amino) hexane-1,2,3,4,5-pentaol: A mixture of D-glucamine (5.00 g, 27.60 mmol, 1.00 equiv) and tetrahydropyran-4-one (4.14 g, 41.39 mmol, 1.50 equiv) in MeOH (15.00 mL ) was stirred at 20 oC for 1h. Then the mixture was heated to 70 oC and stirred for 18 h. LCMS showed that the imine was formed. The mixture was cooled to 20 oC and NaBH4 (3.13 g, 82.79 mmol, 3.00 equiv) was added. The mixture was stirred continuously for a further 2 h. LCMS showed that the desired product was formed. To the reaction mixture was added 5 g of H+ ion exchange resin and stirred for 30 min. The mixture was filtered. The filtrate was concentrated to give a white solid. The solid was dissolved in 20 mL of water and loaded onto an H + ion exchange resin column and eluted with water to remove excess salt. The desired product was eluted with 25% ammonium hydroxide. The eluent containing the product was concentrated under reduced pressure and lyophilized to give D6 (1.58 g, 5.96 mmol, 21.58% yield, 100% purity) as a gum. 1H NMR (400MHz, CD3OD, ppm): 3.96-3.95 (m, 3H), 3.81-3.76 (m, 2H), 3.65-3.63 (m, 3H), 3 .43 (m, 2H), 2.99-2.94 (m, 3H), 1.94-1.92 (m, 2H), 1.56-1.49 (m, 2H).Example 44: (9H-fluoren-9-yl)methyl2-((tert-butoxycarbonyl)amino)acetate (Intermediate D7) A 1000 mL round bottom flask was charged with a solution of 2-[[(tert-butoxy)carbonyl]amino]acetic acid (30 g, 171.25 mmol, 1.00 equiv) in N,N-dimethylformamide ( 500 mL), 9H-fluoren-9-ylmethanol (39 g, 198.73 mmol, 1.20 equiv), DCC (42 g, 203.56 mmol, 1.20 equiv), 4-dimethylaminopyridine (1 g, 8 .19 mmol, 0.05 equiv). The resulting solution was stirred overnight at room temperature. The solids were filtered. The resulting mixture was concentrated under vacuum. This resulted in 40 g (crude) of D7a as colorless oil.Step 2. (9H-Fluoren-9-yl)methyl 2-Aminoacetate (Intermediate D7b)

[00441] A 1000 mL round bottom flask was charged with a solution of 9H-fluoren-9-ylmethyl 2-[[(tert-butoxy)carbonyl]amino] acetate, D7a (40 g, 113.18 mmol, 1 .00 equiv), in 1,4-dioxane (200 mL), hydrogen chloride (6 mol/L) (200 mL). The resulting solution was stirred overnight at room temperature. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 200 mL of ether. Solids were collected by filtration. This resulted in 40 g (gross) of D7b as a white solid. Step 3. (9H-fluoren-9-yl)methyl 2-(((2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl)amino) acetate (Intermediate D7)

[00442] A 500 mL round bottom flask was charged with a solution of 9H-fluoren-9-ylmethyl 2-aminoacetate hydrochloride, D7b (20 g, 69.02 mmol, 1.00 equiv), in DMF/ PBS (140/60 mL), (3R, 4S, 5S, 6R)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol (15 g, 83.26 mmol, 1.20 equiv), NaCNBH3 (3.4 g, 54.11 mmol, 0.80 equiv). The resulting solution was stirred overnight at 30 oC in an oil bath. The solids were filtered. The resulting mixture was concentrated under vacuum. The crude product (10 g) was purified by preparative HPLC with the following conditions (SHIMADZU): Column, Sunfire C18 50 * 150; mobile phase, water with 0.05% TFA and CH3CN (5% CH3CN up to 36% in 13 min); Detector, 254nm. 6 g of product was obtained. This resulted in 5.97 g (21%) of D7 as a white solid. MS (ES, m/z): 418 [M+H]+. 1H-NMR (300 MHz, CD3OD, ppm): 7.82 (d, J =7.5Hz, 2H), 7.65 (d, J = 7.5Hz, 2H), 7.40 (m, 4H), 4.67 (d, J = 6.3 Hz, 2H), 4.33 (m, 1H), 4.10 (m, 1H), 3.99 (s, 2H), 3.79 (m, 4H), 3.22 (m, 2H).Example 45: (2R,3R,4R, 5S)-6-(5-hydroxypentylamino)hexane-1,2,3,4,5-pentaol (Intermediate D8)

[00443] To a mixture of D-glucose monohydrate (3.0 g, 15.14 mmol, 1.0 equiv) in MeOH (100 mL) was added 5-aminopentan-1-ol (1.81 mL, 16.64 mmol, 1.1 equiv). The mixture was stirred at room temperature for 1 h, heated to 60 oC and stirred for 2 h. The mixture was cooled to 10°C and NaBH4 (1.145 g, 30.28 mmol, 2.0 equiv) was added in portions. The mixture was stirred at room temperature for 2 h and water (10 ml) was added. The mixture was allowed to stand at room temperature for 30 minutes and concentrated. The residue was taken up in ethanol and amberlite resin (H+) (6 g) was added. The resulting mixture was stirred at room temperature for 30 minutes and filtered. The filtrate was acidified with a solution of 4.0 M HCl in dioxane to pH 3. The white precipitate was removed by filtration. To the filtrate, ethyl acetate was added dropwise to form a white precipitate. The precipitate was triturated with ether to give 3.5 g (76%) of D8 Salt HCl as a white solid. Example 46: (2R,3R,4R,5S)-6-(2-(morpholinosulfonyl)ethylamino)hexane- 1,2,3,4,5-pentaol (Intermediate D9)

[00444] To a mixture of morpholine (96.9 mg, 1.112 mmol, 1.0 equiv) in DCM (8.0 mL) at 0 oC was added trimethylamine (620μL, 4.45 mmol, 4.0 equiv), followed by slow addition of a solution of 2-chloroethanesulfonyl chloride (116.2μL, 1.112 mmol, 1.0 equiv) in DCM (2.0 mL). The mixture was stirred at 0 oC for 1 h, warmed to room temperature and stirred for another 2 h. The resulting mixture was washed with water (1x), dried, concentrated and column purified to give 120 mg (61%) of D9a as a clear oil. Step 2. (2R, 3R, 4R, 5S)-6-((2-(morpholinosulfonyl)ethyl)amino)hexane-1,2,3,4,5-pentaol (Intermediate D9) A mixture of D-glucamine ( 102.9 mg, 0.568 mmol, 1.0 equiv) in MeOH (1.0 mL) was added to a mixture of 4-(vinylsulfonyl) morpholine (D9a) (100.6 mg, 0.568 mmol, 4.0 equiv) in MeOH (0.5 mL). The mixture was then stirred at room temperature overnight. The white precipitate was collected by filtration to provide 162 mg (80%) of D9 as a white solid. Example 47: ((2R, 3R, 4R, 5S)-6-isocyanatohexane-1,2,3,4,5-pentanyl pentaacetate (Intermediate D10)

[00445] Intermediate D10 was in accordance with the method of Martín Ávalos, Reyes Babiano, Pedro Cintas, Michael B. Hursthouse, José L. Jiménez, Mark E. Light, Juan C. Palacios and Esther MS Pérez. Eur. J. Org. Chem. 2006, 657-671.Example 48: (2R, 3S, 4R, 5S)-5-isocyanate-hexane-1,2,3,4,6-pentanyl penicetate (Intermediate D11)

[00446] A mixture of benzyl ((2S, 3R, 4S, 5R)- 1,3,4,5,6-pentahydroxyhexan-2-yl) carbamate, (557 mg, 1.774 mmol, 1.0 equiv), in pyridine (5.4 mL) at 0 oC, acetic anhydride (7.71 mL) was added dropwise. The mixture was slowly warmed to room temperature and stirred at room temperature overnight. The mixture was poured into ice water and extracted with DCM (2x). The combined organic layers were washed with 1N HCl (1x), sat. NaHCO3 (1x) and brine (1x), dried, concentrated and column purified to give 0.76 g (82%) of D11a as a clear syrup. Step 2. (2R, 3S, 4R, 5S)-5-aminohexane-1,2,3,4,6-pentanyl pentaacetate (Intermediate D11b)

[00447] A mixture of (2R, 3S, 4R, 5S) -5 - (((benzyloxy) carbonyl) amino) hexane-1,2,3,4,6-pentanyl penta-acetate (760 mg, 1.448 mmol , 1.0 equiv.) In MeOH (10 mL) was added 4.0 M HCl in dioxane (0.54 mL, 2.16 mmol, 1.5 equiv.) and 10% palladium on carbon (152 mg ). The mixture was stirred at room temperature under hydrogen for 1 h, filtered and concentrated to give 581 mg (94%) of D11b Salt HCl as a white solid. Step 3. (2R, 3S, 4R, 5S)-5-isocyanate-hexane-1,2,3,4,6-pentanyl penta-acetate (Intermediate D11)

[00448] A mixture of triphosgene (239.5 mg, 0.807 mmol, 1.0 equiv.) in DCM (7.6 mL) was added saturated aqueous NaHCO3 (5.1 mL) and penta-acetate (2R, 3S , 4R, 5S) -5-aminohexane- 1,2,3,4,6-pentanyl (345 mg, 0.807 mmol, 1.0 equiv.). The mixture was stirred at 0 oC for 45 minutes and extracted with DCM. The organic layer was washed with brine (1x), dried and concentrated to give 257.3 mg (62%) of crude product D11 as a clear syrup. Example 49: N-benzyl-5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)-N-((2R,3S ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)pentanamide (I-120)

[00449] A 250 mL round bottom flask was charged with 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-ol, A23 (1.5 g, 5.61 mmol, 1, 00 equiv), methyl 5-[4-(bromomethyl)-2,5-dichlorophenyl]pentanoate, C6 (2.2 g, 6.21 mmol, 1.10 equiv), N,N-dimethylformamide (100 mL) . This was followed by the addition of sodium hydride (60% in oil) (900 mg, 37.50 mmol, 4.00 equiv) in portions at room temperature. The resulting solution was stirred for 1 h at 0°C. The reaction was cooled by adding 20 mL of water. The resulting solution was diluted with 100 mL of water. The resulting solution was extracted with 3 x 100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2 x 150 ml of water and 1 x 100 ml of sat. sodium chloride. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 2.0 g (66%) of 120a as the brown oil. Step 2. 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)pentanoic acid (Intermediate 120b)

[00450] A 100 mL round bottom flask was charged with 5-[2,5-dichloro-4-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxyl]methyl)phenyl]pentanoate methyl, 120a (1.02 g, 1.89 mmol, 1.00 equiv), methanol (15 mL), water (20 mL). This was followed by the addition of LiOH.H2O (400 mg, 9.52 mmol, 5.00 equiv) in portions at room temperature. The resulting solution was stirred for 2 h at 50°C. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 20 mL of water. The resulting mixture was washed with 1x40 ml of ethyl acetate. The pH value of the solution was adjusted to 3-4 with cons. hydrogen chloride. The resulting solution was extracted with 3x50 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 1 x 50 ml of water and 1 x 50 ml of sat. sodium chloride. The mixture was dried over anhydrous sodium sulfate. This resulted in 0.6 g (60%) of 120b as colorless oil. MS: (ES, m/z): 526 [M+H]+. Step 3. N-Benzyl-5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)-N-((2R,3S ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)pentanamide (I-120)

[00451] D1 (12 mg, 0.0456 mmol, 1.2 equiv) was added to a solution of 120b (20 mg, 0.038 mmol, 1.00 equiv), HATU (17 mg, 0.0456 mmol, 1, 20 eq) and DIEA (15 mg, 0.114 mmol, 3.00 equiv) in DMF (0.2 mL). The resulting solution was stirred for 1 h at room temperature. The crude product was purified by preparative HPLC with a CH3CN/H2O gradient containing 0.1% TFA (40% CH3CN to 80% CH3CN for 18 min) to obtain 8 mg (27%) of the title compound (I-120 ) trifluoroacetate salt as a white solid. MS (ES, m/z): 779 [M+H]+; 1H-NMR (400MHz, DMSO-d6, ppm): δ 8.82 (s, 1H), 8.69 (d, J = 5.5 Hz, 1H), 7.54 (d, J = 4.9 Hz, 1H), 7.47 - 7.41 (m, 1H), 7.37 - 7.32 (m, 3H), 7.29 (dd, J = 13.0, 4.7 Hz, 2H) , 7.22 (d, J =7.3 Hz, 1H), 7.15 (d, J = 6.9 Hz, 2H), 7.02 (t, J = 7.5 Hz, 1H), 6 .91 (d, J = 7.1 Hz, 1H), 4.68 (d, J = 15.1 Hz, 1H), 4.43 (d, J = 15.4 Hz, 1H), 4.24 (s, 2H), 3.81 (s, 1H), 3.64 - 3.50 (m, 3H), 3.37 - 3.20 (m, 2H), 2.65 (s, 1H), 1.50 (d, J = 30.5 Hz, 4H), 1.05 (d, J = 13.0 Hz, 4H), 0.62 (d, J = 6.1 Hz, 2H), 0, 33 (s, 2H).Example 50: 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)-N-methyl- N-(2-(((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)ethyl) pentanamide (I-121)

[00452] A solution of 2-methylamine ethanol (3.98 g, 53 mmol, 2.12 equiv) in DCM (35 mL) was cooled to 0° C. Benzyl chloroformate (4.26 g, 25 mmol, 1 .00 equiv) was then added dropwise and the reaction mixture was stirred for 1 h at 0°C and then warmed to room temperature. The solution was concentrated in vacuo and extracted with ethyl acetate (150 ml). The organic extract was washed with 1N HCl (50 mL), water (50 mL), NaHCO3 (50 mL) and brine (50 mL). The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo to yield 4.37 g (84%) of 121a. Step 2. (2R, 3R, 4S, 5R, 6R)-2-(acetoxymethyl)-6-(2- (((benzyloxy)carbonyl)(methyl)amino)ethoxy)tetrahydro-2H-pyran-3, 4,5-tri-yl triacetate (Intermediate 121b)

[00453] Anhydrous Na2SO4 (500 mg, 3.52 mmol, 2.89 equiv.) A mixture of tetra-O-acetylglucopyranosyl bromide (500 mg, 1.22 mmol, 1.00 equiv) and benzyl (2- hydroxyethyl)(methyl) carbamate (347 mg, 1.66 mmol, 1.40 equiv) in dichloromethane (3 mL). The resulting solution was stirred at room temperature for 30min. Ag2CO3 (480 mg, 1.75 mmol, 1.40 equiv.) was then added to the mixture. The resulting reaction was purged with N2, wrapped in aluminum foil, and stirred for 18 hours at room temperature. Reaction progress was monitored by LCMS and TLC (EtOAc/hexane 1:1). Additional tetra-O-acetylglucopyranosyl bromide (340 mg, 0.827 mg, 0.678 equiv) and Ag2CO3 (340 mg, 1.23 mmol, 1.01 equiv) were added to the mixture and stirred for an additional 16 h at room temperature. The reaction mixture was then filtered through a pad of Celite and washed with 5x10 mL of dichloromethane. The crude product was purified using flash chromatography, eluting over SiO2 (50 g) with a 40% to 60% EtOAc/hexane gradient to yield 975 mg of 121b. Step 3. (2R, 3R, 4S, 5R, 6R)-2-(acetoxymethyl)-6-(2-(methylamino)ethoxy)tetrahydro-2H-pyran-3,4,5-triyltriacetate (Intermediate 121c)

[00454] A mixture of 121b (975 mg, 1.81 mmol) and 10% Pd/C (10 wt% C) (120 mg, 1.13 mmol, 0.624 equiv) in methanol (15 mL) was stirred under H2 for 90 min at room temperature. The progress of the reaction was monitored by LCMS. The resulting reaction mixture was filtered through celite and concentrated under vacuum and used without further purification. Step 4. (2R, 3R, 4S, 5R, 6R)-2-(acetoxymethyl)-6-(2-(5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl)cyclopropoxy)methyl)phenyl)-N-methylpentanamido)ethoxy)tetrahydro-2H-pyran-3,4,5-triyltriacetate (Intermediate 121d)

[00455] 121c (23 mg, 0.0570 mmol, 1.20 equiv) was added to an acid solution of 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridine -3-yl)cyclopropoxy)methyl)phenyl)pentanoic acid, 120b (25 mg, 0.0475 mmol, 1.00 equiv), HATU (30 mg, 0.079 mmol, 1.7 equiv) and DIEA (18 mg, 0.142 mmol , 3 equiv) in DMF (0.3 mL). The resulting solution was stirred for 2 h at room temperature and the reaction progress was monitored by LCMS. The crude product was purified by preparative HPLC with a CH3CN/H2O gradient containing 0.1% TFA (10% CH3CN to 80% CH3CN over 18 min) and was used directly. Step 4. 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)-N-methyl-N-(2-(( (2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)ethyl)pentanamide (I-121)

[00456] Sodium methoxide (25% by weight in MeOH) (0.20 mL) was added to the solution of 121d in methanol (0.5 mL). The resulting mixture was stirred for 1 h at room temperature and the reaction progress was monitored by LCMS. The mixture was concentrated in vacuo and the crude product was purified by preparative HPLC with a CH3CN/H2O gradient containing 0.1% TFA (10% CH3CN to 80% CH3CN for 18 min) to give 3 mg (8.6% ) of compound (I-121) trifluoroacetate salt as a white solid. MS (ES, m/z): 745 [M+H]+. 1H-NMR (400MHz, DMSO-d6, ppm): δ 8.79 (s, 1H), 8.66 (d, J = 5.5 Hz, 1H), 7.53 - 7.49 (m, 1H ), 7.43 (t, J = 7.6 Hz, 1H), 7.36 - 7.28 (m, 3H), 7.01 (t, J = 7.4 Hz, 1H), 6.90 (s, 1H), 4.23 (s, 2H), 2.98 (s, 3H), 2.88 (s, 3H), 2.78 (d, J = 8.5 Hz, 3H), 2 .72 (s, 2H), 2.67 (t, J = 7.3 Hz, 5H), 2.63 (s, 4H), 2.39 - 2.24 (m, 4H), 1.90 ( d, J = 0.8 Hz, 4H), 1.50 (s, 4H), 1.03 (d, J = 14.2 Hz, 4H), 0.62 (d, J = 5.8 Hz, 2H), 0.32 (s, 2H). Example 51: 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl) -N-(2,3-dihydroxypropyl)-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)pentanamide (I-122)

[00457] K2CO3 (48 mg, 0.351 mmol, 0.950 equiv) was added to a solution of D1 (100 mg, 0.369 mmol, 1.00 equiv) and benzyl glycidyl ether (58 mg, 0.351 mmol, 0.950 equiv) in water ( 2 mL). The resulting mixture was stirred for 17 h at 60°C. The resulting mixture became an emulsion with the crude product in the oil layer. The solution was decanted and the oil was purified by preparative HPLC with a CH3CN/H2O gradient containing 0.1% TFA (10% CH3CN to 50% CH3CN over 18 min) to provide 74 mg of 122a (30%) as a white solid. Step 2. (2R, 3R, 4R, 5S)-6-((2,3-dihydroxypropyl)amino)hexane-1,2,3,4,5-pentaol (Intermediate 122b)

[00458] Pd/C (10 wt% C) (50 mg, 0.470 mmol, 2.80 equiv.) and concentrated HCl (0.20 mL) were added. 122a (72 mg, 0.165 mmol, 1.00 equiv) in ethanol (2 mL). The resulting mixture was purged with H2 and allowed to stir for 90 min at room temperature. The resulting solution was diluted with methanol (20 mL), washed with 2 x 20 mL of water, dried over anhydrous sodium sulfate and concentrated under reduced pressure to provide 42 mg of 122b which was used without further purification. Step 3. 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)-N-(2,3-dihydroxypropyl) -N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)pentanamide (I-122)

[00459] HATU (63 mg, 0.165 mmol, 1.90 equiv.) was added to a solution of 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridine-3 - yl)cyclopropoxy)methyl)phenyl)pentanoic acid, 120b (46 mg, 0.0867 mmol, 1.00 equiv), 122b (42 mg, 0.165 mmol, 1.90 equiv) and DIEA (64 mg, 0.494 mmol, 3.00 equiv) in DMF (2 mL). The resulting solution was stirred for 16 h at room temperature. The crude product was purified by preparative HPLC with a CH3CN/H2O gradient containing 0.1% TFA (10% CH3CN to 80% CH3CN for 18 min) to provide 41 mg (62%) of the trifluoroacetate salt compound I-122 as a light yellow solid. MS (ES, m/z): 763 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1H), 8.71 (d, J = 5.6 Hz, 1H), 7.60 (d, J = 5.5 Hz, 1H), 7.45 (t, 1H), 7.33 (dt, J = 9.1, 3.9 Hz, 3H), 7.02 (t, J = 7.4 Hz, 1H), 6, 90 (s, 1H), 4.24 (s, 4H), 3.25 (d, 4H), 2.62 (s, 3H), 1.49 (s, 4H), 1.12 - 1.00 (m, 5H), 0.63 (d, J = 6.1 Hz, 2H), 0.33 (s, 2H).

[00460] The compounds in Table 8 Compounds I-123 to I-124 were prepared from commercial or known base materials according to the method described in Example 50 and methods generally known to those skilled in the art. Table 8. Compounds I -123 to I-125

[00461] D1 (53 mg, 0.171 mmol, 2.00 equiv) was added to 5-(2,5-dichloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridine-3-yl) acid solution )cyclopropoxy)methyl)phenyl)pentanoic acid, 120b (45 mg, 0.0856 mmol, 1.00 equiv), HATU (65 mg, 0.171 mmol, 2.00 equiv) and DIEA (33 mg, 0.257 mmol, 3.00 equiv) in DMF (1 mL). The resulting solution was left stirring for 1 h at room temperature. The crude product was purified by preparative HPLC with a CH3CN/H2O gradient containing 0.1% TFA (10% CH3CN to 80% CH3CN over 18 min). Fractions containing the desired product were then neutralized with Amberlyst A26 hydroxide resin and filtered to provide 15 mg (22%) of the title compound I-126 as a white solid. MS (ES, m/s): 779 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.77 (s, 1H), 8.64 (d, J = 5.3 Hz, 1H), 7.45 - 7.38 (m, 2H), 7.37 - 7.26 (m, 5H), 7.23 (d, J = 7.4 Hz, 1H), 7.16 (d, J = 7.0 Hz, 2H), 7.01 (t , J = 7.4 Hz, 1H), 6.94 (d, J = 7.3 Hz, 1H), 4.69 (d, J = 15.4 Hz, 2H), 4.44 (d, J = 15.0 Hz, 1H), 4.25 (s, 2H), 3.82 (s, 1H), 3.57 (t, J = 9.7 Hz, 3H), 3.51 - 3.25 (m, 5H), 2.66 (s, 2H), 1.51 (d, J = 30.1 Hz, 4H), 1.01 (d, J = 9.5 Hz, 4H), 0.62 (d, J = 6.0 Hz, 2H), 0.34 (s, 2H).

[00462] Compounds I-127 to I-131 were prepared from intermediate 120b and commercial or known base materials in accordance with the methods specified in Table 9 and methods generally known to those skilled in the art. Table 9. Compounds I-127 to I-131.

[00463] Compounds I-132 to I-241 in Table 10 were prepared from known commercial base materials or the appropriate intermediates disclosed herein, in accordance with the methods of the examples specified in Table 10 and methods generally known to those skilled in the art. technique.Table 10. Compounds I-132 to I-241 Step 1. 2-(hex-5-yn-1-yl)-2,3-dihydro-1H-isoindole-1,3-dione (Intermediate 242a)

[00464] A solution of 6-chlorohex-1-yne (5 g, 42.89 mmol, 1.00 equiv) and 2-potassium-2,3-dihydro-1H-isoindole-1,3- dione (10.3 g, 55.61 mmol, 1.30 equiv) naN,N-a dimethylformamide (60 mL) was stirred overnight at 80 oC in an oil bath. The reaction mixture was cooled to 15-25°C. The resulting solution was diluted with 500 mL of H2O. The solids were collected by filtration and dried in a reduced pressure oven to yield 9.2 g (94%) of 2-(hex-5-yn-l-yl)-2,3-dihydro-1H-isoindole- l,3-dione (242a) as an off-white solid. Step 2. 2-(5-bromo-hex-5-en-1-yl)-2,3-dihydro-1H-isoindole-1,3-dione (Intermediate 242b)

[00465] To the solution stirred at -78 oC was added 2-(hex-5-yn-1-yl)-2,3-dihydro-1H-isoindole-1,3-dione (17.9 g, 78.76 mmol, 1.00 equiv) in dichloromethane (80 mL) BBr3 (19.6 g, 1.00 equiv.) dropwise. The mixture was stirred for 1 h at room temperature. The reaction was cooled by adding 20 mL of water. The resulting solution was extracted with 2 x 200 mL of dichloromethane and the organic layers were combined and dried over sodium sulfate and concentrated in vacuo. To this were added hexanes (300 mL), acetic acid (18 mL). The resulting solution was stirred overnight at 80°C in an oil bath. The pH value of the solution was adjusted to 7 with sodium bicarbonate. The resulting solution was extracted with 3 x 200 mL of dichloromethane and the organic layers were combined and dried over sodium sulfate and concentrated in vacuo. This resulted in 22.4 g (92%) of 2-(5-bromo-hex-5-en-1-yl)-2,3-dihydro-1H-isoindole-1,3-dione (242b) like light yellow oil. Step 3. 2-Chloro-5-[6-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)hex-1-en-2-yl]benzaldehyde (Intermediate 242c)

[00466] A 500 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with 2-chloro-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (8.1 g , 30.39 mmol, 1.10 equiv), 2-(5-bromohex-5-en-1-yl)-2,3-dihydro-1H-isoindole-1,3-dione (8, 5 g, 27.58 mmol, 1.00 equiv), Pd (PP3)4 (1.60 g, 1.38 mmol, 0.05 equiv), K3PO4 (11.7 g, 55.12 mmol, 2, 00 equiv), dioxane (300 mL) and water (30 mL) were stirred overnight at 80 oC in an oil bath. The reaction was then cooled by adding 500 mL of H2O. The resulting solution was extracted with 3 x 200 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (5:95). This resulted in 5.5 g (54%) of 2-chloro-5-[6-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)hex-1-en- 2-yl]benzaldehyde (242c) as an off-white solid. Step 4. 2-Chloro-5-[6-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)hexan-2-yl]benzaldehyde (Intermediate 242d)

[00467] Hydrogen was introduced into a stirred solution of 2-chloro-5-[6-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)hex-1-en-2 - yl]benzaldehyde (5.5 g, 14.95 mmol, 1.00 equiv) in ethyl acetate (100 mL) and Rh/C (5.5 g). The resulting suspension was stirred overnight at room temperature. The solids were filtered and the resulting mixture was concentrated in vacuo. The crude product (5.5 g) was purified by flash chromatography with the following conditions: Column, silica gel; mobile phase, CH3CN:H2O = 0:100 increasing to CH3CN:H2O = 30:70 in 20 min; Detector, UV 254 nm. 3.5 g of product was obtained. This resulted in 3.5 g (63%) of 2-chloro-5-[6-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)hexan-2-yl] benzaldehyde (242d) as pale yellow oil. Step 5. 2-(5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyll]hexyl)-2,3-di -hydro-1H-isoindole-1,3-dione (Intermediate 242e)

[00468] A 500 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (4, 5 g, 16.90 mmol, 1.00 equiv), 2-chloro-5-[6-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)hexan-2- yl]benzaldehyde (3.23 g, 8.73 mmol, 1.00 equiv) in dichloromethane (300 mL) and TFA (0.5 mL) was added NaBH(OAc)3 (15.5 g, 73.13 mmol , 6.00 equiv), The resulting solution was stirred overnight at 30oC. The reaction mixture was then cooled by adding 500 mL of H2O. The resulting solution was extracted with 3 x 200 mL of dichloromethane and the organic layers combined and dried over sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (30:70). This resulted in 5.5 g (52%) of 2-(5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl ]hexyl)-2,3-dihydro-1H-isoindole-1,3-dione as a pale yellow solid. Step 6. N-[[5-(6-aminohexan-2-yl)-2-chlorophenyl]methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine ( I-242)

[00469] To a 250 mL round bottom flask, 2-(5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino was added )methyl]phenyl]hexyl)-2,3-dihydro-1H-isoindole-1,3-dione (200 mg, 0.32 mmol, 1.00 equiv), methanol (5 mL), tetrahydrofuran ( 5 mL) and hydrazine hydrate (0.2 mL, 10.00 equiv). The resulting solution was stirred for 3 h at 60°C in an oil bath. The solids were filtered. The crude product was purified by Prep-HPLC with the following conditions: Column, XBridge C18 OBD Prep Column, 5.19 mm X 250 mm; mobile phase, Waters (0.05% TFA) and ACN (25% ACN- up to 50% in 10 min); Detector, UV 254nm. 84.4 mg of product were obtained. This resulted in 84.4 mg (53%) of N-[[5-(6-aminohexan-2-yl)-2-chlorophenyl]methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3- yl]cyclopropane-1-amine (I-242) as a pale yellow solid: (ES, m/z): [M+1]: 490; (CD3OD, ppm): δ 9.53 (d, J = 12.8 Hz, 1H), 8.99 (d, J = 5.8 Hz, 1H), 8.03 - 7.92 (m, 1H ), 7.75 - 7.59 (m, 3H), 7.45 (dd, J = 8.0, 2.9 Hz, 2H), 7.42 - 7.24 (m, 2H), 4, 44 - 4.36 (m, 2H), 3.97 - 3.85 (m, 1H), 2.84 (dt, J = 27.5, 7.4 Hz, 3H), 1.66 (q, J = 7.8, 7.3 Hz, 6H), 1.44 - 1.16 (m, 7H), 0.71 (t, J = 5.9 Hz, 2H), 0.54 (d, J = 3.3 Hz, 2H).

[00470] The absolute configuration of the separate enantiomers of the compounds in the examples described in this document has not been determined. As such, the configuration of the resolved materials was arbitrarily assigned as R or S in each case. Examples 54: (S)-N-(5-(6-amino-hexan-2-yl)-2-chlorobenzyl)- 1- (4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropanamine(I-243)e(R)-N-(5-(6-aminohexan-2-yl)-2-chlorobenzyl)-1-( 4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropanamine(I-244)

[00471] 2-(5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]hexyl)-2,3-di -hydro-1H- isoindole-1,3-dione intermediate 242e (5 g, 8.06 mmol, 1.00 equiv) was separated by chiral HPLC and gave 2.1 g (42%) of 243a as an off-white solid . Step 2. (S)-N-(5-(6-aminohexan-2-yl)-2-chlorobenzyl)-1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropanamine (I-243 )

[00472] To a 250 mL round bottom flask, Intermediate 243a (2.1 g, 3.39 mmol, 1.00 equiv), methanol/H2O (20/20 mL) and hydrazine hydrate (1. 69 g, 33.80 mmol, 10.00 equiv). The resulting solution was stirred for 3 h at 60°C in an oil bath. The reaction was then cooled by adding 500 mL of H2O. The resulting solution was extracted with 3 x 30 mL of ethyl acetate and the organic layers combined and dried in a reduced pressure oven and concentrated in vacuo. This resulted in 518.6 mg (31%) of N-([5-[(2S)-6-aminohexan-2-yl]-2-chlorophenyl]methyl)-1-[4-(2-cyclopropoxyphenyl )pyridin-3-yl]cyclopropane-1-amine (I-243) as light yellow oil. (R)-N-(5-(6-aminohexan-2-yl)-2-chlorobenzyl)-1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropanamine (I-244)

[00473] (R)-N-(5-(6-aminohexan-2-yl)-2-chlorobenzyl)-1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropanamine was prepared from of 244b as described above for I-243. Example 55: (5R)-5-[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl] hexan-1-amine(I-245)e(5S)- 5-[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]hexan- 1-amine (I-246)

[00474] To a 250 mL round bottom flask purged and kept under an inert nitrogen atmosphere, a solution of 2-chloro-5-[6-(1,3-dioxo-2,3-dihydro) was placed -1H-isoindol-2-yl)hexan-2-yl]benzaldehyde (560 mg, 1.51 mmol, 1.00 equiv) in tetrahydrofuran (10 mL). To the reaction mixture, LiAlH (OtBu)3 (390 mg, 1.00 equiv) was added in several batches at 0 oC. The resulting solution was stirred at room temperature for 0.5 h. The reaction was then cooled by adding 50 mL of NH4Cl(aq). The resulting solution was extracted with 3 x 30 mL ethyl acetate, and the organic layers combined and dried over sodium sulfate and concentrated in vacuo. This resulted in 0.56 g (99%) of 2-[5-[4-chloro-3-(hydroxymethyl)phenyl]hexyl]-2,3-dihydro-1H-isoindole-1,3-dione ( 245a) as light yellow oil. Step 2. [5-(6-aminohexan-2-yl)-2-chlorophenyl]ethanol (Intermediate 245b)

[00475] To a solution of 2- [5- [4-chloro-3- (hydroxymethyl) phenyl] hexyl] - 2,3-dihydro-1H-isoindole-1,3-dione (1.0 g, 2.69 mmol, 1.00 equiv) in methanol (15 mL) and tetrahydrofuran (15 mL) hydrazine hydrate (1.63 mL, 10.00 equiv) was added. The resulting solution was stirred for 2.5 h at 60°C in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 100 mL of DCM and the solids were filtered. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 700 mg (raw) of [5-(6-aminohexan-2-yl)-2-chlorophenyl] ethanol (245b) as crude yellow oil. Step 3. Tert-Butyl N-[5-[4-chloro-3-(hydroxymethyl)phenyl]hexyl]carbamate (Intermediate 245c)

[00476] To a 500 mL round bottom flask containing a stirred solution of [5-(6-amino-hexan-2-yl)-2-chlorophenyl]methanol (21.1 g, 87.28 mmol, 1, 00 equiv), sodium carbonate (37.1 g, 350.03, 4.00 ml), tetrahydrofuran (100 ml) and water (100 ml) a solution of di-tert-butyl dicarbonate (19 .1 g, 87.52 mmol, 1.00 equiv) in tetrahydrofuran (50 ml) dropwise with stirring at 0oC. The resulting solution was stirred for 12 h at room temperature. The solids were filtered. The resulting solution was diluted with 200 mL of ethyl acetate. The resulting mixture was washed with 3 x 100 ml of water and 2 x 100 ml of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:6). This resulted in 28.2 g (95%) of tert-butyl N-[5-[4-chloro-3-(hydroxymethyl)phenyl]hexyl]carbamate (245c) as yellow oil. Step 4. Tert-Butyl N-[5-[3-(bromomethyl)-4-chlorophenyl]hexyl]carbamate (Intermediate 245d)

[00477] To a 100 mL round-bottom flask purged and maintained under an inert nitrogen atmosphere was added N-[5-[4-chloro-3-(hydroxymethyl)phenyl]hexyl] tert-butyl carbamate (780 mg , 2.28 mmol, 1.00 equiv), dichloromethane (10 mL) and tetrahydrofuran (10 mL). To the reaction mixture was added NBS (651 mg, 3.66 mmol, 1.60 equiv) in portions at 0oC over 30 min. PPh3 (899 mg, 3.43 mmol, 1.50 equiv) was added to the resulting solution in portions at 0oC. The resulting solution was stirred for 1.5 h at 0°C in a water/ice bath. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:13). This resulted in 615 mg (67%) of tert-butyl N-[5-[3-(bromomethyl)-4-chlorophenyl] hexyl] carbamate (245d) as yellow oil. Step 5. N-[5-[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]hexyl]carbamate (Intermediate 245e)

[00478] To a 25 mL round-bottom flask purged and maintained under an inert nitrogen atmosphere, tert-butyl N-[5-[3-(bromomethyl)-4-chlorophenyl]hexyl]carbamate (50 mg) was added. , 0.12 mmol, 1.00 equiv), 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-ol (33 mg, 0.12 mmol, 1.00 equiv), N, N-dimethylformamide (2.5 ml). This was followed by the addition of sodium hydride (10 mg, 0.42 mmol, 2.00 equiv) in portions. The resulting solution was stirred for 40 min at 0°C in a water/ice bath. The reaction was then cooled by adding 20 mL of NH4Cl. The resulting solution was extracted with 3 x 5 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 34 mg (47%) of N-[5-[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]hexyldetert-butyl] carbamate (245e) as yellow oil. Step 6. Tert-Butyl (R)-(5-(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)hexyl)carbamate (Intermediate 245f) and tert-butyl (S)-(5-(4-Chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)hexyl)carbamate (Intermediate 246a)

[00479] 50 g of 245e was separated by chiral HPLC with the following conditions: Column, Chiralpak IB 4.6 * 250 nm; 5μm, HPLC, Chiral-A (IB) 001IB00CE-LA026; mobile phase, Hex (0.1% DEA): EtOH = 70:30; Detector, 254 nm. This resulted in 18 g (72%, 1st peak, ee > 96%) of intermediate 245f as a light yellow semisolid and 15 g (60%, 2nd peak, ee > 97%) of intermediate 246a as a light yellow semisolid. Step 7. N-[(5R)-5-[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyll]hexyl]carbamate (I-245 ) and N-[(5S)-5-[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyll]hexyl]carbamate (I-246)

[00480] I-245: To a stirred solution of N-[(5R)-5-[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl) tert-butyl phenyl]hexyl]carbamate (800 mg, 1.35 mmol, 1.00 equiv) in 1,4-dioxane (20 mL) was added hydrogen chloride (10 mL). The resulting solution was stirred for 2 h at room temperature. The resulting solution was diluted with 100 mL of ethyl acetate. The pH value of the solution was adjusted to 8 with sodium bicarbonate (aq.) (2 mol/L). The resulting solution was extracted with 3 x 100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2x50 mL of brine. The resulting mixture was concentrated under vacuum. This resulted in 508.7 mg (77%) of (5R)-5-[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyll]hexan -1-amine (I-245) as a light yellow semisolid: (ES, m/z): [M+1] = 491.30; (CDCl3, ppm): δ 8.74 (s, 1H), 8.53 (d, J = 5.0 Hz, 1H), 7.41 - 7.24 (m, 3H), 7.22 - 7 .10 (m, 2H), 7.03 - 6.92 (m, 3H), 4.44 (s, 2H), 3.71 (s, 1H), 3.61 - 3.46 (m, 1H) ), 2.79 (t, J = 7.4 Hz, 2H), 2.60 (q, J = 7.1 Hz, 1H), 1.53 (q, J = 7.7 Hz, 2H), 1.36 - 1.14 (m, 7H), 0.98 (d, J = 5.7 Hz, 2H), 0.83 - 0.75 (m, 2H), 0.69 - 0.47 ( m, 4H).

[00481] I-246: To a stirred solution of N-[(5R)-5-[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl) tert-butyl phenyl]hexyl]carbamate (500 mg, 0.85 mmol, 1.00 equiv) in 1,4-dioxane (20 mL) was added hydrogen chloride (10 mL). The resulting solution was stirred for 2 h at room temperature. The resulting solution was diluted with 100 mL of ethyl acetate. The pH value of the solution was adjusted to 9 with sodium bicarbonate (aq.) (2 mol/L). The resulting solution was extracted with 2 x 100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2x50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 322.1 mg (78%) of (5S)-5-[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyll]hexan -1-amine as a light yellow solid: (ES, m/z): [M+1] = 491.20; 1H-NMR (CDCl3, ppm): δ 8.76 (s, 1H), 8.55 (d, J = 5.0 Hz, 1H), 7.44 - 7.28 (m, 3H), 7, 28 - 7.13 (m, 2H), 7.05 - 6.94 (m, 3H), 4.46 (s, 2H), 3.63 - 3.49 (m, 1H), 2.86 ( t, J = 7.4 Hz, 2H), 2.62 (p, J = 7.1 Hz, 1H), 1.74 - 1.52 (m, 4H), 1.39 - 1.16 (m , 5H), 1.01 (s, 2H), 0.85 - 0.77 (m, 2H), 0.72 - 0.49 (m, 4H). Examples 56: acid (R)-5-[ 4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]hexanoic acid(I-247)e(S)-5-[4-chloro acid -3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]hexanoic acid (I-248)

[00482] 2-chloro-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde (B9a, 3.5 g, 13.13 mmol, 1.10 equiv.), 5-[(trifluoromethane ethyl )sulfonyloxy]hex-5-enoate (3.5 g, 12.06 mmol, 1.00 equiv), K3PO4 (7.7 g, 36.27 mmol, 3.00 equiv), Pd (PPh3)4 (1.4 g, 1.21 mmol, 0.10 equiv.) were dissolved in dioxane (120 mL) and water (20 mL). The resulting solution was stirred for 1 night at 80 oC in an oil bath. The reaction was cooled by adding 300 mL of water. The resulting solution was extracted with 300 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (4.5 g) was purified by flash chromatography with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, petroleum ether: ethyl acetate = 100: 0 increasing to petroleum ether: ethyl acetate = 95: 5 in 30 min; Detector, UV 254 nm. This resulted in 2.2 g (65%) of ethyl 5-(4-chloro-3-formylphenyl) hex-5-enoate (247a) as light red oil. Step 2. Ethyl 5-(4-chloro-3-formylphenyl)hexanoate (Intermediate 247b)

[00483] Ethyl 5-(4-chloro-3-formylphenyl)hex-5-enoate (247a, 2.2 g, 7.84 mmol, 1.00 equiv) was placed in a 250 mL round-bottom flask. , Rh (2.2 g, 21.36 mmol, 3.00 equiv), ethyl acetate (50 mL), the vessel was purged with N2 followed by H2 and maintained under H2 atmosphere at ambient pressure. The resulting solution was stirred for 5 h at 30 oC in an oil bath. The resulting solution was diluted with 100 mL of EtOAc. The solids were filtered. The resulting mixture was concentrated under vacuum. The crude product (2.5 g) was purified by flash chromatography with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, petroleum ether: ethyl acetate = 100: 0 increasing to petroleum ether: ethyl acetate = 95: 5 in 30 min; Detector, UV 254 nm. This resulted in 2.1 g (95%) of ethyl 5-(4-chloro-3-formylphenyl) hexanoate (247b) as colorless oil. Step 3. Ethyl 5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]hexanoate (Intermediate 247c)

[00484] To a 25 mL round bottom flask was added ethyl 5-(4-chloro-3-formylphenyl)hexanoate (247b, 382 mg, 1.35 mmol, 1.20 equiv), 1-[4- (2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (A-1, 300 mg, 1.13 mmol, 1.00 equiv), sodium triacetoxyborohydride (957 mg, 4.52 mmol, 4 .00 equiv), AcOH (0.05 mL), dichloromethane (15 mL). The resulting solution was stirred for 1 night at room temperature. The resulting solution was diluted with 1000 mL of DCM. The resulting mixture was washed with 2 x 50 mL of H2O. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (500 g) was purified by flash chromatography with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, petroleum ether: ethyl acetate = 100: 0 increasing to petroleum ether: ethyl acetate = 85: 15 in 30 min; Detector, UV 254 nm. This resulted in 450 mg (75%) of ethyl 5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]hexanoate ( 247c) as colorless oil. Step 4. 5-[4-Chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyll]hexanoic acid (Intermediate 247d)

[00485] To a 25 mL round bottom flask, 5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl was added ]ethyl hexanoate (450 mg, 0.84 mmol, 1.00 equiv), LiOH (122 mg, 5.09 mmol, 6.00 equiv), methanol (6 mL), water (0.5 mL). The resulting solution was stirred for 1 night at room temperature. The pH value of the solution was adjusted to 6.0 with hydrogen chloride (1 mol/L). The resulting solution was extracted with 2 x 50 mL of ethyl acetate and the organic layers combined and dried in a reduced pressure oven and concentrated in vacuo. This resulted in 420 mg (99%) of 5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl] hexanoic acid (247d ) as colorless oil. Step 5. (5R)-5-[4-Chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]hexanoic acid(I-247) e(5S)- 5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]hexanoic acid (I-248)

[00486] The racemic product (1 g) was purified by chiral HPLC with the following conditions: Column, Chiralpak IB 4.6 x 250 mm, 5 μm HPLC Chiral-A (IB) 001IB00CE-LA026; mobile phase, Hex (0.1% DEA): EtOH = 80: 20; Detector, 254 nm. 338.2 mg of product was obtained. This resulted in 338.2 mg (34%) of (5R)-5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl acid ]phenyl]hexanoic acid as a light yellow solid and 225.4 mg (23%) of (5S)-5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3- yl]cyclopropyl]amino)methyl]phenyl]hexanoic acid as a light yellow solid.

[00487] I-247 Retention time 19.4 minutes; MS (ES, m/z): 505.2 [M + H]+; 1H-NMR (methanol-d4, ppm): 8.72 (s, 1H), 8.54 (d, J = 4.9 Hz, 1H), 7.54 - 7.43 (m, 2H), 7 .32 - 7.19 (m, 3H), 7.18 - 7.08 (m, 3H), 3.88 (s, 2H), 3.67 (tt, J = 6.0, 2.9 Hz , 1H), 2.67 (h, J = 6.9 Hz, 1H), 2.33 - 2.17 (m, 2H), 1.65 - 1.31 (m, 5H), 1.20 ( d, J = 6.9 Hz, 3H), 1.10 (s, 2H), 1.01 (s, 2H), 0.62 (d, J = 6.1 Hz, 2H), 0.41 ( d, J = 3.2 Hz, 2H).

[00488] I-248 Retention time 24.26 minutes MS (ES, m/z): 505.15 [M + H]+; 1H-NMR (Methanol-d4, ppm): 8.60 (s, 1H), 8.46 (d, J = 5.6 Hz, 1H), 7.50 - 7.39 (m, 2H), 7 .27 - 7.13 (m, 3H), 7.16 - 7.00 (m, 3H), 3.70 (s, 2H), 3.62 (tt, J = 6.0, 2.9 Hz , 1H), 2.65 (h, J = 7.0 Hz, 1H), 2.32 - 2.15 (m, 2H), 1.64 - 1.33 (m, 4H), 1.19 ( d, J = 6.9 Hz, 3H), 0.92 (s, 2H), 0.85 (s, 2H), 0.67 - 0.56 (m, 2H), 0.43 - 0.37 (m, 2H).

[00489] Compounds I-249 or I-254 (Table 11) were prepared from known commercial base materials, or the appropriate intermediates disclosed herein, using them in accordance with the examples specified in Table 11 and generally known methods those skilled in the art. Table 11. Compounds I-249 to I-254

[00490] A 100 mL round bottom flask was charged with a solution of DSC (259 mg, 1.01 mmol, 1.20 eq) in N,N-dimethylformamide (5 mL), DIEA (159 mg, 1. 23 mmol, 1.50 equiv.). This was followed by the addition of a solution of N-([5-[(2S)-6-aminohexan-2-yl]-2-chlorophenyl]methyl)-1-[4-(2-cyclopropoxyphenyl)pyridin- 3-yl]cyclopropan-1-amine (400 mg, 0.82 mmol, 1.00 equiv) in N,N-dimethylformamide (2 mL) dropwise with stirring at 0 oC. The mixture was stirred for 1 h at room temperature. To the resultant was added (2R, 3R, 4R, 5S)-6-aminohexane-1,2,3,4,5-pentol (192 mg, 1.06 mmol, 1.30 equiv.). The resulting solution was stirred overnight at room temperature. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, OBD Shield XBridge Shield RP18 Column; 5μm 19 x 150mm; mobile phase, 10 mM NH4HCO3 in water and MeCN (35% to 48% in 6 min); Detector, UV 220 nm. This resulted in 109 mg (19%) of the title compound (I-255) as an off-white solid. MS (ES, m/z): 697 [M+H]+; 1H-NMR (CD3OD, ppm): 8.59 (s, 1H), 8.46 (d, J = 5.1 Hz, 1H), 7.45- 7.47 (m, 2H), 7.10 - 7.24 (m, 3H), 7.02-7.09 (m, 3H), 3.61-3.80 (m, 9H), 3.36 (s, 1H), 3.02-3 .35 (m, 3H), 2.64 (d, J = 7.2 Hz, 1H), 1.18-1.57 (m, 9H), 0.65-0.91 (m, 6H), 0.42-0.63 (m, 2H). Example 58: 1-[(5R)-5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyll]hexyl]-3 -[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]urea (I-256)

[00491] A 50 mL round bottom flask was charged with a solution of DSC (251 mg, 0.98 mmol, 1.20 eq) in N,N-dimethylformamide (5 mL), DIEA (159 mg, 1. 23 mmol, 1.50 equiv.). This was followed by the addition of a solution of N-([5-[(2S)-6-aminohexan-2-yl]-2-chlorophenyl]methyl)-1-[4-(2-cyclopropoxyphenyl)pyridin- 3-yl]cyclopropan-1-amine (244) (400 mg, 0.82 mmol, 1.00 equiv) in N,N-dimethylformamide (2 mL) dropwise with stirring at 0 oC. The mixture was stirred for 1 h at room temperature. To this was added (2R, 3R, 4R, 5S)-6-aminohexane-1,2,3,4,5-pentol (192 mg, 1.06 mmol, 1.30 equiv.). The resulting solution was stirred overnight at room temperature. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, OBD Shield XBridge Shield RP18 Column; 5μm, 19x150mm; mobile phase, NH4HCO310 mM in water and MeCN (35% to 48% in 6 min); Detector, UV 220 nm. This resulted in 237.8 mg (42%) of the title compound (I-256) as an off-white solid. MS (ES, m/z): 697 [M+H]+; 1H-NMR (CD3OD, ppm): 8.59 (s, 1H), 8.47 (d, J = 5.0 Hz, 1H), 7.53 - 7.40 (m, 2H), 7.28 - 6.98 (m, 6H), 3.84 - 3.56 (m, 8H), 3.44 - 3.32 (m, 1H), 3.22 - 2.99 (m, 3H), 2 .64 (q, J = 7.2 Hz, 1H), 1.63 - 1.36 (m, 4H), 1.35 - 1.06 (m, 5H), 0.91 (s, 2H), 0.83 (s, 2H), 0.71 - 0.57 (m, 2H), 0.46 - 0.38 (m, 2H). Example 59: 5-[3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-4-methylphenyl]-N-[(2S,3R,4R,5R )2,3,4,5,6-pentahydroxyhexyl]hexanamide dihydrochloride (I-257)

[00492] A 250 mL round-bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of 5-bromo-2-methylbenzaldehyde (3 g, 15.07 mmol, 1.00 equiv) in 1. 4-dioxane (70 mL), 4,4,5,5-tetramethyl-2-(tetramethyl-1,3,2-dioxaborolan-2-yl) - 1,3,2-dioxaborolane (4.23 g, 16 .66 mmol, 1.10 equiv.), KOAc (4.45 g, 45.34 mmol, 3.00 equiv), Pd (dppf) Cl2 (333 mg, 0.46 mmol, 0.03 equiv). The resulting solution was stirred for 2 h at 100oC in an oil bath. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0:100-10:90). This resulted in 3.3 g (89%) of 257a as a light yellow solid. Step 2. Ethyl 5-(3-formyl-4-methylphenyl)hex-5-enoate (Intermediate 257b)

[00493] A 100 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of 2-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl) benzaldehyde (257a , 1 g, 4.06 mmol, 1.20 equiv) in 1,4-dioxane:H2O (10:1), ethyl 5-[(trifluoromethane)sulfonyloxy]hex-5-enoate (1 g, 3.45 mmol, 1.00 equiv), Pd (PP3)4 (400 mg, 0.35 mmol, 0.10 equiv.), K3PO4 (2.2 g, 10.36 mmol, 3.00 equiv). The resulting solution was stirred overnight at 80°C in an oil bath. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0:100-10:90). This resulted in 770 mg (86%) of 257b as a colorless oil. Step 3. Ethyl 5-(3-formyl-4-methylphenyl)hexanoate (Intermediate 257c)

[00494] A 100 mL round bottom flask was charged with ethyl 5-(3-formyl-4-methylphenyl)hex-5-enoate (257b, 770 mg, 2.96 mmol, 1.00 equiv), acetate of ethyl (15 mL), Rh/C (770 mg, 1.00 equiv). For the above hydrogen was introduced into. The resulting solution was stirred for 6 h at 25°C in an oil bath. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0:100-20:80). This resulted in 200 mg (26%) of 257c as a colorless oil. Step 4. Ethyl 5-[3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-4-methylphenyl]hexanoate (Intermediate 257d)

[00495] A 50 mL round bottom flask was charged with a solution of ethyl 5-(3-formyl-4-methylphenyl)hexanoate (257c, 200 mg, 0.76 mmol, 1.00 equiv) in dichloromethane ( 6 mL), 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (250 mg, 0.94 mmol, 1.20 equiv). This was followed by the addition of NaBH(OAc)3 (970 mg, 4.58 mmol, 6.00 equiv) at 0 oC. Four drops of AcOH were added. The resulting solution was stirred overnight at room temperature. The resulting solution was diluted with 25 mL of H2O. The resulting solution was extracted with 3 x 50 mL of dichloromethane and the organic layers combined and dried in a reduced pressure oven and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:3). This resulted in 200 mg (51%) of 257d as a light yellow oil. Step 5. 5-[3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-4-methylphenyl]hexanoic acid (Intermediate 257e)

[00496] A 25 mL round bottom flask was charged with a solution of 5-[3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-4- Ethyl methylphenyl]hexanoate (257d, 200 mg, 0.39 mmol, 1.00 equiv) in ethanol/H2O (10 mL: 1 mL), LiOH (93.8 mg, 3.92 mmol, 10.00 equiv) . The resulting solution was stirred overnight at room temperature. The pH value of the solution was adjusted to 3 with 1M HCl solution. The resulting solution was extracted with 3 x 50 mL of ethyl acetate and the organic layers combined and dried in a reduced pressure oven and concentrated in vacuo. This resulted in 160 mg (85%) of 257e as a colorless oil. Step 6. 5-[3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-4-methylphenyl]-N-[(2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl]hexamide dihydrochloride (I-257)

[00497] A 25 mL round bottom flask was charged with a solution of 5-[3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]- acid 4-methyl-phenyl]hexanoic acid (80 mg, 0.17 mmol, 1.00 equiv) in N,N-dimethylformamide (3 mL), HATU (130 mg, 0.34 mmol, 2.00 equiv), D- glucosamine (60 mg, 2.00 equiv), DIEA (0.11 mL, 4.00 equiv). The resulting solution was stirred for 4 h at room temperature. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, Gemini-NX 5u C18 110A, AXIA Pack, 150 x 21.2 mm; mobile phase, water with 10 mM4 NHHCO3 and MeCN (30.0% MeCN at 54.0% in 9 min); Detector, 254 and 220 nm. This resulted in 81.4 mg (68%) of the title compound as a light yellow solid. MS (ES, m/z): 648.3 [M+H]+; 1H-NMR (CD3OD, ppm): 9.38 (1H, s), 8.88 (1H, d), 7.88 (1H, d), 7.57 (2H, m), 7.31 (1H , d), 7.19 (2H, m), 7.00 (2H, m), 4.12 (2H, s), 3.81 (1H, m), 3.59 (6H, m), 3 .36 (1H, m), 3.15 (1H, m), 2.53 (1H, m), 2.09 (5H, m), 1.50 (4H, m), 1.34 (4H, m), 1.12 (3H, d), 0.62 (2H, m), 0.42 (2H, m).Example 60: (2S,3S,4R,5S)-N-(4-[4 -chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pentyl)-2,3,4,5,6-pentahydroxy-N -methylhexanamide (I-258)

[00498] A 100 mL round bottom flask was charged with 5-[5-[(tert-butyldiphenylsilyl)oxy]pentan-2-yl]-2-chlorobenzaldehyde (B9) (300 mg, 0.65 mmol, 1 .00 equiv), 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (173 mg, 0.65 mmol, 1.00 equiv), dichloromethane (10 mL), NaBH (OAc )3 (689 mg, 5.00 equiv) and AcOH (0.1 mL). The resulting solution was stirred overnight at room temperature. The reaction was cooled by adding 5 mL of water. The resulting solution was extracted with 3x20 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 3x50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:3). This resulted in 389 mg (84%) of 258a as a yellow oil. Step 2. 4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pentan-1-ol (Intermediate 258b)

[00499] A 100 mL round bottom flask was charged with N-[(5-[5-[(tert-butyldiphenylsilyl)oxy]pentan-2-yl]-2-chlorophenyl)methyl]-1-[4- (2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (258a) (2 g, 2.80 mmol, 1.00 equiv), tetrahydrofuran (20 mL), TBAF/THF (4.2 mL , 1.50 equiv.). The resulting solution was stirred for 4 h at room temperature. The resulting solution was extracted with 200 mL of ethyl acetate/diethyl ether (1:1) and the organic layers combined. The resulting mixture was washed with 3 x 200 ml of water. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0:1-1:1). This resulted in 1.3 g (97%) of 258b as a colorless oil. Step 3. 4-[4-Chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pentyl methanesulfonate (Intermediate 258c)

[00500] A 100 mL round bottom flask was charged with 4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl] pentan-1-ol (258b) (300 mg, 0.63 mmol, 1.00 equiv), dichloromethane (15 mL), TEA (0.2 mL, 2.00 equiv), MsCl (0.074 mL, 1.50 equiv.). The resulting solution was stirred for 1 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 290 mg (83%) of 258c as a light yellow solid. Step 4. N-([2-chloro-5-[5-(methylamino)pentan-2-yl]phenyl]methyl)-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1- amine (Intermediate 258d)

[00501] A sealed 2.5 mL tube was charged with 4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl] pentyl methanesulfonate (258c) (290 mg, 0.52 mmol, 1.00 equiv), CH3NH2/THF (2 mL). The resulting solution was stirred overnight at 60 oC in an oil bath. The resulting mixture was concentrated under vacuum. This resulted in 250 mg (98%) of 258d as a light yellow solid. Step 5. (3R,4S,5S,6S)-3,4,5-tris(acetyloxy)-6- [(4-[4-chloro-3-[([1-[4-(2- cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pentyl)(methyl)carbamoyl]oxan-2-yl (Intermediate 258e)

[00502] A 100 mL round bottom flask was charged with N-([2-chloro-5-[5-(methylamino)pentan-2-yl]phenyl]methyl)-1-[4-(2-cyclopropoxyphenyl )pyridin-3-yl]cyclopropane-1-amine (258d) (250 mg, 0.51 mmol, 1.00 equiv), (2S,3S,4S,5R)-3,4,5,6-tetraacetoxytetra acid -hydro-2H-pyran-2- carboxylic acid (185 mg, 0.51 mmol, 1.00 equiv), HATU (291 mg, 1.21 mmol, 1.50 equiv), N,N-dimethylformamide (10 mL) , DIEA (0.25 mL, 3.00 equiv). The resulting solution was stirred for 2 h at room temperature. The resulting solution was extracted with 4 x 20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3x60 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with dichloromethane/methanol (1:1). This resulted in 230 mg (54%) of 258e as a light yellow solid. Step 6. (2S,3S,4S,5R)-N-[4-[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]pentyl ]-3,4,5,6-tetrahydroxy-N-methyloxane-2-carboxamide (Intermediate 258f)

[00503] A 100 mL round bottom flask was charged with (2S,3S,4S,5R)-4,5,6-tris(acetyloxy)-2-([4-[4-chloro-3-( [1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-cyclopropoxy]methyl)phenyl]pentyl](methyl)carbamoyl)oxan-3-yl (258e) (230 mg, 0.28 mmol, 1. 00 equiv), methanol (10 mL), methoxysodium (18 mg, 0.33 mmol, 0.60 equiv). The resulting solution was stirred overnight at room temperature. The reaction was cooled by adding 0.02 mL of water. The resulting mixture was concentrated under vacuum. This resulted in 170 mg (93%) of 258f as a light yellow solid. Step 7. (2S,3S,4R,5S)-N-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl] phenyl]pentyl)-2,3,4,5,6-pentahydroxy-N-methylhexanamide (I-258)

[00504] A 25 mL round bottom flask was charged with (2S,3S,4S,5R)-N-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin - 3-yl]cyclopropyl]amino)methyl]phenyl]pentyl)-3,4,5,6-tetrahydroxy-N-methyloxane-2-carboxamide (258f) (170 mg, 0.26 mmol, 1.00 equiv), methanol (3 mL), sodium borohydride (21 mg, 0.57 mmol, 2.00 equiv). The resulting solution was stirred for 1 h at room temperature. The reaction was cooled by adding 2 mL of water. The crude product was purified by preparative HPLC with the following conditions: Column, Gemini-NX 5μ C18 110A, AXIA Packed, 150 x 21.2 mm; mobile phase, water with 10 mmol NH4HCO3 and MeCN (27.0% MeCN to 55.0% in 6 min); Detector, UV 220 nm. This resulted in 57.1 mg (33%) of the title compound I-258 as a white solid. MS (ES, m/z): 668.35 [M+H]+; 1H NMR (400 MHz, CD3OD) δ 8.58 (d, J = 1.1 Hz, 1H) 8.46 (d, J = 5.0 Hz, 1H), 7.42 - 7.48 (m, 2H), 7.14 - 7.28 (m, 3H), 7.05 (d, J = 18.2 Hz, 3H), 4.60 (s, 1H), 3.84 - 4.61 (m , 1H), 3.55 - 4.46 (m, 8H), 3.27 (s, 2H), 3.04 (s, 1H), 2.86 (d, J = 6.2 Hz, 1H) , 2.67 (s, 1H), 1.56 (m, 4H), 1.16 - 1.24 (m, 3H), 0.89 (s, 2H), 0.82 (s, 2H), 0.63 (s, 2H), 0.41 (s, 2H).Example 61: N-benzyl-5-(3-(((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropyl )amino)methyl)-4-methylphenyl)-N- ((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)hexanamide (I-259)

[00505] Intermediate D1 (50 mg, 0.186 mmol, 2.00 equiv) was added to a solution of Intermediate 257e (45 mg, 0.0928 mmol, 1.00 equiv), HATU (71 mg, 0.186 mmol, 2, 00 equiv) and DIEA (36 mg, 0.278 mmol, 3.00 equiv) in DMF (1 mL). The resulting solution was left stirring for 1 h at room temperature. The crude product was purified by preparative HPLC with a CH3CN/H2O gradient containing 0.1% TFA (10% CH3CN to 80% CH3CN over 18 min). The fractions containing the desired product were then neutralized with Amberlyst A26 hydroxide resin and filtered to provide 29 mg (43%) of compound (I-259) as an off-white solid. MS (ES, m/s): 738.3 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.59 (s, 1H), 8.48 (d, J = 4.9 Hz, 1H), 7.40 (d, J = 3.8 Hz, 2H), 7.26 (d, J = 5.9 Hz, 3H), 7.12 (dd, J = 15.4, 5.9 Hz, 4H), 6.95 (d, J = 15.7 Hz, 2H), 6.80 (s, 1H), 4.96 (s, 1H), 4.64 (s, 2H), 4.52 - 4.23 (m, 6H), 2.08 (d , J = 4.8 Hz, 4H), 1.09 (dd, J =24.0, 6.8 Hz, 3H), 0.79 (s, 2H), 0.63 (s, 4H), 0 .37 (s, 2H).Example 62: 5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]- N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-260) trifluoromethanesulfonate (Intermediate 260a)

[00506] A 250 mL round bottom flask was charged with a solution of 2,5-dichloro-4-formylphenyl trifluoromethanesulfonate (B2c) (4 g, 12.38 mmol, 1.00 equiv) in methanol (50 mL ). This was followed by the addition of NaBH4 (940 mg, 24.85 mmol, 2.00 equiv) in several batches at 0 oC. The resulting solution was stirred for 30 min at 0°C. The reaction was cooled by adding 50 mL of water. The resulting solution was extracted with 3 x 30 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 4 g (99%) of 260a as a pale yellow oil. Step 2. Ethyl 5-[2,5-dichloro-4-(hydroxymethyl)phenyl]hex-5-enoate (Intermediate 260b)

[00507] A 500 mL round bottom flask was charged with a solution of ethyl 5-(tetramethyl-1,3,2-dioxaborolan-2-yl)hex-5-enoate (2.46 g, 9. 17 mmol, 1.10 equiv) in DME/H2O (200/10 mL), 2,5-dichloro-4-(hydroxymethyl)phenyl trifluoromethanesulfonate (260a, 2.7 g, 8.31 mmol, 1.00 equiv ), Pd (PPh3)4 (960 mg, 0.83 mmol, 0.10 equiv.), sodium carbonate (2.65 g, 25.00 mmol, 3.00 equiv.). The resulting solution was stirred overnight at 90 oC in an oil bath. The reaction was then cooled by adding 50 mL of H2O. The resulting solution was extracted with 3 x 30 mL ethyl acetate, and the organic layers combined and dried over sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with PE:EtOAc (95:5). This resulted in 900 mg (34%) of 260b as a colorless oil. Step 3. Ethyl 5-[2,5-dichloro-4-(hydroxymethyl)phenyl]hexanoate (Intermediate 260c)

[00508] A 250 mL round bottom flask was charged with a solution of ethyl 5-[2,5-dichloro-4-(hydroxymethyl)phenyl]hex-5-enoate (260b, 900 mg, 2.84 mmol , 1.00 equiv) in ethyl acetate (20 mL), Rh/C (900 mg). The resulting solution was stirred overnight at room temperature. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with PE:E (95:5). This resulted in 300 mg (33%) of 260c as a pale yellow oil. Step 4. Ethyl 5-(2,5-dichloro-4-formylphenyl)hexanoate (Intermediate 260d)

[00509] A 50 mL round bottom flask was charged with a solution of ethyl 5-[2,5-dichloro-4-(hydroxymethyl)phenyl]hexanoate (260c, 300 mg, 0.94 mmol, 1.00 equiv) in dichloromethane (10 mL), MnO2 (650 mg, 7.48 mmol, 8.00 equiv). The resulting solution was stirred for 5 h at 40 oC in an oil bath. The solids were filtered. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0:100-20:80). This resulted in 110 mg (37%) of 260d as a light yellow oil. Step 5. Ethyl 5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyll]hexanoate (Intermediate 260e)

[00510] A 25 mL round bottom flask was charged with ethyl 5-(2,5-dichloro-4-formylphenyl) hexanoate (260d, 110 mg, 0.35 mmol, 1.00 equiv), dichloromethane (5 mL), 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (150 mg, 0.56 mmol, 1.50 equiv). This was followed by addition of NaBH(OAc)3 (440 mg, 2.08 mmol, 6.00 equiv) dropwise with stirring at 0 oC. For this, cat was added. AcOH (0.06 mL, 0.05 equiv). The resulting solution was stirred overnight at room temperature. The resulting solution was diluted with 120 mL of H2O. The resulting solution was extracted with 3 x 120 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:3). This resulted in 170 mg (86%) of 260e as a light yellow oil. Step 6. 5-[2,5-Dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyll]hexanoic acid (Intermediate 260f)

[00511] A 25 mL round bottom flask was charged with 5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl hexanoate ] phenyl] ethyl (260e, 170 mg, 0.30 mmol, 1.00 equiv), ethanol/H2O (4/0.4 mL), LiOH (72 mg, 3.01 mmol, 10.00 equiv). The resulting solution was stirred for 1 h at 50°C in an oil bath. The pH value of the solution was adjusted to 3 with hydrogen chloride (1 mol/L). The resulting solution was extracted with 3 x 50 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 120 mg (74%) of 260f as a light yellow oil. Step 7. 5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (I-260)

[00512] A 25 mL round bottom flask was charged with a solution of 5-[2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl] acid amino)methyl]phenyl]hexanoic acid (260f, 80 mg, 0.15 mmol, 1.00 equiv) in N,N-dimethylformamide (5 mL), (2R, 3R, 4R, 5S)-6-aminohexane- 1,2,3,4,5- pentol (54 mg, 0.30 mmol, 2.00 equiv), HATU (113 mg, 0.30 mmol, 2.00 equiv), DIEA (77 mg, 0.60 mmol, 4.00 equiv). The resulting solution was stirred overnight at room temperature. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, Gemini-NX 5μ C18 110A, AXIA Packed, 150 x 21.2 mm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (38.0% MeCN to 52.0% in 10 min); Detector, 254 nm. This resulted in 60.1 mg (52%) of the title compound (I-260) as an off-white solid. MS (ES, m/z): 702 [M+H]+; 1H-NMR (CD3OD, ppm): 9.45 (s, 1H), 8.99 (d, J = 6.0Hz, 1H), 7.98 (d, J = 6.0Hz, 1H), 7, 64 - 7.71 (m, 3H), 7.27 - 7.50 (m, 3H), 4.38 (s, 2H), 3.95 (s, 1H), 3.29 - 3.78 ( m, 9H), 2.20 (t, J = 7.6Hz, 2H), 1.21 - 1.65 (m, 11H), 0.77 (s, 2H), 0.58 (s, 2H) .Example 63: 5-(4-chloro-3-(((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropyl)amino)methyl)phenyl)-N-(5-hydroxypentyl)-N - ((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)hexanamide (I-261) Step 1. Ethyl 5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl] hexanoate (Intermediate 261a)

[00513] A 25 mL round bottom flask was charged with ethyl 5-(4-chloro-3-formylphenyl) hexanoate (B10) (382 mg, 1.35 mmol, 1.20 equiv), 1-[4-(2- cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (A- 1, 300 mg, 1.13 mmol, 1.00 equiv), NaBH(OAc)3 (957 mg, 4.52 mmol, 4.00 equiv ), AcOH (0.05 mL), dichloromethane (15 mL). The resulting solution was stirred for 1 night at room temperature. The resulting solution was diluted with 1000 mL of DCM. The resulting mixture was washed with 2 x 50 mL of H 2 O. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (500 mg) was purified by flash chromatography with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ethyl acetate:petroleum ether = 100:0 increasing to ethyl acetate:petroleum ether = 85:15 within 30 min; Detector, UV 254 nm. This resulted in 450 mg (75%) of ethyl 5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl] hexanoate ( 261a) as colorless oil. Step 2. 5-[4-Chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyll]hexanoic acid (Intermediate 261b)

[00514] A 25 mL round bottom flask was charged with 5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl hexanoate [phenyl]ethyl (261a) (450 mg, 0.84 mmol, 1.00 equiv), LiOH (122 mg, 5.09 mmol, 6.00 equiv), methanol (6 mL), water (0.5 mL). The resulting solution was stirred overnight at room temperature. The pH value of the solution was adjusted to 6.0 with hydrogen chloride (1 mol/L). The resulting solution was extracted with 2 x 50 mL of ethyl acetate and the organic layers were combined and dried under reduced pressure. This resulted in 420 mg (99%) of 5-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyll]hexanoic acid (261b ) as colorless oil. Step 3. 5-(4-chloro-3-(((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropyl)amino)methyl)phenyl)-N-(5-hydroxypentyl)-N- ((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)hexanamide (I-261)

[00515] A mixture of 5-(4-chloro-3-(((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropyl)amino)methyl)phenyl)hexanoic acid (261b) (27, 1 mg, 0.0537 mmol, 1.0 equiv) and (2R,3R,4R,5S)-6-((5-hydroxypentyl)amino)hexane-1,2,3,4,5-pentaol (D8) (21.2 mg, 0.0698 mmol, 1.3 equiv), in DMF (0.3 mL) were added N,N-diisopropylethylamine (37.4μL, 0.215 mmol, 4.0 equiv) and HATU ( 26.5 mg, 0.0698 mmol, 1.3 equiv). The mixture was stirred at room temperature for 1 h and purified by preparative HPLC. The HPLC fractions were combined, neutralized with the amberlyst® A26 hydroxide form to pH 6 and lyophilized to give 22.2 mg (55%) of the title compound as a white solid. MS (ES, m/z): 754.3 [M+H]+. 1H-NMR (400MHz, CD3OD) δ 8.66 (s, 1H), 8.51 (d, J = 5.1 Hz, 1H), 7.49 — 7.44 (m, 2H), 7.27 (d, J = 8.0 Hz, 1H), 7.24 — 7.19 (m, 2H), 7.13 — 7.05 (m, 3H), 3.98 - 3.89 (m, 1H ), 3.84 - 3.76 (m, 3H), 3.76 - 3.59 (m, 6H), 3.59 - 3.47 (m, 4H), 3.44 - 3.34 (m , 2H), 2.73 - 2.63 (m, 1H), 2.52 - 2.30 (m, 1H), 1.65 - 1.49 (m, 7H), 1.48 - 1.25 (m, 3H), 1.20 (dd, j = 6.8, 3.4 Hz, 3H), 1.02 - 0.87 (m, 4H), 0.68 - 0.57 (m, 2H ), 0.48 - 0.37 (m, 2H).Example 64: 5-(4-chloro-3-(((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropyl)amino) methyl)phenyl)-N-(2-(morpholinosulfonyl)ethyl)-N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)hexanamide (I-262 )

[00516] A mixture of 5-(4-chloro-3-(((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropyl)amino)methyl)phenyl)hexanoic acid (261b) (25, 3 mg, 0.0501 mmol, 1.0 equiv) and (2R,3R,4R,5S)-6-((2-(morpholinosulfonyl)ethyl)amino)hexane-1,2,3,4,5 -pentaol (D9) (23.3 mg, 0.0651 mmol, 1.3 equiv), in DMF (0.3 mL) N,N-diisopropylethylamine (35.7μL, 0.205 mmol, 4.1 equiv) and HATU (24.7 mg, 0.065 mmol, 1.3 equiv). The mixture was stirred at room temperature for 1 h and purified by preparative HPLC. The HPLC fractions were combined, neutralized with the amberlyst® A26 hydroxide form to pH 6 and lyophilized to give 31.3 mg (74%) of the title compound (I-262) as a white solid. MS (ES, m/z): 845.3 [M+H]+, 1H-NMR (400MHz, CD3OD) δ 8.75 (s, 1H), 8.57 (d, J = 5.2 Hz, 1H), 7.51 - 7.47 (m, 2H), 7.32 - 7.27 (m, 2H), 7.24 (d, J = 7.5 Hz, 1H), 7.21 - 7 .10 (m, 3H), 4.00 - 3.82 (m, 4H), 3.81 - 3.60 (m, 12H), 3.53 (d, J = 6.0 Hz, 1H), 3.41 - 3.34 (m, 2H), 3.27 - 3.17 (m, 5H), 2.77 - 2.62 (m, 1H), 2.52 - 2.31 (m, 1H) ), 1.67 - 1.56 (m, 2H), 1.56 - 1.35 (m, 2H), 1.20 (d, J = 6.8 Hz, 3H), 1.10 - 0, 96 (m, 4H), 0.69 - 0.59 (m, 2H), 0.46 - 0.38 (m, 2H).Example 65: 1- (4- (5-chloro-4 - (( 1- (4- (2-cyclopropoxyphenyl) pyridin-3- yl) cyclopropoxy) methyl) -2-methylphenyl) butyl) -1-ethyl-3 - ((2S, 3R, 4R, 5R) - 2,3,4 ,5,6-pentahydroxyhexyl) urea I-263

[00517] A mixture of (S)-5-(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)hexan-1-amine (I -245) (262.8 mg, 0.535 mmol, 1.0 equiv), into DCM (3 mL) was added trimethylamine (224 μ L, 1.610 mmol, 3.0 equiv), followed by dropwise addition of a solution of (2R,3S,4R,5S -5-isocyanatohexane-1,2,3,4,6-pentyl) penta-acetate (257.3 mg, 0.617 mmol, 1.15 equiv) in DCM (3 mL). The mixture was stirred at room temperature for 1 h and diluted with ethyl acetate. The mixture was washed with water (1x) and brine (1x), dried and concentrated to give a white solid. A mixture of the white solid in MeOH was added. (10 mL) (25 wt% in MeOH, 200μL). The mixture was stirred at room temperature for 30 minutes, concentrated and purified by preparative HPLC (40 - 70% acetonitrile in 0.010 M aqueous NH4HCO3) to give 258 mg (69%) of title compound I-263 as a white solid. MS (ES, m/z): 699.45 [M+H]+, 1H-NMR (400MHz, CD3OD) δ 8.67 (s , 1H), 8.49 (d, J = 5.1 Hz, 1H), 7.44 - 7.29 (m, 3H), 7.28 - 7.20 (m, 2H), 7.07 ( dd, J = 8.2, 2.2 Hz, 1H), 7.01 (td, J = 7.3, 1.4 Hz, 1H), 6.96 (d, J = 2.2 Hz, 1H ), 4.42 (s, 2H), 3.97 (dd, J = 4.9, 2.9 Hz, 1H), 3.85 (q, J = 4.7 Hz, 1H), 3.78 (dd, J = 10.8, 3.3 Hz, 1H), 3.74 - 3.52 (m, 6H), 3.07 (dq, J = 13.2, 6.4 Hz, 2H), 2.71 - 2.53 (m, 1H), 1.61 - 1.51 (m, 2H), 1.51 - 1.34 (m, 2H), 1.34 - 1.24 (m, 1H ), 1.20 (d, J = 6.9 Hz, 4H), 1.02 (t, J = 6.0 Hz, 2H), 0.97 - 0.88 (m, 2H), 0.62 (d, J = 6.0 Hz, 2H), 0.46 - 0.33 (m, 2H). Example 66: 1-[(5R)-5-[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]hexyl]-3-[( 2S,3R,4S,5R)- 1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-264)

[00518] An 8 mL vial purged and maintained under an inert nitrogen atmosphere was charged with 1-[(5R)-5-[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin- 3-yl]cyclopropoxy]methyl)phenyl]hexyl]-3-[(2R,3R,4R,5S,6R)- 2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]urea (226 mg, 0.32 mmol, 1.00 equiv), methanol (1 mL) and NaBH4 (25 mg, 0.68 mmol, 2.00 equiv). The resulting solution was stirred for 1 h at room temperature. The resulting mixture was concentrated under vacuum. The crude product was purified by preparative HPLC with the following conditions: OBD XBridge Shield RP18 column; 5μm 19 x 150mm; mobile phase: water (NH4HCO310 mM) and MeCN (34.0% MeCN to 54.0% in 6 min); Detector, UV 220 nm. This resulted in 75.2 mg (33%) of the title compound I-264 as a white solid. MS (ES, m/z): 698.34 [M+H]+; 1H NMR (300 MHz, Methanol-d4) δ 8.66 (s, 1H), 8.48 (d, J = 5.1 Hz, 1H), 7.17 - 7.46 (m, 5H), 6 .91 - 7.11 (m, 3H), 4.59 (s, 1H), 4.41 (s, 2H), 3.96 (dd, J = 4.9, 2.8 Hz, 1H), 3.49 - 3.90 (m, 9H), 3.06 (td, J = 7.0, 2.4 Hz, 2H), 2.62 (q, J = 7.0 Hz, 1H), 1 .50 (dq, J = 33.5, 7.4, 6.9 Hz, 4H), 1.19 (d, J = 6.9 Hz, 4H), 0.87 - 1.07 (m, 4H ), 0.55 - 0.68 (m, 2H), 0.40 (d, J = 3.8 Hz, 2H).

[00519] Compounds I-265 to I-379 (Table 12) were prepared from known commercial base materials or the appropriate intermediates disclosed herein, using methods from the examples specified in Table 12 and methods generally known to those skilled in the art. Table 12. Compounds I-265 to I-385.

[00520] A 100 mL round bottom flask was charged with 2-chloro-5-[5-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)pent-1- en-2-yl]benzaldehyde (242c, 1.7 g, 4.80 mmol, 1.00 equiv), 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (1, 41 g, 5.29 mmol, 1.10 equiv), dichloromethane (20 mL), NaBH (OAc)3 (4.07 g, 19.20 mmol, 4.00 equiv). The resulting solution was stirred overnight at 25°C in an oil bath. The reaction was cooled by adding 100 mL of water. The resulting solution was extracted with 3 x 150 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3x150 mL of brine. The mixture was dried over anhydrous sodium sulfate. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0%~37%). The collected fractions were combined and concentrated under vacuum. This resulted in 2.8 g (96%) of 2-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl ]pent-4-en-1-yl)-2,3-dihydro-1H-isoindole-1,3-dione (380a) as a colorless solid. Step 2. 2-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]-5-hydroxypentyl)-2, 3-dihydro-1H-isoindole-1,3-dione (Intermediate 380b)

[00521] A 100 mL, three-necked, round-bottom flask, purged and maintained under an inert nitrogen atmosphere, was charged with 2-(4-[4-chloro-3-[([1-[4-( 2-cyclopropoxyphenyl)pyridine]3-yl]cyclopropyl]amino)methyl]phenyl]pent-4-en-1-yl)-2,3-dihydro-1H-isoindole-1,3-dione (380a, 600 mg, 0.99 mmol, 1.00 equiv), tetrahydrofuran (30 mL). This was followed by addition of BH3.Me2S in tetrahydrofuran (2M) (2.48 mL, 5.00 equiv) dropwise with stirring at 0oC in 3 min. The resulting solution was stirred overnight at room temperature. The solution was concentrated in vacuum. Tetrahydrofuran (30 ml) was added. To this was added a mixture of sodium hydroxide (2M) (3 mL) and H2O2 (33%) (1.5 mL) dropwise with stirring at 0 oC in 3 min. The resulting solution was stirred for 1 h at room temperature. The reaction was then quenched by adding 60 mL of sat. aq. Na2S2O3. The resulting solution was extracted with 3 x 100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3x150 mL of brine. The mixture was dried over anhydrous sodium sulfate. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0%~37%). The collected fractions were combined and concentrated under vacuum. This resulted in 200 mg (32%) of 2-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]- 5-hydroxypentyl)-2,3-dihydro-1H-isoindole-1,3-dione (380b) as a white solid. Step 3. 5-Amino-2-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pentan-1-ol (Intermediate 380c)

[00522] A 100 mL round bottom flask was charged with 2-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl ]phenyl]-5-hydroxypentyl)-2,3-dihydro-1H-isoindole-1,3-dione (380b, 200 mg, 0.32 mmol, 1.00 equiv), ethanol (30 mL), mono -hydrazine hydrate (80 mg, 1.60 mmol, 5.00 equiv). The resulting solution was stirred for 2 days at room temperature. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with methanol/DCM (0.1% NH3/H2O) (0% ~ 10%). The collected fractions were combined and concentrated under vacuum. This resulted in 160 mg (raw) of 5-amino-2-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl] pentane -1-ol (380c) as light yellow oil. Step 4. (3R,4S,5S,6S)-3,4,5-tris(acetyloxy)-6- [(4-[4-chloro-3-[([1-[4-(2- cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]-5-hydroxypentyl)carbamoyl]oxan-2-yl (Intermediate 380d)

[00523] A 50 mL round bottom flask was charged with 5-amino-2-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino) methyl]phenyl]pentan-1-ol (380c, 130 mg, 0.26 mmol, 1.00 equiv), acid (2S, 3S, 4S, 5R)-3,4,5,6-tetrakis (acetyloxy) oxane -2- carboxylic acid (115 mg, 0.32 mmol, 1.20 equiv), HATU (120 mg, 0.32 mmol, 1.20 equiv), DIEA (51 mg, 0.39 mmol, 1.50 equiv. ), N,N-dimethylformamide (10 mL). The resulting solution was stirred overnight at room temperature. The reaction was cooled by adding 40 mL of water. The resulting solution was extracted with 3 x 100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3x150 mL of brine. The mixture was dried over anhydrous sodium sulfate. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with dichloromethane/methanol (0%~10%). The collected fractions were combined and concentrated under vacuum. This resulted in 170 mg (77%) of acetate (3R, 4S, 5S, 6S)-3,4,5-tris(acetyloxy)-6-[(4-[4-chloro-3-[([1- [4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]-5-hydroxypentyl)carbamoyl]oxan-2-yl (380d) as a light brown solid. Step 5. (2S,3S,4S,5R)-N-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl] phenyl]-5-hydroxypentyl)-3,4,5,6-tetrahydroxyanoxane-2-carboxamide (Intermediate 380e)

[00524] A 50 mL round bottom flask was charged with (3R,4S,5S,6S)-2,3,5-tris(acetyloxy)-6-[(4-[4-chloro-3- [([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]-5-hydroxypentyl)carbamoyl]oxan-4-yl (380d, 170 mg, 0.20 mmol, 1.00 equiv), methanol (10 mL), MeONa (11 mg, 0.20 mmol, 1.00 equiv). The resulting solution was stirred overnight at room temperature. The resulting mixture was concentrated under vacuum. This resulted in 70 mg (52%) of (2S,3S,4S,5R)-N-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl ]cyclopropyl]amino)methyl]phenyl]-5-hydroxypentyl)-3,4,5,6-tetrahydroxyoxane-2-carboxamide (380e) as a light yellow solid. Step 6. (2S,3S,4R,5S)-N-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl] phenyl]-5-hydroxypentyl)- 2,3,4,5,6-pentahydroxyhexanamide (I-380)

[00525] A 25 mL round bottom flask was charged with (2S,3S,4S,5R)-N-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin - 3-yl]cyclopropyl]amino)methyl]phenyl]-5-hydroxypentyl)-3,4,5,6-tetrahydroxyoxane-2-carboxamide (380e, 70 mg, 0.10 mmol, 1.00 equiv) , methanol (5 mL), NaBH4 (8 mg, 0.21 mmol, 2.00 equiv). The resulting solution was stirred at room temperature for 30 min. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, XBridge Shield RP18 OBD Column; 5μm 19 x 150mm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (24.0% MeCN to 42.0% in 6 min); Detector, UV 220 nm. This resulted in 38 mg (54%) of (2S,3S,4R,5S)-N-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl ]cyclopropyl]amino)methyl]phenyl]-5-hydroxypentyl)-2,3,4,5,6-pentahydroxyhexanamide (I-380) as a white solid: MS (ES, m/z): 670 .20 [M + H]+; 1H NMR (methanol-d4, 400 MHz, ppm) δ 0.41 - 0.47 (m, 2H), 0.66 (d, J = 6.5 Hz, 2H), 0.88 (d, J = 32.3 Hz, 4H), 1.40 (dt, J = 22.4, 11.1 Hz, 2H), 1.54 (s, 1H), 1.79 - 1.89 (m, 1H), 2.70 (dd, J = 10.4, 5.2 Hz, 1H), 3.21 (t, J = 7.0 Hz, 2H), 3.56 - 3.74 (m, 7H), 3 .74 - 3.89 (m, 3H), 4.13 (d, J = 5.9 Hz, 1H), 7.05 - 7.15 (m, 3H), 7.17 - 7.31 (m , 3H), 7.48 (d, J = 3.6 Hz, 2H), 8.48 (d, J = 5.0 Hz, 1H), 8.61 (s, 1H).Example 68: (2S ,3S,4R,5S)-N-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pent-4 -en-1-yl)-2,3,4,5,6-pentahydroxyhexanamide (I-381)

[00526] A 100 mL round bottom flask was charged with 2-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl ]phenyl]pent-4-en-1-yl)-2,3-dihydro-1H-isoindole-1,3-dione (364a, 500 mg, 0.83 mmol, 1.00 equiv), ethanol ( 30 mL) NH2NH2.H2O (124 mg, 2.48 mmol, 3.00 equiv) was added. The resulting solution was stirred for 2 days at room temperature. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with methanol/DCM (0.1% NH3/H2O) (0%~10%). The collected fractions were combined and concentrated under vacuum. This resulted in 330 mg (84%) of N - [[5- (5-aminopent-1-en-2-yl) -2- chlorophenyl] methyl] -1- [4- (2- cyclopropoxyphenyl) pyridin-3 -yl] cyclopropane-1-amine (381b) as light yellow oil. Step 2. (3R,4S,5S,6S)-2,3,5-tris(acetyloxy)-6- [(4-[4-chloro-3-[([1-[4-(2- cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pent-4-en-1-yl)carbamoyl]oxan-4-yl (Intermediate 381c)

[00527] A 50 mL round bottom flask was charged with N-[[5-(5-aminopent-1-en-2-yl)-2-chlorophenyl]methyl]-1-[4-(2-cyclopropoxyphenyl )pyridin-3-yl]cyclopropane-1-amine (381b, 220 mg, 0.46 mmol, 1.00 equiv), (2S,3S,4S,5R)-3,4,5,6-tetrakis acid ( acetyloxy)oxane-2-carboxylic acid (202 mg, 0.56 mmol, 1.20 equiv), HATU (212 mg, 0.56 mmol, 1.20 equiv), DIEA (90 mg, 0.70 mmol, 1, 50 equiv.), N,N-dimethylformamide (10 mL). The resulting solution was stirred overnight at room temperature. The reaction was cooled by adding 50 mL of water. The resulting solution was extracted with 3 x 100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3x150 mL of brine. The mixture was dried over anhydrous sodium sulfate. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with dichloromethane/methanol (0%~10%). The collected fractions were combined and concentrated under vacuum. This resulted in 320 mg (84%) of (3R,4S,5S,6S)-2,3,5-tris(acetyloxy)-6-[(4-[4-chloro-3-[([1-[ 4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pent-4-en-1-yl)carbamoyl]oxan-4-yl (381c) as a light brown solid. Step 3. (2S,3S,4S,5R)-N-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl] phenyl]-5-hydroxypentyl)-3,4,5,6-tetrahydroxyanoxane-2-carboxamide (Intermediate 381d)

[00528] A 25 mL round bottom flask was charged with (3R,4S,5S,6S)-3,4,5-tris(acetyloxy)-6-[(4-[4-chloro-3-[ acetate ([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pent-4-en-1-yl)carbamoyl]oxan-2-yl (281c, 320 mg, 0 .39 mmol, 1.00 equiv), methanol (5 mL), MeONa (21 mg, 0.39 mmol, 1.00 equiv). The resulting solution was stirred for 1 h at 40 oC in an oil bath. The resulting mixture was concentrated under vacuum. This resulted in 254 mg (100%) of (2S,3S,4S,5R)-N-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl ]cyclopropyl]amino)methyl]phenyl]pent-4-en-1-yl)-3,4,5,6-tetrahydroxyoxane-2-carboxamide (381d) as a light yellow solid. Step 4. (2S,3S,4R,5S)-N-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl] phenyl]pent-4-en-1-yl)-2,3,4,5,6-pentahydroxyhexanamide (I-381)

[00529] A 25 mL round bottom flask was charged with (2S,3S,4S,5R)-N-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin - 3-yl]cyclopropyl]amino)methyl]phenyl]-5-hydroxypentyl)-3,4,5,6-tetrahydroxyoxane-2-carboxamide (381d, 254 mg, 0.39 mmol, 1.00 equiv), methanol (5 mL), NaBH4 (30 mg, 0.79 mmol, 2.00 equiv). The resulting solution was stirred at room temperature for 30 min. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, Gemini-NX 5μ C18 110A, AXIA Packed, 150 x 21.2 mm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (34.0% MeCN to 54.0% in 6 min); Detector, 220 nm. This resulted in 88.2 mg (35%) of (2S,3S,4R,5S)-N-(4-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3 -yl]cyclopropyl]amino)methyl]phenyl]pent-4-en-1-yl)-2,3,4,5,6-pentahydroxyhexanamide (I-381) as a white solid: MS (ES , m/z): 652.20 [M + H]+; 1H NMR (methanol-d4, 300 MHz, ppm) δ 0.42 (s, 2H), 0.58 - 0.69 (m, 2H), 0.88 (d, J = 19.0 Hz, 4H) , 1.65 (p, J = 7.2 Hz, 2H), 2.54 (t, J = 7.7 Hz, 2H), 3.26 (t, J = 7.1 Hz, 2H), 3 .55 - 3.70 (m, 3H), 3.73 (s, 2H), 3.83 (tdd, J = 11.6, 5.9, 3.4 Hz, 3H), 4.13 (t , J = 5.5 Hz, 1H), 5.14 (d, J = 1.7 Hz, 1H), 5.25 (d, J = 1.4 Hz, 1H), 7.02 - 7.22 (m, 3H), 7.22 - 7.32 (m, 3H), 7.41 - 7.54 (m, 2H), 8.47 (d, J = 5.0 Hz, 1H), 8, 60 (s, 1H).Example 69: (2S,3S,4R,5S)-N-[3-(1-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin- 3-yl]cyclopropyl]amino)methyl]phenyl]cyclopropyl)propyl]-2,3,4,5,6-pentahydroxyhexanamide (I-382)

[00530] A 100 mL round bottom flask charged with 5-[5-[(tert-butyldiphenylsilyl)oxy]pent-1-en-2-yl]-2-chlorobenzaldehyde (1.7 g, 3.67 mmol , 1.00 equiv) and methanol (10 mL) were added NaBH4 (279 mg, 7.38 mmol, 2.00 equiv) in portions. The resulting solution was stirred for 1 h at room temperature. The reaction was then cooled by adding 100 mL of NH4Cl. The resulting solution was extracted with 3 x 30 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 760 mg (45%) of (5-[5-[(tert-butyldiphenylsilyl)oxy]pent-1-en-2-yl]-2-chlorophenyl)methanol (382a) as yellow oil. Step 2. [5-(1-[3-[(tert-butyldiphenylsilyl)oxy]propyl]cyclopropyl)-2-chlorophenyl]methanol (Intermediate 382b)

[00531] A 100 mL three-neck round bottom flask was purged and maintained under an inert nitrogen atmosphere, charged with (5-[5-[(tert-butyldiphenylsilyl)oxy]pent-1-en-2- yl]-2-chlorophenyl) methanol (382a, 760 mg, 1.63 mmol, 1.00 equiv), diiodomethane (0.8 mL, 6.00 equiv) and DCE (10 mL) was added Et2Zn (6 .5 mL, 6.00 equiv, 1.5 M in hexane) dropwise with stirring at 0 oC. The resulting solution was stirred for 12 h at room temperature. The reaction was then cooled by adding 100 mL of NH4Cl. The resulting solution was extracted with 3 x 30 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:15). This resulted in 550 mg (70%) of [5-(1-[3-[(tert-butyldiphenylsilyl)oxy]propyl]cyclopropyl)-2-chlorophenyl]methanol (382b) as yellow oil. Step 3. 5-(1-[3-[(tert-butyldiphenylsilyl)oxy]propyl]cyclopropyl)-2-chlorobenzaldehyde (Intermediate 382c)

[00532] A [5-(1-[3-[(tert-butyldiphenylsilyl)oxy]propyl]cyclopropyl)-2-chlorophenyl]methanol (382b, 550 mg, 1.15 mmol, 1.00 equiv) in chloroform ( 20 mL) MnO2 (2.99 g, 34.39 mmol, 30.00 equiv) was added. The resulting solution was stirred for 12 h at 60°C in an oil bath. The solids were filtered. The resulting mixture was concentrated under vacuum. The crude product (1.3 g) was purified by flash chromatography with the following conditions: Column, silica gel; mobile phase, ethyl acetate/petroleum ether = 0% increasing to ethyl acetate/petroleum ether = 10% over 30 min; Detector, UV 254 nm to provide 450 mg (82%) of 5-(1-[3-[(tert-butyldiphenylsilyl)oxy]propyl]cyclopropyl)-2-chlorobenzaldehyde (382c) as yellow oil. Step 4. N-[[5-(1-[3-[(tert-butyldiphenylsilyl)oxy]propyl]cyclopropyl)-2-chlorophenyl]methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl ]cyclopropan-1-amine (Intermediate 382d)

[00533] For a solution of 5-(1-[3-[(tert-butyldiphenylsilyl)oxy]propyl]cyclopropyl)-2-chlorobenzaldehyde (382c, 450 mg, 0.94 mmol, 1.00 equiv), 1- [4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (349 mg, 1.31 mmol, 1.00 equiv) in AcOH (0.5 mL) and dichloromethane (10 mL) stirred under a Inert atmosphere of nitrogen was added NaHB (OAc)3 (1.20 g, 5.66 mmol, 6.00 equiv), in portions over 1 h. The resulting solution was stirred for 12 h at room temperature. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 100 mL of ethyl acetate. The resulting mixture was washed with 1 x 50 ml of sodium bicarbonate and 1 x 50 ml of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (1.05 g) was purified by flash chromatography with the following conditions: Column, silica gel; in the mobile phase; ethyl acetate/petroleum ether = 0% increasing to ethyl acetate/petroleum ether = 30% over 50 min; Detector, UV 254 nm. 650 mg of product was obtained. This resulted in 650 mg (95%) of N-[[5-(1-[3-[(tert-butyldiphenylsilyl)oxy]propyl]cyclopropyl)-2-chlorophenyl]methyl]-1-[4-(2- cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (382d) as yellow oil. Step 5. 3-(1-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]cyclopropyl)propan-1-ol ( Intermediate 382e)

[00534] A 50 mL round bottom flask, purged and maintained under an inert nitrogen atmosphere, was placed N-[[5-(1-[3-[(tert-butyldiphenylsilyl)oxy]propyl]cyclopropyl)-2 -chlorophenyl]methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (382d, 650 mg, 0.89 mmol, 1.00 equiv) in THF (10 mL). TBAF (1.34 mL, 1.50 equiv.) was added dropwise with stirring at room temperature. The resulting solution was stirred for 1 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 403 mg (92%) of 3-(1-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]cyclopropyl )propan-1-ol (382e) as yellow oil. Step 6. (3-(1-[4-Chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]cyclopropyl)propyl methanesulfonate (Intermediate 382f)

[00535] A 100 mL round-bottom flask purged and kept under an inert nitrogen atmosphere was placed 3-(1-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin- 3-yl]cyclopropyl]amino)methyl]phenyl]cyclopropyl)propan-1-ol (382e, 403 mg, 0.82 mmol, 1.00 equiv), TEA (0.23 mL, 2.00 equiv), dichloromethane (10 mL). MsCl (0.097 mL, 1.50 equiv) was added dropwise with stirring at 0 oC. The resulting solution was stirred at room temperature for 30 min. The resulting solution was diluted with 100 mL of DCM. The resulting mixture was washed with 2x50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 492 mg (raw) of 3-(1-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]cyclopropyl )propyl methanesulfonate (382f) as yellow crude oil. Step 7. 2-[3-(1-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]cyclopropyl)propyl]- 2,3-dihydro-1H-isoindole-1,3-dione (Intermediate 382g)

[00536] 3-(1-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]cyclopropyl)propyl methanesulfonate (382f, 468 mg, 0.83 mmol, 1.00 equiv), 2-potassium-2,3-dihydro-1H-isoindole-1,3-dione (306 mg, 1.65 mmol, 1.50 equiv) dissolved in DMF (10 mL). The resulting solution was stirred for 2.5 h at 80°C in an oil bath. The resulting solution was diluted with 100 mL of ethyl acetate. The resulting mixture was washed with 3x50 mL of brine. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 450 mg (88%) of 2-[3-(1-[4-chloro-3- [([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl] phenyl]cyclopropyl)propyl]-2,3-dihydro-1H-isoindole-1,3-dione (382g) as yellow oil. Step 8. N-([5-[1-(3-aminopropyl)cyclopropyl]-2-chlorophenyl]methyl)-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (Intermediate 382h)

[00537] 2-[3-(1-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]cyclopropyl)propyl]- 2,3-dihydro-1H-isoindole-1,3-dione (382g, 450 mg, 0.73 mmol, 1.00 equiv), tetrahydrofuran (5 mL), methanol (5 mL) and NH2NH2* H2O (365 mg, 7.30 mmol, 10.00 equiv) was stirred for 12 h at 60 oC in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 100 mL of DCM. The resulting mixture was washed with 3x50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 330 mg (93%) of N-([5-[1-(3-aminopropyl)cyclopropyl]-2-chlorophenyl]methyl)-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropan-1-amine (382h) as a yellow solid. Step 9. (2S,3S,4S,5R)-4,5,6-tris(acetyloxy)-2- [[3-(1-[4-chloro-3-[([1-[4- (2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]cyclopropyl)propyl]carbamoyl]oxan-3-yl (Intermediate 382i)

[00538] N-([5-[1-(3-aminopropyl)cyclopropyl]-2-chlorophenyl]methyl)-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (382h , 210 mg, 0.43 mmol, 1.00 equiv), (2S, 3S, 4S, 5R)-3,4,5,6-tetrakis(acetyloxy)oxane-2-carboxylic acid (156 mg, 0.43 mmol, 1.00 equiv), DIEA (0.28 mL, 4.00 equiv), HATU (245 mg, 0.64 mmol, 1.50 equiv) in dichloromethane (10 mL) was stirred for 3.5 h at room temperature. The resulting solution was diluted with 100 mL of DCM. The resulting mixture was washed with 3x50 mL of brine. The solid was dried in an oven at reduced pressure. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 160 mg (45%) of (2S, 3S, 4S, 5R)-4,5,6-tris(acetyloxy)-2-[[3-(1-[4-chloro-3-[ ([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]cyclopropyl)propyl]carbamoyl]oxan-3-yl (382i) as yellow oil. Step 10. (2S,3S,4S,5R)-N-[3-(1-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino )methyl]phenyl]cyclopropyl)propyl]-3,4,5,6-tetrahydroxy-oxane-2-carboxamide (Intermediate 382j)

[00539] A 50 mL round bottom flask was purged and maintained under an inert nitrogen atmosphere charged with (2S,3S,4S,5R)-4,5,6-tris(acetyloxy)-2-[[3- (1-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]cyclopropyl)propyl]carbamoyl]oxan-3-yl (382i , 160 mg, 0.19 mmol, 1.00 equiv) in methanol (5 mL) was added sodium methoxide (0.39 mL, 2.00 equiv) dropwise with stirring. The resulting solution was stirred at room temperature for 30 min. This resulted in 132 mg (crude) of (2S,3S,4S,5R)-N-[3-(1-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3 -yl]cyclopropyl]amino)methyl]phenyl]cyclopropyl)propyl]-3,4,5,6-tetrahydroxyoxane-2-carboxamide (382j) as yellow oil. Step 11. (2S,3S,4R,5S)-N-[3-(1-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino )methyl]phenyl]cyclopropyl)propyl]-2,3,4,5,6-pentahydroxyhexanamide (I-382)

[00540] A (2S,3S,4S,5R)-N-[3-(1-[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl] amino)methyl]phenyl]cyclopropyl)propyl]-3,4,5,6-tetrahydroxy-oxane-2-carboxamide (382j, 128 mg, 0.19 mmol, 1.00 equiv) in methanol (5 mL) NaBH4 (15 mg, 0.40 mmol, 2.00 equiv) was added in portions. The resulting solution was stirred at room temperature for 40 min. The resulting mixture was concentrated under vacuum. The crude product was purified by Prep-HPLC with the following conditions: Column, XBridge C18 OBD Column Prep; 5μm, 19mm x 250mm; mobile phase NH4HCO310 mM aq.) and MeCN (40.0% MeCN to 60.0% in 10 min); 254 nm UV detector. This resulted in 60.2 mg (47%) of (2S,3S,4R,5S)-N-[3-(1-[4-chloro-3- [([1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]cyclopropyl)propyl]-2,3,4,5,6-pentahydroxyhexanamide (I-382) as a white solid: MS (ES, m/z):[ M+1]+ 666.40; 1H NMR (400 MHz, Methanol-d4) δ 8.57 (s, 1H), 8.46 (d, J = 5.0 Hz, 1H), 7.52 - 7.42 (m, 2H), 7 .26 - 7.05 (m, 6H), 4.59 (s, 1H), 4.09 (t, J = 6.0 Hz, 1H), 3.79 (dddd, J = 15.0, 10 .7, 7.5, 3.4 Hz, 2H), 3.73 - 3.54 (m, 5H), 3.16 (tt, J = 6.9, 3.6 Hz, 2H), 1, 62 - 1.53 (m, 2H), 1.44 (p, J = 7.1 Hz, 2H), 0.94 - 0.80 (m, 4H), 0.67 (dd, J = 27, 5, 6.6 Hz, 6H), 0.43 - 0.37 (m, 2H).

[00541] Compounds I-383 to I-387 in Table 13 below were prepared from known commercial base materials or the appropriate intermediates disclosed herein, using the methods of the examples specified in Table 13 and methods generally known to those skilled in the art. technique.Table 13. Compounds I-383 to I-387 Example 70: (2S,3S,4R,5S)-N-(4-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene] sulfonamido]butyl)- 2,3,4,5,6-pentahydroxyhexanamide (I-388)

[00542] A 250 mL round bottom flask was charged with 5-bromo-2-chlorobenzaldehyde (8.0 g, 36.45 mmol, 1.00 equiv), methanol (150 mL). This was followed by the addition of NaBH4 (14.0 g, 370.08 mmol, 10.00 equiv). The resulting solution was stirred for 30 min at 0°C in a water/ice bath. The resulting solution was diluted with 200 mL of H2O. The resulting solution was extracted with 3 x 200 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 7.7 g (95%) of (5-bromo-2-chlorophenyl) methanol (388a) as colorless oil. Step 2. 4-Bromo-2-(bromomethyl)-1-chlorobenzene (Intermediate 388b)

[00543] A 250 mL round bottom flask was charged with (5-bromo-2-chlorophenyl) methanol (388a, 5.0 g, 22.58 mmol, 1.00 equiv), dichloromethane (75 mL), tetra -hydrofuran (75 mL), NBS (6.03 g, 33.88 mmol, 1.50 equiv), PPh3 (8.93 g, 34.05 mmol, 1.50 equiv). The resulting solution was stirred for 30 min at 0°C in a water/ice bath. The resulting mixture was concentrated under vacuum. The crude product was purified by flash chromatography with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ethyl acetate:petroleum ether = 100:0 increasing to ethyl acetate:petroleum ether = 100:0 within 15 min; Detector, UV 254 nm. 6.8 g of product was obtained. This resulted in 6.8 g (crude) of 4-bromo-2-(bromomethyl)-1-chlorobenzene (388b) as a white solid. Step 3. 3-[1-[(5-bromo-2-chlorophenyl)methoxy]cyclopropyl]-4-(2-cyclopropoxyphenyl)pyridine (Intermediate 388c)

[00544] A 250 mL round bottom flask was charged with 4-bromo-2-(bromomethyl)-1-chlorobenzene (388b, 6.3 g, 22.15 mmol, 1.00 equiv), N,N- dimethylformamide (150 mL), 1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropan-1-ol (6.0 g, 22.44 mmol, 1.00 equiv), sodium hydride (1. 1 g, 45.83 mmol, 2.00 equiv). The resulting solution was stirred for 2 h at 0°C in a salt/ice bath. The resulting solution was diluted with 200 mL of H2O. The resulting solution was extracted with 3 x 100 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 5.5 g (53%) of 3-[1-[(5-bromo-2-chlorophenyl)methoxy]cyclopropyl]-4-(2-cyclopropoxyphenyl)pyridine (388c) as light yellow oil. Step 4. 3-(1-[[5-(benzylsulfanyl)-2-chlorophenyl]methoxy]cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridine (Intermediate 388d)

[00545] A 250 mL round bottom flask was charged with 3-[1-[(5-bromo-2-chlorophenyl)methoxy]cyclopropyl]-4-(2-cyclopropoxyphenyl)pyridine (388c, 2.0 g, 4.25 mmol, 1.00 equiv), phenylmethanethiol (800 mg, 6.44 mmol, 1.20 equiv), DIEA (2 mL, 2.00 equiv), Xantphos (290 mg, 0.50 mmol, 0. 10 equiv), Pd (dba)3 (195 mg, 0.05 equiv), dioxane (50 mL). The resulting solution was stirred for 1 night at 100 oC in an oil bath. The resulting solution was diluted with 200 mL of H2O. The resulting solution was extracted with 3 x 200 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (1.8 g) was purified by flash chromatography with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ethyl acetate:petroleum ether = 100:0 increasing to ethyl acetate:petroleum ether = 70:30 within 30 min; Detector, UV 254 nm. 1.6 g of product was obtained. This resulted in 1.6 g (73%) of 3-(1-[[5-(benzylsulfanyl)-2-chlorophenyl]methoxy]-cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridine (388d) as brown oil. Step 5. 4-Chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene-1-sulfonyl chloride (Intermediate 388e)

[00546] A 100 mL round bottom flask was charged with 3-(1-[[5-(benzylsulfanyl)-2-chlorophenyl]methoxy]cyclopropyl)-4-(2-cyclopropoxyphenyl) pyridine (388d, 400 mg, 0.78 mmol, 1.00 equiv), water (5 mL). This was followed by the addition of AcOH (14 mL). The solution cooled to 0 oC. To this was added NCS (321 mg, 2.40 mmol, 3.10 equiv). The resulting solution was stirred overnight at room temperature. The resulting solution was extracted with 100 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 2x10 mL of brine. The solid was dried in an oven at reduced pressure. This resulted in 350 mg (92%) of 4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene-1-sulfonyl chloride (388e) as oil light yellow raw. Step 6. Tert-Butyl N-(4-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamate ( Intermediate 388f)

[00547] A 25 mL round bottom flask was charged with tert-butyl N-(4-aminobutyl) carbamate (154 mg, 0.82 mmol, 2.00 equiv), DIEA (105 mg, 0.81 mmol, 2.00 equiv), dichloromethane (5 mL). This was followed by the addition of 4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxyl]methyl)benzene-1-sulfonyl chloride (388e, 200 mg, 0.41 mmol, 1.00 equiv) dropwise with stirring at 0 oC. The resulting solution was stirred for 5 min at 0°C in a water/ice bath. The crude product (10 mL) was purified by flash chromatography with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ethyl acetate:petroleum ether = 100:0 increasing to ethyl acetate:petroleum ether = 50:50 within 25 min; Detector, UV 254 nm. This resulted in 0.125 g (48%) of N-(4-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl )tert-butyl carbamate (388f) as light yellow oil. Eapa 7. N-(4-aminobutyl)-4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxyl]methyl)benzene-1-sulfonamide (Intermediate 388g)

[00548] A 50 mL round bottom flask with three necks N-(4-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene ]sulfonamido]butyl) tert-butyl carbamate (388f, 510 mg, 0.79 mmol, 1.00 equiv), dichloromethane (10 mL), lutidine (0.425 g, 5.00 equiv), TMSOTf (0.706 g, 5 .00 equiv). The resulting solution was stirred for 5 min at 0°C in a salt/ice bath. The resulting solution was allowed to react, with stirring, for a further 90 min at room temperature. The reaction was then cooled by adding 20 mL of NH4Cl (aq). The resulting solution was extracted with 200 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with dichloromethane/methanol (15:1). This resulted in 0.25 g (58%) of N-(4-aminobutyl)-4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene- 1-sulfonamide (388g) as yellow oil. Step 8. (2S,3S,4S,5R)-4,5,6-tris(acetyloxy)-2- [(4-[[4-chloro-3-([1-[4-(2- cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamoyl]oxan-3-yl (Intermediate 388h)

[00549] A 25 mL round bottom flask was charged with N-(4-aminobutyl)-4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl) benzene-1-sulfonamide (388g, 220 mg, 0.41 mmol, 1.00 equiv), (2S,3S,4S,5R)-3,4,5,6-tetrakis(acetyloxy)oxane-2-carboxylic acid (442 mg, 1.22 mmol, 3.00 equiv), N,N-dimethylformamide (12 mL), HATU (232 mg, 0.61 mmol, 1.50 equiv), DIEA (105 mg, 0.81 mmol , 2.00 equiv). The resulting solution was stirred overnight at room temperature. The resulting solution was diluted with 200 mL of ethyl acetate. The resulting solution was extracted with 3 x 100 mL of brine and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with dichloromethane/methanol (20:1). This resulted in 200 mg (56%) of (2S,3S,4S,5R)-4,5,6-tris(acetyloxy)-2-[(4-[[4-chloro-3-([1 -[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamoyl]oxan-3-yl (388h) as a light yellow oil. Step 9. (2S,3S,4R,5S)-N-(4-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene] sulfonamido]butyl)-2,3,4,5,6-pentahydroxyhexanamide (I-388) A 250 mL round bottom flask was charged with (2S,3S,4S,5R)-4 acetate, 5,6-tris(acetyloxy)-2-[(4-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl )carbamoyl]oxan-3-yl (388h, 200 mg, 0.23 mmol, 1.00 equiv), methanol (20 mL), sodium methylate (35 mg, 0.65 mmol, 2.50 equiv), NaBH4 (20 mg, 0.53 mmol, 2.50 equiv), methanol (5 mL). The resulting solution was stirred for 1 h at room temperature. The resulting solution was diluted with 2 mL of H2O. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, OBD XBridge Shield RP18 Column; 5μm 19 x 150mm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (30.0% CAN to 50.0% in 6 min); Detector, UV 220 nm. This resulted in 108.5 mg (67%) of (2S,3S,4R,5S)-N-(4-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3 -yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)-2,3,4,5,6-pentahydroxyhexanamide (I-388) as a white solid: MS (ES, m/z): 720; 1H-NMR (CDCl3, ppm): 8.58 (1H, m), 8.45 (1H, m), 7.69 (2H, m), 7.65 (1H, m), 7.35 (2H , m), 7.22 (2H, m), 7.02 (1H, m), 4.47 (2H, m), 4.11 (1H, m), 3.83 (3H, m), 3 .55 (3H, m), 3.19 (2H, m), 2.81 (2H, m), 1.51 (4H, m), 1.01 (4H, m), 0.59 (2H, m), 0.39 (2H, s). Example 71: 1-(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)-3- [(2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-389)

[00550] A 100 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with 2-chloro-5-(chlorosulfonyl)benzoic acid (500 mg, 1.96 mmol, 1.50 equiv.), dichloromethane (15 mL), tert-butyl N-[4-(methylamino)butyl]carbamate (266.3 mg, 1.32 mmol, 1.00 equiv), TEA (0.37 mL). The resulting solution was stirred for 3 h at room temperature. The resulting solution was extracted with 3 x 50 mL of dichloromethane and the organic layers combined and concentrated in vacuo. This resulted in 420 mg (76%) of 5-[(4-[[(tert-butoxy)carbonyl]amino]butyl)(methyl)sulfamoyl]-2-chlorobenzoic acid (389a) as yellow oil. Step 2. Tert-Butyl N-(4-[N-methyl[4-chloro-3-(hydroxymethyl)benzene]sulfonamido]butyl)carbamate (Intermediate 389b)

[00551] A 500 mL round bottom flask was charged with 5-[(4-[[(tert-butoxy)carbonyl]amino]butyl)(methyl)sulfamoyl]-2-chlorobenzoic acid (19 g, 45.14 mmol, 1.00 equiv), chloro(2-methylpropoxy) methanone (389a, 9.25 g, 67.73 mmol, 1.50 equiv), tetrahydrofuran (150 mL), triethylamine (6.85 g, 67 .69 mmol, 1.50 equiv). The resulting solution was stirred for 0.5 h at 0°C and then stirred for 1 h at room temperature. The reaction was then dropwise in NaBH4 (6.8 g, 179.75 mmol, 4.00 equiv) in ethanol (150 mL), with stirring for 0.5 h at 0°C, and then stirred for 1 h at room temperature. The resulting solution was stirred for 3 h at room temperature. The reaction was cooled by adding 100 mL of water. The resulting solution was extracted with 3 x 100 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0-30%). The collected fractions were combined and concentrated under vacuum. This resulted in 12 g (65%) of tert-butyl N-(4-[N-methyl[4-chloro-3-(hydroxymethyl)benzene]sulfonamido]butyl)carbamate (389b) as yellow oil. Step 3. Tert-Butyl N-(4-[N-methyl[3-(bromomethyl)-4-chlorobenzene]sulfonamido]butyl)carbamate (Intermediate 389c)

[00552] A 1000 mL round bottom flask was charged with tert-butyl N-(4-[N-methyl[4-chloro-3-(hydroxymethyl)benzene]sulfonamido]butyl)carbamate (389b, 24 g, 58.98 mmol, 1.00 equiv), DCM/THF (200/200 mL). This was followed by the addition of NBS (17.1 g, 96.08 mmol, 1.63 equiv) in several batches at 0 oC in 5 min. To this end, PPh3 (23.6 g, 89.98 mmol, 1.53 equiv) was added in several batches at 0 oC in 5 min. The resulting solution was stirred for 1 h at 0°C in a water/ice bath. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0-25%). This resulted in 17 g (61%) of tert-butyl N-(4-[N-methyl[3-(bromomethyl)-4-chlorobenzene]sulfonamido]butyl)carbamate (389c) as a white solid. Step 4. Tert N-(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamate - butyl (Intermediate 389d)

[00553] A 500 mL three-neck round-bottom flask was charged with tert-butyl N-(4-[N-methyl[3-(bromomethyl)-4-chlorobenzene]sulfonamido]butyl)carbamate (389c, 5 .9 g, 12.56 mmol, 1.10 equiv.) N,N-dimethylformamide (360 mL), 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-ol (3.06 g, 11.45 mmol, 1.00 equiv). This was followed by addition of sodium hydride (917 mg, 38.21 mmol, 3.34 equiv) in several batches at 0°C in 5 min. The resulting solution was stirred for 20 min at 0°C. The resulting solution was diluted with 50 mL of ethyl acetate. The reaction was then cooled by adding 50 mL of NH4Cl. The residue was dissolved in 50 mL of H2O. The resulting solution was extracted with 3 x 200 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3x300 mL of brine. The mixture was dried over anhydrous sodium sulfate. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 4.0 g (53%) of N-(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl) benzene] sulfonamido] butyl) tert-butyl carbamate (389d) as light yellow oil. Step 5. N-(4-aminobutyl)-4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxyl]methyl)-N-methylbenzene-1-sulfonamide (Intermediate 389e )

[00554] A 1000 mL round bottom flask was charged with N-(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy] tert-butyl methyl)benzene]sulfonamido]butyl)carbamate (389d, 17 g, 25.91 mmol, 1.00 equiv), TFA/DCM (42.5/425 ml). The resulting solution was stirred for 1 h at room temperature. The pH value of the solution was adjusted to 9.0-10.0 with sodium bicarbonate (100%). The resulting solution was extracted with 7 x 500 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with H2O: acetonitrile (0-100%). This resulted in 10.4 g (72%) of N-(4-aminobutyl)-4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-N -methylbenzene-1-sulfonamide (389e) as light yellow oil. Step 6. 1-(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)-3- [(2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-389)

[00555] A 100 mL round bottom flask was charged with N-(4-aminobutyl)-4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl) -N-methylbenzene-1-sulfonamide (389e, 2 g, 3.60 mmol, 1.00 equiv) was dissolved in N,N-dimethylformamide (36 mL, 1 mol/L) and DSC (1.02 g, 3 .96 mmol, 1.1 equiv) were added. The resulting solution was stirred for 1 h at room temperature (monitored by LC/MS). (2R,3S,4R,5S)-5-aminohexane-1,2,3,4,6-pentol (1.63 g, 9.00 mmol, 2.50equiv) was added. The resulting solution was allowed to react, with stirring, for another 30 min at 60oC (monitored by LC/MS). The resulting mixture was concentrated to remove the solvent under vacuum. The reaction mixture was cooled to room temperature with a water bath. The reaction was then quenched by the addition of 44 mL of 10%2 NACO3. The resulting solution was diluted with 50 mL of H2O. The resulting solution was extracted with 10 x 55 mL of ethyl acetate (~4.5% acetylation product was found to be formed). The organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered. The resulting mixture was concentrated under vacuum. Then, the residue was dissolved in 60% MeCN/water (10 mL) and purified by combi-flash with a C18 column using MeCN-water-6.5 mmol/L NH4HCO3 (pH adjusted to 10 with aqueous NH4OH), the products were obtained at ~33% MeCN/water. The solvent was removed and this resulted in 1.8 g (66%) of 1-(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy]methyl)benzene]sulfonamido]butyl)-3-[(2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl] urea (I-389) as a white solid: MS (ES, m/z): [M+1]: 763; 1NMR (400 MHz, Methanol-d^ δ 0.34 - 0.43 (m, 2H), 0.56 - 0.66 (m, 2H), 0.95 - 1.06 (m, 4H), 1 .44 - 1.63 (m, 4H), 2.67 (s, 3H), 2.96 (t, J = 6.6 Hz, 2H), 3.14 (t, J = 6.6 Hz, 2H), 3.52 - 3.73 (m, 6H), 3.73 - 3.90 (m, 2H), 3.96 (dd, J = 4.9, 2.8 Hz, 1H), 4 .47 (s, 2H), 7.02 (td, J = 7.2, 1.5Hz, 1H), 7.19 - 7.29 (m, 2H), 7.31 - 7.43 (m, 2H), 7.55 (d, J = 8.4 Hz, 2H), 7.64 (dd, J = 8.2, 2.3 Hz, 1H), 8.49 (d, J = 5.0 Hz, 1H), 8.66 (d, J = 0.7 Hz, 1H). Example 72: 1-(4-[N-ethyl[4-chloro-3-([1-[4-(2- cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] (I -390)

[00556] A 250 mL 3-neck round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with 4-aminobutan-1-ol (9.8 g, 109.94 mmol, 1.00 equiv). This was followed by the addition of dichloromethane (200 mL). The mixture was stirred for 10 min at 0°C. To this, Boc2O (36 g, 164.95 mmol, 1.50 equiv.), sodium carbonate (47 g, 443.40 mmol, 4.00 equiv.) was added. The resulting solution was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1/2). The collected fractions were combined and concentrated under vacuum. This resulted in 20 g (96%) of tert-butyl N-(4-hydroxybutyl) carbamate (390a) as a yellow solid. Step 2. Tert-butyl N-[4-(methanesulfonyloxy)butyl]carbamate (Intermediate 390b)

[00557] A 250 mL 3-neck round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with tert-butyl N-(4-hydroxybutyl)carbamate (390a, 10 g, 52.84 mmol, 1 .00 equiv), dichloromethane (100 mL). This was followed by the addition of DIEA (28 g, 216.65 mmol, 4.00 equiv). The mixture was stirred for 10 mins at 0°C. To this was added MsCl (12 g, 105.26 mmol, 2.00 equiv). The resulting solution was stirred for 1 h at room temperature. The resulting solution was extracted with 3 x 50 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 1 x 50 ml of sodium chloride. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0-30%). The collected fractions were combined and concentrated under vacuum. This resulted in 10 g (71%) of tert-butyl N-[4-(methanesulfonyloxy)butyl] carbamate (390b) as light yellow crude oil. Step 3. Tert-butyl N-[4-[(2-methoxyethyl)amino]butyl]carbamate (Intermediate 390c)

[00558] A 50 mL round bottom flask was charged with tert-butyl N-[4-(methanesulfonyloxy)butyl]carbamate (390b, 5 g, 18.70 mmol, 1.00 equiv), tetrahydrofuran ( 40 mL), 2-methoxyethane-1-amine (14 g, 186.39 mmol, 10.00 equiv). The resulting solution was stirred for 24 h at room temperature. The resulting solution was extracted with 2 x 300 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2x100 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with dichloromethane/methanol (10:1). This resulted in 2.0 g (43%) of tert-butyl N-[4-[(2-methoxyethyl)amino]butyl]carbamate (390c) as light yellow oil. Step 4. Tert N-(4-[N-ethyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamate -butyl (Intermediate 390d)

[00559] A 250 mL round bottom flask was charged with tert-butyl N-[4-(ethylamino)butyl]carbamate (390c, 406 mg, 1.88 mmol, 2.00 equiv), dichloromethane (5 mL ). This was followed by the addition of DIEA (242 mg, 1.87 mmol, 2.00 equiv). The temperature was cooled to 0°C. To this was added a solution of 4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene-1-sulfonyl chloride (460 mg, 0.94 mmol , 1.00 equiv) in dichloromethane (3 mL). The resulting solution was stirred at room temperature for 5 minutes. The resulting solution was extracted with 200 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 2x50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0-60%). This resulted in 315 mg (50%) of N-(4-[N-ethyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene] tert-butyl sulfonamido]butyl)carbamate (390d) as light yellow oil. Step 5. N-(4-aminobutyl)-4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxyl]methyl)-N-ethylbenzene-1-sulfonamide (Intermediate 390e )

[00560] A 100 mL round bottom flask was charged with N-(4-[N-ethyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy] tert-butyl methyl)benzene]sulfonamido]butyl)carbamate (390d, 315 mg, 0.47 mmol, 1.00 equiv), dioxane (10 mL), hydrogen chloride (5 mL). The resulting solution was stirred for 1 h at room temperature. The resulting solution was diluted with 100 mL of ethyl acetate. The pH value of the solution was adjusted to 10 with sodium bicarbonate. The resulting solution was extracted with 2 x 200 ethyl acetate and the organic layers combined. The resulting mixture was washed with 2x50 mL of brine. The solid was dried in an oven at reduced pressure. This resulted in 250 mg (93%) of N-(4-aminobutyl)-4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-N-ethylbenzene -1- sulfonamide (390e) as light yellow oil. Step 6. 1-(4-[N-ethyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)-3- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-390)

[00561] A 25 mL round bottom flask was charged with DSC (136 mg, 1.20 equiv), N,N-dimethylformamide (5 mL), DIEA (85 mg, 0.66 mmol, 2.00 equiv) . This was followed by the addition of N-(4-aminobutyl)-4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-N-ethylbenzene-1-sulfonamide (390e, 250 mg, 0.44 mmol, 1.00 equiv). The mixture was stirred for 30 min. To this was added (2R, 3R, 4R, 5S)-6-aminohexane-1,2,3,4,5-pentol (158 mg, 0.87 mmol, 1.50 equiv.). The resulting solution was stirred overnight at room temperature. The solids were filtered. The crude product (200 mg) was purified by preparative HPLC with the following conditions: Column, OBD XBridge Shield RP18 Column; 5μm 19 x 150mm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (34.0% MeCN to 47.0% in 6 min); Detector, UV 220 nm. This resulted in 107.5 mg (32%) of 1-(4-[N-ethyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl) benzene]sulfonamido]butyl)-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-390) as a white solid: MS (ES , m/z): [M+1]: 777; 1H-NMR (CD3OD, ppm): 8.57 (d, J = 0.7 Hz, 1H), 8.46 (d, J = 5.0 Hz, 1H), 7.50 - 7.40 (m , 2H), 7.26 - 7.14 (m, 3H), 7.14 - 6.99 (m, 3H), 3.71 - 3.59 (m, 3H), 2.65 (dt, J = 14.3, 7.2 Hz, 3H), 1.64 - 1.42 (m, 4H), 1.34 - 1.11 (m, 5H), 0.90 (s, 2H), 0, 81 (s, 2H), 0.62 (t, J = 6.3 Hz, 2H), 0.45 - 0.39 (m, 2H).Example 73: 1-[4-(N-methyl[2 ,4-dichloro-5-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]benzene]sulfonamido)butyl]-3-[(2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl] urea (I-391)

[00562] A 100 mL round bottom flask was charged with tert-butyl N-(4-aminobutyl)carbamate (600 mg, 3.19 mmol, 1.00 equiv), dichloromethane (15 mL), propan-2 -one (0.47 mL, 2.00 equiv). The resulting solution was stirred for 1 h at room temperature. To this was added NaBH(OAc)3 (3.3 g, 15.57 mmol, 5.00 equiv). The resulting solution was stirred overnight at room temperature. The reaction was cooled by adding 10 mL of water. The resulting solution was diluted with 15 mL of DCM. The pH value of the solution was adjusted to 9 with Na2HCO3 (100%). The resulting solution was extracted with 3 x 15 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered. The resulting mixture was concentrated under vacuum. This resulted in 630 mg (86%) of tert-butyl N-[4-[(propan-2-yl)amino]butyl]carbamate (391b) as yellow oil. Step 2. N-[4-[N-(propan-2-yl)[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido tert-butyl]butyl]carbamate (Intermediate 391b)

[00563] A 100 mL round bottom flask with three necks tert-butyl N-[4-[(propan-2-yl)amino]butyl]carbamate (391a, 188 mg, 0.82 mmol, 2.00 equiv), dichloromethane (10 mL), DIEA (0.08 mL, 1.20 eq). This was followed by the addition of a solution of 4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene-1-sulfonyl chloride (200 mg, 0. 41 mmol, 1.00 equiv) in dichloromethane (3 mL) dropwise with stirring at 0 oC in 10 min. The resulting solution was stirred overnight at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 116 mg (42%) of N-[4-[N-(propan-2-yl)[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] tert-butyl cyclopropoxy]methyl)benzene]sulfonamido]butyl]carbamate (391b) as light yellow oil. Step 3. N-(4-aminobutyl)-4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-N-(propan-2-yl)benzene -1- sulfonamide (Intermediate 391c)

[00564] A 50 mL round bottom flask was charged with N-[4-[N-(propan-2-yl)[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin- tert-butyl 3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl]carbamate (391b, 116 mg, 0.17 mmol, 1.00 equiv), dichloromethane (2.5 mL), trifluoroacetic acid (0.5 mL). The resulting solution was stirred at room temperature for 30 min. The pH value of the solution was adjusted to 9 with sodium bicarbonate (100%). The resulting solution was extracted with 2 x 10 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 84 mg (85%) of N-(4-aminobutyl)-4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-N-( propan-2-yl)benzene-1-sulfonamide (391c) as light yellow oil. Step 4. 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]-1- [4-[N-(propan-2-yl)[4 -chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl]urea (I-391)

[00565] A 50 mL round bottom flask was charged with N-(4-aminobutyl)-4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl) -N-(propan-2-yl)benzene-1-sulfonamide (391c, 84 mg, 0.14 mmol, 1.00 equiv), N,N-dimethylformamide (4 mL), DSC (44 mg, 1.20 equiv), DIEA (55.7 mg, 0.43 mmol, 3.00 equiv). The resulting solution was stirred at room temperature for 1.5 h. To this was added (2R,3R,4R,5S)-6-aminohexane-1,2,3,4,5-pentol (39 mg, 0.22 mmol, 1.50 equiv.). The resulting solution was stirred overnight at room temperature. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, Prep PrepBridge C18 OBD Column, 5μm, 19 mm x 250 mm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (30.0% MeCN to 60.0% in 12 min); Detector, UV 254nm. This resulted in 30.4 mg (27%) of 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]-1-[4-[N- (propan-2-yl)[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-cyclopropoxy]methyl)benzene]sulfonamido]butyl]urea (I-391) as a white solid: (ES, m/z): [M +1]: 791; 1H NMR (400 MHz, methanol-d4) δ 8.66 (s, 1H), 8.49 (d, J = 5.0 Hz, 1H), 7.68 (dd, J = 8.4, 2, 3 Hz, 1H), 7.60 (d, J = 2.2 Hz, 1H), 7.52 (d, J = 8.3 Hz, 1H), 7.45 - 7.32 (m, 2H) , 7.29 - 7.20 (m, 2H), 7.03 (td, J = 7.3, 1.5 Hz, 1H), 4.46 (s, 2H), 3.97 (q, J = 6.7 Hz, 1H), 3.81 - 3.51 (m, 7H), 3.40 (dd, J = 13.9, 4.6 Hz, 1H), 3.22 - 3.05 ( m, 4H), 1.68 - 1.59 (m, 2H), 1.48 (q, J = 7.4 Hz, 2H), 1.01 (dd, J = 15.4, 6.9 Hz , 11H), 0.59 (t, J = 6.4 Hz, 2H), 0.39 (s, 2H). Example 74: 1-[4-(N-methyl[2,4-dichloro-5-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]benzene]sulfonamido) butyl]-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-392)

[00566] A 50 mL round bottom flask was charged with 2,4-dichloro-5-(chlorosulfonyl) benzoic acid (700 mg, 2.42 mmol, 1.00 equiv), dichloromethane (20 mL), N- tert-butyl [4-(methylamino)butyl]carbamate (327.7 mg, 1.62 mmol, 0.67 equiv), TEA (0.32 mL). The resulting solution was stirred at room temperature for 5 h. The resulting solution was diluted with 50 mL of DCM. The reaction was cooled by adding 50 mL of water. The resulting solution was extracted with 2 x 50 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 2x50 mL of brine. The mixture was dried over anhydrous sodium sulfate. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with dichloromethane/methanol (10:1). This resulted in 700 mg (64%) of 5-[(4-[[(tert-butoxy)carbonyl]amino]butyl)(methyl)sulfamoyl]-2,4-dichlorobenzoic acid (392a) as a white solid. Step 2. Tert-Butyl N-(4-[N-methyl[2,4-dichloro-5-(hydroxymethyl)benzene]sulfonamido]butyl)carbamate (Intermediate 392b)

[00567] A 50 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with 5-[(4-[[(tert-butoxy)carbonyl]amino]butyl)(methyl)sulfamoyl]-2,4 -dichlorobenzoic acid (392a, 630 mg, 1.38 mmol, 1.00 equiv), oxolane (10 mL). This was followed by addition of B2H6/THF (1 M, 4.15 mL, 3.00 equiv) dropwise with stirring at 0 oC. The resulting solution was stirred for 2.0 h at 40 oC in an oil bath. The reaction was cooled by adding 10 mL of methanol. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:2). This resulted in 360 mg (59%) of tert-butyl N-(4-[N-methyl[2,4-dichloro-5-(hydroxymethyl)benzene]sulfonamido]butyl)carbamate (392b) as yellow oil. Step 3. Tert-butyl N-[4-[N-methyl(2,4-dichloro-5-formylbenzene)sulfonamido]butyl]carbamate (Intermediate 392c)

[00568] A 50 mL round bottom flask was charged with N-(4-[N-methyl[2,4-dichloro-5-(hydroxymethyl)benzene]sulfonamido]butyl) tert-butyl carbamate (392b, 270 mg, 0.61 mmol, 1.00 equiv), chloroform (10 mL), MnO2 (798 mg, 9.18 mmol, 15.00 equiv). The resulting solution was stirred overnight at 60°C. The solids were filtered. The resulting mixture was concentrated under vacuum. This resulted in 250 mg (93%) of tert-butyl N-[4-[N-methyl(2,4-dichloro-5-formylbenzene)sulfonamido]butyl]carbamate (392c) as a light yellow oil. Step 4. N-[4-(N-methyl[2,4-dichloro-5-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]benzene]sulfonamido) tert-butyl butyl]carbamate (Intermediate 392d)

[00569] A 50 mL round bottom flask was charged with tert-butyl N-[4-[N-methyl(2,4-dichloro-5-formylbenzene)sulfonamido]butyl]carbamate (392c, 250 mg, 0 .57 mmol, 1.00 equiv), 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (151 mg, 0.57 mmol, 1.00 equiv), dichloromethane (10 mL ), NaBH (OAc)3 (724 mg, 6.00 equiv). The resulting solution was stirred overnight at room temperature. The reaction was cooled by adding 10 mL of water. The resulting solution was extracted with 3 x 20 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:1). The collected fractions were combined and concentrated under vacuum. This resulted in 320 mg (82%) of N-[4-(N-methyl[2,4-dichloro-5-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino tert-butyl)methyl]benzene]sulfonamido)butyl]carbamate (392d) as light yellow oil. Step 5. N-(4-aminobutyl)-2,4-dichloro-5-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-N-methylbenzene-1 - sulfonamide (Intermediate 392e)

[00570] A 25 mL round bottom flask was charged with N-[4-(N-methyl[2,4-dichloro-5-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl tert-butyl]cyclopropyl]amino)methyl]benzene]sulfonamido)butyl]carbamate (320 mg, 0.46 mmol, 1.00 equiv), dichloromethane (3 mL), trifluoroacetic acid (2 mL). The resulting solution was stirred at room temperature for 0.5 h. The pH value of the solution was adjusted to 9 with sodium bicarbonate. The residue was applied to a silica gel column with dichloromethane/methanol (30:1). The collected fractions were combined and concentrated under vacuum. This resulted in 240 mg (88%) of N-(4-aminobutyl)-2,4-dichloro-5-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl ]-N-methylbenzene-1-sulfonamide (392e) as light yellow oil. Step 6. 1-[4-(N-methyl[2,4-dichloro-5-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]benzene]sulfonamido) butyl]-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] urea (I-392)

[00571] An 8 mL vial purged and maintained under an inert nitrogen atmosphere was charged with N-(4-aminobutyl)-2,4-dichloro-5-[([1-[4-(2-cyclopropoxyphenyl)pyridin -3-yl]cyclopropyl]amino)methyl]-N-methylbenzene-1-sulfonamide (100 mg, 0.17 mmol, 1.00 equiv), DSC (52.2 mg, 0.20 mmol, 1.20 equiv ), N,N-dimethylformamide (3 mL). This was followed by the addition of DIEA (26.68 mg, 0.22 mmol, 1.30 equiv). The mixture was stirred for 1.5 h at rt. To this was added (2R, 3R, 4R, 5S)-6-aminohexane-1,2,3,4,5-pentol (30.81 mg, 0.17 mmol, 1.00 equiv). The resulting solution was stirred overnight at room temperature. The crude product was purified by preparative HPLC with the following conditions: Column, Prep PrepBridge C18 OBD Column, 5μm, 19 mm x 250 mm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (35.0% MeCN to 50.0% in 10 min); Detector, UV 254nm. This resulted in 28.6 mg (21%) of 1-[4-(N-methyl[2,4-dichloro-5-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl ]amino)methyl]benzene]sulfonamido)butyl]-3-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]urea (I-392) as a solid white: MS (ES, m/z): [M +1]: 796; 1H NMR (400 MHz, methanol-d4) δ 0.39 - 0.45 (m, 2H), 0.66 (d, J = 6.5 Hz, 2H), 0.81 (s, 2H), 0 .90 (s, 2H), 1.46 (p, J = 7.0 Hz, 2H), 1.59 (p, J = 7.1 Hz, 2H), 2.82 (s, 3H), 3 .06 - 3.26 (m, 5H), 3.39 (dd, J = 13.9, 4.5 Hz, 1H), 3.57 - 3.81 (m, 9H), 4.58 (s , 1H), 7.06 - 7.20 (m, 2H), 7.21 - 7.29 (m, 1H), 7.43 - 7.51 (m, 2H), 7.65 (s, 1 H), 7.92 (s, 1H), 8.46 (d, J = 5.0 Hz, 1H), 8.56 (s, 1H). Example 75: 4-chloro-3-([1- [4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-N,N-dimethylbenzene-1-sulfonamide (I-393)

[00572] A 50 mL round bottom flask was charged with dimethylamine/ethanol (0 mg). The solution cooled to 0 oC. This was followed by the addition of 4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxyl]methyl)benzene-1-sulfonyl chloride (200 mg, 0.41 mmol, 1.00 equiv) dropwise with stirring at 0 oC. The resulting solution was stirred at room temperature for 10 min. The resulting solution was extracted with 100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2 x 20 ml of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by preparative HPLC with the following conditions: Column; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (52.0% MeCN to 73.0% in 8 min); Detector, UV 220 nm. The desired product, 4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-N,N-dimethylbenzene-1-sulfonamide, (I-393.9, 0 mg, 39%) was isolated as a white solid. MS (ES, m/z): [M+1] = 499.20; 1H-NMR (CD3OD, ppm): δ 8.66 (d, J = 0.7 Hz, 1H), 8.49 (d, J = 5.1 Hz, 1H), 7.67 - 7.53 ( m, 3H), 7.42 - 7.30 (m, 2H), 7.30 - 7.19 (m, 2H), 7.01 (ddd, J = 7.5, 6.6, 1.9 Hz, 1H), 4.48 (s, 2H), 3.57 (tt, J = 6.0, 2.9 Hz, 1H), 2.64 (s, 6H), 1.06 - 0.93 (m, 4H), 0.66 - 0.56 (m, 2H), 0.43 - 0.35 (m, 2H).

[00573] Compounds I-394 to I-479 (Table 14) were prepared from known commercial base materials or the appropriate intermediates disclosed herein, using methods from the examples specified in Table 14 and methods generally known to those skilled in the art. Table 14. Compounds I-394 to I-479 Example 76: (2S)-2-[4-Chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-6-({[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino)hexanoic acid (I- 483)

[00574] A solution of 388e (56 mg, 0.11 mmol, 1.0 equiv) in acetonitrile (0.5 mL) at 0 °C was added AcOH (33 mg, 0.55 mmol, 5.0 equiv ), H2O (12 mg, 0.66 mmol, 6.0 equiv) and finally NCS (44 mg, 0.32 mmol, 3.0 equiv). After 30 minutes the reaction mixture was warmed to room temperature. After another 2 hours, the reaction was completed by LCMS. The solvent was removed and the product azeotroped twice from toluene. The residue was diluted with DCM (1 mL) and (2-amino-6-(tert-butoxycarbonylamino)hexanoatode (S)-tert-butyl HCl (23.4 mg, 0.061 mmol, 1.1 equiv) and TEA ( 24.6 mg, 0.24 mmol, 4.4 equiv) were added. After 20 minutes the reaction was complete. The crude reaction mixture was applied directly to silica gel (4.0 g) and purified by flash chromatography. (100% DCM to 100% EtOAc over 10 minutes) gave 29.3 mg (64%) of 483b Step 2. 6-amino-2-(3-chloro-4-((1-(4. (S)-tert-butyl-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenylsulfonamido)hexanoate (Intermediate 483c)

[00575] A solution of 483b (30 mg, 0.039 mmol, 1.0 equiv) in DCM (1 mL) was added TFA (0.25 mL) at 0°C. After 30 minutes the reaction was completed and quenched with Na2CO3 (5 mL). The product was extracted with DCM (3 x 10 mL) and dried over Na2SO4 to give 16.1 mg (65%) of 483c which was used without further purification. Step 3. 2-(3-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenylsulfonamido)-6-(3-((2S,3R,4R, (S)-tert-butyl 5R)-2,3,4,5,6-pentahydroxyhexyl)ureido)hexanoate (Intermediate 483d)

[00576] A solution of 483c (16 mg, 0.025 mmol, 1.0 equiv) in DMF (0.25 mL) was added DSC (7.0 mg, 0.028 mmol, 1.1 equiv). After 30 minutes, LCMS indicated complete conversion to the carbamate intermediate. D-Glucamine (9.0 mg, 0.05 mmol, 2.0 equiv) was added and the reaction mixture was heated to 60°C. After 30 minutes, LCMS indicated that the reaction was complete and the crude mixture was cooled, diluted with EtOAc (10 mL) and washed successively with NaHCO3 (10 mL) and water (10 mL). The combined aqueous phases were extracted with DCM (3 x 10 mL) and the organic layers were combined and dried over Na2SO4. Purification by flash chromatography (4 g SiO2, 0% to 20% MeOH in DCM for 10 minutes) gave 9.7 mg (45%) of 483d. Step 4. (2S)-2-[4-Chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-6-({[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino)hexanoic acid (I-483)

[00577] 483d (9.7 mg, 0.011 mmol, 1.0 equiv) was dissolved in DCM (1.0 mL) and TFA (0.25 mL) was added. After 45 minutes the reaction was complete and the solvent was removed. The crude residue was diluted with MeCN (0.5 mL) and water (1.5 mL) and purified by preparative HPLC (10% to 55% MeCN in H2O with 0.1% TFA over 18 minutes) to give 2.3 mg (25%) of (2S)-2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]- 6-({[(2S,3R,4R,5R)-2,3,4,6-6-pentahydroxyhexyl]carbamoyl}amino)hexanoic acid (I-483) as a salt of TFA. MS (ES, m/z): 807.20 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.79 (s, 1H), 8.60 (d, J = 5.2 Hz, 1H), 8.23 (d, J = 8.9 Hz, 1H), 7.66 (dd, J = 8.4, 2.0 Hz, 1H), 7.59 (d, J = 8.4 Hz, 2H), 7.44-7.25 (m, 5H ), 7.02 (t, J = 7.6 Hz, 1H), 4.39 (s, 2H), 3.70-3.60 (m, 5H), 3.23 - 3.08 (m, 6H), 3.06 - 2.95 (m, 3H), 2.96 - 2.81 (M, 5H), 1.23 (s, 4H), 0.93 (d, J = 18.8 Hz , 4H), 0.64 (d, J = 7.4 Hz, 2H), 0.39 (s, 2H). Example 77: (S)-2-amino-6-(3-chloro-4-) acid ((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenylsulfonamido)-hexanoic acid (I-484)

[00578] A solution of 388d (338 mg, 0.66 mmol, 1.0 equiv) in MeCN (3.3 mL) was added AcOH (198 mg, 3.3 mmol, 5.0 equiv) and H2O (71 .2 mg, 3.96 mmol, 6.0 equiv). The reaction mixture was cooled to 0°C and NCS (246 mg, 1.98 mmol, 3.0 equiv) was added in 3 portions. The reaction was stirred at 0°C for 30 minutes and then at room temperature for a further 45 minutes, at which point LCMS indicated the reaction was complete. The crude mixture was diluted with DCM (30 mL) and washed with brine (2 x 30 mL). The combined aqueous layers were extracted with additional DCM (30 mL) and the combined organic layers were dried over Na2SO4 and the solvent was removed. The crude sulfonyl chloride was diluted with DCM (1.5 mL) and added dropwise to a solution of (S)-methyl HCl 6-amino-2-(tert-butoxycarbonylamino)hexanoate (172 mg, 0 .66 mmol, 1.0 equiv) and TEA (101 mg, 1.0 mmol, 1.5 equiv) in DCM (1.5 mL) at 0°C. After 45 minutes the reaction was complete. The crude reaction mixture was applied directly to silica gel (4.0 g) and purification via flash chromatography (0% to 10% MeOH in DCM over 10 minutes) gave 314.9 mg (67%) of 484b as a yellow oil. Step 2. (S)-Methyl 2-amino-6-(3-chloro-4-((1-(4-(2-cyclopropoxyphenyl)-yridin-3-yl)cyclopropoxy)methyl)phenylsulfonamido)hexanoate (Intermediate 484c)

[00579] A solution of 484b (315 mg, 0.442 mmol, 1.0 equiv) in dioxane (2 mL) was added to a solution of HCl (4 M in dioxane, 0.44 mL, 1.76 mmol, 4.0 equiv ). After 40 minutes additional HCl solution (4M in dioxane, 0.44 mL, 1.76 mmol, 4.0 equiv) was added. After another 3 hours, the reaction was complete and the solvent was removed. The crude residue was diluted with DCM (30 mL) and neutralized with saturated NaHCO3 solution. The mixture was extracted with DCM (4 x 30 mL) and dried over Na2SO4. Removal of the solvent gave 281.8 mg (100%) of 484c. Step 3. (S)-2-Amino-6-(3-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenylsulfonamido)-hexanoic acid (I- 484)

[00580] A solution of 484c (50 mg, 0.082 mmol, 1.0 equiv) in MeOH (0.3 mL) and THF (0.2 mL) was added LiOH (2 M in water, 0.163 mL, 0.326 mmol, 4.0 equiv). After 90 minutes more LiOH (2M in water, 0.163 ml, 0.326 mmol, 4.0 equiv) was added. The reaction was completed after another 20 minutes. The crude mixture was diluted with MeCN (1.0 mL) and H2O (3.0 mL) and acidified with TFA. Additional MeCN (0.5 mL) was added and the mixture was filtered. Purification by preparative HPLC (30% to 95% MeCN in water with 0.1% TFA for 18 minutes) gave 11.5 mg (24%) of I-484 as a TFA salt. MS (ES, m/z): 600.20 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 8.85 (s, 1H), 8.65 (d, J = 5.8 Hz, 1H), 7.68 (d, J = 5.8 Hz, 1H) , 7.61 (dd, J = 8.3, 2.3 Hz, 1H), 7.50 (d, J = 2.3 Hz, 1H), 7.46 (d, J = 8.4 Hz, 1H), 7.42 - 7.34 (m, 1H), 7.34 - 7.11 (m, 3H), 7.00 (td, J = 7.4, 1.0 Hz, 1H), 4 .41 (s, 2H), 4.26 (s, 1H), 3.85 (t, J = 6.3 Hz, 1H), 3.51 (tt, J = 6.0, 2.9 Hz, 1H), 2.74 (t, 6.3Hz, 2H), 1.90 (s, 1H), 1.89 - 1.72 (m, 2H), 1.54 - 1.30 (m, 4H ), 1.19 - 0.95 (m, 4H), 0.65 - 0.51 (m, 2H), 0.43 - 0.27 (m, 2H).Example 78: Acid (S) -6 - (3-chloro-4 - ((1- (4- (2-cyclopropoxyphenyl) pyridin-3- yl) cyclopropoxy) methyl) phenylsulfonamido) -2- (3 - ((2S,3R, 4R, 5R) -2 ,3,4,5,6-pentahydroxyhexyl) hexanoic ureido (I-485)

[00581] A solution of 22c (231 mg, 0.377 mmol, 1.0 equiv) in DMF (1.0 mL) was added DSC (106 mg, 0.414 mmol, 1.1 equiv). After 30 minutes D-glucamine (136 mg, 0.754 mmol, 2.0 equiv) was added and the reaction mixture was heated to 60°C. After an additional 1 hour, the reaction was completed and the crude mixture was cooled. Saturated NaHCO 3 solution (50 mL) was added and the mixture was washed with a 10% IPA in DCM mixture (4 x 50 mL). The combined organic layers were dried over Na2SO4 and concentrated to give petroleum 485b in quantitative yield. Step 2. Acid (S)-6-(3-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenylsulfonamido)-2-(3-((2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)ureido)hexanoic acid (I-485)

[00582] 485b (336 mg, 0.377 mmol, 1.0 equiv) was dissolved in MeOH (3.0 mL) and THF (2.0 mL). LiOH (2N in water, 0.38 mL, 0.76 mmol, 2.0 equiv) was added. After 45 minutes the reaction was complete and the solvent was removed. The crude residue was diluted with MeCN (1.8 mL) and H2O (4.2 mL), filtered and purified by preparative HPLC (10% to 70% MeCN in 0.01 N NH4HCO3 solution for 20 minutes) to give 61 mg (20%) of I-485 as a free base. MS (ES, m/z): 807.22 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ 8.71 (s, 1H), 8.53 (d, J = 4.9 Hz, 1H), 7.70 - 7.55 (m, 3H), 7.42 - 7.28 (m, 2H), 7.24 (d, J = 7.4 Hz1, 1H), 7.16 (d, J = 4.9 Hz, 1H), 6.98 (t, J = 7.4 Hz, 1H), 6.21 (s, 1H), 6.15 (s, 1H), 4.84 (s, 1H), 4.39 (s, 4H), 4.30 (s, 1H), 3.85 (s, 1H), 3.68 - 3.59 (m, 1H), 3.59 - 3.41 (m, 4H), 3.41 - 3.34 (m , 3H), 3.13 - 2.77 (m, 4H), 2.66 (t, J = 6.8 Hz, 2H), 1.62 - 1.48 (m, 1H), 1.48 - 1.38 (m, 1H), 1.34 (s, 2H), 1.24 (s, 2H), 0.91 (d, J = 13.9 Hz, 4H), 0.60 (d, J = 6.2 Hz, 2H), 0.34 (s, 2H).Example 79: (S)-2-amino-6 -(3-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenylsulfonamido)-N-ethylhexamide (I-486)

[00583] (S)-methyl 6-amino-2-(tert-butoxycarbonylamino)hexanoate: A solution of (S)-6-amino-2-(tert-butoxycarbonylamino) hexanoic acid (167 mg, 0.66 mmol , 1.0 equiv) in DCM (2.6 mL) and MeOH (0.6 mL) was cooled to 0°C under a nitrogen atmosphere. TMS-diazomethane (2 M in ether, 0.5 mL, 1.0 mmol, 1.5 eq) was added dropwise. After 45 minutes the reaction mixture was concentrated to give 486b, which was used without further purification. Step 2. 2-(tert-butoxycarbonylamino)-6-(3-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenylsulfonamido)hexanoatode(S)-methyl (Intermediate 486c)

[00584] 3-(1-(4-(benzylthio)-2-chlorobenzyloxy)cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridine (338 mg, 0.66 mmol, 1.0 equiv) was dissolved in MeCN (3 .3 mL) with AcOH (198 mg, 3.3 mmol, 5.0 equiv) and H2O (71 mg, 3.96 mmol, 6.0 equiv). The mixture was cooled to 0°C and NCS (246 mg, 1.98 mmol, 3.0 equiv) was added in 3 portions over 10 minutes. After 45 minutes the reaction mixture was warmed to room temperature. After another 45 minutes, the reaction was complete. The crude mixture was diluted with DCM (40 mL) and washed with brine (2 x 30 mL). The combined aqueous layers were extracted with additional DCM (30 mL) and the combined organic layers were dried over Na2SO4 and the solvent was removed to give the crude sulfonyl chloride. Freshly prepared 486b (170 mg, 0.66 mmol, 1.0 equiv) was dissolved in DCM (2 mL) with TEA (100 mg, 0.99 mmol, 1.5 equiv). A solution of the sulfonyl chloride in DCM (2 mL) was added dropwise. After 5 minutes the reaction was complete and the crude mixture was purified directly by flash chromatography (12 g SiO2, 0% to 10% MeOH in DCM for 15 minutes) to give 333 mg (71%) of 486c. Step 3. 6-(3-Chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenylsulfonamido)-1-(ethylamino)-1-oxohexan-2-ylcarbamate of (S)-tert-butyl (Intermediate 486d)

[00585] 486c (300 mg, 0.42 mmol, 1.0 equiv) was dissolved in THF (1.5 mL) and MeOH (1.5 mL). LiOH (2M in water, 0.42 mL, 0.84 mmol, 2.0 equiv) was added and the reaction mixture was stirred at room temperature for 30 minutes. The solvent was removed and the crude residue was diluted with EtOAc (20 mL) and washed successively with 1N HCl (10 mL), water (15 mL), saturated Na2CO3 (15 mL) and brine (10 mL). The organic layer was dried over Na2SO4 and concentrated to give the crude acid in quantitative yield, which was dissolved in DMF (3.0 mL). Ethylamine (2M in THF, 0.21 ml, 0.42 mmol, 1.0 equiv), TEA (63 mg, 0.63 mmol, 1.5 equiv) and finally HATU (175 mg, 0.46 equiv) were added. mmol, 1.1 equiv). After 15 minutes the reaction was complete and EtOAc (15 mL) was added. The crude mixture was washed successively with water (2 x 15 ml) and brine (10 ml) and dried over Na2SO4. Purification by flash chromatography (24 g SiO2, 0% to 5% MeOH in DCM over 20 minutes) gave 302 mg (97%) of 486d. Step 4. (S)-2-amino-6-(3-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenylsulfonamido)-N-ethylhexanamide (I-486)

[00586] TFA (0.2 mL) was added to the solution of 486d (60 mg, 0.082 mmol, 1.0 equiv) in DCM (0.2 mL). After 30 minutes the solvent was removed and the crude residue was diluted with MeCN (1.5 ml) and water (1.5 ml). Purification by preparative HPLC (10% to 55% MeCN in water with 0.1% TFA for 18 minutes) gave 5.1 mg (10%) of I-486 as a TFA salt. MS (ES, m/z): 627.19 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 8.89 (s, 1H), 8.69 (d, J = 5.6 Hz, 1H), 8.34 (s, 1H), 7.71 - 7, 64 (m, 2H), 7.59 (s, 1H), 7.53 (d, J = 8.3 Hz, 1H), 7.47 - 7.41 (m, 1H), 7.38 (d , J = 8.4 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.06 (t, J = 7.4 Hz, 1H), 4.49 (s, 2H ), 3.75 (t, J = 6.4 Hz, 1H), 3.62 - 3.55 (m, 1H), 2.81 (t, J = 6.6 Hz, 2H), 1.88 - 1.74 (m, 2H), 1.59 - 1.37 (m, 4H), 1.22 - 1.04 (m, 7H), 0.63 (d, J = 5.9 Hz, 2H ), 0.41 (s, 2H).Example 80: (S)-6-(3-chloro-4-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenylsulfonamido )-N-ethyl-2-(3- ((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)ureido)hexanamide (I-487)

[00587] A solution of I-486 (140 mg, 0.22 mol, 1.0 equiv) in DMF (1.0 mL) was added to DSC (57 mg, 0.22 mmol, 1.0 equiv). After 5 minutes, D-Glucamine (60 mg, 0.33 mmol, 1.5 equiv) was added and the reaction mixture was heated to 60° C. After a further 90 minutes the reaction was completed and cooled to room temperature. MeCN (2.0 mL), TFA and water (8.0 mL) were added and the mixture was filtered. Purification by preparative HPLC (10% to 55% MeCN in water with 0.1% TFA for 18 minutes) gave 88 mg (48%) of I-487 as a TFA salt. MS (ES, m/z): 834.25 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 8.95 (s, 1H), 8.74 (d, J = 5.8 Hz, 1H), 7.81 (d, J = 5.9 Hz, 1H) , 7.69 (dd, J = 8.3, 2.2 Hz, 1H), 7.59 (d, J = 1.8 Hz, 1H), 7.54 (d, J = 8.4 Hz, 1H), 7.52 - 7.44 (m, 1H), 7.40 (d, J = 8.3 Hz, 1H), 7.36 (dd, J = 7.6, 1.6 Hz, 1H ), 7.30 - 7.19 (m, 1H), 7.08 (t, J = 7.4 Hz, 1H), 4.50 (s, 2H), 4.07 (dd, J = 8, 6, 5.5 Hz, 1H), 3.81 - 3.73 (m, 3H), 3.73 - 3.65 (m, 1H), 3.65 - 3.56 (m, 3H), 3 .37 (dd, J = 14.2, 4.3 Hz, 1H), 3.27 - 3.14 (m, 3H), 2.79 (t, J = 6.8 Hz, 2H), 1, 76 - 1.59 (m, 1H), 1.59 - 1.42 (m, 3H), 1.42 - 1.31 (m, 2H), 1.29 (d, J = 0.6 Hz, 3H), 1.18 (s, 2H), 1.10 (t, J = 7.1 Hz, 5H), 0.72 - 0.60 (m, 2H), 0.50 - 0.36 (m , 2H). Example 81: Ethyl 5-[(6-Formyl-5-methylpyridin-2-yl)sulfanyl]pentanoate (Intermediate E1)

[00588] A 100 mL (1 atm) round bottom flask purified and maintained under an inert nitrogen atmosphere was charged with ethyl 5-(acetylsulfanyl) pentanoate (4 g, 19.58 mmol, 1.00 equiv), ethanol (50 mL) and potassium carbonate (4.06 g, 29.38 mmol, 1.50 equiv). The resulting solution was stirred for 3-4 h at 40°C in an oil bath. The resulting solution was diluted with 100 mL of ethyl acetate. The resulting mixture was washed with 1 x 55 ml of water and 1 x 55 ml of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 3 g (94%) of ethyl 5-sulfanylpentanoate (E1a) as a yellow oil. Step 2. 5-(6-(hydroxymethyl)-5-methylpyridin-2-ylthio)pentanoatodeethyl (Intermediate E1b)

[00589] A 100 mL (1 atm) round bottom flask purified and maintained under an inert nitrogen atmosphere was charged with (6-chloro-3-methylpyridin-2-yl) methanol (1 g, 6.35 mmol , 1.00 equiv), ethyl 5-sulfanylpentanoate (E1a, 1.55 g, 9.55 mmol, 1.50 equiv), dioxane (20 mL), DIEA (1.64 g, 12.69 mmol, 2 .00 equiv), xanth-Phos (0.37 g, 0.10 equiv) and Pd2(dba)3 (580 mg, 0.63 mmol, 0.10 equiv). The resulting solution was stirred overnight at 110 oC in an oil bath. The resulting solution was diluted with 80 mL of ethyl acetate. The resulting mixture was washed with 1 x 50 ml of water and 1 x 50 ml of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0%-50%). This resulted in 1.03 g (57%) of ethyl 5-[[6-(hydroxymethyl)-5-methylpyridin-2-yl]sulfanyl]pentanoate (E1b) as a yellow oil. Step 3. Ethyl 5-(6-Formyl-5-methylpyridin-2-ylthio)pentanoate (Intermediate E1)

[00590] A 50 mL (1 atm) round bottom flask was charged with a solution of ethyl 5-[[6-(hydroxymethyl)-5-methylpyridin-2-yl]sulfanyl]pentanoate (E1b, 400 mg, 1.41 mmol, 1.00 equiv) in DCM (20 mL), MnO2 (1.23 g, 14.15 mmol, 10.00 equiv). The resulting solution was stirred at room temperature for 4-5 h. Solids were collected by filtration. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (3.5:1). This resulted in 100 mg (25%) of ethyl 5-[(6-formyl-5-methylpyridin-2-yl)sulfanyl]pentanoate (E1) as a colorless oil.Example 82: 4-[(4-Chloro- Ethyl 3-formylbenzene)sulfinyl]butanoate (Intermediate E2)

[00591] A 50 mL round bottom flask was charged with ethyl 4-[[4-chloro-3-(hydroxymethyl)phenyl]sulfanyl]butanoate (300 mg, 1.04 mmol, 1.00 equiv), dichloromethane (10 mL). This was followed by the addition of m-CPBA (164.58 mg, 1.04 mmol, 1.00 equiv) in several batches at 0oC in 1 min. The resulting solution was stirred for 1 h at room temperature. The resulting solution was diluted with 10 mL of dichloromethane. The reaction was cooled by adding 10 mL of water. The resulting solution was extracted with 3 x 20 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 2 x 20 ml of brine. The mixture was dried over anhydrous sodium sulfate. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (2:1). This resulted in 283 mg (89%) of ethyl 4-[[4-chloro-3-(hydroxymethyl)benzene]sulfinyl]butanoate (E2a) as light brown oil. Step 2. Ethyl 4-[(4-Chloro-3-formylbenzene)sulfinyl]butanoate (Intermediate E2)

[00592] A 50 mL round bottom flask was charged with ethyl 4-[[4-chloro-3-(hydroxymethyl)benzene]sulfinyl]butanoate (E2a, 283 mg, 0.93 mmol, 1.00 equiv) , chloroform (15 mL), MnO2 (809.34 mg, 9.31 mmol, 10.03 equiv). The resulting solution was stirred for 2 h at 60°C in an oil bath. The reaction mixture was cooled with a water bath. The solids were filtered. The resulting mixture was concentrated under vacuum. This resulted in 286 mg (raw) of ethyl 4-[(4-chloro-3-formylbenzene)sulfinyl]butanoate (E2) as a light yellow oil.Example 83: 5-Methyl-2-(methylsulfanyl)pyrimidine- 4-carbaldehyde (Intermediate E3)

[00593] A 250 mL round bottom flask was charged with a solution of 2-chloro-5-methylpyrimidine (3 g, 23.34 mmol, 1.00 equiv) in DMF (50 mL) and MeSNa (16.4 g, 234.3 mmol, 10.00 equiv). The resulting solution was stirred overnight at room temperature. The reaction was then cooled by adding 200 mL of H2O. The resulting solution was extracted with 3 x 50 mL ethyl acetate, and the organic layers combined and dried over sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with PE:EA (92:8). This resulted in 2.8 g (86%) of 5-methyl-2-(methylsulfanyl) pyrimidine (E3a) as a pale yellow oil. Step 2. 5,6-dimethyl-2-(methylsulfanyl)-1,6-dihydropyrimidine (Intermediate E3b)

[00594] A 100 mL 3-neck round-bottom flask, purged and maintained under an inert nitrogen atmosphere, was charged with a solution of 5-methyl-2-(methylsulfanyl)pyrimidine (E3a, 2.8 g, 19 .97 mmol, 1.00 equiv) in ether (60 mL). This was followed by the addition of CH3Li (1.6 M) (13.8 mL, 1.10 equiv.) dropwise with stirring at 0 oC. The resulting solution was stirred at room temperature for 60 min. The reaction was then cooled by adding 50 mL of NH4Cl (aq). The resulting solution was extracted with 3 x 50 mL ethyl acetate, and the organic layers combined and dried over sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with DCM:MeOH (10:1). This resulted in 2.6 g (83%) of 5,6-dimethyl-2-(methylsulfanyl)-1,6-dihydropyrimidine (E3b) as a light yellow oil. Step 3. 4,5-dimethyl-2-(methylsulfanyl)pyrimidine (Intermediate E3c)

[00595] A 250 mL round bottom flask was charged with a solution of 5,6-dimethyl-2-(methylsulfanyl)-1,6-dihydropyrimidine (E3b, 2.6 g, 16.64 mmol, 1 .00 equiv) in THF (30 mL) and water (390 mg, 21.67 mmol, 1.30 equiv). This was followed by adding a solution of DDQ (4.16 g, 18.33 mmol, 1.10 equiv) in THF (30 mL) dropwise with stirring. The resulting solution was stirred at room temperature for 30 min. To this was added hexane (20 mL) dropwise with stirring at 0 oC. To the mixture was added NaOH (3M) (14 mL, 2.50 equiv) dropwise with stirring at 0oC. The resulting solution was stirred for 5 min at 0°C. The mixture was dried over sodium sulfate. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with PE:EA (95:5). This resulted in 2 g (78%) of 4,5-dimethyl-2-(methylsulfanyl) pyrimidine (E3c) as a light yellow oil. Step 4. 4-(bromomethyl)-5-methyl-2-(methylsulfanyl)pyrimidine (Intermediate E3d)

[00596] A 250 mL round bottom flask was charged with a solution of 4,5-dimethyl-2-(methylsulfanyl)pyrimidine (E3c, 3.3 g, 21.40 mmol, 1.00 equiv) in acetic acid (50 mL), Br2 (3.77 g, 23.59 mmol, 1.10 equiv). The resulting solution was stirred for 5 h at 80°C. The pH value of the solution was adjusted to 7-8 with sodium bicarbonate (aq) (10%). The resulting solution was extracted with 3 x 50 mL of ethyl acetate and the organic layers combined. The mixture was dried over sodium sulfate. The residue was applied to a silica gel column with PE:EA (99:1). This resulted in 3 g (60%) of 4-(bromomethyl)-5-methyl-2-(methylsulfanyl)pyrimidine (E3d) as an off-white solid. Step 5. 5-Methyl-2-(methylsulfanyl)pyrimidine-4-carbaldehyde (Intermediate E3)

[00597] A 250 mL round bottom flask was charged with 4-(bromomethyl)-5-methyl-2-(methylsulfanyl)pyrimidine (E3d, 3 g, 12.87 mmol, 1.00 equiv), DMSO (30 mL). The resulting solution was stirred overnight at room temperature. The reaction was then cooled by adding 200 mL of H2O. The resulting solution was extracted with 3 x 50 mL ethyl acetate, and the organic layers combined and dried over sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with PE:EA (95:5). This resulted in 1.5 g (69%) of 5-methyl-2-(methylsulfanyl)pyrimidine-4-carbaldehyde (E3) as a light yellow solid.Example 84: 4-[[3-(Bromomethyl)-4- ethylphenyl]sulfanyl]butanoate (Intermediate E4)

[00598] A 500 mL 3-neck round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with 2-ethylbenzoic acid (10.0 g, 66.59 mmol, 1.00 equiv) and THF (100 mL). This was followed by addition of BH3-THF (200 mL, 3.00 equiv) dropwise with stirring at 0 oC. The resulting solution was stirred at room temperature for 10 min. The reaction was cooled by adding 50 mL of methanol. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 100 mL of ethyl acetate. The resulting mixture was washed with 3x50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 8.3 g (92%) of (2-ethylphenyl) methanol (E4a) as a yellow oil. Step 2. 2-ethylbenzaldehyde (Intermediate E4b)

[00599] A 250 mL round bottom flask was charged with (2-ethylphenyl) methanol (9.1 g, 66.82 mmol, 1.00 equiv), MnO2 (E4a, 58.3 g, 10.00 equiv ) and chloroform (100 ml). The resulting solution was stirred for 12 h at 60°C in an oil bath. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 6.5 g (73%) of 2-ethylbenzaldehyde (E4b) as a yellow oil. Step 3. 5-Bromo-2-ethylbenzaldehyde (Intermediate E4c)

[00600] A 250 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with 2-ethylbenzaldehyde (E4b, 6.5 g, 48.44 mmol, 1.00 equiv) and DCM (30 mL) . This was followed by the addition of AlCl3 (11.0 g, 1.70 equiv) in portions at 0 oC. To this end, a solution of Br2 (7.76 g, 48.56 mmol, 1.00 equiv) in dichloromethane (30 mL) was added dropwise with stirring at 0 oC. The resulting solution was stirred for 2 h at 0°C in a water/ice bath. The resulting solution was allowed to react, with stirring, for a further 12 h at room temperature. The reaction was cooled by adding 100 mL of water/ice. The resulting solution was extracted with 3 x 30 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 2 x 50 mL of hydrogen chloride (2 M) and 1 x 50 mL of sodium bicarbonate (sat.). The resulting mixture was washed with 1x50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 8.2 g (79%) of 5-bromo-2-ethylbenzaldehyde (E4c) as a yellow crude oil. Step 4. (5-bromo-2-ethylphenyl)methanol (Intermediate E4d)

[00601] A 250 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with 5-bromo-2-ethylbenzaldehyde (E4c, 3.0 g, 14.08 mmol, 1.00 equiv), methanol (25 mL), tetrahydrofuran (2 mL). This was followed by the addition of sodium borane (1.6 g, 43.45 mmol, 3.00 equiv) in portions at 0°C. The resulting solution was stirred for 2 h at room temperature. The reaction was then cooled by adding 50 mL of NH4Cl. The resulting solution was diluted with 50 mL of water. The resulting solution was extracted with 3 x 30 mL ethyl acetate, and the organic layers combined and concentrated in vacuo. This resulted in 2.9 g (96%) of (5-bromo-2-ethylphenyl) methanol (E4d) as a yellow crude oil. Step 5. Ethyl 4-[[4-ethyl-3-(hydroxymethyl)phenyl]sulfanyl]butanoate (Intermediate E4e)

[00602] A 250 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with (5-bromo-2-ethylphenyl) methanol (E4d, 2.9 g, 13.48 mmol, 1.00 equiv ), 4- ethyl sulphanylbutanoate (800 mg, 5.40 mmol, 1.00 equiv), Pd2(dba)3.CHCl3 (280 mg, 0.05 equiv), Xantphos (313 mg, 0.54 mmol, 0 .10 equiv), DIEA (1.81 mL, 2.00 equiv), dioxane (100 mL). The resulting solution was stirred for 12 h at 100 oC in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 100 mL of ethyl acetate. The resulting mixture was washed with 3 x 50 ml of water and 1 x 50 ml of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:4). This resulted in 320 mg (8%) of ethyl 4-[[4-ethyl-3-(hydroxymethyl)phenyl]sulfanyl]butanoate (E4e) as a yellow oil. Step 6. Ethyl 4-[[3-(bromomethyl)-4-ethylphenyl]sulfanyl]butanoate (Intermediate E4)

[00603] A 100 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with ethyl 4-[[4-ethyl-3-(hydroxymethyl)phenyl]sulfanyl]butanoate (100 mg, 0.35 mmol, 1.00 equiv), dichloromethane (5 mL), tetrahydrofuran (5 mL). This was followed by the addition of 1-bromopyrrolidine-2,5-dione (101 mg, 0.57 mmol, 1.60 equiv) in portions at 0°C. To this end, PPh3 (139 mg, 0.53 mmol, 1.50 equiv) was added in portions at 0 oC. The resulting solution was stirred for 30 min at 0°C in a water/ice bath. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:5). This resulted in 100 mg (82%) of ethyl 4-[[3-(bromomethyl)-4-ethylphenyl]sulfanyl]butanoate (E4) as a yellow oil. Example 85: 4-[[3-(bromomethyl)- Methyl 4-chlorophenyl]sulfanyl]butanoate (Intermediate E5)

[00604] A 250 mL round bottom flask was charged with methyl 4-sulfanylbutanoate (900 mg, 6.71 mmol, 1.00 equiv), (2-chloro-5-iodophenyl) methanol (2.4 g, 8.94 mmol, 1.20 equiv), DIEA (1.93 g, 14.93 mmol, 2.00 equiv), Pd2(dba)3 (340 mg, 0.37 mmol, 0.05 equiv), Xantphos (440 mg, 0.76 mmol, 0.10 equiv) and dioxane (100 mL). The resulting solution was stirred for 1 night at 100 oC in an oil bath. The resulting solution was diluted with 500 mL of ethyl acetate. The resulting mixture was washed with 300 ml of water and then with 2 x 300 ml of brine. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (2.0 mg) was purified by flash chromatography with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ethyl acetate:petroleum ether = 100:0 increasing to ethyl acetate:petroleum ether = 85:15 within 30 min; Detector, UV 254 nm. 1.7 g of product was obtained. This resulted in 1.7 g (92%) of methyl 4-[[4-chloro-3-(hydroxymethyl)phenyl]sulfanyl]butanoate (E5a) as brown oil. Step 2. 4-[[3-(bromomethyl)-4-chlorophenyl]sulfanyl]butanoate (Intermediate E5)

[00605] A 25 mL round bottom flask was charged with methyl 4-[[4-chloro-3-(hydroxymethyl)phenyl]sulfanyl]butanoate (E5a, 100 mg, 0.36 mmol, 1.00 equiv) , dichloromethane (5 mL), NBS (97 mg, 0.55 mmol, 1.50 equiv), PPh3 (145 mg, 0.55 mmol, 1.50 equiv). The resulting solution was stirred for 10 min at 0°C in a salt/ice bath. The resulting mixture was concentrated under vacuum. The crude product was purified by flash chromatography with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ethyl acetate:petroleum ether = 100:0 increasing to ethyl acetate:petroleum ether = 95:5 within 20 min; Detector, UV 254 nm. 100 mg of product was obtained. This resulted in 100 mg (81%) of methyl 4-[[3-(bromomethyl)-4-chlorophenyl]sulfanyl]butanoate (E5) as a colorless oil. Example 85a: 1-(5-[[4-Chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]pentyl)-3-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-488)

[00606] A 250 mL round bottom flask was charged with 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-ol (A23) (3.65 g, 13.65 mmol, 1 .00 equiv), 2-(bromomethyl)-1-chloro-4-iodobenzene (5.43 g, 16.39 mmol, 1.20 equiv) and DMF (150 mL). This was followed by the addition of sodium hydride (60% in oil) (1.09 g, 45.42 mmol, 2.00 equiv) in portions at 0°C. The resulting solution was stirred for 30 min at 0°C. The resulting solution was allowed to react, with stirring, for a further 1 h at room temperature. The reaction was cooled by adding 100 mL of water. The resulting solution was extracted with 3 x 100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2 x 200 ml of water and 1 x 200 ml of sat. sodium chloride. The mixture was dried over anhydrous sodium sulfate. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:7-1:4). This resulted in 3.75 g (53%) of 3-[1-[(2-chloro-5-iodophenyl)methoxy]cyclopropyl]-4-(2-cyclopropoxyphenyl)pyridine (488a) as a brown oil. Step 2. 5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]ethyl (Intermediate 488b)

[00607] A 100 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with 3-[1-[(2-chloro-5-iodophenyl)methoxy]cyclopropyl]-4-(2-cyclopropoxyphenyl) pyridine (488a, 1.0 g, 1.93 mmol, 1.10 equiv), ethyl 5-sulfanylpentanoate (285 mg, 1.76 mmol, 1.00 equiv), 1,4-dioxane (32 mL), DIEA (455 mg, 3.52 mmol, 2.00 equiv), Pd2(dba)3CHCl3 (91 mg, 0.05 equiv) and Xantphos (102 mg, 0.18 mmol, 0.10 equiv). The resulting solution was stirred overnight at 100oC in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was extracted with 3x50 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (020%). The collected fractions were combined and concentrated under vacuum. This resulted in 800 mg (82%) of 5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxyl]methyl)phenyl]sulfanyl]ethyl pentanoate ( 488b) as a light yellow oil. Step 3. 5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]pentan-1-ol (Intermediate 488c)

[00608] A 250 mL round bottom flask was charged with 5 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxyl] methyl) phenyl] sulphanyl] ethyl pentanoate (488b, 4.8 g, 8.70 mmol, 1.00 equiv), tetrahydrofuran (100 mL), LiAlH4 (500 mg, 13.0 mmol, 1.50 equiv). The resulting solution was stirred for 2 h at 0°C. The reaction was then quenched by adding 0.5 mL of water, 0.5 mL of 2 M NaOH and 1.5 mL of water. The resulting mixture was diluted in 100 mL of EtOAc and stirred for 30 min, the solids were removed by filtration. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0-30%). The collected fractions were combined and concentrated under vacuum. This resulted in 3.77 g (86%) (488c) of 5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl ]pentan-1-ol in the form of a light yellow oil. Step 4. 5-[[4-Chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]pentyl methanesulfonate (Intermediate 488d)

[00609] A 50 mL round bottom flask was charged with 5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl] pentan-1-ol (488c, 300 mg, 0.59 mmol, 1.00 equiv), dichloromethane (20 mL), TEA (119 mg, 1.18 mmol, 2.00 equiv), and MsCl (101 mg, 1 .50 equiv.). The resulting solution was stirred at room temperature for 0.5 h. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (0-70%). The collected fractions were combined and concentrated under vacuum. This resulted in 280 mg (81%) of 5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]pentyl methanesulfonate ( 488d) as a light yellow oil. Step 5.2- (5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-cyclopropoxy]methyl)phenyl]sulfanyl]pentyl)-2,3-di- hydro-1H- isoindole- 1,3-dione (Intermediate 488e)

[00610] A 50 mL round bottom flask filled with 5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl methanesulfonate ]pentyl (488d, 290 mg, 0.49 mmol, 1.00 equiv), DMF (15 mL) and 1H,2H,4H-benzo[d]1-aza-2-potassacyclohexane-1,4-dione (182.8 mg, 0.98 mmol, 1.99 equiv). The resulting solution was stirred for 1.5 h at 80°C in an oil bath. The reaction mixture was cooled to room temperature with a water bath. The resulting solution was diluted with 50 mL of ethyl acetate. The residue was dissolved in 30 mL of H2O. The resulting solution was extracted with 2 x 30 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3 x 20 ml of brine. The mixture was dried over anhydrous sodium sulfate. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 238 mg (76%) of 2-(5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]pentyl )-2,3-dihydro-1H-isoindole-1,3-dione (488e) as a brown oil. Step 6. 3-[1-([5-[(5-aminopentyl)sulfanyl]-2-chlorophenyl]methoxy)cyclopropyl]-4-(2-cyclopropoxyphenyl)pyridine (Intermediate 488f)

[00611] A 50 mL round bottom flask filled with 2-(5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl] sulfanyl]pentyl)-2,3-dihydro-1H-isoindole-1,3-dione (488e, 238 mg, 0.37 mmol, 1.00 equiv), ethanol (15 mL) and NH2NH2.H2O (93 .34 mg). The resulting solution was stirred for 1 day at room temperature. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with dichloromethane/methanol (10:1). This resulted in 100 mg (53%) of 3-[1-([5-[(5-aminopentyl)sulfanyl]-2-chlorophenyl]methoxy)cyclopropyl]-4-(2-cyclopropoxyphenyl)pyridine (488f) as a brown oil. Step 7. 1-(5-[[4-Chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]pentyl)-3-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-488)

[00612] A 25 mL round bottom flask was charged with 3-[1-([5-[(5-aminopentyl)sulfanyl]-2-chlorophenyl]methoxy)cyclopropyl]-4-(2-cyclopropoxyphenyl)pyridine ( 488f, 100 mg, 0.20 mmol, 1.00 equiv), (2R,3R,4R,5S)-6-aminohexane-1,2,3,4,5-pentol (107 mg, 0.59 mmol, 3.00 equiv), DIEA (33 mg, 0.26 mmol, 1.30 equiv.), DSC (66 mg, 1.30 equiv.), N,N-dimethylformamide (4 mL). The resulting solution was stirred overnight at room temperature. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, OBD XBridge Shield RP18 Column; 5μm 19 x 150mm; mobile phase, water with 10mM NH 4HCO3 and MeCN (35.0% MeCN to 65.0% in 8 min); Detector, UV 254nm. This resulted in 61.6 mg (44%) of 1-(5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl ]pentyl)-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-488) as a white solid. MS (ES, m/z): 716 [M+H]+; 1H-NMR (300 MHz, CD3OD) δ 0.34 (s, 2H), 0.50 - 0.61 (m, 2H), 0.96 (d, J = 5.0 Hz, 4H), 1, 43 (dd, J = 6.7, 3.3 Hz, 4H), 1.58 (t, J = 7.0 Hz, 2H), 2.84 (t, J = 7.2 Hz, 2H), 3.11 (dt, J = 22.5, 6.4 Hz, 3H), 3.29 - 3.51 (m, 2H), 3.52 - 3.80 (m, 6H), 4.32 ( s, 2H), 6.92 - 7.03 (m, 2H), 7.06 - 7.43 (m, 6H), 8.44 (d, J = 5.1 Hz, 1H), 8.60 (s, 1H).Example 86: (2S,3S,4R,5S)-N-(5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy]methyl)phenyl]sulfanyl]pentyl)-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl]hexanamide (I-489)

[00613] A 50 mL round bottom flask was charged with 5 - [[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl] pentyl methanesulfonate (488d, 280 mg, 0.48 mmol, 1.00 equiv), 2-(2-aminoethoxy)ethan-1-ol (266 mg, 2.53 mmol, 5.00 equiv), and THF (5 mL ). The resulting solution was stirred overnight at 50 oC in an oil bath. The resulting solution was extracted with 3 x 30 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3 x 100 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with DCM/MeOH (10:1). This resulted in 240 mg (84%) of 2-[2-[(5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl ]sulfanyl]pentyl)amino]ethoxy]ethan-1-ol (489a) as a light yellow oil. Step 2. (3R,4S,5S,6S)-3,4,5-tris(acetyloxy)-6-[(5-[[4-chloro-3-([1-[4-(2-) acetate cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]pentyl)[2-(2-hydroxyethoxy)ethyl]carbamoyl]oxan-2-yl (Intermediate 489b)

[00614] A 50 mL round bottom flask was charged with 2-[2-[(5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy ]methyl)phenyl]sulfanyl]pentyl)amino]ethoxy]ethan-1-ol (489a, 240 mg, 0.40 mmol, 1.00 equiv), acid (2S,3S,4S,5R)-3.4, 5,6-tetrakis(acetyloxy)oxane-2-carboxylic acid (160 mg, 0.44 mmol, 1.10 equiv), HATU (183 mg, 0.48 mmol, 1.20 equiv), DIEA (78 mg, 0 .60 mmol, 1.50 equiv) and DMF (10 mL). The resulting solution was stirred overnight at room temperature. The reaction was cooled by adding 50 mL of water. The resulting solution was extracted with 3 x 100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3x150 mL of brine. The mixture was dried over anhydrous sodium sulfate. The solids were filtered. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with DCM/MeOH (0%:10%). The collected fractions were combined and concentrated under vacuum. This resulted in 380 mg (100%) of (3R,4S,5S,6S)-3,4,5-tris(acetyloxy)-6-[(5-[[4-chloro-3-([1 -[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]pentyl)[2-(2-hydroxyethoxy)ethyl]carbamoyl]oxan-2-yl (489b) as a light brown solid . Step 3. (2S,3S,4S,5R)-N-(5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl] sulfanyl]pentyl)-3,4,5,6-tetrahydroxy-N-[2-(2-hydroxyethoxy)ethyl]oxane-2-carboxamide (Intermediate 489c)

[00615] A 25 mL round bottom flask was charged with (3R,4S,5S,6S)-3,4,5-tris(acetyloxy)-6-[(5-[[4-chloro-3 - ([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]pentyl)[2-(2-hydroxyethoxy)ethyl]carbamoyl]oxan-2-yl (489b, 380 mg, 0.40 mmol, 1.00 equiv), methanol (5 mL) and MeONa (22 mg, 0.41 mmol, 1.00 equiv). The resulting solution was stirred overnight at room temperature. The resulting mixture was concentrated under vacuum. This resulted in 200 mg (64%) of (2S, 3S, 4S, 5R)-N-(5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl ]cyclopropoxy]methyl)phenyl]sulfanyl]pentyl)-3,4,5,6-tetrahydroxy-N-[2-(2-hydroxyethoxy)ethyl]oxane-2-carboxamide (489c) as a light yellow solid. Step 4. (2S,3S,4R,5S)-N-(5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl] sulfanyl]pentyl)-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl]hexanamide (I-489)

[00616] A 25 mL round bottom flask was charged with (2S,3S,4S,5R)-N-(5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin - 3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]pentyl)-3,4,5,6-tetrahydroxy-N-[2-(2-hydroxyethoxy)ethyl]oxane-2-carboxamide (489c, 200 mg , 0.26 mmol, 1.00 equiv), methanol (10 mL), NaBH4 (20 mg, 0.53 mmol, 2.00 equiv). The resulting solution was stirred at room temperature for 30 min. The solids were filtered. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 5 mL of methanol. The crude product was purified by preparative HPLC with the following conditions (HPLC-SHIMADZU Analysis #2 (HPLC-10)): Column, Gemini-NX 5 μ C18 110A, AXIA Packed, 150 x 21.2 mm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (36.0% MeCN - to 56.0% in 6 min); Detector, UV 220 nm. 150 mL of product were obtained and concentrated under vacuum. This resulted in 96.9 mg (48%) of (2S,3S,4R,5S)-N-(5-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3 -yl]cyclopropoxy]methyl)phenyl]sulfanyl]pentyl)-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl]hexanamide (I-489) as a white solid . MS (ES, m/z): 775.1 [M+H]+; 1H-NMR (300 MHz, CD3OD) δ 0.39 (s, 2H), 0.55 - 0.66 (m, 2H), 0.96 - 1.05 (m, 4H), 1.47 (s , 2H), 1.64 (dt, J = 18.5, 8.7 Hz, 4H), 2.91 (q, J = 6.7 Hz, 2H), 3.38 - 3.99 (m, 16H), 4.37 (s, 2H), 6.97 - 7.08 (m, 2H), 7.13 - 7.31 (m, 4H), 7.32 - 7.47 (m, 2H) , 8.49 (d, J = 5.1 Hz, 1H), 8.64 (s, 1H). Example 87: 1-[2-(2-[[4-Chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]ethoxy)ethyl]- 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-490)

[00617] A 50 mL round bottom flask was charged with 3-[1-[(2-chloro-5-iodophenyl)methoxy]cyclopropyl]-4-(2-cyclopropoxyphenyl) pyridine (488 to 250 mg, 0.48 mmol, 1.00 equiv), tert-butyl N-[2-(2-sulfanilethoxy)ethyl]carbamate (97.29 mg, 0.44 mmol, 0.91 equiv), dioxane (8.05 mL), DIEA (0.15 mL), Xantphos (25.46 mg, 0.04 mmol, 0.09 equiv) and Pd 2(dba)3CHCl3 (22.75 mg, 0.02 mmol, 0.05 equiv). The resulting solution was stirred overnight at 100 oC in an oil bath. The resulting mixture was concentrated under vacuum. The residue was dissolved in 200 ml of ethyl acetate. The resulting mixture was washed with 3 x 50 mL of H2O. The resulting mixture was washed with 2x50 mL of brine. The mixture was dried over anhydrous sodium sulfate. The solids were filtered. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 230 mg (78%) of N-[2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl] tert-butylsulfanyl]ethoxy)ethyl]carbamate (490a) as a brown oil. Step 2. 2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-cyclopropoxy]methyl)phenyl]sulfanyl]ethoxy)ethan-1-amine (Intermediate 490b)

[00618] A 50 mL round bottom flask was charged with N-[2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy] tert-butyl methyl)phenyl]sulfanyl]ethoxy)ethyl]carbamate (490a, 230 mg, 0.38 mmol, 1.00 equiv), TFA/DCM (10/10 mL). The resulting solution was stirred for 1 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was dissolved in 200 ml of ethyl acetate. The pH value of the solution was adjusted to 9.0 with sodium bicarbonate (100%). The resulting solution was extracted with 2 x 30 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2x50 mL of brine. The mixture was dried over anhydrous sodium sulfate. The solids were filtered. This resulted in 216 mg (raw) of 2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]ethoxy )ethane-1-amine (490b) as a brown solid. Step 3. 1-[2-(2-[[4-Chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]ethoxy)ethyl]- 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-490)

[00619] A 50 mL round bottom flask was charged with 2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl ]sulfanyl]ethoxy) ethan-1-amine (490b, 216 mg, 0.42 mmol, 1.00 equiv), N,N-dimethylformamide (5 mL), DIEA (0.091 mL), DSC (140.7 mg) , (2R, 3R, 4R, 5S) -6-aminohexane-1,2,3,4,5-pentol (153.3 mg, 0.85 mmol, 2.00 equiv). The resulting solution was stirred at room temperature for 1.5 h. The resulting solution was allowed to react, with stirring, for a further 1 night at room temperature. The resulting solution was diluted with 50 mL of ethyl acetate. The solids were filtered. The resulting mixture was concentrated under vacuum. The crude product was purified by preparative HPLC with the following conditions: Column, OBD XBridge Shield RP18 Column; 5μm 19 x 150mm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (30.0% MeCN to 54.0% in 8 min); Detector, UV 254 nm. Product was obtained. This resulted in 127 mg (42%) of 1-[2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl] sulfanyl] ethoxy) ethyl] -3 - [(2S, 3R, 4R, 5R) - 2,3,4,5,6-pentahydroxyhexyl] urea (I-490) as a white solid. MS (ES, m/z): 718 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 0.38 (s, 2H), 0.55 - 0.65 (m, 2H), 0.99 (d, J = 9.0 Hz, 4H), 3, 06 (t, J = 6.7 Hz, 2H), 3.17 (dd, J = 13.9, 6.9 Hz, 1H), 3.26 (t, J = 5.4 Hz, 2H), 3.34 - 3.55 (m, 4H), 3.56 - 3.81 (m, 8H), 4.36 (s, 2H), 6.96 - 7.07 (m, 2H), 7, 17 - 7.29 (m, 4H), 7.30 - 7.44 (m, 2H), 8.47 (d, J = 5.0 Hz, 1H), 8.63 (s, 1H). Example 88: 1- [2- (2 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) benzene] sulfinyl] ethoxy) ethyl] - 3 -[(2S, 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl] urea

[00620] A 25 mL round bottom flask was charged with a solution of N-[2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl ] cyclopropoxy] methyl) phenyl] sulfanyl] ethoxy) ethyl] tert-butyl carbamate (200 mg, 0.33 mmol, 1.00 equiv) in DCM (8 mL). The resulting solution was stirred for 5 min at 0°C. This was followed by the addition of mCPBA (51 mg, 0.32 mmol, 1.00 equiv) in several batches at 0 oC. The resulting solution was stirred for 2-3 h at 0°C in a salt/ice bath. The resulting solution was diluted with 30 mL of H2O. The resulting solution was extracted with 2 x 20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1 x 50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 200 mg (97%) of N-[2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene] sulfinyl] ethoxy) ethyl] tert-butyl carbamate (491a) as a light yellow oil. Step 2. 2- (2 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] - cyclopropoxy] methyl) benzene] sulfinyl] ethoxy) ethan-1-amine (Intermediate 491b)

[00621] A 25 mL round bottom flask was charged with N-[2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy] methyl) benzene] sulfinyl] ethoxy) ethyl] detert-butyl carbamate (200 mg, 0.32 mmol, 1.00 equiv). The solution was stirred for 5 min at 0 oC. This was followed by the addition of hydrogen chloride/dioxane (3/6 mL) dropwise with stirring at 0oC. The resulting solution was stirred for 0.5-1 h in a water/ice bath. The resulting solution was diluted with 30 mL of H2O. The pH value of the solution was adjusted to 8 with sodium carbonate (1 mol/L). The resulting solution was extracted with 2 x 20 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1 x 30 ml of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 150 mg (89%) of 2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfinyl]ethoxy ) ethane-1-amine (491b) as a light yellow oil. Step 3. 1- [2- (2 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) benzene] sulfinyl] ethoxy) ethyl] - 3 - [(2S, 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl] urea (I-491)

[00622] A 100 mL round bottom flask was charged with 2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene ] sulfinyl] ethoxy) ethan-1-amine (227 mg, 0.43 mmol, 1.00 equiv), DSC (133 mg, 0.52 mmol, 1.20 eq). This was followed by the addition of a solution of DIEA (0.11 mL, 1.50 equiv) in N,N-dimethylformamide (20 mL). The solution was stirred for 1 h at room temperature. To this was added (2R, 3R, 4R, 5S)-6-aminohexane-1,2,3,4,5-pentol (102 mg, 0.56 mmol, 1.30 equiv.). The resulting solution was stirred overnight at room temperature. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, OBD XBridge Shield RP18 Column; 5μm 19 x 150mm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (25.0% MeCN to 50.0% in 10 min); Detector, UV 220 nm. This resulted in 65.8 mg (21%) of 1-[2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl) benzene] sulfinyl] ethoxy) ethyl] -3 - [(2S, 3R, 4R, 5R) - 2,3,4,5,6-pentahydroxyhexyl] urea (I-491) as a white solid. MS (ES, m/z): 734.4 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 8.65 (s, 1H), 8.48 (d, J = 5.1 Hz, 1H), 7.56 (t, J = 1.3 Hz, 2H) , 7.43 - 7.20 (m, 5H), 7.01 (td, J = 7.4, 1.2 Hz, 1H), 4.46 (s, 2H), 3.90 - 3.82 (m, 1H), 3.82 - 3.56 (m, 7H), 3.56 - 3.47 (m, 3H), 3.45 - 3.35 (m, 1H), 3.29 (d , J = 5.1 Hz, 2H), 3.14 - 3.00 (m, 3H), 1.02 (dd, J = 11.1, 6.9 Hz, 4H), 0.60 (dd, J = 6.1, 1.9 Hz, 2H), 0.36 (p, J = 3.0 Hz, 2H). Example 89: 1- [2- (2 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) benzene] sulfonyl] ethoxy) ethyl] - 3 - [(2S, 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl] urea (I-492)

[00623] A 25 mL round bottom flask was charged with a solution of N-[2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl ] cyclopropoxy] methyl) phenyl] sulfanyl] ethoxy) ethyl] tert-butyl carbamate (400 mg, 0.65 mmol, 1.00 equiv) in DCM (10 mL). The solution was stirred for 5 min at 0 oC. This was followed by adding a solution of RuCl3 (4 mg, 0.02 mmol, 0.03 equiv) in water (2 mL) dropwise with stirring at 0 oC. To this end, a solution of NaIO4 (702 mg, 3.28 mmol, 5.00 equiv) in water (8 mL) was added drop by drop with stirring at 0 oC. The resulting solution was stirred for 1–2 h in an ice/water bath. The resulting solution was diluted with 80 mL of H2O. The resulting solution was extracted with 2 x 40 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1 x 50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 400 mg (95%) of N-[2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene] sulfonyl] ethoxy) ethyl] tert-butyl carbamate (492a) as a yellow oil. Step 2. 2- (2 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] - cyclopropoxy] methyl) benzene] sulfonyl] ethoxy) ethan-1-amine (Intermediate 492b)

[00624] A 25 mL round bottom flask was charged with N-[2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy] methyl) benzene] sulfonyl] ethoxy) ethyl] detert-butyl carbamate (400 mg, 0.62 mmol, 1.00 equiv). The solution was stirred for 5 min at 0 oC. This was followed by addition of hydrogen chloride/dioxane (4.5/9 mL) dropwise with stirring at 0oC. The resulting solution was stirred for 0.5-1 h in a water/ice bath. The resulting solution was diluted with 50 mL of H2O. The pH value of the solution was adjusted to 8 with sodium carbonate (1 mol/L). The resulting solution was extracted with 2 x 50 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1 x 80 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 330 mg (98%) of 2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonyl]ethoxy )ethane-1-amine (492b) as a yellow oil. Step 3. 1-[2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfinyl]ethoxy)ethyl]- 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-492)

[00625] A 25 mL round bottom flask was charged with 2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene ] sulfonyl] ethoxy) ethan-1-amine (330 mg, 0.61 mmol, 1.00 equiv) and DSC (187 mg, 0.73 mmol, 1.20 equiv). This was followed by the addition of a solution of DIEA (0.15 mL, 1.50 equiv) in DMF (8 mL). The solution was stirred for 1 h at room temperature. To this was added (2R, 3R, 4R, 5S)-6-aminohexane-1,2,3,4,5-pentol (143 mg, 0.79 mmol, 1.30 equiv.). The resulting solution was stirred overnight at room temperature. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, OBD XBridge Shield RP18 Column; 5μm 19 x 150mm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (30.0% MeCN to 41.0% in 8 min); Detector, UV 220 nm. This resulted in 121.2 mg (27%) of 1[2-(2-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene ] sulfonyl] ethoxy) ethyl] -3 - [(2S, 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl] urea (I-492) as a white solid. MS (ES, m/z): 750.3 [M+H]+; 1H- NMR (400 MHz, CD3OD) δ 8.66 (d, J = 0.7 Hz, 1H), 8.48 (d, J = 5.1 Hz, 1H), 7.78 (dd, J = 8.4, 2.4 Hz, 1H), 7.69 (d, J = 2.3 Hz, 1H), 7.59 (d, J = 8.3 Hz, 1H), 7.43 - 7, 31 (m, 2H), 7.29 - 7.19 (m, 2H), 7.03 (td, J = 7.3, 1.5 Hz, 1H), 4.48 (s, 2H), 3 .82 - 3.51 (m, 9H), 3.47 (t, J = 5.7 Hz, 2H), 3.41 - 3.30 (m, 2H), 3.20 - 3.04 (m , 3H), 1.08 - 0.94 (m, 4H), 0.66 - 0.56 (m, 2H), 0.44 - 0.35 (m, 2H).Example 90: 1- (2 - (2- (4-Chloro-3 - ((1- (4- (2- (oxetan-3-yloxy) phenyl) pyridin-3-yl) cyclopropoxy) methyl) phenylthio) ethoxy) ethyl) -3 - ( (2S, 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl) urea (I-493)

[00626] Sodium hydride (60% in oil, 116 mg, 2.8 mmol) was added to a solution of 1- (4- (2- (oxetan-3-yloxy) phenyl) pyridin-3-yl) cyclopropanol (A26) (398 mg, 1.40 mmol) and 4-bromo-2-(bromomethyl)-1-chlorobenzene (480 mg, 1.69 mmol) in DMF (8.0 mL) at 0 oC. After 20 minutes, the reaction was quenched by the addition of 50% saturated NaHCO3 (40 mL). The product was extracted into EtOAc (3 x 30 mL). The combined organic layers were washed with water (2 x 25 mL) and brine (25 mL), dried (Na2SO4) and concentrated. The crude product was combined with another assay (0.35 mmol scale) and purified by flash chromatography (40 g SiO2, eluting with 0-40% EtOAc/DCM), giving the title compound (564 mg, 66% ). Step 2. 2-(2-(4-chloro-3-((1-(4-(2-(oxetan-3-yloxy)phenyl)pyridin-3-yl)cyclopropoxy)ethyl)phenylthio)ethoxy)ethylcarbamate tert-butyl (Intermediate 493b)

[00627] 3- (1- (5-bromo-2-chlorobenzyloxy) cyclopropyl) -4 (2- (oxetan-3-yloxy) phenyl) pyridine (564 mg, 1.16 mmol) and 2- (2-mercaptoethoxy ) tert-butyl ethylcarbamate (310 mg, 1.40 mmol) were dissolved in dioxane (15 mL). The vial was evacuated and then purged with nitrogen. This was repeated 4 times. Xantphos (60 mg, 0.10 mmol), Pd2(dba)3 (53 mg, 0.058 mmol) and DIEA (0.40 mL, 2.32 mmol) were added and the nitrogen evacuation/purge cycle was repeated 5x . The reaction was heated to 100°C for 3 hours, at which time it was cooled, concentrated and purified by flash chromatography on silica gel (50-80% EtOAc/hexane) to give the title compound (493b) (660 mg, 90 %). Step 3. 2- (2- (4-chloro-3 - ((1- (4- (2- (oxetan-3-yloxy) phenyl) pyridin-3-yl) cyclopropoxy) methyl) phenylthio) ethoxy) ethanamine ( Intermediate 493c)

[00628] Trifluoroacetic acid (0.5 mL) was added to a solution of 2- (2- (4-chloro-3 - ((1- (4- (2- (oxetan-3-yloxy) phenyl) pyridin- tert-butyl 3-yl)cyclopropoxy)methyl)phenylthio)ethoxy)ethylcarbamate (494b, 43 mg, 0.068 mmol) in DCM (0.5 mL). After 45 minutes, the solvent was removed under reduced pressure. 10% Na2CO3 (5 mL) was added and the product was extracted with DCM (4 x 10 mL). The combined organic layers were washed with water (5 mL) and brine (5 mL) and then dried (Na2SO4) and concentrated to give the crude amine (493c). Step 4. 1- (2- (2- (4-chloro-3 - ((1- (4- (2- (oxetan-3-yloxy) phenyl) pyridin-3-yl) cyclopropoxy) methyl) phenylthio) ethoxyl ) ethyl) -3 - ((2S, 3R, 4R, 5R) - 2,3,4,5,6-pentahydroxyhexyl) urea (I-493)

[00629] A solution of 2- (2- (4-chloro-3 - ((1- (4- (2- (oxetan-3-yloxy) phenyl) pyridin-3-yl) cyclopropoxy) methyl) phenylthio) ethoxy ) ethanamine (493c) in DMF (0.7 mL) was treated with disuccinimidyl carbonate (19 mg, 0.075 mmol) and stirred at room temperature. After 30 minutes, the amine was consumed. D-glucamine (24.5 mg, 0.136 mmol) was added and the reaction was heated to 60°C. After heating for 30 minutes, the reaction was completed by LC/MS. The cooled reaction mixture was diluted with 1:1 MeCN/water and purified by reverse phase HPLC (MeCN/0.01M NH4HCO3) to give the title compound (I-493) (33 mg). MS (ES, m/z): 734.2 (M+H)+, 1H NMR (400 MHz, CD3OD) δ 8.65 (s, 1H), 8.53 (d, J = 5.1 Hz, 1H), 7.37-7.31 (m, 3H), 7.23 (s, 2H), 7.04 (t, J =7.7 Hz, 1H), 6.97 (s, 1H), 6.55 (d, J = 8.2 Hz, 1H), 4.92 (m, 1H), 4.74 (t, J = 6.9 Hz, 2H), 4.36 (s, 2H), 4.32 (t, J = 5.3 Hz, 2H), 3.78-3.67 (m, 4H), 3.63-3.59 (m, 4H), 3.47 (t, J = 5.4 Hz, 2H), 3.38 (dd, J = 13.7 Hz, J = 4.3 Hz, 1H), 3.27 (t, J =5.3 Hz, 2H), 3.17 (dd, J = 13.9 Hz, J = 6.7 Hz, 1H), 3.07 (t, J = 6.6 Hz), 1.05 (s, 4H).Example 91: 1-[5 -([4-Chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]sulfanyl)pentyl]-3- [(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]urea (I-494)

[00630] A 100 mL round bottom flask was charged with a solution of 2-chloro-5-iodobenzaldehyde (500 mg, 1.88 mmol, 1.10 equiv) in DCM (50 mL). This was followed by the addition of 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (500 mg, 1.88 mmol, 1.00 equiv). The mixture was stirred for 1 h at rt. To this was added NaBH(OAc)3 (1.5 g, 7.08 mmol, 4.00 equiv) at 0°C and AcOH (0.05 mL, 0.01 equiv). The resulting solution was stirred for 1 night at room temperature. The reaction was cooled by adding 500 mL of water. The resulting solution was extracted with 3 x 100 mL of ethyl acetate and the organic layers combined. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:3). This resulted in 600 mg (62%) of N-[(2-chloro-5-iodophenyl)methyl]-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (494a) as an off-white solid. Step 2. 5 - ([4-chloro-3 - [([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl] amino) methyl] phenyl] sulphanyl) ethyl pentanoate (Intermediate 494b)

[00631] A 50 mL round bottom flask was charged with N - [(5-bromo-2-chlorophenyl) methyl] -1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropan-1-amine (800 mg, 1.70 mmol, 1.20 equiv), ethyl 5-sulfanylpentanoate (230 mg, 1.42 mmol, 1.00 equiv), dioxane (15 mL), Xantphos (96 mg, 0.17 mmol , 0.10 equiv), Pd (dba)3 (65 mg, 0.05 equiv) and DIEA (366 mg, 2.83 mmol, 2.00 equiv). The resulting solution was stirred overnight at 110 oC in an oil bath. The resulting solution was diluted with 100 mL of ethyl acetate. The resulting mixture was washed with 2x100 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (1 g) was purified by flash chromatography with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, petroleum ether: ethyl acetate = 100: 0 increasing to petroleum ether: ethyl acetate = 50: 50 in 30 min; Detector, UV 254 nm. 880 mg of product was obtained. This resulted in 880 mg (raw) of 5-([4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]sulfanyl)pentanoate of ethyl (494b) as a colorless oil. Step 3. 5 - ([4-chloro-3 - [([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl] amino) methyl] phenyl] sulphanyl) pentan-1-ol (Intermediate 494c )

[00632] A 50 mL round bottom flask was charged with 5 - ([4-chloro-3 - [([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl] amino) methyl] phenyl ] sulfanyl) ethyl pentanoate (880 mg, 1.60 mmol, 1.00 equiv), THF (20 mL) and LiAlH4 (150 mg, 3.95 mmol, 2.50 equiv). The resulting solution was stirred at room temperature for 30 min. The resulting solution was diluted with 50 mL of ethyl acetate. The resulting mixture was washed with 2x50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (800 mg) was purified by flash chromatography with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, petroleum ether: ethyl acetate = 100: 0 increasing to petroleum ether: ethyl acetate = 50: 50 in 30 min; Detector, UV 254 nm. 750 mg of product was obtained. This resulted in 750 mg (92%) of 5 - ([4-chloro-3 - [([1[4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl] amino) methyl] phenyl] sulfanyl) pentane - 1-ol (494c) as a colorless oil. Step 4. 5-[4-Chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl]pentyl methanesulfonate (Intermediate 494d)

[00633] A 50 mL round bottom flask was charged with 5 - ([4-chloro-3 - [([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl] amino) methyl] phenyl ] sulfanil) pentan-1-ol (750 mg, 1.47 mmol, 1.00 equiv), DCM (20 mL), MsCl (420 mg, 3.68 mmol, 2.50 equiv) and DIEA (880 mg, 6.81 mmol, 5.00 equiv). The resulting solution was stirred for 1 h at room temperature. The resulting solution was diluted with 50 mL of H2O. The resulting solution was extracted with 2x50 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (700 mg) was purified by flash chromatography with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ethyl acetate:petroleum ether = 100:0 increasing to ethyl acetate:petroleum ether = 50:50 within 30 min; Detector, UV 254 nm. 600 mg of product was obtained. This resulted in 600 mg (69%) of 5 - ([4-chloro-3 - [([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl] amino) methyl] phenyl] sulfanyl) pentyl methanesulfonate (494d) as colorless oil. Step 5. N - ([5 - [(5-azidopentyl)sulfanyl] -2-chlorophenyl] methyl) -1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropan-1-amine (Intermediate 494e)

[00634] A 100 mL round bottom flask was charged with 5-([4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl methanesulfonate ] phenyl] sulfanyl) pentyl (600 mg, 1.02 mmol, 1.00 equiv), DMSO (10 mL) and NaN3 (167 mg, 2.57 mmol, 2.50 equiv). The resulting solution was stirred for 1 overnight at 50 oC in an oil bath. The resulting solution was diluted with 50 mL of ethyl acetate. The resulting mixture was washed with 3 x 30 ml of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 500 mg (92%) of N-([5-[(5-azidopentyl)sulfanyl]-2-chlorophenyl]methyl)-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropane- 1-amine (494e) as a colorless oil. Step 6. N - ([5 - [(5-aminopentyl)sulfanyl] -2-chlorophenyl] methyl) -1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropan-1-amine (Intermediate 494f)

[00635] A 250 mL round bottom flask was charged with N-([5-[(5-azidopentyl)sulfanyl]-2-chlorophenyl]methyl)-1-[4-(2-cyclopropoxyphenyl)pyridin-3- il] cyclopropane -1-amine (500 mg, 0.94 mmol, 1.00 equiv), EtOH (20 mL) and Rh/C (400 mg). The resulting mixture was stirred overnight under 1 atm H2 at room temperature. The resulting mixture was diluted with 50 mL of methanol and the solids were filtered. The resulting solution was concentrated in vacuo. This resulted in 400 mg (84%) of N-([5-[(5-azidopentyl)sulfanyl]-2-chlorophenyl]methyl)-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropane- 1-amine (494f) as a colorless oil. Step 7. 1- [5 - ([4-Chloro-3 - [([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl] amino) methyl] phenyl] sulfanyl) pentyl] -3- [(2S, 3R, 4R, 5R) - 2,3,4,5,6-pentahydroxyhexyl] urea (I-494)

[00636] A 25 mL round bottom flask was charged with DSC (121 mg, 0.47 mmol, 1.20 equiv), DIEA (77 mg, 0.60 mmol, 1.50 equiv), N, N- dimethylformamide (5 mL), N-([5-[(5-aminopentyl)sulfanyl]-2-chlorophenyl]methyl)-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine ( 200 mg, 0.39 mmol, 1.00 equiv), (2R, 3R, 4R, 5S) -6-aminohexane- 1,2,3,4,5- pentol (214 mg, 1.18 mmol, 3.00 equiv). The resulting solution was stirred overnight at room temperature. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, OBD XBridge Shield RP18 Column; 5μm 19 x 150mm; mobile phase, 10 mM NH4HCO3 and MeCN (37.0% MeCN to 45.0% in 8 min); Detector, UV 220 nm. This resulted in 61.9 mg (22%) of 1-[5-([4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl] phenyl] sulfanyl) pentyl] -3 - [(2S, 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl] urea (I-494) as a light yellow oil. MS (ES, m/z): 715 [M+H]+; 1H-NMR (400 MHz, CDCl3) δ 8.46 (1H, m), 8.45 (1H, m), 7.46 (2H, m), 7.22 (5H, m), 7.15 (1H, m), 3.63 (9H, m ), 3.31 (1H, m), 3.11 (1H, m), 3.09 (2H, m), 2.88 (2H, m), 1.61 (2H, m), 1.46 (4H, m), 0.90 (4H, m) , 0.64 (2H, s), 0.43 (2H, s).Example 92: 5 - ([6 - [([1- [4- (2-cyclopropoxyphenyl) pyridin-3- yl] cyclopropyl] amino) methyl] - 5-methylpyridin-2-yl]sulfanyl)-N-methyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide (I-495)

[00637] A 100 mL round bottom flask charged with ethyl 5 - [(6-formyl-5-methylpyridin-2-yl) sulfanyl] pentanoate (120 mg, 0.43 mmol, 1.00 equiv). This was followed by the addition of a solution of 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (170.4 mg, 0.64 mmol, 1.50 equiv) in DCM (5 .0 mL) and NaBH (OAc)3 (543.2 mg, 2.56 mmol, 6.00 equiv) in several batches at 0 oC. The resulting solution was stirred for 4–5 h in an ice/water bath. The resulting solution was diluted with 20 mL of DCM. The reaction was cooled by adding 30 mL of water. The resulting solution was extracted with 20 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 2 x 30 ml of water and 2 x 30 ml of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (2.5:1). This resulted in 107 mg (47%) of 5 - ([6 - [([1- [4(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-5-methylpyridin-2-yl]sulfanyl ) ethyl pentanoate (495a) as a colorless oil. Step 2. 5-([6-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-5-methylpyridin-2-yl]sulfanyl)pentanoic acid (intermediate 495b )

[00638] A 500 mL (1 atm) round bottom flask was charged with a solution of 5 - ([6 - [([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl] amino )methyl]-5-methylpyridin-2-yl]sulfanyl) ethyl pentanoate (167 mg, 0.31 mmol, 1.00 equiv) in EtOH (6 mL). This was followed by adding water (0.5 mL) dropwise with stirring. To this was added LiOH (45.2 mg, 1.89 mmol, 6.00 equiv). The resulting solution was stirred for 1 h at 50°C in an oil bath. The pH value of the solution was adjusted to 7 with hydrogen chloride (1 mol/L). The resulting solution was extracted with 2 x 30 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2 x 20 ml of water and 2 x 20 ml of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 150 mg (95%) of 5-([6-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-5-methylpyridin-2-yl] sulfanyl) pentanoic acid (495b) as a colorless oil. Step 3. 5 - ([6 - [([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl] amino) methyl] -5- methylpyridin-2-yl] sulphanyl) -N-methyl- N - [(2S, 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl] pentanamide (I-495)

[00639] A 25 mL round-bottom flask purged and maintained under an inert nitrogen atmosphere was charged with 5-([6-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl acid ]amino) methyl] -5- methylpyridin-2-yl] sulphanyl) pentanoic acid (75 mg, 0.15 mmol, 1.00 equiv), (2R, 3R, 4R, 5S) -6- (methylamino) hexane-1 ,2,3,4, 5-pentol (54.5 mg, 0.28 mmol, 2.00 equiv) in DMF (6 mL), HATU (113.1 mg, 0.30 mmol, 2.00 equiv) and DIEA (100 mg, 0.77 mmol, 4.00 equiv). The resulting solution was stirred overnight at room temperature. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, Gemini-NX 5μ C18 110A, AXIA Packed, 150 x 21.2 mm; mobile phase, water with 10 mM NH4HCO3 and MeCN (25% MeCN to 55% in 8 min); Detector, UV 254 nm. This resulted in 52.9 mg (52%) of 5-([6-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-5-methylpyridin-2- yl]sulfanyl)-N-methyl-N-[(2S,3R,4R,5R)-2,3,4,5,6-hydroxydecyloxy] pentanamide (I-495) as an off-white solid. MS (ES, m/z): 681.2 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 8.66 (s, 1H), 8.50 (d, J = 4.9 Hz, 1H), 7.48 - 7.33 (m, 2H), 7, 21 (dd, J = 7.5, 1.4 Hz, 2H), 7.13 - 7.03 (m, 2H), 6.94 (d, J = 7.9 Hz, 1H), 3.93 (d, J = 3.5 Hz, 1H), 3.80 - 3.59 (m, 8H), 3.54 (dd, J = 6.2, 3.2 Hz, 1H), 3.42 ( d, J = 7.6 Hz, 1H), 3.05 (s, 5H), 2.32 (d, J = 7.0 Hz, 2H), 2.16 (s, 3H), 0.89 ( s, 3H), 0.59 (s, 2H), 0.45 (s, 2H). Example 93: 1-[4-(2-Cyclopropoxyphenyl)pyridin-3-yl]-N-[[5-methyl -2-(methylsulfanyl)pyrimidin-4-yl]methyl]cyclopropan-1-amine (I-496)

[00640] A 50 mL round bottom flask was charged with a solution of 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine (70 mg, 0.26 mmol, 1.00 equiv) in dichloromethane (5 mL), 5-methyl-2-(methylsulfanyl) pyrimidine-4-carbaldehyde (53 mg, 0.32 mmol, 1.20 equiv), NaBH(OAc)3 (167 mg, 0.79 mmol, 6.00 equiv). The resulting solution was stirred overnight at 25°C. The reaction was then cooled by adding 50 mL of H2O. The resulting solution was extracted with 3 x 30 mL of dichloromethane and the organic layers combined and dried over sodium sulfate and concentrated in vacuo. The crude product was purified by the following conditions: Column: XBridge Prep C18 OBD Column, 5 μm, 19 x 150 mm; Mobile Phase A: water with 10 mM NH4HCO3, Mobile Phase B: MeCN; Flow rate: 20 mL/min; Gradient: 35% B to 65% B in 8 min; 254 nm. This resulted in 46.7 mg (42%) of 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-[[5-methyl-2-(methylsulfanyl)pyrimidin-4-yl]methyl] cyclopropan-1-amine (I-496) as an off-white solid. MS (ES, m/z): 419 [M+H]+; 1H-NMR (400 MHz, CD3OD) δ 8.57 (s, 1H), 8.42 (d, J =4.8Hz, 1H), 8.22 (s, 1H), 7.44-7.51 (m, 2H), 7.28 (dd, J =7.6Hz, 1H), 7.12-7.16 (m, 2H), 3.69 (s, 2H), 3.52-3.56 (m, 1H), 2.45 (s, 3H), 2.12 (s, 3H), 0.98 (s, 3H), 0.82 (s, 2H), 0.58 (d, J =4.2Hz, 2H), 0.35-0.36 (m, 2H).Example 94: 4 - [[3 - ([1- [4- (2- cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-4-ethylphenyl]sulfanyl]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-497)

[00641] A 100 mL round-bottom flask purged and maintained under an inert nitrogen atmosphere was charged with ethyl 4-[[3-(bromomethyl)-4-ethylphenyl]sulfanyl]butanoate (300 mg, 0.87 mmol , 1.00 equiv), 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-ol (232 mg, 0.87 mmol, 1.00 equiv) and DMF (16 g, 218. 91 mmol, 251.96 equiv). This was followed by the addition of sodium hydride (70 mg, 0.02 mmol, 2.00 equiv, 0.6%) in portions at 0 oC. The resulting solution was stirred for 30 min at 0°C in a water/ice bath. The reaction was then cooled by adding 100 mL of NH4Cl. The resulting solution was extracted with 3 x 50 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1x50 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 340 mg (74%) of ethyl 4-[[3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-4-ethylphenyl]sulfanyl]butanoate (497a ) as a yellow oil. Step 2. 4-[[3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-4-ethylphenyl]sulfanyl]butanoic acid (Intermediate 497b)

[00642] A 50 mL round bottom flask was charged with 4 - [[3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) -4-ethylphenyl] sulfanyl] butanoate of ethyl (340 mg, 0.64 mmol, 1.00 equiv), LiOH.H2O (81 mg, 1.93 mmol, 3.00 equiv), MeOH (10 mL) and water (2 mL). The resulting solution was stirred for 2.5 h at 60°C in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 20 mL of water. The pH value of the solution was adjusted to 3 with hydrogen chloride (12 mol/L). The resulting solution was extracted with 3x10 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 310 mg (96%) of 4-[[3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-4-ethylphenyl]sulfanyl]butanoic acid (497b) as a yellow gross solid. Step 3. 4 - [[3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) -4-ethylphenyl] sulphanyl] -N - [(2S, 3R, 4R, 5R )-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-497)

[00643] A 100 mL round-bottom flask was charged with 4-[[3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-4-ethylphenyl]sulfanyl] acid. butanoic acid (150 mg, 0.30 mmol, 1.00 equiv), (2R, 3R, 4R, 5S) -6-aminohexane-1,2,3,4,5-pentol (70 mg, 0.39 mmol, 1.20 equiv), DIEA (0.2 mL, 4.00 equiv) N,N-dimethylformamide (5 mL), HATU (170 mg, 0.45 mmol, 1.50 equiv). The resulting solution was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum. The crude product was purified by preparative HPLC with the following conditions: Column, OBD XBridge Shield RP18 Column; 5μm,19 x 150mm; mobile phase, 10 mM NH4HCO3 and MeCN (29.0% MeCN to 59.0% in 8 min); Detector, 254 and 220 nm. This resulted in 57.3 mg (29%) of 4-[[3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-4-ethylphenyl]sulfanyl]-N- [(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-497) as a blank sold. MS (ES, m/z): 667 [M+H]+; 1H-NMR (300 MHz, CD3OD) δ 8.68 (s, 1H), 8.48 (d, J = 5.1 Hz, 1H), 7.43 - 7.31 (m, 2H), 7, 30 - 7.13 (m, 3H), 7.11 - 6.93 (m, 3H), 4.88 (s, 1H), 4.36 (s, 2H), 3.85 - 3.52 ( m, 7H), 3.45 (dd, J = 13.7, 4.6 Hz, 1H), 3.23 (dd, J = 13.8, 7.4 Hz, 1H), 2.88 (t , J = 7.2 Hz, 2H), 2.52 - 2.28 (m, 4H), 1.87 (p, J = 7.4 Hz, 2H), 1.14 - 0.87 (m, 7H), 0.64 (t, J = 6.6 Hz, 2H), 0.50 - 0.38 (m, 2H). Example 95: 4-[[4-Chlorine-3-([1-[ 4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]butanamide (I -498)

[00644] A 50 mL round bottom flask was charged with 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-ol (220 mg, 0.82 mmol, 1.00 equiv), methyl 4-[[3-(bromomethyl)-4-chlorophenyl]sulfanyl]butanoate (320 mg, 0.95 mmol, 1.00 equiv), DMF (12 mL), and sodium hydride (70 mg, 2.92 mmol , 2.00 equiv). The resulting solution was stirred for 2 h at 0°C in a salt/ice bath. The resulting solution was diluted with 100 mL of ethyl acetate. The resulting mixture was washed with 1 x 50 ml of water and 2 x 50 ml of brine. The solid was dried in an oven at reduced pressure. The crude product was purified by flash chromatography with the following conditions (IntelFlash-1): Column, silica gel; mobile phase, ethyl acetate:petroleum ether = 100:0 increasing to ethyl acetate:petroleum ether = 85:15 within 30 min; Detector, UV 254 nm. 160 mg of product was obtained. This resulted in 160 mg (37%) of 4-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]methyl butanoate ( 498a) as a light yellow oil. Step 2. 4-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]butanoic acid (Intermediate 498b)

[00645] A 25 mL round bottom flask was charged with 4 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) phenyl] sulfanyl] methyl butanoate (230 mg, 0.44 mmol, 1.00 equiv), methanol (5 mL), water (1 mL), LiOH (65 mg, 2.71 mmol, 6.00 equiv). The resulting solution was stirred for 1 h at 60 oC in an oil bath. The pH value of the solution was adjusted to 1.0 with hydrogen chloride (1 mol/L). The resulting solution was extracted with 3 x 50 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 220 mg (98%) of 4-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl]butanoic acid (498b ) as a light yellow oil. Step 3. 4-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy] methyl)phenyl]sulfanyl]-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide (I-498)

[00646] A 25 mL round bottom flask was charged with 4-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)phenyl]sulfanyl acid ] butanoic (110 mg, 0.22 mmol, 1.00 equiv), (2R, 3R, 4R, 5S) -6-aminohexane-1,2,3,4,5-pentol (130 mg, 0. 72 mmol, 2.00 equiv), HATU (180 mg, 0.47 mmol, 2.00 equiv), DIEA (150 mg, 1.16 mmol, 4.00 equiv) and DMF (3 mL). The resulting solution was stirred overnight at room temperature. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, XBridge BEH C18 OBD Prepared Column, 5μm, 19 mm 250 mm; mobile phase, water with 0.05% TFA and MeCN (25.0% MeCN to 49.0% in 8 min); Detector, 254 nm. This resulted in 81.7 mg (56%) of 4 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) phenyl] sulphanyl] -N - [(2S, 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl] butanamide (I-498) as a white solid. MS (ES, m/z): 673 [M+H]+; 1H-NMR (300 MHz, CD3OD) δ 0.39 (2H,s), 0.64 (2H, d), 1.19 (4H, m), 1.91 (2H, m), 2.37 ( 2H, m), 2.93 (2H, m), 3.22 (1H, m), 3.42 (1H, m), 3.71 (8H, m), 4.38 (2H, s), 6.95 (1H, m), 7.09 (1H, m), 7.21 (2H, m), 7.40 (2H, m), 7.51 (2H, m), 7.81(1H , m), 8.72 (1H, m), 8.73 (1H, m).

[00647] Compounds I-499 to I-695 in Table 15 were prepared from known commercial base materials or the appropriate intermediates disclosed herein, in accordance with the methods of the examples specified in Table 15 and methods generally known to those skilled in the art. technique. Table 15. Compounds I-499 to I-695 Example 96: 1- [4- (N-ethyl [4-chloro-3 - [([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl] amino) methyl] benzene] sulfonamido) butyl] -3 - [(2S, 3R, 4S, 5R) -1,3,4,5,6-pentahydroxyhexan-2-yl] urea (I-696)

[00648] A 100 mL round bottom flask was charged with N-(4-aminobutyl)-4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino )methyl]-N-ethylbenzene-1-sulfonamide (140 mg, 0.25 mmol, 1.00 equiv), N,N-dimethylformamide (4 mL), DSC (76 mg, 1.20 equiv), DIEA (148 mg, 1.15 mmol, 5.00 equiv). The resulting solution was stirred for 1.5 h at room temperature. To this was added (2R, 3R, 4R, 5S, 6R)-3-amino-6-(hydroxymethyl)oxane-2,4,5-triol hydrochloride (159 mg, 0.74 mmol, 3.00 equiv) . The resulting solution was stirred overnight at room temperature. The reaction was cooled by adding 10 mL of water. The resulting solution was extracted with 6 x 10 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 150 mg (79%) of 3-[4-(N-ethyl[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl ] benzene] sulfonamido) butyl] -1 - [(2R, 3R, 4R, 5S, 6R) -2,4,5- trihydroxy-6- (hydroxymethyl) oxan-3-yl] urea (696a) as oil light yellow. Step 2. 1- [4- (N-ethyl [4-chloro-3 - [([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl] amino) methyl] benzene] sulfonamido) butyl] -3 - [(2S, 3R, 4S, 5R) -1,3,4,5,6-pentahydroxyhexan-2-yl] urea (I-696b)

[00649] A 50 mL round bottom flask was charged with 3-[4-(N-ethyl[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl ]amino) methyl] benzene] sulfonamido) butyl] -1 - [(2R, 3R, 4R, 5S, 6R) -2,4,5- trihydroxy-6- (hydroxymethyl) oxan-3-yl] urea ( 190 mg, 0.25 mmol, 1.00 equiv), methanol (5 mL), NaBH4 (18 mg, 0.48 mmol, 2.00 equiv). The resulting solution was stirred for 1 h at room temperature. The reaction was cooled by adding 0.5 mL of water. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, Gemini-NX C18 AXAI Packed, 21.2 x 150 mm 5μm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (36.0% MeCN to 40.0% in 12 min); Detector, UV 220 nm. This resulted in 25.7 mg (13%) of 1-[4-(N-ethyl[4-chloro-3-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino ) methyl] benzene] sulfonamido) butyl] -3 - [(2S, 3R, 4S, 5R) -1,3,4,5,6-pentahydroxyhexan-2-yl] urea (I-696b) as a white solid: (ES, m/z):[M+1] = 776. 1H NMR (400 MHz, Methanol- d4) δ 0.40 (s, 2H), 0.64 (s, 2H), 0 .82 (s, 2H), 0.92 (s, 2H), 1.08 (t, J = 7.1 Hz, 3H), 1.48 (d, J = 7.9 Hz, 2H), 1 .57 (d, J = 7.7 Hz, 2H), 3.08 - 3.23 (m, 7H), 3.48 (p, J = 1.6 Hz, 1H), 3.53 - 3, 72 (m, 6H), 3.72 - 3.80 (m, 3H), 3.80 - 3.90 (m, 1H), 3.96 (dd, J = 4.9, 2.8 Hz, 1H), 7.11 (ddd, J = 8.0, 5.2, 3.2 Hz, 1H), 7.15 - 7.20 (m, 1H), 7.22 - 7.27 (m, 1H), 7.43 - 7.48 (m, 2H), 7.54 (d, J = 8.3 Hz, 1H), 7.65 (dd, J = 8.3, 2.4 Hz, 1H ), 7.69 (d, J = 2.3 Hz, 1H), 8.46 (d, J = 5.1 Hz, 1H), 8.58 (d, J = 0.7 Hz, 1H). Example 97: 3- [1 - [(2-chloro-5- [methyl [4 - ([[(3R, 4S, 5R) - 1,3,4,5,6-pentahydroxy-hexan-2- yl] carbamoyl] amino) butyl] sulfamoyl] phenyl) methoxy] cyclopropyl] -4- (2-cyclopropoxyphenyl) pyridin-1-ium-1-olate (I-697)

[00650] A 100 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with 1-(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl ) pyridin-3-yl] cyclopropoxy] methyl) benzene] sulfonamido] butyl) -3 - [(3R, 4S, 5R) - 1,3,4,5,6-pentahydroxy-hexan-2-yl] ureaI -389 (110 mg, 0.14 mmol, 1.00 equiv), dichloromethane (10 mL), m-CPBA (29.9 mg, 1.20 equiv). The resulting solution was stirred for 1 h at room temperature. The crude product was purified by preparative HPLC with the following conditions: Column, OBD XBridge Shield RP18 Column; 5μm 19 x 150mm; mobile phase, water (0.05% NH3/H2O) and MeCN (25.0% MeCN to 36.0% in 10 min); Detector, UV 254nm. This resulted in 48.5 mg (43%) of 3[1 - [(2-chloro-5- [methyl [4 - ([[(3R, 4S, 5R) - 1,3,4,5,6- pentahydroxyhexane 2-yl] carbamoyl] amino) butyl] sulfamoyl] phenyl) methoxy] cyclopropyl] -4- (2-cyclopropoxyphenyl) pyridin-1-ium-1-olate (I-697) as a white solid: (ES, m/z): [M +1]: 779; 1H NMR (400 MHz, methanol-d4) δ 0.41 (dt, J = 5.5, 2.6 Hz, 2H), 0.63 (t, J = 6.2 Hz, 2H), 1.01 - 1.12 (m, 4H), 1.48 - 1.61 (m, 4H), 2.67 (s, 3H), 2.97 (t, J = 6.6 Hz, 2H), 3, 14 (t, J = 6.5 Hz, 2H), 3.52 - 3.72 (m, 6H), 3.72 - 3.89 (m, 2H), 3.96 (dd, J = 4, 9, 2.8 Hz, 1H), 4.50 (s, 2H), 7.03 (td, J = 7.4, 1.3 Hz, 1H), 7.28 - 7.45 (m, 4H ), 7.49 - 7.60 (m, 2H), 7.65 (dd, J = 8.3, 2.3 Hz, 1H), 8.30 (dd, J = 6.6, 2.0 Hz, 1H), 8.47 (d, J = 2.0 Hz, 1H). Example 98: 4- [3- [1 - ([2-chloro-5 - [(2S) -6 - ([[(2S, 3R,4S, 5R) -1,3,4,5,6-penta -hydroxyhexan-2-yl] carbamoyl] amino) hexan-2-yl] phenyl] methoxy) cyclopropyl] -1-oxidopyridin-1-yl-4-yl] -3-cyclopropoxybenzene-1-ide (I698)

[00651] Compound I-698 was prepared from 1 - [(5S) -5- [4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) phenyl] hexyl] -3 - [(2S, 3R, 4S, 5R) -1,3,4,5,6-pentahydroxy-hexan-2-yl] urea according to the procedure used in I-697 68 .3 mg (36%) to provide the desired compound as a white solid. MS (ES, m/z): [M+1]:714; 1H NMR (400 MHz, Methanol-d4) δ 0.40 (s, 2H), 0.63 (dd, J = 6.3, 1.8 Hz, 2H), 0.98 (s, 2H), 1 .05 (d, J = 4.8 Hz, 2H), 1.15 - 1.31 (m, 4H), 1.44 (s, 2H), 1.54 (d, J = 7.8 Hz, 2H), 2.56 - 2.65 (m, 1H), 3.05 (q, J = 6.5 Hz, 2H), 3.51 - 3.72 (m, 6H), 3.79 (ddd , J = 25.3, 10.5, 4.2 Hz, 2H), 3.95 (dd, J = 4.9, 2.9 Hz, 1H), 4.42 (s, 2H), 4, 59 (s, 1H), 6.90 (d, J = 2.1 Hz, 1H), 6.97 - 7.10 (m, 2H), 7.22 (d, J = 8.2 Hz, 1H ), 7.30 - 7.45 (m, 4H), 8.29 (dd, J = 6.6, 2.0 Hz, 1H), 8.45 (d, J = 2.0 Hz, 1H) .Example 99: 3- [1 - [(2-chloro-5- [ethyl [4 - ([[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl ] carbamoyl] amino) butyl] sulfamoyl] phenyl) methoxy] cyclopropyl] -4- (2-cyclopropoxyphenyl) pyridin-1-ium-1-olate (I-699)

[00652] Compound I-699 was prepared from 1- (4-[N-ethyl [4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) benzene] sulfonamido] butyl) -3- [(2S, 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl] urea according to the procedure used in I-697 to provide 59 .8 mg (59%) of 3- [1 - [(2-chloro-5- [ethyl [4 - ([[(2S, 3R, 4R, 5R) -2,3,4,5,6- penta -hydroxyhexyl] carbamoyl] amino) butyl] sulfamoyl] phenyl) methoxy] cyclopropyl] - 4- (2-cyclopropoxyphenyl) pyridin-1-ium-1-olate (I-699) as a white solid: MS (ES, m/z): [M +1]: 793; 1H NMR (400 MHz, Methanol-d4) δ 0.41 (s, 2H), 0.58 - 0.68 (m, 2H), 1.01 - 1.12 (m, 7H), 1.51 ( dq, J = 33.3, 7.8 Hz, 4H), 3.06 - 3.22 (m, 7H), 3.27 (s, 1H), 3.39 (dd, J = 13.9, 4.5 Hz, 1H), 3.53 - 3.81 (m, 6H), 4.49 (s, 2H), 6.99 - 7.08 (m, 1H), 7.28 - 7.46 (m, 4H), 7.54 (dd, J = 5.3, 3.1 Hz, 2H), 7.68 (dd, J = 8.4, 2.3 Hz, 1H), 8.31 ( dd, J = 6.6, 2.0 Hz, 1H), 8.47 (d, J = 2.0 Hz, 1H). Example 100: 2,5-dichloro-4 - [([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl] amino) methyl] phenol (I-700)

[00653] A 100 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with 2,5-dichloro-3-formylphenyl trifluoromethanesulfonate (B2c400 mg, 1.24 mmol, 1.00 equiv), dichloromethane (30 mL), 1-[2-(2-cyclopropoxyphenyl)phenyl]cyclopropan-1-amine (329.76 mg, 1.24 mmol, 1.00 equiv). This was followed by the addition of acetic acid (0.1 mL). The mixture was stirred for 1 h at rt. To this was added NaBH(OAc)3 (1.31 g, 6.18 mmol, 5.00 equiv). The resulting solution was stirred overnight at room temperature. The resulting solution was extracted with 3 x 50 mL of ethyl acetate and the organic layers combined. This resulted in 709.95 mg (raw) of 2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenyl trifluoromethanesulfonate as a yellow oil. Step 2. 2,5-dichloro-4 - [([1- [4- (2-cyclopropoxyphenyl) pyridin- 3- yl] cyclopropyl] amino) methyl] phenol (I-700)

[00654] A 100 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with 2,5-dichloro-4 - [([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl] amino) methyl] phenyl trifluoromethanesulfonate (709.95 mg, 1.24 mmol, 1.00 equiv), toluene (20 mL), Cs2CO3 (1.21 g, 3.70 mmol, 3.00 equiv). The resulting solution was stirred overnight at 80°C in an oil bath. The resulting solution was extracted with 3 x 50 mL of ethyl acetate and the organic layers combined. The crude product was purified by preparative HPLC with the following conditions: Column, SunFire Prep C18 OBD Column, 19 x 150 mm 5μm 10 nm; mobile phase, 10 mM aqueous NH4HCO3 and MeCN (55.0% MeCN to 65.0% in 10 min); Detector, UV 254 nm. This resulted in 200.6 mg (37%) of 2,5-dichloro-4-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]phenol (I-700 ) as a white solid: MS (ES, m/z): [M+1]:441; 1H NMR (400 MHz, DMSO- d6) δ 0.32 - 0.41 (m, 2H), 0.64 (td, J = 5.6, 2.1 Hz, 4H), 0.76 (d, J = 2.3 Hz, 2H), 1.86 (t, J = 7.5 Hz, 1H), 3.45 (d, J = 7.4 Hz, 2H), 3.71 (tt, J = 6.0, 2.9 Hz, 1H), 6.91 (s, 1H), 6.98 - 7.10 (m, 2H), 7.14 (s, 1H), 7.21 - 7.28 (m, 1H), 7.37 - 7.47 (m, 2H), 8.45 (d, J = 4.9 Hz, 1H), 8.56 (s, 1H), 10.48 (s, 1H). Example 101: 3-(1-(2-chloro-5-(N-ethyl-N-(4-(3-((2S, 3R, 4R, 5R))-2,3,4,5,6 chloride -pentahydroxyhexyl) ureido) butyl) sulfamoyl)benzyloxy) cyclopropyl) -4- (2-cyclopropoxyphenyl) -1- (pivaloyloxymethyl) pyridinium (I701)

[00655] In a 50 mL round bottom flask, 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-ethyl-N-( 4- ( 3 - ((2S, 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl) ureido) butyl) (I-390) (100 mg, 0.13 mmol, 1.0 equiv) and NaI (19 mg, 0.129 mmol, 1.0 equiv) in MeCN (0.5 mL). Chloromethyl pivalate (21.3 mg, 0.142 mmol, 1.1 equiv) was added and the reaction mixture was heated to 60°C, at which time a yellow solution formed and the reaction vessel was covered in foil. After 5 hours, LCMS indicated complete conversion. The reaction mixture was cooled and diluted with IPA:MeCN (3:1, 25 mL). Dowex 1 x 2 Cl resin (1.7 g, washed with MeOH) was added and TLC indicated complete conversion to the hydrochloride salt. The mixture was filtered and purified by flash chromatography (12 g SiO2, DCM 20% MeOH in DCM). Lyophilization gave 60 mg (50%) of the title compound as a white solid. MS (ES, m/z): 891.13 [M - Cl]+; 1H-NMR (D2O, ppm): δ 8.89 (s, 1H), 8.69 (d, J = 6.4 Hz, 1H), 7.68 (d, J = 6.3 Hz, 1H) , 7.44 - 7.37 (m, 1H, 7.29 (d, J = 8.4 Hz, 1H), 7.20 (d, J = 7.3 Hz, 1H), 7.12 (dd , J = 13.0, 8.1 Hz, 2H), 7.04 (s, 1H), 6.80 (s, 1H), 6.14 (s, 2H), 4.16 (s, 2H) , 3.50 (d, J = 2.8 Hz, 1H), 3.47 (s, 1H), 3.45 - 3.40 (m, 2H), 3.37 - 3.28 (m, 3H ), 3.03 (d, J = 4.5 Hz, 1H), 2.84 (dt, J = 21.2, 7.2 Hz, 5H), 2.73 (t, J = 6.8 Hz , 2H), 1.19 (s, 2H), 1.07 (s, 2H), 0.98 (d, J = 20.5 Hz, 4H), 0.89 (s, 9H), 0.73 (t, J = 7.1 Hz, 3H), 0.36 (d, J = 7.4 Hz, 2H), 0.10 (s, 1H). acetoxyethyl) (methyl) carbamoyloxy) methyl) -3- (1- (2-chloro-5- (N-ethyl-N- (4- (3 - ((2S, 3R, 4R, 5R) - 2.3, 4,5,6-pentahydroxyhexyl) ureido) butyl) sulfamoyl) benzyloxy) cyclopropyl) -4- (2-cyclopropoxyphenyl) pyridinium (I-702)

[00656] A solution of 2-(methylamino) ethanol (292 mg, 3.9 mmol, 1.0 equiv) and DIEA (505 mg, 3.9 mmol, 1.0 eq) in DCM (25 mL) was cooled at 0 °C under an N2 atmosphere. Chloromethyl chloroformate (521 mg, 4.0 mmol, 1.05 eq) was added dropwise and the reaction was maintained at 0°C for 1 hour, at which time TLC indicated that no starting material remained. DIEA (645 mg, 5.0 mmol, 1.3 equiv) and then Ac2O (400 mg, 3.9 mmol, 1.0 eq) were added at 0°C followed by DMAP (5 mg, catalytic). The ice bath was removed. After 50 minutes the reaction was complete and the reaction mixture was quenched with HCl (0.25 M, 20 mL) and then washed successively with water (10 mL) and brine (10 mL). The resulting solution was dried over Na2SO4 and purified by flash chromatography (24 g SiO2, DCM 100% EtOAc, ELSD detector) to yield 910 mg (quantitative) of Intermediate 702a as a clear oil. Step 2. 1 - (((2-acetoxyethyl) (methyl) carbamoyloxy) methyl) chloride -3- (1- (2-chloro-5- (N-ethyl-N- (4- (3 - ((2S) , 3R, 4R, 5R) - 2,3,4,5,6-pentahydroxyhexyl) ureido) butyl) sulfamoyl) benzyloxy) cyclopropyl) -4- (2-cyclopropoxyphenyl) pyridinium (I-702)

[00657] A suspension of 4-chloro-3 - ((1- (4- (2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) -N-ethyl-N- (4- (3 - ((2S , 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl) ureido) butyl) benzenesulfonamide I-390(100 mg, 0.129 mmol, 1.0 eq), NaI (19 mg, 0.129 mmol, 1.0 eq) in MeCN (0.5 mL) was added 2-(((chloromethoxy)carbonyl)(methyl)amino)ethyl acetate (30 mg, 0.142 mmol, 1.1 eq) in MeCN ( 0.5 mL). The reaction mixture was heated to 60 °C and wrapped in foil. After 2 hours more 2-(((chloromethoxy)carbonyl)(methyl)amino)ethyl acetate (10 mg, 0.048 mmol, 0.37 eq) was added. After another 3 hours, the reaction was complete. The reaction mixture was cooled and diluted with IPA:MeCN (3:1, 25 mL). Dowex 1 x 2 Cl resin (1.45 g, washed with MeOH) was added and TLC indicated complete conversion to the hydrochloride salt. The resulting mixture was filtered and purified by flash chromatography (12 g SiO2, DCM 20% MeOH in DCM). Lyophilization gave 63 mg (51%) of the title compound I-702 as a white solid. MS (ES, m/z): 950.14 [M - Cl]+; 1H-NMR D2O, ppm): δ 9.23 (d, J = 7.7 Hz, 1H), 9.08 - 8.96 (m, 1H), 8.02 (d, J = 6.2 Hz , 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.62 (d, J = 8.5 Hz, 1H), 7.52 (dd, J = 12.1, 6, 3 Hz, 2H), 7.39 (s, 2H), 7.12 (t, J = 7.4 Hz, 1H), 6.45 (d, J = 13.9 Hz, 2H), 5.14 (d, J = 5.9 Hz, 1H), 4.52 (d, J = 5.5 Hz, 2H), 4.25 (dt, J = 16.3, 5.2 Hz, 2H), 3 .93 - 3.75 (m, 5H), 3.75 - 3.59 (m, 5H), 3.59 - 3.44 (m, 1H), 3.38 (dd, J = 4.4 Hz , 1H), 3.29 - 3.11 (m, 6H), 3.11 - 2.98 (m, 4H), 2.94 (d, J = 7.8 Hz, 2H), 2.78 ( s, 1H), 2.19 - 1.99 (m, 1H), 1.97 (s, 1H), 1.90 (s, 1H), 1.53 (s, 2H), 1.42 (d , J = 7.9Hz, 2H), 1.30 (d, J = 23.5Hz, 4H), 1.06 (t, J = 7.1Hz, 3H), 0.73 (s, 2H) , 0.49 (s, 1H). Example 103: 5-[6-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-5-methylpyridin-2-yl]-N-[trihydrochloride (2S, 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl] pentanamide (I-703)

[00658] To a solution of methyl 5-(6-formyl-5-methylpyridin-2-yl) pentanoate (B11) (160 mg, 0.68 mmol, 1.00 equiv), intermediateA1 (182 mg, 0. 68 mmol, 1.00 equiv) in dichloromethane (10 mL) and AcOH (0.01 mL) was added NaBH (OAc) 3 (721 mg). The resulting solution was stirred overnight at 25°C in an oil bath. The reaction mixture was cooled by adding 5 mL of water. The resulting solution was extracted with 3 x 10 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1/100-20/100). This resulted in 200 mg (60%) of 5-[6-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-5-methylpyridin-2-yl]pentanoate of methyl (703a) as a light brown solid. Step 2. 5-([6-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-5-methylpyridin-2-yl]sulfanyl)pentanoic acid (intermediate 703b )

[00659] To a solution of 5- [6 - [([1- [4- (2- cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl] amino) methyl] -5- methylpyridin-2-yl] methyl pentanoate ( 200 mg, 0.41 mmol, 1.00 equiv) in methanol (5 mL) was added LiOH.H2O (52 mg, 1.24 mmol, 3.01 equiv) in water (1 mL). The resulting solution was stirred for 1 h at 60°C in an oil bath. The pH value of the solution was adjusted to 7 with HCl (2 mol/L). The resulting solution was extracted with 3 x 10 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. This resulted in 150 mg (77%) 5-[6-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-5-methylpyridin-2-yl] acid pentanoic acid (703b) as a light brown solid. Step 3. 5-[6-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-5-methylpyridin-2-yl]-N-[trihydrochloride (2S, 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl] pentanamide (I-703)

[00660] To a solution of 5- [6 - [([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl] amino) methyl] -5- methylpyridin-2-yl] pentanoic acid (150 mg, 0.32 mmol, 1.00 equiv), (2R, 3R, 4R, 5S) -6-aminohexane-1,2,3,4,5-pentol (86.5 mg, 0.48 mmol , 1.50 equiv), in N,N-dimethylformamide (5 mL) and DIEA (123 mg, 0.95 mmol, 2.99 equiv) was added HATU (362.5 mg, 0.95 mmol, 3.00 equiv). The resulting solution was stirred overnight at 25°C in an oil bath. The resulting solution was diluted with 5 mL of H2O. The resulting solution was extracted with 4 x 10 mL ethyl acetate, and the organic layers combined and dried over anhydrous sodium sulfate and concentrated in vacuo. The solids were filtered. The crude product was purified by preparative HPLC with the following conditions: Column, XBridge Shield RP18 OBD Column, 5 μm, 19 * 150 mm; mobile phase, water with 10 mmol NH4HCO3 and ACN (maintain 37.0% ACN in 10 min); Detector, UV 254 nm. After lyophilization, the product was dissolved in 2 ml of ACN/20 ml of H2O, 10 drops of HCl (1 M) were added. After lyophilization, this resulted in 57.6 mg (24%) of 5-[6-[([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl]amino)methyl]-5-methylpyridin- 2-yl trihydrochloride] -N - [(2S, 3R, 4R, 5R) - 2,3,4,5,6-pentahydroxyhexyl] pentanamide (I-703) as a white solid: ( ES, m/z): [M +1]: 743. 1H-NMR: (400 MHz, MeOD, ppm): δ 9.16 (s, 1H), 8.87- 8.87(d, 1H) , 8.86-7.23 (m, 7H), 4.91 (s, 2H), 3.87-3.03 (m, 10H), 2.43 (s, 3H), 2.35-2 .33 (t, 2H), 2.06 (s, 3H), 1.79-1.70 (m, 4H), 1.68-1.14 (m, 4H), 0.78-0.58 (m, 4H).

[00661] Compounds I-704 to I-709 (Table 16) were prepared from known commercial base materials or the appropriate intermediates disclosed herein using methods from the examples specified in Table 16 and methods generally known to those skilled in the art. Table 16. Compounds I-703 to I-709

[00662] A mixture of cerium trichloride (417.8 mg, 1.695 mmol, 4.0 equiv) in THF (3 mL) was stirred at room temperature for 2 h and cooled to -78 ° C. To the mixture was added a solution of methyl lithium (1.6 M in ether, 1.06 mL, 1.70 mmol, 4.0 equiv) dropwise. The reaction mixture was stirred at -78°C for 30 minutes. A solution of 4-(2-cyclopropoxyphenyl) nicotinonitrile (A-1a, 100 mg, 0.424 mmol, 1.0 equiv) in THF (0.5 mL) was added dropwise. The mixture was warmed to room temperature and stirred at room temperature overnight. The reaction was quenched with a few drops of saturated aqueous ammonium chloride, followed by addition of 28% ammonium hydroxide solution (~1 mL). The resulting mixture was filtered and the filtrate was extracted with ethyl acetate. The organic extract was washed with brine, dried over Na2SO4, then concentrated to dryness. The residue was purified by flash column chromatography on silica mobile phase of 0 - 20% MeOH/DCM to give 10 mg (9%) of 723a as yellow syrup. Step 2. 2-(4-(2-Cyclopropoxyphenyl)pyridin-3-yl)-N-(2,5-dichlorobenzyl)propan-2-amine (I-723)

[00663] A mixture of 2- (4- (2-cyclopropoxyphenyl) pyridin-3-yl) propan-2-amine (723a, 10 mg, 0.037 mmol, 1.0 equiv) in dichloroethane (0.5 mL) 2,5-dichlorobenzylaldehyde (6.5 mg, 0.037 mmol, 1.0 equiv) was added. The mixture was stirred at room temperature for 30 minutes. NaBH (OAc)3 (15.8 mg, 0.075 mmol, 2.0 equiv) and acetic acid (2.1μL, 0.037 mmol, 1.0 equiv) were added. The resulting mixture was stirred at room temperature for 3 h and more NaBH(OAc)3 (15.8 mg, 0.089 mmol, 2.4 equiv) was added. The mixture was stirred at room temperature overnight, quenched with saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with brine, dried, concentrated and purified by preparative HPLC to give 9.9 mg (49%) of I-723 TFA Salt as a yellow solid. MS (ES, m/z): 427.03 [M+H]+; 1H NMR (400 MHz, CD3OD): δ 9.03 (s, 1H), 8.63 (d, J = 5.1 Hz, 1H), 7.62 - 7.43 (m, 5H), 7, 28 (d, J = 5.2 Hz, 1H), 7.22 (dd, J = 7.5, 1.7 Hz, 1H), 7.14 (td, J = 7.3, 1.3 Hz , 1H), 4.12 (s, 2H), 3.82 (tt, J = 6.0, 2.9 Hz, 1H), 1.69 (s, 3H), 1.59 (s, 3H) , 0.81 - 0.61 (m, 2H), 0.59 - 0.38 (m, 2H). Example 105: 4- (4-Chloro-3 - ((1- (4- (2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenethyl) -N-((2S, 3R, 4R, 5R) - 2,3,4,5,6-pentahydroxyhexyl) benzamide (I-724)

[00664] To a mixture of 3- (1 - ((2-chloro-5-iodobenzyl) oxy) - cyclopropyl) -4- (2-cyclopropoxyphenyl) pyridine (Intermediate 488a, 119.9 mg, 0.232 mmol, 1, 0 equiv) in DMF (270 μL) was added methyl 4-ethynylbenzoate (44.5 mg, 0.278 mmol, 1.2 equiv), triethylamine (390 μL), Pd (PPh3)2Cl2 (8.2 mg, 0.012 mmol , 0.05 equiv) and CuI (4.4 mg, 0.023 mmol, 0.1 equiv). The mixture was purged with N2 and stirred under N2 at 50°C overnight, diluted with ethyl acetate, washed with water (2x) brine, dried over Na2SO4, filtered, concentrated and the residue was purified by chromatography. flash column on silica with ethyl acetate/hexanes to give 98.1 mg (77%) of 724a as a yellow solid. Step 2. 4-(4-Chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenethyl)methyl benzoate (Intermediate 724b)

[00665] To a mixture 4 - ((4-chloro-3 - ((1- (4- (2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenyl) ethynyl) methyl benzoate (724a, 94, 2 mg, 0.171 mmol) in ethyl acetate (3 mL) was added 5% by weight. of Rh in alumina (95 mg). The mixture was stirred under hydrogen for 3 h and added 5 wt%. Rh in alumina (100 mg) was added. The resulting mixture was stirred under hydrogen overnight and filtered. The filtrate was concentrated to give 91.6 mg (97%) of 724b as yellow syrup. Step 3. 4-(4-Chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenethyl)benzoic acid (Intermediate 724c)

[00666] To a solution of 4- (4-chloro-3 - ((1- (4- (2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenethyl) methyl benzoate (724b, 91.6 mg , 0.166 mmol, 1 equiv) in THF (0.8 mL) and water (0.4 mL) was added lithium hydroxide monohydrate (10.4 mg, 0.248 mmol, 1.5 equiv). The mixture was stirred at room temperature overnight and an aqueous NaOH solution (5 M, 50 μL, 1.5 equiv) was added. The resulting mixture was stirred overnight and more NaOH solution (5 M, 50 μL, 1.5 equiv) was added. The mixture was stirred at room temperature for 5 h, acidified with 10% citric acid solution and extracted with ethyl acetate (2x) and DCM (5x). The combined organic layers were dried and concentrated to give 74 mg (82%) of 724c as a white solid. Step 4. 4- (4-Chloro-3 - ((1- (4- (2-cyclopropoxyphenyl) pyridin- 3- yl) cyclopropoxy) methyl) phenethyl) -N - ((2S, 3R, 4R, 5R) - 2,3 4,5,6-pentahydroxyhexyl) benzamide (I-724)

[00667] To a mixture of 4- (4-chloro-3 - ((1- (4(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenethyl) benzoic acid, (724c, 23.4 mg, 0.043 mmol, 1.0 equiv) and D-glucamine (9.4 mg, 0.052 mmol, 1.2 equiv) in DMF (0.2 mL) were added N,N-diisopropylethylamine (38, 0.22 mmol , 5.0 equiv) and HATU (19.8 mg, 0.521 mmol, 1.2 equiv). The mixture was stirred at room temperature for 1 h and purified by preparative HPLC to give I-724 (21.4 mg, 70%) as a white solid. MS (ES, m/z): 703.3 [M+H]+, 1H-NMR (400MHz, CD3OD) δ 8.63 (s, 1H), 8.47 (d, J = 5.1 Hz, 1H), 7.74 (d, J = 7.6 Hz, 2H), 7.40 - 7.30 (m, 2H), 7.27 (d, J = 7.5 Hz, 1H), 7, 25 - 7.19 (m, 3H), 7.15 (d, J = 8.2 Hz, 1H), 7.01 - 6.94 (m, 2H), 6.88 (s, 1H), 4 .35 (s, 2H), 4.01 - 3.92 (m, 1H), 3.84 - 3.76 (m, 2H), 3.75 - 3.60 (m, 4H), 3.56 - 3.41 (m, 2H), 2.97 - 2.79 (m, 4H), 1.00 - 0.87 (m, 4H), 0.63 - 0.55 (m, 2H), 0 .42 - 0.33 (m, 2H).Example 106: 4-Chloro-3 - ((1- (4- (2-cyclopropoxyphenyl)pyridin-3-yl) cyclopropoxy) methyl) -N,N-dimethylbenzamide ( I-725)

[00668] A mixture of 1- (4- (2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropanol (A-23, 93.5 mg, 0.35 mmol, 1.0 equiv) and 3- (bromomethyl) Methyl -4-chlorobenzoate (110.6 mg, 0.42 mmol, 1.2 equiv) in DMF (1.4 mL) at 0°C was added NaH (60% in mineral oil, 19.6 mg, 0 .49 mmol, 1.4 equiv). The mixture was stirred at 0°C for 1 h. The resulting mixture was quenched with 10% citric acid and extracted with ethyl acetate. The organic layer was washed with water (2x) and brine (1x), dried and concentrated. The residue was dissolved in DCM (3 mL)/MeOH (1 mL) and cooled to 0°C. (Trimethylsilyl)diazomethane solution (2M in ether, 0.4 mL, 0.8 mmol, 2.3 equiv) was added. The mixture was stirred at 0°C for 30 minutes, concentrated and purified by flash column chromatography on silica eluting with ethyl acetate/hexanes to give 130.8 mg (83%) of 725a as orange syrup. Step 2. 4-Chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)benzoic acid (Intermediate 725b)

[00669] To a solution of 4-chloro-3 - ((1- (4- (2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) methyl benzoate (725a, 12.3 mg, 0.0274 mmol , 1.0 equiv) in THF (0.2 mL) 1 M NaOH solution (41, 0.041 mmol, 1.5 equiv) was added. The mixture was stirred at room temperature for 3 h and more 1 M NaOH solution (41, 0.041 mmol, 1.5 equiv) was added. The mixture was stirred at room temperature overnight, acidified with 10% citric acid and extracted with ethyl acetate. The organic layer was washed with brine (1x), dried and concentrated to give 725b which was used without purification. Step 3. 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N,N-dimethylbenzamide (I-725).

[00670] To a mixture of 4-chloro-3 - ((1- (4- (2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) benzoic acid (725b, 0.0274 mmol, 1.0 equiv) and dimethylamine (40 wt% in H2O, 6.9 μL, 0.055 mmol, 2.0 equiv) in DMF (0.2 mL) were added N,N-diisopropylethylamine (23.2 μL, 0.137 mmol, 5 .0 equiv) and HATU (20.8 mg, 0.0548 mmol, 2.0 equiv). The mixture was stirred at room temperature overnight and purified by preparative HPLC to give 4.6 mg (29%, 2 steps) of the title compound I-725 TFA salt as a white solid. MS (ES, m/z): 463.2 [M + H]+; 1H-NMR (400MHz, CD3OD) δ 8.93 (s, 1H), 8.74 (d, J = 5.9 Hz, 1H), 7.83 (d, J = 5.9 Hz, 1H), 7.49 - 7.34 (m, 4H), 7.30 (d, J = 8.2 Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H), 7.02 (s , 1H), 4.45 (s, 2H), 3.57 (d, J = 1.4 Hz, 1H), 3.12 (s, 3H), 2.93 (s, 3H), 1.24 - 1.09 (m, 4H), 0.71 - 0.58 (m, 2H), 0.45 - 0.36 (m, 2H).Example 107: 1-(5-(4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenoxy)pentyl)-3-((2S,3R,4R,5R)- 2,3,4,5,6 -pentahydroxyhexyl)urea (I-726)

[00671] To a mixture of (3-(bromomethyl)-4-chlorophenoxy) (tert-butyl) dimethylsilane (320 mg, 0.953 mmol, 1.0 equiv) in THF (5.8 mL) at 0°C added if 1 M TBAF in THF (1.05 mL, 1.05 mmol, 1.1 equiv). The mixture was stirred at 0°C for 10 minutes, quenched with water and extracted with ethyl acetate. The organic layer was washed with brine (1x), dried, concentrated and purified by flash column chromatography on silica eluting with 0-30% ethyl acetate/hexanes to give 186 mg (88%) of 726a as a white solid. . Step 2. Tert-Butyl (5-(3-(bromomethyl)-4-chlorophenoxy)pentyl)carbamate (Intermediate 726b)

[00672] To a solution of 3-(bromomethyl)-4-chlorophenol (726a, 127 mg, 0.575 mmol, 1.00 equiv), (5-hydroxypentyl) tert-butyl carbamate (146 mg, 0.718 mmol, 1.25 equiv) and PPh3 (188 mg, 0.718 mmol, 1.25 equiv) in toluene (2 mL) at 0°C was added DIAD (141, 0.718 mmol, 1.25 equiv) dropwise. The mixture was stirred at 0°C for 2 h, quenched with water and extracted with ethyl acetate. The organic layer was washed with brine (1x), dried, concentrated and purified by flash column chromatography on silica eluting with 0 - 40% ethyl acetate/hexanes to give 215 mg (92%) of 726b as a clear syrup. . Step 3. Tert-butyl (5-(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenoxy)pentyl) tert-butyl carbamate (Intermediate 726c)

[00673] To a mixture of 1- (4- (2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropanol (A-23, 118 mg, 0.44 mmol, 1.0 equiv) and (5- (3- ( bromomethyl)-4-chlorophenoxy) pentyl) tert-butyl carbamate (726b, 215 mg, 0.53 mmol, 1.2 equiv) in DMF (1.7 mL) at 0°C was added NaH (60% in mineral oil, 24.7 mg, 0.62 mmol, 1.4 equiv). The mixture was stirred at 0°C for 10 minutes and at room temperature for 1 h. The resulting mixture was quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic layer was washed with water (2x) and brine (1x), dried and concentrated and purified by column chromatography to give 186.5 mg (71%) of 726c as an orange syrup. Step 4. 5-(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenoxy)pentan-1-amine (Intermediate 726d)

[00674] For a mixture of (5- (4-chloro-3 - ((1- (4- (2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenoxy) pentyl) tert-butyl carbamate (726c , 186.5 mg, 0.314 mmol) in DCM (0.2 mL) was added 4.0 M HCl in dioxane (3 mL). The mixture was stirred at room temperature for 1 h, and concentrated. The residue was diluted with ethyl acetate, washed with saturated NaHCO3 (1x) and brine (1x), dried and concentrated to give 726d which was used without further purification. Step 5. 1-(5-(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenoxy)pentyl)-3-((2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl)urea (I-726)

[00675] To a mixture of 5-(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenoxy)pentan-1-amine (726d, 0.169 mmol , 1.0 equiv) in DMF (1 mL) was added disuccinimidyl N,N'-carbonate (54.6 mg, 0.213 mmol, 1.3 equiv). The mixture was stirred at room temperature for 1 h. D-glucamine (73.5 mg, 0.406 mmol, 2.4 equiv) was added. The mixture was stirred at 60°C overnight and purified by preparative HPLC to give 54.5 mg (46%, 2 steps) of the title compound I-726 as a white solid. MS (ES, m/z): 700.3 [M+H]+. 1H-NMR (400MHz, CD3OD) δ.8.64 (s, 1H), 8.47 (d, J = 5.1 Hz, 1H), 7.42 - 7.30 (m, 2H), 7, 28 (d, J = 7.5 Hz, 1H), 7.22 (d, J = 5.1 Hz, 1H), 7.16 (d, J = 8.7 Hz, 1H), 6.98 ( dd, J = 10.4, 4.2 Hz, 1H), 6.75 (dd, J = 8.7, 2.8 Hz, 1H), 6.63 (d, J = 2.7 Hz, 1H ), 4.35 (s, 2H), 3.88 (t, J = 6.2 Hz, 2H), 3.80 - 3.72 (m, 3H), 3.72 - 3.65 (m, 1H), 3.65 - 3.57 (m, 2H), 3.56 - 3.49 (m, 1H), 3.40 (dd, J = 13.9, 4.5 Hz, 1H), 3 .23 - 3.10 (m, 3H), 1.81 - 1.70 (m, 2H), 1.61 - 1.45 (m, 4H), 1.04 - 0.85 (m, 4H) , 0.65 - 0.54 (m, 2H), 0.43 - 0.33 (m, 2H).Example 108: 3 - ((4-chloro-3 - ((1- (4- (2- cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) benzyl) oxy) -N-((2S, 3R, 4R, 5R) -2,3,4,5,6- pentahydroxyhexyl) benzamide (I- 727) Step 1. (3-(bromomethyl)-4-chlorophenyl) methanol (Intermediate 727a)

[00676] To a mixture of methyl 3-(bromomethyl)-4-chlorobenzoate (1.570 g, 5.96 mmol, 1.0 equiv) in toluene (16 mL) at 0°C was added DIBALH (1 M in DCM, 11.9 mL, 11.9 mmol, 2.0 equiv) dropwise. The mixture was stirred at 0°C for 2 h, quenched with 1M HCl and extracted with ethyl acetate (2x). The combined organic layers were washed with brine (1x), dried, concentrated and purified by flash column chromatography on silica eluting with ethyl acetate/hexanes to give 820 mg (58%) of 727a as a white solid. Step 2. ((3-(bromomethyl)-4-chlorobenzyl)oxy)(tert-butyl)dimethylsilane (Intermediate 727b)

[00677] To a solution of (3-(bromomethyl)-4-chlorophenyl) methanol (727a, 750 mg, 3.19 mmol, 1.0 equiv) in DCM (15 mL) was added TBMDSCl (576 mg, 3.0 equiv) 82 mmol, 1.2 equiv) and imidazole (434 mg, 6.37 mmol, 2.0 equiv). The mixture was stirred at 0°C for 30 minutes, quenched with water and extracted with ethyl acetate. The organic layer was washed with 1M HCl (1x), saturated NaHCO3 (1x) and brine (1x), dried, concentrated and purified by flash column chromatography on silica eluting with 0 - 10% ethyl acetate/ hexanes to give 1.10 g (99%) of 727b as a clear syrup. Step 3. 3- (1 - ((5 - (((tert-butyldimethylsilyl) oxy) methyl) -2- chlorobenzyl) oxy) cyclopropyl) -4- (2- cyclopropoxyphenyl) pyridine (Intermediate 727c)

[00678] A mixture of 1- (4- (2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropanol (A-23, 553 mg, 2.069 mmol, 1.0 equiv) and ((3- (bromomethyl) -4 -chlorobenzyl)oxy) (tert-butyl) dimethylsilane (727b, 796 mg, 2.28 mmol, 1.1 equiv) in DMF (16 mL) at 0°C was added NaH (60% in mineral oil, 116 mg , 2.896 mmol, 1.4 equiv). The mixture was stirred at 0 °C for 40 minutes. The resulting mixture was quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic layer was washed with water (2x) and brine (1x), dried and concentrated and purified by flash column chromatography on silica eluting with ethyl acetate/hexanes to give 882 mg (79%) of 727c as a syrup yellow. Step 4. (4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)methanol (Intermediate 727d)

[00679] For a mixture of 3- (1 - ((5 - (((tert-butyldimethylsilyl)oxy) methyl) -2-chlorobenzyl) oxy) cyclopropyl) -4- (2-cyclopropoxyphenyl) pyridine (727c, 831 mg , 1.552 mmol, 1.0 equiv) in THF (9 mL) at 0°C was added 1 M TBAF in THF (1.71 mL, 1.71 mmol, 1.1 equiv). The mixture was stirred at 0°C for 20 minutes, quenched with water and extracted with ethyl acetate. The organic layer was washed with brine (1x), dried, concentrated and purified by flash column chromatography on silica eluting with 0 - 60% ethyl acetate/hexanes to give 648 mg (99%) of 727b as a clear syrup . Step 5. 3 - ((4-chloro-3 - ((1- (4- (2-cyclopropoxyphenyl) pyridin-3- yl) cyclopropoxy) methyl) benzyl) oxy) methyl benzoate (Intermediate 727e)

[00680] To a solution of (4-chloro-3 - ((1- (4- (2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenyl) methanol (727d, 51 mg, 0.121 mmol, 1, 00 equiv), methyl 3-hydroxybenzoate (23 mg, 0.151 mmol, 1.25 equiv) and PPh3 (39.7 mg, 0.151 mmol, 1.25 equiv) in toluene (0.4 mL) at 0°C DIAD (30, 0.151 mmol, 1.25 equiv) was added dropwise. The mixture was slowly warmed to room temperature and stirred at room temperature overnight. The resulting mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with brine (1x), dried, concentrated and purified by column chromatography to give 69.3 mg (103%) of 727e. Step 6. 3-((4-Chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)benzyl)oxy)benzoic acid (Intermediate 727f)

[00681] To a solution of 3 - ((4-chloro-3 - ((1- (4- (2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) benzyl) oxy) methyl benzoate (727e, 69 3 mg, 0.124 mmol, 1.0 equiv) in THF (0.9 mL) was added 1 M NaOH solution (0.187 mL, 0.187 mmol, 1.5 equiv). The mixture was stirred at room temperature overnight and more 1M NaOH solution (0.248 mL, 0.248 mmol, 2.0 equiv) was added. The mixture was stirred at room temperature for 5 h and 5 M NaOH solution (50, 0.25 mmol, 2.0 equiv) was added. The resulting mixture was stirred at room temperature overnight, acidified with 10% citric acid and extracted with ethyl acetate. The organic layer was washed with brine (1x), dried and concentrated to give 56.4 mg (84%) of 727f which was used without purification. Step 7. 3-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)benzyl)oxy)-N-((2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl)benzamide (I-727)

[00682] To a mixture of 3 - ((4-chloro-3 - ((1- (4(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) benzyl) oxy) benzoic acid (727f, 22.9 mg, 0.0423 mmol, 1.0 equiv) and D-glucamine (10.7 mg, 0.0591 mmol, 1.4 equiv) in DMF (0.3 mL) were added N,N-diisopropylethylamine ( 35.9 μL, 0.212 mmol, 5.0 equiv) and HATU (22.5 mg, 0.059 mmol, 1.4 equiv). The mixture was stirred at room temperature for 1 h and purified by preparative HPLC to give 23.1 mg (77%) of the title compound I-727 as a white solid. MS (ES, m/z): 705.3 [M+H]+; 1H-NMR (400MHz, CD3OD) δ 8.63 (s, 1H), 8.49 - 8.39 (m, 1H), 7.52 - 7.34 (m, 3H), 7.35 - 7, 22 (m, 5H), 7.22 - 7.10 (m, 3H), 6.95 (t, J = 7.1 Hz, 1H), 5.04 (s, 2H), 4.40 (s , 2H), 4.03 - 3.92 (m, 1H), 3.86 - 3.58 (m, 6H), 3.52 - 3.40 (m, 2H), 1.07 - 0.82 (m, 4H), 0.63 - 0.48 (m, 2H), 0.42 - 0.26 (m, 2H).Example 109: (2S,3S,4R,5S)-2,3,4 ,5,6-pentahydroxy-N-[4-[N-(propan-2-yl)[4-chloro-5-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy ]methyl)-2-fluorobenzene]sulfonamido]butyl]hexanamide (I-728)

[00683] A 100 mL 3-neck round bottom flask was charged with a solution of 2-chloro-4-fluorobenzoic acid (15 g, 85.93 mmol, 1.0 equiv), chlorosulfonic acid (45 mL) , Br2 (1.52 mL), S (113 mg, 3.53 mmol, 0.04 equiv). The resulting solution was stirred overnight at 70°C in an oil bath. The reaction was then quenched by adding 200 mL of water/ice. The solids were collected by filtration to provide 16 g (73%) of 5-bromo-2-chloro-4-fluorobenzoic acid 728a as a light yellow solid. Step 2. Methyl 5-bromo-2-chloro-4-fluorobenzoate (Intermediate 728b)

[00684] A 500 mL 3-neck round bottom flask was charged with a solution of 5-bromo-2-chloro-4-fluorobenzoic acid (728a, 16.2 g, 63.92 mmol, 1.0 equiv) in dichloromethane/CH3OH (150/50 mL). This was followed by addition of (diazomethyl)trimethylsilane (64 mL, 2M in Et2O) dropwise with stirring at room temperature in 20 min. The resulting solution was stirred at room temperature for 0.5 h. The resulting mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 6.83 g (40%) of methyl 5-bromo-2-chloro-4-fluorobenzoate 728b as a light yellow oil. Step 3. Methyl 5-(benzylsulfanyl)-2-chloro-4-fluorobenzoate (Intermediate 728c)

[00685] A 1000 mL round bottom flask was charged with a solution of methyl 5-bromo-2-chloro-4-fluorobenzoate (728b, 6.833 g, 25.55 mmol, 1.0 equiv), phenylmethanethiol (3 .1 mL), (8.6 mL). The resulting solution was stirred overnight at 80°C in an oil bath and then concentrated in vacuo. The resulting solution was extracted with 3 x 300 ml of ethyl acetate and the combined organic layers were washed with 3 x 200 ml of brine. The mixture was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The resulting residue was purified via silica gel column with ethyl acetate/petroleum ether (0-20%) to provide 6.8 g (86%) of methyl 5-(benzylsulfanyl)-2-chloro-4-fluorobenzoate 728c as a light yellow oil. Step 4. Methyl 2-Chloro-5-(chlorosulfonyl)-4-fluorobenzoate (Intermediate 728d)

[00686] A 250 mL round bottom flask was charged with a solution of methyl 5-(benzylsulfanyl)-2-chloro-4-fluorobenzoate (728c, 2.5 g, 8.04 mmol, 1.0 equiv) , NCS (3.23 g, 24.2 mmol, 3.01 equiv) in AcOH (100.8 mL) and water (11.2 mL) and the resulting solution was stirred for 1.5 h at room temperature. The reaction mixture was cooled to 5-10°C with a water/ice bath and then diluted with 200 mL of ethyl acetate. The organic layer was washed with 2 x 100 ml of H2O and 3 x 200 ml of saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to provide 2.5 g (crude) of 2 Methyl -chloro-5-(chlorosulfonyl)-4-fluorobenzoate 728d as a light yellow oil. Step 5. 5 - Methyl [(4-[[(tert-butoxy)carbonyl]amino]butyl)(propan-2-yl)sulfamoyl]-2-chloro-4-fluorobenzoate (Intermediate 728e)

[00687] A 25 mL round bottom flask was charged with a solution of tert-butyl N-4-[(propan-2-yl)amino]butylcarbamate (2.8 g, 12.2 mmol, 1.51 equiv.) TEA (2.25 mL), methyl 2-chloro-5-(chlorosulfonyl)-4-fluorobenzoate (728d, 2.31 g, 8.06 mmol, 1.0 equiv), dichloromethane (10 mL) and the resulting solution was stirred for 1.5 h at room temperature. The resulting mixture was diluted with ethyl acetate, washed with 2 x 100 ml of brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The resulting residue was purified through a silica gel column eluting with ethyl acetate/petroleum ether (0 to 20%) to provide 1.5 g (39%) of 5 - [(4 - [[(tert-butoxy) methyl carbonyl]amino]butyl) (propan-2-yl)sulfamoyl]-2-chloro-4-fluorobenzoate 728e as a white solid. Step6. 5-[(4-[[(tert-butoxy)carbonyl]amino]butyl)(propan-2-yl)sulfamoyl]-2-chloro-4-fluorobenzoic acid (Intermediate 728f)

[00688] A 100 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of 5 - [(4 - [[(tert-butoxy) carbonyl] amino] butyl) (propan-2- il)sulfamoyl]-methyl-2-chloro-4-fluorobenzoate (728e, 2 g, 4.16 mmol, 1.0 equiv) in THF (20 mL, 5.0 equiv) and water (4 mL, 1.0 equiv). LiOH^H2O (523.4 mg, 21.86 mmol, 3.0 equiv) was added and the resulting solution was stirred for 30 min at 60°C in an oil bath. The pH value of the solution was then adjusted to 6 with hydrogen chloride (4 M). The resulting solution was extracted with 3 x 50 mL of ethyl acetate and the combined organic layers were concentrated in vacuo to provide 1.74 g (90%) of 5-[(4-[[(tert-butoxy)carbonyl] acid amino]butyl)(propan-2-yl)sulfamoyl]-2-chloro-4-fluorobenzoic 728f as a white solid. Step 7. N-[4-[N-(propan-2-yl)[4-chloro-2-fluoro-5-(hydroxymethyl)benzene]sulfonamido]butyl]carbamatedetert-butyl (Intermediate 728g)

[00689] A 250 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of 5-[(4-[[(tert-butoxy)carbonyl]amino]butyl)(propan-2) acid -yl)sulfamoyl]-2-chloro-4-fluorobenzoic acid (728f1.74 g, 3.73 mmol, 1.0 equiv), IBCF (0.58 mL, 1.2 equiv.) in THF (30 mL). TEA (0.6 mL, 1.2 equiv) was then added and the resulting mixture was stirred for 1 h at 0°C. To this, NaBH4 (564 mg, 14.91 mmol, 4.0 equiv) in ethanol (30 mL) was added and the resulting solution was stirred for 10 min at 0°C in an ice/salt bath. The resulting mixture was concentrated in vacuo, extracted with 3 x 20 ml of ethyl acetate and the combined organic layers were concentrated in vacuo. The resulting residue was purified via silica gel column chromatography eluting with ethyl acetate/petroleum ether (0 to 30%) to provide 1.49 g (88%) of N-[4-[ N-(propan-2 -yl)[4-chloro-2-fluoro-5-(hydroxymethyl)benzene]tert-butylsulfonamido]butyl]carbamate 728g as a yellow oil. Table 8. N-[4-[N-(propan-2-yl)[5-(bromomethyl)-4-chloro-2-fluorobenzene]sulfonamido]butyl]tert-butyl carbamate (Intermediate 728h)

[00690] A 100 mL, three-neck, round-bottom flask, purged and maintained under an inert nitrogen atmosphere was charged with a solution of N-[4-[N-(propan-2-yl)[4-chloro tert-butyl-2-fluoro-5-(hydroxymethyl)benzene] sulfonamido] butyl] carbamate (728g, 1.485 g, 3.28 mmol, 1.0 equiv) in dichloromethane (20 mL) and tetrahydrofuran (20 mL , 1.0 equiv) and then cooled to 0 oC. NBS (933.68 mg, 5.25 mmol, 1.6 equiv) and PPh3 (1.29 g, 4.92 mmol, 1.5 equiv) were then added and the resulting solution was stirred for 30 min at room temperature and then concentrated under vacuum. The resulting residue was purified by silica gel column chromatography eluting with ethyl acetate/petroleum ether (0 to 20%) to give 1.15 g (68%) N-[4- [ N-(propan-2- il) [5-(bromomethyl)-4-chloro-2-fluorobenzene] tert-butyl sulfonamido] butyl] carbamate 728h as a white solid. Step 9. N-[4-[N-(propan-2-yl)[4-chloro-5-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2- fluorobenzene] sulfonamido] butyl] tert-butyl carbamate (Intermediate 728i)

[00691] A 250 mL 3-neck round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of N-[4-[N-(propan-2-yl)[5-(bromomethyl) tert-butyl-4-chloro-2-fluorobenzene]sulfonamido]butyl]carbamate (728h, 1.15 g, 2.22 mmol, 1.0 equiv), 1-[4-(2-cyclopropoxyphenyl)pyridin-3 -il] cyclopropan-1-ol (592.6 mg, 2.22 mmol, 1.0 equiv) and DMF (70 mL). The mixture was stirred at 0°C and NaH (106.5 mg, 4.44 mmol, 2.0 eq) was then added in portions at 0°C. The resulting solution was stirred for 20 min at 0°C in a water/ice bath and then quenched by adding 10 ml of NH4Cl (sat). The resulting mixture was extracted with 3 x 20 ml of ethyl acetate and the combined organic layers were concentrated in vacuo. The resulting residue was purified via silica gel column eluting with ethyl acetate/petroleum ether (0 to 25%) to provide 1.32 g (85%) of N-[4-[ N-(propan-2-yl ) [4-chloro-5-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-fluorobenzene]sulfonamido]butyl]tert-butyl728i carbamate as a white solid. Step 10. N-(4-aminobutyl)-4-chloro-5 - ([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-fluoro-N-(propan-2 -yl) benzene-1-sulfonamide (Intermediate 728j)

[00692] A 100 mL round bottom flask was purged and kept under an inert nitrogen atmosphere and was charged with a solution of N-[4-[N-(propan-2-yl)[4-chloro-5- tert-butyl([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-fluorobenzene]sulfonamido]butyl]tert-butyl carbamate (728i, 1.323 g, 1.88 mmol, 1, 0 equiv) in dichloromethane (3 mL, 1.0 equiv) and trifluoroacetic acid (30 mL, 10.0 equiv) and the resulting solution was stirred for 20 min at room temperature. The reaction was quenched by the addition of 10 mL of sodium bicarbonate and the resulting solution was extracted with 3 x 20 mL of ethyl acetate and the combined organic layers were concentrated in vacuo to provide 1.21 g (crude) of N- (4-aminobutyl)-4-chloro-5-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-fluoro-N-(propan-2-yl)benzene- 1-sulfonamide 728j as a white solid. Step 11. (2S, 3S, 4S, 5R) -4,5,6-tris(acetyloxy) -2 - ([4- [N-(propan-2-yl) [4-chloro-5 - ([1 -[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-fluorobenzene]sulfonamido]butyl]carbamoyl)oxan-3 ethyl acetate (Intermediate 728k)

[00693] A 25 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of N-(4-aminobutyl)-4-chloro-5-([1-[4-(2- cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-fluoro-N-(propan-2-yl)benzene-1-sulfonamide (728j, 500 mg, 0.83 mmol, 1.0 equiv), acid ( 2S, 3S, 4S, 5R) -3,4,5,6- tetrakis (acetyloxy) oxane-2-carboxylic acid (301 mg, 0.83 mmol, 1.00 equiv), DIEA (321.9 mg, 2, 49 mmol, 3.0 equiv) and HATU (473.3 mg, 1.24 mmol, 1.5 equiv) in DMF (10 mL). The resulting solution was stirred for 2 h at room temperature, diluted with water, extracted with 3 x 20 ml of ethyl acetate and the combined organic layers were concentrated in vacuo. The resulting residue was purified via silica gel column chromatography eluting with ethyl acetate/petroleum ether (0 to 100%) to provide 601 mg (76%) of (2S, 3S, 4S, 5R) - 4.5, 6-tris(acetyloxy)-2-([4-[N-(propan-2-yl)[4-chloro-5-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy] methyl) -2-fluorobenzene] sulfonamido] butyl] carbamoyl) oxan-3 ethyl acetate 728k as a white solid. Step 12. (2S, 3S, 4R, 5S) -2,3,4,5,6-pentahydroxy- N-[4- [ N-(propan-2-yl) [4-chloro-5 - ( [1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-fluorobenzene]sulfonamido]butyl]hexamide (I-728)

[00694] An 8 mL vial was charged with a solution of (2S, 3S, 4S, 5R)-4,5,6-tris(acetyloxy)-2-([4-[N-(propan-2-yl )[4-chloro-5-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-fluorobenzene]sulfonamido]butyl]carbamoyl)oxa3-yl acetate (728k, 200 mg , 0.21 mmol, 1.0 equiv), MeONa (1.06 mL, 0.5 equiv) in methanol (3 mL). NaBH4 (16.0 mg, 0.42 mmol, 2.0 equiv) was added and the reaction mixture was stirred for 30 min at room temperature. The resulting mixture was concentrated and the resulting residue was purified by preparative HPLC using the following conditions: Column, Gemini-NX C18 AXAI Packed, 21.2 x 150 mm, 5um; mobile phase, Waters (0.05% NH4OH) and ACN (30% ACN to 55% in 9 min); Detector, UV 254nm to deliver 107.4 mg (65%) of (2S, 3S, 4R, 5S)-2,3,4,5,6-penta-hydroxy-N-[4-[N-(propan- 2-yl)[4-chloro-5-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-fluorobenzene]sulfonamido]butyl]hexamide I-728 as a white solid . (ES, m/z): [M+1]: 780 1H NMR (300 MHz, Methanol-d4) δ 0.43 (s, 2H), 0.64 (h, J = 5.4, 4.9 Hz, 2H), 0.94 - 1.15 (m, 10H), 1.60 (dq, J = 33.3, 7.8 Hz, 4H), 3.18 - 3.35 (m, 4H) , 3.53 - 3.73 (m, 3H), 3.72 - 4.03 (m, 4H), 4.13 (d, J = 5.9 Hz, 1H), 4.42 (s, 2H ), 7.01 (t, J = 7.3 Hz, 1H), 7.18 - 7.45 (m, 5H), 7.65 (d, J = 7.7 Hz, 1H), 8.48 (d, J = 5.1 Hz, 1H), 8.64 (s, 1H).Example 110: N-[[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3 - yl] cyclopropoxy] methyl) benzene] sulfonyl] (I-729)

[00695] A 100 mL three-necked round-bottom flask, purged and maintained under an inert nitrogen atmosphere, was charged with a solution of 4-chloro-3- ([l-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]cyclopropoxy]methyl chloride)benzene-1-sulfonyl (200 mg, 0.41 mmol, 1.0 equiv) in dichloromethane (10 mL). To the above mixture, NH3(g) was added and the resulting solution was stirred for 30 min at room temperature. The resulting mixture was concentrated in vacuo and the crude residue was purified via silica gel column chromatography eluting with ethyl acetate/petroleum ether (2:3) to provide 200 mg (69%) of 4-chloro-3 - ([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene-1-sulfonamide 729a as a yellow solid. Step 2. N-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonyl]acetamide (I-729)

[00696] A 250 mL round bottom flask was charged with a solution of 4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxyl]methyl)benzene-1-sulfonamide (729a, 180 mg, 0.38 mmol, 1.0 equiv) in 50% aqueous sodium hydroxide (0.51 mL) and acetic anhydride (10 mL) and the resulting solution was stirred for 12 h at 80 °C in a oil bath. The reaction mixture was concentrated under vacuum and diluted with 100 mL of ethyl acetate. The organic layer was washed with 2 x 30 ml of sodium bicarbonate and 1 x 30 ml of water, dried and concentrated in vacuo. The crude product was further purified by preparative HPLC with the following conditions: Column, XBridge C18 OBD Preparative Column, 19 mm x 250 mm; mobile phase, water (NH4HCO3 10 mmol/L) and ACN (15.0% to 50.0% ACN in 8 min); Detector, UV 254 nm to deliver 64.0 mg (33%) of N-[[4-chloro-3 - ([1- [4- (2- cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) benzene] sulfonyl] acetamide I-729 as a white solid. (ES, m/z): [M+1]: 513; 1H NMR (300 MHz, DMSO-d6) δ 12.17 (s, 1H), 8.71 (s, 1H), 8.53 (d, J = 4.9 Hz, 1H), 7.78 (dd , J = 8.3, 2.3 Hz, 1H), 7.71 - 7.58 (m, 2H), 7.43 - 7.21 (m, 3H), 7.16 (d, J = 4 .9 Hz, 1H), 7.07 - 6.96 (m, 1H), 4.40 (s, 2H), 3.61 (dt, J = 6.1, 3.1 Hz, 1H), 2 .08 (s, 0H), 1.89 (s, 3H), 0.91 (d, J = 7.4 Hz, 4H), 0.66 - 0.53 (m, 2H), 0.34 ( s, 2H).Example 111: 4-chloro-5-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-methoxy-N,N-dimethylbenzene-1-sulfonamide (I-730)

[00697] A 25 mL round bottom flask was charged with a solution of dimethylamine (2.82 mL) and 4-chloro-5-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy ]methyl) - 2-fluorobenzene-1-sulfonyl chloride (286.5 mg, 0.56 mmol, 1.0 equiv) in DCM (2 mL). The resulting solution was stirred for 1 h at 16-20°C and then concentrated in vacuo. The resulting residue was purified via silica gel column chromatography eluting with ethyl acetate/petroleum ether (2:1) to provide 180 mg (62%) of 4-chloro-5-([1-[4-(2 -cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-fluoro-N,N-dimethylbenzene-1-sulfonamide 730a as a light yellow oil. Step 2. 4-Chloro-5-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-methoxy-N,N-dimethylbenzene-1-sulfonamide (I-730)

[00698] A 25 mL round bottom flask was charged with a solution of 4-chloro-5-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-fluoro- N,N-dimethylbenzene-1-sulfonamide (730a, 170 mg, 0.33 mmol, 1.0 equiv) N,N-dimethylformamide (5 mL) followed by the addition of sodium methoxide (53.3 mg, 0.99 mmol, 3.0 equiv). The resulting solution was stirred for 0.5 h at 16-20°C and then quenched by adding 0.5 ml of water. The crude product was purified by preparative HPLC using the following conditions: Column, XBridge C18 Prep Column, 19 mm x 250 mm; mobile phase, water (0.05% NH4OH) and ACN (42% to 62% ACN in 8 min); Detector, UV 254 nm to deliver 84 mg (48%) of 4-chloro-5-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-methoxy-N,N -dimethylbenzene-1-sulfonamide I-730 as a white solid. (ES, m/z): [M+1]+: 529; 1H NMR (400 MHz, Methanol-d4) δ 0.45 (dh, J = 5.4, 3.1 Hz, 2H), 0.65 (ddd, J = 7.3, 4.4, 3.1 Hz, 2H), 0.91 (s, 2H), 0.99 (d, J = 5.2 Hz, 2H), 2.77 (s, 6H), 3.65 (tt, J = 6.0 , 2.9 Hz, 1H), 3.90 (s, 3H), 4.39 (s, 2H), 7.00 (ddd, J = 7.5, 4.9, 3.6 Hz, 1H) , 7.18 - 7.31 (m, 3H), 7.31 - 7.41 (m, 2H), 7.64 (s, 1H), 8.47 (d, J = 5.1 Hz, 1H ), 8.64 (d, J = 0.8 Hz, 1H). Example 112: 4-chloro-5 - ([1- [4- (2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy] methyl)- 2-methoxy-N,N-dimethylbenzene-1-sulfonamide (I-731)

[00699] To a solution of (4-methoxyphenyl) methanol (80 mg, 0.58 mmol, 1.2 equiv) and 730a (250 mg, 0.48 mmol, 1.0 equiv) in N,N-dimethylformamide ( 5 mL) was sodium hydride (35 mg, 1.46 mmol, 3.02 equiv). The resulting solution was stirred for 2 h at room temperature and then diluted with 20 ml of EtOAc. The reaction was then cooled by adding 20 mL of NH4Cl. The resulting solution was extracted with 2 x 50 ml of ethyl acetate and the combined organic layers were washed with 3 x 100 ml of brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by silica gel column chromatography eluting with ethyl acetate/petroleum ether (1:1) to provide 270 mg (88%) of 4-chloro-5- ([1-[4- (2-cyclopropoxyphenyl)pyridine-3-yl]cyclopropoxy]methyl)-2-[(4-methoxyphenyl)methoxy]-N,N-dimethylbenzene-1-sulfonamide 731a as a white solid. Step 2. 4-Chloro-5-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-methoxy-N,N-dimethylbenzene-1-sulfonamide (I-731)

[00700] To a solution of 4-chloro-5 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) -2 - [(4-methoxyphenyl) methoxy] -N, N -dimethylbenzene-1-sulfonamide (731a, 270 mg, 0.43 mmol, 1.0 equiv) in dichloromethane (10 mL) was added trifluoroacetic acid (4 mL). The resulting mixture was stirred for 30 min at room temperature and then concentrated under vacuum. The reaction mixture was diluted with 20 mL of ethyl acetate and the pH value of the solution was adjusted to 8.0 with sodium bicarbonate (100%). The resulting solution was extracted with 2 x 50 ml of ethyl acetate and the combined organic layers were washed with 50 ml of brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product (10 mL) was purified by preparative HPLC using the following conditions: Column, XBridge C18 Prep Column, 19 mm x 250 mm; mobile phase, water (0.05% NH 4OH) and ACN (18% to 38% ACN in 8 min); Detector, UV 254 nm to deliver 90.6 mg (41%) of 4-chloro-5-([1[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-2-methoxy-N,N- dimethylbenzene-1-sulfonamide I-731 as white solid. (ES, m/z): [M+1]+: 515; 1H NMR (300 MHz, DMSO-d6) δ 0.33 - 0.45 (m, 2H), 0.57 - 0.70 (m, 2H), 0.80 (d, J = 17.7 Hz, 4H), 2.67 (s, 6H), 3.70 (dq, J = 6.0, 3.0 Hz, 1H), 4.20 (s, 2H), 6.82 (s, 1H), 6.86 - 6.98 (m, 1H), 7.12 (d, J = 5.0 Hz, 1H), 7.20 - 7.36 (m, 3H), 7.40 (s, 1H) , 8.47 (d, J = 5.0 Hz, 1H), 8.65 (s, 1H).Example 113: 1- (4 - [[4-chloro-3 - ([1- [4- ( 2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonyl]-1,4-diazepan-1-yl)ethan-1-one (I-732) Step 1. 4 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy] methyl) - benzene] sulfonyl] -1,4-diazepane-1-carboxylate tert-butyl (Intermediate 732a)

[00701] A 100 mL round bottom flask was charged with a solution of tert-butyl 1,4-diazepan-1-carboxylate (184 mg, 0.92 mmol, 1.5 equiv) in TEA (0.34 mL, 4.0 equiv) and dichloromethane (10 mL) and 4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-cyclopropoxy]methyl)benzene-1-sulfonyl chloride (300 mg, 0.61 mmol, 1.0 equiv) and the solution was stirred for 12 h at room temperature and then concentrated in vacuo. The crude residue was purified by silica gel column chromatography eluting with ethyl acetate/petroleum ether (2:1) to provide 300 mg (75%) of 4 - [[4-chloro-3 - ([1- tert-butyl [4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonyl]-1,4-diazepan-1-carboxylate 732a as a yellow solid. Step 2. 1 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) - benzene] sulfonyl] -1,4-diazepane-1,4 - tert-butyl diazepane (Intermediate 732b)

[00702] A 25 mL round bottom flask was charged with a solution of 4 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) benzene ]sulfonyl] tert-butyl-1,4-diazepane-1-carboxylate (732a, 300 mg, 0.46 mmol, 1.0 equiv) in dichloromethane (10 mL) and trifluoroacetic acid (2 mL) and the resulting solution it was stirred for 2.5 h at room temperature and then concentrated in vacuo. The resulting solution was diluted with 50 ml of ethyl acetate and the organic layer was washed with 2 x 20 ml of sodium bicarbonate, 1 x 20 ml of water and 1 x 20 ml of brine, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. This provided 198 mg (78%) of 1 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) benzene] sulfonyl] -1,4- diazepane 732b as a white solid. Step 3. 1-(4-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonyl]-1,4-diazepan-1 -il) etan-1-one (I-732)

[00703] A 100 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of 1 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin- 3-yl]cyclopropoxy]methyl)benzene]sulfonyl]-1,4-diazepane (732b, 178 mg, 0.32 mmol, 1.0 equiv) and TEA (130 mg, 1.28 mmol, 4.0 equiv) in dichloromethane (10 mg, 0.12 mmol, 0.37 equiv). Acetyl chloride (39 mg, 0.50 mmol, 1.5 eq) was then added dropwise with stirring and the resulting solution was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum and diluted with 100 ml of ethyl acetate. The organic layer was washed with 30 ml of sodium bicarbonate, 30 ml of water and 30 ml of brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by preparative HPLC using the following conditions: Column, Prep PrepBridge C18 OBD Column, 19 mm x 250 mm; mobile phase, water (0.05% NH4OH) and ACN (35% to 58% ACN over 8 min); Detector, UV 254 nm, to deliver 76.2 mg (40%) of 1-(4-[[4-chloro-3-([1[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl )benzene]sulfonyl]-1,4-diazepan-1-yl)etan-1-one I-732 as a white solid. (ES, m/z): [M+1]: 596.20. 1H NMR (300 MHz, DMSO-d6) δ 8.71 (s, 1H), 8.53 (d, J = 5.0 Hz, 1H), 7.66 (dtd, J = 11.3, 8, 4, 2.4 Hz, 2H), 7.54 (dd, J = 5.1, 2.1 Hz, 1H), 7.43 - 7.24 (m, 3H), 7.17 (d, J = 5.0 Hz, 1H), 6.97 (t, J = 7.3 Hz, 1H), 4.40 (s, 2H), 3.65 (tt, J = 6.0, 3.0 Hz , 1H), 3.58 - 3.38 (m, 4H), 3.20 (q, J = 5.5 Hz, 3H), 2.08 (s, 1H), 1.95 (s, 3H) , 1.74 (dp, J = 23.6, 5.9 Hz, 2H), 0.92 (d, J = 7.3 Hz, 4H), 0.63 (d, J = 6.2 Hz, 2H), 0.34 (s, 2H). Example 114: 6 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) benzene] sulfonyl] -2-methoxy-5,6,7, 8-tetrahydro-1,6-naphthyridine (I-733)

[00704] Step 1. 2-chloro-6 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) benzene] sulfonyl] -5.6 ,7,8-tetrahydro-1,6-naphthyridine (Intermediate 733a)

[00705] A 25 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of 4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-hydrochloride yl]cyclopropoxy]methyl)benzene-1-sulfonyl (150 mg, 0.31 mmol, 1.0 equiv), 2-chloro-5,6,7,8-tetrahydro-1,6-naphthyridine hydrochloride ( 537.8 mg, 2.62 mmol, 1.5 equiv) in TEA (0.407 mL, 4.0 equiv) and dichloromethane (10 mL) and the resulting solution was stirred for 10 min at room temperature. The reaction mixture was diluted with water, extracted with 3 x 10 ml of ethyl acetate and the combined layers were concentrated in vacuo. The crude product was purified via silica gel column chromatography eluting with ethyl acetate/petroleum ether to provide 275 mg of 2-chloro-6 - [[4-chloro-3 - ([1- [4- (2 -cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonyl]-5,6,7,8-tetrahydro-1,6-naphthyridine 733a as a yellow solid. Step 2. 6 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) benzene] sulfonyl]-2-methoxy-5,6,7, 8-tetrahydro - 1,6-naphthyridine (I-733)

[00706] A 10 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of (733a, 200 mg, 0.32 mmol, 1.0 equiv) and MeONa (173.54 mg, 10.0 equiv) in dioxane (5.7 mL) and the resulting solution was stirred overnight at 115 °C in an oil bath. The crude product was purified by preparative HPLC using the following conditions: Column, XBridge C18 OBD Prep Column, 19 mm x 250 mm; mobile phase, water (0.05% NH4OH) and ACN (62.0% to 80.0% ACN over 8 min); Detector, UV 254 nm, to provide 34.1 mg (17%) of 6 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) benzene ]sulfonyl]-2-methoxy-5,6,7,8-tetrahydro-1,6-naphthyridine (I-733) as a white solid. (ES, m/z): [M+1]: 618; 1H NMR (300 MHz, DMSO-d6) δ 0.32 (s, 2H), 0.59 (d, J = 6.6 Hz, 2H), 0.79 - 0.94 (m, 4H), 1 .95 (s, 1H), 2.47 (s, 4H), 2.76 (q, J = 15.4, 10.8 Hz, 2H), 3.06 - 3.18 (m, 1H), 3.60 (s, 1H), 3.75 (s, 3H), 4.10 (s, 2H), 4.36 (s, 2H), 6.60 (d, J = 8.3 Hz, 1H ), 6.93 (t, J = 7.3 Hz, 1H), 7.13 (d, J = 5.0 Hz, 1H), 7.29 (q, J = 8.5 Hz, 3H), 7.42 (d, J = 8.5 Hz, 1H), 7.54 (s, 1H), 7.66 (q, J = 8.3 Hz, 2H), 8.50 (d, J = 4 .9 Hz, 1H), 8.68 (s, 1H).Example 115: 6 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl ) naphthyridin-2-ol (I-734)

[00707] A 25 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of 2-chloro-5,6,7,8-tetrahydro-1,6-naphthyridine-6- tert-butyl carboxylate (241 mg, 0.90 mmol, 1.0 equiv) and (4-methoxyphenyl) methanol (185.9 mg, 1.35 mmol, 1.5 equiv) in dioxane (8 mL), followed by addition of potassium tert-butoxide (251.6 mg, 2.24 mmol, 0.8 equiv) and the resulting solution was stirred for 2 h at 115 °C in an oil bath. The reaction mixture was quenched with water, extracted with 3 x 10 mL of ethyl acetate and the combined organic layers were concentrated and purified via silica gel column chromatography eluting with dichloromethane/methanol (10:1) to provide 131 mg (54 %) of 2-[(4-methoxyphenyl)methoxy]-5,6,7,8-tetrahydro-1,6-naphthyridine 734a as a yellow solid. Step 2. 6 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) benzene] sulfonyl]-2-methoxy-5,6,7, 8-tetrahydro - 1,6-naphthyridine (734b)

[00708] A 50 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of 2-[(4-methoxyphenyl)methoxy]-5,6,7,8-tetrahydro-1 ,6-naphthyridine (734a, 131 mg, 0.48 mmol, 1.0 equiv) and 4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl chloride ) benzene-1-sulfonyl (356 mg, 0.73 ± 1.5 mmol, 4.0 equiv) and dichloromethane (9 mL) and the resulting solution was stirred for 30 min at room temperature. The mixture was extracted with 3 x 10 mL of ethyl acetate and the combined organic layers were concentrated. The crude product was purified via silica gel column chromatography eluting with ethyl acetate/petroleum ether (2:1) to provide 198 mg (56%) of 6 - [[4-chloro-3 - ([1- [4-(2cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonyl]-2-[(4-methoxyphenyl)methoxy]-5,6,7,8-tetrahydro-1,6-naphthyridine 734b as a yellow solid. Step 3. 6 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) - benzene] sulfonyl] -5,6,7,8-tetra -hydro- 1,6- naphthyridin-2-ol (I-734)

[00709] A 25 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of 6 - [[4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin- 3-yl]cyclopropoxy]methyl)benzene]sulfonyl]-2-[(4-methoxyphenyl)methoxy]-5,6,7,8-tetrahydro-1,6-naphthyridine (734b, 180 mg, 0.25 mmol, 1.0 equiv) in dichloromethane (9 mL, 1.0 equiv) and trifluoroacetic acid (3 mL, 3.0 equiv). The resulting solution was stirred at room temperature for 30 min. The pH value of the solution was adjusted to 8 with sodium bicarbonate (sat). The resulting solution was extracted with 50 mL of dichloromethane and the organic layers were combined and dried over sodium sulfate and concentrated in vacuo. The crude product was purified by preparative HPLC with the following conditions: Column, Prep PrepBridge C18 OBD Column, 19 mm x 250 mm; mobile phase, water (0.05% NH4OH) and ACN (48% ACN to 65% in 8 min); Detector, UV 254 nm, to deliver 76.7 mg (51%) of 6 - [[4-chloro-3 - ([1- [4- (2- cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) benzene ]sulfonyl]-5,6,7,8-tetrahydro-1,6-naphthyridine-2-ol I-734 as a white solid. (ES, m/z): [M+1] : 604; 1H NMR (300 MHz, Methanol-d4) δ 0.39 (s, 2H), 0.61 (d, J = 6.2 Hz, 2H), 1.01 (d, J = 8.8 Hz, 4H ), 2.69 (d, J = 6.1 Hz, 2H), 3.35 (t, J = 5.7 Hz, 2H), 3.52 - 3.61 (m, 1H), 4.01 (s, 2H), 4.47 (s, 2H), 6.37 (d, J = 9.3 Hz, 1H), 6.96 - 7.08 (m, 1H), 7.18 - 7, 41 (m, 5H), 7.57 (d, J = 9.1 Hz, 2H), 7.72 (dd, J = 8.3, 2.3 Hz, 1H), 8.48 (d, J = 5.1 Hz, 1H), 8.66 (s, 1H).

[00710] Example 116: 1- (4- [N-methyl [4-chloro-3 - ([1- [4- (2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy] methyl) benzene] sulfonamido] (d8 ) butyl) -3- [(2S, 3R, 4S, 5R) -1,3,4,5,6-pentahydroxy-hexan-2-yl] urea (I-735)

[00711] A 100 mL 3-neck round bottom flask was purged and kept under an inert nitrogen atmosphere and charged with a solution of 2-methylpropan-2-ol (9.5 g, 128.17 mmol, 1. 0 equiv) in pyridine (12.8 mL) and dichloromethane (22 mL). Phenyl chloroformate (20 g, 127.74 mmol, 1.0 equiv) was then added dropwise with stirring at room temperature for 60 min and the resulting solution was stirred for 3 h at room temperature. The reaction was then cooled by adding 32 mL of water and diluted with 100 mL of DCM. The resulting mixture was washed with 2 x 32 ml of H2M2SO4 and 1 x 100 ml of brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by distillation under reduced pressure (2 mmHg) and the fraction collected at 90°C. from 17 g (69%) of tert-butyl phenyl carbonate 735a as colorless oil. Step 2. Tert-butyl N-[4-amino(d8)butyl] carbamate (Intermediate 735b)

[00712] A 250 mL round bottom flask was charged with a solution of tert-butyl phenyl carbonate (735a, 574.2 mg, 2.96 mmol, 1.0 equiv), (d8) 1-butane dihydrochloride 1,4-diamine (500 mg, 2.96 mmol, 1.0 equiv) and sodium bicarbonate (994 mg, 11.83 mmol, 4.0 equiv) in ethanol (45 mL) and the resulting solution was stirred for overnight at 80° C in an oil bath and then concentrated under vacuum. The crude residue was dissolved in 50 mL of H2O and the pH value of the solution was adjusted to 3.0 with hydrogen chloride (2 mol/L). The resulting solution was washed with 4 x 80 ml of dichloromethane. The pH of the aqueous layer was adjusted to 11.0 using sodium hydroxide (2 mol/L) and the resulting solution was extracted with 5 x 100 mL of dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated to provide 285 mg (49%) of tert-butyl N-[4-amino(d8)butyl] carbamate 735b as orange oil. Step 3. Tert N-(4-[[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido](d8)butyl)carbamate -butyl (Intermediate 735c)

[00713] A 50 mL 3-neck round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of tert-butyl N-[4-amino-(d8)-butyl]carbamate (735b, 285 mg, 1.45 mmol, 1.0 equiv) in dichloromethane (20 mL) and TEA (0.821 mL). 4-Chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-cyclopropoxy] methyl)benzene-1-sulfonyl chloride (1.29 g, 2.63 mmol, 1.81 equiv) was then added dropwise with stirring at 15-25°C over 15 min and the resulting solution was stirred overnight at room temperature. The reaction mixture was diluted with 20 mL of DCM, quenched by adding 50 mL of water and extracted with 2 x 50 mL of ethyl acetate. The combined organic layers were washed with 100 mL of brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified via silica gel column chromatography eluting with ethyl acetate/petroleum ether (1:1) to provide 650 mg (69%) of N-(4-[[4-chloro-3-( tert-Butyl [1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]-(d8)-butyl)carbamate 735c as a white solid. Step 4. N-(4-[N-methyl [4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]-(d8)- butyl) tert-butyl carbamate (Intermediate 735d)

[00714] A 25 mL 3-neck round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of N-(4-[[4-chloro-3-([1-[4-( tert-butyl 2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]-(d8)-butyl)carbamate (780 mg, 1.20 mmol, 1.0 equiv), methanol (0.105 mL) and PPh3 (680 mg, 2.59 mmol, 2.16 equiv) in tetrahydrofuran (8 mL). A solution of DEAD (0.4 mL) in toluene (0.73 mL) was then added dropwise with stirring at 0-5°C for 20-30 min and the resulting solution was stirred overnight at room temperature and concentrated under vacuum. The crude residue was purified via silica gel column chromatography eluting with ethyl acetate/petroleum ether (1:1) to provide 770 mg (97%) of N-(4-[N-methyl[4-chloro- tert-Butyl 3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]-(d8)-butyl)carbamate 735d as a white solid. Step 5. N-[4-amino(d8)butyl]-4-chloro-3-[1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-N-methylbenzene-1-sulfonamide (Intermediate 735e)

[00715] A 100 mL round bottom flask was charged with a solution of N-(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl tert-butyl]cyclopropoxy]methyl)benzene]sulfonamido]-(d8)-butyl)carbamate (735d, 770 mg, 1.16 mmol, 1.0 equiv) in TFA/DCM (5/20 mL) and the solution resultant was stirred for 1 h at room temperature. The pH value of the solution was adjusted to ~9.0-10.0 with sodium bicarbonate (100%) and the resulting solution was extracted with 3 x 200 mL of ethyl acetate. The combined organic layers were washed with 1 x 100 mL of brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by silica gel column chromatography eluting with dichloromethane/methanol (10:1) to provide 591 mg (90%) of N-[4-amino-(d8)-butyl]-4-chloro-3 -([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-N-methylbenzene-1-sulfonamide 735e as a white solid. Step 6. 1-(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido](d8)butyl) -3- [(2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea (I-735)

[00716] A 100 mL round bottom flask was charged with a solution of N-[4-amino-(d8)-butyl]-4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin -3-yl]cyclopropoxy]methyl)-N-methylbenzene-1-sulfonamide (735e, 1.034 g, 1.83 mmol, 1.0 equiv) in N,N-dimethylformamide (18.3 mL) and DSC (516. 2mg). The mixture was stirred at room temperature for 1 hour and then (2R, 3S, 4R, 5S)-5-aminohexane-1,2,3,4,6-pentol (995 mg, 5.49 mmol, 3.0 equiv). The resulting solution was stirred for 1 h at room temperature and then for a further 3 h at 60 °C in an oil bath. The reaction mixture was diluted with 25 mL of H2O and extracted with 5 x 50 mL of ethyl acetate. The combined organic fractions were dried over anhydrous sodium sulfate, filtered and concentrated. The crude residue was purified by preparative HPLC chromatography eluting with ACN/H2O (0 to 40%) to provide 0.84 g (59%) of 1-(4-[4-N-methyl[4-chloro-3- ([1-[4-(2-cyclopropoxyphenyl)pyridin-3- yl]cyclopropoxy]methyl)benzene]sulfonamido]-(d8)-butyl)-3-[(2S,3R,4S,5R)- 1,3 ,4,5,6-pentahydroxyhexan-2-yl]urea I-735 as a white solid. (ES, m/z): [M+1]: 771; 1H NMR (400 MHz, Methanol-d4) δ 0.34 - 0.43 (m, 2H), 0.56 - 0.66 (m, 2H), 0.95 - 1.04 (m, 4H), 2.66 (s, 3H), 3.52 - 3.72 (m, 6H), 3.73 - 3.89 (m, 2H), 3.96 (dd, J = 4.9, 2.8 Hz, 1H), 4.47 (s, 2H), 7.02 (td, J = 7.2, 1.6 Hz, 1H), 7.20 - 7.30 (m, 2H), 7.31 - 7.43 (m, 2H), 7.49 - 7.59 (m, 2H), 7.64 (dd, J = 8.5, 2.2 Hz, 1H), 8.49 (d, J = 5.1 Hz, 1H), 8.66 (d, J = 0.7 Hz, 1H).Example 117: 3-(4-[4-[N-[4-chloro-3-([1- [4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)-1-[2- (2-[2-[([4-[([2-[2-( 2-[[(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamoyl]amino] ethoxy)ethoxy]ethyl]c arbamoyl)amino]butyl]carbamoyl)amino]ethoxy]ethoxy)ethyl]urea(I-736)

[00717] An 8 mL vial was charged with a solution of N-(4-aminobutyl)-4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl) -N-methylbenzene-1-sulfonamide (389e, 183.2 mg, 0.33 mmol, 1.0 equiv) and DSC (93 mg, 1.1 equiv) in N,N-dimethylformamide (3.3 mL). The mixture was stirred at room temperature for 1 hour and then tert-butyl [2-[2-(2-aminoethoxy)ethoxy]ethyl]carbamate (270 mg, 1.09 mmol, 3.0 equiv) was added. . The resulting solution was stirred for 60 minutes at 60°C in an oil bath. The reaction was then quenched by the addition of 4.1 ml of 10% Na2CO3 and extracted with 3 x 20 ml of ethyl acetate and the combined organic layers were concentrated in vacuo. The crude residue was purified via silica gel column chromatography eluting with dichloromethane/methanol (5:1). This resulted in 273 mg (100%) of N-[2-[2-(2-[[(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin tert-butyl -3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamoyl]amino]ethoxy)ethoxy]ethyl]c arbamate 736a as a yellow solid. Step 2. 3-[2-[2-(2-aminoethoxy)ethoxy]ethyl]-1-(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin -3- yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)urea (Intermediate 736b)

[00718] A 250 mL round bottom flask was charged with a solution of N-[2-[2-(2-[[(4-[N-methyl[4-chloro-3-([1-[4 tert-butyl -(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamoyl]amino]ethoxy)ethoxy]ethyl]c tert-butyl arbamate (736a, 273 mg, 0.33 mmol, 1 .0 equiv) in dichloromethane (8 mL, 10.0 equiv) and trifluoroacetic acid (0.8 mL, 1.0 equiv) and the resulting solution was stirred for 1 h at room temperature. The pH value of the solution was adjusted to ~9.0-10.0 with sodium bicarbonate and then extracted with 3 x 20 mL of ethyl acetate. The combined organic layers were concentrated in vacuo and the crude residue was silica gel column chromatography purified via elution with dichloromethane/methanol (5:1) to provide 164 mg (68%) of 3-[2-[2-( 2-aminoethoxy)ethoxy]ethyl]-1-(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido ]butyl)urea 736b as a yellow solid. Step 3. 3-(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)-1- [2-(2-[2-[([4-[([2-[2-(2-[[(4-[N-methyl[4-chloro-3-([1-[4-(2 -cyclopropoxyphenyl)pyridin-3- yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamoyl]amino]ethoxy)ethoxy]ethyl]carbamoyl)amino]butyl]carbamoyl)amino]ethoxy]ethoxy)ethyl]urea (I- 736)

[00719] To a solution of 3-[2-[2-(2-aminoethoxy)ethoxy]ethyl]-1-(4-[N-methyl[4-chloro-3-([1-[4-(2 -cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-benzene]sulfonamido]butyl)urea (736b, 50 mg, 0.07 mmol, 1.0 equiv) in N,N-dimethylformamide (0.46 mL) was 1,4-diisocyanatobutane (4.3 mg, 0.03 mmol, 0.5 equiv) was added and the resulting solution was stirred for 1 h at 60°C in an oil bath. The resulting mixture was concentrated in vacuo and the crude residue was purified via silica gel column chromatography eluting with ACN:H2O (0% to 35%) to provide 30 mg (27%) of 3-(4-[N- [4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)-1-[2-(2-[2-[([ 4-[([2-[2-(2-[[(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl )benzene]sulfonamido]butyl)carbamoyl]amino]ethoxy)ethoxy]ethyl]c arbamoyl)amino]butyl]carbamoyl)amino]ethoxy]ethoxy)ethyl]urea I-736 as a white solid. (ES, m/z): [M+1] :1599; 1H NMR (400 MHz, Methanol-d4) δ 0.39 (d, J = 2.8 Hz, 2H), 0.57 - 0.66 (m, 2H), 0.94 - 1.03 (m, 4H), 1.44 - 1.60 (m, 6H), 2.66 (s, 3H), 2.96 (t, J = 6.5 Hz, 2H), 3.08 - 3.17 (m , 3H), 3.24 - 3.35 (m, 7H), 3.47 - 3.63 (m, 9H), 4.47 (s, 2H), 7.01 (td, J = 7.2 , 1.6 Hz, 1H), 7.19 - 7.29 (m, 2H), 7.31 - 7.43 (m, 2H), 7.51 - 7.58 (m, 2H), 7, 64 (dd, J = 8.2, 2.3 Hz, 1H), 8.48 (d,J = 5.0 Hz, 1H), 8.66 (s, 1H).Example 118: 3-(4 -[N-[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)-1-[2-(2-[2 -[([2-[2-(2-[[(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl) benzene]sulfonamido]butyl)carbamoyl]amino]ethoxy)ethoxy]ethyl]arbamoyl)amino]ethoxy]ethoxy)ethyl]urea (I-737) Step 1. N-[2-[2-(2-[[(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy] methyl)benzene]sulfonamido]butyl)carbamoyl]amino]ethoxy)ethoxy]ethyl]-1H-imidazole-1-carboxamide (Intermediate 737a)

[00720] An 8 mL vial was charged with a solution of CDI (33.3 mg, 0.21 mmol, 3.0 equiv) and 3-[2-[2-(2-aminoethoxy)ethoxy]ethyl]- 1-(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-benzene]sulfonamido]butyl)urea (736b, 50 mg, 0.07 mmol, 1.0 equiv) in tetrahydrofuran (0.45 mL) and the resulting solution was stirred for 1 h at 30°C in an oil bath and then concentrated in vacuo. The crude residue was purified by silica gel column chromatography eluting with dichloromethane/methanol (1:5) to provide 38 mg (67%) of N-[2-[2-(2-[[(4-[N -methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamoyl]amino]ethoxy)ethoxy]ethyl]- 1H- imidazole-1-carboxamide 737a as a yellow solid. Step 2. 3-(4-[N-[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)-1-[ 2-(2-[2-[([2-[2-(2-[[(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3 - yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamoyl]amino]ethoxy)ethoxy]ethyl]c arbamoyl)amino]ethoxy]ethoxy)ethyl]urea (I-737)

[00721] A 50 mL round bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of 3-[2-[2-(2-aminoethoxy)ethoxy]ethyl]-1-(4-[ N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)-benzene]sulfonamido]butyl)urea (736b, 38 mg, 0.05 mmol , 1.0 equiv) and N-[2-[2-(2-[[(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3- yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamoyl]amino]ethoxy)ethoxy]ethyl]-1H-imidazole-1-carboxamide (737a, 34 mg, 0.04 mmol, 1.0 equiv) in tetrahydrofuran (1 ml) and the resulting solution was stirred for 2 h at 70°C in an oil bath and then concentrated in vacuo. The crude residue was purified by silica gel column chromatography eluting with ACN:H2O (0%-30%) to provide 23.7 mg (31%) of 3-(4-[N-[4-chloro-3- ([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)-1-[2- (2-[2-[([2-[2-(2 -[[(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamoyl]amino]ethoxy )ethoxy]ethyl]c arbamoyl)amino]ethoxy]ethoxy)ethyl] urea I-737 as a white solid. (ES, m/z): [M+1]+ : 1485; 1H NMR (400 MHz, Methanol-d4) δ 0.34 - 0.43 (m, 2H), 0.56 - 0.66 (m, 2H), 0.94 - 1.05 (m, 4H), 1.31 (d, J = 17.8 Hz, 1H), 1.53 (tdd, J = 14.7, 7.3, 3.9 Hz, 4H), 2.66 (s, 3H), 2 .96 (t, J = 6.6 Hz, 2H), 3.13 (t, J = 6.6 Hz, 2H), 3.29 (d, J = 5.1 Hz, 1H), 3.48 - 3.63 (m, 9H), 4.47 (s, 2H), 4.74 (s, 1H), 7.01 (td, J = 7.2, 1.6 Hz, 1H), 7, 17 - 7.29 (m, 2H), 7.30 - 7.42 (m, 2H), 7.48 - 7.58 (m, 2H), 7.63 (dd, J = 8.3, 2 .4 Hz, 1H), 8.48 (d, J = 5.1 Hz, 1H), 8.66 (s, 1H). Example 119: (2R, 3S, 4R, 5S)-5-[ Propanoate [(4-[N-methyl[4-chloro-3-([1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamoyl]amino]-1, 2,4,6-tetrakis(propanoyloxy)hexane-3-yl (I-738)

[00722] A 100 mL three-neck round-bottom flask purged and maintained under an inert nitrogen atmosphere was charged with a solution of 1-(4-[4-[N-[4-chloro-3-([1 -[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)-3-[(2S,3R,4S,5R)-1,3,4,5,6-penta -hydroxyhexan-2-yl]urea (I-389, 200 mg, 0.26 mmol, 1.0 equiv) in pyridine (10 mL). Propanoyl propanoate (4 mL, 3.0 equiv) was then added at 10°C and the resulting solution was stirred overnight at room temperature and concentrated in vacuo. The crude product was purified by preparative HPLC with the following conditions: Column, XBridge Prep C18 OBD 5um Column, 19 x 150 mm; mobile phase, water (0.05% TFA) and ACN (54.0% to 74.0% ACN over 8 min); Detector, UV 220 nm, to provide 212.6 mg (78%) of (2R,3S,4R,5S)-5-[[(4-[N-methyl[4-chloro-3-([1 -[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy]methyl)benzene]sulfonamido]butyl)carbamoyl]amino]-1,2,4,6-tetrakis(propanoyloxy)hexane-3-yl I-738 as an off-white solid. [M+1]+: 1043; 1H NMR (400 MHz, Methanol-d4) δ 8.98 (s, 1H), 8.77 (d, J = 5.8 Hz, 1H), 7.84 (d, J = 5.8 Hz, 1H ), 7.68 (dd, J = 8.4, 2.3 Hz, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.55 - 7.36 (m, 4H) , 7.11 (td, J = 7.4, 1.1 Hz, 1H), 5.50 (dd, J = 7.4, 4.1 Hz, 1H), 5.37 (dd, J = 5 .7, 4.1 Hz, 1H), 5.22 - 5.13 (m, 1H), 4.53 (s, 2H), 4.36 - 4.25 (m, 2H), 4.21 - 4.00 (m, 3H), 3.66 (tt, J = 6.0, 2.9 Hz, 1H), 3.15 (t, J = 6.6 Hz, 2H), 2.99 (t , J = 6.6 Hz, 2H), 2.70 (s, 3H), 2.50 - 2.27 (m, 10H), 1.61 - 1.50 (m, 4H), 1.25 - 1.06 (m, 21H), 0.73 - 0.64 (m, 2H), 0.44 (q, J = 5.4, 4.4 Hz, 2H).

[00723] Compounds I-739 to I-780 (Table 17) were prepared from known commercial base materials or the appropriate intermediates disclosed herein, using methods from the examples specified in Table 17 and methods generally known to those skilled in the art. Table 17. Compounds I-739 to I-780

[00724] A primary cell-based assay used HEK293 cells stably transfected with a gene encoding human TGR5. Cells were treated with candidate TGR5 activators and assessed for increased intercellular cAMP levels.

[00725] TGR5-mediated cAMP generation was measured using a homogeneous time-resolved fluorescence detection (HTRF) method (Cisbio). Test compounds were dissolved in DMSO to a final concentration of 10 mM. 3-fold serial dilutions of the stock solution were made in DMSO, and these solutions were diluted 100-fold in Hanks' Balanced Salt Solution supplemented with 10 mM HEPES pH 7.4, 0.003% Tween 20 and 0.5 mM isobutylmethylxanthine. Five microliters of diluted test compounds were added to the wells of a black 384-well plate.

[00726] Cells grown overnight at 37° C/5% CO2 were harvested and resuspended in Hanks' Balanced Salt Solution containing 10 mM HEPES at a concentration of 50,000 cells/mL. Five microliters (2500 cells) were dispensed into each well of the 384-well plate containing compound dilutions and incubated at 37°C for 30 minutes. Each compound was tested in duplicate at 12 concentrations ranging from 0.05 nM to 10 μM.

[00727] After incubation with the test compounds, cAMP was detected by successively adding 5 μL each of cAMP labeled with the dye modified allophycocyanin d2 (cAMP-d2) and crypt-labeled anticAMP in lysis buffer, and reading HTRF according to the manufacturer's instructions.

[00728] A standard curve was used to convert the raw HTRF data into [cAMP]. The cAMP concentration was plotted against log [test compound] and the resulting curves were fitted to a 3-parameter logistic equation using GraphPad Prism to determine pEC50 (the negative log of EC50) and the magnitude of the response. The magnitude of the maximum response was typically between 50 and 200% of the maximum response elicited by a reference compound that had a maximum response similar to that elicited by lithocholic acid. The results of this assay are presented in Table 18. Table 18: pEC50 Values of Representative Compounds* *pEC50 values are expressed as the following ranges: A is a pEC50 of >7, B is a pEC50 of 6 to 6.9, C is a pEC50 of 5.0 to 5.9, D is a pEC50 of 4.3 to 4.9.

Example 121: In vivo measurement of diarrhea in a chemotherapy-induced diarrhea model

[00729] Four groups of adult female CD-1 mice on normal chow were dosed with the following BID starting on day 1: 2 groups, vehicle (10% hydroxypropyl-p-cyclodextrin in PBS; PO; 5 mL/kg); 1 group, compound I-388 at 30 mg/kg in vehicle (PO; 5 mL/kg); and 1 group, teduglutide 0.4 mg/kg (American Peptide, Sunnyvale, CA; reconstituted in PBS; SQ; 10 mL/kg) 0.4 mg/kg SQ. On Days 5-11, groups of mice also received QD IP injections (5 mL/kg) of the following treatments: first group vehicle, PBS and remaining groups, 5-fluorouracil (5-FU) 60 mg/kg (Fresenius Kabi USA, Lake Zurich, IL) diluted in PBS to induce mucositis with diarrhea. Body weight was measured throughout the study and fecal form was scored on day 11-13 of the study according to the following scale: 0, normal stool; 1, slightly wet and loose stools; 2, wet, unformed feces with moderate perianal hair color; 3, watery stools with severe perianal hair staining.

[00730] As shown in Figure 1 (FIG. 1), I-388 significantly improved the cumulative fecal shape score (FFS), as did Teuduglutide in mice with 5-FU-induced diarrhea. All mice were dosed on day 1-13 with vehicle, with 0.4 mg/kg teduglutide, or with 30 mg/kg compound I-388 (vehicle and compound I-388: PO, 5 mg/kg and teduglutide : SQ, 10 mL/kg). PBS or 5-FU at 60 mg/kg (used to induce mucositis and diarrhea) were administered interperially (IP; 5 mL/kg) on days 5-11. FFS were measured on days 11–13 and summed for cumulative FFS (animals that did not defecate within the 30 min observation period in each session did not receive a score and were excluded from analysis). These data are presented as median values and analyzed for statistical significance using the Kruskal-Wallis test followed by the Dunn test.

Example 122: In Vivo Measurement of Colon Length, Weight, and Inflammation in an Inflammatory Bowel Disease Model

[00731] Six week old female C57BL/6 were acclimatized for 2 days. Starting on Day -2, 5 groups of mice were dosed PO (mL/kg) BID with 1) vehicle (10% HPCD); 2) vehicle; 3) vehicle; mice had sitagliptin (3.6 g/l for a dose of ~800 mg/kg/day) added to their drinking water; 4) I-389 30 mg/kg; or 5) I-389 30 mg/kg; mice had sitagliptin (3.6 g/l for a dose of ~800 mg/kg/day) added to their drinking water. On Day 0, mice in groups 2-5 were placed in drinking water containing 1.5% DSS to induce colitis. Note: Groups 3 & 5 were drinking water containing both DSS and sitagliptin. On day 7, mice were removed from DSS treatment and given regular drinking water (Groups 1, 2, and 4) or drank water with sitagliptin (Groups 3 and 5). On day 8, mice were transferred to a separate container for DAI scoring, which consists of evaluating stool consistency, blood in stool, incidence of rectal prolapse, and body condition according to the scoring system shown in Table 19. DAI score is a sum of each individual score in each category (columns) for a single animal. Mice were sacrificed, blood was collected for plasma, colons were removed for length measurement, cytokine analysis and histological staining, pathological analysis and scoring of colon tissue damage. Colonic tissue damage was classified according to the microscopic changes observed based on the following scheme: 0 = no significant change, 1 = minimal, 2 = mild, 3 = moderate and 4 = severe. Parametric data for each group are presented as mean ± SEM. Statistical analysis was performed using one-way ANOVA followed by the Holm-Sidak multiple comparison test. Statistical significance versus DSS/vehicle is marked as *, P <0.05; **, P <0.01, ***, P <0.001 and ****, P <0.0001. Statistical significance versus DSS/I-389 is marked as fft, P < 0.001. Nonparametric data for each group are shown as a dot blot with median (line). Statistical analysis was performed using the Kruskal-Wallis test, followed by Dunn's test, to detect differences between groups. Table 19: Disease Activity Index Scoring Scheme

[00732] Treatment of mice with I-389 combined with sitagliptin or treatment with sitagliptin alone partially abrogated DSS-induced colonic damage. Compared to the vehicle/DSS group, the I-389 + sitagliptin/DSS group had a significantly lower disease activity score (5.6 versus 2.6, respectively); Figure 2 (FIG. 2), increased colon length (4.7 ± 0.1 versus 6.0 ± 0.2 cm, respectively); Figure 3 (FIG. 3), KC/Gro colon cytokine level (56.5 ± 14.6 versus 690.5 ± 124.8 pg/100 μg of tissue, respectively); Figure 4 (FIG. 4) and colon histology score (4.0 versus 2.5, respectively); Figure 5 (FIG. 5). Sitagliptin/DDS also had a significant decrease in DAI score (3.0) and increase in colon length (5.6 ± 0.2 cm), but to a lesser extent than when it was combined with I-389.

Example 123: Pharmacodynamic Effects on Acute Phosphate Uptake in Mice

[00733] The compounds are tested for the ability to reduce the appearance of circulating radiolabeled phosphate subsequent to administration to the alimentary canal in mice. The rate of accumulation of radiolabeled phosphate tracer in the blood of mice is taken as a surrogate for the rate of intestinal absorption of a phosphate meal from the gastrointestinal tract. To this end, circulating radiolabeled phosphate is monitored following intragastric co-administration to mice of a phosphate tracer meal together with a compound of Formula (I') or Formula (I). However, since some of the compounds tested potentially possessed properties that could impede this assay, such as possible gastrointestinal motility effects (e.g., delaying gastric emptying) or being purposely chemically unstable in the gastrointestinal tract, direct intraduodenal bolus administrations of Phosphate are also sometimes carried out.

[00734] 8-week-old male Sprague-Dawley mice are purchased from Charles River Laboratories (Hollister, CA). To allow for blood sampling, mice are purchased with catheters surgically implanted in the jugular vein by the seller. For studies requiring intraduodenal administration, an additional catheter is surgically implanted by the vendor to allow direct infusion into the lumen of the duodenum. Mice are fed a regular cereal-based chow (Harlan Teklad, Madison, WI; 2018 Teklad Global 18% Protein Rodent Diet) containing 0.65% P, 1% Ca; 1.5 IU/g of vitamin D3 and given water ad libitum leading up to the study.

[00735] After an overnight fast, mice are given a phosphate solution containing [33P] orthophosphate (PerkinElmer, Waltham, MA) as a tracer with or without test articles dispersed in the solution at the indicated dose. This dosing solution typically contains 8 mM monobasic sodium phosphate (1.25 μCi [33P] orthophosphate/μmol), 4 mM calcium chloride, 0.4% (w/v) hydroxypropylmethcellulose, and 2% (w /v). Dosing solutions are prepared in water for an intragastric tube at 10 ml/kg and in saline if administered intraduodenally using a previously implanted catheter at a 5 ml/kg bolus.

[00736] Blood is sampled from the jugular vein through catheters implanted from conscious mice after dosing and the radioisotope associated with the resulting plasma is determined by scintillation counting. The relative amount of phosphate absorption from the administered dose to plasma is assessed using body weight estimation of total circulating plasma. See Bijsterbosch et al. Experience. 37: 381-382, 1981 (The plasma volume of the Wistar rat in relation to the body weight). The comparative amount of phosphate uptake at 15 min post-dose for each group (n = 6) is expressed as a percentage relative to the study vehicle group (n = 6) as mean ± SEM. Statistical comparisons of each test group means compared to the vehicle group mean are determined by one-way analysis of variance followed by Dunnett test analysis. posthoc and P <0.05 is accepted as statistically significant (ns, not significant; *, P <0.05; ** P <0.01; and *** P <0.001).

Example 124: Tissue flow rate measurements using a wear chamber

[00737] Segments of duodenum and jejunum are immediately removed from anesthetized animals and opened along the mesenteric line and fixed on a Pyrex plate with the mucosal surface facing up. Epithelial tissues are stripped from muscle layers and mounted in computer-controlled Ussing chambers (National Physiology Instrument, California) with an exposed area of 100 mm.2. Tissues are incubated on both sides with 13 mL of an isotonic buffer solution (pH 6.0 or pH 7.4) containing (mmol/L) NaCl 125.4, KCl 5.4, CaCl21.2 NaHCO321, Na2HPO40, 3 NaH2PO41.2. Functional viability and tissue integrity at the beginning and end of flow measurements are ensured by measuring the short circuit current (Isc) in response to theophylline (10 mM serous) or glucose (10 mM mucosa) or L- alanine (5 mM mucosa).

[00738] For calculations of unidirectional Pi flow rates (Jms: flow from the mucosal side to the serosal side, Jsm: flow in the opposite direction), 185 KBq [33P]-orthophosphate (370 MBq/mL, Perkin-Elmer) and compounds test are added to one side of the fabric. Samples (0.1 ml) are taken from the marked side 20 minutes later and subsequently at at least three 10 min intervals from the unmarked side (0.5 ml) of the Ussing chamber. All samples taken from the unlabeled side are replaced with equal volumes of isosmotic bath fluid. Net fluxes (Jnet) are calculated as differences between Jms and Jsm of paired tissues whose conductances do not differ by more than 25%. In another series of experiments, flow measurements are made before and after the addition of arsenate (mucosa) or ouabain (serosal) to the bath solution. Radioactivity measurements are measured on a TopCount liquid scintillation counter (Perkin Elmer).

Example 125: In Vitro - Ex Vivo Assays

[00739] Segments of duodenum and jejunum (5 cm) are removed from animals anesthetized with sodium pentobarbitone, washed with ice-cold 0.9% saline and everted onto glass rods. Samples are securely mounted on the rod and pre-incubated for 5 min at 37 °C in oxygenated buffer, pH 7.4 or 6.0, containing in mM: hydroxyethylpiperazine-N'-2-ethanesulfonic acid 16, glucose 10, KCl 3.5, MgSO4 10, CaCl2 1, NaCl 125, followed by 2 min incubation in the same buffer containing 100 mM 33Pi (33Pi specific activity 1.85 MBq/mL) and test compounds. The buffer is rapidly agitated using a magnetic bar to minimize the effects of static water layers on the mucosal surface.

[00740] Absorption is terminated by exposing the tissue for 10 minutes at room temperature to phosphate-buffered saline containing a 10-fold excess of non-radioactive phosphate. This procedure is followed by a further 10 minutes of washing in phosphate buffered saline at room temperature and the samples are then dried and recorded. Samples are digested overnight in Protosol (PerkinElmer). Scintillation counting of the digested sample and initial absorption solution allows calculation of tissue phosphate retention (in nmol/g).

Example 126: Inhibition of Sodium and Phosphate Absorption in the Intestine

[00741] To evaluate the ability of examples of selected compounds of Formula (I') or Formula (I) to inhibit phosphate absorption from the intestinal lumen, the balance of phosphate intake and excretion is measured in mice. Eight-week-old Sprague Dawley mice are purchased from Charles River Laboratories (Hollister, CA) and acclimatized for at least 6 days with free access to food and water. During this time and throughout the study, mice can be fed a standard diet (Harlan Teklad, Madison, WI; 2018 Teklad Global 18% Protein Rodent Diet) or a purified egg purified diet consisting of 0.6% Ca and 0.35 or 0.6% phosphorus. (Harlan Teklad; TD.84122 and TD.130318, respectively).

[00742] One day before the start of the study, mice are acclimated to individual metabolic cages with free access to water and a powdered version of the diets listed above. Animals are dosed approximately 1 hour before the onset of the dark phase, whether determined PO to 10 ml/kg with an effective dose of the test article or through food mixed with drug) based on the daily mass of chow mice for consumption. With both dosing paradigms, each mouse receives free access to water and an aliquot of powdered chow for each day they are housed in the metabolic cage that is the average daily chow. Ad Libitum consumption for this type of chow, for the same type of mice (i.e., 8-week-old male mice consume an average of 18 g/d of the purified diets listed above). This is done to reduce variability and simplify subsequent 24-hour measurements of consumption and excretion. Daily measurements of water and feed consumption, as well as daily urine and feces collections, occur on 1 to 4 consecutive days.

[00743] The phosphate, sodium and potassium content of urine samples is determined by ion chromatography. Urine samples are processed by gravimetric volume determinations, followed by acidification with 6N HCl. Acidified samples are briefly centrifuged (3,600 x g) and supernatants are then diluted with 10 mM HCl. The diluted samples, calibration standards (Sigma/Fluka Analytical) and QC samples (in-house prepared standards) are filtered before injection into an ion exchange chromatography system (Dionex ICS-3000). Sodium and potassium are resolved using an isocratic method consisting of a 25 mM methanesulfonic acid mobile phase and a Dionex CS12A cation exchange analytical column. Phosphate is resolved using an isocratic method consisting of a 35 mM potassium hydroxide mobile phase and a Dionex AS18 ion exchange analytical column. Quantitative analysis is performed using Dionex Chromeleon software. All sample concentrations are interpolated from a calibration curve based on chromatographic peak areas.

[00744] The phosphate, sodium, calcium and potassium contents of each 24-hour fecal sample are determined by atomic emission spectroscopy. Dried fecal pellets or a representative sample of dried homogenized feces are digested with repeated additions of concentrated nitric acid and hydrogen peroxide for 2-3 hours at 65-95° C. The sample solutions are then diluted with 1% nitric acid before analysis with an atomic emission spectrometer (Agilent 4100 MP-AES) at the following element emission wavelengths: calcium (422.673 nm), sodium (588.995 nm), potassium (766.491 nm) and phosphorus (214.915 or 213.618 nm) . A cesium solution is used as an ionization buffer and an internal standard. Data analysis is performed using Agilent MP Expert software.

[00745] The daily production of phosphate in urine and feces in relation to the P consumed in the diet for each animal on each day measured is calculated. The percentage of inhibition of phosphorus absorption is expressed by determining the reduction of these ratios compared to the control group (animals without drug in the diet). This can also be done with other ions of interest. If there are multiple days tested, these may represent replicates for measuring steady-state phosphate balance for each mouse, in which case regular daily intake by the animals is a prerequisite. The increase in fecal phosphate with an approximate concomitant decrease in urinary P to maintain a neutral balance in the mice is an indication of an overall decrease in phosphate absorption in mice treated with example compounds (i.e., compounds of Formula (I') or Formula (I)).

Example 127: Effects in a mouse model of chronic kidney disease (CKD).

[00746] To evaluate the ability of selected example compounds of Formula (I') or Formula (I) to impact the soft tissue calcification often associated with later stages of CKD, the 5/6 nephrectomy mouse model (5/6 Nx) is used to examine mineral homeostasis in a diseased state. A commonly used model to study various aspects of CKD, the 5/6Nx mouse is typically not hyperphosphatemic unless challenged with dietary phosphate (See Shobeiri et al. Am J Nephrol. 31:471-481, 2010, Vascular Calcification in Animal Models of CKD: A Review). Therefore, to ensure efficient and steady progression of phosphatemic vascular calcification in these animals, a combination of dietary enhanced bioavailable phosphate and vitamin D3 treatment is implemented as adapted from the protocol developed by the Lopez group (See Lopez et al. J. Am. Soc . Nephrol. 17: 795-804, 2006. Calcimimetic R-568 Decreases Extraosseous Calcifications in Uremic Rats Treated with Calcitriol).

[00747] Male nephrectomized Sprague-Dawley 5/6 mice are purchased from Charles River Laboratories (Hollister, CA) with surgical procedures performed by the seller. Reduction of functional renal mass is achieved by two surgeries: sub-total nephrectomy of the left kidney, followed by a 1-week recovery before non-total nephrectomy of the right kidney. After a 3-day recovery period from the second surgery, mice are transported to the testing facility at 9 weeks of age.

[00748] Upon arrival and throughout the study, mice are fed a purified powdered diet consisting of 0.9% inorganic phosphorus (P) and 0.6% Ca (TD.10809, Harlan-Teklad, Madison , WI). Maternal serum is obtained by retro-orbital or tail vein bleeding and only animals with serum creatinine levels of 0.9 to 1.2 mg/dl are included in the study with groups (n = 12) stratified based on creatinine. serum and body weight. Mice enrolled in treatment groups are treated with drug on the same diet as the vehicle group described above. Additionally, a regimen of calcitriol (active vitamin D3 80 ng/kg i.p.) administration 3 times per week is initiated.

[00749] Renal function, phosphate status as well as other parameters are monitored weekly with appropriate serum marker measurements through standard chemical analysis or ELISA. Mice with serum creatinine greater than 2 mg/dL or with a body weight of 80% or less of the cohort mean body weight are removed from the study due to advanced disease status. Urine markers for kidney function can also be measured by placing mice in metabolic cages to allow collection of excreta.

[00750] After 4 weeks, the mice are euthanized and the organs are collected and weighed. The mineralization of the aortic arch, heart, stomach and rest of the kidney are determined. Whole tissue samples are digested with repeated additions of concentrated nitric acid and hydrogen peroxide for 2-3 hours at 65-95° C. Sample solutions are then diluted with 1% nitric acid prior to analysis with an emission spectrometer atomic (Agilent 4100 MP-AES) at the following element emission wavelengths: calcium (422.673 nm), sodium (588.995 nm), potassium (766.491 nm) and phosphorus (214.915 or 213.618 nm). A cesium solution is used as an ionization buffer and an internal standard. Data analysis is performed using Agilent MP Expert software.

[00751] A reduction in vascular calcification in animals treated with the test articles compared to their untreated counterparts is consistent with the reported inhibition of dietary phosphate absorption that is necessary to drive the disease state in this CKD mouse model.

Example 128: In vivo assessment of liver enzymes, triglycerides and fibrosis in a mouse model of non-alcoholic steatohepatitis (NASH)

[00752] NASH is established in male mice by a single subcutaneous injection of streptozotocin (Sigma, USA) after birth and feeding with a high-fat diet (CLEA Japan, Japan). ad libitum after 4 weeks of age (day 28 ± 2). Normal and NASH mice are randomized into 6 groups of 8-12 mice at 6 weeks of age (day 42 ± 2). All groups are dosed BID (with vehicle or test agent; PO; 5mL/kg) daily, except normal mice that receive no treatment. Groups: 1) normal mice are fed a normal diet ad libitum without any treatment; 2) vehicle (10% hydroxypropyl-beta-cyclodextran in 10 mM PBS); 3) linagliptin 10 mg/kg - QD in PM and vehicle - QD in AM; 4) I-389 30 mg/kg; 5) linagliptin 10 mg/kg + I-389 30 mg/kg - QD in PM and I-389 - QD in AM; and 5) telmisartan 10 mg/kg - QD in PM and vehicle - QD in AM. Individual body weight, survival, clinical signs are assessed/measured daily during the treatment period. Mice in all groups are sacrificed under heavy anesthesia after 12 weeks of treatment. Blood and tissues are collected. Of these, the following are measured: 1) liver weight (liver-to-body weight ratios are calculated); 2) plasma levels of liver enzymes; 3) hepatic triglycerides (quantified by the Triglyceride E-test kit [Wako, Japan]); 4) NAFLD Activity score based on histological analyzes of H&E-stained liver sections; and 5) area of fibrosis based on histological analysis of red-stained Sirius liver sections.

[00753] Statistical tests are performed using Bonferroni Multiple Comparison (parametric data is tested by the following analyses: for more than one factor, Two-Way ANOVA followed by Bonferroni post-hoc multiple comparison test; for one factor and more than two groups, One-way ANOVA followed by the Holm-Sidak post-hoc test and, for one factor and 2 groups, the Student's t-test. Non-parametric analyzes of one-factor data with more than two groups are analyzed by Kruskal-Wallis. followed by Dunn's post hoc test. P values < 0.05 are considered statistically significant.

Example 129: Measurement of Intestinal Motility Independent of Gastric Emptying

[00754] Seven and eight week old male C57BL/6 mice were acclimatized for four days. Mice were then divided into 2 groups and fasted for 2-1/2 h, followed by a PO dose (10 mL/kg) of vehicle (10% 2-hydroxypropyl-β-cyclodextrin [HPCD] in 10 mM of PBS containing 0.1% tween 80; HPCD/tween 80) or I389 30 mg/kg. One hour later, carmine red dye (6% in sterile water; 100 μL/mouse) was infused through the duodenal catheter and the mice were euthanized fifteen minutes thereafter. The entire length of the small intestine and the distance from the stomach to the dye front in the small intestine were measured and used to calculate the percentage of the small intestine that the dye front had traveled during the 15 min period.

[00755] As shown in Figure 6 (FIG. 6), I-389 treatment resulted in a statistically significant increase in the percentage that the carmine red dye front traveled into the small intestine when compared to vehicle treatment showing I-389 decreased the intestinal transit time. These data are reported as ± SEM values were analyzed for statistical significance by unpaired Student's t-test, * p < 0.05.

Example 130: In Vivo Assessment of Small Intestine Length and Weight, Small Intestine Villus/Crypt Length, and Colon Crypt Depth in Mice

[00756] Vehicle (HPCD/tween 80) or I-389, 30 or 100 mg/kg, was administered PO BID, with or without sitagliptin (a dipeptidyl peptidase 4 inhibitor [DPP-4 inhibitor] used to block degradation of GLP-1 and GLP-2) 3.6 g/L in drinking water (dose ~ 800 mg/kg/day) to female CD-1 mice for ten consecutive days. Tedulgutide (a GLP-2 receptor agonist; American Peptide, catalog # 304076, provided by Bachem) 50 μg/kg I-389 was injected SC into a BID control group during the same period. Terminal plasma was collected to measure GLP-1 and GLP-2 concentrations. The small intestine and colon were collected, washed with cold PBS to remove contents, sectioned, weighed, and trimmed again for histological analysis. Morphometric analysis was performed to determine villus/crypt length in the proximal jejunum and distal ileum and crypt depth (length) in the proximal colon.

[00757] After treatments in female CD-1 mice for ten consecutive days, teduglutide significantly increased the weight of the small intestine (48%) and showed a tendency to increase the weight of the colon (14%), Figure 7 (FIG. 7). I-389 increased colon weight significantly at a dose of 100 mg/kg when co-administered with sitagliptin (31%), Figure 8 (FIG. 8). I-389 (100 mg/kg) combined with sitagliptin, such as teduglutide, increased villus-crypt length in the proximal jejunum (teduglutide: 55%, I-389 100 mg/kg + sitagliptin: 32%) Figure 9 (FIG. 9). and ileodistal (teduglutide: 30%; I-389 100 mg/kg + sitagliptin: 22%) Figure 10 (FIG. 10). None of the treatments significantly affected colon crypt depth, Figure 11 (FIG. 11). Active GLP-1 levels were significantly increased I-389 (100 mg/kg) + sitagliptin treatment compared to vehicle (>3000%) or either treatment alone, Figure 12 (FIG. 12). Total GLP-2 levels were not statistically different comparing each treatment group to vehicle, Figure 13 (FIG. 13). Data for each group are presented as mean ± SEM. Statistical analyzes were performed using one-way ANOVA followed by the Holm-Sidak multiple comparisons test. Statistical significance compared to vehicle (WD) is marked as *, P < 0.05; **, P <0.01, ***, P <0.001 and ****, P <0.0001.

Example 131: In vivo assessment of plasma glucose and insulin levels and hepatic triglycerides and total cholesterol levels in a mouse model of NAFLD and diabetes mellitus, mice fed a Western diet (WD)

[00758] Seven-week-old male C57BL/6 mice were housed 5/cage. Two cages of mice were placed on normal chow (Harlan Teklad 2018), and the remaining cages of mice were placed on WD (Harlan Teklad, TD.88137, 62% fat/0.2% cholesterol) to induce NAFLD. After 10 weeks, mice were weighed and fasted for 4 h. Blood was collected to measure fasting glucose levels, processed to plasma for measurement of insulin, triglycerides, and total cholesterol. This process was repeated on day 29 of treatment. Based on body weight and fasting glucose and insulin levels, mice were divided into 5 treatment groups (n = 10/group), Table 20. Vehicle-1 consisted of HPCD/tween 80 and was used for formulation of I-389 and linagliptin (a DPP-4 inhibitor); vehicle-2 consisted of sterilized water and was used for the formulation of liraglutide (a GLP-1 analog; BACHEM, Torrance, CA). Mice were weighed twice a week during the study. On the last day of the study (day 30, 8 hours after food removal), the mice were euthanized. Blood was collected in tubes with inhibitors to block DPP-4 activity and processed to plasma for measurement of liver enzymes and GLP levels using an Ace Alera clinical analyzer and the Mesoscale Discovery Multi-Assay System, respectively. The entire liver was collected, weighed, and a sample was collected and weighed to measure triglycerides and total cholesterol. Table 20. Study group work

[00759] As shown in Figure 14 (FIG. 14), I-389 was effective in inducing active release of GLP-1, total GLP-1 levels were highly elevated in both I-389 groups of WD diets Figure 15 ( FIG. 15). Furthermore, the high active levels of GLP-1 in the I-389 and linagliptin combo group indicates that the linagliptin dosing paradigm was sufficient to preserve the intact form of GLP-1, but that linagliptin alone did not induce secretion of GLP-1. GLP-1 (as indicated by low levels of active GLP-1 and total GLP-1 with this treatment). Mice on WD had significantly increased body weight, 4-hour fasting glucose and insulin levels, liver weight, and triglyceride and total cholesterol levels compared to mice on a normal diet (Table 21). . The positive control, liraglutide, partially or completely reversed these effects. I-389, linagliptin, and the combination of both agents did not significantly affect body weight (data not shown). However, all three treatments significantly reduced plasma glucose and insulin levels and fasting liver weight. I-389 alone and combined with linagliptin lowered liver triglycerides, but I389 only lowered liver total cholesterol levels. Linagliptin alone increased total cholesterol levels in the liver. Data for each group are presented as mean ± SEM. Statistical analyzes were performed using one-way ANOVA followed by the Holm-Sidak multiple comparisons test. For LPG levels, statistical significance compared to vehicle (WD) is marked as *, P <0.05; **, P <0.01, ***, P <0.001 and ****, P <0.0001; of linagliptin (WD) versus I-389 alone (WD) or linagliptin + I-389 (WD) is marked as f, P <0.05; ff, P < 0.01, TTT, P < 0.001, and fftt, P <0.0001; and of I-389 (WD) versus linagliptin (WD) + I-389 (WD) is labeled A, P <0.05; AA, P <0.01, AAA, P <0.001 and AAAA, P <0.0001. For the remaining parameters, the statistical significance compared to vehicle (WD) is marked as *, P <0.05; **, P <0.01, ***, P <0.001 and ****, P <0.0001. Table 21 Effect of Liraglutide, I-389 and Linagliptin on Measures of Diabetes and Hepatic Steatosis in Mice Fed Normal or Western Diet

Equivalents

[00760] Those skilled in the art will recognize, or be able to verify, using no more than routine experimentation, that numerous equivalents to the specific embodiments are specifically described herein. Such equivalents are intended to fall within the scope of the following claims.

Claims (50)

1. Compound of Formula (I): or a pharmaceutically acceptable salt, and a tautomer thereof characterized in that: Q is C = (O), -CH2-, -NR5- or -O-; when Q is C =(O) then Qi is -NR5-, when Q is -NR5- or -O- then Qi is -CH2-, or when Q is -CH2- then Qi is -O(CH2)hi- or -NR5-; X1 be CR6 or N; X2 be CR7 or N; X3 be CR8 or N; X4 be CR9 or N; Y be CRb or N; Ra and Rb are each independently H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, or halogen; Ri be (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, halogen, -S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from the group consisting of halogen, (Ci -C4) alkoxy, -OH, -NH2, -NH(C1-C4) alkyl and -N((C1-C4) alkyl)2; or Ri and Ra, together with the atoms to which they are bonded, form a heterocycloalkyl; or R1 and R3, when on adjacent atoms, together with the carbon atoms to which they are attached form a heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1C6) haloalkoxy and halogen; R2 will be (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl or (C1C6) haloalkoxy; R2' is (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl or (C1C6) haloalkoxy; or R2 and R2', together with the carbon atom to which they are attached form (C3-C8) cycloalkyl or heterocycloalkyl; each R3 being independently, at each occurrence, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, halogen, - S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl, or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from the group which consist of halogen, (C1-C4) alkoxy, -OH, -NH2, -NH (C1-C4) alkyl and -N((C1-C4) alkyl)2; or R1 and R3 together with the carbon atoms to which they are attached form a heterocycloalkyl optionally substituted with one or more substituents selected from the group consisting of (C1-C6) alkyl, (C1-C6) alkoxy, (C1- C6) haloalkyl, (C1-C6) haloalkoxy and halogen; R4 be H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8 ) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S(O)m(C1-C6) alkyl, -NH(C1-C4) alkyl, or -N((C1-C4) alkyl)2; each R5 is independently H, (C1-C6) alkyl, -C(O)NR10R11, -C(O)(C1-C6) alkyl, or -C(O)O(C1-C6) alkyl; each R6 and R9 independently be H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, - S(O)o(C1-C6) alkyl, -NH(C1-C4) alkyl, or -N((C1-C4) alkyl)2; each R7 and R8 independently be H, (C1-C8) alkenyl, (C1C8) alkynyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1 -C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, (C3-C8) cycloalkenyl, heterocycloalkyl, -OH, -NH2, -S(O)qNH2, -S(O)qOH, CN or (C1C18) alkyl, wherein 0 to 7 methylene of the (C1-C18) alkyl is optionally substituted by a moiety selected from the group consisting of -O-, -NR13-, -(SO)q-, -C(O)-, - C(CH2)-, and -C(NH)-, provided that when any two methylenes in the alkyl are substituted, then two -O-, two -S(O)q- or two -NR13- and -O- and -NR13- are not contiguous, wherein the alkyl is optionally substituted by one or more R12, and wherein the cycloalkyl and cycloalkenyl are optionally substituted by one or more R13; R10 and R11 are each independently H or (C1-C6) alkyl optionally substituted with one or more substituents independently selected from -NH2 and OH; R12 be D, -OH, halogen, -NH2, -NH(C1-C6) alkyl, -N((C1-C6) alkyl)2, -C(O)OH, -OC(O)(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl, heteroaryl or R17, wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more substituents selected from -OH, -NH2, -NH (C1-C6) alkyl, -N((C1-C6) alkyl)2, halogen and R14; R13 is H, -OH, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl, heteroaryl or (C1-C12) alkyl, wherein 0 to 7 methylene of the (C1-C12) alkyl is optionally substituted by a portion selected from the group consisting of -O-, -NR13-, -S(O)r-, -C(O)-, and -C(NH)-, provided that when any two methylenes in the alkyl are substituted , then O and N are not contiguous and wherein the alkyl is optionally substituted with one or more R15, and wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more substituents selected from the group consisting of- OH, -C(O)OH, -NH2, -NH(Ci-Ce) alkyl and -N((Ci-Ce) alkyl)2; R14 will be (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl, -O-heterocycloalkyl, (C1-C12) alkyl or (C2-C12) alkenyl, wherein 0 to 7 methylene of (Ci- Ci2) alkyl and (C2-Ci2) alkenyl are optionally substituted by a moiety selected from the group consisting of -O-, -NRi3-, -S(O)r-, -C(O)- and -C( NH)-, provided that when any two methylene in the alkyl or alkenyl is replaced, then O and N are not contiguous and wherein the alkyl and alkenyl are optionally substituted with one or more Ri5, and the cycloalkyl and heterocycloalkyl are optionally substituted with one or more Ri6; or when Ri2 is cycloalkyl or heterocycloalkyl, two Ri4 together with the atom to which they are attached form C=(O); or when Ri2 is cycloalkyl or heterocycloalkyl, two Ri4 together with the atoms to which they are attached form a (C3-C8) cycloalkyl or heterocycloalkyl optionally substituted with one or more Ri3; or when Ri2 is cycloalkyl or heterocycloalkyl, two Ri4 together with the atom to which they are attached form a (C3-C8) spirocycloalkyl or a spiroheterocycloalkyl optionally substituted with one or more Ri3; or when Ri2 is cycloalkyl or heterocycloalkyl, two Ri4 together with the atom to which they are attached form a (C6-C10) aryl or heteroaryl optionally substituted with one or more Ri3; R15 will be -OH, -NH2, -NH(CI-C6) alkyl, -N((CI-C6)alkyl)2, (C3C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the (C3 -C8) cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from the group consisting of (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, -C(O)OH, -OH, -NH2, - NH(C1-C6) alkyl, - N((C1-C6) alkyl)2 and oxo; R16 will be -OH, -C(O)OH, -NH2, -NH(C1-C6) alkyl, -N((C1-C6) alkyl)2, (C1-C6) alkoxy, (C1-C6) hydroxyalkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl, -O-heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted with one or plus substituents selected from the group consisting of (C1-C6) hydroxyalkyl, (Ci-Cβ) aminoalkyl, -C(O)OH, -OH, -NH2, -NH(Ci-Cβ) alkyl, - N(( C1-C6) alkyl)2 and oxo; Ri7 is (C1-C18) alkyl or (C2-C18) alkenyl, wherein 0 to 8 methylene of the (C1-C18) alkyl and (C2-C18) alkenyl are optionally substituted by a moiety selected from the group consisting of -O-, -NRi3-, -S(O)r-, -C(O)-, and -C(NH)-, provided that when any two methylenes in the alkyl or alkenyl are substituted, then O and N are not contiguous and in which the alkyl and alkenyl are optionally substituted by one or more Ri8; Ri8 is Ri9, (Cβ-Ci0) aryl, or heteroaryl optionally substituted with one or more R2i; Ri9 be (Ci-Ci8) alkyl wherein 0 to 8 methylene of the (Ci-Ci8) alkyl is optionally substituted by a moiety selected from the group consisting of -O-, -NRi3-, -S(O)r- , -C(O)- and -C(NH)-, provided that when any two methylenes in the alkyl or alkenyl are substituted, then O and N are not contiguous and wherein the alkyl is optionally substituted with one or more R20; R20 is (Cβ-Ci0) aryl or heteroaryl optionally substituted with one or more R2i; R2i is H, (Ci-Cβ) alkyl, (Ci-Cβ) alkoxy, (Ci-Cβ) haloalkyl, (Ci-Cβ) haloalkoxy or halogen; or two R2i together when on adjacent atoms form a cycloalkyl or heterocycloalkyl optionally substituted with one or more R22; R22 be -C(O)NH2, -C(O)NH(Ci-Cβ) alkyl, -C(O)N((Ci-Cβ) alkyl)2, -C(O) (C3-C7) cycloalkyl, or -C(O) heterocycloalkyl, wherein the cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents independently selected from the group consisting of -OH and CN; each m, o, p, qer is independently, in each occurrence, 0, i or 2; en be 0, 1 or 2. 2. Compound according to claim 1, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that Q is -NH or -O-. 3. Compound according to claim 1, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that R3 is halogen. 4. Compound according to claim 1, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that X1 is CR6 and R6 is H or halogen. 5. Compound, according to claim 1, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that (i) X2 is CR7 and R7 is H or halogen; or (ii) X2 is N. 6. Compound according to claim 1, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that X3 is CR8. 7. Compound, according to claim 1, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that X4 is N. 8. Compound according to claim 1, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that n is 0 or 1. 9. Compound, according to claim 1, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that: Q is - NR5- or -O-; Qi be -CH2-; X1 be CR6 or N; X2 be CR7 or N; X3 be CR8 or N; X4 be CR9 or N; Y be CH; Ra be H; Ri ser , (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, halogen, -S(O)p(C1-C6) alkyl, (C3-C8 ) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl, or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from the group consisting of halogen, ( C1-C4) alkoxy, -OH, -NH2, -NH(C1-C4) alkyl and -N((C1-C4) alkyl)2; R2 and R2' are each independently (C1-C6) alkyl, (C1C6) alkoxy, (C1-C6) haloalkyl or (C1-C6) haloalkoxy; or R2 and R2', together with the carbon atom to which they are attached form (C3-C8) cycloalkyl or heterocycloalkyl; each R3 being independently, at each occurrence, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, halogen, - S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl, or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from the group which consists of halogen, (C1-C4) alkoxy, -OH, -NH2, -NH(Ci-C4) alkyl and -N((C1-C4) alkyl)2; R4 be H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8 ) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S(O)m(C1-C6) alkyl, -NH(C1-C4) alkyl or -N((C1-C4) alkyl)2; R5 is H, (C1-C6) alkyl, -C(O)NR10R11, -C(O)(C1-C6) alkyl, or - C(O)O(C1-C6) alkyl; each R6 and R9 independently be H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, - S(O)o(C1-C6) alkyl, -NH(C1-C4) alkyl or -N((C1-C4) alkyl )two; each R7 and R8 independently be H, (C1-C8) alkenyl, (C1C8) alkynyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1 -C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, (C3-C8) cycloalkenyl, heterocycloalkyl, -OH, -NH2, -S(O)qNH2, -S(O)qOH, CN or (C1C18) alkyl, wherein 0 to 7 methylene of the (C1-C18) alkyl is optionally substituted by a moiety selected from the group consisting of -O-, -NR13-, -(SO)q-, -C(O)-, - C(CH2)-, and -C(NH)-, provided that when any two methylenes in the alkyl are substituted, then two -O-, two -S(O)q- or two -NR13- and -O- and -NR13- are non-contiguous, wherein the alkyl is optionally substituted by one or more R12, and wherein the cycloalkyl and cycloalkenyl are optionally substituted with one or more R13; R10 and R11 are each independently H or (C1-C6) alkyl optionally substituted with one or more substituents independently selected from the group consisting of -NH2 and OH; R12 will be -OH, -NH2, -NH(C1-C6) alkyl, -N((C1-C6) alkyl)2, - C(O)OH, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more substituents selected from the group consisting of -OH, -NH2, -NH(C1-C6) alkyl, -N((C1 -C6) alkyl)2 and R14; R13 is H, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl, heteroaryl or (C1-C12) alkyl, wherein 0 to 7 methylene of the (C1-C12) alkyl is optionally substituted by a portion selected from from the group consisting of -O-, -NR13-, -S(O)r-, -C(O)- or -C(NH)-, provided that when any two methylenes in the alkyl are substituted, then O and N are not contiguous and wherein the alkyl is optionally substituted with one or more R15 and wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more substituents selected from the group consisting of -OH, -C( O)OH, -NH2, -NH(C1-C6) alkyl and -N((C1-C6) alkyl)2; R14 will be (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl, -O-heterocycloalkyl, (C1-C12) alkyl or (C2-C12) alkenyl, wherein 0 to 7 methylene of (C1- C12) alkyl and (C2-C12) alkenyl are optionally substituted by a moiety selected from the group consisting of -O-, -NR13-, -S(O)r-, -C(O)- or -C( NH)-, provided that when any two methylenes in the alkyl or alkenyl are substituted, then O and N are not contiguous and wherein the alkyl and alkenyl are optionally substituted with one or more R15, and the cycloalkyl and heterocycloalkyl are optionally substituted with one or more R16; or when R12 is cycloalkyl or heterocycloalkyl, two R14 together with the atom to which they are attached form C=(O); or when R12 is cycloalkyl or heterocycloalkyl, two R14 together with the atoms to which they are attached form a (C3-C8) cycloalkyl or heterocycloalkyl optionally substituted with one or more R13; or when R12 is cycloalkyl or heterocycloalkyl, two R14 together with the atom to which they are attached form a (C3-C8) spirocycloalkyl or a spiroheterocycloalkyl optionally substituted with one or more R13; Ri5 will be -OH, -NH2, -NH(Ci-Cβ) alkyl, -N((Ci-Cβ) alkyl)2, (C3C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the (C3 -C8) cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents selected from the group consisting of (Ci-Cβ) hydroxyalkyl, (Ci-Cβ) aminoalkyl, -C(O)OH, -OH, -NH2, - NH(Ci-Cβ) alkyl, - N((Ci-Cβ) alkyl)2 and oxo; Riβ be -OH, -C(O)OH, -NH2, -NH(Ci-Cβ) alkyl, -N((Ci-Cβ) alkyl)2, (Ci-Cβ) alkoxy, (Ci-Cβ) hydroxyalkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, -O-heterocycloalkyl, (Cβ-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted with one or plus substituents selected from the group consisting of (Ci-Cβ) hydroxyalkyl, (Ci-Cβ) aminoalkyl, -C(O)OH, -OH, -NH2, -NH(Ci-Cβ) alkyl, - N(( Ci-Cβ) alkyl)2 and oxo; each m, o, p, q and r being independently, in each occurrence, 0, i or 2; and n be 0, i or 2. 10. Compound according to claim i, or a pharmaceutically acceptable salt or tautomer thereof characterized by having the Formula selected from the group consisting of: 11. Compound, according to claim 1, or a pharmaceutically acceptable salt, or automer thereof, characterized by having the formula: 12. Compound according to claim 1, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that it is selected from the group consisting of: 1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]-N-[( 2,5-dichlorophenyl) methyl] cyclopropan-1-amine; N-[(2,5-dichlorophenyl) methyl]-1-{4-[2-(propan-2-yloxy) phenyl] pyridin-3-yl} cyclopropan-1-amine; 1-[4-(2-cyclopropoxy-5-fluorophenyl)pyridin-3-yl]-N-[(2,5-dichlorophenyl)methyl]cyclopropan-1-amine; N-[(2,5-dichlorophenyl) methyl]-1-[4-(2-methoxyphenyl) pyridin-3-yl] cyclopropan-1-amine; 1-[4-(2-cyclobutoxyphenyl) pyridin-3-yl]-N-[(2,5-dichlorophenyl) methyl] cyclopropan-1-amino; N-[(2,5-dichlorophenyl) methyl]-1-[4-(2-methylphenyl) pyridin-3-yl] cyclopropan-1-amine; N-[(2,5-dichlorophenyl) methyl]-1-{4-[2-(methylsulfanyl) phenyl] pyridin-3-yl} cyclopropan-1-amine; N-[(2,5-dichlorophenyl) methyl]-1-{4-[2-(2,2,2-trifluoroethoxy) phenyl] pyridin-3-yl} cyclopropan-1-amine; N-[(2,5-dichlorophenyl) methyl]-1-[4-(2-ethylphenyl) pyridin-3-yl] cyclopropan-1-amine; 1-[4-(2-cyclopropylphenyl) pyridin-3-yl]-N-[(2,5-dichlorophenyl) methyl] cyclopropan-1-amine; N-[(2,5-dichlorophenyl) methyl]-1-{4-[2-(trifluoromethoxy) phenyl] pyridin-3-yl} cyclopropan-1-amine; N-[(2,5-dichlorophenyl) methyl]-1-{4-[2-(methoxymethyl) phenyl] pyridin-3-yl} cyclopropan-1-amine; 1-(4-{2-[(tert-butoxy)methyl]phenyl}pyridin-3-yl)-N-[(2,5-dichlorophenyl)methyl]cyclopropan-1-amine; N-[(2,5-dichlorophenyl) methyl]-1-[4-(2-ethoxy-4,5-difluorophenyl) pyridin-3-yl] cyclopropan-1-amine; 1-[4-(2-chlorophenyl) pyridin-3-yl]-N-[(2,5-dichlorophenyl) methyl] cyclopropan-1-amine; N-[(2,5-dichlorophenyl) methyl]-1-[4-(2-fluorophenyl) pyridin-3-yl] cyclopropan-1-amine; 1-[4-(2-cyclopropoxy-4-fluorophenyl) pyridin-3-yl]-N-[(2,5-dichlorophenyl) methyl] cyclopropan-1-amine; N-[(2,5-dichlorophenyl) methyl]-1-{4-[2-(oxetan-3-yloxy) phenyl] pyridin-3-yl} cyclopropan-1-amine; 2-{2-[3-(1-{[(2,5-dichlorophenyl) methyl] amino} cyclopropyl) pyridin-4-yl] phenoxy} propan-1-ol; N-[(2,5-dichlorophenyl) methyl]-1-{4-[2-(oxolan-3-yloxy) phenyl] pyridin-3-yl} cyclopropan-1-amine; (3R,4R)-4-{2-[3-(1 -{[(2,5-dichlorophenyl) methyl] amino} cyclopropyl) pyridin-4-yl] phenoxy} oxolan-3-ol; N-{[2-chloro-5-(methylsulfanyl)phenyl]methyl}-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine; 1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]-N-[(2,5-dimethylphenyl) methyl] cyclopropan-1-amine; 1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]-N-{[3-methyl-6-(methylsulfanyl) pyridin-2-yl] methyl} cyclopropan-1-amine; 1-[4-(2-cyclopropoxyphenyl) cyclopropan-1-amino; 1-[4-(2-cyclopropoxyphenyl) methyl] cyclopropan-1-amine; 1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]-N-[(2,5-dichlorophenyl) methyl] cyclopropan-1-amino; 1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]-N-[(4-methoxy-2,5-dimethylphenyl) methyl] cyclopropan-1-amine; N-{[5-chloro-2-(trifluoromethyl)phenyl]methyl}-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine; N-[(2-chloro-5-cyclopropylphenyl) methyl]-1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropan-1-amine; N-{[2-chloro-5-(methylsulfanyl)phenyl]methyl}-1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropan-1-amine; cyclopropoxyphenyl) pyridin-3-yl] cyclopropan-1-amine; 1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]-N-{[2-methyl-5-(trifluoromethyl) phenyl] methyl} cyclopropan-1-amine; 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-{[4-methoxy-2-methyl-5-(propan-2-yl)phenyl]methyl}cyclopropan-1-amine; 1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]-N-{[3-methyl-5-(methylsulfanyl) pyridin-2-yl] methyl} cyclopropan-1-amine; N-[(5-chloro-2-methylphenyl) methyl]-1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropan-1-amine; 1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]-N-{[2-methyl-5-(methylsulfanyl) pyridin-4-yl] methyl} cyclopropan-1-amine; N-[(5-chloro-2-methanesulfonylphenyl) methyl]-1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropan-1-amine; 1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]-N-[(3,5-dichlorophenyl) methyl] cyclopropan-1-amine 3-{1-[(2,5-dichlorophenyl) methoxy] cyclopropyl } -4-(2-methoxyphenyl) pyridine; 4-(2-cyclopropoxyphenyl)-3-{1-[(2,5-dichlorophenyl)methoxy]cyclopropyl}pyridine; 4-(2-cyclopropoxyphenyl)-3-{1-[(2,3-dichlorophenyl)methoxy]cyclopropyl}pyridine; 4-(2-cyclopropoxyphenyl)-3-{1-[(2,4-dichlorophenyl)methoxy]cyclopropyl}pyridine; 4-(2-cyclobutoxyphenyl)-3-{1-[(2,5-dichlorophenyl)methoxy]cyclopropyl}pyridine; 3-{1-[(2,5-dichlorophenyl)methoxy]cyclopropyl}-4-(2-fluorophenyl)pyridine; 3-(1-{[5-chloro-2-(trifluoromethyl)phenyl]methoxy}cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridine; 3-(1-{[2-chloro-5-(trifluoromethyl)phenyl]methoxy}cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridine; 3-{1-[(2-chloro-5-cyclopropylphenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)pyridine; 3-{1-[(2-chloro-5-methylphenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)pyridine; 3-{1-[(5-chloro-2-methylphenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)pyridine; 4-(2-cyclopropoxyphenyl)-3-{1-[(3,5-dichlorophenyl)methoxy]cyclopropyl}pyridine; 1-{1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl}-1-[(2,5-dichlorophenyl) methyl] urea; 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-N-[(2,5-dichlorophenyl)methyl]-N-methylcyclopropan-1-amine; 4-(2-cyclopropoxyphenyl)-3-{3-[(2,5-dichlorophenyl) methoxy] oxetan-3-yl} pyridine; 1-(5-{2,5-dichloro-4 -[({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropyl} amino) methyl] phenyl} pentyl)-3 -[(2S , 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} pentanoic acid; 5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} -N-[(2S, 3R, 4R, 5R )-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 4 -[(4-{2,5-dichloro-4 -[({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropyl} amino) methyl] phenyl} butyl)[(2S, 3R , 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl] butanoic acid; 1-{4-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} -3 -[(2S, 3R, 4R, 5R )-2,3,4,5,6-pentahydroxyhexyl] urea; 1-{4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-2-methyl-phenyl] butyl} -3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; (2R, 3R, 4R, 5S)-6 -({4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl } amino) hexane- 1,2,3,4,5-pentol; N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} -N-[(2S, 3R, 4R , 5R)-2,3,4,5,6-pentahydroxyhexyl] oxane-4-carboxamide; N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} -N-[(2S, 3R, 4R , 5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide; N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} -2-methyl-N-[(2S , 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide; 3-(benzenesulfonyl) -N-{4- [2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} -N-[ (2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide; N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} -N-[(2S, 3R, 4R , 5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide; N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} 2-methoxy-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide; N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} -N-[(2S, 3R, 4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide; N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} -N-[(2S, 3R, 4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} 3-methoxy-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide; 1-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} -3-(2-methoxyethyl)-1 -[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; (5S)-3-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} -5 -[(1S , 2R, 3R)-1, 2, 3, 4-tetrahydroxybutyl]-1, 3-oxazolidin-2-one; (2S)-4-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] -[(1S 2R, 3R)-1,2,3 ,4-tetrahydroxybutyl]-1,4- -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] butyl}-3-methyl-1-[(2S,3R,4R,5R) -2,3,4,5,6- -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} -N-[(2S, 3R, 4R, 5R )-2,3,4,5,6-pentahydroxyhexyl] formamide; (2R, 3S, 4R, 5R)-N-{4-[2,5-dichloro-4 -({1-[4 -(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} -2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl) hexanamide (2S, 3S, 4R; , 5S)-N- (Carbamoylmethyl)-N-{4-[2,5-dichloro-4 -({1-[4(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} - 2,3,4,5,6-pentahydroxyhexanamide; (2R, 3S, 4R, 5R)-N-{4-[2,5-dichloro-4-({1-[4-(2- cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} 2,3,4,5,6-pentahydroxy-N-(6-hydroxyhexyl) hexanamide (2R, 3S, 4R, 5R)-N; -{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} -2,3,4,5,6- pentahydroxy-N-(2-sulfamoylethyl) hexanamide; (2S, 3S, 4R, 5S)-N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} 2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl]hexamide; 1-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl}-1-[2-(2-hydroxyethoxy )ethyl]-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 2-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-[(2S, 3R, 4R, 5R )-2,3,4,5,6-pentahydroxyhexyl] pentanamido} acetic acid; 2-(4-{5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentanoyl} piperazin-1-yl) acid acetic; 2-(4-{5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentanoyl} piperazin-1-yl)- N-methyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide; 2-[4-(2-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentanamido} ethyl) piperazin acid - 1-yl] acetic; 5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-1-{4 -[(2S, 3R, 4S, 5R )-2,3,4,5,6-pentahydroxyhexyl] piperazin-1-yl} pentan-1-one; acid (2S, 3S, 4R, 5R, 6S)-6 -({5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentanamido} methyl)-3,4,5-trihydroxy-oxane-2-carboxylic acid; 1-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methyl-phenyl]butyl}-3-ethyl-3- [(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-{4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-2-methyl-phenyl] butyl} -3 -[(2S, 3R, 4S, 5R)-1,3,4,5,6-pentahydroxyhexan-2-yl] urea; 1-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methyl-phenyl]butyl}-1-ethyl-3- [(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-{4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-2-methyl-phenyl] butyl} -1 -(2-hydroxyethyl )-3-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 2-(4-{5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentanoyl} piperazin-1-yl)- N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide; 5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropoxy} methyl) phenyl]-N-{2-[4 -({[(2S , 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl} methyl) piperazin-1-yl] ethyl} pentanamide; 5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-{2-[4 -({methyl[(2S , 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl} methyl) piperazin-1-yl] ethyl} pentanamide; 4-(2-carboxyethyl)-4-{5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentanamido} - acid heptanedioic; 5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-1-{4 -[(2S, 3R, 4R, 5R )-2,3,5,6-tetrahydroxy-4 -{[(2S, 3R, 4S, 5R, 6R)-3,4,5- trihydroxy-6-(hydroxymethyl) oxan-2 -yl] oxy} hexyl] piperazin- 1-yl} pentan-1-one; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-{[(3R, 4R, 5S, 6R)- 3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-yl] methyl} pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-(2-hydroxyethyl)-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; (2R, 3R, 4S, 5R)-2 -[({4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) acid -2- methylphenyl] butyl} carbamoyl) amino]-3,4,5,6-tetrahydroxyhexanoic acid; 1-{4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-2-methyl-phenyl] butyl} -3 -(2-hydroxyethyl )-3-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-ethyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 3-{4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-2-methylphenyl] butyl} -1 -{[(2S, 3R , 4R, 5S, 6R)-3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-yl] methyl} urea; acid (2S, 3S, 4R, 5R, 6S)-6 -{[({4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) -2-methylphenyl] butyl} carbamoyl) amino] methyl} -3,4,5-trihydroxy-oxane-2-carboxylic acid; 2-(2-{2-[({4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin- 3- yl] cyclopropoxy} methyl)-2-methylphenyl] butyl} carbamoyl) amino] acetamido} acetamido) acetic acid; acid (2S)-2 -[(2S)-2 -[(2S)-2 -[({4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl ]cyclopropoxy} methyl)-2-methylphenyl] butyl} carbamoyl) amino] propanamido] propanamido] propanoic; acid (2S)-5-carbamimidamido-2 -[({4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-2-methylphenyl] butyl} carbamoyl) amino] pentanoic; N-{4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropoxy} methyl)-2-methyl-phenyl] butyl} -4 -[(2S , 3R, 4S, 5R)-2,3,4,5,6-pentahydroxyhexyl]piperazine-1-carboxamide; 1-{4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-2-methyl-phenyl] butyl} -3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-{4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-2-methyl-phenyl] butyl} -1 -(2-methoxyethyl )-3-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-{4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-2-methyl-phenyl] butyl} -1-[2-( 2-hydroxyethoxy)ethyl-3-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-{4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methyl-phenyl]butyl}-1-(5-hydroxypentyl )-3 -[(2S, 3R, 4R, 5R)- 2,3,4,5,6-pentahydroxyhexyl] urea; (2R)-6-amino-2 -[({4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-2-methylphenyl] butyl } carbamoyl) amino] hexanoic acid; N-benzyl-5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-[(2R, 3S, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-methyl-N-(2 -{[(2R, 3R, 4S, 5S, 6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}ethyl)pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-(2,3-dihydroxypropyl)-N-[( 2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-[(2R)-2-hydroxybutyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-[(2R)-2-hydroxy-3-methoxypropyl ]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-[(2S)-2-hydroxy-3-methoxypropyl ]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; N-benzyl-5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-(2-methoxyethyl)-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-ethyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]-N-(propan-2-yl)pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-[(2S, 3R, 4R, 5R)-2 ,3,4,5,6-pentahydroxyhexyl]-N-propylpentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-(2-methanesulfonylethyl)-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-(oxan-4-yl)-N-[( 2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; (2S, 3S, 4R, 5S)-N-{4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-2-methylphenyl] butyl } -2,3,4,5,6-pentahydroxy-N-methylhexanamide; 5-{2,5-dichloro-4-[({1-[4-(2-methoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} -N-[(2S, 3R, 4R, 5R )-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-{2,5-dichloro-4-[({1-[4-(2-methoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} -N-methyl-N-[(2S, 3R , 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-[(2S, 3R, 4R, 5R)-2 ,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-methyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropyl} amino) methyl] phenyl} -N-methyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 1-(4-{2,5-dichloro-4 -[({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropyl} amino) methyl] phenyl} butyl)-3 -[(2S , 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-2-methyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N,2-dimethyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 1-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl}-3-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 5-{5-chloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-2-methylphenyl}-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-{5-chloro-4 -[({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropyl} amino) methyl] 2-methylphenyl} -N-methyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-2,2-dimethyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methyl-phenyl]-N-[(2S, 3R, 4R, 5R )-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methyl-phenyl]-N-methyl-N-[(2S, 3R , 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 1-(4-{4 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl]- 2,5-dimethyl-phenyl} butyl)-3 -[(2S , 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 5-{4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-2,5-dimethyl-phenyl}-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-{4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-2,5-dimethyl-phenyl}-N-methyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 1-{4-[4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)2,5-dimethylphenyl]butyl}-3-[(2S, 3R, 4R, 5R )-2,3,4,5,6-pentahydroxyhexyl] urea; 1-(4-{5-chloro-4 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl]- 2methyl-phenyl} butyl)-3-[(2S , 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 2-{2-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] ethoxy} -N-[(2S, 3R, 4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide; acid (2R, 3R, 4S, 5R)-2-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentanamido } 3,4,5,6 tetrahydroxyhexanoic acid; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-[(2R, 3R, 4R, 5S, 6R) -2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl] pentanamide; 2-{2-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] ethoxy} -N-methyl-N-[(2S , 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide; 5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropoxy} methyl) phenyl]-N-[(2S, 3R, 4S, 5R)- 1 3,4,5,6-pentahydroxyhexan-2-yl] pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentanoic acid; 1-(1-{5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentanoyl} piperidin-4-yl)- 3 -[(2S, 3R, 4R, 5R)- 2,3,4,5,6-pentahydroxyhexyl] urea; 1-(1-{5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentanoyl} piperidin-4-yl)- 3-methyl-3 -[(2S, 3R, 4R, 5R)- 2,3,4,5,6-pentahydroxyhexyl] urea; 5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropoxy} methyl) phenyl]-N-[(2S, 3R, 4S, 5R)- 3 4,5,6-tetrahydroxy-1-(morpholin-4-yl)hexan-2-yl] pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-[(2S, 3R, 4R, 5R)-2 ,3,4,5,6-pentahydroxyhexyl] hexanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-methyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] hexanamide; 1-(5-{2,5-dichloro-4 -[({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropyl} amino) methyl] phenyl} pentyl)-3 -methyl-3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 2-{[(2S, 3R, 4S, 5R)-2-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl acid )phenyl] pentanamido} -3,4,5,6- tetrahydroxyhexyl] (methyl) amino} acetic; 5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropoxy} methyl) phenyl]-N-[(2S, 3R, 4S, 5R)- 1-(dimethylamino)-3,4,5,6-tetrahydroxyhexan-2-yl] pentanamide; 4-[5-chloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-methyl-phenyl]butan-1-amine; 1-{4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-2-methyl-phenyl] butyl} -3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N, N-bis(2 -{[(2S, 3R , 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl} ethyl) pentanamide; 5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N, N-bis(2-{methyl[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl} ethyl) pentanamide; 5-{2,5-dichloro-4 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} -N, N-bis(2 -{[( 2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl} ethyl) pentanamide; 5-{2,5-dichloro-4 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} -N, N-bis(2-{methyl[ (2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl} ethyl) pentanamide; (2S, 3S, 4R, 5S)-N-{4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-2-methylphenyl] butyl } -2,3,4,5,6-pentahydroxyhexamide; (2S, 3S, 4R, 5S)-6 -[(1-{5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl acid )phenyl]pentanoyl}piperidin-4-yl)amino]-2,3,4,5-tetrahydroxyhexanoic acid; 1-[4-(2,5-dichloro-4 -{[(1-{4-[2-(oxetan-3-yloxy) phenyl] pyridin-3-yl} cyclopropyl) amino] methyl} phenyl) butyl] -3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-[4-(2,5-dichloro-4 -{[(1-{4-[2-(oxetan-3-yloxy) phenyl] pyridin-3-yl} cyclopropyl) amino] methyl} phenyl) butyl] 3-methyl-3-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; (2S, 3S, 4R, 5S)-N-{4-[5-chloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-2-methylphenyl] butyl } -2,3,4,5-tetrahydroxy-6- (morpholin-4-yl) hexanamide; 5-(2,5-dichloro-4-{[(1-{4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropyl)amino]methyl}phenyl)-N-methyl- N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 3-(5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropyl} amino) methyl]-phenyl} -N-[(2S) acid , 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]propanoic acid; ({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} 2,3,4,5-tetrahydroxy-6-(morpholin-4-yl) hexanamide; (2S, 3S, 4R, 5S)-6 -[(3-{5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-methylpentanamido}propyl)amino]-2,3,4,5-tetrahydroxyhexanoic acid; 2R, 3S, 4R, 6S)-4,6-diamino- 3 -{[(2S, 3R, 4S, 5S, 6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl) oxan- 2- yl]oxy} - 2-hydroxycyclohexyl] oxy} -3,4,5-trihydroxy-oxan-2-yl] methyl} - 5-[2,5-dichloro-4 -({1- [4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentanamide; -3-yl] cyclopropoxy} methyl) phenyl] butyl} [(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl) butanoic acid; 3-{5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-[(2S, 3R, 4R, 5R ) -2,3,4,5,6-pentahydroxyhexyl] pentanamido} propanoic acid; (2S, 3S, 4R, 5S)-N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} 2,3,4,5,6-pentahydroxy-N-methylhexanamide; (2S, 3S, 4R, 5S)-N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} -2,3,4,5,6-pentahydroxyhexanamide; 2 -({4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl}[(2S, 3R, 4R, 5R )-2,3,4,5,6-pentahydroxyhexyl] carbamoyl)methoxy] acetic; 3 -({4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl}[(2S, 3R, 4R, 5R )-2,3,4,5,6-pentahydroxyhexyl] carbamoyl) propanoic acid; (2S, 3S, 4R, 5S)-N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} 2,3,4,5-tetrahydroxy-N-methyl-6-(morpholin-4-yl)hexamide; 1-(4-{5-chloro-2-methyl-4 -[(1-{4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropoxy)methyl]phenyl}butyl)- 3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-(4-{5-chloro-2-methyl-4 -[(1-{4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropoxy)methyl]phenyl}butyl)- 3-methyl-3-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 5-{2,5-dichloro-4-[(1-{4-[2-(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropoxy)methyl]phenyl}-N-methyl-N-[ (2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 1-(4-{2,5-dichloro-4 -[(1-{4-[2-(oxetan-3-yloxy) phenyl] pyridin-3- yl} cyclopropoxy) methyl] phenyl} butyl)- 3 - [(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-({4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3- yl] cyclopropoxy} methyl) phenyl] butyl}sulfamoyl}-3-methyl-3- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; -cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl}[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl)methyl](methyl )amino} acetic acid; , 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl)-3,3-dimethyl butanoic acid; ({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl}[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxy -hexyl] carbamoyl)amino] acetic acid; butyl}[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl)amino] propanoic acid; 4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3- yl] cyclopropoxy} methyl) phenyl]-butyl}[(2S, 3R, 4R, 5R)-2,3,4,5,6- pentahydroxyhexyl] carbamoyl)amino] butanoic acid; acid 2 -({[(4-{2,5-dichloro-4 -[({1-[4-(2-cyclopropoxyphenyl) pyridin a- 3-yl] cyclopropyl} amino) methyl] phenyl} butyl)[( 2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl] methyl} (methyl) amino) acetic; acid 4 -[(4-{2,5-dichloro-4 -[({1-[4-(2-cyclopropoxyphenyl) pyridin a- 3-yl] cyclopropyl} amino) methyl] phenyl} butyl)[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl]-3,3-dimethyl butanoic acid; N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl}-2-methanesulfonyl-N-[(2S , 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide; N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl}-2-[dimethylamino)-N-[ (2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide; 1-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl}-1-methyl-3-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; (2S, 3S, 4R, 5S)-N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} 2,3,4,5,6-pentahydroxy-N-propylhexamide; (2S, 3S, 4R, 5S)-N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} 2,3,4,5,6-pentahydroxy-N(2-methoxyethyl)hexanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-ethyl-N-[2-(dimethylaminoethyl]-N -[(2S, 3R, 4R, 5R)- 2,3,4,5,6-pentahydroxyhexyl] pentanamide; -[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl ] pentanamide; (2S, 3S, 4R, 5S)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl ]butyl}-N-ethyl-2,3,4,5,6-pentahydroxyhexanamide; 1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}2,3,4,5,6-pentahydroxy-N(propan-2-yl)hexanamide (2S; , 3S, 4R, 5S)-N-(Cyclopropylmethyl)-N-{4-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl) phenyl]butyl}-2,3,4,5,6-pentahydroxyhexanamide; 4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]butyl}2,3,4,5,6-pentahydroxy-N(3-methoxypropyl)hexanamide; (2S, 3S, 4R, 5S)-N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} 2,3,4,5,6-pentahydroxy-N(2-hydroxyethyl)hexanamide; (2S, 3S, 4R, 5S)-N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} 2,3,4,5,6-pentahydroxy-N-[(2-R)2-hydroxypropyl]hexanamide; (2S, 3S, 4R, 5S)-N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} 2,3,4,5,6-pentahydroxy-N[(2S)-2-hydroxypropyl)hexanamide; (2S, 3S, 4R, 5S)-N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} 2,3,4,5,6-pentahydroxy-N(oxan-4-yl)hexanamide; (2S, 3S, 4R, 5S)-N-{4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] butyl} 2,3,4,5,6-pentahydroxy-N(3-hydroxypropyl)hexanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-(3-hydroxypropyl)-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-[(methylcarbamoyl)methyl]-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-(3-methoxypropyl)-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-[(dimethylcarbamoyl)methyl]-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide; 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-[2-(dimethylcarbamoyl)ethyl]-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide; N-(2-carbamoylethyl)-5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; (2S, 3S, 4R, 5S)-N-{5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentyl} 2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl]hexamide; 1-{5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentyl}-3-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; (2S, 3S, 4R, 5S)-N-{5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentyl} 2,3,4,5,6-pentahydroxy-N-(2-methylsulfonyl ethyl) hexanamide; (2S, 3S, 4R, 5S)-N- {4-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentyl} -N-[2-(ethanesulfonyl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide; (2S, 3S, 4R, 5S)-N-{5-[2,5-dichloro-4 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentyl} 2,3,4,5,6-pentahydroxy-N-methylhexanamide; 5-[4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)- 2,5-dimethyl-phenyl]-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]pentanamide; 5-[4-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2,5-dimethyl-phenyl]-N-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide; 5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-phenyl]-N-[(2S, 3R, 4R, 5R)-2, 3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-methyl-N-[(2S,3R,4R,5R) -2,3,4,5,6-pentahydroxyhexyl]pentanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]pentanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} -N-methyl-N-[(2S, 3R, 4R , 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-[-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]-N-[(2S, 3R, 4R, 5R)-2,3 ,4,5,6-pentahydroxyhexyl] pentanamide; 5-[-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]-N-methyl-N-[(2S,3R,4R,5R) -2,3,4,5,6-pentahydroxyhexyl]pentanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(2S, 3R, 4R, 5R)-2 ,3,4,5,6-pentahydroxyhexyl] pentanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropyl} amino) methyl] 4-methylphenyl} -N-methyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 1-{4-[3-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-4-methylphenyl] butyl} -3 -[(2S, 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl] urea; 1-(4-{3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] 4-dimethyl-phenyl} butyl)-3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) pyridin -3-yl] cyclopropyl} amino) methyl] phenyl} butyl)-3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; N-{[5-(6-aminohexan-2-yl)-2-chlorophenyl] methyl}-1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropan-1-amine; N-({5-[(2S)-6-amino-hexan-2-yl]-2-chlorophenyl} methyl)-1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropan-1-amine ; N-({5-[(2R)-6-Aminohexan-2-yl]-2-chlorophenyl} methyl)-1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropan-1-amine; (5S)-5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] hexan-1-amine; (5R)-5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] hexan-1-amine; (5S)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} hexanoic acid; (5R)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} hexanoic acid; 6-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} heptanoic acid; N-({5-[(2S)-5-aminopentan-2-yl]-2-chlorophenyl} methyl)-1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropan-1-amine; N-({5-[(2R)-5-Aminopentan-2-yl]-2-chlorophenyl} methyl)-1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropan-1-amine; N-{[5-(5-aminopentan-2-yl)-2-chlorophenyl] methyl}-1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropan-1-amine; (5S)-5-{3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl]-4-methylphenyl} hexanoic acid; (5R)-5-{3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl]-4-methylphenyl} hexanoic acid; 1-[(5S)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropyl} amino) methyl] phenyl} hexyl)-3 -[ (2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-[(5R)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropyl} amino) methyl] phenyl} hexyl)-3 -[ (2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(2S, 3R, 4R, 5R)-2 ,3,4,5,6-pentahydroxyhexyl] hexanamide; (2S, 3S, 4R, 5S)-N-(4-{4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} pentyl )-2,3,4,5,6-pentahydroxy-N-methylhexamide; N-benzyl-5-{3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl]-4-methylphenyl} -N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] hexanamide; 5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropyl} amino) methyl] phenyl} -N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} -N-(5-hydroxypentyl)-N-[(2S 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} -N-[2-(morpholine-4-sulfonyl) ethyl ]-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] hexanamide; 1 -[(5S)-5-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] hexyl]-3 -[(2S, 3R , 4S, 5R)-1,3,4,5,6-pentahydroxyhexan-2-yl] urea; 1 -[(5R)-5-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropoxy} methyl) phenyl] hexyl]-3 -[(2S, 3R, 4S, 5R)-1,3,4,5,6-pentahydroxyhexan-2-yl] urea; 1-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) cyclopropyl} amino) methyl] phenyl} hydroxyhexyl] urea; 1-(5-{4-chloro-3 cyclopropyl}amino)methyl]phenyl}hydroxyhexan-2-yl]urea; 1-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)cyclopropyl}amino)methyl]phenyl } hexyl]-3 -[(2S, 3R, 4R, hydroxyhexyl] urea; 1-(6-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) cyclopropyl} amino) methyl ]phenyl} heptyl)-3 -[(2S, 3R, 4R, hydroxyhexyl] urea; 1-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) cyclopropyl} amino ) methyl] phenyl} hexyl) 1-methyl-3 -[(2S, 3R, pentahydroxyhexyl] urea; 1-(5-{4-chloro-3-[({1-[4-(2- cyclopropoxyphenyl) pyridin a-3-yl] pentyl)-3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-penta- -[({1-[4-(2-cyclopropoxyphenyl ) hexyl)-3 -[(2S, 3R, 4S, pyridin-3-yl] 5R)-1,3,4,5,6-penta-pyridin a-3-yl] 5R)-2,3,4 ,5,6-penta-pyridin a-3-yl] 5R)-2,3,4,5,6-penta-pyridin a-3-yl] 4R, 5R)-2,3,4,5,6 - pyridin a-3-yl] cyclopropyl} amino) methyl] phenyl} hexyl)-1-[2-(2-hydroxyethoxy)ethyl]- 3 -[(2S, 3R, 4R, 5R)-2,3,4 ,5,6-pentahydroxyhexyl] urea; 1-(4-{3-[({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropyl} amino) methyl]-4-methylphenyl} pentyl)-3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-(5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}hexyl)-3-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1 -[(5R)-5-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropoxy} methyl) phenyl] hexyl]-3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1 -[(5S)-5-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] hexyl]-3 -[(2S, 3R , 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-{5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl] hexyl}-3-[(2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl]urea; 1-{5-[3-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-4-methylphenyl] hexyl} -3 -[(2S, 3R, 4R, 5R) -2,3,4,5,6-pentahydroxyhexyl] urea; (2S, 3S, 4R, 5S)-N-(4-{4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} pentyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-oxo-imidazolidin-1-yl) ethyl] hexanamide; (2S, 3S, 4R, 5S)-N-(4-{4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} pentyl )-2,3,4,5,6-pentahydroxyhexamide; (2S, 3S, 4R, 5S)-N-(5-{4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} hexyl )-2,3,4,5,6-pentahydroxyhexamide; (2S, 3S, 4R, 5S)-N-(6-{4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} heptyl )-2,3,4,5,6-pentahydroxyhexamide; (2S,3S,4R,5S)-N-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenylly}hexyl )-2,3,4,5,6-pentahydroxy-N-methylhexanamide; (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(2-methoxyethyl)hexanamide; (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide; (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(3-methoxypropyl)hexanamide; (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide; (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide; (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(oxan-4-ylmethyl)hexanamide; (2S,3S,4R,5S)-N-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenylly}hexyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl]hexanamide; (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl)hexanamide; (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-N-(4-acetamidobutyl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenylly}hexyl )-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl)hexanamide; (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl)hexanamide; (2S, 3S, 4R, 5S)-N-(4-{4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} pentyl )-N-[2-(ethanesulfonyl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-[3-(2-oxopyrrolidin-1-yl)propyl] hexanamide; (2S, 3S, 4R, 5S)-N-(4-{4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} pentyl )-N-(1,1-dioxo-1À6-tian-4-yl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenylly}hexyl )-N-[2-(ethanesulfonyl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(4-methanesulfonamidobutyl) hexanamide; (2S, 3S, 4R, 5S)-N-(4-{4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} pentyl )-N-[2-(1,1-dioxo-1À64-thiomorpholin-4-yl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide; (2S, 3S, 4R, 5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3- yl] cyclopropyl} amino) methyl]-4-methylphenyl} pentyl) -2,3,4,5,6-pentahydroxyhexamide; (2S, 3S, 4R, 5S)-N-(5-{3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl]-4-methylphenyl} hexyl) -2,3,4,5,6-pentahydroxyhexanamide; (2S, 3S, 4R, 5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3- yl] cyclopropyl} amino) methyl]-4-methylphenyl} pentyl) -2,3,4,5,6-pentahydroxy-N-methylhexamide; (2S,3S,4R,5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}pentyl) -2,3,4,5,6-pentahydroxy-N-(2-methoxyethyl)hexanamide; (2S,3S,4R,5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}pentyl) -2,3,4,5,6-pentahydroxy-N-(3-methoxypropyl)hexanamide; (2S,3S,4R,5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}pentyl) -2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide; (2S,3S,4R,5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}pentyl) -2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl) hexanamide; (2S, 3S, 4R, 5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3- yl] cyclopropyl} amino) methyl]-4-methylphenyl} pentyl) -N-(1,1-dioxo-1À6-tian-4-yl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}pentyl) -N-[2-(ethanesulfonyl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide; (2S, 3S, 4R, 5S)-N-{5-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] hexyl} -2 3,4,5,6-pentahydroxyhexanamide; (2S, 3S, 4R, 5S)-N-{4-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentyl} -2 3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl)-hexanamide; (2S, 3S, 4R, 5S)-N-{4-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentyl} -N -[2-(ethanesulfonyl) ethyl]-2,3,4,5,6-pentahydroxyhexanamide; (2S, 3S, 4R, 5S)-N-{4-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] pentyl} -N -(1,1-dioxo-1À6-tian-4-yl)-2,3,4,5,6-pentahydroxyhexanamide; (2S, 3S, 4R, 5S)-N-{5-[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]hexyl}-2, 3,4,5,6-pentahydroxyhexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S, 3R, 4S, 5R)- 1,3,4,5,6-pentahydroxyhexan-2-yl] hexanamide; (5S)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; (5R)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]hexanamide; 6-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]heptanamide; (2S, 3S, 4R, 5S)-6 -{[1-(5-{4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl ]phenyl}hexanoyl)piperidin-4-yl]amino}-2,3,4,5-tetrahydroxyhexanoic acid; 4-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} hexanoyl)-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]piperazine-1-carboxamide; 1-[1-(5-{4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) cyclopropyl} amino) methyl] phenyl} hexanoyl) piperidin-4-yl]-3 -[(2S , 2,3,4,5,6-pentahydroxyhexyl] urea; ) methyl] phenyl} hexanoyl) piperazin-1-yl]-N-[(2S, 2,3,4,5,6-pentahydroxyhexyl] acetamide; 4-[2-(5-{4-chloro -3 -[({1-[4-(2-cyclopropoxyphenyl) 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; -[4-(2-cyclopropoxyphenyl) pyridin-3- yl] cyclopropyl} amino) methyl] phenyl} -N-{2-[4 -({[(2S, 3R, 4R, 5R)-2,3,4 ,5,6-pentahydroxyhexyl] carbamoyl} methyl) piperazin-1-yl] ethyl} hexamide (5S)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl); )pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide (5R) -5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino )methyl]phenyl}-N-methyl-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; (6S)-6-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]heptanamide; (6R)-6-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]heptanamide; 6-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]heptanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} -N-(2-hydroxyethyl)-N-[(2R 3S, 4S, 5S)-2,3,4,5,6-pentahydroxyhexyl] hexanamide; N-(carbamoylmethyl)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} -N-(2-methoxyethyl)-N-[(2R 3S, 4S, 5S)-2,3,4,5,6-pentahydroxyhexyl] hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-(3-hydroxypropyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; N-(2-carbamoylethyl)-5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(methylcarbamoyl)methyl]-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[2-(dimethylamino)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-(3-methoxypropyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} -N-(oxan-4-yl)-N-[ (2R, 3S, 4S, 5S)-2,3,4,5,6-pentahydroxyhexyl] hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(dimethylcarbamoyl)methyl]-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} -N-(3-hydroxy-2,2-dimethylpropyl) -N-[(2R, 3S, 4S, 5S)-2,3,4,5,6-pentahydroxyhexyl] hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[2-(2-hydroxyethoxy)ethyl]- N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[(2R, 3S, 4S, 5S)- 2,3,4,5,6-pentahydroxyhexyl]-N-[(1s,4s)-4-hydroxycyclohexyl]hexamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[2-(ethylcarbamoyl)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[2-(dimethylcarbamoyl)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-(2-methanesulfonylethyl)-N-[(2R ,3S,4S,5S)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-(3-methanesulfonylpropyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-[2-(dimethylsulfamoyl)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-ethylphenyl}-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]hexanamide; (5S)-5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methyl-phenyl}-N-methyl-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; (5R)-5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methyl-phenyl}-N-methyl-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-methyl-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]-N-(propan-2-yl)hexanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]-N-propylhexamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(2-hydroxyethyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; N-(Carbamoylmethyl)-5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(2-methoxyethyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(3-hydroxypropyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; N-(2-carbamoylethyl)-5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(methylcarbamoyl)methyl]-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[2-(dimethylamino)ethyl]-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(3-methoxypropyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(oxan-4-yl)-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[(dimethylcarbamoyl)methyl]-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[2-(ethylcarbamoyl)ethyl]-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-[2-(dimethylcarbamoyl)ethyl]-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; (5S)-5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methyl-phenyl}-N-(2-methanesulfonylethyl)- N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] hexamide; (5R)-5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methyl-phenyl}-N-(2-methanesulfonylethyl)- N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] hexamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(2-methanesulfonylethyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-N-(3-methanesulfonylpropyl)-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 2-[4-(5-{3-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl]-4-methyl-phenyl} hexanoyl) piperazin-1-yl ]-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide; 5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-ethyl-N-[(2S,3R,4R,5R) -2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-N-(2-hydroxyethyl)-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]-N-ethyl-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]hexanamide; 5-[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]-N-(2-hydroxyethyl)-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pentyl)-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; N-(5-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}hexyl)-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; 5-{2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-N-methyl-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]hexanamide; (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}- 5-hydroxypentyl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pent -4-en-1-yl)-2,3,4,5,6-pentahydroxyhexamide; (2S, 3S, 4R, 5S)-N-[3-(1-{4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl}cyclopropyl)propyl]-2,3,4,5,6-pentahydroxyhexanamide; 1-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}pent-4-en-1-yl)- 3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-(4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}-5-hydroxypentyl)-3-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-[3-(1-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}cyclopropyl)propyl]-3-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; (2S,3S,4R,5S)-N-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-5 -hydroxypentyl)-2,3,4,5,6-pentahydroxyhexanamide; 1-(4-{3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}-5-hydroxypentyl)-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; (2S,3S,4R,5S)-N-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]butyl}-2 ,3,4,5,6-pentahydroxyhexanamide; 1-{4-[N-methyl-4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]-cyclopropoxy} methyl) benzenesulfonamido] butyl} -3 -[(2S, 3R, 4S 5R)-1,3,4,5,6-pentahydroxyhexan-2-yl] urea; 1-{4-[N-ethyl-4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido] butyl} -3 -[(2S, 3R , 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 3-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]-1-{4-[N-(propan-2-yl)4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido] butyl} urea; 1-(4-{N-methyl 2,4-dichloro-5 -[({1-[4-(2-cyclopropoxyphenyl) pyridin a- 3-yl] cyclopropyl} amino) methyl] benzenesulfonamido} butyl)-3 - [(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N,N-dimethylbenzene-1-sulfonamide; 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N-methylbenzene-1-sulfonamide; 3-(1-{[2-chloro-5-(pyrrolidine-1-sulfonyl)phenyl]methoxy}-cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridine; 3-(1-{[2-chloro-5-(piperidine-1-sulfonyl)phenyl]methoxy}-cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridine; (2S, 3R, 4R, 5R)-S-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-2,3,4, 5,6-pentahydroxyhexane-1-sulfonamido; (2S, 3R, 4R, 5R)-S-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-2,3,4, 5,6-pentahydroxy-N-methylhexane-1-sulfonamido; N-[2-(2-aminoethoxy)ethyl]-4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzene-1-sulfonamide; N-[2-(2-aminoethoxy)ethyl]-4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N-methylbenzene-1-sulfonamide; 1-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl]urea; 1-{4-[N-methyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-(2-{2-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido] ethoxy} ethyl)-3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-(2-{2-[N-methyl-4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropoxy} methyl) benzenesulfonamido] ethoxy} ethyl)-3 -[(2S, 3R, 4R, 5R)- 2,3,4,5,6-pentahydroxyhexyl] urea; 1-{5-[N-methyl-4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido] pentyl} -3 -[(2S, 3R , 4S 5R)-1,3,4,5,6-pentahydroxyhexan-2-yl] urea; 1-(2-{2-[N-methyl-4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropoxy} methyl) benzenesulfonamido] ethoxy} ethyl)-3 -[(2S, 3R, 4S, 5R)- 1,3,4,5,6-pentahydroxyhexan-2-yl] urea; 1-{4-[N-(2-methoxyethyl)4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]butyl}-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-(2-{2-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido] ethoxy} ethyl)-3 -[(2S, 3R, 4S, 5R)-1,3,4,5,6-pentahydroxyhexan-2-yl] urea; 1-{5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]pentyl}-3-[(2S,3R,4S,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 1-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4S,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 1-(2-{2-[N-ethyl-4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropoxy} methyl) benzenesulfonamido] ethoxy} ethyl)-3 -[(2S, 3R, 4R, 5R)- 2,3,4,5,6-pentahydroxyhexyl] urea; 1-{5-[N-(2-methoxyethyl)4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]pentyl}-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-{5-[N-(2-methoxyethyl)4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]pentyl}-3-[( 2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 1-{4-[N-(2-hydroxyethyl)4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]butyl}-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-(2-{2-[N-ethyl-4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropoxy} methyl) benzenesulfonamido] ethoxy} ethyl)-3 -[(2S, 3R, 4S, 5R)- 1,3,4,5,6-pentahydroxyhexan-2-yl] urea; 1-{4-[N-(2-methoxyethyl)4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]butyl}-3-[( 2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 1-(2-{1-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonyl] piperidin-4-yl} ethyl)-3- [(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]-1 -[(1r, 4r)-4- [4-chloro-3 -({ 1-[4Cyclopropoxy}methyl)benzenesulfonamido]cyclohexyl]urea; 3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]-1 -[(1s, 4s)- 4-[4-chloro-3 -({ 1-[4Cyclopropoxy}methyl)benzenesulfonamido]cyclohexyl]urea; 1 -({1-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonyl] pyrrolidin-3-yl} methyl)-3 -[( 2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-(2-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}ethyl)-3- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-(4-{2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]ethyl}cyclohexyl)-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-(3-{4-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonyl] piperazin-1-yl} propyl)-3- [(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-({1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperidin-4-yl}methyl)-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-(2-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperazin-1-yl}ethyl)-3- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-({1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperidin-3-yl}methyl)-3-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}-3-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-{7-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonyl]-7-azaspiro[3. 5] nonan-2-yl} -3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]pyrrolidin-3-yl}-3-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-{2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonyl]-2-azaspiro[3. 3] heptan-6-yl} -3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 6-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-[(2S,3R,4R,5R)-2,3 ,4,5,6-pentahydroxyhexyl]hexanamide; 7-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-[(2S, 3R, 4R, 5R)-2,3 4,5,6-pentahydroxyhexyl] heptanamide; 5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-[(2S,3R,4R,5R)-2,3 ,4,5,6-pentahydroxyhexyl]pentanamide; 3-[N-methyl-4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-[(2S, 3R, 4R, 5R) -2 3,4,5,6-pentahydroxyhexyl]propanamide; (1R, 5S, 6S)-3-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonyl]-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]-3-azabicyclo[3. 1. 0] hexane-6-carboxamide; (1r, 4r)-4-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamidomethyl]-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]cyclohexane-1-carboxamide; 1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonyl]-N-[(2S, 3R, 4R, 5R)-2,3 4,5,6-pentahydroxyhexyl]-piperidine-4-carboxamide; 2-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; 3-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido]-N-[(2S, 3R, 4R, 5R)-2 , 3,4,5,6-pentahydroxyhexyl]cyclopentane-1-carboxamide; 2-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperazin-1-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; 2-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperidin-4-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; (1r, 4r)-4-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido]-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]cyclohexane-1-carboxamide; 3-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperazin-1-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide; 2-({1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperidin-4-yl}oxy)-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; 4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-[(2S, 3R, 4R, 5R)-2,3 4,5,6-pentahydroxyhexyl] bicyclo[2. two. 2] octane-1-carboxamide; (2E)-3-{1-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropoxy} methyl) benzenesulfonyl] azetidine-3-yl} -N- [(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]prop-2-enamide; 2-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]-cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}-N-methyl- N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide; 3-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide; 3-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]piperidin-4-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide; (2E)-3-{1-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonyl] pyrrolidin-3-yl} -N-[ (2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] prop-2-enamide; 3-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]pyrrolidin-3-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide; (2E)-4-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]but-2-enamide; 4-{1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 2-({1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}oxy)-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; 2 -({1-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonyl] pyrrolidin-3-yl} methoxy)-N- [(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide; 2-({1-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]azetidin-3-yl}methoxy)-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; (2S, 3S, 4R, 5S)-N-{4-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido] butyl} -2 3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl)hexanamide; (2S, 3S, 4R, 5S)-2,3,4,5,6-pentahydroxy-N-{4-[N-methyl-4-chloro-3 -({1-[4-(2- cyclopropoxyphenyl)] pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido] butyl} hexanamide; (2S, 3S, 4R, 5S)-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl)-N-{4-[N-methyl-4-chloro-3 -(1 -1[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}hexanamide; (2S,3S,4R,5S)-N-{4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]butyl}-2 ,3,4,5,6-pentahydroxy-N-methylhexanamide; (2S, 3S, 4R, 5S)-2,3,4,5,6-pentahydroxy-N-methyl-N-{4-[N-methyl-4-chloro-3-({1-[4 -(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido] butyl} hexanamide; (2S, 3S, 4R, 5S)-N-(2-{1-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonyl] piperidine -4-yl}ethyl)-2,3,4,5,6-pentahydroxyhexanamide; N-(4-aminobutyl)-4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N-ethylbenzene-1-sulfonamide; 1-(4-{N-methyl-4-chloro-3 -[(1-{4-[2-(oxetan-3-yloxy) phenyl] pyridin-3-yl} cyclopropoxy) methyl] benzenesulfonamido} butyl)- 3-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-{4-[N-ethyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4S ,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 1-{4-[N-methyl4-chloro-5-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-2-fluorobenzenesulfonamido]butyl}-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-{4-[N-methyl2,4-dichloro-5-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]butyl}-3-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-(4-{N-methyl3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl]-4-(trifluoromethyl) benzenesulfonamido} butyl)-3 -[( 2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-{4-[N-methyl3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-(trifluoromethyl)benzenesulfonamido]butyl}-3-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-(4-{N-methyl3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl]-4-(trifluoromethyl) benzenesulfonamido} butyl)-3 -[( 2S, 3R, 4S, 5R)-1,3,4,5,6-pentahydroxyhexan-2-yl] urea; 1-(4-{N-methyl4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]benzenesulfonamido}butyl)-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-(4-{N-methyl4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]benzenesulfonamido}butyl)-3-[(2S, 3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 1-(4-{N-ethyl4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]benzenesulfonamido}butyl)-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-(4-{N-methyl4-chloro-5-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-2-fluorobenzenesulfonamido}butyl)-3-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-(4-{N-methyl-4-chloro-5 -[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-2-fluorobenzenesulfonamido}butyl)-3 -[(2S, 3R, 4S, 5R)-1,3,4,5,6-pentahydroxyhexan-2-yl] urea; 1-(4-{N-methyl2,4-dichloro-5-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]benzenesulfonamido}butyl)-3-[( 2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 1-(4-{N-methyl3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylbenzenesulfonamido}butyl)-3-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-(4-{N-methyl3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylbenzenesulfonamido}butyl)-3-[(2S,3R ,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 1-{4-[N-methyl3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylbenzenesulfonamido]butyl}-3-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]urea; (2S)-5-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropoxy} methyl) benzenesulfonamido]-2 -{[(2,3,4, 5 6-pentahydroxyhexyl) carbamoyl] amino} pentanoic acid; (2R)-2-amino-6-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-ethylhexanamide; (2R)-6-[4-Chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido]-N-ethyl-2 -({[( 2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl} amino) hexanamide; (2S)-2-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido]-6 -({[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl} amino) hexanoic acid; (2S)-2-amino-6-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido] hexanoic acid; (2S)-6-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido]-2 -({[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl} amino) hexanoic acid; (2S)-2-amino-6-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-ethylhexanamide; (2S)-6-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]-N-ethyl-2-({[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino)hexanamide; 1-(5 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulfanyl} pentyl)-3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; (2S, 3S, 4R, 5S)-N-(5 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulfanyl} pentyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl]hexamide; 1-[2-(2 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulfanyl} ethoxy) ethyl]-3-( 2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-(2-{2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfinyl]ethoxy}ethyl)-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-(2-{2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]ethoxy}ethyl)-3-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-{2-[2 -({4-chloro-3 -[(1-{4-[2-(oxetan-3-yloxy) phenyl] pyridin-3- yl} cyclopropoxy) methyl] phenyl} sulfanyl) ethoxy ] ethyl} -3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-[5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)pentyl]-3-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 5 -({6 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl]-5-methylpyridin-2-yl} sulphanyl)-N-methyl-N-[ (2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]-N-{[5-methyl-2-(methylsulfanyl) pyrimidin-4-yl] methyl} cyclopropan-1-amine; 4 -{[3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)- 4-ethylphenyl] sulphanyl} -N-[(2S, 3R, 4R, 5R)-2 3,4,5,6-pentahydroxyhexyl] butanamide; 4 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulphanyl} -N-[(2S, 3R, 4R, 5R)- 2,3,4,5,6-pentahydroxyhexyl] butanamide; N-[5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)pentyl]-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; N-(3 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropoxy} methyl) phenyl] sulphanyl} propyl)-N-[(2S, 3R , 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide; N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl)-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)propyl]-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)butyl]-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; N-[2 -({4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin a-3-yl] cyclopropyl} amino) methyl] phenyl} sulphanyl) ethyl]-N-[( 2S 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide; N-(2-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}ethyl)-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; (2S, 3S, 4R, 5S)-N-[4 -({4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-methylhexanamide; (2S,3S,4R,5S)-N-[5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)pentyl]-2,3,4,5,6-pentahydroxy-N-methylhexanamide; (2S, 3S, 4R, 5S)-N-(3 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulfanyl} propyl )-2,3,4,5,6-pentahydroxy-N-methylhexanamide; (2S, 3S, 4R, 5S)-N-(5 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulfanyl} pentyl )-2,3,4,5,6-pentahydroxy-N-methylhexanamide; (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-methylhexanamide; (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-methylhexanamide; (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide; (2S, 3S, 4R, 5S)-N-(4 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulfanyl} butylyl )-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl) hexanamide; (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide; (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-[3-(2-oxopyrrolidin-1-yl)propyl] hexanamide; (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-(oxan-4-ylmethyl)hexanamide; (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-oxoimidazolidin-1-yl)ethyl] hexanamide; (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide; (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide; (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-[3-(2-oxopyrrolidin-1-yl)propyl] hexanamide; (2S, 3S, 4R, 5S)-N-(3 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulfanyl} propyl )-N-[2-(1,1-dioxo-1À64-thiomorpholin-4-yl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-(oxan-4-ylmethyl)hexanamide; (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl) hexanamide; (2S, 3S, 4R, 5S)-N-(4 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulfanyl} butylyl )-N-[2-(1,1-dioxo-1À64-thiomorpholin-4-yl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl)hexamide; (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide; (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide; (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide; (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-[3-(2-oxopyrrolidin-1-yl)propyl]hexanamide; (2S, 3S, 4R, 5S)-N-[3 -({4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} sulfanyl) propyl]-N-[2-(1,1-dioxo-1À6 4-thiomorpholin-4-yl) ethyl]-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-[2-(2-oxoimidazolidin-1-yl)ethyl]hexanamide; (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl) hexanamide; (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide; (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide; (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide; (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(oxan-4-ylmethyl)hexanamide; (2S, 3S, 4R, 5S)-N-(3 -{[3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-4-methylphenyl] sulfanyl} propyl) 2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl) hexanamide; (2S, 3S, 4R, 5S)-N-(3 -{[3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)-4-methylphenyl] sulfanyl} propyl) 2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl]hexamide; (2S,3S,4R,5S)-N-(3-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}propyl) -2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide; (2S,3S,4R,5S)-N-(3-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}propyl) -2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide; (2S,3S,4R,5S)-N-(4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}butyl) -2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide; (2S,3S,4R,5S)-N-[2-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)ethyl]-2,3,4,5,6-pentahydroxy-N-methylhexanamide; (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-[2-(2-oxoimidazolidin-1-yl)ethyl] hexanamide; (2S,3S,4R,5S)-N-[3-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )propyl]-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl)hexamide; (2S,3S,4R,5S)-N-[3-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )propyl]-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl]hexamide; (2S,3S,4R,5S)-N-[3-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )propyl]-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexamide; (2S,3S,4R,5S)-N-[3-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )propyl]-2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide; (2S,3S,4R,5S)-N-[4-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )butyl]-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl) hexanamide; (2S,3S,4R,5S)-N-[4-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )butyl]-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide; (2S,3S,4R,5S)-N-[4-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )butyl]-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl) hexanamide; (2S,3S,4R,5S)-N-(4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}butyl) -2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide; (2S, 3S, 4R, 5S)-N-[3 -({4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} sulfanyl) propyl]-N-(1,1-dioxo-1À6-tian-4-yl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(oxan-4-ylmethyl)hexamide; (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-[3-(2-oxopyrrolidin-1-yl)propyl]hexanamide; (2S,3S,4R,5S)-N-(2-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}ethyl )-2,3,4,5,6-pentahydroxy-N-methylhexanamide; (2S, 3S, 4R, 5S)-N-(3 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulfanyl} propyl )-N-(1,1-dioxo-1À6-tian-4-yl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-N-[2-(1,1-dioxo-1À6,4-thiomorpholin-4-yl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonylpropyl) hexanamide; (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl)hexanamide; (2S,3S,4R,5S)-N-[4-({3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-4-methylphenyl}sulfanyl )butyl]-2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide; (2S,3S,4R,5S)-N-(4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}butyl) -2,3,4,5,6-pentahydroxy-N-(3-mehanesulphonylpropyl)hexanamide; (2S,3S,4R,5S)-N-(4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}butyl) -2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide; (2S, 3S, 4R, 5S)-N-[4 -({4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} sulfanyl)butyl]-N-(2-acetamidoethyl)-2,3,4,5,6-pentahydroxyhexanamide; (2S, 3S, 4R, 5S)-N-(4 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulfanyl} butylyl )-N-(2-acetamidoethyl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-(oxan-4-yl)hexanamide; (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-N-(3-acetamidopropyl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-N-(4-acetamidobutyl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-N-(4-acetamidobutyl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-N-(1,1-dioxo-1ÀMhian-4-yl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-(4-methanesulfonamidobutyl) hexanamide; (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonamidoethyl) hexanamide; N-{2 -[(2S, 3S, 4R, 5S)-N-[4 -({4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl ethyl} amino) methyl] phenyl} sulfanyl) butyl]-2,3,4,5,6-pentahydroxyhexanamido] ethyl} carbamate; (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-N-(3-acetamidopropyl)-2,3,4,5,6-pentahydroxyhexanamide; N-{3 -[(2S, 3S, 4R, 5S)-N-[4 -({4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl ethyl} amino) methyl] phenyl} sulfanyl) butyl]-2,3,4,5,6-pentahydroxyhexamido] propyl} carbamate; (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonamidoethyl) hexanamide; N-{2 -[(2S, 3S, 4R, 5S)-N-(4 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxyl} methyl )phenyl]sulfanyl}butyl)-2,3,4,5,6-pentahydroxyhexanamido]ethyl}carbamate; (2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl )-2,3,4,5,6-pentahydroxy-N-(3-mehanesulphonamidopropyl) hexanamide; ethyl N-{3-[(2S,3S,4R,5S)-N-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy} methyl)phenyl]sulfanyl}butyl)-2,3,4,5,6-pentahydroxyhexanamido]propyl} carbamate; (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl )-N-(4-acetamidobutyl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-(4-methanesulfonamidobutyl) hexanamide; (2S, 3S, 4R, 5S)-N-[4 -({4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} sulfanyl)butyl]-N-(1,1-dioxo-1À6-tian-4-yl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(4-methanesulfonamidobutyl) hexanamide; (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl) hexanamide; (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl) hexanamide; (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonamidoethyl) hexanamide; (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-N-(2-acetamidoethyl)-2,3,4,5,6-pentahydroxyhexanamide; ethyl N-{2-[(2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropyl }amino)methyl]phenyl}sulfanyl)propyl]-2,3,4,5,6-pentahydroxyhexamido]ethyl} carbamate; (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonamido-propyl)hexanamide; (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-N-(3-acetamidopropyl)-2,3,4,5,6-pentahydroxyhexanamide; ethyl N-{3-[(2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropyl }amino)methyl]phenyl}sulfanyl)propyl]-2,3,4,5,6-pentahydroxyhexamido]propyl} carbamate; (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonamidopropyl)hexamide; (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-(3-methanesulfonamidopropyl) hexanamide; (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl )-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonamidoethyl) hexanamide; (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl )-N-(3-acetamidopropyl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl )-N-(2-acetamidoethyl)-2,3,4,5,6-pentahydroxyhexanamide; ethyl N-{3-[(2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy} methyl)phenyl]sulfanyl}propyl)-2,3,4,5,6-pentahydroxyhexamido]propyl} carbamate; ethyl N-{2-[(2S,3S,4R,5S)-N-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy} methyl)phenyl]sulfanyl}propyl)-2,3,4,5,6-pentahydroxyhexanamido]ethyl} carbamate; (2S,3S,4R,5S)-N-[5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)pentyl]-2,3,4,5,6-pentahydroxy-N-[2-(2-hydroxyethoxy)ethyl] hexanamide; (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-2,3,4,5,6-pentahydroxy-N-(4-methanesulfonamidobutyl) hexanamide; (2S,3S,4R,5S)-N-[5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)pentyl]-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide; (2S,3S,4R,5S)-N-[5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)pentyl]-2,3,4,5,6-pentahydroxy-N-(5-hydroxypentyl) hexanamide; (2S,3S,4R,5S)-N-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)propyl]-N-(4-acetamidobutyl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(2-methanesulfonylethyl) hexanamide; (2S, 3S, 4R, 5S)-N-(5 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulfanyl} pentyl )-N-[2-(ethanesulfonyl)ethyl]-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(4-hydroxybutyl)hexanamide; (2S,3S,4R,5S)-N-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}pentyl )-2,3,4,5,6-pentahydroxy-N-(5-hydroxypentyl)hexanamide; (2S, 3S, 4R, 5S)-N-{5-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfinyl] pentyl} -2 3,4,5,6-pentahydroxyhexamide; (2S, 3S, 4R, 5S)-N-{5-[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonyl] pentyl} -2 3,4,5,6-pentahydroxyhexamide; (2S, 3S, 4R, 5S)-N-(Carbamoylmethyl)-N-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl )phenyl]sulfanyl}pentyl)-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N- (Carbamoylmethyl)-N-[5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl}sulfanyl)pentyl]-2,3,4,5,6-pentahydroxyhexanamide; (2S,3S,4R,5S)-N-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}pentyl )-2,3,4,5,6-pentahydroxyhexanamide; (2R, 3R, 4R, 5S)-6 -[(4 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulfanyl} butyl)(2-methanesulfonylethyl)amino] hexane-1,2,3,4,5-pentol; (2R, 3R, 4R, 5S)-6 -[(3 -{[3 -({1-[4-(2-cyclopropoxyphenyl) pyridin- 3-yl] cyclopropoxy} methyl)-4-methylphenyl] sulfanyl} propyl )(2-methanesulfonylethyl)amino] hexane-1,2,3,4,5-pentol; (2R, 3R, 4R, 5S)-6 -[(4 -{[3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3- yl] cyclopropoxy} methyl)-4-methylphenyl] sulfanyl} butyl )(2-methanesulfonylethyl)amino] hexane-1,2,3,4,5-pentol; 3-(1-{[2-chloro-5-(methylsulfanyl)phenyl]methoxy}cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridine; [4-(2-cyclopropoxyphenyl) pyridin-3-yl]-N-{[5-methyl-2-(methylsulfanyl) pyridin-4-yl] methyl} cyclopropan-1-amine; 4 -{[3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)- 4-(propan-2-yl) phenyl] sulphanyl} -N-methyl-N-[ (2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 1-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl)-3-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-[3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)propyl]-3-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)butyl]-3-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; (2S,3S,4R,5S)-N-[4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl} amino)methyl]phenyl} sulfanyl)butyl]-2,3,4,5,6-pentahydroxy-N-[2-(2-oxoimidazolidin-1-yl)ethyl]hexanamide; 1-(3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}propyl)-3-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]urea; 1-{2-[2 -({4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} sulfanyl) ethoxy] ethyl} - 3 -[(2S, 3R, 4R, 5R)- 2,3,4,5,6-pentahydroxyhexyl] urea; 1-(4 -{[(5 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulphanyl} pentyl) carbamoyl] amino} butyl)-3 -[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl)-3-[(2S,3R, 4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 1-(4-{[(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl)carbamoyl]amino} butyl)-3-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] urea; 1-(5 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulphanyl} pentyl)-3 -[(1r, 4r) 4 -({[(2S, 3R, 4R, 5R)- 2,3,4,5,6-pentahydroxyhexyl] carbamoyl} amino) cyclohexyl] urea; 2-(4 -{[(5 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulphanyl} pentyl) carbamoyl] amino} piperidin-1-yl)-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide; 1-(4 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl]sulfanyl} butyl)-3 -[(1r, 4r) -4 -({[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl} amino) cyclohexyl] urea; 2-(4-{[(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl)carbamoyl]amino} piperidin-1-yl)-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; 1-(5 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulphanyl} pentyl)-3 -[(1s, 4s) 4 -({[(2S, 3R, 4R, 5R)- 2,3,4,5,6-pentahydroxyhexyl] carbamoyl} amino) cyclohexyl] urea; 1-(4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}butyl)-3-[(1s,4s) -4-({[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl}amino) cyclohexyl]urea; 1-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}pentyl)-3-[(2S,3R, 4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 1-[2-(2-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}ethoxy)ethyl]-3-[ (2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 1-{5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfinyl]pentyl}-3-[(2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl]urea; 1-{5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]pentyl}-3-[(2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl]urea; 1-(2-{2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]ethoxy}ethyl)-3-[(2S, 3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 1-{5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfinyl]pentyl}-3-[(2S,3R,4S,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 1-{5-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]pentyl}-3-[(2S,3R,4S,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 1-(2-{2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfinyl]ethoxy}ethyl)-3-[(2S, 3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 5 -({6 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl]-5-methylpyridin-2-yl} sulphanyl)-N-[(2S, 3R , 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]benzenesulfonyl}-N-methyl-N-[(2S, 3R, 4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]benzenesulfinyl}-N-methyl-N-[(2S, 3R, 4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4 -({4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} sulphanyl)-N-methyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}-N-[(2S,3R,4R,5R)-2 ,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-methylphenyl]sulfanyl}-N-methyl-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-({6-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-5-methylpyridin-2-yl}sulfanyl)-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-({6-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-5-methylpyridin-2-yl}sulfanyl)-N-methyl-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-({4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-5-methylpyrimidin-2-yl}sulfanyl)-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-({4-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]-5-methyl-pyrimidin-2-yl}sulfanyl)-N-methyl-N - [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 5 -{[6 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)- 5-methylpyridin-2-yl] sulphanyl} -N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 5 -{[6 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl)- 5-methylpyridin-2-yl] sulfanyl} -N-methyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-ethyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(2-hydroxyethyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(3-hydroxypropyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[2-(dimethylamino)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] butanamide; N-(carbamoylmethyl)-4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(2-methoxyethyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(2-methanesulfonylethyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]-N-propylbutanamide; N-benzyl-4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[(2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl]-N-(propan-2-yl)butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(oxan-4-yl)-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[(methylcarbamoyl)methyl]-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[2-(dimethylcarbamoyl)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[2-(ethylcarbamoyl)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(3-methoxypropyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[(dimethylcarbamoyl)methyl]-N-[( 2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; N-(2-carbamoylethyl)-4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)phenyl]sulfanyl}-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 3-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)-N-methyl-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide; 3-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]propanamide; 5-({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)-N-methyl-N-[(2S, 3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide; 2-[1 -({[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulfanyl} methyl) cyclopropyl]-N-methyl-N -[(2S, 3R, 4R, 5R)- 2,3,4,5,6-pentahydroxyhexyl] acetamide; 4-[({4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}sulfanyl)methyl]-N-methyl-N-[ (2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]benzamide; 2-{1 -[({4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenyl} sulfanyl) methyl] cyclopropyl} -N- methyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] acetamide; 5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]pentanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[2-(2-hydroxyethoxy)ethyl]- N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(5-hydroxypentyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4 -({[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulphanyl} methyl)-N-methyl-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] benzamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[2-(morpholino-4-sulfonyl)ethyl ]-N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] butanamide; 4 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulphanyl} -N-(3-hydroxy-2,2-dimethylpropyl) -N-[(2R, 3S, 4S, 5S)-2,3,4,5,6-pentahydroxyhexyl] butanamide; 4 -{[4-chloro-3 -({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) phenyl] sulphanyl} -N-[(2R, 3S, 4S, 5S)- 2,3,4,5,6-pentahydroxyhexyl]-N-[(1s,4s)-4-hydroxycyclohexyl]butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N,2-dimethyl-N-[(2S,3R ,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-2-methyl-N-[(2S,3R,4R ,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-4-ethylphenyl]sulfanyl}-N-methyl-N-[(2S,3R,4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-(4-hydroxybutyl)-N-[(2S ,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[2-(dimethylsulfamoyl)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] butanamide; 4-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}-N-[2-(methylsulfamoyl)ethyl]-N- [(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl] butanamide; N-(5-{[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]sulfanyl}pentyl)-N-[(2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl]acetamide; 1-(4-{N-ethyl-4-chloro-3-[({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]benzenesulfonamido}butyl)-3-[( 2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea; 2,5-dichloro-4-[({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropyl} amino) methyl] phenol; 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N,N-diethylbenzene-1-sulfonamide; 2-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido] ethane-1-sulfonic acid; 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzene-1-sulfonamide; 1-{2-[2 -({4-chloro-3 -[(1-{4-[2-(oxetan-3-yloxy) phenyl] pyridin-3- yl} cyclopropoxy) methyl] phenyl} sulfanyl) ethoxy ] ethyl} -3 -[(2S, 3R, 4S, 5R)-1,3,4,5,6-pentahydroxyhexan-2-yl] urea; 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N-methyl-N-(propan-2-yl)benzene-1-sulfonamide; 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N-(propan-2-yl)benzene-1-sulfonamide; 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N-methyl-N-propylbenzene-1-sulfonamide; 4-chloro-N-cyclopentyl-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N-methylbenzene-1-sulfonamide; 4-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonyl]-3,3-dimethylmorpholine; 3 -[(2S, 3R, 4S, 5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]-1-{4-[N-(propan-2-yl) 4 -chloro-3-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido] butyl} urea; (2S, 3S, 4R, 5S)-2,3,4,5,6-pentahydroxy-N-{4-[N-(propan-2-yl) 4-chloro-3 -({1-[ 4-(2-cyclopropoxyphenyl))pyridin-3-yl] cyclopropoxy} methyl) benzenesulfonamido] butyl} hexanamide; N-tert-butyl-4-chloro-3-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl] cyclopropoxy} methyl) benzene-1-sulfonamide; 4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)-N-(oxan-4-yl)benzene-1-sulfonamide; (2S)-S-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy}methyl)phenyl]-1-hydroxypropane-2-sulfonamido; (2R)-S-[4-chloro-3-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]-cyclopropoxy} methyl) phenyl]-1-hydroxypropane-2-sulfonamido; 2-(4-(2-cyclopropoxyphenyl) pyridin-3-yl)-N-(2,5-dichlorobenzyl) propan-2-amine; 4-(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenethyl)-N-((2S, 3R, 4R, 5R)-2,3 4,5,6-pentahydroxyhexyl) benzamide; 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N,N-dimethylbenzamide; 1-(5-(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenoxy) pentyl)-3 -((2S, 3R, 4R, 5R )-2,3,4,5,6-pentahydroxyhexyl) urea; 3 -((4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) benzyl) oxy)-N-((2S, 3R, 4R, 5R)- 2,3,4,5,6-pentahydroxyhexyl) benzamide; 4-chloro-5-((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl)-2-fluoro-N-isopropyl-N-(4-(3 -((2S, 3R , 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl) ureido) butyl) benzenesulfonamide; N-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)phenyl)sulfonyl)acetamide; 4-chloro-5-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-methoxy-N,N-dimethylbenzenesulfonamide; 4-chloro-5-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-hydroxy-N,N-dimethylbenzenesulfonamide; 1-(4 -((4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenyl) sulfonyl)-1,4-diazepan-1-yl) ethan-1-one; 6 -((4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenyl) sulfonyl)-2-methoxy-5,6,7,8-tetra -hydro -1,6-naphthyridine; 6 -((4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenyl) sulfonyl)-5,6,7,8-tetrahydro-1 ,6-naphthyridin-2-ol; 4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl)-N-methyl-N-(4-(3 -((2S, 3R, 4S, 5R )-1,3,4,5,6-pentahydroxyhexan-2-yl) ureido) butyl-1,1,2,2,3,3,4,4-d8) benzenesulfonamide; (2R, 3S, 4R, 5S)-5-(3-(4 -((4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl)-N -methylphenyl)sulfonamido)butyl)ureido)hexane-1,2,3,4,6-pentayl-pentapropionate; 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-(methylthio)phenyl)pyridine; 4-(2-cyclopropoxyphenyl)-3-(2-((2,5-dichlorobenzyl)oxy)propan-2-yl)pyridine; 4-(2-cyclopropoxyphenyl)-3-(1-((2,5-dichlorobenzyl)oxy)cyclobutyl)pyridine; 4-(2-cyclopropoxyphenyl)-3-(1-((2,5-dichlorobenzyl)oxy)cyclopentyl)pyridine; 4-(2-cyclopropoxyphenyl)-3-(3-((2,5-dichlorobenzyl)oxy)tetrahydrofuran-3-yl)pyridine; 4-chloro-3-(((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropyl) amino) methyl)-N-isopropyl-N-(4-(3 -((2S, 3R, 4S, 5R)-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl)benzenesulfonamide; 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclobutoxy) methyl)-N-isopropyl-N-(4-(3 -((2S, 3R, 4S, 5R )-1,3,4,5,6-pentahydroxyhexan-2-yl) ureido) butyl) benzenesulfonamide; 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclobutoxy) methyl)-N-isopropyl-N-(4-(3 -((2S, 3R, 4R, 5R )-2,3,4,5,6-pentahydroxyhexyl) ureido) butyl) benzenesulfonamide; 5-(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenethyl)-N-((2S, 3R, 4R, 5R)-2,3 4,5,6-pentahydroxyhexyl) picolinamide; 4-chloro-3 -(((3-(4-(2-cyclopropoxyphenyl) pyridin-3- yl) tetrahydrofuran-3-yl) oxy) methyl)-N-isopropyl-N-(4-(3 - ((2S, 3R, 4S, 5R)-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl)benzenesulfonamide; 4-chloro-3 -(((3-(4-(2-cyclopropoxyphenyl) pyridin-3- yl) tetrahydrofuran-3-yl) oxy) methyl)-N-isopropyl-N-(4-(3 - ((2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl) ureido) butyl) benzenesulfonamide; 4-chloro-3-(((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropyl)amino)methyl)-N-isopropyl-N-(4-(3-((2S,3R, 4R,5R)-2,3,4,5,6-pentahydroxyhexyl)ureido)butyl)benzenesulfonamide; 4-chloro-3-(((2-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)propan-2-yl)amino)methyl)-N-isopropyl-N-(4-(3-(( 2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl)benzenesulfonamide; 1-(4-(4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenoxy) butyl)-3 -((2S, 3R, 4R, 5R )-2,3,4,5,6-pentahydroxyhexyl) urea; 3 -((4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) benzyl) oxy)-N-((2S, 3R, 4S, 5R)- 1,3,4,5,6-pentahydroxyhexan-2-yl) benzamide; 6 -((4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) benzyl) oxy)-N-((2S, 3R, 4S, 5R)- 1,3,4,5,6-pentahydroxyhexan-2-yl) nicotinamide; 2 -((4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) benzyl) thio)-1-methyl-N-((2S, 3R, 4R , 5R)-2,3,4,5,6-pentahydroxyhexyl)-1H-imidazole-5-carboxamide; 2 -((4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) benzyl) thio)-1-methyl-N-((2S, 3R, 4S 5R)-1,3,4,5,6-pentahydroxyhexan-2-yl)-1H-imidazole-5-carboxamide; 1-(5-(4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenoxy) pentyl)-3 -((2S, 3R, 4S, 5R )-1,3,4,5,6-pentahydroxyhexan-2-yl) urea; 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-isobutyl-N-(4-(3-((2S,3R,4S,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl)benzenesulfonamide; 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-isobutyl-N-(4-(3-((2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl)ureido)butyl)benzenesulfonamide; 4-chloro-5-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-2-fluoro-N-isopropyl-N-(4-(3-((2S,3R ,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl)benzenesulfonamide; 4-chloro-5-((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl)-2-fluoro-N-isopropyl-N-(4-(3 -((2S, 3R , 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl) ureido) butyl) benzenesulfonamide; 4-(2-chloro-6-methoxyphenyl)-3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)pyridine; N-(4-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-methylphenyl)sulfonamido)butyl)acetamide; 4-(2-chlorophenyl)-3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)pyridine; 1 -((4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenyl) sulfonyl)-4-methyl-1,4-diazepane; 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-(thiazol-2-yl)benzenesulfonamide; 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-phenylbenzenesulfonamide; 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-(2,2,2-trifluoroethyl)benzenesulfonamide; 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(o-tolyl)pyridine; 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-methoxy-4-methylphenyl)pyridine; 3-(1-((2-chloro-5-(N-(4-((2S,3S,4R,5S)-2,3,4,5,6-pentahydroxyhexanamido)butyl)sulfamoyl)benzyl)oxy) cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridine 1-oxide 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-methyl-N-( 4-(3-((2S,3R,4R,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl)benzenesulfonamide; (1S, 4S)-2 -((4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenyl) sulfonyl)-5-methyl-2,5 -diazabicyclo[2. two. 1] heptane; 1 -((1S, 4S)-5 -((4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3- yl) cyclopropoxy) methyl) phenyl) sulfonyl)-2,5- diazabicyclo[2. two. 1] heptan-2-yl) etan-1-one; 4-(2-cyclopropoxyphenyl)-3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)pyridazine; 1-(4-(2-cyclopropoxyphenyl) pyridazin-3-yl)-N-(2,5-dichlorobenzyl) cyclopropan-1-amine; 4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl)-6-ethylpyridin-3-yl) cyclopropoxy) methyl)-N-methyl-N-(4-(3 -((2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl) ureido) butyl) benzenesulfonamide; 4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl)-6-ethylpyridin-3-yl) cyclopropoxy) methyl)-N-methyl-N-(4-(3-methyl-3 -( 2S , 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl) ureido) butyl) benzenesulfonamide; 4-(2-cyclopropoxyphenyl)-5-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-2-ethylpyridine; 1-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-5H-chromeno[3,4-c]pyridine; 1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl)-N-(2,5-dichlorophenyl) cyclopropane-1-carboxamide; 4-(2-cyclopropoxyphenyl)-3-(1-((2,5-dichlorophenoxy) methyl) cyclopropyl) pyridine; 6 -((4-chloro-3 -((1-(4-(2-cyclopropoxyphenyl) pyridin-3-yl) cyclopropoxy) methyl) phenoxy) methyl)-N-((2S, 3R, 4R, 5R)- 2,3,4,5,6-pentahydroxyhexyl) nicotinamide; 4-(2-cyclopropoxyphenyl)-3-(1-(((2,5-dichlorobenzyl)oxy)methyl)cyclopropyl)pyridine; 6-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)benzyl)oxy)-N-((2S,3R,4R,5R)- 2,3,4,5,6-pentahydroxyhexyl)nicotinamide; 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-methoxy-6-methylphenyl)pyridine; 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-methoxy-3-methylphenyl)pyridine; 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy)methyl)-N-methyl-N-(4-(3-((2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl)ureido)butyl)benzamide; 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-methoxy-5-(trifluoromethoxy)phenyl)pyridine; 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-methoxy-5-(trifluoromethyl)phenyl)pyridine; 4-(3-chloro-2-methoxyphenyl)-3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)pyridine; 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-methoxy-5-methylphenyl)pyridine; 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2,2-difluorobenzo[d][1,3]dioxol-4-yl)pyridine; and 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(2-(methylsulfonyl)phenyl)pyridine. 13. A compound, or a salt, pharmaceutically acceptable tautomer thereof, characterized in that the compound is: 4-(2-cyclopropoxyphenyl)-3-(1-((2,5-dichlorobenzyl)oxy)ethyl)pyridine; 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)ethoxy)methyl)-N-isopropyl-N-(4-(3-((2S,3R,4S,5R )-1,3,4,5,6-pentahydroxyhexan-2-yl)ureido)butyl)benzenesulfonamide; 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)ethoxy)methyl)-N-isopropyl-N-(4-(3-((2S,3R,4R,5R )-2,3,4,5,6-pentahydroxyhexyl)ureido)butyl)benzenesulfonamide; 4-(2-cyclopropoxyphenyl)-3-(1-((2,5-dichlorobenzyl)oxy)propyl)pyridine; N-[(2,5-dichlorophenyl)methyl]-1-(4-phenylpyridin-3-yl)cyclopropan-1-amine; 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-5-ethoxy-4-phenylpyridine; 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-5-methoxy-4-phenylpyridine; 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-phenylpyridine; 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(3-methoxyphenyl)pyridine; 4-(3-chlorophenyl)-3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)pyridine; 3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)-4-(4-methoxyphenyl)pyridine; or 4-(4-chlorophenyl)-3-(1-((2,5-dichlorobenzyl)oxy)cyclopropyl)pyridine. 14. Compound of Formula (II') or Formula (II): characterized in that: P is selected from -O, -CH2OC(O)(C1-C6) alkyl or - CH2OC(O)NRs (C1-C6) alkyl, wherein the alkyl is optionally substituted by - OC(O) (C1-C3) alkyl; and R is H or (C1-C6) alkyl; Q will be C=(O), -CH2-, -NR5- or -O-; when Q is C=(O) then Qi is -NR&- when Q is -NR5- or -O— then Qi is -CH2-, or when Q is -CH2- then Qi is -O (CH2)OI- or - NR5-; X1 be CR6 or N; X2 be CR7 or N; X3 be CR8 or N; X4 be CR9 or N; Y be CRb or N; Ra and Rb are each independently H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, or halogen; R1 be (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, halogen, -S(O)p (C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O- (C3-C8) cycloalkyl, or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents independently selected from halogen, (C1-C4) alkoxy, -OH, -NH2, -NH (C1-C4) alkyl and -N((C1-C4) alkyl)2; or R1 and Ra, together with the atoms to which they are attached, form a heterocycloalkyl ring; or R1 and R3, when on adjacent atoms, together with the carbon atoms to which they are attached form a heterocycloalkyl optionally substituted with one or more substituents independently selected from (C1-C6) alkyl, (C1-C6) alkoxy, (C1- C6) haloalkyl, (C1-C6) haloalkoxy and halogen; R2 is (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, or (C1-C6) haloalkoxy; or R2' is (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, or (C1-C6) haloalkoxy; or R2 and R2', together with the carbon atom to which they are attached form (C3-C8) cycloalkyl or heterocycloalkyl; each R3 being independently, at each occurrence, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, halogen, - S(O)p(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl, or -O-heterocycloalkyl, wherein the alkyl, alkoxy, cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents independently selected from the group consisting of halogen, (C1-C4) alkoxy, -OH, -NH2, -NH (C1-C4) alkyl and -N((CI-C4) aiquji)2; or R1 and R3 together with the carbon atoms to which they are attached form a heterocycloalkyl optionally substituted with one or more substituents independently selected from the group consisting of (C1-C6) alkyl, (C1-C6) alkoxy, (C1 -C6) haloalkyl, (C1-C6) haloalkoxy and halogen; R4 be H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8 ) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, -S(O)m(C1-C6) alkyl, -NH(C1-C4) alkyl, or -N((C1-C4) alkyl)2; R5 is independently H, (C1-C6) alkyl, -C(O)NR10R11, -C(O)(C1-C6) alkyl, or -C(O)O(C1-C6) alkyl; each R6 and R9 independently be H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, heterocycloalkyl, -OH, -NH2, CN, - S(O)o(C1-C6) alkyl, -NH(C1-C4) alkyl, or -N((C1-C4) alkyl)2; each R7 and R8 independently be H, (C1-C8) alkenyl, (C1C8) alkynyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, (C1-C6) hydroxyalkyl, (C1 -C6) aminoalkyl, halogen, (C3-C8) cycloalkyl, (C3-C8) cycloalkenyl, heterocycloalkyl, -OH, -NH2, -S(O)qNH2, -S(O)qOH, CN or (C1C18) alkyl, wherein 0 to 7 methylene of the (C1-C18) alkyl is optionally substituted by a moiety selected from the group consisting of -O-, -NR13-, -(SO)q-, -C(O)-, - C(CH2)-, and -C(NH)-, provided that when any two methylenes in the alkyl are substituted, then two -O-, two -S(O)q- or two -NR13- and -O- and -NR13- are not contiguous, wherein the alkyl is optionally substituted by one or more R12, and wherein the cycloalkyl and cycloalkenyl are optionally substituted by one or more R13; R10 and R11 are each independently H or (C1-C6) alkyl optionally substituted with one or more substituents independently selected from -NH2 and OH; R12 be D, -OH, halogen, -NH2, -NH(C1-C6) alkyl, -N((C1-C6) alkyl)2, -C(O)OH, -OC(O)(C1-C6) alkyl, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl, heteroaryl or R17, wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more substituents independently selected from -OH, -NH2, - NH(C1-C6) alkyl, -N((C1-C6) alkyl)2, halogen and R14; R13 is H, -OH, (C3-C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl, heteroaryl or (C1-C12) alkyl, wherein 0 to 7 methylene of the (C1-C12) alkyl is optionally substituted by a portion selected from the group consisting of -O-, -NR13-, -S(O)r-, -C(O)-, or -C(NH)-, provided that when any two methylenes in the alkyl are substituted , then O and N are not contiguous and wherein the alkyl is optionally substituted with one or more R15, and wherein the cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with one or more substituents independently selected from the group consisting of -OH, -C(O)OH, -NH2, -NH(CI-C6) alkyl and - N((C1-C6) alkyl)2; R14 will be (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl, -O-heterocycloalkyl, (C1-C12) alkyl or (C2-C12) alkenyl, wherein 0 to 7 methylene of (C1- C12) alkyl and (C2-C12) alkenyl are optionally substituted by a moiety selected from the group consisting of -O-, -NR13-, -S(O)r-, -C(O)- or -C( NH)-, provided that when any two methylene in the alkyl or alkenyl is replaced, then O and N are not contiguous and wherein the alkyl and alkenyl are optionally substituted with one or more R15, and the cycloalkyl and heterocycloalkyl are optionally substituted with one or more R16; or when R12 is cycloalkyl or heterocycloalkyl, two R14 together with the atom to which they are attached form C=(O); or when R12 is cycloalkyl or heterocycloalkyl, two R14 together with the atoms to which they are attached form a (C3-C8) cycloalkyl or heterocycloalkyl optionally substituted with one or more R13; or when R12 is cycloalkyl or heterocycloalkyl, two R14 together with the atom to which they are attached form a (C3-C8) spirocycloalkyl or a spiroheterocycloalkyl optionally substituted with one or more R13; or when R12 is cycloalkyl or heterocycloalkyl, two R14 together with the atom to which they are attached form a (C6-C10) aryl or heteroaryl optionally substituted with one or more R13; R15 will be -OH, -NH2, -NH(C1-C6) alkyl, -N((C1-C6) alkyl)2, (C3C8) cycloalkyl, heterocycloalkyl, (C6-C10) aryl or heteroaryl, where the (C3 -C8) cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents independently selected from the group consisting of (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, -C(O)OH, -OH, -NH2, -NH(C1-C6) alkyl, -N((CI-C6) alkyl)2 and oxo; Ri6 will be -OH, -C(O)OH, -NH2, -NH(Ci-Cβ) alkyl, -N((Ci-Ce) alkyl)2, (C1-C6) alkoxy, (C1-C6) hydroxyalkyl, (C3-C8) cycloalkyl, heterocycloalkyl, -O-(C3-C8) cycloalkyl, -O-heterocycloalkyl, (C6-C10) aryl or heteroaryl, wherein the (C3-C8) cycloalkyl and heterocycloalkyl are optionally substituted with one or plus substituents independently selected from the group consisting of (C1-C6) hydroxyalkyl, (C1-C6) aminoalkyl, -C(O)OH, -OH, -NH2, -NH(C1-C6) alkyl, -N( (CI-C6)alkyl)2e oxo; Ri7 is (C1-C18) alkyl or (C2-C18) alkenyl, wherein 0 to 8 methylene of the (C1-C18) alkyl and (C2-C18) alkenyl are optionally substituted by a moiety selected from the group consisting of -O-, -NRi3-, -S(O)r-, -C(O)-, or -C(NH)-, provided that when any two methylenes in the alkyl or alkenyl are substituted, then O and N are not contiguous and in which the alkyl and alkenyl are optionally substituted by one or more Ri8; R18 is R19, (C6-C10) aryl, or heteroaryl optionally substituted with one or more R2i; Ri9 be (Ci-Ci8) alkyl wherein 0 to 8 methylene of the (Ci-Ci8) alkyl is optionally substituted by a moiety selected from the group consisting of -O-, -NRi3-, -S(O)r- , -C(O)- or -C(NH)-, provided that when any two methylenes in the alkyl or alkenyl are substituted, then O and N are not contiguous and wherein the alkyl is optionally substituted with one or more R20; R20 is (C6-C10) aryl or heteroaryl optionally substituted with one or more R2i; R2iser H, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy or halogen; or two R2i together when on adjacent atoms form a cycloalkyl or heterocycloalkyl optionally substituted with one or more R22; R22 will be -C(O)NH2, -C(O)NH(CI-C6) alkyl, -C(O)N((CI-C6) alkyl)2, -C(O) (C3-C7) cycloalkyl, or -C(O) heterocycloalkyl, wherein the cycloalkyl and heterocycloalkyl are optionally substituted with one or more substituents independently selected from the group consisting of -OH and CN; each m, o, p, q wants to be independently, in each occurrence, 0, 1 or 2; en be 0, 1 or 2. 15. Compound according to claim 14, characterized in that P is -O, -CH2OC(O) C (CH3)3or -CH2OC(O) N (CH3)CH2CH2OC(O) CH3. 16. Compound according to claim 14, characterized in that it is selected from the group consisting of: 3-{1 -[(2-chloro-5-{methyl[4 -({[(2S, 3R, 4S, 5R) -1,3,4,5,6- penta-hydroxyhexan-2-yl] carbamoyl} amino) butyl] sulfamoyl} phenyl) methoxy] cyclopropyl} - 4-(2- cyclopropoxyphenyl) pyridin-1-io-1 -olate; 3-[1 -({2-chloro-5 -[(2S)-6 -({[(2S, 3R, 4S, 5R)-1,3,4,5,6-penta-hydroxyhexan-2 -yl] carbamoyl} amino) hexan-2-yl] phenyl} methoxy) cyclopropyl]-4-(2-cyclopropoxyphenyl) pyridin-1-io-1-olate; 3-{1 -[(2-chloro-5-{ethyl[4 -({[(2S, 3R, 4R, 5R)-2,3,4,5,6-penta-hydroxyhexyl] carbamoyl} amino )butyl]sulfamoyl}phenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)pyridin-1-io-olato; 3-{1 -[(2-chloro-5-{ethyl[4 -({[(2S, 3R, 4R, 5R)-2,3,4,5,6-penta-hydroxyhexyl] carbamoyl} amino )butyl]sulfamoyl}phenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)-1-{[(2,2-dimethylpropanoyl)oxy]methyl}pyridin-1-ium; 1 -[({[2-(acetyloxy) ethyl](methyl) carbamoyl} oxy) methyl]-3-{1 -[(2-chloro-5-{ethyl[4 -({[(2S, 3R, 4R 5R)-2,3,4,5,6-pentahydroxyhexyl] carbamoyl} amino) butyl] sulfamoyl} phenyl) methoxy]-cyclopropyl} -4-(2-cyclopropoxyphenyl) pyridin-1-ium; 3-(1-{[2-chloro-5-(ethylsulfamoyl)phenyl]methoxy}cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridin-1-io-1-olate; 3-(1-{[2-chloro-5-(methylsulfamoyl)phenyl]methoxy}cyclopropyl)-4-(2-cyclopropoxyphenyl)pyridin-1-io-1-olate; 3-{1-[(2-chloro-5-sulfamoylphenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)pyridin-1-io-1-olate; 3-{1 -[(2-chloro-5 -{[4 -({[(2S, 3R, 4R, 5R)-2,3,4,5,6-penta-hydroxyhexyl] carbamoyl} amino) butyl](propaN-2-yl)sulfamoyl}phenyl)methoxy]cyclopropyl}-4-(2-cyclopropoxyphenyl)pyridin-1-io-1-olate; and 3-(1 -((2-chloro-5-(N-(4 -((2S, 3S, 4R, 5S)-2,3,4,5,6-penta-hydroxyhexanamido) butyl) sulfamoyl ) benzyl) oxy) 1-cyclopropyl oxide)-4-(2-cyclopropoxyphenyl) pyridine. 17. Pharmaceutical composition, characterized in that it comprises a compound as defined in any one of the preceding claims, or a pharmaceutically acceptable salt, or tautomer thereof and a pharmaceutically acceptable carrier. 18. Pharmaceutical composition according to claim 17, characterized in that the pharmaceutical composition comprises 1-{4-[N-methyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy}methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea, or a pharmaceutically acceptable salt, or tautomer thereof , and a pharmaceutically acceptable carrier. 19. Pharmaceutical composition according to claim 17, characterized in that the pharmaceutical composition comprises 1-{4-[N-methyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy}methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea, or a pharmaceutically acceptable salt thereof, and a carrier pharmaceutically acceptable. 20. Pharmaceutical composition according to claim 17, characterized in that the pharmaceutical composition comprises 1-{4-[N-methyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy}methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea and a pharmaceutically acceptable carrier. 21. Compound according to claim 1, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that it is 1-{2-[2-({4-chloro-3-[(1-{4-[2 -(oxetan-3-yloxy)phenyl]pyridin-3-yl}cyclopropoxy)methyl]phenyl}suphanyl)ethoxy]ethyl}-3-[(2S,3R,4R,5R)-2,3,4,5, 6-pentahydroxyhexyl] urea. 22. Compound according to claim 1, or a salt, or pharmaceutically acceptable tautomer thereof, characterized in that it is 4- [(4-{2,5-dichloro-4-[({1-[4-(2 -cyclopropoxyphenyl)pyridin-3-yl]cyclopropyl}amino)methyl]phenyl}butyl)[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl]carbamoyl] butanoic acid. 23. Compound, according to claim 1, or a salt, or pharmaceutically acceptable tautomer thereof, characterized by being 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin- 3-yl]cyclopropoxy}methyl)phenyl]-1-{4-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl]piperazin-1-yl}penta -1-one. 24. Compound, according to claim 1, or a salt, or pharmaceutically acceptable tautomer thereof, characterized by being 5-[2,5-dichloro-4-({1-[4-(2-cyclopropoxyphenyl)pyridin- 3-yl]cyclopropoxy}methyl)phenyl]-N-(2,3-dihydroxypropyl)-N-[(2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl] pentanamide. 25. Compound according to claim 1, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that it is N- ({5-[(2S)-6-amino-hexan-2-yl]-2-chlorophenyl }methyl)-1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]cyclopropan-1-amine. 26. Compound, according to claim 1, or a salt, or pharmaceutically acceptable tautomer thereof, characterized by being (5S)- 5-{4-chloro-3 -[({1-[4-(2-cyclopropoxyphenyl )pyridin-3-yl]cyclopropyl}amino)methyl]phenyl} hexanoic acid. 27. Compound according to claim 1, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that it is 1-{4-[N-methyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl )pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4R,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea. 28. Compound according to claim 1, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that it is 4-(4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3- yl)cyclopropoxy)methyl)phenethyl)-N-((2S, 3R, 4R, 5R)-2,3,4,5,6-pentahydroxyhexyl)benzamide. 29. Compound according to claim 1, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that it is 4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3-yl)cyclopropoxy )methyl)N,N-dimethylbenzamide. 30. Compound according to claim 1, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that it is 6-((4-chloro-3-((1-(4-(2-cyclopropoxyphenyl)pyridin-3 -yl)cyclopropoxy)methyl)phenyl)sulfonyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-2-ol. 31. Compound, characterized by being according to any one of claims 1 to 16 and 21 to 30, or a pharmaceutically acceptable salt thereof. 32. Compound, characterized by being according to any one of claims 1 to 16 and 21 to 30. 33. Compound according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that the compound is 1-{4-[N-methyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl) pyridin-3-yl]cyclopropoxy}methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea. 34. Compound according to claim 1, characterized in that the compound is 1-{4-[N-methyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl]cyclopropoxy} methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4S,5R)-1,3,4,5,6-pentahydroxyhexan-2-yl]urea. 35. Use of a compound as defined in any one of claims 1 to 16 and 21 to 30, or a pharmaceutically acceptable salt or tautomer thereof, characterized in that it is for the manufacture of a medicament to treat a disease or disorder associated with TGR5 activation selected from the group consisting of chemotherapy-induced diarrhea, diabetes, Type II diabetes mellitus, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ischemia, infarction myocardial disease, retinopathy, vascular restenosis, hypercholesterolemia, hypertriglyceridamia, dyslipidamia or hyperlipidamia, lipid disorders such as low HDL cholesterol or high LDL cholesterol, arterial hypertension, angina pectoris, coronary artery disease, atherosclerosis, cardiac hypertrophy, hyperphosphatemia, rheumatoid arthritis, asthma , chronic obstructive pulmonary disease (COPD), psoriasis, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition, especially during small bowel syndrome, irritable bowel syndrome (IBS), allergic diseases, fatty liver disease, fatty liver disease non-alcoholic liver disease (NAFLD), liver fibrosis, non-alcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), liver cirrhosis, primary biliary cirrhosis (PBC), renal fibrosis, anorexia nervosa, bulimia nervosa and neurological disorders such as Alzheimer's, multiple sclerosis, schizophrenia, kidney disease, impaired cognition, dysmotility, Parkinson's bowel (DIOS), Cystic Fibrosis bowel, intestinal motility and Gastroparesis. 36. Use according to claim 35, characterized in that the disease or disorder is liver fibrosis. 37. Use according to claim 35, characterized in that the disease or disorder is fatty liver disease. 38. Use according to claim 35, characterized in that the disease or disorder is non-alcoholic fatty liver disease (NAFLD). 39. Use according to claim 35, characterized in that the disease or disorder is non-alcoholic steatohepatitis (NASH). 40. Use according to claim 35, characterized in that the disease or disorder is diabetes. 41. Use according to claim 35, characterized in that the disease or disorder is type II diabetes mellitus. 42. Use according to claim 35, characterized in that the disease or disorder is obesity. 43. Use, according to claim 35, characterized by being use of 1-{4-[N-methyl4-chloro-3-({1-[4-(2-cyclopropoxyphenyl)pyridin-3-yl] cyclopropoxy} methyl)benzenesulfonamido]butyl}-3-[(2S,3R,4S,5R)-1,3,4,5,6pentahydroxyhexan-2-yl]urea, or a pharmaceutically acceptable salt thereof. 44. Use according to claim 43, characterized in that the disease or disorder is liver fibrosis. 45. Use according to claim 43, characterized in that the disease or disorder is fatty liver disease. 46. Use according to claim 43, characterized in that the disease or disorder is non-alcoholic fatty liver disease (NAFLD). 47. Use according to claim 43, characterized in that the disease or disorder is non-alcoholic steatohepatitis (NASH). 48. Use according to claim 43, characterized in that the disease or disorder is diabetes. 49. Use according to claim 43, characterized in that the disease or disorder is type II diabetes mellitus. 50. Use according to claim 43, characterized in that the disease or disorder is obesity.