TW201534593A - Substituted alkyl carboxylic acid derivatives as GPR agonists - Google Patents

Abstract

The present invention relates to substituted alkyl carboxylic acid derivatives (the compounds of Formula (I)), processes for their preparation, pharmaceutical compositions containing said compounds, their use as GPR (G-protein coupled receptor) agonists, particularly as GPR40 agonists and methods of using these compounds in the treatment of GPR40 mediated diseases or conditions.

Description

Substituted alkyl carboxylic acid derivatives as GPR agonists

The present invention relates to a substituted alkylcarboxylic acid derivative (a compound of the formula (I)), a preparation procedure thereof, a pharmaceutical composition comprising the compound, and a GPR (G protein coupled receptor) agonist, particularly as The use of GPR40 agonists and methods of using these compounds for the treatment of GPR40 vector diseases or conditions.

Obesity is a major health problem worldwide. It is a risk factor for developing insulin resistance, type 2 diabetes, hypertension, and cardiovascular disease (Circulation, 2003, 107: 1448-1453). In the United States, only about one-third of adults are considered to be "normal" weight, and similar trends are being observed around the world (Nature, 2006, 444(14): 840-46). Obesity is typically associated with elevated amounts of free fatty acids (FFA) and is associated with glucose intolerance and type 2 diabetes (Cell Metab., 2005, 1(4): 245-58). .

According to one report, in 2000, the prevalence of diabetes in the world was 171 million patients, and it is expected to grow to 366 million in 2030 (30 million in the United States) (Diabetes Care, 2004, 27 (5) ): 1047-53). Increasing incidence is driven by a sharp rise in obesity, especially in Western societies. Type 2 diabetes accounts for 90-95% of all diabetes. When the insulin receptor is stimulated, it activates a complex network of message-transmission pathways, but in patients with type 2 diabetes, those in tissues such as muscle, fat, and liver cells become more insulin-sensitive. Not sensitive or more resistant. Furthermore, patients with type 2 diabetes are typically characterized by reduced glucose-stimulated insulin secretion (GSIS) (Expert Opin. Ther. Patents, 2009, 19(2): 237-264).

Metabolic syndrome, also known as Syndrome-X, is characterized by a group of symptoms including insulin resistance, obesity, hypertension, and dyslipidemia. Persistent obesity dysregulates metabolic processes, including the effects of insulin on glucose-lipid-free fatty acid metabolism, and severely affects the process of controlling blood sugar, blood pressure, and lipids. It is also recognized that people with obesity and metabolic syndrome have an increased risk of developing type 2 diabetes and cardiovascular disease. The prevalence of obesity and metabolic syndrome has increased rapidly in developing countries over the past decades and has already led to an increased risk of cardiovascular disease and consequent morbidity and mortality (JRAAS, 2006, 7(1): S12- S18; J. Clin. Endocrinol. Metab., 2008, 93(11): S9–S30).

It is well known that insulin production is critical for carbohydrate and lipid metabolism, and insulin disorders result in symptoms of type 2 diabetes, such as the severe metabolic disease discussed above. Relatively recently, G-protein coupled receptors, particularly G-protein coupled receptors (GPR40), have been shown to regulate insulin secretion, providing insight into the regulation of carbohydrate and lipid metabolism. This has led to the development of therapeutic agents for diseases such as obesity, diabetes, cardiovascular disease and dyslipidemia.

G-protein coupled receptors (GPCRs) constitute a membrane protein superfamily that is activated by a variety of endogenous ligands such as hormones, neurotransmitters, peptides, proteins, steroids, and fatty acids (FA) and other lipids (Diabetes Obes. Metab. , 2009, 11(4): 1-18). Impaired GSIS is a distinct feature of dominant type 2 diabetes, and FFA is known to affect insulin secretion via beta cells primarily through enhanced GSIS. G protein-coupled receptors (GPCRs) such as GPR40, whose endogenous ligands are medium and long chain free fatty acids, play an important role in insulin release.

The G protein coupled receptor, GPR40, or FFA receptor 1, is a member of the G _α q-coupled class 1 GPCR and a small family of fatty acid sensing GPCRs. GPR40 is preferentially expressed in beta cells and is activated by medium to long chain FFA, which in turn triggers a signaling cascade, resulting in an increase in the amount of [Ca ²⁺ ] in the beta cell line (Diabetes, 2008, 57:2280- 87 and Bioorganic & Medicinal Chemistry Letters, 2012, 22:1267–1270).

Studies in animals (mouse) further established the loss of GPR40 to protect mice from hyperglycemia induced by obesity, glucose intolerance, hyperinsulinemia, fatty liver development, hepatic glucose output (hepatic glucose output) and hypertriglyceridemia (Diabetes, 2008, 57: 2280-87).

Confirmation of the role of the G protein-coupled receptor GPR40 in regulating insulin secretion and its role in lipid metabolism thus triggers the concern that GPR40 agonists are considered to be potential targets for the development of therapeutic agents, such as in the treatment of metabolic diseases such as obesity Type 2 diabetes, cardiovascular disease, and hypertriglyceridemia can be useful.

Several small molecule GPR agonists are known and reported in various publications and patents. PCT Publication No. WO2005086661A2 discloses compounds capable of modulating the G protein-coupled receptor GPR40, compositions comprising the same, and methods for controlling the amount of insulin in vivo, such as type 2 diabetes, hypertension, ketoacidosis ( Ketoacidosis), obesity, glucose intolerance, and hypercholesterolemia symptoms and methods for treating diseases associated with abnormally high or low levels of plasma lipoprotein, triglyceride or glucose.

PCT Publication No. WO200801931A1 discloses a fused ring compound useful as an insulin secretagogue or as a prophylactic or therapeutic agent for diabetes and related diseases. PCT Publication No. WO2009111056 A1 and WO2010045258A2 disclose the use of spiro compounds which act as GPR40 Modulators, compositions comprising such compounds, and their methods of treatment or prevention of metabolic diseases, particularly Type 2 diabetes, obesity and related diseases. PCT Publication No. WO2010123016A1 and WO2012011125 disclose a carboxylic acid compound having GPR40 agonist activity, and are useful as a prophylactic and therapeutic agent for diabetes. PCT Publication No. WO2012011125A1 discloses compounds having the ability to modulate GPR40 activity, compositions comprising these compounds, and diseases thereof associated with GPR40 activity, particularly metabolic symptoms such as diabetes, obesity, hyperglycemia, insulin resistance, hypercholesterolemia Use of the disease and related diseases.

Thus, in view of the role of GPR, such as GPR40, in the pathophysiology of metabolic diseases, there is a continuing medical need for safe and effective compounds that can act as GPR agonists.

In one aspect, the invention relates to a compound of formula (I) (as described herein) or an isotopic form thereof, a stereoisomer, a tautomer, a pharmaceutically acceptable salt, pharmaceutically acceptable Solvates, prodrugs, polymorphs, N oxides, S oxides or carboxylic acid isoelectronic alignments.

In another aspect of the invention, there is provided a process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof.

In a further aspect, the invention relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) or an isotopic form thereof, a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof And at least one pharmaceutically acceptable carrier or excipient.

In a further aspect, the invention relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I), or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof; A further therapeutically active agent with at least one pharmaceutically acceptable carrier or excipient.

In another further aspect, the invention relates to a method of modulating GPR40 function in a cell, the method comprising administering a therapeutically effective amount of a compound of formula (I), or a stereoisomer, tautomer or pharmaceutically thereof thereof Accepted salt contact.

In yet another aspect, the invention provides a compound of formula (I), or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof; for use in the treatment or prevention of a disease or condition of a GPR40 vector.

In still a further aspect, the invention provides a method of treating or preventing a disease or condition of a GPR40 vector, the method comprising administering a therapeutically effective amount of a compound of formula (I), or a stereoisomer, tautomer thereof or Pharmaceutically acceptable salts are administered to patients in need thereof.

In yet another aspect, the invention relates to the use of a compound of formula (I), or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of a disease or condition of a GPR40 vector Or prevention.

In another further aspect, the invention relates to the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, in combination with a further therapeutically active agent for the treatment or prevention of a disease or condition of the GPR40 vector.

These and other aspects and objects of the present invention will be apparent to those skilled in the art from this description.

The present invention relates to a compound of formula (I): Formula (I) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl; R ₂ together with R ₃ forms a saturated or partially unsaturated a 3- to 9-membered heterocyclic group containing one or two heteroatoms selected from the group consisting of O, N and S; or R ₂ and R ₃ together form a saturated or partially unsaturated ( C ₄ -C ₈ )cycloalkyl; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, - a group consisting of O(C ₁ -C ₆ )alkyl, (C ₆ -C ₁₀ )aryl, amine, cyano, nitro, -C(O)R ₉ and -S(O) _p R ₆ Groups; R _v and R _w are independently selected from the group consisting of hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ ) alkane a group consisting of an amino group, an amine group, a cyano group, a -C(O)R ₉ , a (C ₃ -C ₈ )cycloalkyl group, a (C ₆ -C ₁₀ )aryl group, a heterocyclic group, and a heteroaryl group; R _x and R _y are independently selected from the group consisting of A-CH(R ₇ )-X, AX-CH(R ₇ ) and R ₅ ; specifying at least one of R _x and R _y is A-CH (R ₇ )-X or AX-CH(R ₇ ); R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ Alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₆ -C ₁₀ )aryl, amine, cyano, nitro, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkylamino or dialkylamino; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X Is CR ₈ R ₈ , O, NR ₈ or S; Q is O, NR ₈ or S(O) _p ; R ₈ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, ( C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic, heteroaryl, cyano, -C(O)(C ₁ -C ₆ )alkyl, -C(O a group consisting of O(C ₁ -C ₆ )alkyl, -C(O)NH ₂ and -S(O) _p R ₆ ; wherein R ₆ is as defined above; R ₉ is (C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic Heteroaryl, R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ are independently selected from hydrogen and (C ₁ -C ₆ )alkyl; or R ₁₀ and R ₁₁ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₂ and R ₁₃ are hydrogen; or R ₁₂ and R ₁₃ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₀ and R ₁₁ are hydrogen; R ₁₄ is independently selected from hydrogen in each case, C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, -O(C ₃ -C ₈ )cycloalkyl, -O(C ₁ -C ₆ )alkylheterocyclyl, -O-heterocyclyl, halo(C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O _p R ₆ , (C ₆ -C ₁₀ ) aryl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ ) aryl, amine, cyano, nitro, -C(O) a group consisting of R ₉ , —S(O) _p R ₆ , —(CH ₂ ) _s NR ₁₅ R ₁₆ and —X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X, R ₆ and R ₉ are as R ₁₅ and R ₁₆ are independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3; m An integer from 1 to 4; p is an integer from 0 to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is from 1 to 4. An integer; * represents a point of X connected to CH(R ₇ )-X; or -X-CH(R ₇ )

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkane , (C ₆ -C ₁₀ ) aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S (O) a group consisting of _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ ) aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) Alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, -O(C ₆ -C ₁₀ )aryl, (C ₁ -C ₆ )alkylheterocyclyl, Heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ and -O(CH ₂ a group consisting of _s C[=NO(C ₁ -C ₆ )alkyl]R ₈ ; wherein R ₆ , R ₈ , R ₉ , s and p are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ - C ₈ ) alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ - C ₆ ) alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -(C ₁ - C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl- a group consisting of S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ - C ₈ ) alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ - C ₆ ) alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O) a group consisting of R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

Halogen is selected from the group consisting of chlorine, bromine, iodine or fluorine; or an isotopic form thereof, a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a prodrug, a polymorph, N An oxide, S oxide or carboxylic acid isoelectronic alignment. definition

The following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the invention and the scope of the appended claims. These definitions should not be interpreted literally as they are not a general definition and are used only in this application.

It will be understood that "substitution", "substituted" or "substituted with" means that one or more hydrogens of a particular moiety are replaced by a suitable substituent. Also included are implicit conditions which result in the formation of a stable compound based on the valence of the substituted atom and the substituent.

The terms "a", "an" and "the" are used in the context of this specification to mean "one or more". Thus, for example, reference to "a compound" may include a plurality of such compounds, or reference to "a disease" or "a condition" includes plural diseases or symptoms. .

In the context of the present invention, as used herein, the term "(C ₁ -C ₆ )alkyl ((C ₁ -C ₆ )alkyl)" or "alkyl", alone or as The moiety of a substituent group means an aliphatic group, including a straight or branched alkyl group. The linear or branched alkyl group has six or fewer carbon atoms in its skeleton, for example, a linear C ₁ -C _{6 group} and a branched C ₃ -C _{6 group} . Suitable alkyl groups contain from one to six carbon atoms including, but not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, 1-methylbutyl , secondary butyl, tertiary pentyl, neopentyl, 2,2-dimethylbutyl, 2-methylpentyl, 3-methylpentyl or 3-methylpentyl.

Furthermore, unless otherwise indicated, an alkyl group may be unsubstituted or substituted with one or more substituents, for example one to five substituents, independently selected from (C ₁ -C ₆ Alkyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ ) alkane , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, -heterocyclyl-(C ₁ -C ₆ )alkyl-OH,heteroaryl,amino a group consisting of cyano, nitro, -S(O) _p R ₆ , -C(O)R ₉ or -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; R ₆ , R ₉ and p are as defined above. Examples of substituted alkyl groups include, but are not limited to, hydroxymethyl, 2-chlorobutyl, trifluoromethyl, aminoethyl or benzyl.

In the context of the present invention, as used herein, the term "(C ₂ -C ₈ ) alkenyl ((C ₂ -C ₈ )alkenyl)" or "alkenyl", alone or as By moiety of a substituent group is meant an unsaturated straight or branched hydrocarbon radical comprising at least one carbon-carbon double bond (two adjacent sp ² carbon atoms). For example, "(C ₂ -C ₈ )alkenyl" means an alkenyl group having two to eight carbon atoms. Depending on the choice of the double bond and the substituent, the geometry of the double bond may be trans (entgegen, E) or cis (zusammen, Z), cis (cis) or trans (trans). Examples of alkenyl groups include, but are not limited to, vinyl, propenyl or 2 propenyl. Unless otherwise indicated, an alkenyl group may be unsubstituted or substituted with one or more substituents independently selected from (C ₁ -C ₆ )alkyl, halo, halo (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, a group consisting of an amine group, a nitro group, a cyano group, -C(O)R ₉ and -OC(O)CH ₃ ; wherein R ₉ is as defined above.

In the context of the present invention and as used herein, the term "(C ₂ -C ₈ ) alkynyl ((C ₂ -C ₈ )alkynyl)" or "alkynyl" means having two to An unsaturated, branched or straight chain of eight carbon atoms and at least one carbon-carbon triple bond (two adjacent sp carbon atoms). Examples of alkynyl groups include, but are not limited to, ethynyl, 1-propynyl, 3-propynyl and 4-butynyl. Unless otherwise indicated, an alkynyl group can be unsubstituted or substituted with one or more substituents independently selected from (C ₁ -C ₆ )alkyl, halo, halo (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, a group consisting of an amine group, a nitro group, a cyano group, -C(O)R ₉ and -OC(O)CH ₃ ; wherein R ₉ is as defined above.

As used herein and in the text before and after the present application, the term "haloalkyl (haloalkyl)" or "halo (C ₁ -C ₆₎ alkyl _{(halo (C 1 -C 6)} alkyl) " is intended to By free radical, wherein one or more hydrogen atoms of the alkyl group are replaced by one or more halogens, the monohaloalkyl radical, for example, may have a chlorine, bromine, iodine or fluorine atom. The dihalo and polyhaloalkyl radicals may have two or more identical or different halogen atoms. Examples of "haloalkyl" or "halo(C ₁ -C ₆ )alkyl" include, but are not limited to, chloromethyl, dichloromethyl, trichloromethyl, dichloroethyl, dichloropropyl, fluoro Methyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl or difluoropropyl.

In the context of the present application and as used herein, the term "alkoxy" means a (C ₁ -C ₆ )alkyl group having an oxygen radical attached thereto. Whenever the term alkoxy or -O(C ₁ -C ₆ )alkyl is used in this specification, it has the same meaning. Representative alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, isobutoxy and tertiary butoxy. -O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , hetero a group consisting of a cyclic group -(C ₁ -C ₆ )alkyl-OH, -S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above.

Before and after the text of the present application and as used herein, the term "haloalkoxy (haloalkoxy)" or "halo (C ₁ -C ₆₎ alkoxy _{(halo (C 1 -C 6)} alkoxy) By free radical, wherein one or more hydrogen atoms of the alkoxy group are replaced by one or more halogens. Representative examples of "haloalkoxy" or "halo(C ₁ -C ₆ )alkoxy" include, but are not limited to, difluoromethoxy (OCHF ₂ ), trifluoromethoxy (OCF ₃ ) or Trifluoroethoxy (OCH ₂ CF ₃ ).

Before and after the text of the present application and as used herein, the term "(C ₃ -C ₈₎ cycloalkyl, _{((C 3 -C 8) cycloalkyl} ) " or "cycloalkyl (cycloalkyl)" means comprising A monocyclic hydrocarbon ring of three to eight carbon atoms. Representative (C ₃ -C ₈ )cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl. Unless otherwise specified, (C ₃ -C ₈ )cycloalkyl may be unsubstituted or substituted with one or more substituents independently selected from (C ₁ -C ₆ )alkyl, halo , halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic a group consisting of a heteroaryl group, an amine group, a cyano group, a nitro group, -C(O)R ₉ and -OC(O)CH ₃ , wherein R ₉ is as defined above. A cycloalkyl group includes a saturated cycloalkyl ring system that does not contain any double bond in the ring, or a partially unsaturated naphthenic ring that may contain one or more double bonds in a ring system that is stable and does not form an aromatic ring system. Base ring system.

In the context of the present application and as used herein, the term "(C ₆ -C ₁₀ )aryl ((C ₆ -C ₁₀ ) aryl)" or "aryl" means having up to ten A monocyclic or bicyclic hydrocarbon ring system of ring carbon atoms in which at least one ring of carbocyclic rings has a p-electron system. Examples of (C ₆ -C ₁₀ ) aryl ring systems include, but are not limited to, phenyl or naphthyl. Unless otherwise indicated, an aryl group may be unsubstituted or substituted with one or more substituents independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, thiol, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, -O(C ₆ -C ₁₀ )aryl, (C ₁ -C ₆ )alkyl Heterocyclyl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ , -OC(O)CH ₃ , -S(O) _p R ₆ and -O(C _a group consisting of ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above.

The aryl group can be substituted at any desired position. For example, in a monosubstituted phenyl group, the substituent may be at the 2, 3, 4 or 5 position. If the phenyl group has two substituents, they may be located at the 2, 3, 2, 4, 2, 5, 2, 6, 3, 4 or 3, 5 positions. Examples of monosubstituted phenyl groups include, but are not limited to, 3-trifluoromethylphenyl, 4-chlorophenyl, 4-cyanophenyl or the like. Examples of disubstituted phenyl groups include, but are not limited to, 4-methoxy-3-trifluoromethylphenyl, 2-methyl-5-trifluoromethylphenyl, 2-methoxy-5-three Fluoromethylphenyl, 4-methyl-3-trifluoromethylphenyl, 3-methoxy-4-trifluoromethylphenyl, 3-fluoro-4-trifluoromethylphenyl, 3- Fluoro-5-trifluoromethoxyphenyl, 3-fluoro-4-trifluoromethoxyphenyl or 2-fluoro-3-trifluoromethylphenyl.

As used herein before and as used herein, the term "heterocyclyl" means a 3 to 9 membered saturated or partially unsaturated monocyclic or bicyclic ring containing one to four identical or different heteroatoms. In the ring system, the hetero atom is selected from the group consisting of nitrogen (N), sulfur (S) or oxygen (O) atoms. Heterocyclyl groups include saturated heterocyclic ring systems that do not contain any double bonds. A partially unsaturated heterocyclic ring system comprising at least one double bond but does not form an aromatic system containing a hetero atom. The term "heterocyclyl" includes fused, bridged or spiro rings. The heterocyclic ring can form a fused or spiro ring system with a cycloalkyl, aryl, heterocyclyl or heteroaryl ring. Suitable saturated and partially unsaturated non-aromatic heterocyclic groups include, but are not limited to, oxycyclobutane, hydrazine, thiocyclobutane, tetrahydrofuran, tetrahydrothiophene, pyrrolidine, dihydropyran, tetrahydropyran , thiodihydropyran, thiotetrahydropyran, piperidine, piperazine, morpholine, 1,3-oxazine, 1,3-thiazine, 4,5,6-tetrahydropyrimidine, 2, 3-dihydrofuran, dihydrothiophene, dioxopidine, tetrahydropyridine, isoxazole, pyrazole, spiro[茚-1,4'-piperidine], spiro[isoporphyrin-1,4 '-Piperidine], spiro[porphyrin-3,4'-piperidine], azabicyclooctane or diazabicyclooctane.

Unless otherwise indicated, a heterocyclic group may be unsubstituted or substituted with one or more substituents independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) alkene , (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) alkane Oxyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -(C ₁ -C ₆ ) alkane -OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl, -C(O)R ₉ , -OC(O)CH ₃ and O(C ₁ -C ₆ ) a group consisting of alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above.

The ring system having a monocyclic or bicyclic heterocyclic group containing an aromatic ring of a hetero atom herein is referred to as "heteroaryl". In the context of the present invention and as used herein, the term "heteroaryl" means a 3 to 10 membered aromatic monocyclic or bicyclic ring system comprising one to four identical or different heteroatoms, The atom is selected from the group consisting of nitrogen (N), sulfur (S) or oxygen (O) atoms. Representative examples of heteroaryl include, but are not limited to, thiophene, furan, pyridine, oxazole, thiazole, pyrazine, pyrimidine, pyrrole, pyrazole, isoxazole, triazole, tetrazole, pyridazine, isothiazole, benzene And thiazole, benzoxazole, benzimidazole, quinoline or isoquinoline. The heteroaryl group may be unsubstituted or substituted with one or more substituents independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, thiol, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ Alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₃ -C ₈ )cycloalkyl-cyano, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine , cyano, nitro, (C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl, -C(O)R ₉ ,- a group consisting of OC(O)CH ₃ , -S(O) _p R ₆ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are As defined above. The nitrogen or sulfur atom of the "heterocyclyl" or "heteroaryl" can be optionally oxidized to the corresponding N oxide, S oxide or S, S dioxide.

The term "heteroatom" as used herein includes nitrogen (N), oxygen (O) and sulfur (S). It is assumed that any hetero atom that does not satisfy the valency has a hydrogen atom to satisfy the valence of the atom, or when the hetero atom is N, it may be selected from (C ₁ -C ₆ )alkyl, -C(O) ( Substitution of a C ₁ -C ₆ )alkyl group or a -S(O) ₂ (C ₁ -C ₆ ) alkyl group. Suitable (C ₁ -C ₆ )alkyl groups include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or isobutyl.

The phrase "-(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl" means an alkyl group substituted by an aryl group, wherein the alkyl and aryl groups are as defined above.

As used herein, the term "-O-(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl" means a (C ₁ -C ₆ )alkyl group attached to an oxygen atom (C). _6- C ₁₀ ) aryl group, wherein the term (C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ ) aryl is as defined above.

The term "(C ₁ -C ₆ )alkylheterocyclyl" as used herein means an alkyl group substituted by a heterocyclic group, wherein the alkyl group and the heterocyclic group are as defined above. .

As used herein, the term "halogen" or "halo", unless otherwise indicated, means a bromine, chlorine, fluorine or iodine atom.

The term "amino" means a group "NH ₂ " which may be unsubstituted or substituted with one or more substituents. Examples of substituents include, but are not limited to, (C ₁ -C ₄ )alkyl, (C ₆ -C ₁₀ )aryl or the like.

In the context of the present invention and as used interchangeably throughout the present application, the terms "compound of formula (I)", "substituted alkyl carboxylic acid derivative (I)" and "compound of the invention" include all isotopes. Forms, stereoisomers, and tautomeric forms, as well as mixtures thereof in all ratios, as well as pharmaceutically acceptable salts, solvates, polymorphs, prodrugs, carboxylic acid homo-alignments, N-oxides and S Oxide. Further, in the context of the present invention, the reference to the compound of the formula (I) may include a compound represented by the compound of the formula (Ia) herein and/or a compound represented by the compound of the formula (Ib) herein. Compounds of formula I or formula (Ia) or formula (Ib) and/or pharmaceutically acceptable salts thereof may also be referred to herein as "active compounds" or "active ingredients."

In the context of the present application and as used interchangeably throughout the application, the term "isotopic form" or "isotopically labeled form" is used in the isotopic form of a compound of formula (I). In general terms, one or more atoms of the compound of formula (I) are substituted by their respective isotopes. All isotopes of any given particular atom or element are contemplated within the scope of the compounds of the invention. Examples of isotopes that can be incorporated into the compounds disclosed herein include, but are not limited to, isotopes of hydrogen such as ² H (氘 or D) and ³ H, isotopes of carbon such as ¹¹ C, ¹³ C and ¹⁴ C, isotopes of nitrogen such as ¹³ N and ¹⁵ N, isotopes of oxygen such as ¹⁵ O, ¹⁷ O and ¹⁸ O, isotopes of chlorine such as ³⁶ Cl, isotopes of fluorine such as ¹⁸ F and isotopes of sulfur such as ³⁵ S. Substitution with heavier isotopes, such as substitution of one or more key carbon-hydrogen bonds with carbon-oxime bonds, may exhibit specific therapeutic advantages due to longer metabolic cycles (eg, increased in vivo half-life or reduced dosage requirements) ), improved safety or better results, and thus may be preferred in some cases.

Representative examples of isotopic forms of the compounds of formula (I) may include, but are not limited to, deuterated compounds of formula (I). The term "deuterated" as used herein, as used herein, or to modify a compound or group, refers to a substitution of one or more hydrogen atoms attached to a carbon by a ruthenium atom. For example, if applicable, compounds of formula (I) may be included in the various variables R ₁ , R ₄ , R ₅ , R ₆ , R ₇ , R ₈ , R ₉ , R ₁₀ , R ₁₁ , R ₁₂ , R ₁₃ And R ₁₄ , R ₁₅ and R ₁₆ , anthracene, deuterated alkyl, deuterated alkoxy, deuterated cycloalkyl, deuterated heterocyclic, deuterated aryl, deuterated heteroaryl, and the like More in the definition.

The term "deuterated-alkyl" means a (C ₁ -C ₆ )alkyl group as defined herein, wherein at least one hydrogen atom attached to the carbon is replaced by deuterium. That is, in the deuterated alkyl group, at least one carbon atom is attached to the hydrazine. In a deuterated alkyl group, it is possible that a carbon atom is attached to more than one hydrazine; it is also possible that a carbon atom of more than one alkyl group is attached to hydrazine. Similarly, the term "deuterated" and the term deuterated heterocyclyl, deuterated heteroaryl, deuterated cycloalkyl, deuterated aryl, deuterated alkoxy each means corresponding a chemical moiety in which at least one carbon is attached to the hydrazine.

In the context of the present invention and as used herein, the term "stereoisomer" is a general term for all isomers of individual compounds which are only in their spatial orientation. different. The term stereoisomers include mirror image isomers (enantiomers), mixture of mirror image isomers (racemates, racemic mixtures), geometric (cis/trans or E/Z) isomers, And isomers (non-image isomers) of more than one palm center, not mirror images of each other.

In the context of the present invention and as used herein, the term "tautomer" means two (or more) different from each other in the position of one (or more) of the changing atoms and the distribution of electrons. Coexistence of the compounds, for example, keto-enol tautomers.

As used herein, the term "pharmaceutically acceptable salts" includes the active compounds, ie, the salts of the compounds of formula (I), which are found on the compounds described herein via a suitable acid or base. The specific substituent is prepared by treating the compound.

In the context of the present invention and as used herein, "N oxide" means an oxide of a nitrogen-containing heteroaryl or a heterocyclic nitrogen atom. The N oxide can be formed in the presence of an oxidizing agent such as a peroxide such as m-chloro-benzoic acid or hydrogen peroxide. N-oxide means an amine oxide, also known as an amine-N-oxide, and is a chemical compound containing a NàO bond.

In the context of the present invention and as used herein, "S oxide" means an oxide of a sulfur-containing heteroaryl or heterocyclic sulfur atom (S oxide) or a sulfur atom (S, S dioxide). The S oxide and the S, S dioxide can be formed in the presence of an oxidizing agent such as a peroxide such as m-chloro-benzoic acid or an oxone.

In the context of the present invention and as used herein, the term "solvate" or "solvates" describes a compound of the formula (I) of the present invention in a proportion of a solvent molecule. Complex. A specific solvate in which the solvent is water is referred to as a hydrate.

In the context of the present invention and as used herein, the term "prodrug" or "prodrugs" means a compound which is a drug precursor which, after administration, is subjected to a chemical or metabolic procedure. The drug is released in the body, for example, a prodrug that is carried to a physiological pH environment or through an enzyme activity is converted into a desired drug.

In the context of the present invention and as used herein, the term "polymorph" or "polymorphic form" or "polymorphs" means the arrangement of molecules only in the crystal lattice and / or crystals of the same compound that are different in configuration.

As used herein before and as used herein, the phrase "carboxylic acid isostere" means physically and chemically similar to a carboxylic acid group, produced and produced by a carboxylic acid group. Those similar to biological effects of the group or molecule. Examples of carboxylic acid isoelectronic alignments include those selected from the group consisting of hydroxamic, mercapto cyanamide, phosphonates, sulfonates, sulfonamides, tetrazoles, hydroxyisoxazoles, and oxadiazolons. The Practice of Medicinal Chemistry, Edited by Camille G. Wermuth, Second Edition, 2003, 189-214.

In the context of the present invention and as used herein, the term "GPR agonist" or "GPR agonist" means a compound of the formula (I) of the present invention which is bonded to , activating, increasing, stimulating, potentiating, sensitizing or positively regulating one or more of G-protein coupled receptors that are reported to play an important physiological role in insulin release. For example, a G protein coupled receptor can be a GPR40 that has been reported to play a physiological role in insulin release.

In the context of the present invention and as used herein, the term "GPR40 agonist" or "GPR40 agonist" means a compound of the formula (I) of the present invention which is bonded to , activates, increases, stimulates, potentiates, sensitizes or positively regulates the GPR40 receptor and promotes glucose-induced insulin secretion.

As used herein, the term "therapeutically effective amount" generally means that when treated with a compound, the amount of the compound (eg, a compound of formula (I)) or a composition comprising the compound will cause tissue or disease. Biological or medical response. In particular, the term "therapeutically effective amount" includes when administered, the amount of the compound elicits a positive modulation of the disease or condition being treated, or is sufficient to prevent the development of symptoms or disorders of one or more patients to be treated, Or reduce to a certain extent. In terms of a therapeutically effective amount of the compound, within the scope of sound medical judgment, the amount of the compound for treatment of the patient is also considered to be low enough to avoid excessive or severe side effects. The therapeutically effective amount of the compound or composition will depend on the particular condition being treated (eg, Type 2 diabetes or related metabolic disorders), the age and physiological condition of the patient (patient), the severity of the condition to be treated or prevented, The duration of treatment, the nature of the concurrent therapy, the particular compound or composition employed, the use of a particular pharmaceutically acceptable carrier, and other factors will vary.

As used herein, the terms "treatment," "treat," and "therapy," and the like, mean reducing, delaying, preventing, attenuating, or curing an existing disease (for example, Metabolic disorders). Treatment also includes preventing the development of one or more signs of the disease or condition being treated or reducing it to some extent.

As used herein, the term "prophylaxis" encompasses a range of subclinical disease states or prophylactic treatment of symptoms of a patient (eg, a human) with the goal of reducing the incidence of clinical disease states. Patients are selected for prophylaxis as a factor known to increase the risk of clinical disease states or symptoms compared to the average person. "Prevention" treatment can be divided into (a) primary prevention and (b) secondary prevention. Primary prevention is defined as the treatment of patients who have not yet demonstrated clinical disease status or symptoms, while secondary prevention is defined as preventing secondary occurrence of the same or similar clinical disease states.

As used herein, the term "subject" means an animal, preferably a mammal, preferably a human.

As used herein, the term "mammal" means a warm-blooded vertebrate of the mammalian family, including humans, characterized by hair that coats the skin and a mammary gland that feeds the young child to produce milk in the female. The term mammal includes animals such as cats, dogs, rabbits, bears, foxes, wolves, monkeys, deer, rats, pigs, and humans. Specific embodiment

In a particular embodiment, the invention includes a compound of formula (I) wherein Z is -COOR ₁ or CON(R ₁ ) ₂ , and R ₁ is independently selected from hydrogen, methyl, and B in each case Base or propyl.

In a particular embodiment, the invention includes a compound of formula (I) wherein Z is -COOR ₁ and R ₁ is hydrogen, methyl, ethyl or propyl.

In another embodiment, the invention includes a compound of formula (I) wherein Z is -CON(R ₁ ) ₂ and each R ₁ is independently selected from hydrogen, methyl, ethyl or propyl The group that makes up.

In another embodiment, the invention includes a compound of formula (I) wherein R ₂ and R ₃ together form a saturated or partially unsaturated 3 to 9 membered heterocyclic ring, the ring comprising one or Two groups are independently selected from the group consisting of O, N and S heteroatoms.

In another embodiment, the invention includes a compound of formula (I) wherein R ₂ and R ₃ together form a saturated or partially unsaturated, 3 to 9 membered heterocyclic group containing one or two O atoms. Ring.

In another embodiment, the invention includes a compound of formula (I) wherein R ₂ and R ₃ together form a saturated or partially unsaturated ring comprising a 4- to 6-membered heterocyclic ring of an O atom.

In yet another embodiment, the invention includes a compound of formula (I) wherein R ₂ and R ₃ together form an oxetane ring.

In another embodiment, the invention includes a compound of formula (I) wherein R ₂ and R ₃ together form a saturated or partially unsaturated group, one or two independently selected from the group consisting of N and S atoms. a heterocyclic ring of a hetero atom; when the hetero atom is N, it is hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ -C ₆ )alkyl or -S(O) ₂ (C ₁ -C ₆ ) substituted by an alkyl group.

In still another embodiment, the invention includes a compound of formula (I) wherein R ₂ and R ₃ together form a thietane ring, a thiocyclobutane 1-oxide ring or a thiocyclobutane Alkene 1,1-dioxide ring.

In yet another embodiment, the invention includes a compound of formula (I) wherein R ₂ and R ₃ together form an azetidine ring.

In another embodiment, the invention includes a compound of formula (I) wherein R ₂ and R ₃ together form a saturated or partially unsaturated (C ₄ -C ₈ )cycloalkyl ring.

In another embodiment, the invention includes a compound of formula (I) wherein R _x is A-CH(R ₇ )-X and R _y is R ₅ ; wherein X, R ₅ , R ₇ and A are As defined above.

In still another embodiment, the invention includes a compound of formula (I) wherein R _x and R _y both represent A-CH(R ₇ )-X; wherein X, R ₇ and A are as defined above By.

In still a further embodiment, the invention includes a compound of formula (I) wherein R _x is R ₅ and R _y is A-CH(R ₇ )-X; wherein X, R ₅ , R ₇ are A is as defined above.

In still a further embodiment, the invention includes a compound of formula (I) wherein R _x is A-CH(R ₇ )-X and R _y is AX-CH(R ₇ ); wherein X, R ₇ and A are as defined above.

In another embodiment, the invention includes a compound of formula (I) wherein R _x is AX-CH(R ₇ ) and R _y is R ₅ ; wherein X, R ₅ , R ₇ and A are as described above Defined by.

In still another embodiment, the invention includes a compound of formula (I) wherein both R _x and R _y represent AX-CH(R ₇ ); wherein X, R ₇ and A are as defined above.

In still a further embodiment, the invention includes a compound of formula (I) wherein R _x is R ₅ and R _y is AX-CH(R ₇ ); wherein X, R ₅ , R ₇ and A are As defined above.

In still a further embodiment, the invention includes a compound of formula (I) wherein R _x is AX-CH(R ₇ ) and R _y is A-CH(R ₇ )-X; wherein X, R ₇ and A are as defined above.

In another embodiment, the invention includes a compound of formula (I) wherein R _x is A-CH(R ₇ )-X and R _y is R ₅ ; wherein X is O and R ₅ , R ₇ are A is as defined above.

In still another embodiment, the invention includes a compound of formula (I) wherein R _x and R _y both represent A-CH(R ₇ )-X; wherein X is O and R ₇ and A are as described above Defined by.

In still a further embodiment, the invention includes a compound of formula (I) wherein R _x is R ₅ and R _y is A-CH(R ₇ )-X; wherein X is O and R ₅ , R ₇ and A are as defined above.

In another embodiment, the invention includes a compound of formula (I) wherein R _x is A-X-CH(R ₇ ) and R _y is R ₅ ; wherein X is O and R ₅ , R ₇ are A is as defined above.

In another embodiment, the invention includes a compound of formula (I) wherein both R _x and R _y represent AX-CH(R ₇ ); wherein X is O and R ₅ , R ₇ and A are as The above defined.

In still a further embodiment, the invention includes a compound of formula (I) wherein R _x is R ₅ and R _y is AX-CH(R ₇ ); wherein X is O and R ₅ , R ₇ are A is as defined above.

In still a further embodiment, the invention includes a compound of formula (I) wherein R _x is AX-CH(R ₇ ) and R _y is A-CH(R ₇ )-X; wherein X is O And R ₇ and A are as defined above.

In still a further embodiment, the invention includes a compound of formula (I) wherein R _x is A-CH(R ₇ )-X and R _y is AX-CH(R ₇ ); wherein X is O And R ₇ and A are as defined above.

In a further embodiment, the invention includes a compound of formula (I) wherein R _x is A-CH(R ₇ )-X and R _y is R ₅ ; and wherein X is CR ₈ R ₈ , S or NR ₈ , wherein R _{8 is,} in each case, independently selected from hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ -C ₆ )alkyl, -C(O)O ( a group consisting of C ₁ -C ₆ )alkyl, -C(O)NH ₂ or -S(O) _p R ₆ wherein R ₅ , R ₆ , R ₇ , A and p are as defined above .

In still another embodiment, the invention includes a compound of formula (I), wherein both R _x and R _y represent A-CH(R ₇ )-X; and wherein X is CR ₈ R ₈ , S or NR ₈ wherein R ₈ is independently selected from hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ -C ₆ )alkyl, -C(O)O(C) in each case _a group consisting of ₁ -C ₆ )alkyl, -C(O)NH ₂ and -S(O) _p R ₆ wherein R ₆ , R ₇ , A and p are as defined above.

In still a further embodiment, the invention includes a compound of formula (I) wherein R _x is R ₅ and R _y is A-CH(R ₇ )-X; and wherein X is CR ₈ R ₈ , S or NR ₈ , wherein R ₈ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ -C ₆ )alkyl, -C(O) a group consisting of O(C ₁ -C ₆ )alkyl, -C(O)NH ₂ and -S(O) _p R ₆ wherein R ₅ , R ₆ , R ₇ , A and p are as described above Definer.

In another embodiment, the invention includes a compound of formula (I) wherein R _x is AX-CH(R ₇ ) and R _y is R ₅ ; wherein X is CR ₈ R ₈ , S or NR ₈ , Wherein R ₈ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ -C ₆ )alkyl, -C(O)O(C ₁ - a group of C ₆ )alkyl, -C(O)NH ₂ and -S(O) _p R ₆ wherein R ₅ , R ₆ , R ₇ , A and p are as defined above.

In another embodiment, the invention includes a compound of formula (I), wherein both R _x and R _y represent AX-CH(R ₇ ); wherein X is independently selected from CR ₈ in each case a group consisting of R ₈ , S and NR ₈ wherein R ₈ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ -C ₆ ) a group consisting of an alkyl group, -C(O)O(C ₁ -C ₆ )alkyl, -C(O)NH ₂ and -S(O) _p R ₆ wherein R ₅ , R ₆ , R ₇ , A and p are as defined above.

In still a further embodiment, the invention includes a compound of formula (I) wherein R _x is R ₅ and R _y is AX-CH(R ₇ ); wherein X is CR ₈ R ₈ , S or NR ₈ wherein R ₈ is independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ -C ₆ )alkyl, -C(O)O(C) _a group consisting of ₁ -C ₆ )alkyl, -C(O)NH ₂ and -S(O) _p R ₆ wherein R ₅ , R ₆ , R ₇ , A and p are as defined above.

In still a further embodiment, the invention includes a compound of formula (I) wherein R _x is AX-CH(R ₇ ) and R _y is A-CH(R ₇ )X; wherein X is CR ₈ R ₈ , S or NR ₈ , wherein R ₈ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ -C ₆ )alkyl, -C (O) a group consisting of O(C ₁ -C ₆ )alkyl, -C(O)NH ₂ and -S(O) _p R ₆ wherein R ₅ , R ₆ , R ₇ , A and p are As defined above.

In still a further embodiment, the invention includes a compound of formula (I) wherein R _x is A-CH(R ₇ )X and R _y is AX-CH(R ₇ ); wherein X is CR ₈ R ₈ , S or NR ₈ , wherein R ₈ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ -C ₆ )alkyl, -C (O) a group consisting of O(C ₁ -C ₆ )alkyl, -C(O)NH ₂ and -S(O) _p R ₆ wherein R ₅ , R ₆ , R ₇ , A and p are As defined above.

In a specific embodiment, the invention includes a compound of formula (I) wherein A is Wherein R ₁₀ , R ₁₁ , R ₁₂ , R ₁₃ , R ₁₄ , q, r and * are as defined above.

In yet another embodiment, the invention includes a compound of formula (I), Wherein A is wherein R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ represent (C ₁ -C ₆ )alkyl; and * is as defined above.

In another embodiment, the invention includes a compound of formula (I) wherein A is Wherein R _{14 is,} in each case, independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ ) Alkyl, halo(C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₁ -C ₆ )alkyl-heterocycle , -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ )aryl, -O-heterocyclyl, cyano, -S(O) _p R ₆ , -(CH ₂ ) _s NR ₁₅ a group consisting of R ₁₆ and -X(CH ₂ ) _s NR ₁₅ R ₁₆ wherein X, R ₆ , R ₁₅ , R ₁₆ , p, q, r, s and * are as defined above; The C ₁ -C ₆ )alkyl group may be unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, amine, cyano, nitro, -C(O) a group consisting of R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ wherein R ₆ , R ₉ and p are as defined above; and the heterocyclic group may be unsubstituted Substituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, cyano, nitro, -(C ₁ - C ₆ )alkyl-OH, -(C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl a group consisting of -S(O) _p R ₆ wherein R ₆ , R ₉ and p are as defined above.

In yet another embodiment, the invention includes a compound of formula (I) wherein A is Wherein R _{14 is,} in each case, independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and halogen; and * is as defined above.

In a particular embodiment, the invention includes a compound of formula (I) wherein A is (C ₆ -C ₁₀ )aryl or heteroaryl; wherein (C ₆ -C ₁₀ )aryl is unsubstituted Or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, (C ₁ -C ₆ )alkylheterocyclyl,heteroaryl,amino, a group consisting of cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ wherein R ₆ , R ₉ and p are as described above As defined; heterocyclyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halo, halo (C ₁ -C) ₆ ) alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, heterocyclyl, amine, cyanide a group consisting of a nitro group, a nitro group, a -C(O)R ₉ and a -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ wherein R ₆ , R ₉ and p are as defined above Definer.

In another embodiment, the invention includes a compound of formula (I) wherein R _{14 is,} in each instance, independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halo, halo (C) ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkylheterocyclyl, -O-heterocyclyl, halo (C ₁ - group C ₆₎ alkoxy, -O (C ₁ -C ₆₎ alkyl -S (O) _p R _6, cyano, -S (O) _p R ₆ consisting of; wherein p and R ₆ is As defined above.

In another embodiment, the invention includes a compound of formula (I), wherein R _{14 is,} in each instance, independently selected from the group consisting of hydrogen, methyl, -CH ₂ CN, fluorine, chlorine, hydroxyl, -CHF ₂ , -CF ₃ , -OCH ₃ , -OC ₃ H ₇ , -O-CH ₂ C(CH ₃ ) ₂ -OC ₅ H ₁₁ , -O-isopentyl, -OCH ₂ -oxycyclobutane- CH ₂ -OH, -OCH ₂ -tetrahydrothiophenyl 1,1-dioxide, -OCH ₂ -tetrahydropyranyl, -O-tetrahydro-2H-thienyl 1,1-dioxide, - O-CH ₂ -tetrahydro-2H-thienyl 1,1-dioxide, benzyloxy, -OCF ₃ , -O(CH ₂ ) ₃ SO ₂ CH ₃ , cyano, -SCH ₃ , -S a group consisting of (C ₄ H ₉ ), -S-CH(CH ₃ ) ₂ , -S(O) ₂ CH ₃ , -S(O)CH ₃ and -S(O) ₂ N(CH ₃ ) ₂ group.

In another embodiment, the invention includes a compound of formula (I) wherein Q is O.

In another embodiment, the invention includes a compound of formula (I) wherein Q is NR ₈ ; wherein R ₈ is hydrogen, (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkane , (C ₆ -C ₁₀ ) aryl, heterocyclic, heteroaryl, cyano, -C(O)(C ₁ -C ₆ )alkyl, -C(O)O(C ₁ -C ₆ An alkyl group, -C(O)NH ₂ or -S(O) _p R ₆ , and R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine group, monoalkylamino group or dialkylamine Base, and p is an integer from 0 to 2.

In another embodiment, the invention includes a compound of formula (I) wherein Q is S(O) _p , wherein p is an integer from 0 to 2.

In another embodiment, the invention includes a compound of formula (I) wherein R _v is hydrogen and R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo (C ₁ - C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ ) Aryl, heterocyclic or heteroaryl.

In another embodiment, the invention includes a compound of formula (I) wherein R _v is hydrogen and R _w is (C ₁ -C ₆ )alkyl.

In another embodiment, the invention includes a compound of formula (I) wherein R _v and R _w are hydrogen.

In another embodiment, the invention includes a compound of formula (I) wherein R ₄ is hydrogen, halogen or (C ₁ -C ₆ )alkyl.

In another embodiment, the invention includes a compound of formula (I) wherein m is 1.

In a particular embodiment, the compound of formula (I) comprises a compound of formula (Ia), Formula (Ia) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl; R ₂ together with R ₃ forms a saturated or partially unsaturated a ring of 3 to 9 membered heterocyclyl containing one or two heteroatoms independently selected from the group consisting of O, N and S; or R ₂ and R ₃ together forming a saturated or partially unsaturated (C ₄ -C ₈ )cycloalkyl ring; R _{4 is,} in each case, independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl , hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₆ -C ₁₀ )aryl, amine, cyano, nitro, -C(O)R ₉ and -S(O) _p R ₆ a group consisting of; R _v and R _w are independently selected from the group consisting of hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ - C ₆ ) alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic and heteroaryl a group; R _y is A-CH(R ₇ )-X, AX-CH(R ₇ ) or R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halogen (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₆ -C ₁₀ )aryl, amine, cyano, nitro , -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkylamino or dialkylamino; R ₇ Is hydrogen or (C ₁ -C ₆ )alkyl; X is CR ₈ R ₈ , O, NR ₈ or S; Q is O, NR ₈ or S; R _{8 is} in each case independently selected from hydrogen, (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, cyano, -C(O) (C ₁ a group of -C ₆ )alkyl, -C(O)O(C ₁ -C ₆ )alkyl, -C(O)NH ₂ and -S(O) _p R ₆ ; wherein R ₆ is as Wherein defined above; R ₉ is (C ₁ -C ₆ )alkyl, O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, heteroaryl, R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ are independently selected from hydrogen and (C ₁ -C ₆ )alkyl; or R ₁₀ and R ₁₁ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₂ and R ₁₃ are hydrogen; or R ₁₂ and R ₁₃ may together form a (C ₃ -C ₈ )cycloalkyl ring; and R ₁₀ and R ₁₁ are hydrogen; R ₁₄ is independently selected from halogen in each case (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, -O(C ₃ -C ₈ )cycloalkane , halo(C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₁ -C ₆ )alkyl-heterocyclyl , -O-heterocyclyl, (C ₆ -C ₁₀ )aryl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ ) aryl, amine, cyano, nitro, -C (O) a group consisting of R ₉ , S(O) _p R ₆ , -(CH ₂ ) _s NR ₁₅ R ₁₆ and -X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X, R ₆ and R ₉ R ₁₅ and R ₁₆ are independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3; m is 1 to An integer of 4; p is an integer from 0 to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is an integer from 1 to 4; * indicates connection CH (R ₇₎ -X is -CH or -X-CH (R ₇₎ of a point X; wherein,

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkane , (C ₆ -C ₁₀ ) aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S (O) a group consisting of _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ ) aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) Alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, -O(C ₆ -C ₁₀ )aryl, (C ₁ -C ₆ )alkylheterocyclyl, Heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ and -O(CH ₂ a group consisting of _s C[=NO(C ₁ -C ₆ )alkyl]R ₈ ; wherein R ₆ , R ₈ , R ₉ , s and p are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ - C ₈ ) alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ - C ₆ ) alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -(C ₁ - C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl, C(O)R ₉ and O(C ₁ -C ₆ )alkyl-S ( O) a group consisting of _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ - C ₈ ) alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ - C ₆ ) alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O) a group consisting of R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

Halogen is selected from the group consisting of chlorine, bromine, iodine or fluorine; or an isotopic form thereof, a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a prodrug, a polymorph, N An oxide, S oxide or carboxylic acid isoelectronic alignment.

In a particular embodiment, the compound of formula (I) includes a compound of formula (Ia); wherein R _y is R ₅ and R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ - C ₆ ) alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₆ -C ₁₀ )aryl, amine, cyano, nitro, -C(O)R ₉ or -S ( O) _p R ₆ ; and Z, R _v , R _w , Q, X, A, R ₂ , R ₃ , R ₄ , R ₆ , R ₇ , R ₉ , m and n are as defined above.

In a particular embodiment, the compound of formula (I) comprises a compound of formula (Ia),

Wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl; R ₂ together with R ₃ forms a saturated or partially unsaturated 3 to 9 member. a ring of a heterocyclic ring containing one or two heteroatoms independently selected from the group consisting of O, N and S; R ₄ is independently selected in each case from hydrogen, (C ₁ -C) ₆ ) alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ and -S ( O) a group consisting of _p R ₆ ; R _v and R _w are independently selected from the group consisting of hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl,- O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl and a group consisting of heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine group, single alkylamino or dialkylamino group; R ₇ is hydrogen or (C ₁ -C ₆₎ alkyl; X is _{CR 8 R 8, O, NR} 8 or S; Q is O; R ₈ in A case where the system is independently selected from the group consisting of hydrogen, (C ₁ -C _{6) alkyl, -C (O) (C 1} -C 6) alkyl, -C (O) O (C 1 -C 6) alkyl a group consisting of -C(O)NH ₂ and -S(O) _p R ₆ wherein R ₆ is as defined above; R ₉ is (C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is (C ₆ -C ₁₀ )aryl, heteroaryl, R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ are independently selected from hydrogen and (C ₁ -C ₆ )alkyl; or R ₁₀ and R ₁₁ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₂ and R ₁₃ are hydrogen; or R ₁₂ and R ₁₃ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₀ and R ₁₁ are hydrogen; R _{14 is} in each case independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, -O(C ₃ -C ₈ )cycloalkyl , halogenated (C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₁ -C ₆ )alkyl-heterocyclyl, -O-heterocyclyl, (C ₆ -C ₁₀ )aryl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ ) aryl, amine, cyano, nitro, -C ( O) R ₉ , -S(O) _p R ₆ , -(CH ₂ ) _s NR ₁₅ R ₁₆ and -X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X, R ₆ and R ₉ R ₁ and R ₁₆ are independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3 m is an integer from 1 to 4; p is an integer from 0 to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is 1 to An integer of 4; *table a point of X of -CH or -X-CH(R ₇ ) connected to CH(R ₇ )-X; wherein

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, a group consisting of an amine group, a cyano group, a nitro group, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p As defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ )aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, (C ₁ -C ₆ Alkylheterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ a group; wherein R ₆ , R ₉ and p are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, Cyano, nitro, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ ) a group consisting of alkyl-S(O) _p R ₆ ; wherein R ₆ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl,heteroaryl a group consisting of a heterocyclic group, an amine group, a cyano group, a nitro group, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In a particular embodiment, the compound of formula (I) includes a compound of formula (Ia) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a saturated or partially unsaturated 3 to 6 membered heterocyclic ring containing one or two oxygen atoms; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R _a group consisting of ₉ and -S(O) _p R ₆ ; R _v is hydrogen and R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ ) alkane , -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, hetero Cyclo or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ - C ₆ ) alkyl, amine, cyano, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkyl Amino or dialkylamino; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X is CR ₈ R ₈ , O, NR ₈ or S; Q is O; ₈ in each case independently selected from hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ -C ₆ )alkyl, -C(O)O(C ₁ -C ₆ a group consisting of an alkyl group, -C(O)NH ₂ and -S(O) _p R ₆ wherein R ₆ is as defined above; R ₉ is (C ₁ -C ₄ )alkyl, - O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ are independently selected from hydrogen and (C ₁ -C ₆ )alkyl; or R ₁₀ and R ₁₁ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₂ and R ₁₃ are hydrogen; or R ₁₂ and R ₁₃ may together form a (C ₃ -C ₈ )cycloalkyl ring; and R ₁₀ and R ₁₁ are hydrogen; R ₁₄ is independently selected from hydrogen in each case (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, -O(C ₃ -C ₈ )cycloalkane , halo(C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₁ -C ₆ )alkyl-heterocyclyl , -O-heterocyclyl, (C ₆ -C ₁₀ )aryl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ ) aryl, amine, cyano, nitro, -C (O) a group consisting of R ₉ , -S(O) _p R ₆ , -(CH ₂ ) _s NR ₁₅ R ₁₆ and -X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X, R ₆ and R ₉ is as defined above; R ₁₅ and R ₁₆ are independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and (CH ₂ ) _t OH; n is an integer from 1 to 3. m is an integer from 1 to 4; p is an integer from 0 to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is 1 to An integer of 4; * indicates the point of -CH connected to CH(R ₇ )-X;

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine a group consisting of a cyano group, a cyano group, a nitro group, a C(O)R _{9 group} and an O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ group; wherein R ₆ , R ₉ and p are as described above Defined by;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, (C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -S (O) a group consisting of _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ )aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, (C ₁ -C ₆ ) Alkylheterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ and -O ( a group of CH ₂ ) _s C[=NO(C ₁ -C ₆ )alkyl]R ₈ ; wherein R ₆ , R ₈ , R ₉ , s and p are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, cyanide Base, nitro, (C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and O(C ₁ -C ₆ )alkyl- a group consisting of S(O) _p R ₆ ; wherein R ₆ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl,heteroaryl, a group consisting of an amine group, a cyano group, a nitro group, a C(O)R _{9 group} and an O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ group; wherein R ₆ , R ₉ and p are as The above defined;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In a particular embodiment, the compound of formula (I) includes a compound of formula (Ia) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a saturated or partially unsaturated 3 to 6 membered heterocyclic ring containing one or two oxygen atoms; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R _a group consisting of ₉ and -S(O) _p R ₆ ; R _v is hydrogen and R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ ) alkane , -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, hetero Cyclo or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ - C ₆ ) alkyl, amine, cyano, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkyl Amino or dialkylamino; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X and Q are O; R ₉ is (C ₁ -C ₄ )alkyl, -O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ are independently selected from hydrogen and (C ₁ -C ₆ )alkyl; or R ₁₀ and R ₁₁ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₂ and R ₁₃ are hydrogen; or R ₁₂ and R ₁₃ may together form a (C ₃ -C ₈ )cycloalkyl ring; and R ₁₀ and R ₁₁ are hydrogen; R ₁₄ is independently selected from hydrogen in each case (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, -O(C ₃ -C ₈ )cycloalkane , halo(C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₁ -C ₆ )alkyl-heterocyclyl , -O-heterocyclyl, (C ₆ -C ₁₀ )aryl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ ) aryl, amine, cyano, nitro, -C (O) a group consisting of R ₉ , -S(O) _p R ₆ , -(CH ₂ ) _s NR ₁₅ R ₁₆ and -X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X, R ₆ and R ₉ is as defined above; R ₁₅ and R ₁₆ are independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is 1 to 3 An integer; m is an integer from 1 to 4; p is an integer from 0 to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is 1 An integer to 4 ; * indicates the point of -CH connected to CH(R ₇ )-X;

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine a group consisting of a cyano group, a cyano group, a nitro group, a C(O)R _{9 group} and an O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ group; wherein R ₆ , R ₉ and p are as described above Defined by;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, (C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -S (O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ )aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, (C ₁ -C ₆ ) Alkylheterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ and -O ( a group of CH ₂ ) _s C[=NO(C ₁ -C ₆ )alkyl]R ₈ ; wherein R ₆ , R ₈ , R ₉ , s and p are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, cyanide Base, nitro, (C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and O(C ₁ -C ₆ )alkyl- a group consisting of S(O) _p R ₆ ; wherein R ₆ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl,heteroaryl, a group consisting of an amine group, a cyano group, a nitro group, a C(O)R _{9 group} and an O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ group; wherein R ₆ , R ₉ and p are as The above defined;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In a particular embodiment, the compound of formula (I) includes a compound of formula (Ia) wherein R ₁ is hydrogen or (C ₁ -C ₆ )alkyl; R ₂ and R ₃ together form a saturated or a portion of the a saturated 3 to 6 membered heterocyclic ring containing one or two oxygen atoms; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halogenated a group consisting of (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ and -S(O) _p R ₆ Group; R _v is hydrogen and R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, Amino, cyano or -C(O)R ₉ ; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy , -O(C ₁ -C ₆ )alkyl, aminyl, cyano, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl An amine group, a monoalkylamino group or a dialkylamino group; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X and Q are O; R ₉ is (C ₁ -C ₄ )alkyl, -O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ are (C ₁ -C ₆ )alkyl; R ₁₅ and R ₁₆ are independently selected from hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _a group consisting of _t OH; n is an integer from 1 to 3; m is an integer from 1 to 4; p is an integer from 0 to 2; s is an integer from 1 to 4; t is from 1 to 4. An integer; * indicates the point of -CH connected to CH(R ₇ )-X;

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl- a group consisting of S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from hydroxy, halo, amine, -(C ₁ -C ₆ ) Alkyl-S(O) _p R ₆ , -S(O) _p R ₆ , -NR ₁₅ R ₁₆ and - (CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s a group consisting of those defined as above;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In a particular embodiment, the compound of formula (I) includes a compound of formula (Ia) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a saturated or partially unsaturated 3 to 6 membered heterocyclic ring containing one or two oxygen atoms; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R _a group consisting of ₉ and -S(O) _p R ₆ ; R _v is hydrogen and R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ ) alkane , -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, hetero Cyclo or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ - C ₆ ) alkyl, amine, cyano, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkyl Amino or dialkylamino; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X and Q are O; R ₉ is (C ₁ -C ₆ )alkyl, O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is R _{14 is,} in each case, independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ ) Alkyl, halogenated (C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₃ -C ₈ )cycloalkyl, - O(C ₁ -C ₆ )alkyl-heterocyclyl, -O(C ₁ -C ₆ )alkyl(C ₆ -C ₁₀ )aryl, -O-heterocyclyl, cyano, -S(O a group consisting of _p R ₆ , —(CH ₂ ) _s NR ₁₅ R ₁₆ and —X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X and R ₆ are as defined above; R ₁₅ and R ₁₆ Is independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3; m is an integer from 1 to 4; p is An integer from 0 to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is an integer from 1 to 4; * indicates a connection to CH (R) ₇ ) -X's -CH point; where,

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₆ -C ₁₀ )aryl, amine, cyano, nitro, -C(O)R ₉ and -O a group consisting of (C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -S(O _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are groups as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogen ( C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, cyanide Base, nitro, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ ) alkane a group consisting of s-S(O) _p R ₆ ; wherein R ₆ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In a particular embodiment, the compound of formula (I) includes a compound of formula (Ia) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a saturated or partially unsaturated 3 to 6 membered heterocyclic ring containing one or two oxygen atoms; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R _a group consisting of ₉ or -S(O) _p R ₆ ; R _v is hydrogen and R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ ) alkane , -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, hetero Cyclo or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ - C ₆ ) alkyl, amine, cyano, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkyl Amino or dialkylamino; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X and Q are O; R ₉ is (C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is R ₁₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, hydroxy, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ ) alkane , halo(C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₃ -C ₈ )cycloalkyl, -O (C ₁ -C ₆ )alkyl-heterocyclyl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ )aryl, -O-heterocyclyl, cyano, -S(O) _a group consisting of _p R ₆ , —(CH ₂ ) _s NR ₁₅ R ₁₆ and —X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X and R ₆ are as defined above; R ₁₅ and R ₁₆ are Independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3; m is an integer from 1 to 4; p is 0 An integer up to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is an integer from 1 to 4; * indicates a connection to CH (R ₇ )-X's point of -CH; where

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ a group of -C ₆ )alkyl, hydroxy, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ Wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, -(C ₁ -C ₆ )alkyl-OH, -(C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ )alkyl-S ( O) a group consisting of _p R ₆ ; wherein R ₆ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In a particular embodiment, the compound of formula (I) includes a compound of formula (Ia) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a saturated or partially unsaturated 3 to 6 membered heterocyclic ring containing one or two oxygen atoms; R ₄ is hydrogen; R _v is hydrogen and R _w is hydrogen , halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O) R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ ) Alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is selected from hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkylamino or dialkylamino; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl X and Q are O; R ₉ is (C ₁ -C ₆ )alkyl, O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is R ₁₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, hydroxy, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ ) alkane , halo(C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₃ -C ₈ )cycloalkyl, -O (C ₁ -C ₆ )alkyl-heterocyclyl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ )aryl, -O-heterocyclyl, cyano, -S(O) _a group consisting of _p R ₆ , —(CH ₂ ) _s NR ₁₅ R ₁₆ and —X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X and R ₆ are as defined above; R ₁₅ and R ₁₆ are Independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3; m is an integer from 1 to 4; p is 0 An integer up to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is an integer from 1 to 4; * indicates a connection to CH (R ₇ )-X's point of -CH; where

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ a group of -C ₆ )alkyl, hydroxy, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ Wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, -(C ₁ -C ₆ )alkyl-OH, -(C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ )alkyl-S ( O) a group consisting of _p R ₆ ; wherein R ₆ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In a particular embodiment, the compound of formula (I) includes a compound of formula (Ia) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a saturated or partially unsaturated 3 to 6 membered heterocyclic ring containing one or two oxygen atoms; R ₄ is hydrogen; R _v is hydrogen and R _w is hydrogen , halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O) R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ ) Alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkylamino or dialkylamino; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X And Q is O; R ₉ is (C ₁ -C ₆ )alkyl, O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is R ₁₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, hydroxy, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ ) alkane , halo(C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₃ -C ₈ )cycloalkyl, -O (C ₁ -C ₆ )alkyl-heterocyclyl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ )aryl, -O-heterocyclyl, cyano, -S(O) _a group consisting of _p R ₆ , —(CH ₂ ) _s NR ₁₅ R ₁₆ and —X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X and R ₆ are as defined above; R ₁₅ and R ₁₆ are Independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3; m is an integer from 1 to 4; p is 0 An integer up to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is an integer from 1 to 4; * indicates a connection to CH (R ₇ )-X's point of -CH; where

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ a group of -C ₆ )alkyl, hydroxy, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ Wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, -(C ₁ -C ₆ )alkyl-OH, -(C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ )alkyl-S ( O) a group consisting of _p R ₆ ; wherein R ₆ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In a particular embodiment, the compound of formula (I) includes a compound of formula (Ia) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a saturated or partially unsaturated 3 to 6 membered heterocyclic ring containing one or two oxygen atoms; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R _a group consisting of ₉ and -S(O) _p R ₆ ; R _v is hydrogen and R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ ) alkane , -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, hetero Cyclo or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ - C ₆ ) alkyl, amine, cyano, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkyl Amino or dialkylamino; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X and Q are O; R ₉ is (C ₁ -C ₄ )alkyl, -O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is (C ₆ -C ₁₀ )aryl or heteroaryl; n is an integer from 1 to 3; m is an integer from 1 to 4; p is 0 to An integer of 2;

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ a group of -C ₆ )alkyl, hydroxy, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ Wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ )aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, -O(C ₆ -C ₁₀ )aryl, (C ₁ - C ₆ )alkylheterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ and a group consisting of -O(CH ₂ ) _s C[=NO(C ₁ -C ₆ )alkyl]R ₈ ; wherein R ₆ , R ₈ , R ₉ , s and p are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ )alkyl-S(O a group consisting of _p R ₆ ; wherein R ₆ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, amine, cyano, nitro, (C ₆ - C ₁₀₎ aryl group, a heterocyclic _{group, -C (O) R 9 (} C 1 -C 6) alkyl -S (O) _p R ₆ of the group consisting of -O; wherein R _6, R ₉ and p is as defined above;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In a particular embodiment, the compound of formula (I) includes a compound of formula (Ia) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a saturated or partially unsaturated 3 to 6 membered heterocyclic ring containing one or two oxygen atoms; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R _a group consisting of ₉ and -S(O) _p R ₆ ; R _v is hydrogen and R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ ) alkane , -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, hetero Cyclo or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ - C ₆ ) alkyl, amine, cyano, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkyl Amino or dialkylamino; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X is NR ₈ ; Q is O; R ₈ is hydrogen or (C ₁ -C ₆ ) Alkyl; R ₉ is (C ₁ -C ₄ )alkyl, -O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ are independently selected from hydrogen and (C ₁ -C ₆ )alkyl; or R ₁₀ and R ₁₁ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₂ and R ₁₃ are hydrogen; or R ₁₂ and R ₁₃ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₀ and R ₁₁ are hydrogen; R _{14 is} in each case independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₃ -C ₈ )cycloalkyl, -O(C ₁ -C ₆ )alkylheterocyclyl,- O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ ) aryl, -O-heterocyclyl, (C ₆ -C ₁₀ ) aryl, amine, cyano, nitro, -C(O a group consisting of R ₉ , -S(O) _p R ₆ , -(CH ₂ ) _s NR ₁₅ R ₁₆ and -X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X, R ₆ and R ₉ are R ₁₅ and R ₁₆ are independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3; m is an integer from 1 to 4; p is an integer from 0 to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is from 1 to 4 An integer * indicates the point of -CH connected to CH(R ₇ )-X;

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine a group consisting of a cyano group, a cyano group, a nitro group, a C(O)R _{9 group} and an O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ group; wherein R ₆ , R ₉ and p are as described above Defined by;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -S(O) _p R ₆ , -NR _a group consisting of ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ ) aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl,heteroaryl,amino a group consisting of cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as The above defined;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, Cyano, nitro, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ ) a group consisting of alkyl-S(O) _p R ₆ ; wherein R ₆ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl,heteroaryl a group consisting of an amine group, a cyano group, a nitro group, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ and R ₉ are p is as defined above;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In a particular embodiment, the compound of formula (I) includes a compound of formula (Ia) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a saturated or partially unsaturated 3 to 6 membered heterocyclic ring containing one or two oxygen atoms; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R _a group consisting of ₉ and -S(O) _p R ₆ ; R _v is hydrogen and R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ ) alkane , -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, hetero Cyclo or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ - C ₆ ) alkyl, amine, cyano, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkyl Amino or dialkylamino; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X is NR ₈ ; Q is O; R ₈ is hydrogen or (C ₁ -C ₆ ) Alkyl; R ₉ is (C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is R ₁₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ ) alkane , halo(C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₃ -C ₈ )cycloalkyl, -O (C ₁ -C ₆ )alkyl-heterocyclyl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ )aryl, -O-heterocyclyl, cyano, -S(O) _a group consisting of _p R ₆ , —(CH ₂ ) _s NR ₁₅ R ₁₆ and —X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X and R ₆ are as defined above; R ₁₅ and R ₁₆ are Independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3; m is an integer from 1 to 4; p is 0 An integer up to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is an integer from 1 to 4; * indicates a connection to CH (R ₇ ) -X's -CH point; where,

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ a group of -C ₆ )alkyl, hydroxy, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ Wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -S(O) _p R ₆ , -NR ₁₅ R ₁₆ and _{- (CH 2) s NR 15} R 16; wherein _{R 6, R 15, R 16} , p and s are as defined above by;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ )alkyl-S(O a group consisting of _p R ₆ ; wherein R ₆ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In a particular embodiment, the compound of formula (I) includes a compound of formula (Ia) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a saturated or partially unsaturated 3 to 6 membered heterocyclic ring containing one or two heteroatoms independently selected from N or S atoms, when the heteroatom is N , which is substituted by hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ -C ₆ )alkyl or -S(O) ₂ (C ₁ -C ₆ )alkyl; R ₄ in each case independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl a group consisting of an amine group, a cyano group, -C(O)R ₉ or -S(O) _p R ₆ ; R _v and R _w are independently selected from hydrogen, halogen, hydroxy, (C ₁ -C) ₆ ) alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ ) a group consisting of a cycloalkyl group, a (C ₆ -C ₁₀ ) aryl group, a heterocyclic group, and a heteroaryl group; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, Halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₄ ) alkyl or amine; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X is CR ₈ R ₈ , O , NR ₈ or S; Q is O; R ₈ is independently selected from hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ -C ₆ ) in each case a group consisting of an alkyl group, -C(O)O(C ₁ -C ₆ )alkyl, -C(O)NH ₂ or -S(O) _p R ₆ wherein R ₆ is as defined above ; R ₉ is (C ₁ -C ₄ )alkyl, -O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is (C ₆ -C ₁₀ )aryl, heteroaryl, R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ are independently selected from hydrogen and (C ₁ -C ₆ )alkyl; or R ₁₀ and R ₁₁ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₂ and R ₁₃ are hydrogen; or R ₁₂ and R ₁₃ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₀ and R ₁₁ are hydrogen; R _{14 is} in each case independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₃ -C ₈ )cycloalkyl, -O(C ₁ -C ₆ )alkyl-heterocyclyl, -O-heterocyclyl, (C ₆ -C ₁₀ )aryl, amine, cyano, nitro, -C(O)R ₉ , -S(O) _p R ₆ , -(CH ₂ ) _s NR _a group consisting of ₁₅ R ₁₆ and -X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X, R ₆ and R ₉ are as defined above; R ₁₅ and R ₁₆ are independently selected from hydrogen, (C _a group consisting of ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3; m is an integer from 1 to 4; p is an integer from 0 to 2; q is an integer of 1 to 4; r is an integer from 1 to 5; and S is an integer of 1 to 4; t is an integer from 1 to 4; and * represents a bond to a CH (R ₇₎ -X is the -CH ; among them,

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, a group consisting of an amine group, a cyano group, a nitro group, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p As defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -S(O) _p R ₆ , -NR _a group consisting of ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ )aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, (C ₁ -C ₆ Alkylheterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ and -O a group consisting of (CH ₂ ) _s C[=NO(C ₁ -C ₆ )alkyl]R ₈ ; wherein R ₆ , R ₈ , R ₉ , s and p are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, Cyano, nitro, -C(O)R ₉ , -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and a group consisting of O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl,heteroaryl a group consisting of an amine group, a cyano group, a nitro group, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ and R ₉ are p is as defined above;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In a particular embodiment, the compound of formula (I) includes a compound of formula (Ia) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl ; R ₂ and R ₃ together form part of a saturated or unsaturated (C ₄ -C ₈₎ cycloalkyl ring; R ₄ is independently selected from the group consisting of hydrogen based in each case, (C ₁ -C ₆₎ alkyl Base, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ and -S(O) _p a group consisting of R ₆ ; R _v and R _w are independently selected from the group consisting of hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic and heteroaryl a group consisting of; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ ) alkyl, amine, cyano, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkylamine Or a dialkylamino group; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X is CR ₈ R ₈ , O, NR ₈ or S; Q is O; R ₈ is Each case is independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ -C ₆ )alkyl, -C(O)O(C ₁ -C ₆ ) alkane a group consisting of -C(O)NH ₂ and -S(O) _p R ₆ ; wherein R ₆ is as defined above; R ₉ is (C ₁ -C ₄ )alkyl, -O( C ₁ -C ₆ )alkyl, hydroxy or amine; A is (C ₆ -C ₁₀ )aryl, heteroaryl, R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ are independently selected from hydrogen and (C ₁ -C ₆ )alkyl; or R ₁₀ and R ₁₁ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₂ and R ₁₃ are hydrogen; or R ₁₂ and R ₁₃ may together form a (C ₃ -C ₈ )cycloalkyl ring; and R ₁₀ and R ₁₁ are hydrogen; R ₁₄ is independently selected from hydrogen in each case (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ )alkoxy , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₃ -C ₈ )cycloalkyl, -O(C ₁ -C ₆ )alkyl-heterocyclyl , -O-heterocyclyl, (C ₆ -C ₁₀ ) aryl, amine, cyano, nitro, -C(O)R ₉ , -S(O) _p R ₆ , -(CH ₂ ) _s a group consisting of NR ₁₅ R ₁₆ and -X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X, R ₆ and R ₉ are as defined above; R ₁₅ and R ₁₆ are independently selected from hydrogen, ( a group consisting of C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3; m is an integer from 1 to 4; p is an integer from 0 to 2; a is an integer of 1 to 4; r is an integer from 1 to 5; and S is an integer of 1 to 4; t is an integer from 1 to 4; and * represents a bond to a CH (R ₇₎ -X is -CH Point; which,

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, a group consisting of an amine group, a cyano group, a nitro group, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p As defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, hydroxy, halogen, amine , cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ a group of constituents; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ )aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, (C ₁ -C ₆ Alkylheterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ and -O a group consisting of (CH ₂ ) _s C[=NO(C ₁ -C ₆ )alkyl]R ₈ ; wherein R ₆ , R ₈ , R ₉ , s and p are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, Cyano, nitro, -C(O)R ₉ , -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and a group consisting of O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl,heteroaryl a group consisting of an amine group, a cyano group, a nitro group, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ and R ₉ are p is as defined above;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In a particular embodiment, the compound of formula (I) comprises a compound of formula (Ib), Formula (Ib) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl; R ₂ together with R ₃ forms a saturated or partially unsaturated a ring of 3 to 9 membered heterocyclic ring containing one or two heteroatoms independently selected from O, N and S; or R ₂ and R ₃ together form a saturated or partially unsaturated (C ₄ - C ₈ ) a cycloalkyl ring; R _{4 is,} in each case, independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, - a group consisting of O(C ₁ -C ₆ )alkyl, (C ₆ -C ₁₀ )aryl, amine, cyano, nitro, -C(O)R ₉ and -S(O) _p R ₆ Groups; R _v and R _w are independently selected from the group consisting of hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ ) alkane a group consisting of an amino group, an amine group, a cyano group, a -C(O)R ₉ , a (C ₃ -C ₈ )cycloalkyl group, a (C ₆ -C ₁₀ )aryl group, a heterocyclic group, and a heteroaryl group; R _x is A-CH(R ₇ )-X, AX-CH(R ₇ ) or R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ ) Alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₆ -C ₁₀ )aryl, amine, cyano, nitro, -C(O)R ₉ or -S(O _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkylamino or dialkylamino; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X is CR ₈ R ₈ , O, NR ₈ or S; Q is O, NR ₈ or S(O) _p ; R ₈ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic, heteroaryl, cyano, -C(O)(C ₁ -C ₆ )alkyl, -C (O) a group consisting of O(C ₁ -C ₆ )alkyl, -C(O)NH ₂ and -S(O) _p R ₆ ; wherein R ₆ is as defined above; R ₉ is ( C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, hetero Cyclic group, heteroaryl group, R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ are independently selected from hydrogen or (C ₁ -C ₆ )alkyl; or R ₁₀ and R ₁₁ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₂ and R ₁₃ are hydrogen; or R ₁₂ and R ₁₃ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₀ and R ₁₁ are hydrogen; R _{14 is} in each case independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₃ -C ₈ )cycloalkyl, -O(C ₁ -C ₆ )alkyl-heterocyclyl, -O-heterocyclyl, (C ₆ -C ₁₀ )aryl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ ) aryl, amine, cyano, nitro, -C ( O) R ₉ , -S(O) _p R ₆ , -(CH ₂ ) _s NR ₁₅ R ₁₆ and -X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X, R ₆ and R ₉ R ₁ and R ₁₆ are independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3 m is an integer from 1 to 4; p is an integer from 0 to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is 1 to An integer of 4; * indicates the point of X connected to -CH or -X-CH(R ₇ ) of CH(R ₇ )-X;

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkane , (C ₆ -C ₁₀ ) aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S (O) a group consisting of _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ ) aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) Alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, (C ₁ -C ₆ )alkylheterocyclyl, heterocyclyl, heteroaryl, amine, cyanide Base, nitro, -C(O)R ₉ , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ and -O(CH ₂ ) _s C[=NO(C ₁ -C ₆ a group consisting of alkyl]R ₈ ; wherein R ₆ , R ₈ , R ₉ , s and p are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ - C ₈ ) alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ - C ₆ ) alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O) R ₉ , —(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ )alkyl- a group consisting of S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ - C ₈ ) alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ - C ₆ ) alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O) a group consisting of R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In a specific embodiment, the present invention comprises a compound of formula (I) of the, Z is -COOR ₁ or _{-CON (R 1) 2; R} 1 is hydrogen or (C ₁ -C ₆₎ alkyl; R ₂ and R ₃ together form an oxycyclobutane ring; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy a group consisting of -O(C ₁ -C ₆ )alkyl, aminyl, cyano, nitro, -C(O)R ₉ and -S(O) _p R ₆ ; R _v and R _w Independently selected from the group consisting of hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amine, cyano, a group consisting of -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl and heteroaryl; R _x is A-CH(R ₇ )-X; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ An alkyl group, an amine group, a cyano group, a nitro group, -C(O)R ₉ or -S(O) _p R ₆ ; X and Q are O; A is a (C ₆ -C ₁₀ ) aryl group, a heteroaryl group base, m is 1; R ₆ , R ₇ , R ₉ , R ₁₀ , R ₁₁ , R ₁₂ , R ₁₃ , R ₁₄ , n, p, q and r are as defined above; * means connected to CH (R ₇ ) -X's -CH point; where,

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkane , (C ₆ -C ₁₀ ) aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S (O) a group consisting of _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ ) aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) alkane Oxyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, (C ₁ -C ₆ )alkylheterocyclyl, heterocyclyl, heteroaryl, amine, cyano , nitro, -C(O)R ₉ , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ and -O(CH ₂ ) _s C[=NO(C ₁ -C ₆ ) a group consisting of alkyl]R ₈ ; wherein R ₆ , R ₈ , R ₉ , s and p are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogen (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine , cyano, nitro, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ a group consisting of alkyl-S(O) _p R ₆ ; wherein R ₆ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ - C ₈ ) alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ - C ₆ ) alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O) a group consisting of R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In another embodiment, the invention includes a compound of formula (I) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl; ₂ together with R ₃ form an oxycyclobutane ring; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl a group consisting of a hydroxyl group, a -O(C ₁ -C ₆ )alkyl group, an amine group, a cyano group, a nitro group, -C(O)R ₉ and -S(O) _p R ₆ ; R _v is hydrogen And R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic or heteroaryl; R _x is A-CH(R ₇ )-X; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine Base, cyano, nitro, -C(O)R ₉ or -S(O) _p R ₆ ; X and Q are O; A is m is 1; R ₆ , R ₇ , R ₉ , R ₁₄ , n, p, q and r are as defined in the above formula (I); * represents -CH which is bonded to CH(R ₇ )-X Point;

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkane , (C ₆ -C ₁₀ ) aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S (O) a group consisting of _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ ) aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) Alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ , a group consisting of -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ and -O(CH ₂ ) _s C[=NO(C ₁ -C ₆ )alkyl]R ₈ ; R ₆ , R ₈ , R ₉ , s and p are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, Cyano, nitro, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ ) a group consisting of alkyl-S(O) _p R ₆ ; wherein R ₆ and p are as defined above;

A heteroaryl group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ - C ₈ ) alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ - C ₆ ) alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O) a group consisting of R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

In another embodiment, the invention includes a compound of formula (I) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl; ₂ together with R ₃ form an oxycyclobutane ring; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl a group consisting of hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, nitro, -C(O)R ₉ and -S(O) _p R ₆ ; R _v is hydrogen And R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic or heteroaryl; R _x is A-X-CH(R ₇ ) ; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine Base, cyano, nitro, -C(O)R ₉ or -S(O) _p R ₆ ; X and Q are O; A is m is 1; R ₆ , R ₇ , R ₉ , R ₁₄ , n, p, q and r are as defined in the above formula (I); * represents -CH which is bonded to CH(R ₇ )-X Point;

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkane , (C ₆ -C ₁₀ ) aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S (O) a group consisting of _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ ) aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) Alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ , a group consisting of -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ and -O(CH ₂ ) _s C[=NO(C ₁ -C ₆ )alkyl]R ₈ ; R ₆ , R ₈ , R ₉ , s and p are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, Cyano, nitro, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ ) a group consisting of alkyl-S(O) _p R ₆ ; wherein R ₆ and p are as defined above;

A heteroaryl group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ - C ₈ ) alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ - C ₆ ) alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O) a group consisting of R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; or isotopic forms thereof, stereoisomers, tautomers, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N oxides , S oxide or carboxylic acid isoelectronic alignment.

Representative compounds of formula (I) encompassed according to the invention include: methyl 2-((3-(4-((2',6'-dimethyl-4'-(3-(methylsulfonyl))) Propyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4) -((2',6'-dimethyl-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl Oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-([1,1'-biphenyl]-3-ylmethoxy)phenyl)oxycyclobutane) Alkyl-3-yl)oxy)acetic acid; 2-((3-(4-([1,1'-biphenyl]-3-ylmethoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetic acid; methyl 2-((3-(4-((4'-)(trifluoromethyl)-[1,1'-biphenyl)-4-yl)methoxy)phenyl)oxy Cyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-)(trifluoromethyl)-[1,1'-biphenyl]-4-yl)) Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((5,5,8,8-tetramethyl-5,6, 7,8-tetrahydronaphthalen-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((5,5, 8,8-Tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-( (3-(4-((3-phenoxybenzyl)oxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-(3-phenoxybenzyl)oxy)phenyl)oxycyclobutan-3-yl Oxy) acetic acid; methyl 2-((3-(4-(4-phenoxybenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; -((3-(4-(4-phenoxybenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-( (2-phenoxybenzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-(2-phenoxybenzyl)) Oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-(4-(4-fluorophenoxy)benzyl)oxy)benzene Oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3-(4-fluorophenoxy)benzyl)oxy)phenyl)oxy) Butyl-3-yl)oxy)acetic acid; methyl 2-((3-(4-((4'-methyl-[1,1'-biphenyl]-3-yl)methoxy)benzene) Oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-methyl-[1,1'-biphenyl]-3-yl)) Oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; methyl 2-((3-(4-((4'-methoxy-[1,1'-biphenyl]-) 3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4')-methoxy-[1,1' -biphenyl]-3-yl)methoxy) Oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2',4'-dimethyl-[1,1'-biphenyl]-3) -yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2',4'-dimethyl-[1, 1'-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2'-chloro-)- [1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2') -chloro-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-( (4'-hydroxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3- 4-((4'-hydroxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-(( 3-(4-((3'-hydroxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetate; 2 -((3-(4-((3'-hydroxy-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; Methyl 2-((3-(4-((2'-fluoro-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy Acetate; 2-((3-(4-((2'-fluoro-[1,1'-biphenyl)-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((4'-(methylthio))-[1,1'-biphenyl]-3-yl)) Methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-(methylthio))-[1,1'-linked Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((3')-cyano-[1, 1'-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3')-cyano) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2) '-Fluoro-5'-(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate ; 2-((3-(4-((2'-fluoro-5'-(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxy ring Butyl-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2'-fluoro-4'-(trifluoromethyl)-[1,1'-biphenyl]-) 3-()(methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-fluoro-4'-)) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-( (2'-(Trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy) Acid ester; 2-((3-(4-((2'-)-trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetic acid; methyl 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonyl)propoxy)-[1,1'- Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-chloro-4'-) (3-(Methanesulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-((3-(hydroxymethyl))oxycyclobutane-3-yl)methoxy)-[1,1'-linked Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-chloro-4'-) (3-(Hydroxymethyl)oxycyclobutane-3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3- Methyl)oxy)acetic acid; methyl 2-((3-(4-((2)-chloro-4'-((1,1-dioxoindolyl-4-hydrothiophen-3-yl)methoxy)) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2) '-Chloro-4'-((1,1-dioxainyltetrahydrothiophen-3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl Oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2'-chloro-4'-((1,1-dioxo)) Tetrahydro-2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy ) acetate; 2-((3-(4-((2'-chloro-4'-((1,1-dioxo)-tetrahydro-2H-thiopyran-4-yl)methoxy) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2) '-Chloro-4'-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)acetate; 2-((3-(4-((2)-chloro-4'-((tetrahydro-2H-pyran-4-yl)methoxy)) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((4) '-((3-(Hydroxymethyl)oxycyclobutane-3-yl)methoxy)-2',6'-dimethyl-[1,1'-biphenyl]-3-yl) A Oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-)(3-(hydroxymethyl)oxycyclobutane-) 3-yl)methoxy)-2',6'-dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy Acetate; methyl 2-((3-(4-((4)-((1,1-dioxy)tetrahydrothiophen-3-yl)methoxy)-2',6'-di Methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate 2-((3-(4-((4'-((1,1-Dioxy)tetrahydrothiophen-3-yl)methoxy)-2',6'-dimethyl-[1 , 1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2',6) '-Dimethyl-4'-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxy Cyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2',6'-dimethyl-4'-((tetrahydro-2H-pyran-4) -yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3) -(4-((4'-((1,1-dioxy)tetrahydro-2H-thiopyran-4-yl)oxy)-2',6'-dimethyl-[1,1' -biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-((1, 1-Dioxy-ionic tetrahydro-2H-thiopyran-4-yl)oxy)-2',6'-dimethyl-[1,1'-biphenyl]-3-yl)methoxy) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((4-()))) Methyl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4-())) - piperidine]-1'-ylmethyl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3- 4-((4-((1-methylspiro[pyridin-3,4'-piperidine]-1'-yl)methyl)benzyl)oxy)phenyl)oxycyclobutane-3 -yl)oxy)acetate; 2-((3-(4-((4-(())))) Benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; methyl 2-((3-(4-((4-fluoro-4'-methyl-[ , 1'-biphenyl]-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-(4-fluoro-) 4'-Methyl-[1,1'-biphenyl]-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3- 4-((2'-(Benzyloxy)-4-fluoro-[1,1'-biphenyl]-2-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy Acetate; 2-((3-(4-((2'-(benzyloxy)-4-fluoro-[1,1'-biphenyl]-2-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-(4-fluoro-[1,1'-biphenyl]-2-yl)methoxy)) Phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-(4-fluoro-[1,1'-biphenyl]-2-yl)methoxy) Phenyl)oxycyclobutan-3-yl)oxy)acetic acid; methyl 2-((3-(4-((3',4-difluoro-[1,1'-biphenyl]-) 2-()-methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3')4-difluoro-[1,1 '- Benzene-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((4'-(3-)) Mercapto)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3) -(4-((4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid; methyl 2-((3-(4-((4'-((3-(hydroxymethyl))oxycyclobutane-3-yl)methoxy)-[1, 1'-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-(( 3-(Hydroxymethyl)oxycyclobutane-3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl Oxy)acetic acid; methyl 2-((3-(4-((4'-((1,1-dioxy)-tetrahydrothiophen-3-yl)methoxy)-[1,1' -biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-((1, 1-Dioxy-ionic tetrahydrothiophen-3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy Acetate; methyl 2-((3-(4-((4)-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl]-3 -yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2 -((3-(4-((4)-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((4-(o)))))))))) Butyl-3-yl)oxy)acetate; 2-((3-(4-(4-(o-tolyloxy)benzyl)oxy)phenyl)oxycyclobutane-3- Ethyl)oxy)acetic acid; ethyl 2-((3-(4-((3'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)benzene) Oxycyclobutane-3-yl)oxy)propionate; 2-((3-(4-((3'-fluoro-2'-methyl-[1,1'-biphenyl]-) 3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionic acid; ethyl 2-((3-(4-((2'-)-trifluoromethyl)-[ 1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionate; 2-((3-(4-((2'-) (trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionic acid; ethyl 2-((3) -(4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)propionate; 2 -((3-(4-((2'-methyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)propane Acid; ethyl 2-((3-(4-((2)-chloro-4'-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'- Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionate; 2-((3-(4-((2'-chloro-4'-) (tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy Propionic acid; ethyl 2-((3-(4-((2)-chloro-4'-((1,1-dioxo)tetrahydrothiophen-3-yl)methoxy)-[1 , 1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionate; 2-((3-(4-((2')-) -4'-((1,1-Dioxal-tetrahydrothiophen-3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxy ring Butyl-3-yl)oxy)propanoic acid; ethyl 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonyl))propoxy)-[1 , 1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionate; 2-((3-(4-((2')-) -4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy Propionic acid; ethyl 2-((3-(4-((2'-chloro-4'-((1,1-dioxo)tetrahydro-2H-thiopyran-4-yl)methoxy) )-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionate; 2-((3-(4-(( 2'-Chloro-4'-((1,1-dioxal tetrahydro-2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl ]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)propionic acid; ethyl 2-((3-(4-((4')-fluoro-2'--) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; ethyl 2-((3-(4- ((3-(4-Methylthiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; ethyl 2-((3-(4) -((3'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate ; 2-((3-(4-((3'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid; methyl 2-((3-(4-((2'-methyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxy ring Butyl-3-yl)oxy)acetate; 2-((3-(4-((2'-methyl-[1,1'-biphenyl)-3-yl)methoxy)benzene) Ethylcyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3'-chloro-2'-methyl-[1,1'-biphenyl]-) 3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3'-chloro-2'-methyl-[ 1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2'-) Chloro-4'-((1,1-dioxal tetrahydro-2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl) Oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-chloro-4'-((1,1-dioxy)) Tetrahydro-2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetic acid; ethyl 2-((3-(4-(3-(3,5-dimethylisoxazol-4-yl)benzyl)oxy)phenyl)oxycyclobutane-3- Ethyl)oxy)acetate; ethyl 2-((3-(4-((3-(5-(hydroxymethyl))thiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)acetate; ethyl 2-((3-(4-((3-(4-(hydroxymethyl))thiazol-2-yl)benzyl)oxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate; ethyl 2-((3-(4-((4'-)(3-(hydroxymethyl))oxycyclobutane-3-yl) Methoxy)-2'-(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy) Ethyl ester; ethyl 2-((3-(4-((2',6'-bis(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2',6'-bis(trifluoromethyl)-[1,1'-biphenyl) ]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((4')-cyano-2'-) Keto-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate; ethyl 2-((3-(4-(3-(5-(hydroxymethyl))-3-methylthiophen-2-yl)benzyl)oxy) Phenyl)oxycyclobutane-3-yl)oxy)acetate; ethyl 2-((3-(4-(4-(5-methylthiophen-2-yl)benzyl)) Oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; ethyl 2-((3-(4-((2'-(difluoromethyl))-[1,1' -biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; ethyl 2-((3-(4-((3-(3-) Methylthiophen-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; ethyl 2-((3-(4-((4'-) N,N-dimethylaminesulfonyl)-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy Acetate; ethyl 2-((3-(4-((2'-chloro-4'-((1,1-dioxy)tetrahydro-2H-thiopyran-4-yl)oxy) —(1,1′-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-( (2'-Chloro-4'-((1,1-dioxoindolizhan-2H-thiopyran-4-yl)oxy)-[1,1'-biphenyl]-3-yl) A Oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((4'-((1,1-dioxy)-tetrahydro-2H) -thiopyran-4-yl)methoxy)-2',6'-dimethyl-[1,1'-linked ]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-((1,1-) Oxygen-based tetrahydro-2H-thiopyran-4-yl)methoxy)-2',6'-dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl Oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((3-(2-fluoro)pyridin-3-yl)))yloxy)phenyl)oxy Cyclobutane-3-yl)oxy)acetate; 2-((3-(4-(3-(2-fluoropyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2'-chloro-4'-(isopentyloxy)-[1,1'-biphenyl]-3) -yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-chloro-4'-(isopentyloxy)) )-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-(( 2'-Chloro-3'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2- ((3-(4-((2'-Chloro-3'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetic acid; methyl 2-((3-(4-((3'-chloro-2'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3'-chloro-2'-methoxy-[1,1] '-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2'-)-) '-Methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3- 4-((2'-Chloro-4'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid ; methyl 2-((3-(4-((2',6'-dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-(yl)oxy)acetate; 2-((3-(4-((2',6'-dimethyl-[1,1'-biphenyl]-3-yl)methoxy)) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((4'-propoxy)-[1,1'-biphenyl]-3-yl) Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-propoxy-[1,1'-biphenyl)) ]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2'-chloro-4'-methyl)) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2) '-Chloro-4'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-( (3-(4-((4'-(pentyloxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3- Oxy)acetate; 2-((3-(4-((4'-)-pentyloxy)-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxy Cyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((4'-)-isobutoxy-[1,1'-biphenyl]-3-yl)methoxy) Phenyl)oxycyclobutan-3-yl)oxy)acetate; 2-((3-(4-((4'-isobutoxy-[1,1'-biphenyl]-) 3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((4'-(butylthio))-[1, 1'-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-) Thio)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4- ((4'-(isopropylthio)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; -((3-(4-((4'-(isopropylthio)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetic acid; ethyl 2-((3-(4-((4'-)(trifluoromethyl)-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxy Cyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-)(trifluoromethyl)-[1,1'-biphenyl]-3-yl)) Methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2'-chloro-4'-propyl) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-(( 2'-Chloro-4'-propoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2 -((3-(4-(3-(2-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2- ((3-(4-(3-(2-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; ethyl 2-( (3-(4-((4'-(Methanesulfonyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy ) acetate; 2-((3-(4-((4'-(methylsulfonyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)acetic acid; ethyl 2-((3-(4-(3-(5-(1-cyanocyclopropyl))thiophen-2-yl)benzyl)oxy) Phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-(3-(5-(1-cyanocyclopropyl)thiophen-2-yl))) Benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((4'-(methylsulfinyl))-[1, 1'-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-)) Sulfosyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxy Cyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-(3-(3-(trifluoromethyl)pyridin-4-yl)benzyl)oxy)benzene Oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-(3-(3-(trifluoromethyl)pyridin-4-yl)benzyl)oxy) Phenyl)oxycyclobutan-3-yl)oxy)acetic acid; ethyl 2-((3-(4-(3-(2-(trifluoromethyl)pyridin-3-yl)benzyl) Ethyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3-(2-(trifluoromethyl))) Benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-(3-(pyrimidin-5-yl)benzyl)) Oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3-(pyrimidin-5-yl))yl)oxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3-(4-methyl)pyrimidin-5-yl)benzyl)oxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3-(4-methylpyrimidin-5-yl))yl)oxy)phenyl)oxy) Cyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3-(2-methoxypyrimidin-3-yl)benzyl)oxy)phenyl)oxy) Cyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3-(2-methoxypyrimidin-3-yl)benzyl)oxy)phenyl)oxy) Ring -3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3-(pyrazin-2-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl) Oxy)acetate; 2-((3-(4-((3-(pyrazin-2-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy) Acetic acid; ethyl 2-((3-(4-((3-(6-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy) Acid ester; 2-((3-(4-((3-(6-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; Ethyl 2-((3-(4-((2'-(cyanomethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetate; 2-((3-(4-((2'-(cyanomethyl)-[1,1'-biphenyl)-3-yl)methoxy)benzene Oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3-(pyridin-3-yl))yl)oxy)phenyl)oxy) Alk-3-yl)oxy)acetate; 2-((3-(4-((3-(pyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl) Ethyl)acetic acid; ethyl 2-((3-(4-((3-(pyridin-4-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy) Acid ester; 2-((3-(4-((3-(pyridin-4-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; ((3-(4-((2'-)) —(1,1′-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-( (2'-(Trifluoromethoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2 -((3-(4-((4'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl) Oxy)acetate; 2-((3-(4-((4'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((5'-fluoro-2'-methyl-[1,1'-biphenyl]-3) -yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((5')-fluoro-2'-methyl-[1 ,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2')-fluoro) -6'-Methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3- (4-((2'-Fluoro-6'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid Ethyl 2-((3-(4-((2'-(methylthio))-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetate; 2-((3-(4-((2'-(methylthio))-[1,1'-biphenyl)-3-yl)methoxy)phenyl) )oxygen Butyl-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2'-(methylsulfonyl)-[1,1'-biphenyl]-3-yl)) Oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-(methylsulfonyl))-[1,1'-linked Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2'-)) )-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-(( 2'-(methylsulfinyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2- ((3-(4-(3-(5-Methoxy-2-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy) Acid ester; 2-((3-(4-((3-(5-methoxy-2-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl) Oxy)acetic acid; methyl 2-((3-(4-((2'-methoxy-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)acetate; 2-((3-(4-((2'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)benzene) Oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((6-(2-(trifluoromethyl)phenyl)pyridin-2-yl)) Oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-(6-(2-(Trifluoromethyl)phenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy) Acetic acid; ethyl 2-((3-(4-((6-(2-chloro-4-methoxyphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutan-3-yl) Oxy)acetate; 2-((3-(4-((6-(2-chloro-4-methoxyphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid; ethyl 2-((3-(4-((6-(2,4-dimethylphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate; 2-((3-(4-((6-(2,4-dimethylphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid; ethyl 2-((3-(4-(6-(3-fluoro-2-methylphenyl)pyridin-2-yl)methoxy)phenyl)oxy Cyclobutane-3-yl)oxy)acetate; 2-((3-(4-((6-(3-fluoro-2-methylphenyl)pyridin-2-yl)methoxy)benzene) Oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((5-(2-(trifluoromethyl)phenyl)thiophen-2-yl)) Oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((5-(2-(trifluoromethyl)phenyl)thiophene-2) -yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2-(3-fluoro-2-methylbenzene)))) Thiazol-4-yl)methoxy)benzene Oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2-(3-))))) Phenyl)oxycyclobutan-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2-(o-toly))))) Phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2-(o-tolyl))thiazol-4-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-(2-(2-(trifluoromethyl)phenyl)thiazol-5-yl)methoxy) Phenyl)oxycyclobutan-3-yl)oxy)acetate; 2-((3-(4-((2-(2-(trifluoromethyl)phenyl)thiazole-5-) Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((5-(3-chloro-2-methylphenyl))thiophene) 2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((5-(3-chloro-2-methyl))) Benzene)thiophen-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((6-(3-chloro-2-)) -methylbenzene)pyridin-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((6-(3-) Chloro-2-methylphenyl)pyridin-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2- (2-(trifluoromethyl) Phenyl)thiazol-4-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2-(2-(3- Fluoromethyl)phenyl)thiazol-4-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2-) 3-fluoro-2-methylphenyl)thiazol-5-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-(( 2-(3-fluoro-2-methylphenyl)thiazol-5-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4) -((2'-(Difluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-(Difluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl Ethyl)acetic acid; ethyl 2-((3-(4-((4'-(3-(methylsulfonyl))propoxy)-2'-(trifluoromethyl)-[1,1 '-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; ethyl 2-((3-(4-((3')-fluoro) -2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)-2-methylbenzene)oxycyclobutane-3-yl)oxy)acetate; 2- ((3-(4-((3'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)-2-methylphenyl)oxycyclobutane- 3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3'-chloro-2'-methyl)) -[1,1'-biphenyl]-3-yl)methoxy)-2-methylbenzene)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4) -((3'-Chloro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)-2-methylphenyl)oxycyclobutan-3-yl)oxy Acetic acid; ethyl 2-((3-(2-methyl-4-((2'-methyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxy ring Butyl-3-yl)oxy)acetate; 2-((3-(2-methyl-4-((2'-methyl-[1,1'-biphenyl]-3-yl)) Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(2-fluoro-4-((3'-fluoro-2'-methyl-[ 1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(2-fluoro-4-) (3'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2 -((3-(4-((3'-chloro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)-2-fluorophenyl)oxycyclobutane -3-yl)oxy)acetate; 2-((3-(4-((3'-chloro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy) 2-(2-fluorophenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(2-fluoro-4-((2'-methyl-[1,1) '-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(2-fluoro-4-((2') -methyl-[1,1'-linked Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2'-chloro-6'-) Trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3- 4-((2'-Chloro-6'-(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy Acetate; ethyl 2-((3-(4-((4'-propyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetate; 2-((3-(4-((4'-propyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxyl) Butyl-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2-(5,5-dimethylcyclopent-1-en-1-yl)-2'-) Fluoro-5'-methoxy-[1,1'-biphenyl]-4-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; ethyl 2- ((3-(4-(2-(3-chloro-2-methylphenyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate ; 2-((3-(4-(2-(3-chloro-2-methylphenyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy) Acetic acid; ethyl 2-((3-(4-(3-(4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)benzyl)oxy)phenyl)oxy ring Butyl-3-yl)oxy)acetate; 2-((3-(4-((3-(4,5,6,7-tetrahydrobenzo[b]]] Thiophen-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3-(4,5,6) ,7-tetrahydrobenzo[d]thiazol-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4- ((3-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; 2-((3-(4-(4'-cyclopropyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate; 2-((3-(4-((4'-cyclopropyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3-(5,6,7,8-tetrahydronaphthalen-2-yl)benzyl)oxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-(3-(5,6,7,8-tetrahydronaphthalen-2-yl)benzyl)oxy) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-(4-(2-(methoxy)))-2-(p-) Tolyl)ethoxy)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; and 2-((3-(4-((4-(2-) Methoxyimido)-2-(p-tolyl)ethoxy)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; or its isotopic form, stereoisomerism Mutual variation Thereof, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N-oxide, S-oxide or carboxylic acid isosteres.

In another specific embodiment, the invention comprises selected from the group consisting of: 2-((3-(4-((2',6'-dimethyl-4'-(3-(methylsulfonyl))propoxy) )-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-([1, 1'-Biphenyl]-3-ylmethoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4'-)-trifluoromethyl) )-[1,1'-biphenyl]-4-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((5, 5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-( (3-(4-((3-phenoxybenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4-benzene) Oxybenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-(2-phenoxybenzyl)oxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-(3-(4-fluorophenoxy)benzyl)oxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid; 2-((3-(4-((4'-methyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid; 2-((3-(4-((4'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxy) Cyclobutane-3-yl)oxy)acetic acid; 2- ((3-(4-((2',4'-Dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate; 2-((3-(4-((2'-chloro-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetic acid; 2-((3-(4-((4'-hydroxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl) Ethoxy)acetic acid; 2-((3-(4-((3'-hydroxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3- 2-((3-(4-((2'-fluoro-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid; 2-((3-(4-((4'-(methylthio))-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxy Cyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3'-cyano)-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-fluoro-5'-(trifluoromethyl)-[1,1'-biphenyl]] -3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2')-fluoro-4'-(trifluoromethyl) )-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2') -(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3- 4-((2'-chloro-4) '-(3-(Methanesulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid ; 2-((3-(4-((2'-chloro-4'-((3-(hydroxymethyl))oxycyclobutane-3-yl)methoxy)-[1,1'-linked Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-((1) ,1-dioxyindolyltetrahydrothiophen-3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl) Oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-((1,1-dioxo)-tetrahydro-2H-thiopyran-4-yl)methoxy) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-) Chloro-4'-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane- 3-()-oxy)acetic acid; 2-((3-(4-((4'-((3-(hydroxymethyl))oxycyclobutane-3-yl)methoxy)-2',6 '-Dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4- ((4'-((1,1-Dioxy)tetrahydrothiophen-3-yl)methoxy)-2',6'-dimethyl-[1,1'-biphenyl]-3- Methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2',6'-dimethyl-4'-(( Tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy) Acetic acid; 2-((3-(4-((4'-((1,1-dioxy)tetrahydro-2H-thiopyran-4-yl)oxy)-2',6'-dimethyl -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4- (Spiro[茚-1,4'-piperidinyl]-1'-ylmethyl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3- (4-((4-Methylspiro[pyridin-3,4'-piperidinyl]-1'-yl)methyl)benzyl)oxy)phenyl)oxycyclobutane- 3-()-oxy)acetic acid; 2-((3-(4-((4-fluoro-4'-methyl-[1,1'-biphenyl)-2-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-(benzyloxy)-4-fluoro-[1,1'-biphenyl]-) 2-()(methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; 2-((3-(4-((4-fluoro-[1,1'-biphenyl]-) 2-()(methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; 2-((3-(4-((3',4-difluoro-[1,1'-) Biphenyl]-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4'-(3-(methylsulfonyl)) Propyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-( (3-(4-((4'-((3-(Hydroxymethyl)oxycyclobutan-3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy Phenyl)oxycyclobutan-3-yl)oxy)acetic acid; 2-((3-(4-((4'-((1,1-dioxo)-tetrahydrothiophen-3-yl) Methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4- ((4'-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-()-oxy)acetic acid; 2-((3-(4-((4-(o-to))))oxy)) Acetic acid; 2-((3-(4-((3'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-()-oxy)propionic acid; 2-((3-(4-((2'-)(trifluoromethyl)-[1,1'-biphenyl)-3-yl)methoxy)benzene Oxycyclobutane-3-yl)oxy)propionic acid; 2-((3-(4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy) Phenyl)oxycyclobutane-3-yl)oxy)propionic acid; 2-((3-(4-((2'-chloro-4'-((tetrahydro-2H-pyran-4) -yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)propionic acid; 2-((3- (4-((2'-Chloro-4'-((1,1-dioxainyltetrahydrothiophen-3-yl)methoxy)-[1,1'-biphenyl]-3-yl) A Phenyl)oxycyclobutane-3-yl)oxy)propionic acid; 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonyl))propoxy) ()-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)propionic acid; 2-((3-(4-(( 2'-Chloro-4'-((1,1-dioxoisotetrahydro-2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl) A Oxy)phenyl)oxycyclobutane-3-yl)oxy)propionic acid; 2-((3-(4-((3'-fluoro-2'-methyl-[1,1'-linked) Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-methyl-[1,1') -biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3'-chloro-2'-) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2') -Chloro-4'-((1,1-dioxal tetrahydro-2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2',6'-bis(trifluoromethyl))-[1,1'-linked Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-((1) ,1-dioxy-ionic tetrahydro-2H-thiopyrimidin-4-yl)oxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3 - Ethyl)acetic acid; 2-((3-(4-((4)-((1,1-dioxy)tetrahydro-2H-thiopyran-4-yl)methoxy)-2', 6'-Dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4) -((3-(2-fluoropyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2) '-Chloro-4'-(isopentyloxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; -((3-(4-((2'-chloro-3'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl Oxy)acetic acid; 2-((3-(4-((3'-chloro-2'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-methoxy-[1,1'-biphenyl]-3-yl) Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2',6'-dimethyl-[1,1'-linked) Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4'-propoxy-[1,1] '-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-) Methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4) '-( Oxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-(( 4'-Isobutoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3- 4-((4'-(butylthio)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2- ((3-(4-((4'-(isopropylthio)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate; 2-((3-(4-((4'-)-trifluoromethyl)-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-propoxy-[1,1'-biphenyl]-3-yl)methoxy) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3-(2-methylpyridin-3-yl)benzyl)oxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4'-(methylsulfonyl)-[1,1'-biphenyl]-3-yl)) Methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-(3-(5-(1-cyanocyclopropyl))thiophene-2- Benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4'-(methylsulfinyl))-[1, 1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3- 4-((3-(3-(Trifluoromethyl)pyridin-4-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; 2-((3- (4-((3-(2-(Trifluoromethyl)pyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; 2-((3 -(4-((3-(pyrimidin-5-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3) -(4-methylpyrimidin-5-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3-(2) -Methoxypyrimidin-3-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3-(pyrazine)- 2-()-benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3-(6-methylpyridin-3-yl))) Benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-(cyanomethyl))-[1,1' -biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-(3-(pyridin-3-yl))) Benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3-(pyridin-4-yl)benzyl)oxy)benzene) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-)-trifluoromethoxy)-[1,1'-biphenyl]-3- Methoxy)phenyl)oxocyclobutane-3-yl) Acetate; 2-((3-(4-((4')-fluoro-2'-methyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)acetic acid; 2-((3-(4-((5'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-fluoro-6'-methyl-[1,1'-biphenyl]-) 3-()(methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-(methylthio))-[1,1' -biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-(methylsulfonyl))) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-) (methylsulfinyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3- 4-((3-(5-methoxy-2-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-(( 3-(4-((2'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; -((3-(4-(6-(2-(Trifluoromethyl)phenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid ; 2-((3-(4-(6-(2-chloro-4-methoxyphenyl)pyridin-2-yl)methoxy)phenyl)oxy ring Butyl-3-yl)oxy)acetic acid; 2-((3-(4-(6-(2,4-dimethylphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid; 2-((3-(4-((6-(3-fluoro-2-methylphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)acetic acid; 2-((3-(4-((5-(2-(trifluoromethyl)phenyl)thiophen-2-yl)methoxy)phenyl)oxy) Cyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2-(3-fluoro-2-methylphenyl)thiazol-4-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2-(o-tolyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid; 2-((3-(4-((2-(2-(trifluoromethyl)phenyl)thiazol-5-yl)methoxy)phenyl)oxy) Butyl-3-yl)oxy)acetic acid; 2-((3-(4-((5-(3-chloro-2-methylphenyl)thiophen-2-yl)methoxy)phenyl)oxy) Cyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-(6-(3-chloro-2-methylphenyl)pyridin-2-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2-(2-(trifluoromethyl)phenyl)thiazol-4-yl)methoxy)benzene) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2-(3-))))))) Phenyl)oxycyclobutane-3-yl) Acetate; 2-((3-(4-((2'-)difluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid; 2-((3-(4-((3'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)) 2-(methylphenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3'-chloro-2'-methyl-[1,1'-linked) Benzyl-3-yl)methoxy)-2-methylphenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(2-methyl-4-((2') -methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(2-fluoro-) 4-((3'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3'-Chloro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)-2-fluorophenyl)oxycyclobutane Alkyl-3-yl)oxy)acetic acid; 2-((3-(2-fluoro-4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-6'-(trifluoromethyl))-[1,1'-linked Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4'-propyl-[1,1') -biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2-(3-chloro-2-)-2- Methylbenzene)thiazol-4-yl)A Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; and 2-((3-(4-((4-(2-(2-(4-(4-(4-(4-(4-(4-(4-(4-(2-(4-(4-(4-(((( a compound of the group consisting of ethoxy)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; or an isotopic form thereof, a stereoisomer, a tautomer thereof A pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a prodrug, a polymorph, an N-oxide, an S-oxide or a carboxylic acid homo-arrangement.

In another specific embodiment, the invention comprises selected from: 2-((3-(4-((2')))) Oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-)(trifluoromethyl)-[1,1'-biphenyl) [3-(4-(4-((2'-chloro-4'-(3-(4-(())))) (Methanesulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid calcium; 2-( (3-(4-((2'-Chloro-4'-((1,1-dioxo)tetrahydrothiophen-3-yl)methoxy)-[1,1'-biphenyl]-3 -yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid calcium; 2-((3-(4-((2'-chloro-4'-((tetrahydro-2H)) -pyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2 -((3-(4-((4'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl) Oxy) calcium acetate; 2-((3-(4-((3-(4-methylthiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy) Calcium acetate; 2-((3-(4-((3'-fluoro-2'-methyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxy ring Butyl-3-yl)oxy)acetate; 2-((3-(4-((2')-methyl-[1,1 '-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid calcium; 2-((3-(4-((3'-chloro-2') -methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-( (2'-Chloro-4'-((1,1-dioxoindolizhan-2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl) Calcium methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3-(3,5-dimethylisooxazol-4-yl)) Benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3-(5-(hydroxymethyl))thiophen-2-) Calcium benzyl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-(4-(4-(hydroxymethyl))thiazole-2) -yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid calcium; 2-((3-(4-((4'-((3-(hydroxymethyl)))) Oxycyclobutane-3-yl)methoxy)-2'-(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane- Calcium 3-yl)oxy)acetate; 2-((3-(4-((2',6'-bis(trifluoromethyl)-[1,1'-biphenyl]-3-yl)) Oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4')-cyano-2'-methyl-[1,1'- Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate 2-((3-(4-(3-(5-(hydroxymethyl))-3-methylthiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl) Calcium acetate; 2-((3-(4-((3-(5-methylthiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy) Calcium acetate; 2-((3-(4-((2'-)difluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate; 2-((3-(4-(3-(3-methylthiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3 -yl)oxy)calcium acetate; 2-((3-(4-((4'-(N,N-dimethylaminesulfonyl)-2'-methyl-[1,1'-linked Benzyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-chloro-4')-methoxy) Calcium-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4) '-(3-(Methanesulfonyl)propoxy)-2'-(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxetane Alkyl-3-yl)oxy)acetate; 2-((3-(4-((2-(5,5-dimethylcyclopent-1-en-1-yl)-2'-fluoro-) 5'-Methoxy-[1,1'-biphenyl]-4-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3- 4-((2',4'-Dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3- Metformin salt of oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonyl)propoxy))-[1,1'-linked Metformin salt of phenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-4') -((1,1-dioxal-tetrahydrothiophen-3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- Metformin salts of 3-yl)oxy)acetic acid; and 2-((3-(4-((2',6'-dimethyl-[1,1'-biphenyl]-3-yl)) A compound of the group consisting of metformin salts of oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid.

The invention also relates to a process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof. Compounds of formula (I) can be prepared as described herein below, but are not limited thereto. The starting materials and reagents employed in the preparation of the compounds of formula (I) can be either commercially available or can be prepared via procedures known in the art. plan 1 Reaction conditions: Step 1a: Benzene bromide, potassium carbonate, acetonitrile, reflux; Step 1b: n-butyllithium, THF, -78 ° C; Step 1c: 60% sodium hydride, THF, 0 ° C - RT; Hydrogen/palladium carbon, EtOH, RT; Step 1e: cesium carbonate (Cs ₂ CO ₃ ), DMF, RT; Step 1f: LiOH.H ₂ O, tetrahydrofuran (THF), methanol (MeOH), hydrochloric acid (HCl), RT.

In a specific embodiment, there is provided a process for the preparation of a compound of formula (I) wherein Z is COOR ₁ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl; R ₂ and R ₃ together form one or a saturated or partially unsaturated 3 to 9 membered heterocyclic group of one of two heteroatoms selected from O, N or S; or R ₂ and R ₃ together form a saturated or partially unsaturated ( C ₄ -C ₈ )cycloalkyl; R _{4 is,} in each case, independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, a group consisting of -O(C ₁ -C ₆ )alkyl, aminyl, cyano, nitro, -C(O)R ₉ and -S(O) _p R ₆ ; R _x is A-CH ( R ₇ )-X; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ ) alkyl, amine, cyano, nitro, -C(O)R ₉ or -S(O) _p R ₆ ; X is O; A is (C ₆ - C ₁₀ ) aryl, heteroaryl , R _v and R _w are independently selected from the group consisting of hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, a group consisting of an amine group, a cyano group, a -C(O)R ₉ , a (C ₃ -C ₈ )cycloalkyl group, a (C ₆ -C ₁₀ )aryl group, a heterocyclic group, and a heteroaryl group; O, NR ₈ or S(O) _p ; R ₆ , R ₇ , R ₉ , R ₁₀ , R ₁₁ , R ₁₂ , R ₁₃ , R ₁₄ , m, n, p, q and r are as in the above chemical formula (I) Among those defined in ;

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkane , (C ₆ -C ₁₀ ) aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S (O) a group consisting of _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ ) aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) alkane Oxyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, (C ₁ -C ₆ )alkylheterocyclyl, heterocyclyl, heteroaryl, amine, cyano a group consisting of nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above By;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogen (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine , cyano, nitro, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ a group consisting of alkyl-S(O) _p R ₆ ; wherein R ₆ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ )alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O a group consisting of R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; consisting of the reaction steps outlined in Scheme 1 above, as described herein below: Step 1a:

The compound of the formula (1) is in a base such as n-butyllithium, sodium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate or triethylamine and is selected from the group consisting of dioxane, THF, toluene, acetonitrile or dimethoxy. The benzene is reacted with benzene in the presence of a solvent of ethane or a mixture thereof to obtain a compound of the formula (2).

Alternatively, the compound of formula (2) can be obtained from commercial sources. Step 1b:

The compound of the formula (2) and the compound of the formula R ₃ -(C=Q)-R ₂ are selected from a base such as n-butyllithium, sodium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate or triethylamine. Reacting in the presence of a solvent of dioxane, THF, toluene, acetonitrile or dimethoxyethane or a mixture thereof, wherein R ₂ and R ₃ together form a saturated or partially unsaturated group comprising one or two heteroatoms a 3- to 9-membered heterocyclic group selected from O, N or S; or R ₂ and R ₃ together form a saturated or partially unsaturated (C ₄ -C ₈ )cycloalkyl group, and Q-selected From O, NR ₈ or S(O) _p ; for example, oxycyclobutane-3-one, oxycyclobutane-3-thione, N-(oxocyclobutane-3-ylidene)methylamine, hydrazine a ketone or thioxanthone to obtain a compound of formula (3). Step 1c:

A compound of the formula (3) and a compound of the formula Br-(CR _v R _w ) _m COOR ₁ are selected from a base such as n-butyllithium, sodium hydride, sodium hydroxide, potassium hydroxide, potassium carbonate or triethylamine. The reaction is carried out in the presence of a solvent of dioxane, THF, toluene, acetonitrile or dimethoxyethane or a mixture thereof to obtain a compound of the formula (4) wherein R ₁ is (C ₁ -C ₆ )alkyl. Step 1d:

In this step, the presence of a compound of formula (4) wherein R ₁ is (C ₁ -C ₆ )alkyl is present in a catalyst such as palladium on carbon and a solvent selected from the group consisting of ethanol, methanol, isopropanol, tetrahydrofuran or mixtures thereof Catalytic reduction is carried out to obtain a compound of the formula (5) wherein R ₁ is (C ₁ -C ₆ )alkyl. Step 1e:

In this step, the compound of the formula (5) wherein R ₁ is (C ₁ -C ₆ )alkyl is in a base selected from the group consisting of cesium carbonate (Cs ₂ CO ₃ ) or potassium carbonate (K ₂ CO ₃ ) and Treatment with a compound of formula A-CH(R ₇ )-Br in the presence of a solvent such as dimethylformamide to obtain a compound of formula (I) wherein R ₁ is (C ₁ -C ₆ )alkyl. Step 1f:

A compound of formula (I) wherein R ₁ is (C ₁ -C ₆ )alkyl (obtained in step 1e) according to the procedure described in J. Med. Chem., 1995, 38(3): 1386-96 Ingesting a solvent selected from the group consisting of THF, ethanol, MeOH, water or a mixture thereof, and hydrolyzing with a base selected from the group consisting of NaOH, KOH, lithium hydroxide (LiOH) or barium hydroxide (Ba(OH) ₂ ), HCl followed by neutralization, to obtain a compound of formula (I) of which R ₁ is hydrogen.

Alternatively, certain embodiments of the compounds of formula (I) may be prepared according to procedures involving the reaction steps described in Scheme 2 below: Scheme 2 Reaction conditions: Step 2a and Step 2a': cesium carbonate (Cs ₂ CO ₃ ), DMF, RT; (20 ° C - 25 ° C); Step 2b and Step 2b': tetratriphenylphosphine palladium (0), K ₂ CO ₃ , dioxane, water, 80-85 ° C; Step 2c and Step 2c': LiOH.H ₂ O, tetrahydrofuran (THF), methanol (MeOH), hydrochloric acid (HCl), RT.

In another embodiment, the process for the preparation of a compound of formula (I) wherein R ₁ is hydrogen or (C ₁ -C ₆ )alkyl; R ₂ together with R ₃ forms one of one or two heteroatoms a saturated or partially unsaturated 3 to 9 membered heterocyclic group selected from O, N or S; or R ₂ and R ₃ together form a saturated or partially unsaturated (C ₄ -C ₈ ) Cycloalkyl; R _{4 is,} in each case, independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ - a group of C ₆ ) alkyl, amine, cyano, nitro, -C(O)R ₉ and -S(O) _p R ₆ ; R _x is A-CH(R ₇ )-X; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine Base, cyano, nitro, -C(O)R ₉ or -S(O) _p R ₆ ; X is O; A is R _v and R _w are independently selected from the group consisting of hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, a group consisting of an amine group, a cyano group, a -C(O)R ₉ , a (C ₃ -C ₈ )cycloalkyl group, a (C ₆ -C ₁₀ )aryl group, a heterocyclic group or a heteroaryl group; O, NR ₈ or S; R ₆ , R ₇ , R ₈ , R ₉ , R ₁₄ , m, n, p, q and r are as defined in the above formula (I);

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkane , (C ₆ -C ₁₀ ) aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S (O) a group consisting of _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ ) aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) Alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are groups as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogen ( C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, cyanide Base, nitro, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ ) alkane a group consisting of s-S(O) _p R ₆ ; wherein R ₆ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C) ₈ ) alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R _a group consisting of ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; consisting of the reaction steps as outlined in Scheme 2 above, as described herein below: Step 2a and Step 2a':

In this procedure step, the compound of formula (5) wherein R ₁ is (C ₁ -C ₆ )alkyl (step 1d, Scheme 1) is selected from the group consisting of cesium carbonate (Cs ₂ CO ₃ ) or potassium carbonate (K) ₂ CO ₃ ) of a base and a solvent such as dimethylformamide in the presence of a chemical formula Compound or chemical formula Compounds are treated to obtain compounds of formula (6) and (6'), respectively, wherein R ₁ is (C ₁ -C ₆ )alkyl. Step 2b and step 2b':

In this procedure step, a compound of formula (6) and (6') wherein R ₁ is (C ₁ -C ₆ )alkyl, in a catalyst such as tetrakistriphenylphosphine palladium (0), selected from potassium carbonate a chemical formula in the presence of a base of sodium carbonate, potassium hydrogencarbonate or sodium hydrogencarbonate and a solvent selected from the group consisting of dioxane, water or a mixture thereof The compound is treated to obtain a compound of the formula (7A) and (7'A) wherein R ₁ is a (C ₁ -C ₆ )alkyl group. The compounds of the formulae (7A) and (7'A) are specific examples of the compound of the formula (I). Step 2c and step 2c':

Compounds of formula (7A) and (7'A) (obtained in step 2b and step 2b', wherein R is obtained according to the method described in J. Med. Chem., 1995, 38(3): 1386-96 ₁ is (C ₁ -C ₆ )alkyl) is taken up in a solvent selected from THF, ethanol, MeOH, water or a mixture thereof, and is selected from the group consisting of NaOH, KOH, lithium hydroxide (LiOH) or barium hydroxide (Ba The base of (OH) ₂ ) is hydrolyzed, followed by neutralization with HCl to obtain compounds of formula (7B) and (7'B) wherein R ₁ is hydrogen. The compounds of the formulae (7B) and (7'B) are specific examples of the compound of the formula (I).

Alternatively, certain embodiments of the compounds of formula (I) can be prepared according to procedures involving the reaction steps described in Scheme 3 below. Option 3 Reaction conditions: Step 3a and Step 3b: palladium catalyst, potassium carbonate (K ₂ CO ₃ ), dioxane, water, 80-85 ° C; Step 3c: palladium catalyst, potassium carbonate (K ₂ CO ₃ ), dioxins Alkane, water, 70 ° C; Step 3d and Step 3e: cesium carbonate (Cs ₂ CO ₃ ), DMF, room temperature (20 to 25 ° C) to 80 ° C; Step 3e': sodium bicarbonate and tetratriphenyl Phenylphosphine palladium; Step 3f and Step 3g: LiOH.H ₂ O, tetrahydrofuran (THF), methanol (MeOH), hydrochloric acid (HCl), RT.

In another embodiment, the process for the preparation of a compound of formula (I) wherein R ₁ is hydrogen or (C ₁ -C ₆ )alkyl; R ₂ together with R ₃ forms one of one or two heteroatoms a saturated or partially unsaturated 3 to 9 membered heterocyclic group selected from O, N or S; or R ₂ and R ₃ together form a saturated or partially unsaturated (C ₄ -C ₈ ) Cycloalkyl; R _{4 is,} in each case, independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ - a group of C ₆ ) alkyl, amine, cyano, nitro, -C(O)R ₉ and -S(O) _p R ₆ ; R _x is A-CH(R ₇ )-X; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine , cyano, nitro, -C(O)R ₉ or -S(O) _p R ₆ ; X is O; R _v and R _w are independently selected from hydrogen, halogen, hydroxy, (C ₁ -C) ₆ ) alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ ) the group consisting of cycloalkyl, (C ₆ -C ₁₀₎ aryl, heteroaryl and heterocyclyl; Q is O, NR ₈ or S A is or Wherein R _{14 is,} in certain embodiments, R _14a or R _14b ; R _14a is -O(CH ₂ )-(C ₁ -C ₅ )alkyl-S(O) _p R ₆ or -CH ₂ - a heterocyclic group; and R _14b is -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -(C ₁ -C ₆ )alkylheterocyclyl or heterocyclyl; R ₆ , R ₇ And R ₈ , R ₉ , R ₁₄ , m, n, p and q are as defined in the above formula (I); r is an integer from 1 to 4;

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkane , (C ₆ -C ₁₀ ) aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S (O) a group consisting of _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ ) aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) Alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and a group consisting of -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, Cyano, nitro, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ ) a group consisting of alkyl-S(O) _p R ₆ ; wherein R ₆ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ - C ₈ ) alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ - C ₆ ) alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O) a group consisting of R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; consisting of the reaction steps as outlined in Scheme 3, described below herein: Step 3a:

In this procedure step, a compound of formula (6) wherein R ₁ is (C ₁ -C ₆ )alkyl (step 2a, scheme 2), in a catalyst such as a palladium catalyst, selected from the group consisting of potassium carbonate, sodium carbonate, carbonic acid a chemical formula in the presence of a base of potassium hydrogen or sodium hydrogencarbonate and a solvent selected from the group consisting of dioxane, water or a mixture thereof The compound is treated to obtain a compound of the formula (9). Step 3b:

Alternatively, a compound of the formula (6) wherein R ₁ is (C ₁ -C ₆ )alkyl is used in a catalyst such as a palladium catalyst, selected from the group consisting of potassium carbonate, sodium carbonate, potassium hydrogencarbonate or sodium hydrogencarbonate, and Treatment with a boron compound such as bis(pinacolato) diboron in the presence of a solvent of dioxane, water or a mixture thereof to obtain a compound of formula (8). Step 3c:

In this step, the compound of the formula (8) is on a catalyst such as a palladium catalyst, a base selected from the group consisting of potassium carbonate, sodium carbonate, potassium hydrogencarbonate or sodium hydrogencarbonate, and a solvent selected from the group consisting of dioxane, water or a mixture thereof. Chemical formula The compound is treated to obtain a compound of the formula (9). Step 3d:

In this procedure step, the compound of formula (9) is present in the presence of a base selected from the group consisting of cesium carbonate (Cs ₂ CO ₃ ) or potassium carbonate (K ₂ CO ₃ ) and a solvent such as dimethylformamide Treatment of a compound of the formula L-CH ₂ -(C ₁ -C ₅ )alkyl-S(O) _p R ₆ or L-CH ₂ -heterocyclyl; wherein L is a cleavage group such as chloro, bromo or methanesulfonyl Or tolsulfonyl to obtain a compound of formula (10) wherein R _14a is -O-CH ₂ -(C ₁ -C ₅ )alkyl-S(O) _p R ₆ or -O-CH ₂ - A cyclic group and R ₁ is (C ₁ -C ₆ )alkyl. The compound of the formula (10) is a specific example of the compound of the formula (I). Step 3e:

In this procedure step, the compound of formula (9) is present in the presence of a base selected from the group consisting of cesium carbonate (Cs ₂ CO ₃ ) or potassium carbonate (K ₂ CO ₃ ) and a solvent such as dimethylformamide Treatment with a compound of the formula L-(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , L-(C ₁ -C ₆ )alkylheterocyclyl or L-heterocyclyl; wherein L is a leaving group For example, chlorine, bromine, methanesulfonyl or toluenesulfonyl to obtain a compound of formula (11) wherein R _14a is -O-(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- O-(C ₁ -C ₆ )alkylheterocyclyl or -O-heterocyclyl and R ₁ is (C ₁ -C ₆ )alkyl. The compound of the formula (11) is a specific example of the compound of the formula (I). Step 3e':

In this procedure step, the compound of formula (8) is on a catalyst such as a palladium catalyst selected from the group consisting of cesium carbonate (Cs ₂ CO ₃ ), potassium carbonate (K ₂ CO ₃ ), sodium hydrogencarbonate (NaHCO ₃ ), potassium hydrogencarbonate. Chemical formula in the presence of a base of (KHCO ₃ ) Compound treatment to obtain a compound of formula (11) wherein R _14b is -O-(C ₁ -C ₆ )alkyl-S(O) _p R ₆ and R ₁ is (C ₁ -C ₆ )alkyl . The compound of the formula (11) is a specific example of the compound of the formula (I). Steps 3f and 3g:

Compounds of formula (10) and (11) wherein R ₁ is (C ₁ -C ₆ )alkyl, according to the method described in J. Med. Chem., 1995, 38(3): 1386-96 In step 3d and step 3e, the ingestion is carried out in a solvent selected from the group consisting of THF, ethanol, MeOH, water or a mixture thereof, and is selected from the group consisting of NaOH, KOH, lithium hydroxide (LiOH) or barium hydroxide (Ba ( The base of OH) ₂ ) is hydrolyzed, followed by neutralization with HCl to obtain compounds of formula (10A) and (11A), respectively, wherein R ₁ is hydrogen. The compounds of the formulae (10A) and (11A) are specific examples of the compound of the formula (I).

Alternatively, certain embodiments of the compounds of formula (I) can be prepared according to procedures involving the reaction steps described in Scheme 4 below. Option 4 Reaction conditions: Step 4a, Step 4b and Step 4c: cesium carbonate (Cs ₂ CO ₃ ), DMF, room temperature (20 to 25 ° C); Step 4d and Step 4e: LiOH.H ₂ O, tetrahydrofuran (THF), Methanol (MeOH), hydrochloric acid (HCl), RT.

In another embodiment, the process for the preparation of a compound of formula (I) wherein R ₁ is hydrogen or (C ₁ -C ₆ )alkyl; R ₂ together with R ₃ forms one of one or two heteroatoms a saturated or partially unsaturated 3 to 9 membered heterocyclic group selected from O, N or S; or R ₂ and R ₃ together form a saturated or partially unsaturated (C ₄ -C ₈ ) Cycloalkyl; R _{4 is,} in each case, independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ - a group of C ₆ ) alkyl, amine, cyano, nitro, -C(O)R ₉ and -S(O) _p R ₆ ; R _x is A-CH(R ₇ )-X; Wherein R ₇ is hydrogen; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ ) an alkyl group, an amine group, a cyano group, a nitro group, -C(O)R ₉ or -S(O) _p R ₆ ; X is O; A is a (C ₆ -C ₁₀ ) aryl group; _6- C ₁₀ ) aryl is selected from (C ₁ -C ₆ ) alkane of spiro[茚-1,4'-piperidine] and 1-methylspiro[porphyrin-3,4'-piperidine] substituted heterocyclic group; R _v and R _w are independently selected from the group consisting of hydrogen based, halo, hydroxy (C ₁ -C ₆₎ alkyl, halo (C ₁ -C ₆₎ alkyl, -O (C ₁ -C ₆₎ alkyl, amino, _{cyano, -C (O) R 9,} (C ₃ -C ₈₎ cycloalkyl, (C ₆ -C ₁₀₎ aryl group, a heterocyclic group and the heteroaryl group consisting of aryl; Q is O, NR ₈ or _{S; R 6, R 8,} R 9, m, n and p are as defined in the above formula (I);

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkane , (C ₆ -C ₁₀ ) aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S (O) a group consisting of _p R ₆ , wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ ) aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) Alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, (C ₁ -C ₆ )alkylheterocyclyl, heterocyclyl, heteroaryl, amine, cyanide a group consisting of a nitro group, a nitro group, a -C(O)R ₉ and a -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above Definer

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, Cyano, nitro, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ ) a group consisting of alkyl-S(O) _p R ₆ ; wherein R ₆ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ - C ₈ ) alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ - C ₆ ) alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O) a group consisting of R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; consisting of the reaction steps as outlined in Scheme 4, described below herein: Step 4a:

In this procedure step, the compound of formula (5) (step 1d, scheme 1) is present in the presence of a base selected from the group consisting of cesium carbonate, potassium hydrogencarbonate or sodium hydrogencarbonate, and a solvent such as dimethylformamide. Treatment with 1,4-bis(bromomethyl)benzene to obtain a compound of formula (12). Step 4b:

In this procedural step, a compound of formula (12) is present in the presence of a base selected from the group consisting of cesium carbonate, potassium carbonate, sodium carbonate, potassium hydrogencarbonate or sodium hydrogencarbonate, and a solvent such as dimethylformamide. in 1-methyl-spiro [indoline-3,4'-piperidine], so as to obtain a compound of formula (13), wherein R ₁ is (C ₁ -C ₆₎ alkyl. The compound of the formula (13) is a specific example of the compound of the formula (I). Step 4c:

In this procedural step, a compound of formula (12) is present in the presence of a base selected from the group consisting of cesium carbonate, potassium carbonate, sodium carbonate, potassium hydrogencarbonate or sodium hydrogencarbonate, and a solvent such as dimethylformamide. Treatment with spiro[茚-1,4'-piperidine] to obtain a compound of formula (14) wherein R ₁ is (C ₁ -C ₆ )alkyl. The compound of the formula (14) is a specific example of the compound of the formula (I). Steps 4d and 4f:

According to the method described in J. Med. Chem., 1995, 38(3): 1386-96, the compounds of the formulae (13) and (14) are obtained in steps 4b and 4c, respectively, wherein R ₁ is (C ₁ -C ₆ )alkyl) is taken up in a solvent selected from the group consisting of THF, ethanol, MeOH, water or a mixture thereof, and is selected from the group consisting of NaOH, KOH, lithium hydroxide (LiOH) or barium hydroxide (Ba(OH) The bases of ₂ ) are hydrolyzed, followed by neutralization with HCl to obtain compounds of the formulae (13A) and (14A), wherein R ₁ is hydrogen. The compounds of the formulae (13A) and (14A) are specific examples of the compound of the formula (I).

Alternatively, certain embodiments of the compounds of formula (I) can be prepared according to procedures involving the reaction steps described in Scheme 5 below. Option 5 Reaction conditions: Step 5a: palladium acetate, potassium phosphate; Step 5b: lithium aluminum hydride, THF, 0 ° C; Step 5c: triphenylphosphine, diethyl azodicarboxylate (DEAD), dichloromethane; Step 5d: LiOH.H ₂ O, tetrahydrofuran (THF), methanol (MeOH), hydrochloric acid (HCl), RT.

In another embodiment, the process for the preparation of a compound of formula (I) wherein R ₁ is hydrogen or (C ₁ -C ₆ )alkyl; R ₂ together with R ₃ forms one of one or two heteroatoms a saturated or partially unsaturated 3 to 9 membered heterocyclic group selected from O, N or S; or R ₂ and R ₃ together form a saturated or partially unsaturated (C ₄ -C ₈ ) Cycloalkyl; R _{4 is,} in each case, independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ - a group of C ₆ ) alkyl, amine, cyano, nitro, -C(O)R ₉ and -S(O) _p R ₆ ; R _x is A-CH(R ₇ )-X; Wherein R ₇ is hydrogen; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ ) alkyl, amine, cyano, nitro, -C(O)R ₉ or -S(O) _p R ₆ ; X is O; A is R _v and R _w are independently selected from the group consisting of hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, a group consisting of an amine group, a cyano group, a -C(O)R ₉ , a (C ₃ -C ₈ )cycloalkyl group, a (C ₆ -C ₁₀ )aryl group, a heterocyclic group, and a heteroaryl group; Or O, NR ₈ or S; R ₆ , R ₈ , R ₉ , R ₁₄ , m, n, p, q and r are as defined in the above formula (I);

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkane , (C ₆ -C ₁₀ ) aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S (O) a group consisting of _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ ) aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) Alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and a group consisting of -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, Cyano, nitro, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ ) a group consisting of alkyl-S(O) _p R ₆ ; wherein R ₆ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ - C ₈ ) alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ - C ₆ ) alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O) a group consisting of R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; consisting of the reaction steps as outlined in Scheme 5, described below herein: Step 5a:

In this procedure step, the compound of formula (15) is in the presence of a catalyst such as palladium acetate and a base selected from the group consisting of potassium carbonate or sodium carbonate, cesium carbonate, sodium acetate, sodium hydroxide, potassium phosphate, dipotassium hydrogen phosphate. Treatment with a compound of formula (16) to obtain a compound of formula (17). Step 5b:

In this procedural step, the compound of the formula (17) is subjected to reduction in the presence of a reducing agent such as lithium aluminum hydride (LiAlH ₄ ) and a solvent selected from the group consisting of ethanol, methanol, isopropanol, tetrahydrofuran or a mixture thereof to obtain A compound of formula (18) wherein R ₇ is hydrogen. Step 5c:

In this procedure, a compound of formula (18) wherein R ₁ is (C ₁ -C ₆ )alkyl is in triphenylphosphine, diethyl azodicarboxylate and selected from the group consisting of dichloromethane, 1 , in the presence of a solvent of 2-dichloroethane, chloroform, diethyl ether, ethyl acetate or a mixture thereof, is treated with a compound of the formula (5) (step 1d, scheme 1) (step 1d, scheme 1) to obtain a chemical formula. Compound of (19). The compound of the formula (19) is a specific example of the compound of the formula (I). Step 5d:

a compound of formula (19) wherein R ₁ is (C ₁ -C ₆ )alkyl (obtained in step 5c) according to the procedure described in J. Med. Chem., 1995, 38(3): 1386-96 Ingesting a solvent selected from the group consisting of THF, ethanol, MeOH, water or a mixture thereof, and hydrolyzing with a base selected from the group consisting of NaOH, KOH, lithium hydroxide (LiOH) or barium hydroxide (Ba(OH) ₂ ), HCl followed by neutralization, to obtain a compound of formula (. 19A) of which R ₁ is hydrogen. The compound of the formula (19A) is a specific example of the compound of the formula (I).

Alternatively, certain embodiments of the compounds of formula (I) can be prepared according to procedures involving the reaction steps described in Scheme 6 below. Option 6 Reaction conditions: Step 6a: glacial acetic acid, sodium acetate, acetic acid, 80 ° C; Step 6b: potassium carbonate, acetonitrile, reflux; Step 6c: triphenylphosphine, diethyl azodicarboxylate (DEAD), THF , RT; Step 6d: LiOH.H ₂ O, tetrahydrofuran (THF) methanol (MeOH), RT.

In another embodiment, the process for the preparation of a compound of formula (I) wherein R ₁ is hydrogen or (C ₁ -C ₆ )alkyl; R ₂ together with R ₃ forms one of one or two heteroatoms a saturated or partially unsaturated 3 to 9 membered heterocyclic group selected from O, N or S; or R ₂ and R ₃ together form a saturated or partially unsaturated (C ₄ -C ₈ ) Cycloalkyl; R _{4 is,} in each case, independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ - a group of C ₆ ) alkyl, amine, cyano, nitro, -C(O)R ₉ and -S(O) _p R ₆ ; R _x is A-CH(R ₇ )-X; Wherein R ₇ is hydrogen; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ ) alkyl, amine, cyano, nitro, -C(O)R ₉ or S(O) _p R ₆ ; X is O; A is (C ₆ -C ₁₄ ) aryl; R _v and R _{The w} is independently selected from the group consisting of hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amine, cyanide , -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic, and hetero a group consisting of aryl groups; Q is selected from O, NR ₈ or S; R ₆ , R ₈ , R ₉ , R ₁₄ , m, n, p, q and r are as defined in the above formula (I) Where;

(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkane , (C ₆ -C ₁₀ ) aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S (O) a group consisting of _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

-O(C ₁ -C ₆ )alkyl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ,- a group consisting of S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above;

(C ₆ -C ₁₀ ) aryl is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ ) Alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) Alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ , a group consisting of -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ and -O(CH ₂ ) _s C[=NO(C ₁ -C ₆ )alkyl]R ₈ ; R ₆ , R ₈ , R ₉ , s and p are as defined above;

The heterocyclic group is a 3- to 9-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, Cyano, nitro, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ ) a group consisting of alkyl-S(O) _p R ₆ ; wherein R ₆ and p are as defined above;

A heteroaryl group is a 3- to 10-membered ring which is unsubstituted or substituted with one or more groups independently selected from (C ₁ -C ₆ )alkyl, (C ₂ - C ₈ ) alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ - C ₆ ) alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O) a group consisting of R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above;

Halogen is chlorine, bromine, iodine or fluorine; consisting of the reaction steps as outlined in Scheme 6, as described herein below: Step 6a:

In this procedure step, the compound of the formula (20) is in the presence of glacial acetic acid and a base selected from the group consisting of potassium carbonate or sodium carbonate, cesium carbonate, sodium acetate, sodium hydroxide, potassium phosphate, and dipotassium hydrogen phosphate. O-methylhydroxylamine hydrochloride is treated to obtain a compound of formula (21). Step 6b:

In this procedure step, the compound of formula (21) is chemically The compound is, for example, 4-hydroxybenzyl alcohol, and a solvent selected from the group consisting of dioxane, THF, toluene, acetonitrile or dimethoxyethane or a mixture thereof to obtain a compound of the formula (22), wherein R ₇ is hydrogen. Step 6c:

In this procedure step, a compound of formula (22) wherein R ₁ is (C ₁ -C ₆ )alkyl, in triphenylphosphine, diethylazodicarboxylate and selected from dichloromethane, The compound of the formula (5) (step 1d, scheme 1) is treated in the presence of a solvent of 1,2-dichloroethane, chloroform, diethyl ether, tetrahydrofuran, ethyl acetate or a mixture thereof to obtain the chemical formula (23). Compound. The compound of the formula (23) is a specific example of the compound of the formula (I). Step 6d:

A compound of the formula (23) wherein R ₁ is (C ₁ -C ₆ )alkyl (obtained in step 6c) according to the method described in J. Med. Chem., 1995, 38(3): 1386-96 Ingesting a solvent selected from the group consisting of THF, ethanol, MeOH, water or a mixture thereof, and hydrolyzing with a base selected from the group consisting of NaOH, KOH, lithium hydroxide (LiOH) or barium hydroxide (Ba(OH) ₂ ), HCl followed by neutralization, to obtain a compound of formula (. 23A) of which R ₁ is hydrogen. The compound of the formula (23A) is a specific example of the compound of the formula (I).

The compound of the formula (I) wherein Q is S can be further oxidized to obtain a compound of the formula (I) wherein Q is SO or SO ₂ .

Those skilled in the art will recognize that the compounds of formula (I) of the present invention contain asymmetric or palmitic centers and therefore exist in different stereoisomeric forms, such as racemic mixtures of mirror image isomers, non-image isomers The mixture is either a mirror image or an optically pure compound. The term "chiral" means a molecule having the characteristics of a non-overlapping group of mirrors, and the term "achiral" means a molecule that is superimposable in its mirroring partner. It is intended that all stereoisomeric forms of the compounds of the invention, including but not limited to, non-image isomers and mirror image isomers, as well as mixtures thereof such as racemic mixtures, geometric isomers, form part of the invention.

When the compound of formula (I) of the present invention comprises a palmitic center, the compound exists in two mirror image isoform forms, and the present invention includes both mirror image isomers and mixture of mirror image isomers, for example, Spin a specific 50:50 mixture of the mixture. The mirror image isomers can be resolved by methods known to those skilled in the art, such as the formation of isolated non-an image isomer salts, for example, via crystallization (see CRC Handbook of Optical Resolutions via Diastereomeric Salt Formation by David Kozma (CRC Press, 2001)); the formation of isolated non-image-isomerized derivatives or complexes, for example, via crystallization, gas-liquid or liquid chromatography; a mirror image isomer and mirror image Selective reaction of an isomer-specific reagent, for example, enzymatic esterification; or in a palmitic environment, for example, in the palm support, for example, a palmitic ligand associated with cerium oxide or Gas-liquid or liquid chromatography in the presence of a palm solvent. It will be understood that when the mirror image isomer is converted to another chemical entity in one of the above separation procedures, further steps are required to liberate the desired mirror image isomer form. Alternatively, optically active reagents, substrates, catalysts or solvents can be used to synthesize specific mirror image isomers via asymmetric synthesis, or to convert one mirror image isomer to another via asymmetric transformation. One. The designation of a particular absolute configuration of the palmitic carbon of a compound of the invention is understood to mean that the specified mirror image isomer form of the compound is enantiomeric excess (ee) or in other words substantially no other Mirroring isomers. For example, the "R" form of a compound is substantially "S" in the absence of a compound and is therefore in excess of the Spiegelmer in the "S" form. Conversely, the "S" form of the compound is substantially "R" in the absence of a compound and is therefore in excess of the Spiegel isomer in the "R" form. As used herein, the amount of Spiegelmer is greater than 50% for the presence of a particular mirror image isomer. In a particular embodiment, when a particular absolute configuration is specified, the compound of the depicted compound has an excess of at least about 90%. When the compound of the formula (I) of the present invention has two or more palmitic carbons, it may have more than two optical isomers and may exist in the form of a non-image isomer. For example, when there are two palmitic carbons, the compound can have up to 4 optical isomers and 2 pairs of mirror image isomers ((S,S)/(R,R) and (R,S)/( S, R)). The pair of mirror image isomers are mirror images of each other (e.g., (S, S) / (R, R)). Stereoisomers that are not mirror images (eg, (S, S) and (R, S)) are non-image isomers. The pairing of the non-image isomers can be separated by methods known to those skilled in the art, for example, chromatography or crystallization, and the individual mirror image isomers in each pair can be separated as described above. The present invention includes each of the non-image isomers of such compounds, as well as mixtures thereof.

Isotopically labeled forms of the compounds of formula (I) can be prepared by conventional techniques known to those skilled in the art or by procedures analogous to those described above or in the exemplified in the subsequent sections, using the corresponding isotopically labeled reagents in place of the non-labeled reagents.

In a particular embodiment, the compound of formula (I) is present as a tautomer and is intended to comprise all tautomeric forms of the compound within the scope of the invention.

In a particular embodiment, the compound of formula (I) in its free base form is converted to its corresponding pharmaceutically acceptable salt. Depending on the particular substituents found on the compounds described herein, the pharmaceutically acceptable salts of the compounds of formula (I) are prepared as relatively non-toxic acids or bases. When the compounds of the formula (I) of the present invention contain an acidic group, they may form an addition salt with a suitable base. For example, a pharmaceutically acceptable base addition salt of a compound of the invention may include an alkali metal salt thereof such as sodium, potassium, calcium, magnesium, ammonium, or an organic base addition salt. Pharmaceutically acceptable organic base addition salts of the compounds of this invention include those derived from an organic base such as lysine, arginine, guanidine, diethanolamine, metformin or other organic bases known to those skilled in the art. Those.

When the compound of the formula (I) of the present invention contains one or more basic groups, they may form an addition salt with an inorganic acid or an organic acid. Examples of pharmaceutically acceptable acid addition salts include derivatives derived from inorganic acids such as boric acid, perchloric acid, hydrochloric acid, hydrobromic acid, hydrofluoric acid, hydroiodic acid, nitric acid, carbonic acid, monohydrogencarbonic acid, phosphoric acid. Phosphoric acid, monohydrogenphosphoric acid, dihydrogenphosphoric acid, sulfuric acid, monohydrogensulfuric acid, phosphorous acids or other inorganic acids known to those skilled in the art Those of those. Further, examples of pharmaceutically acceptable acid addition salts include derivatives derived from organic acids such as acetic acid, propionic acid, isobutyric acid, oxalic acid, malic acid, tartaric acid. , citric acid, ascorbic, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid (suberic acid), fumaric acid, mandelic acid, phthalic acid, benzenesulfonic acid, toluenesulfonic acid, methanesulfonic acid Methanesulfonic acid), glucuronic acid, galacturonic acid, naphthoic acid, camphoric acid or other inorganic acid salts known to those skilled in the art . Certain specific compounds of the invention contain both basic and acidic functional groups, allowing the compounds to be converted to base or acid addition salts.

In a particular embodiment of the invention, a compound of formula (I) or a compound of formula (Ia) is provided as a pharmaceutically acceptable salt.

The pharmaceutically acceptable salt of the compound of formula (I) is selected from the group consisting of acetate, ascorbate, calcium salt, cinnamate, citrate, crotonate, Gluconate, glutarate, hydrochloride, lactate, maleate, malonate, metformin, methanesulfonate Methanesulfonate), oxalate, tartrate or toluenesulfonate.

In a particular embodiment of the invention, the pharmaceutically acceptable salt of the compound of formula (I) is a calcium salt.

The pharmaceutically acceptable salts of the present invention can be synthesized from a host compound, that is, a compound of the formula (I) containing a basic or acidic moiety via conventional chemical methods. Generally, the salts are prepared by contacting the free base or acid with the desired salt to form an inorganic or organic acid or base in a suitable solvent or dispersion, or by anion exchange or cation exchange with other salts. Suitable solvents are, for example, ethyl acetate, ethers, alcohols, acetone or mixtures of these solvents.

Further, the present invention includes all solvates of the compound of the formula (I), for example, hydrates and solvates formed with other crystallization solvents selected from alcohols such as methanol, ethanol, 1-propanol, 2-propanol Ethers such as diethyl ether, diisopropyl ether or tetrahydrofuran, esters such as methyl acetate or ethyl acetate, ketones such as acetone or mixtures thereof. Certain compounds of the invention may exist in unsolvated as well as solvated forms, including hydrated forms.

It is further intended that various polymorphs of the compounds of formula (I) are included within the scope of the invention. The various polymorphs of the compounds of the invention can be prepared via standard crystallization procedures known in the art. The crystallization technique employed can utilize a variety of solvents or mixtures thereof, temperature conditions, and various cooling modes ranging from very fast to very slow cooling. The presence of polymorphs can be by IR (infrared) spectroscopy, solid-state probe NMR (nuclear magnetic resonance) spectroscopy, differential scanning calorimetry, powder X-ray diffraction or other standard techniques. to make sure.

Furthermore, the invention also includes prodrugs of the compounds of formula (I). A prodrug of a compound of the present invention is a derivative of the above-described compound of the present invention which undergoes a chemical transformation by metabolism or chemical process when administered to a patient in need thereof to release a source derived from the prodrug in vivo. Maternal medicine. Preferred prodrugs are pharmaceutically acceptable ester derivatives such as alkyl esters, cycloalkyl esters, alkenyl esters, benzyl esters, monosubstituted alkyl esters or disubstituted alkyl esters which are physiologically It can be converted to the parent carboxylic acid by solvolysis under conditions and those conventionally used in the art.

The invention further relates to carboxylic acid isomers of the compounds of formula (I).

The invention also relates to N-oxide derivatives of the compounds of formula (I).

The invention also relates to S-oxide derivatives of the compounds of formula (I).

In one aspect of the invention, the compound of formula (I) is a GPR40 agonist.

In a particular embodiment of the invention, the use of a compound of formula (I) for the treatment of a disease or condition mediated by GPR40 is found.

In another aspect, the invention relates to a method of treatment of a disease or condition of a GPR40 vector comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I) or a stereoisomer thereof, tautomerism thereof A construct, a pharmaceutically acceptable salt or solvate.

In a specific embodiment, the invention relates to a method of treating a disease or condition of a GPR40 vector comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I) or a stereoisomer thereof or Tautomers or pharmaceutically acceptable salts.

In yet another aspect, the invention provides the use of a compound of formula (I), or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate thereof, for the treatment of a disease or condition of a GPR40 vector.

In a specific embodiment, the invention relates to the use of a compound of formula (I) or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate thereof for the treatment of a disease or condition of GPR40 vector use.

According to a particular embodiment, the invention relates to the manufacture of a medicament for the treatment of a disease or condition of a GPR40 vector of a compound of formula (I) or a stereoisomer or tautomer thereof or a pharmaceutically acceptable salt thereof.

As used herein, the phrase "disease or symptom of GPR40 vector" or "disease or symptom of GPR40 vector" means a disease characterized by inappropriate, for example, less or more than normal GPR40 activity. Or disorders or symptoms. The disease or condition of the GPR40 vector can be completely or partially mediated by inappropriate GPR40 activity.

In a particular embodiment of the invention, the disease or condition mediated by GPR40 is selected from the group consisting of diabetes, obesity, hyperglycemia, glucose intolerance, insulin resistance, hyperinsulinemia, hypercholesterolemia, hypertension, high Lipoproteinemia, hyperlipidemia, hypertriglyceridemia, dyslipidemia, metabolic syndrome, X syndrome, cardiovascular disease, atherosclerosis, kidney disease, polycystic ovarian syndrome, ketoacidosis, thrombosis Disease, kidney disease, diabetic neuropathy, diabetic retinopathy, sexual dysfunction, fatty liver development, skin disease, dyspepsia, hypoglycemia, cancer, edema, and disorders associated with glucose levels such as pancreatic beta cell regeneration Group.

In a particular embodiment of the invention, the disease or condition mediated by GPR40 is selected from the group consisting of diabetes, obesity, insulin resistance, hyperglycemia, glucose intolerance, hypercholesterolemia, hypertriglyceridemia, dyslipidemia , a group consisting of hyperlipoproteinemia, hyperinsulinemia, atherosclerosis, diabetic neuropathy, diabetic retinopathy, metabolic syndrome, X syndrome, hypertension, and pancreatic beta cell degeneration.

In a specific embodiment of the invention, the disease or condition mediated by GPR40 is selected from the group consisting of diabetes, obesity, insulin resistance, hyperglycemia, glucose intolerance, metabolic syndrome, X syndrome, and pancreatic beta cell degeneration. Group.

In a particular embodiment of the invention, the diabetes is type 2 diabetes.

In a particular embodiment, the disease or condition mediated by GPR40 is a metabolic disorder, which means one or more of the above identified diseases or conditions.

Accordingly, the present invention relates to a method of treating metabolic disorders comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I) or a stereoisomer or tautomer thereof or pharmaceutically acceptable Accepted salts.

In a particular embodiment, the invention provides the use of a compound of formula (I), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, for the treatment of a metabolic disorder.

According to a particular embodiment, the invention relates to the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment of metabolic disorders.

As used herein, the term "metabolic disorder" means a disorder associated with an abnormal metabolism. Therefore, all disorders concerning metabolic abnormalities in the context of the present invention are included in the term "metabolic disorder".

In a specific embodiment, the metabolic disorder is selected from the group consisting of diabetes, obesity, cardiovascular disease, hypertension, ketoacidosis, insulin resistance, glucose intolerance, hyperglycemia, hypertriglyceridemia, polycystic Ovarian syndrome, hypercholesterolemia, hyperlipoproteinemia, dyslipidemia, metabolic syndrome, X syndrome, hyperlipidemia, diabetic neuropathy, diabetic retinopathy, edema, and abnormal plasma lipoproteins, triglycerides Or a disorder associated with pancreatic beta cell degeneration.

The term "diabetes mellitus" or "diabetes" means a chronic disease or condition that occurs when the pancreas does not produce sufficient insulin, or when the body is unable to effectively use insulin produced by the pancreas. This results in an increase in the concentration of glucose in the blood (hyperglycemia). The two main forms of diabetes are Type 1 diabetes (insulin-dependent diabetes) and Type 2 diabetes (Non-insulin dependent diabetes mellitus (NIDDM)). Type 1 diabetes is an autoimmune condition in which the beta cells of the pancreas producing insulin are impaired, often resulting in an absolute deficiency of the hormone insulin that regulates glucose utilization. Type 2 diabetes is usually preceded by normal or even elevated amounts of insulin and can be attributed to the tissue's appropriate response to insulin. Other types of diabetes include gestational diabetes (hyperglycemia developed during pregnancy) and "other" more rare causes (genetic syndrome, acquired procedures such as pancreatitis, diseases such as cyst fibrosis, exposure to certain drugs, Virus and unknown cause). In a particular embodiment of the invention, diabetes means Type 2 diabetes.

The term "metabolic syndrome" means a collection of metabolic abnormalities including abdominal obesity, insulin resistance, glucose intolerance, diabetes, hypertension, and dyslipidemia. These abnormalities are known to be associated with an increased risk of vascular events.

As used herein, the term "cardiovascular disease" means any disease of the heart or blood vessels. One or more heart diseases included in the term "cardiovascular disease" are selected from, but are not limited to, angina, arrhythmia, coronary artery disease (CAD), cardiomyopathy. , myocardial infarction, heart failure, hypertrophic cardiomyopathy, mitral regurgitation, mitral valve prolapse, pulmonary stenosis )Wait. The vascular disease included in the term "cardiovascular disease" is selected from, but not limited to, for example, peripheral vascular disease, artery disease, carotid artery disease, deep vein. Deep vein thrombosis, venous diseases, atherosclerosis, and the like.

In a specific embodiment, the metabolic disorder is selected from the group consisting of: diabetes, obesity, insulin resistance, hyperglycemia, glucose intolerance, hypercholesterolemia, hypertriglyceridemia, dyslipidemia, hyperlipoproteinemia Hyperinsulinemia, atherosclerosis, diabetic neuropathy, diabetic retinopathy, metabolic syndrome, X syndrome, hypertension, or pancreatic beta cell degeneration.

In a specific embodiment, the metabolic disorder is selected from the group consisting of diabetes, obesity, insulin resistance, glucose intolerance, dyslipidemia, hyperinsulinemia, X syndrome, metabolic syndrome, or pancreatic beta cell degeneration.

In a specific embodiment, the metabolic disorder is type 2 diabetes. Pharmaceutical composition

Further, the present invention relates to a pharmaceutical composition comprising a therapeutically effective amount of at least one compound of the formula (I) or a physiologically acceptable salt thereof in addition to a conventional pharmaceutically acceptable carrier, and to the production of a pharmaceutical composition a step comprising the incorporation of at least one compound of formula (I) into a suitable administration using a pharmaceutically suitable and physiologically acceptable excipient and, if appropriate, a further suitable active compound, additive or adjuvant In the form.

According to a specific embodiment, the present invention relates to a pharmaceutical composition comprising a substituted alkylcarboxylic acid derivative, a compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable compound A composition for the treatment of a disease or condition of a GPR40 agonist and a GPR40 vector.

As used herein, the term "pharmaceutically acceptable" means that the carrier, diluent, excipient and/or salt must be compatible with the other ingredients of the formulation and not deleterious to the recipient.

As used herein, the term "pharmaceutically acceptable carrier" means any type of non-toxic, inert solid, semi-solid, diluent, encapsulating material or formulation auxiliary. Some examples of materials that can serve as pharmaceutically acceptable carriers are lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethylcellulose, ethylcellulose, and cellulose B. Acid ester; malt; gelatin; talc; and other non-toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweeteners, flavoring agents, and aromatics Preservatives and antioxidants may also be present in the compositions at the discretion of the formulator.

It is further intended that the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in combination with at least one pharmaceutically active compound as a GPR40 agonist is within the scope of the invention.

According to a specific embodiment, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, and at least one further therapeutically active agent, which is pharmaceutically acceptable a.

In a particular embodiment, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt thereof, for use in combination with a further therapeutically active agent for the treatment of a disease or condition in a GPR40 vector.

The therapeutically active agent used to bind one or more compounds of formula (I) may be selected from those known for use in diabetes and other conditions such as obesity, insulin resistance, hyperglycemia, glucose intolerance, hypercholesterolemia, high school A compound or active substance for the treatment of acid glyceride, dyslipidemia, hyperlipoproteinemia, hyperinsulinemia or atherosclerosis. According to the present invention, a therapeutically active agent for use in combination with a compound of formula (I) of the present invention may be selected from, but not limited to, insulin, sulfonylurea, biguanide, meglitinides, oxadiazolidinedione. (oxadiazolidinediones), thiazolidinediones, glucosidase inhibitors, glycophosphorylase inhibitors, glycosidic antagonists, HMGCoA reductase inhibitors, GLP-1 (glycogenoid-1) agonist, Potassium channel opener, dipeptidyl peptidase IV inhibitor (DPP-IV), insulin sensitizer, glucose uptake/glucose transport/glucose reuptake regulator, sodium-dependent glucose transporter 1 or 2 (SGLT1, SGLT2) Compounds that alter lipid metabolism, such as antihyperlipidemic active ingredients and antilipidemic active ingredients, PPAR gamma agonists, and agents that bind PPAR alpha and gamma, and ATP-dependent potassium ions that act on beta cells. The active ingredient of the channel.

In a particular embodiment, a compound of formula (I) can be used to bind a PPAR gamma agonist selected from the group consisting of rosiglitazone, pioglitazone, rivoglittazone, and the like.

In a particular embodiment, a compound of formula (I) can be used in combination with simvastatin, fluvastatin, pravastatin, lovastatin, atorvastatin ( Atorvastatin), cerivastatin, rosuvastatin, and the like, HMGCoA reductase inhibitors.

In a particular embodiment, the compound of formula (I) can be used in combination with tolbutamide, glibenclamide, glipizide, glimepiride, and the like. Sulfonamides.

In another embodiment, a compound of formula (I) can be used in combination with a meglitinide selected from the group consisting of repaglinide, nateglinide, mitiglinide, and the like. Meglitinides).

In another specific embodiment, the compound of formula (I) can be used in combination with exenatide, liraglutide, taspoglutide, albiglutide. , lixisenatide and the like GLP-1 agonist.

In another specific embodiment, the compound of formula (I) can be used in combination with alogliptin, gemigliptin, linagliptin, saxagliptin. , sitagliptin, vildagliptin, and the like, DPP-IV inhibitors.

Thus, a further therapeutically active agent that can be used in a particular embodiment to bind one or more compounds of formula (I) contained within the invention can be selected from one or more of the agents, including but not limited to Insulin, rosiglitazone, pioglitazone, gliglitazone, simvastatin, fluvastatin, pravastatin, lovastatin, atorvastatin, simvastatin, rosuvastatin, tolbutamide, grid Lebenone, glipizide, glimepiride, repaglinide, nateglinide, mitiglinide, exenatide, liraglutide, tabolubicin, albendide, Cinapeptide, alogliptin, glistatin, linagliptin, saxagliptin, sitagliptin, vildagliptin, and the like.

The pharmaceutical compositions according to the invention are prepared in a manner known and familiar to those skilled in the art. In addition to the compound of the formula (I) and/or its pharmaceutically acceptable salts, pharmaceutically acceptable inert inorganic and/or organic carriers and/or additives may be employed. For the production of pills, tablets, coated tablets and hard gelatine capsules, it is possible to use, for example, lactose, corn starch or derivatives thereof, gum arabic, magnesium oxide or glucose, and the like. The carrier of the soft gelatin capsule and the suppository is, for example, a fat, a wax, a natural or hardened oil, and the like. Solution For example, a suitable carrier for the production of an injectable solution or emulsion or syrup is, for example, water, a physiological sodium chloride solution or an alcohol such as ethanol, propanol or glycerol, a sugar solution such as a glucose solution or a mannitol solution, or the mentioned A mixture of various solvents.

Further, the pharmaceutical composition of the present invention also contains an additive such as, for example, a filler, an antioxidant, an emulsifier, a preservative, a flavoring agent, a solubilizing agent or a coloring agent. The pharmaceutical composition of the present invention may further comprise two or more substituted alkylcarboxylic acid derivatives, ie, a compound of formula (I) and/or a physiologically acceptable salt, and the pharmaceutical composition may also comprise one or more Other active ingredients for treatment or prevention.

The pharmaceutical composition normally comprises from about 1 to 99% by weight, for example, from about 10 to 80% of a compound of formula (I) or a pharmaceutically acceptable salt thereof.

The amount of the active ingredient, substituted alkylcarboxylic acid derivative, i.e., the compound of formula (I) or a pharmaceutically acceptable salt thereof in the pharmaceutical composition may vary, for example, from about 1 to 500 mg. In the case of a higher body weight mammal in need of treatment, the pharmaceutical composition may comprise a compound of formula (I) in an amount ranging from 5 to 1000 mg. The desired dosage of the substituted alkylcarboxylic acid derivative, i.e., the compound of formula (I), can be selected within a wide range. The daily dose to be administered is selected to achieve the desired therapeutic effect for the metabolic disorder patient to be treated. The substituted alkylcarboxylic acid derivative, i.e., the compound of formula (I) or a pharmaceutically acceptable salt thereof, can be administered at a dose of about 0.05 to 50 mg/kg/day. In the case of a higher body weight mammal in need of treatment, the compound of formula (I) or a pharmaceutically acceptable salt thereof can be administered at a dose of from about 0.1 to 100 mg/kg/day. Higher or lower daily doses may also be administered if desired. The actual dosage level of the active ingredient in the pharmaceutical composition of the present invention can be varied to obtain an amount of the active ingredient effective to achieve the therapeutic response required for a particular patient, composition and mode of administration without toxicity to the patient. The selected dose level can be readily determined by a skilled physician, including the condition to be treated (disease or disorder), depending on factors such as the age, weight status, and physical health and response of the individual patient. The chosen route of administration, pharmacokinetics, severity of the disease, and factors such as are known in the medical arts.

The pharmaceutical compositions according to the invention may be administered orally, for example in the form of pills, tablets, coated tablets, capsules, granules or granules. However, it can also be administered rectally, for example, in the form of a suppository, or parenterally in the form of an injectable sterile solution or suspension, for example, intravenous, intramuscular or subcutaneous injection, or topical administration. For example, in the form of a solution or a skin infiltration patch, or otherwise, for example in the form of a spray or nasal spray.

In the context of the present invention, reference to a compound of formula (I) in one or more specific embodiments of the invention includes reference to a compound of formula (Ia) and/or a compound of formula (Ib).

In a particular embodiment, reference to a compound of formula (I) includes reference to a compound of formula (Ia).

Modifications to the activity of the various embodiments that do not substantially affect the invention are intended to be included within the scope of the invention disclosed herein. Accordingly, the following examples are intended to illustrate, but not to limit, the scope of the invention. Experimental

The nomenclature of the compounds exemplified in the present invention is from Cambridge Soft Corporation, Chemdraw Ultra version 9.0.1.

The reagents were purchased from commercial suppliers such as Frontier Scientific Utah, US; Alpha Aesar US; A. K Scientific, Inc., US; Combi-Blocks Inc., CA; and Sigma Aldrich Chemical company and used herein.

All temperatures are in degrees Celsius unless otherwise indicated. In addition, in these and other places, abbreviations have the following meanings:

Abbreviations and terms used in this article: Salt preparation method

I. General Method for Preparation of Calcium Salt Method A: A sodium hydroxide solution is added to a solution of the compound of formula (I) in THF, and the reaction mixture is stirred for 1 to 3 hours. Calcium chloride was added and the reaction mixture was further stirred overnight at RT. After the reaction was completed, the reaction mixture was concentrated and the residue was suspended in water (20 ml), stirred, filtered, washed with water and dried to obtain a calcium salt of the compound of formula (I). The salts thus obtained were characterized by NMR. Method B: A turbid solution of calcium hydroxide in water is added to a stirred solution of the compound of formula (I) in 1,4-dioxane. The reaction mixture was stirred at RT overnight. After completion of the reaction, the reaction mixture was filtered; the residue was washed with 1,4-dioxane, acetonitrile and ethyl acetate to obtain a calcium salt of the compound of formula (I). The salts thus obtained were characterized by NMR.

II. General procedure for the preparation of metformin salts Metformin was added to a stirred solution of the compound of formula (I) in THF, and the reaction mixture was stirred at RT for 2 hours. The reaction mixture was concentrated and the residue was triturated with petroleum ether and ethyl acetate to give the compound of the compound of formula (I). The salts thus obtained were characterized by NMR. Example 1 Methyl 2-((3-(4-((2',6'-dimethyl-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl) ]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate (Compound 1) Step 1: 3-(4-(Benzyloxy)phenyl)oxy Synthesis of cyclobutane-3-ol

Add n-butyllithium (n-BuLi, 2.5 M in THF) (11.68 g, 182 mmol) to 1-(benzyloxy) in anhydrous THF (100 ml) cooled to -78 ° C under nitrogen atmosphere. A stirred suspension of 4-bromobenzene (commercial source, 30.0 g, 114 mmol) and the reaction mixture was stirred at -78 °C for 1 h. At this temperature, a solution of oxycyclobutane-3-one (9.86 g, 137 mmol) in THF was added and the mixture was slowly warmed to RT and stirred for 2 h. The mixture was reacted at an ice level. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined and washed with brine, dried over anhydrous sodium sulfate This was further purified by flash column chromatography eluting with EtOAc EtOAc EtOAc Yield: 82%; ¹ H NMR (CDCl ₃ , 300 MHz): d 7.51 (d, J = 5.1 Hz, 2H), 7.34-7.46 (m, 5H), 7.03 (d, J = 5.1 Hz, 2H) , 5.11 (s, 2H), 4.93 (d, J = 4.2 Hz, 2H), 4.90 (d, J = 4.2 Hz, 2H), 2.49 (s, 1H); MS: m/z 257.2 [M+H] . Step 2: Synthesis of methyl 2-((3-(4-(benzyloxy)phenyl)oxycyclobutane-3-yl)oxy)acetate

A stirred suspension of NaH (60%) (0.375 g, 15.61 mmol) in THF (30 ml) was cooled to 0 <0>C under N2, and 3-(4-(phenyloxy) A solution of phenyl)oxocyclobutane-3-ol (Compound of Step 1, 2.0 g, 7.80 mmol) was obtained and the mixture was stirred at 0 ° C for 1 h. Next, methyl 2-bromoacetate (2.98 g, 19.51 mmol) was added at 0 ° C, and the mixture was warmed to RT and stirred for 2 h. The mixture was reacted with ice and concentrated. The crude mass was redissolved in ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium This was further purified by combiflash and EtOAc (EtOAc:EtOAc) Yield: 86%; ¹ H NMR (CDCl ₃ , 300 MHz): d 7.36-7.51 (m, 7H), 7.03 (d, J = 4.2 Hz, 2H), 5.11 (s, 2H), 5.00 (d, J = 4.2 Hz, 2H), 4.87 (d, J = 3.9 Hz, 2H), 3.85 (s, 2H), 3.73 (s, 3H); MS: m/z 351.2 [M+Na].

Alternatively, ethyl 2-((3-(4-(benzyloxy)phenyl)oxycyclobutane-3-yl)oxy)acetate is passed according to the procedure above and using 2-bromoacetic acid Ester-substituted 2-bromoacetate methyl ester synthesis. Step 3: Synthesis of methyl 2-((3-(4-hydroxyphenyl)oxycyclobutane-3-yl)oxy)acetate

Add Pd-C (10%) (6.88 g, 64.6 mmol) to methyl 2-((3-(4-(benzyloxy)phenyl)oxycyclobutane-3 in ethanol (80 ml) A stirred solution of the compound of the oxyloxyacetate (Compound of Step 2, 8.6 g, 26.2 mmol), and the reaction mixture was stirred for 1 h under hydrogen atmosphere of RT. The reaction mixture was filtered with EtOAc EtOAc (EtOAc)EtOAc. Yield: 75%; ¹ H NMR (CDCl ₃ , 300 MHz): d 7.29 (d, J = 4.8 Hz, 2H), 6.88 (d, J = 5.1 Hz, 2H) 5.53 (s, 1H), 5.01 ( d, J = 3.9 Hz, 2H), 4.88 (d, J = 3.9 Hz, 2H), 3.85 (s, 2H), 3.73 (s, 3H); MS: m/z261.2 [M+Na].

Alternatively, ethyl 2-((3-(4-hydroxyphenyl)oxycyclobutane-3-yl)oxy)acetate was passed according to the procedure described above and using ethyl 2-((3-(4) -(Benzyloxy)phenyl)oxycyclobutane-3-yl)oxy)acetate substituted methyl 2-((3-(4-(benzyloxy)phenyl)oxycyclobutane Synthesis of -3-yl)oxy)acetate. Step 4: Methyl 2-((3-(4-((2',6'-dimethyl-4'-(3-(methylsulfonyl)propoxy)-[1,1'-linked Synthesis of Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate

Step 4a: Synthesis of 3'-(bromomethyl)-2,6-dimethyl-4-(3-(methylsulfonyl)propoxy)-1,1'-biphenyl

Add (4',6'-dimethyl-4'-(3-(methylsulfonyl)propoxy) to carbon tetrabromide (263 mg, 0.793 mM) at 0 °C in DCM (4 ml) )-[1,1'-Biphenyl]-3-yl)methanol in a solution of triphenylphosphine (260 mg, 0.991 mM). The reaction mixture was stirred at 0 °C for 15 min, allowed to warm to RT and stirred 1 h. The solvent was evaporated, and the obtained crude product was purified eluting eluting eluting eluting eluting

Preparation of (2',6'-dimethyl-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]- according to the method described in PCT Publication No. WO2008001931 A2 3-based) methanol.

Step 4b: methyl 2-((3-(4-((2',6'-dimethyl-4'-(3-(methylsulfonyl)propoxy)-[1,1'-linked Synthesis of Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate

Adding Cs ₂ CO ₃ (2 eq.) to methyl 2-((3-(4-hydroxyphenyl)oxycyclobutane-3-yl)oxy)B in anhydrous DMF (2 ml) Acid ester (compound of step 3, 1 equivalent) and methyl 2-((3-(4-((2',6'-dimethyl-4'-(3-(methylsulfonyl))propoxy) a solution of -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound of step 4a, 1 equivalent) . The reaction mixture was stirred at RT for 3-4 h. The organic layer was washed with brine, dried over Na ₂ SO ₄ and concentrated to afford crude. The crude product was purified by flash column chromatography (EtOAc:EtOAc:EtOAc ¹ H NMR (CDCl ₃ , 300 MHz): d 7.34-7.48 (m, 4H), 7.19 (s, 1H), 7.11 (d, J = 6.9 Hz, 1H), 7.03 (d, J = 8.7 Hz, 2H ), 6.66 (s, 2H), 5.15 (s, 2H), 4.99 (d, J = 6.6 Hz, 2H), 4.86 (d, J = 6.6 Hz, 2H), 4.14 (t, J = 5.4 Hz, 2H ), 3.84 (s, 2H), 3.72 (s, 3H), 3.28 (t, J = 7.5 Hz, 2H), 2.98 (s, 3H), 2.34-2.39 (m, 2H), 2.00 (s , 6H) ;MS: m/z 591.0 [M+ Na]. Example 2 2-((3-(4-((2',6'-Dimethyl-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]- 3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (Compound 2)

LiOH (5 eq.) was added to the methyl 2-((3-(4-((2',6'- dimethyl-4'-) (3) THF (2 ml) and MeOH (0.5 ml) -(Methanesulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (example A solution of 1 compound, 1 eq.), and the reaction mixture was stirred at RT for 2 to 3 h. The solvent was removed, the reaction mixture was acidified with saturated NH ₄ Cl solution (pH 6-6.5). The organic layer was washed with brine, dried in Na ₂ SO ₄ and concentrated to obtain the title compound. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.46-7.48 (m, 2H), 7.31 (s, 2H), 7.18 (s, 1H), 7.11 (d, J = 6.9 Hz, 1H), 7.04 (d , J = 8.4 Hz, 2H), 6.65 (s, 2H), 5.15 (s, 2H), 4.93-4.95 (m, 4H), 4.14 (t, J = 5.4 Hz, 2H), 3.85 (s, 2H) , 3.28 (t, J = 7.2 Hz, 2H), 2.98 (s, 3H), 2.33-2.37 (m, 2H), 1.99 (s, 6H); MS: m/z 552.7 [M-1].

Compounds of Examples 3, 5, 7, 9, 11, 13, and 15 were prepared via the procedure exemplified in Example 1. Compounds of Examples 4, 6, 8, 10, 12, 14 and 16 were prepared via the procedure exemplified in Example 2. The compound property data for Examples 3-16 are described below. Example 3 Methyl 2-((3-(4-([1,1'-biphenyl]-3-ylmethoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate ( Compound 3)

The title compound was prepared in a similar manner as Compound 1 of Example 1 to methyl 2-(3-(4-hydroxyphenyl)oxycyclobutane-3-yl)acetate (Compound of Step 3 of Example 1) Reaction with 3-(bromomethyl)-1,1'-biphenyl. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.68 (s, 2H), 7.58-7.63 (m, 2H), 7.47-7.51 (m, 4H), 7.37 (d, J = 8.7 Hz, 3H), 7.07 (d, J = 8.4 Hz, 2H), 5.16 (s, 2H), 4.99 (d, J = 6.6 Hz, 2H), 4.87 (d, J = 6.9 Hz, 2H), 3.85 (s, 2H), 3.72 (s, 3H); MS: m/z 427.0 [M +Na]. Example 4 2-((3-(4-([1,1'-Biphenyl]-3-ylmethoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (Compound 4)

The title compound was prepared in a similar manner as Compound 2 of Example 2. Compound 4 was obtained by hydrolysis of the compound of Example 3. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.63 (s, 2H), 7.58-7.63 (m, 2H), 7.46-7.51 (m, 4H), 7.34 (d, J = 8.7 Hz, 1H), 7.31 (s, 2H), 7.07 (d, J = 8.4 Hz, 2H), 5.16 (s, 2H), 4.95 (m, 4H), 3.85 (s, 2H); MS: m/z 389 [M – H] . Example 5 Methyl 2-((3-(4-((4'-)-trifluoromethyl)-[1,1'-biphenyl]-4-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate (compound 5)

The title compound was prepared in a similar manner as Compound 1 of Example 1 to methyl 2-(3-(4-hydroxyphenyl)oxycyclobutane-3-yl)acetate (Compound of Step 3 of Example 1) Reaction with 4-(bromomethyl)-4'-(trifluoromethyl)-1,1'-biphenyl. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.68-7.72 (m, 5H), 7.50-7.60 (m, 3H), 7.38 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 8.4 Hz , 2H), 5.17 (s, 2H), 4.99 (d, J = 6.9 Hz, 2H), 4.87 (d, J = 6.9 Hz, 2H), 3.85 (s, 2H), 3.72 (s, 3H); MS :m/z 473.5 [M + 1]. Example 6 2-((3-(4-((4'-)(Trifluoromethyl)-[1,1'-biphenyl]-4-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid (compound 6)

The title compound was prepared in a similar manner as Compound 2 of Example 2. Compound 6 was obtained by hydrolysis of the compound of Example 5. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.72 (s, 3H), 7.61 (s, 2H), 7.58 (m, 1H), 7.55 (d, J = 7.5 Hz, 2H), 7.34 (d, J = 8.7, 2H), 7.07 (d, J = 8.4 Hz, 2H), 5.18 (s, 2H), 4.95 (m, 4H), 3.85 (s, 2H); MS: m/z 481 [M + Na] . Example 7 Methyl 2-((3-(4-((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate (compound 7)

The title compound was prepared in a similar manner as Compound 1 of Example 1 to methyl 2-(3-(4-hydroxyphenyl)oxycyclobutane-3-yl)acetate (Compound of Step 3 of Example 1) Reaction with 6-(bromomethyl)-1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.21-7.38 (m, 5H), 7.03 (d, J = 8.4 Hz, 2H), 5.02 (s, 2H), 5.00 (d, J = 6.9 Hz, 2H ), 4.87 (d, J = 6.9 Hz, 2H), 3.85 (s, 2H), 3.72 (s, 3H), 1.71(s, 4H), 1.30 (s, 12H); MS: m/z 437.2 [M - 1]. Example 8 2-((3-(4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)methoxy)phenyl)oxy ring Butan-3-yl)oxy)acetic acid (compound 8)

The title compound was prepared in a similar manner as Compound 2 of Example 2. Compound 8 was obtained by hydrolysis of the compound of Example 7. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.36 (m, 3H), 7.23 (m, 2H), 7.07 (m, 2H), 5.02 (s, 2H), 4.95 (m, 4H), 3.87 (s , 2H), 1.58 (s, 4H), 0.89 (s, 12H); MS: m/z 424 [M] ⁺ . Example 9 Methyl 2-((3-(4-(3-phenoxybenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate (Compound 9)

The title compound was prepared in a similar manner as Compound 1 of Example 1 to methyl 2-(3-(4-hydroxyphenyl)oxycyclobutane-3-yl)acetate (Compound of Step 3 of Example 1) Reaction with 1-(bromomethyl)-3-phenoxybenzene. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.35-7.38 (m, 5H), 7.11-7.19 (m, 3H), 6.97-7.05 (m, 5H), 5.07 (s, 2H), 5.01 (d, J = 6.9 Hz, 2H), 4.87 (d, J = 6.9 Hz, 2H), 3.85 (s, 2H), 3.72 (s, 3H); MS: m/z 443.1 [M + Na]. Example 10 2-((3-(4-(3-Benzyloxybenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (Compound 10)

The title compound was prepared in a similar manner as Compound 2 of Example 2. Compound 10 was obtained by hydrolysis of the compound of Example 9. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.36 (m, 6H), 7.18 (m, 3H), 7.04 (m, 4H), 5.06 (s, 2H), 4.95 (m, 4H), 3.85 (s , 2H), MS: m/z 405 [M–1]. Example 11 Methyl 2-((3-(4-(4-phenoxybenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate (Compound 11)

The title compound was prepared in a similar manner as Compound 1 of Example 1 to methyl 2-(3-(4-hydroxyphenyl)oxycyclobutane-3-yl)acetate (Compound of Step 3 of Example 1) Reaction with 1-(bromomethyl)-4-phenoxybenzene. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.34-7.43 (m, 6H), 7.03-7.16 (m, 7H), 5.06 (s, 2H), 5.00 (d, J = 6.9 Hz, 2H), 4.87 (d, J = 6.9 Hz, 2H), 3.85 (s, 2H), 3.73 (s, 3H); MS: m/z 443.2 [M + Na]. Example 12 2-((3-(4-(4-Benzyloxybenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (Compound 12)

The title compound was prepared in a similar manner as Compound 2 of Example 2. Compound 12 was obtained by hydrolysis of the compound of Example 11. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.40 (d, J = 8.4, 3H), 7.34 (m, 4H), 7.14 (m, 2H), 7.06 (d, J = 8.1, 4H), 5.06 ( s, 2H), 4.95 (m, 4H), 3.85 (s, 2H); MS: m/z 405 [M - H]. Example 13 Methyl 2-((3-(4-(2-phenoxybenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate (Compound 13)

The title compound was prepared in a similar manner as Compound 1 of Example 1 to methyl 2-(3-(4-hydroxyphenyl)oxycyclobutane-3-yl)acetate (Compound of Step 3 of Example 1) Reaction with 1-(bromomethyl)-2-phenoxybenzene. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.61 (d, J = 7.5 Hz, 2H), 7.32-7.38 (m, 4H), 7.09-7.20 (m, 2H), 6.92-7.02 (m, 5H) , 5.19 (s, 2H), 5.00 (d, J = 6.9 Hz, 2H), 4.87 (d, J = 6.9 Hz, 2H), 3.83 (s, 2H), 3.71 (s, 3H); MS: m/ z 420.7 [M ] ⁺ . Example 14 2-((3-(4-((2-Benzyloxybenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (Compound 14)

The title compound was prepared in a similar manner as Compound 2 of Example 2. Compound 14 was obtained by hydrolysis of the compound of Example 13. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.60 (d, J = 7.2 Hz, 1H), 7.35 (m, 2H), 7.31 (s, 2H), 7.11 (m, 2H), 7.02 (d, J = 6.9 Hz, 4H), 6.95 (d, J = 8.1Hz, 2H), 5.19 (s, 2H), 4.95 (m, 4H), 3.85 (s, 2H); MS: m/z 405.1 [M-1 ]. Example 15 Methyl 2-((3-(4-((3-(4-fluorophenoxy)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate ( Compound 15)

The title compound was prepared in a similar manner as Compound 1 of Example 1 to methyl 2-(3-(4-hydroxyphenyl)oxycyclobutane-3-yl)acetate (Compound of Step 3 of Example 1) Reaction with 1-(bromomethyl)-3-(4-fluorophenoxy)benzene. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.50-7.72 (m, 8H), 7.37 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 8.4 Hz, 2H), 5.17 (s, 2H) ), 5.02 (d, J = 6.9 Hz, 2H), 4.87 (d, J = 6.9 Hz, 2H), 3.91 (s, 2H), 3.72 (s, 3H); MS: m/z 439.0 [M + 1 ]. Example 16 2-((3-(4-(3-(4-Fluorophenoxy)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (Compound 16)

The title compound was prepared in a similar manner as Compound 2 of Example 2. Compound 16 was obtained by hydrolysis of the compound of Example 15. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.52 (d, J = 8.7, 2H), 7.44 (m, 6H), 7.37 (m, 2H), 7.04 (d, J = 8.7, 2H), 5.06 ( s, 2H), 4.95 (m, 4H), 3.85 (s, 2H); MS: m/z 424 (M+). Example 17 Methyl 2-((3-(4-((4'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl) Ethoxy)acetate (Compound 17) Step 1: Methyl 2-((3-(4-((3-)-bromobenzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy ) Synthesis of acetate

Adding Cs ₂ CO ₃ (5.13 g, 15.74 mmol) to methyl 2-((3-(4-hydroxyphenyl)oxycyclobutane-3-yl)oxy)acetate in DMF (example A stirred solution of the compound of Step 3, 2.5 g, 10.49 mmol), and the mixture was stirred at RT for 10 min. 1-Bromo-3-(bromomethyl)benzene (2.62 g, 10.48 mmol) was added and the mixture was stirred at 80 ° C for 1 h. After the reaction was completed, the mixture was reacted with ice and concentrated. The residue was dissolved in ethyl acetate and washed with water, dried over anhydrous sodium sulfate It was further purified by combiflash and was eluted with a gradient of 5-30% ethyl acetate in petroleum ether to give the title compound as white solid. Yield: 82%. ¹ H NMR (CDCl ₃ , 500 MHz): d 7.62 (s, 1H), 7.49 (d, J = 7.5 Hz, 1H), 7.37-7.39 (m, 3H), 7.28-7.30 (m, 1H), 7.02 (d, J = 8.5 Hz, 2H), 5.07 (s, 2H), 5.00 (d, J = 7.0 Hz, 2H), 4.88 (d, J = 6.5 Hz, 2H), 3.86 (s, 2H), 3.73 (s, 3H); MS: m/z 429.1 [M+Na].

Alternatively, methyl 2-((3-(4) is substituted with ethyl 2-((3-(4-hydroxyphenyl)oxycyclobutane-3-yl)oxy)acetate) according to the procedure described above. -Hydroxyphenyl)oxocyclobutan-3-yl)oxy)acetate to synthesize (i) ethyl 2-((3-(4-((3-))))) Oxycyclobutane-3-yl)oxy)acetate.

Substituting 2-bromo-6-(bromomethyl)pyridine for 1-bromo-3-(bromomethyl)benzene according to the above procedure to synthesize (ii) ethyl 2-((3-(4-(( 6-Bromopyridin-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate.

Substituting 2-bromo-5-(bromomethyl)thiophene for 1-bromo-3-(bromomethyl)benzene according to the above procedure to synthesize (iii) ethyl 2-((3-(4-(( 5-bromothiophen-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate.

Substituting 2-bromo-4-(bromomethyl)thiazole for 1-bromo-3-(bromomethyl)benzene according to the above procedure to synthesize (iv) ethyl 2-((3-(4-(( 2-Bromothiazol-4-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate. Step 2: Methyl 2-((3-(4-((4'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3- Synthesis of oxy)acetate

Add potassium carbonate (3 equivalents) to methyl 2-((3-(4-(3-bromobenzyl)oxy)phenyl)oxycyclobutane in dioxane:water (4:1) A solution of alk-3-yl)oxy)acetate (compound of Example 17 Step 1, 1 eq.) and p-tolylboronic acid (5 eq.), and the mixture was degassed with argon for 10 min. Tetrakis(triphenylphosphine)palladium(0) (0.05 eq.) was added to the resulting solution, and the mixture was heated in a microwave at 80-90 °C for 15 minutes or at 80-90 °C for 1 to 2 hours. After the reaction was completed, the reaction mixture was evaporated, evaporated, evaporated ¹ H NMR (CDCl ₃ , 300 MHz): d 7.58 (s, 1H), 7.26-7.56 (m, 9H), 7.06 (d, J = 8.4 Hz, 2H), 5.15 (s, 2H), 5.02 (d , J = 6.9 Hz, 2H), 4.89 (d, J = 6.9Hz, 2H), 3.85 (s, 2H), 3.71 (s, 3H), 2.41 (s, 3H); MS: m/z 416.7 [MH ]. Example 18 2-((3-(4-((4'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate (compound 18)

Add LiOH (5 equivalents) to methyl 2-((3-(4-((4'-methyl-[1,1'-biphenyl]-3-) in THF:MeOH (1:4) A solution of methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound of Example 17, 1 eq.), and the reaction mixture was stirred at RT for 2 to 3 h. The solvent was removed, the reaction mixture was acidified with saturated NH ₄ Cl solution (pH 6-6.5), and extracted with ethyl acetate. The organic layer was washed with brine, dried over Na ₂ SO ₄ and concentrated to obtain the title compound. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.65 (s, 1H), 7.45 (m, 9H), 7.04 (d, J = 9 Hz, 2H), 5.15 (s, 2H), 4.95 (m, 4H) ), 3.87 (s, 2H), 2.41 (s, 3H); MS: m/z 402.8 [M-1].

Compounds of Examples 19, 21, 23, 25, 27, 29, 31, 33, 35, 37 and 39 were prepared by following the procedure exemplified in Example 17, Step 2. Compounds of Examples 20, 22, 24, 26, 28, 30, 32, 34, 36, 38 and 40 were prepared by following the procedure as exemplified in Example 18. The characterization data for the compounds of Examples 19-40 are described below. Example 19 Methyl 2-((3-(4-((4'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3- Acetyl)acetate (compound 19)

The title compound was prepared in a similar manner as Compound 17 of Example 17 to methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (the compound of Step 1 of Example 17) with (4-methoxyphenyl)boronic acid. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.63 (s, 1H), 7.54-7.57 (m, 3H), 7.46 (t, J = 8.0 Hz, 1H), 7.37-7.40 (m, 3H), 7.06 (d, J = 8.0 Hz, 2H), 7.01 (d, J = 8.5 Hz, 2H), 5.15 (s, 2H), 5.00 (d, J = 6.5 Hz, 2H), 4.88 (d, J = 7.0 Hz , 2H), 3.87 (s, 3H), 3.86 (s, 2H), 3.72 (s, 3H); MS: m/z 457.4 [M+Na]. Example 20 2-((3-(4-((4'-Methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetic acid (compound 20)

The title compound was prepared in a similar manner as Compound 18 of Example 18. Compound 20 was obtained by hydrolysis of the compound of Example 19. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.63 (s, 1H), 7.56 (d, J = 10Hz, 3H), 7.48 (d, J = 10Hz, 1H), 7.40 (d, J = 5Hz, 1H ), 7.33 (m, 2H), 7.07 (d, J = 10Hz, 2H), 7.01 (d, J = 10Hz, 2H), 5.16 (s, 2H), 4.95 (m, 4H), 3.87 (s, 5H) ); MS: m/z 420.8 [M+1]. Example 21 methyl 2-((3-(4-((2')-)-dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate (compound 21)

The title compound was prepared in a similar manner as Compound 17 of Example 17 to methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (the compound of Step 1 of Example 17) with (2,4-dimethylbenzene)boronic acid. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.27-7.45 (m, 6H), 7.02-7.17 (m, 5H), 5.14 (s, 2H), 5.03 (d, J = 6.9 Hz, 2H), 4.88 (d, J = 6.9 Hz, 2H), 4.19 (q, 2H), 3.83 (s, 2H), 2.38 (s, 3H), 2.24 (s, 3H), 1.25 (t, 3H); MS: m/ z 455.4 [M+Na]. Example 22 2-((3-(4-((2',4'-Dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid (compound 22)

The title compound was prepared in a similar manner as Compound 18 of Example 18. The compound of Example 21 was hydrolyzed to obtain Compound 22. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.41-7.46 (m, 3H), 7.31-7.33 (m, 3H), 7.04-7.16 (m, 5H), 5.14 (s, 2H), 4.95 (m, 4H), 3.86 (s, 2H), 2.38 (s, 3H), 2.24 (s, 3H); MS: m/z 417.0 [M-1]. Example 22a 2-((3-(4-((2',4'-Dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -Phenyloxy)calcium Acetate (Compound 22a) The title compound was prepared via a general procedure for the preparation of the calcium salt as described in Method B, using Compound 22. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 2.16 (s, 3H), 2.29 (s, 3H), 3.35 (s, 2H), 4.64 (d, J = 6.6 Hz, 2H), 4.84 (d , J = 6.6 Hz, 2H), 5.15 (s, 2H), 7.02-7.09 (m, 5H), 7.26 (d, J = 6.3 Hz, 1H), 7.36-7.43 (m, 5H); MS: (m /z) 417 [MH]. Example 22b 2-((3-(4-((2',4'-Dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 Metformin salt of -yl)oxy)acetic acid (Compound 22b) The title compound was prepared via a general procedure as described for the above-mentioned metformin salt, using compound 22. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.37–7.45 (m, 5H ), 7.25-7.27 (m, 1H ), 7.03-7.10 (m, 9H), 5.17 (s, 2H ), 4.83 (d, J = 6.6 Hz, 2H), 4.64 (d, J = 6.6 Hz, 2H), 3.33 (s, 2H), 2.9 (s, 6H), 2.50 (s, 3H), 2.30 (s, 3H); MS: (m/z) 546.9 [M] ⁺ . Example 23 Methyl 2-((3-(4-((2'-chloro-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound 23)

The title compound was prepared in a similar manner as Compound 17 of Example 17 to methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (the compound of Step 1 of Example 17) with (2-chlorophenyl)boronic acid. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.53 (s, 1H), 7.48-7.50 (m, 3H), 7.45 (s, 1H), 7.30-7.38 (m, 5H), 7.06 (d, J = 8 Hz, 2H), 5.16 (s, 2H), 5.05 (d, J = 7.2 Hz, 2H), 4.89 (d, J = 6.5 Hz, 2H), 3.86 (s, 2H), 3.72 (s, 3H) ;MS: m/z 461.3 [M+Na]. Example 24 2-((3-(4-((2'-Chloro-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy ) acetic acid (compound 24)

The title compound was prepared in a similar manner as Compound 18 of Example 18. The compound of Example 23 was hydrolyzed to obtain Compound 24. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.45-7.53 (m, 4H), 7.31-7.38 (m, 6H), 7.06 (d, J = 10Hz, 2H), 5.16 (s, 2H), 4.95 ( m, 4H), 3.86 (s, 2H); MS: m/z 423.0 [M-1]. Example 25 Methyl 2-((3-(4-((4'-hydroxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound 25)

The title compound was prepared in a similar manner as Compound 17 of Example 17 to methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (the compound of Step 1 of Example 17) with (4-hydroxyphenyl)boronic acid. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.62 (s, 1H), 7.44-7.54 (m, 4H), 7.37-7.39 (m, 3H), 7.06 (d, J = 8Hz, 2H), 6.92 ( d, J = 8.5 Hz, 2H), 5.16 (s, 2H), 5.25 (d, J = 7Hz, 2H), 4.89 (d, J =7 Hz, 2H), 3.86 (s, 2H), 3.72 (s , 3H); MS: m/z 443.3 [M+Na]. Example 26 2-((3-(4-((4'-Hydroxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy ) acetic acid (compound 26)

The title compound was prepared in a similar manner as Compound 18 of Example 18. Compound 26 was obtained by hydrolysis of the compound of Example 25. ¹ H NMR (CDCl ₃ , 300 MHz): d 8.63 (br s, 1H), 7.55 (s, 1H), 7.44 -7.47 (m, 1H), 7.38-7.41 (m, 3H), 7.31-7.34 (m , 3H), 6.97 (d, J = 8.4 Hz, 2H), 6.86 (d, J = 8.4 Hz, 2H), 5.07 (s, 2H), 4.94 (d, J = 6.9 Hz, 2H), 4.78 (d , J = 6.6 Hz, 2H), 3.74 (s, 2H); MS: m/z 404.9 [M-1]. Example 27 Methyl 2-((3-(4-((3'-hydroxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound 27)

The title compound was prepared in a similar manner as Compound 17 of Example 17 to methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (the compound of Step 1 of Example 17) with (3-hydroxyphenyl)boronic acid. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.55 (s, 1H), 7.31 -7.49 (m, 6H), 7.19 (d, J = 7.5 Hz, 1H), 7.06 (s, 3H), 6.86 (d , J = 8Hz, 1H), 5.17 (s, 2H), 5.02 (d, J = 6.5 Hz, 2H), 4.90 (d, J = 6.5Hz, 2H), 3.86 (s, 2H), 3.82 (s, 3H); MS: m/z 443.2 [M+Na]. Example 28 2-((3-(4-((3'-hydroxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy ) acetic acid (compound 28)

The title compound was prepared in a similar manner as Compound 18 of Example 18. Compound 28 was obtained by hydrolysis of the compound of Example 27. ¹ H NMR (DMSO d ₆ , 300 MHz): d 7.38 -7.49 (m, 6H), 7.22 (d, J = 9 Hz, 1H), 6.99-7.03 (m, 3H), 6.92 (s, 1H), 6.73 (d, J = 9.0 Hz, 1H), 5.21 (s, 2H), 4.83 (m, 4H), 3.86 (s, 2H); MS: m/z 404.8 [M-1]. Example 29 Methyl 2-((3-(4-((2'-fluoro-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound 29)

The title compound was prepared in a similar manner as Compound 17 of Example 17 to methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (the compound of Step 1 of Example 17) with (2-fluorophenyl)boronic acid. ¹ H NMR (CDCl ₃ , 500 MHz): d 7.64 (s, 1H), 7.34-7.55 (m, 7H), 7.16-7.25 (m, 2H), 7.06 (d, J = 8.5 Hz, 2H), 5.21 (s, 2H), 5.01 (d, J = 6.5 Hz, 2H), 4.89 (d, J = 6.5 Hz, 2H), 3.86 (s, 2H), 3.72 (s, 3H); MS: m/z 423.2 [M+1]. Example 30 2-((3-(4-((2'-Fluoro-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy ) acetic acid (compound 30)

The title compound was prepared in a similar manner as Compound 18 of Example 18. The compound of Example 29 was obtained by hydrolysis to obtain Compound 30. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.49 (s, 1H), 7.34-7.40 (m, 4H), 7.27-7.31 (m, 3H), 7.14-7.26 (m, 2H), 7.07 (d, J = 9 Hz, 2H), 5.16 (s, 2H), 4.95 (m, 4H), 3.86 (s, 2H); MS: m/z 406.9 [M-1]. Example 31 Methyl 2-((3-(4-((4'-(methylthio))-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetate (compound 31)

The title compound was prepared in a similar manner as Compound 17 of Example 17 to methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (the compound of Step 1 of Example 17) with (4-(methylthio)phenyl)boronic acid. ¹ H NMR (CDCl ₃ , 500 MHz): d δ 7.65 (s, 1H), 7.34-7.56 (m, 9H), 7.06 (d, J = 8 Hz, 2H), 5.32 (s, 2H), 5.02 ( d, J = 6.5 Hz, 2H), 4.89 (d, J = 6.5, 2H), 4.15 (s, 2H), 3.86 (s, 3H), 2.54 (s, 3H); MS: m/z 451.3 [M +1]. Example 32 2-((3-(4-((4'-(methylthio))-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3- Alkyloxyacetic acid (compound 32)

The title compound was prepared in a similar manner as Compound 18 of Example 18. The compound of Example 31 was hydrolyzed to obtain Compound 32. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.75 (s, 1H), 7.65 (s, 1H), 7.43-7.50 (m, 4H), 7.31-7.40 (m, 4H), 7.06 (d, J = 9 Hz, 2H), 5.31 (s, 2H), 4.98 (m, 4H), 3.86 (s, 2H), 2.54 (s, 3H); MS: m/z 434.9 [M-1]. Example 33 Methyl 2-((3-(4-((3'-)-cyano-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl) )oxy)acetate (compound 33)

The title compound was prepared in a similar manner as Compound 17 of Example 17 to methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (the compound of Step 1 of Example 17) with (3-cyanophenyl)boronic acid. ¹ H NMR (CDCl ₃ , 500 MHz): d δ 7.90 (s, 1H), 7.85 (d, J = 7.5, 1H), 7.67 (s, 2H), 7.51-7.59 (m, 4H), 7.40 (d , J = 8 Hz, 2H), 7.07 (d, J = 8 Hz, 2H), 5.17 (s, 2H), 5.02 (d, J = 7 Hz, 2H), 4.89 (d, J = 6.5 Hz, 2H ), 3.86 (s, 2H), 3.73 (s, 3H); MS: m/z 452.2 [M+Na]. Example 34 2-((3-(4-((3'-Cyano-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate (compound 34)

The title compound was prepared in a similar manner as Compound 18 of Example 18. Compound 34 was obtained by hydrolysis of the compound of Example 33. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.82-7.85 (m, 2H), 7.59 (s, 2H), 7.50-7.59 (m, 4H), 7.35 (d, J = 9 Hz, 2H), 7.04 -7.07 (m, 2H), 5.31 (s, 2H), 4.98 (m, 4H), 3.86 (s, 2H); MS: m/z 438.1 [M+Na]. Example 35 Ethyl 2-((3-(4-((2'-fluoro-5'-(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate (compound 35)

The title compound was prepared in a similar manner as Compound 17 of Example 17 to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) The reaction of oxy)acetate (the compound of Step 1 of Example 17) with (2-fluoro-5-(trifluoromethyl)phenyl)boronic acid. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.70-7.78 (m, 1H), 7.60-7.68 (m, 2H), 7.50-7.53 (m, 3H), 739 (d, J = 8.7 Hz, 2H) , 7.26-7.32 (m, 1H), 7.05 (d, J = 8.7 Hz, 2H), 5.17 (s, 2H), 5.00 (d, J = 6.9 Hz, 2H), 4.87 (d, J = 6.9 Hz, 2H), 4.17 (q, J = 7.2 Hz, 2H), 3.84 (s, 2H), 1.25 (t, J = 14.1 Hz, 3H); MS: m/z 527.4 [M+Na]. Example 36 2-((3-(4-((2'-Fluoro-5'-(trifluoromethyl)-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxy Cyclobutane-3-yl)oxy)acetic acid (compound 36)

The title compound was prepared in a similar manner as Compound 18 of Example 18. Compound 36 was obtained by hydrolysis of the compound of Example 35. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.80-7.90 (m, 2H), 7.70 (s, 1H), 7.50-7.60 (m, 4H), 7.38 (d, J = 8.7 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H), 5.21 (s, 2H), 4.80 (d, J = 7.1 Hz, 2H), 4.74 (d, J = 6.9 Hz, 2H), 3.73 (s, 2H); MS :m/z 499.1 [M+Na]. Example 37 Ethyl 2-((3-(4-((2'-fluoro-4'-(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate (Compound 37)

The title compound was prepared in a similar manner as Compound 17 of Example 17 to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (the compound of Step 1 of Example 17) with (2-fluoro-4-(trifluoromethyl)phenyl)boronic acid. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.47-7.64 (m, 6H), 7.38-7.44 (m, 3H), 7.07 (d, J = 8.7 Hz, 2H), 5.17 (s, 2H), 5.03 (d, J = 6.9 Hz, 2H), 4.88 (d, J = 6.9 Hz, 2H), 4.22 (q, J = 7.2 Hz, 2H), 3.84 (s, 2H), 1.28 (t, J = 6.3 Hz , 3H); MS: m/z 527.4 [M+Na]. Example 38 2-((3-(4-((2'-Fluoro-4'-(trifluoromethyl)-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxy Cyclobutane-3-yl)oxy)acetic acid (compound 38)

The title compound was prepared in a similar manner as Compound 18 of Example 18. Compound 38 was obtained by hydrolysis of the compound of Example 37. ¹ H NMR (DMSO d ₆ , 300 MHz): d 7.83-7.69 (m, 4H), 7.56 (s, 3H), 7.44 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 8.1 Hz, 2H), 5.20 (s, 2H), 4.82 (m, 4H), 3.14 (s, 2H); MS: m/z 499.1 [M+Na]. Example 39 Ethyl 2-((3-(4-((2'-)-trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate (compound 39)

The title compound was prepared in a similar manner as Compound 17 of Example 17 to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (the compound of Step 1 of Example 17) with (2-(trifluoromethyl)phenyl)boronic acid. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.78 (s, 1H), 7.61-7.30 (m, 9H), 7.04 (d, J = 8.7 Hz, 2H), 5.31 (s, 2H), 5.02 (d , J = 6.9Hz, 2H), 4.88 (d, J = 7.2Hz, 2H), 4.19 (q, J = 7.2 Hz, 2H), 3.83 (s, 2H), 1.25 (t, J = 6.9 Hz, 3H MS: m/z 509.4 [M+Na]. Example 40 2-((3-(4-((2'-)(Trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid (compound 40)

The title compound was prepared in a similar manner as Compound 18 of Example 18. Compound 40 was obtained by hydrolysis of the compound of Example 39. ¹ H NMR (DMSO d ₆ , 300 MHz): d 7.85 (d, J = 7.8, 1H), 7.59-7.75 (m, 2H), 7.37-7.53 (m, 6H), 7.29 (d, J = 6.9 Hz , 1H), 7.06 (d, J = 8.4 Hz, 2H), 5.17 (s, 2H), 4.82 (m, 4H), 3.41 (s, 2H); MS: m/z 457.1 [M-1]. Example 40a 2-((3-(4-((2'-)(Trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)calcium acetate (compound 40a)

The title compound was prepared via the general procedure prepared according to the calcium salt as described in Method B, using Compound 40. ¹ H NMR (300 MHz, CDCl ₃ ): δ 7.83 (d, J = 7.8 Hz, 1H), 7.73 (m, 1H), 7.62 (d, J = 7.8 Hz, 1H), 7.54 (m, 1H), 7.44 (s, 1H), 7.42 (m, 1H), 7.39 (d, J = 5.1 Hz, 3H), 7.27 (d, J = 6.9 Hz, 1H), 7.03 (d, J = 8.4 Hz, 2H), 5.14 (s, 2H), 4.84 (d, J = 6.9Hz, 2H), 4.64 (d, J = 6.9Hz, 2H), 3.42 (s, 2H); MS (m/z) M+ 457.3, M+H 458.2, MH 456.2. Example 41 Methyl 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl) Methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetate (Compound 41) Step 1: Methyl 2-((3-(4-((2'-chloro-4')) Synthesis of -hydroxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate

Add potassium carbonate (3 equivalents) to methyl 2-((3-(4-(3-bromobenzyl)oxy)phenyl)oxycyclobutane in dioxane:water (4:1) Alkyl-3-yl)oxy)acetate (Compound of Example 17 Step 1, 1.0 g, 2.455 mmol) and (2-chloro-4-hydroxyphenyl)boronic acid (634 mg, 3.68 mmol), The mixture was degassed with argon for 30 minutes. Tetrakis(triphenylphosphine)palladium(0) (140 mg, 0.121 mmol) was added to the resulting solution, and the mixture was degassed for 2 min. The reaction mixture was stirred at 70 ° C for 4 h. After the reaction was completed, the reaction mixture was allowed to warm to RT and dried with ice and concentrated. The crude compound was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and evaporated. It was further purified by combi-flash using a gradient of 5-40% ethyl acetate in petroleum ether as a solvent to obtain the title compound as a viscous liquid. Yield: 30.4%; ¹ H NMR (CDCl ₃ , 300 MHz): d 7.49-7.46 (m, 1H), 7.44-7.41 (m, 3H), 7.38-7.35 (m, 2H), 7.24-7.21 (m , 1H), 7.06-6.99 (m, 3H), 6.83-6.80 (m, 1H), 5.36-5.31(m, 1H), 5.14 (s, 2H), 5.02-5.00 (d, J = 6.9 Hz, 2H ), 4.90-4.88 (d, J = 6.9 Hz, 2H), 3.85 (s, 2H), 3.72 (s, 3H); MS: m/z 477.0 [M+Na]. Step 2: Methyl 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3- Synthesis of methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate

Adding Cs ₂ CO ₃ (1.5 equivalents) to methyl 2-((3-(4-((2'-chloro-4'-hydroxy-[1,1'- linkage) in DMF under RT, nitrogen atmosphere a stirred solution of phenyl]-3-yl)methoxy)phenyl)oxocyclobutan-3-yl)oxy)acetate (compound of step 1, 1 equivalent), and the reaction mixture is taken at RT Stir for 10 minutes. Add 1-methyl-4-((3-(methylsulfonyl)propyl)sulfonyl)benzene or 1-bromo-3-(methylsulfonyl)propane (1 equivalent) to the reaction mixture, The reaction mixture was heated at 80 °C for 2 h. The reaction mixture was quenched with ice and concentrated. The residue was dissolved in ethyl acetate and washed with water, dried over anhydrous sodium sulfate. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.45-7.54 (m, 3H), 7.27-7.38 (m, 4H), 7.03-7.06 (d, J = 8.7 Hz, 3H), 6.86-6.89 (m, 1H), 5.14 (s, 2H), 4.99 (d, J = 6.9 Hz, 2H), 4.86 (d, J = 6.9 Hz, 2H), 4.17 (t, J = 5.7, 5.7 Hz, 2H), 3.85 ( s, 2H), 3.72 ( s, 3H), 3.28 (t, J = 7.8 Hz, 2H), 2.99 ( s, 3H), 2.35-2.44 (m, 2H); MS: m/z 596.8 [M+Na ]. Example 42 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl) A Oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (compound 42)

Add LiOH.H ₂ O (5 equivalents) to methyl 2-((3-(4-((2'-chloro-4'-(3-(methane))) in THF:MeOH (1:4) Mercapto)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound of Example 41, 1 equivalent) of the solution, and the reaction mixture was stirred at RT for 2 to 3 h. The solvent was removed, the reaction mixture was acidified with saturated NH ₄ Cl solution (pH 6-6.5), and extracted with ethyl acetate. The organic layer was washed with brine, dried over Na ₂ SO ₄ and concentrated to obtain the title compound. ¹ H NMR (CDCl ₃ , 300 MHz): d7.45-7.47 (m, 3H), 7.38-7.41 (m, 1H), 7.26-7.33 (m, 3H), 7.03-7.06 (m, 3H), 6.86 -6.89 (m, 1H), 5.15 (s, 2H), 4.91-4.97 (m, 4H), 4.17 (t, J = 5.4 Hz, 2H), 3.86 (m, 2H), 3.28 (t, J = 7.5 Hz, 2H), 2.99 (s, 3H), 2.33-2.43 (m, 2H); MS: m/z 582.8 [M+Na]. Example 42a 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)) Oxyphenyl)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound 42a)

The title compound was prepared via the general procedure prepared according to the calcium salt as described in Method B, using Compound 42. ¹ H NMR (DMSO, 300 MHz): δ 7.46-7.44 (m, 3H), 7.41 (s, 2H), 7.37-7.32 (m, 2H), 7.16 (d, J = 2.7 Hz, 1H), 7.06- 7.03 (m, 2H), 7.01 - 7.00 (m, 1H), 5.16 ( s, 2H), 4.85 (d, J = 6.9 Hz, 2H), 4.66 (d, J = 6.9Hz, 2H), 4.16( t , J = 6.0Hz, 2H), 3.38 (s, 2H), 3.31-3.26 (m, 2H), 3.03 (s, 3H), 2.18-2.13 (m, 2H); MS (m/z) 599.2 [M+ K]. Example 42b 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)) Metformin salt of oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (compound 42b)

The title compound was prepared via the general procedure as described for the metformin salt as described above, using compound 42. ¹ H NMR (DMSO, 300 M Hz): δ 7.47-7.46 (m, 2H), 7.42-7.33 (m, 3H), 7.15 (s, 2H), 7.06- 7.03 (m, 4H), 5.17 (s, 2H), 4.83 (d, J= 6.6Hz, 2H), 4.64 (d, J= 6.6 Hz, 2H), 4.16 (t, J= 6.3 Hz, 2H), 3.28-3.26 (m, 5H), 3.03 ( s, 2H), 2.91 (s, 6H), 2.18-2.13 (m, 2H); MS: (m/z) 559.1 [MH].

The compounds of Examples 43, 45, 47, 49 were prepared by following the procedure as exemplified in Example 41, Step 2. Compounds of Examples 44, 46, 48, 50 were prepared by following the procedure as exemplified in Example 42. The characterization data for the compounds of Examples 43-50 are described below. Example 43 Methyl 2-((3-(4-((2'-chloro-4'-((3-(hydroxymethyl))oxycyclobutane-3-yl)methoxy)-[1,1 '-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound 43)

The title compound was prepared in a similar manner as Compound 41 of Example 41, which was taken to methyl 2-((3-(4-((2'-chloro-4'-hydroxy-[1,1'-biphenyl]-3) -yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound of step 1 of Example 41) and (3-(bromomethyl)oxocyclobutane-3- Base) methanol reaction. ¹ H NMR (CDCl ₃ , 300 MHz): d7.45-7.49 (m, 3H), 7.36-7.41 (m, 3H), 7.27-7.31 (m, 1H), 7.06-7.09 (m, 3H), 6.94 -7.03 (m, 1H), 5.15 (s, 2H), 4.99 (d, J = 6.6 Hz, 2H), 4.86 (d, J = 6.9 Hz, 2H), 4.61 ( m, 4H), 4.30 (s, 2H), 4.06-4.08 (m, 2H), 3.85 (s, 2H), 3.72 (s, 3H); MS: m/z 576.8 [M+Na]. Example 44 2-((3-(4-((2'-Chloro-4'-((3-(hydroxymethyl))oxycyclobutane-3-yl)methoxy)-[1,1'- Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (Compound 44)

The title compound was prepared in a similar manner as Compound 42 of Example 42. Compound 44 was hydrolyzed by hydrolysis of the compound of Example 43. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.41-7.46 (m, 4H), 7.27-7.33 (m, 3H), 7.03-7.08 (m, 3H), 6.91-6.93 (m, 1H), 5.16 ( s, 2H), 4.91-4.98 (m, 4H), 4.61 (m, 4H), 4.29 (s, 2H), 4.06 (s, 2H), 3.85 (s, 2H); MS: m/z 562.9 [M +Na]. Example 45 Methyl 2-((3-(4-((2)-chloro-4'-((1,1-dioxo)tetrahydrothiophen-3-yl)methoxy)-[1,1 '-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound 45)

The title compound was prepared in a similar manner as Compound 41 of Example 41, which was taken to methyl 2-((3-(4-((2'-chloro-4'-hydroxy-[1,1'-biphenyl]-3) -yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound of step 1 of Example 41) and 3-(bromomethyl)tetrahydrothiophene 1,1-di The reaction of the oxide. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.45-7.49 (m, 3H), 7.36-7.39 (m, 3H), 7.27-7.31 (m, 1H), 7.03-7.05 (d, J = 8.4 Hz, 3H), 6.87-6.89 (m, 1H), 5.15 (s, 2H), 4.99 (d, J = 6.9 Hz, 2H), 4.86 (d, J = 6.9 Hz, 2H), 4.06-4.12 (m, 2H) ), 3.85 (s, 2H), 3.72 ( s, 3H), 3.25-3.26 (m, 2H), 3.14-3.16 (m, 1H), 3.02-3.10 (m, 2H), 2.46 (m, 1H), 2.19-2.23 (m, 1H); MS: m/z 608.8 [M+Na]. Example 46 2-((3-(4-((2'-Chloro-4'-((1,1-dioxo)tetrahydrothiophen-3-yl)methoxy)-[1,1'- Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (Compound 46)

The title compound was prepared in a similar manner as Compound 42 of Example 42. Compound 46 was obtained by hydrolysis of the compound of Example 45. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.45-7.47 (m, 3H), 7.33-7.40 (m, 2H), 7.27-7.30 (m, 2H), 7.03-7.06 (d, J = 8.7 Hz, 3H), 6.86-6.89 (m, 1H), 5.15 (s, 2H), 4.91-4.97 (m, 4H), 4.06-4.15 (m, 2H), 3.86 (s, 2H), 3.25-3.38 (m, 2H), 3.14-3.19 (m, 1H), 2.98-3.10 (m, 2H), 2.45-2.47 (m, 1H), 2.15-2.25 (m, 1H); MS: m/z 594.8 [M+Na] . Example 46a 2-((3-(4-((2'-Chloro-4'-((1,1-dioxo)tetrahydrothiophen-3-yl)methoxy)-[1,1'- Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid calcium (compound 46a)

The title compound was prepared via the general procedure prepared according to the calcium salt as described in Method B, using Compound 46. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 7.45-7.43 (m, 4H), 7.40 (s, 1H), 7.33-7.30 (m, 2H), 7.16-7.15 (m, 1H), 7.04- 7.00 (m, 3H), 5.15 (s, 2H), 4.84 (d, J = 6.9 Hz, 2H), 4.64 (d, J = 6.9 Hz, 2H), 4.11 (d, J = 6.0Hz, 2H), 3.55 (s, 2H), 3.24-3.20 (m, 2H), 3.15-3.08 (m, 1H), 2.97-2.84 (m, 2H), 2.31-2.30 (m, 1H), 1.98-1.90 (m, 1H) ); MS (m/z) 571.0.1 [M-H] (mass of the parent acid). Example 46b 2-((3-(4-((2'-Chloro-4'-((1,1-dioxo)tetrahydrothiophen-3-yl)methoxy)-[1,1'- Metformin salt of biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (compound 46b)

The title compound was prepared via the general procedure prepared according to the above-described metformin salt, using compound 46. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 7.47 (d, J = 3.3 Hz, 3H), 7.42-7.33 (m, 4H), 7.18 (d, J = 2.4 Hz, 1H), 7.06 – 7.03 (m, 3H), 5.17 (s, 2H), 4.83 (d, J = 6.6Hz, 2H), 4.64 (d, J= 6.6Hz, 2H), 4.13( d, J= 6.0 Hz, 2H), 3.28 (s, 2H), 3.26-3.24 (m, 3H), 3.12-3.10 (m, 1H), 2.91 (s, 6H), 2.93-2.89 (m, 2H), 2.33-2.31 (m, 1H); MS :(m/z) 559.1 [M- H]. Example 47 Methyl 2-((3-(4-((2,1-dioxy)tetrahydro-2H-thiopyran-4-yl)methoxy)- [1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate (Compound 47)

The title compound was prepared in a similar manner as Compound 41 of Example 41, which was taken to methyl 2-((3-(4-((2'-chloro-4'-hydroxy-[1,1'-biphenyl]-3) -yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound of step 1 of Example 41) and 4-(bromomethyl)tetrahydro-2H-thiopyran 1 , 1-dioxide reaction. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.45-7.49 (m, 4H), 7.36-7.39 (m, 3H), 7.06 (s, 1H), 7.01-7.02 (m, 2H), 6.85-6.89 ( m, 1H), 5.15 (s, 2H), 4.99 ( d, J = 7.2 Hz, 2H), 4.86 (d, J = 6.9 Hz, 2H), 3.90v (d, J = 4.8 Hz, 2H), 3.85 (s, 2H), 3.72 (s, 3H), 3.07-3.19 (m, 4H), 2.30 (m, 2H), 2.06-2.11 (m, 3H); MS: m/z 602.1 [M+H]. Example 48 2-((3-(4-((1,1-Dioxy)yltetrahydro-2H-thiopyran-4-yl)methoxy)-[1 ,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (Compound 48)

The title compound was prepared in a similar manner as Compound 42 of Example 42. Compound 44 was hydrolyzed by hydrolysis of the compound of Example 43. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.45-7.48 (m, 3H), 7.38-7.41 (m, 1H), 7.30-7.33 (m, 3H), 7.01 - 7.06 (m, 3H), 6.85- 6.88 (m, 1H), 5.16 (s, 2H), 4.92-4.97 ( m, 4H), 3.90 (d, J = 4.2 Hz, 2H), 3.87 (s, 2H), 3.07- 3.19 (m, 4H) , 2.30 (m, 2H), 2.06-2.15 (m, 3H); MS: m/z 585.1 [MH]. Example 49 Methyl 2-((3-(4-((2)-chloro-4'-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl) ]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate (Compound 49)

The title compound was prepared in a similar manner as Compound 41 of Example 41, which was taken to methyl 2-((3-(4-((2'-chloro-4'-hydroxy-[1,1'-biphenyl]-3) -yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound of step 1 of Example 41) and 4-(bromomethyl)tetrahydro-2H-pyran reaction. ¹ H NMR (CDCl ₃ , 500 MHz): d 7.48 (s, 1H), 7.40-7.41 (m, 3H), 7.31-7.38 (m, 2H), 7.27-7.28 (m, 1H), 7.03- 7.06 ( m, 3H), 6.87-6.89 (m, 1H), 5.16 (s, 2H), 5.00 (d, J = 6.5 Hz, 2H), 4.87 (d, J = 7.0 Hz, 2H), 4.04-4.06 (m , 2H), 3.85 (s, 4H), 3.72 (s, 3H), 3.45-3.50 (m, 2H), 2.06-2.15 (m, 1H), 1.78-1.80 (m, 2H), 1.46-1.50 (m , 2H); MS: m/z 575.3 [M+Na]. Example 50 2-((3-(4-((2H-Chloro-4-yl)methoxy)-[1,1'-biphenyl]- 3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (Compound 50)

The title compound was prepared in a similar manner as Compound 42 of Example 42. Compound 44 was hydrolyzed by hydrolysis of the compound of Example 43. ¹ H NMR (CDCl ₃ , 500 MHz): d 7.50 (s, 1H), 7.45-7.47 (m, 2H), 7.40-7.42 (m, 1H), 7.31-7.33 (m, 2H), 7.03- 7.06 ( m, 3H), 6.87-6.89 (m, 2H), 5.16 (s, 2H), 4.93-4.97 (m, 4H), 4.04-4.06 (m, 2H), 3.85-3.87 (m, 4H), 3.45- 3.50 (m, 2H), 2.12 (m, 1H), 1.77-1.80 (m, 2H), 1.46-1.50 (m, 2H); MS: m/z 540.2 [M+2]. Example 50a 2-((3-(4-((2H-Chloro-4-yl)methoxy)-[1,1'-biphenyl]- 3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid calcium (compound 50a)

The title compound was prepared via the general procedure prepared according to the calcium salt as described in Method B, using Compound 50. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 7.45-7.44 (m, 3H), 7.40 (s, 2H), 7.34-7.32 (m, 1H), 7.29 (s, 1H), 7.12 (d, J = 2.1 Hz, 1H), 7.04 (s, 2H), 7.01-6.98 (m, 1H), 5.15 (s, 2H), 4.83-4.76 (m, 3H), 4.70 (d, J = 6.6 Hz, 1H ), 3.90-3.85 (m, 4H), 3.72-3.69 (m, 2H), 3.35-3.25 (m, 2H), 1.97-1.96 (m, 1H), 1.69-1.65 (m, 2H), 1.34-1.29 (m, 2H); MS ( m / z) 553.0 [m + NH 4] ( mass of acid). Example 51 2-((3-(4-((2',6'-Dimethyl-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]- 3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (Compound 1)

In addition to the procedure described in Example 1, for the synthesis of Compound 1, Compound 1 was also synthesized via the following procedure: Step 1 ': Methyl 2-((3-(4-(3-(4,4, Synthesis of 5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate

Adding bis pinacolato diboron (436 mg, 1.72 mmol) to methyl 2-((3-(4-((3-) a stirred solution of bromobenzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound of Example 17 Step 1, 700 mg, 1.719 mmol), followed by [1,1 Addition of '-bis(diphenylphosphino)ferrocene]palladium(II) chloride, a complex [PdCl ₂ (dppf)] (12.58 mg, 0.017 mmol). K ₂ CO ₃ (506 mg, 5.16 mmol) was added to the reaction mixture, and the mixture was refluxed at 80 ° C overnight. The reaction mixture was cooled to RT and the solvent was evaporated. The crude solid was dissolved in dichloromethane, filtered through a pad of Celite® and washed with DCM. The organic layer was collected and washed with water and brine, dried over anhydrous sodium sulfate, ¹ H NMR (CDCl ₃ , 300 MHz): d 7.88 (s, 1H), 7.79-7.81 (m, 1H), 7.55-7.58 (m, 1H), 7.34-7.44 (m, 3H), 7.01-7.04 ( d, J = 8.7 Hz, 2H), 5.09 ( s, 2H), 4.99 ( d, J = 6.9 Hz, 2H), 4.86 (d, J = 6.9 Hz, 2H), 3.84 (s, 2H), 3.72 ( s, 3H), 1.37 (s, 12H); MS: m/z 477.1 [M+Na]. Step 2': methyl 2-((3-(4-((4'-hydroxy-2',6'-dimethyl-[1,1'-biphenyl]-3-yl)methoxy)) Synthesis of Phenyl)oxocyclobutane-3-yl)oxy)acetate

K ₂ CO ₃ (580 mg, 4.20 mmol) was added at RT to 20 ml of dioxane: methyl 2-(4-(4-(4) in water (4:1) 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound of step 1 ', 950 mg, 2.091 mmol) and a solution of 4-bromo-3,5-dimethylphenol (280 mg, 1.393 mmol). The resulting solution was degassed with argon with stirring for 30 minutes. Tetrakis(triphenylphosphine)palladium(0) (81 mg, 0.070 mmol) was added to the resulting solution and degassed for 2 min. The reaction mixture was allowed to stir at 70 ° C for 4 h. The reaction mixture was cooled to RT, quenched with ice and concentrated to give a crude compound. The crude compound was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated and then purified with EtOAc EtOAc EtOAc ¹ H NMR (CDCl ₃ , 500 MHz): d 7.44-7.47 (m, 1H), 7.40-7.41 (m, 1H), 7.35-7.37 (m, 2H), 7.20 (s, 1H), 7.10-7.12 ( m, 1H), 7.02-7.03 (m, 2H), 6.61(s, 2H), 5.15 (s, 2H), 5.00 (d , J = 7.0 Hz, 2H), 4.87 (d, J = 6.5 Hz, 2H ), 3.84 (s, 2H), 3.73 (s, 3H), 1.98 (s, 6H); MS: m/z 471.4 [M+Na]. Step 3: Methyl 2-((3-(4-((2',6'-dimethyl-4'-(3-(methylsulfonyl)propoxy)-[1,1'-linked Synthesis of Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate

Add Cs ₂ CO ₃ (1.5 eq.) to methyl 2-((3-(4-((4'-hydroxy-2',6'-dimethyl-[ a stirred solution of 1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound of step 2', 1 equivalent), The reaction mixture was stirred at RT for 10 minutes. Add 1-methyl-4-((3-(methylsulfonyl)propyl)sulfonyl)benzene or 1-bromo-3-(methylsulfonyl)propane (1 equivalent) to the reaction mixture, and The reaction mixture was heated at 80 °C for 2 h. The reaction mixture was quenched with ice and concentrated. The residue was dissolved in ethyl acetate and washed with EtOAc EtOAc EtOAc. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.34-7.48 (m, 4H), 7.19 (s, 1H), 7.11 (d, J = 6.9 Hz, 1H), 7.03 (d, J = 8.7 Hz, 2H ), 6.66 (s, 2H), 5.15 (s, 2H), 4.99 (d, J = 6.6 Hz, 2H), 4.86 (d, J = 6.6 Hz, 2H), 4.14 (t, J = 5.4 Hz, 2H ), 3.84 (s, 2H), 3.72 (s, 3H), 3.28 (t, J = 7.5 Hz, 2H), 2.98 (s, 3H), 2.34-2.39 (m, 2H), 2.00 (s , 6H) ;MS: m/z 591.0 [M+ Na]. Example 52 2-((3-(4-((2',6'-Dimethyl-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]- 3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (Compound 2)

The method of synthesizing the title compound is as described in Example 2 above.

The compounds of Examples 53, 55, 57 and 59 were prepared by following the procedure exemplified in Example 51, Step 3. Compounds of Examples 54, 56, 58 and 60 were prepared by following the procedure exemplified in Example 2. The characterization data for the compounds of Examples 53-60 are described below. Example 53 Methyl 2-((3-(4-((4-(hydroxymethyl))oxycyclobutane-3-yl)methoxy)-2',6'-dimethyl -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound 51)

The title compound was prepared in a similar manner as Compound 1' of Example 50, which was taken to methyl 2-((3-(4-((4'-hydroxy-2',6'-dimethyl-[1,1') -biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound of step 2 of Example 51) and (3-(bromomethyl)oxy Reaction of cyclobutane-3-yl)methanol. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.42-7.48 (m, 2H), 7.34-7.40 (m, 2H), 7.19 (s, 2H), 7.09-7.12 (m, 1H), 7.00-7.03 ( m, 2H), 6.72 (s, 2H), 5.15 (s, 2H), 4.99 (d , J = 6.9 Hz, 2H), 4.85 (d, J = 6.9 Hz, 2H), 4.61 (s, 4H), 4.29 (s, 2H), 4.07 (s, 2H), 3.84 (s, 2H), 3.72 (s, 3H), 2.01 (s, 6H); MS: m/z 571.3 [M+Na]. Example 54 2-((3-(4-((4'-((3-(Hydroxymethyl)oxycyclobutane-3-yl)methoxy)-2',6'-dimethyl-[ 1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (Compound 52)

The title compound was prepared in a similar manner as Compound 2 of Example 2. The compound of Example 53 was hydrolyzed to obtain Compound 54. ¹ H NMR (CDCl ₃ , 500 MHz): d 7.45-7.48 (m, 1H), 7.40-7.41 (m, 1H), 7.29-7.31 (m, 2H), 7.17 (s, 1H), 7.10-7.12 ( m, 1H), 7.02-7.03 (m, 2H), 6.71 (s, 2H), 5.31-5.32 (m, 1H), 5.17 (s, 2H), 4.96 (d, J = 7.0 Hz, 2H), 4.92 (d, J = 7.0 Hz, 2H), 4.61 (s, 4H), 4.30 (s, 2H), 4.07 (s, 2H), 3.84 (s, 2H), 2.00 (s, 6H); MS: m/ z 557.3 [M+Na]. Example 55 Methyl 2-((3-(4-((4)-((1,1-dioxy)tetrahydrothiophen-3-yl)methoxy)-2',6'-dimethyl -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate (Compound 53)

The title compound was prepared in a similar manner as Compound 1' of Example 51, which was taken to methyl 2-((3-(4-((4'-hydroxy-2',6'-dimethyl-[1,1') -biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound of step 2 of Example 51) and 3-(bromomethyl)tetrahydrogen Reaction of thiophene 1,1-dioxide. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.42-7.48 (m, 2H), 7.34-7.40 (m, 2H), 7.19 (s, 1H), 7.09-7.11 (m, 1H), 7.00-7.03 ( m, 2H), 6.66 (s, 2H), 5.14 (s, 2H), 4.99 (d, J = 6.9 Hz, 2H), 4.85 (d, J = 6.6 Hz, 2H), 4.04-4.07 (m, 2H ), 3.84 (s, 2H), 3.72 (s, 3H), 3.26-3.37 (m, 2H), 3.07-3.13 (m, 3H), 2.39- 2.50 (m, 1H), 2.15-2.27 (m, 1H) ), 2.00 (s, 6H); MS: m/z 603.3 [M+Na]. Example 56 2-((3-(4-((4'-((1,1-Dioxy)tetrahydrothiophen-3-yl)methoxy)-2',6'-dimethyl-[ 1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (Compound 54)

The title compound was prepared in a similar manner as Compound 2 of Example 2. Compound 56 was hydrolyzed by hydrolysis of the compound of Example 55. ¹ H NMR (CDCl ₃ , 500 MHz): d 7.45-7.48 (m, 1H), 7.40-7.42 (m, 1H), 7.28-7.31 (m, 2H), 7.18 (s, 1H), 7.10-7.11 ( m, 1H), 7.02-7.04 (m, 2H), 6.66 (s, 2H), 5.32 ( s, 1H), 5.16 (s, 2H), 4.96 ( d, J = 7.0 Hz, 2H), 4.91 (d , J= 7.0 Hz, 2H), 4.03-4.07 (m, 2H), 3.85 (s, 2H), 3.29-3.36 (m, 1H), 3.12-3.17 (m, 1H), 3.05-3.11 (m, 1H) ), 2.97-2.99 (m, 1H) 2.45- 2.46 (m, 1H), 2.12-2.19 (m, 1H), 1.99 (s, 6H); MS: m/z 589.2 [M+Na]. Example 57 methyl 2-((3-(4-((2',6'-dimethyl-4'-((tetrahydro-2H-pyran-4-yl)methoxy)-[1, 1'-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound 55)

The title compound was prepared in a similar manner as Compound 1' of Example 51, which was taken to methyl 2-((3-(4-((4'-hydroxy-2',6'-dimethyl-[1,1') -biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound of step 2 of Example 51) and 4-(bromomethyl)tetrahydrogen -2H-pyran reaction. ¹ H NMR (CDCl ₃ , 500 MHz): d 7.44-7.47 (m, 1H), 7.40-7.41 (m, 1H), 7.35-7.37 (m, 2H), 7.20 (s, 1H), 7.11-7.12 ( m, 1H), 7.01-7.03 (d, J = 8.5 Hz, 2H), 6.67 (s, 2H), 5.15 (s, 2H), 5.00 (d, J = 6.5 Hz, 2H), 4.86(d, J = 6.5 Hz, 2H), 4.04-4.05 (m, 2H), 3.83-3.84 (m, 4H), 3.73 (s, 3H), 3.48 (t, J = 11.5 Hz, 2H), 2.09 (m, 1H) , 2.00 (s, 6H), 1.79-1.81 (m, 2H), 1.45-1.47 (m, 2H); MS: m/z 569.3 [M+Na]. Example 58 2-((3-(4-((2',6'-Dimethyl-4'-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1' -biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (Compound 56)

The title compound was prepared in a similar manner as Compound 2 of Example 2. The compound of Example 57 was hydrolyzed to obtain compound 58. ¹ H NMR (CDCl ₃ , 500 MHz): d 7.43-7.46 (m, 1H), 7.39-7.41 (m, 1H), 7.28-7.30 (m, 2H), 7.20 (s, 1H), 7.11-7.12 ( m, 1H), 7.01 (d, J = 8.5 Hz, 2H), 6.67 (s, 2H), 5.14 (s, 2H), 4.90-4.96 (m, 4H), 4.04-4.05 ( m, 2H), 3.77 -3.84 (m, 4H), 3.45-3.51 (m, 2H), 2.09 (m, 1H), 2.00 (s, 6H), 1.78-1.81 (m, 2H), 1.45-1.47 ( m, 2H); MS :m/z 533.3 [M+H]. Example 59 Methyl 2-((3-(4-((4)-((1,1-dioxy)tetrahydro-2H-thiopyran-4-yl)oxy)-2',6'- Dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound 57)

The title compound was prepared in a similar manner as Compound 1' of Example 51, which was taken to methyl 2-((3-(4-((4'-hydroxy-2',6'-dimethyl-[1,1') -biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound of step 2 of Example 51) and 4-(bromomethyl)tetrahydrogen -2H-thiophene 1,1-dioxide reaction. ¹ H NMR (CDCl ₃ , 500 MHz): d 7.41-7.48 (m, 2H), 7.36-7.37 (m, 2H), 7.20 (s, 1H), 7.10-7.11 (m, 1H), 7.01 (d, J = 8.5 Hz, 2H), 6.69 (s, 2H), 5.15 (s, 2H), 5.00 ( d, J = 7.0 Hz, 2H), 4.86 (d, J = 7.0 Hz, 2H), 4.69 (m, 1H), 3.85 (s, 2H), 3.73 (s, 3H), 3.47 (t, J = 12.0 Hz, 2H), 2.95 (d, J = 12.0 Hz, 2H), 2.51 (d, J = 14.5 Hz, 2H), 2.39 ( t, J = 13.5 Hz, 2H), 2.00 (s, 6H); MS: m/z 603.3 [M+Na]. Example 60 2-((3-(4-((4)-((1,1-Dioxy)tetrahydro-2H-thiopyran-4-yl)oxy)-2',6'-dimethyl Base-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (Compound 58)

The title compound was prepared in a similar manner as Compound 2 of Example 2. Compound 60 was hydrolyzed by hydrolysis of the compound of Example 59. ¹ H NMR (CDCl ₃ , 500MHz): d 7.45-7.47 (m, 1H), 7.41-7.43 (m, 1H), 7.30-7.31 (m, 2H), 7.19 (s, 1H), 7.10-7.12 ( m , 1H), 7.02-7.04 (d, J = 8.0 Hz, 2H), 6.69 (s, 2H), 5.16 (s, 2H), 4.92-4.97 (m, 4H), 4.68 (m, 1H), 3.86 ( s, 2H), 3.44-3.47 (m, 2H), 2.95 (d, J = 13.0 Hz, 2H), 2.50-2.53 (d, J = 14.0 Hz, 2H), 2.39-2.42 (m, 2H), 2.00 (s, 6H); MS: m/z 589.2 [M+Na]. Example 61 Methyl 2-((3-(4-(4-(spiro[茚-1,4'-piperidine]-1'-ylmethyl)benzyl)oxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)acetate (Compound 59) Step 1: Methyl 2-((3-(4-((4-(bromomethyl)benzyl)oxy)phenyl)oxy) Synthesis of Butane-3-yl)oxy)acetate

Adding Cs ₂ CO ₃ (1.5 eq.) to methyl 2-((3-(4-hydroxyphenyl)oxycyclobutane-3-yl)oxy)acetic acid in DMF under RT, nitrogen atmosphere A stirred solution of the ester (compound of Step 3 of Example 1, 1 eq.) and the reaction mixture was stirred at RT for 10 min. To the reaction mixture was added 1,4-bis(bromomethyl)benzene (1 equivalent), and the reaction mixture was heated at 80 ° C for 2 h. The reaction mixture was quenched with ice and concentrated. The residue was dissolved in ethyl acetate and washed with EtOAc EtOAc EtOAc. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.43 (s, 4H), 7.35 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 8.4 Hz, 2H), 5.09 (s, 2H), 4.99 (d, J = 6.6 Hz, 2H), 4.86 (d, J = 6.6 Hz, 2H), 4.62 (s, 2H), 4.52 (s, 2H), 3.85 (s, 2H), 3.72 (s, 3H) ); MS: m/z 443.0 [M+Na]. Step 2: Methyl 2-((3-(4-((4-())))))) Synthesis of Butane-3-yl)oxy)acetate

Add Cs ₂ CO ₃ (1.5 eq.) to methyl 2-((3-(4-(4-(bromomethyl)benzyl)oxy)phenyl) in DMF under RT and nitrogen. A stirred solution of oxocyclobutane-3-yl)oxy)acetate (Compound of Step 3 of Example 1, 1 eq.), and the mixture was stirred at RT for 10 min. Spiro[茚-1,4'-piperidine] (1 equivalent) was added to the reaction mixture, and the reaction mixture was heated at 80 ° C for 2 h. The reaction mixture was quenched with ice and concentrated. The residue was dissolved in ethyl acetate and washed with EtOAc EtOAc EtOAc. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.21-7.43 (m, 10H), 7.02 (d, J = 8.4 Hz, 2H), 6.86 (d, J = 5.7 Hz, 1H), 6.74 (d, J = 5.4 Hz, 1H), 5.09 (s, 2H), 5.01 (d, J = 6.9 Hz, 2H), 4.86 (d, J = 6.9 Hz, 2H), 3.85 (s, 2H), 3.72 (s, 3H) ), 2.98 (d, J = 11.4 Hz, 2H), 2.19-2.43 (m, 8H); MS: m/z 526.1 [M+H]. Example 62 2-((3-(4-((4-())))))))))) 3-yl)oxy)acetic acid (compound 60)

The title compound was prepared in a similar manner as Compound 2 of Example 2. Compound 60 was obtained by hydrolysis of Compound 59 of Example 61. ¹ H NMR (CD ₃ OD, 300 MHz): d 7.18-7.55 (m, 10 H) 6.88-7.06 (m, 4H), 5.18 (br s, 2H), 4.80-5.01 (m, 4H), 4.25 ( s, 2H), 3.12-3.49 (m, 4H), 2.31-2.41 (m, 2H), 2.16 (s, 2H), 1.20-1.50 (m, 2H); MS: m/z 512.1 [M+H] . Example 63 Methyl 2-((3-(4-((4-((1-methyl-)-[[([(-]]]]]] Phenyl)oxycyclobutane-3-yl)oxy)acetate (compound 61)

The title compound was prepared in a similar manner as Compound 59 of Example 61, which was taken to methyl 2-((3-(4-((4-(bromomethyl)) benzyl) oxy)) Reaction of 3-yl)oxy)acetate (the compound of Step 1 of Example 61) with 1-methylspiro[porphyrin-3,4'-piperidine]. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.35-7.41 (m, 6H), 7.02-7.14 (m, 4H), 6.71 (t, J = 7.2 Hz, 1H), 6.50 (d, J = 7.8 Hz , 1H), 5.08 (s, 2H), 5.01 (d, J = 6.6 Hz, 2H), 4.86 (d, J = 6.6 Hz, 2H) 3.85 (s, 2H), 3.72 (s, 2H), 3.58 ( s, 2H), 3.21 (s, 2H), 2.90 (d, J = 10.5 Hz, 2H), 2.78 (s, 3H), 1.92-2.19 (m, 4H), 1.65-1.74 (m, 3H); MS : m/z 543.2 [M+H]. Example 64 2-((3-(4-((4-((1-methyl)]]]]]]]] Phenyl)oxycyclobutane-3-yl)oxy)acetic acid (compound 62)

The title compound was prepared in a similar manner as Compound 2 of Example 2. Compound 62 was obtained by hydrolysis of compound 61 of Example 63. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.38-7.51 (m, 6H), 7.02-7.17 (m, 4H), 6.74 (t, J = 7.2 Hz, 1H), 6.50 (d, J = 7.5 Hz , 1H), 4.85-5.10 (m, 6H), 4.03 (s, 2H), 3.79 (s, 2H), 3.18-3.23 (m, 4H), 2.78 (s, 3H), 1.85-2.15 (m, 6H MS: m/z 529.1 [M+H]. Example 65 methyl 2-((3-(4-(4-fluoro-4'-methyl-[1,1'-biphenyl]-2-yl)methoxy)phenyl)oxycyclobutane 3-yl)oxy)acetate (compound 63) Step 1: methyl 2-((3-(4-((2-bromo-5-fluorobenzyl)oxy)phenyl)oxy) Synthesis of alk-3-yl)oxy)acetate

Adding Cs ₂ CO ₃ (5.13 g, 15.74 mmol) to methyl 2-((3-(4-hydroxyphenyl)oxycyclobutane-3-yl)oxy)acetate in DMF (example A stirred solution of the compound of Step 3, 2.5 g, 10.49 mmol), and the mixture was stirred at RT for 10 min. 1-Bromo-2-(bromomethyl)-4-fluorobenzene (10.48 mmol) was added thereto, and the reaction mixture was stirred at 80 ° C for 1 h. After the reaction was completed, the mixture was reacted with ice and concentrated. The residue was dissolved in ethyl acetate and washed with water, dried over anhydrous sodium sulfate It was further purified by combiflash and was eluted with a gradient of 5-30% ethyl acetate in petroleum ether to give the title compound as white solid. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.53-7.58 (m, 1H), 7.39 (d, J = 8.7 Hz, 2H), 7.39-7.42 (m, 1H), 7.02 (d, J = 8.4 Hz , 2H), 6.92-6.97 (m, 1H), 5.12 (s, 2H), 5.00 (d, J = 6.9 Hz, 2H), 4.88 (d, J = 6.9 Hz, 2H), 3.86 (s, 2H) , 3.73 (s, 3H); MS: m/z 447.0 [M+Na]. Step 2: Methyl 2-((3-(4-(4-fluoro-4'-methyl-[1,1'-biphenyl]-2-yl)methoxy)phenyl)oxycyclobutane Synthesis of alk-3-yl)oxy)acetate

Add potassium carbonate (3 equivalents) to methyl 2-((3-(4-(2-bromo-5-fluorobenzyl)oxy)phenyl) in dioxane:water (4:1) a solution of oxycyclobutane-3-yl)oxy)acetate (compound of Example 65, Step 1, 1 eq.) and p-tolylboronic acid (5 eq.), and the mixture was degassed with argon for 10 minutes. . Tetrakis(triphenylphosphine)palladium(0) (0.05 eq.) was added to the resulting solution, and the mixture was heated in a microwave at 80-90 °C for 15 minutes or at 80-90 °C for 1 to 2 hours. After the reaction was completed, the reaction mixture was evaporated, evaporated, evaporated ¹ H NMR (CDCl ₃ , 300 MHz): d 8.16 (d, J = 6.0 Hz, 1H), 7.27-7.36 (m, 7H), 7.11–7.12 (m, 1H ), 6.90 (d, J = 6.0 Hz , 2H ), 4.94-4.96 (m, 4H ), 4.86 (d, J = 6.0 Hz, 2H), 3.83 (s, 2H), 3.72 (s, 3H), 2.41 (s, 3H ); MS: m/ z 437 [M+1]. Example 66 2-((3-(4-(4-Fluoro-4'-methyl-[1,1'-biphenyl]-2-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid (compound 64)

Adding LiOH (5 equivalents) to methyl 2-((3-(4-(4-fluoro-4'-methyl-[1,1'-biphenyl)) in THF:MeOH (1:4) a solution of 2-yl)methoxy)phenyl)oxocyclobutan-3-yl)oxy)acetate (compound of Example 65, 1 eq.), and the reaction mixture was stirred at RT 2 Until 3 h. The solvent was removed, the reaction mixture was acidified with saturated NH ₄ Cl solution (pH 6-6.5), and extracted with ethyl acetate. The organic layer was washed with brine, dried over Na ₂ SO ₄ and concentrated to obtain the title compound. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.23-7.36 (m, 7H), 7.02–7.12 (m, 2H), 6.76 (d, J = 9.0 Hz, 2H), 4.88-4.90 (m, 6H) , 3.84 (s, 2H), 2.41 (s, 3H); MS: m/z 421 (M-1).

Compounds of Examples 67, 69 and 71 were prepared by following the procedure exemplified in Step 2 of Example 65. Compounds of Examples 68, 70 and 72 were prepared by following the procedure as exemplified in Example 66. The characterization data for the compounds of Examples 67-72 are described below. Example 67 Methyl 2-((3-(4-((2'-(benzyloxy)-4-fluoro-[1,1'-biphenyl]-2-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate (Compound 65)

The title compound was prepared in a similar manner as Compound 63 of Example 65, which was taken to methyl 2-((3-(4-((2-bromo-5-fluorobenzyl)oxy)phenyl)oxycyclobutane - Reaction of 3-yl)oxy)acetate (the compound of Step 1 of Example 65) with (2-(benzyloxy)phenyl)boronic acid. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.09 - 7.39 (m, 9H ), 7.15 (d, J = 5 Hz, 2H ), 7.06–7.09 (m, 3H ), 6.80 (d, J = 5.0 Hz , 2H), 5.07 (s, 2H), 4.94-5.01 (m, 3H), 4.79 – 4.80 (m, 3H), 3.78 (s, 2H), 3.71 (s, 3H); MS: m/z 527.6 [ M-1]. Example 68 2-((3-(4-((2'-(Benzyloxy)-4-fluoro-[1,1'-biphenyl)-2-yl)methoxy)phenyl)oxycarbonyl Butan-3-yl)oxy)acetic acid (compound 66)

The title compound was prepared in a similar manner as Compound 64 of Example 66. The compound of Example 67 was obtained by hydrolysis of the compound of Example 67. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.19-7.40 (m, 9H ), 7.03–7.10 (m, 5H ), 6.80 (d, J = 6.0 Hz, 2H ), 5.07 (s, 2H ), 4.42 -4.97 (m, 6H), 3.79 (s, 2H); MS: m/z 537.2 [ M + Na ]. Example 69 Methyl 2-((3-(4-(4-fluoro-[1,1'-biphenyl]-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate (compound 67)

The title compound was prepared in a similar manner as Compound 63 of Example 65, which was taken to methyl 2-((3-(4-((2-bromo-5-fluorobenzyl)oxy)phenyl)oxycyclobutane - Reaction of 3-yl)oxy)acetate (the compound of Step 1 of Example 65) with phenylboronic acid. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.30-7.44 (m, 9H ), 7.09–7.13 (m, 1H ), 6.89 (d, J = 5.0 Hz, 2H ), 5.00 (d, J = 5.0 Hz , 2H ), 4.96 (d, 2H), 4.86 (d, J = 5.0 Hz, 2H), 3.83 (s, 2H), 3.72 (s, 3H); MS: m/z 445 [M+Na]. Example 70 2-((3-(4-(4-Fluoro-[1,1'-biphenyl]-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy) Acetic acid (compound 68)

The title compound was prepared in a similar manner as Compound 64 of Example 66. The compound of Example 70 was obtained by hydrolysis of the compound of Example 69. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.25 - 7.44 (m, 9H), 7.09–7.14 (m, 1H), 6.89 (d, J = 6.0 Hz, 2H), 5.13 (s, 2H), 4.89 - 4.96 (m, 4H), 3.85 (s, 2H); MS: m/z 407.1 [M-1]. Example 71 Methyl 2-((3-(4-((3',4-difluoro-[1,1'-biphenyl]-2-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetate (compound 69)

The title compound was prepared in a similar manner as Compound 63 of Example 65, which was taken to methyl 2-((3-(4-((2-bromo-5-fluorobenzyl)oxy)phenyl)oxycyclobutane - Reaction of 3-yl)oxy)acetate (the compound of Step 1 of Example 65) with (3-fluorophenyl)boronic acid. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.30-7.40 (m, 5H), 7.07-7.14 (m, 4H), 6.90 (d, J = 5.0 Hz, 2H ), 5.06 (d, J = 5.0 Hz , 2H), 4.94 (s, 2H ), 4.82 (d, J = 5.0 Hz, 2H), 3.84 (s, 2H), 3.72 (s, 3H); MS: m/z 463.2 [M+Na]. Example 72 2-((3-(4-((3')-Difluoro-[1,1'-biphenyl]-2-yl)methoxy)phenyl)oxycyclobutan-3-yl )oxy)acetic acid (compound 70)

The title compound was prepared in a similar manner as Compound 64 of Example 66. The compound of Example 71 was obtained by hydrolysis of the compound of Example 71. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.22-7.48 (m, 9H), 6.90 (d, J = 5.0 Hz, 2H), 4.9 (s, 2H ), 4.84 (d, J = 5.0 Hz, 2H ), 4.72 (d, J = 5.0 Hz, 2H), 3.71 (s, 2H); MS: m/z 425 [M-1]. Example 73 Methyl 2-((3-(4-((4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy) Phenyl)oxycyclobutane-3-yl)oxy)acetate (compound 71)

Add Cs ₂ CO ₃ (1.5 eq.) to methyl 2-((3-(4-((4'-hydroxy-[1,1'-biphenyl]-3) in DMF under RT, nitrogen atmosphere To a stirred solution of methoxy)phenyl)oxocyclobutan-3-yl)oxy)acetate (Compound 25, 1 eq.), and the mixture was stirred at RT for 10 min. Add 1-methyl-4-((3-(methylsulfonyl)propyl)sulfonyl)benzene or 1-bromo-3-(methylsulfonyl)propane (1 equivalent) to the reaction mixture, and The reaction mixture was heated at 80 °C for 2 h. The reaction mixture was quenched with ice and concentrated. The residue was dissolved in ethyl acetate and washed with EtOAc EtOAc EtOAc. ¹ H NMR (CDCl ₃ , 500 MHz): d 7.69 (s, 1H), 7.63-7.67 (m, 1H), 7.53-7.56 (m, 3H), 7.45-7.48 (m, 1H), 7.37-7.41 ( m, 3H), 7.05 (d, J = 5.1 Hz, 1H), 6.97 (d, J = 5.1 Hz, 2H), 5.15 (s, 2H), 5.00 (d, J = 3.9 Hz, 2H), 4.87 ( d, J = 3.9 Hz, 2H), 4.17-4.19 (m, 2H), 3.86 (s, 2H), 3.72 (s, 3H), 3.29-3.32 (t, J = 7.5 Hz, 2H), 2.99 (s , 3H), 2.40-2.41 (m, 2H); MS: m/z 563.2 [M+Na]. Example 74 2-((3-(4-((4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl Oxycyclobutane-3-yl)oxy)acetic acid (Compound 72)

Adding LiOH (5 equivalents) to methyl 2-((3-(4-((4'-(3-(methylsulfonyl))propoxy)-) a solution of 1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound of Example 73, 1 equivalent), and The reaction mixture was stirred at RT for 2 to 3 h. The solvent was removed, the reaction mixture was acidified with saturated NH ₄ Cl solution (pH 6-6.5), and extracted with ethyl acetate. The organic layer was washed with brine, dried over Na ₂ SO ₄ and concentrated to obtain the title compound. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.69 (s, 1H), 7.60-7.62 (m, 3H), 7.38-7.44 (m, 4H), 6.99-7.06 (m, 4H), 5.17 (s, 2H) , 4.68-4.80 (m, 4H), 4.13(m, 2H), 3.43 (m, 2H), 3.26-3.33 (m, 2H), 3.02 (s, 3H), 2.49 (m, 2H); MS: m /z 549 [M+Na].

Compounds of Examples 75, 77 and 79 were prepared by following the procedure as exemplified in Example 73. Compounds of Examples 76, 78 and 80 were prepared by following the procedure as exemplified in Example 74. The characterization data for the compounds of Examples 75-80 are described below. Example 75 methyl 2-((3-(4-((4)-((3-(hydroxymethyl))oxycyclobutane-3-yl)methoxy)-[1,1'-biphenyl] 3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound 73)

The title compound was prepared in a similar manner as Compound 71 of Example 73, which was taken to methyl 2-((3-(4-((4)-hydroxy-[1,1'-biphenyl]-3-yl) methoxy) Phenyl)oxycyclobutane-3-yl)oxy)acetate (compound of Example 71) with (3-(bromomethyl)oxocyclobutane-3-yl)methanol or (3-( Reaction of toluenesulfonylmethyl)oxycyclobutane-3-yl)methanol. ¹ H NMR (CDCl ₃ , 500 MHz): d 7.69 (s, 1H), 7.54-7.58 (m, 3H), 7.45-7.48 (m, 1H), 7.37-7.41 (m, 3H), 7.03-7.07 ( m, 4H), 5.15 (s, 2H), 5.00 (d, J = 4.2 Hz, 2H), 4.87 (d, J = 3.9 Hz, 2H), 4.61-4.64 (m, 4H), 4.32 (s, 2H ), 4.08-4.09 (m, 2H), 3.86 (s, 2H), 3.72 (s, 3H); MS: m/z 543.3 [M+Na]. Example 76 2-((3-(4-((4'-((3-(Hydroxymethyl)oxycyclobutane-3-yl)methoxy)-[1,1'-biphenyl]-3 -yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (compound 74)

The title compound was prepared in a similar manner as Compound 72 of Example 74. The compound of Example 75 was obtained by hydrolysis of the compound of Example 75. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.61 (s, 1H), 7.53-7.56 (m, 3H), 7.44-7.49 (m, 1H), 7.38-7.40 (m, 1H), 7.31-7.34 (m, 2H), 7.01-7.07 (m, 4H), 5.16 (s, 2H), 4.91-4.98 (m, 4H), 4.60-4.64 (m, 4H), 4.31 (s, 2H), 4.08 (s, 2H) , 3.86 (s, 2H); MS: m/z 505.1 [MH]. Example 77 Methyl 2-((3-(4-((4,1-dioxo)tetrahydrothiophen-3-yl)methoxy)-[1,1'-biphenyl] 3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound 75)

The title compound was prepared in a similar manner as Compound 71 of Example 73, which was taken to methyl 2-((3-(4-((4)-hydroxy-[1,1'-biphenyl]-3-yl) methoxy) Phenyl)oxycyclobutane-3-yl)oxy)acetate (compound of Example 71) with 3-(bromomethyl)tetrahydrothiophene 1,1-dioxide or 3-(toluene) Reaction of mercaptomethyl)tetrahydrothiophene 1,1-dioxide. ¹ H NMR (CDCl ₃ , 500 MHz): d 7.63 (s, 1H), 7.53-7.57 (m, 3H), 7.45-7.48 (m, 1H), 7.37-7.41 (m, 3H), 7.05 (d, J = 8.5 Hz, 2H), 6.97 (d, J = 8.5 Hz, 2H), 5.15 (s, 2H), 5.00 (d, J = 6.5 Hz, 2H), 4.87 (d, J = 7.0 Hz, 2H), 4.06 -4.11 (m, 2H), 3.86 (s, 2H), 3.72 (s, 3H), 3.27-3.37 (m, 2H), 2.97-3.17 (m, 2H), 2.46- 2.47 (m, 1H), 2.17 - 2.25 (m, 2H); MS: m/z 575.2 [M+Na]. Example 78 2-((3-(4-((4'-((1,1-Dioxy)tetrahydrothiophen-3-yl)methoxy)-[1,1'-biphenyl]-3 -yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (compound 76)

The title compound was prepared in a similar manner as Compound 72 of Example 74. The compound of Example 77 was obtained by hydrolysis of the compound of Example 77. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.62 (s, 1H), 7.52-7.56 (m, 3H), 7.47-7.49 (m, 1H), 7.38-7.44 (m, 1H), 7.31-7.34 (m, 2H), 7.04 (d, J = 8.7 Hz, 2H), 6.96 (d, J = 8.7 Hz, 2H), 5.15 (s, 2H), 4.91-4.98 (m, 4H), 4.04- 4.10 (m, 2H) ), 3.86 (s, 2H), 3.25-3.38 (m, 1H), 2.97-3.19 (m, 3H), 2.45- 2.47 (m, 1H), 2.14- 2.27 (m, 2H); MS: m/z 537.0 [MH]. Example 79 Methyl 2-((3-(4-((4)-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl) Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound 77)

The title compound was prepared in a similar manner as Compound 71 of Example 73, which was taken to methyl 2-((3-(4-((4)-hydroxy-[1,1'-biphenyl]-3-yl) methoxy) Phenyl)oxycyclobutan-3-yl)oxy)acetate (compound of Example 71) with 4-(bromomethyl)tetrahydro-2H-pyran or 4-(toluenesulfonyl) Reaction of tetrahydro-2H-pyran. ¹ H NMR (CDCl ₃ , 500 MHz): d 7.63 (s, 1H), 7.54-7.55 (m, 3H), 7.45-7.48 (m, 1H), 7.37-7.39 (m, 3H), 7.05 (d, J = 8.5 Hz, 2H), 6.98 (d, J = 8.5 Hz, 2H), 5.15 (s, 2H), 5.00 (d, J = 6.5 Hz, 2H), 4.87 (d, J = 7.0 Hz, 2H), 4.04 -4.06 (m, 2H), 3.86-3.88 (m, 4H), 3.72 (s, 3H), 3.48 (t, J = 11.5 Hz, 2H), 2.10-2.12 (m, 1H), 1.79 (d, J = 12.5 HZ, 2H), 1.49-1.51 (m, 2H); MS: m/z 541.3 [M+Na]. Example 80 2-((3-(4-((4'-)(tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl) A Oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (compound 78)

The title compound was prepared in a similar manner as Compound 72 of Example 74. The compound of Example 79 was obtained by hydrolysis of the compound of Example 79. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.62 (s, 1H), 7.53-7.56 (m, 3H), 7.46-7.48 (m, 1H), 7.39-7.43 (m, 1H), 7.31-7.37 ( m, 2H), 7.04 (d, J = 8.7 Hz, 2H), 6.97 (d, J = 8.7 Hz, 2H), 5.15 (s, 2H), 4.92-4.98 (m, 4H), 4.02-4.07 (m , 2H), 3.86-3.87 (m, 4H), 3.47 (t, J = 11.4 Hz, 2H), 2.10-2.12 (m, 1H), 1.78-1.82 (m, 2H), 1.48-1.52 (m, 2H MS: m/z 505.1 [M+H]. Example 81 Methyl 2-((3-(4-((4-(o-to))))oxy)phenyl)oxycyclobutan-3-yl)oxy)acetate (Compound) 79) Step 1: Synthesis of methyl 4-(o-tolyloxy)benzoate

Di-tert-butyl (2,4,6-triisopropyl-[1,1-biphenyl]-2-yl)phosphine (8.24 mg, 0.028 mmol), potassium phosphate (395 mg, 1.86 mmol) and Palladium acetate (4.18 mg, 0.02 mmol) was added to methyl 4-bromobenzoate (commercial source, 200 mg, 0.93 mmol) and o-cresol in toluene (5 ml) under argon (commercial sources, 101 mg, 0.93 mmol) was stirred, followed by being allowed to stir for 12 h at 100 ^o C. The reaction mixture was filtered though EtOAc (EtOAc)EtOAcEtOAc The crude product was purified by flash chromatography to give the title compound. Yield: 79%; ¹ H NMR (CDCl ₃ , 300 MHz): d 8.00 (d, J = 6.0 Hz, 2H), 7.13-7.28 (m, 2H), 7.01 (d, J = 6.0 Hz, 2H) , 6.9 (d , J = 6.0 Hz, 2H), 3.90 (s, 3H ), 2.20 (s, 3H ); MS: m/z 243.3 [M+1]. Step 2: Synthesis of (4-(o-tolyloxy)phenyl)methanol

Lithium aluminum hydride (2.06 ml, 2.06 mmol) was added at 0 ^o C (in THF 1M) to in MeOH (5 ml) of methyl 4- (o- tolyloxy) benzoate (Example 81 The resulting reaction mixture was stirred at RT for 3 h in a stirred solution of the compound from step 1 (100 mg, 0.41 mmol). The RM was extracted with EtOAc (EtOAc)EtOAc. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.26-7.33 (m, 3H), 7.07-7.21 (m, 2H), 6.89 (m, 3H), 4.67 (s, 2H), 2.25 (s, 3H) ;MS: m/z LCMS 214.3 [M] ⁺ . Step 3: Methyl 2-((3-(4-((4-(o-tolyloxy)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetate synthesis

(4-(o-Tolyloxy)phenyl)methanol (compound of step 2) was added to methyl 2-((3-(4-hydroxyphenyl)oxycyclobutane) in DCM at 0 °C The addition of triphenylphosphine (1.5 equivalents) is followed by a solution of -3-yl)oxy)acetate (compound of Example 1, Step 3). The resulting reaction mixture was stirred for 3 h. After completion, the reaction mixture was poured into water and extracted with ethyl acetate. The organic solvent was evaporated to give a crude compound which was purified by flash chromatography to afford the title compound. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.39 (d, J = 6.0 Hz, 4H), 7.06-7.22 (m, 3H), 7.04 (d, J = 6.0 Hz, 2H ), 6.91 (m, 3H) ), 4.99-5.03 (m, 4H), 4.89 (d, J = 6Hz, 2H), 3.90 (s, 2H), 3.72 (s, 3H), 2.25 (s, 3H); MS: m/z 457.1 [ M+Na]. Example 82 2-((3-(4-((4-(o-tolyloxy)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (Compound 80)

The title compound was prepared in a similar manner as Compound 72 of Example 74. The compound of Example 81 was obtained by hydrolysis of the compound of Example 81. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.07-7.39 (m, 7H), 7.04 (d, J = 8.4 Hz, 2H), 6.94 (d, J = 8.4 Hz, 3H), 5.03 (s, 2H) ), 4.91-4.99 (m, 4H), 3.88 (s, 2H), 2.25 (s, 3H); MS: m/z 420.4 [M] ⁺ . Example 83 Ethyl 2-((3-(4-((3'-fluoro-2'-methyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)propionate (Compound 81) Step 1: 2-((3-(4-(Benzyloxy)phenyl)oxycyclobutan-3-yl)oxy)propane Acid ester synthesis

A solution of 3-(4-(benzyloxy)phenyl)oxycyclobutan-3-ol (Compound of Example 1, Step 1, 500 mg, 1.951 mmol) was added at 0<0> In a stirred solution of sodium hydride (156 mg, 6.50 mmol) in ml). The reaction mixture was stirred at 0<0>C for 1 h then ethyl 2-bromopropionate (0.633 ml, 4.88 mmol) The reaction mixture was ice-water subsided, extracted with ethyl acetate, dried over anhydrous sodium sulfate through, concentrated and purified by flash chromatography to obtain the title compound of semi-solid (440 mg) Yield: 63.30%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.47-7.39 (m, 3H), 7.38-7.35 (m, 2H), 7.33-7.30 (m, 2H), 7.02-6.99 (m, 2H), 5.09 (s, 2H) ), 5.05-5.03 (m, 1H), 4.96-4.87 (m, 3H), 4.02-3.95 (m, 2H), 3.85-3.78 (m, 1H), 1.34 (d, J = 6.9 Hz, 3H), 1.17 (t, J = 7.2 Hz, 3H); MS (m/z) 357.1 [M+ H]. Step 2: Synthesis of ethyl 2-((3-(4-hydroxyphenyl)oxycyclobutane-3-yl)oxy)propionate

Add Pd-C (200 mg, 1.879 mmol) to ethyl 2-((3-(4-(benzyloxy)phenyl)oxycyclobutane-3-yl)oxy)propane in ethanol A stirred solution of the ester (compound of Step 1, 400 mg, 1.122 mmol) was taken and the mixture was stirred at room temperature under hydrogen atmosphere (with hydrogen balloon) for 2 h. The reaction mixture was filtered through a pad of Celite® and washed with EtOAc. The filtrate was concentrated and purified with EtOAc (EtOAc) Yield: 83.66%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.27-7.26 (m, 1H), 7.25-7.23 (m, 1H), 6.87-6.82 (m, 2H), 5.41 (s, 1H) ), 5.06-5.04 (m, 1H), 4.96-4.89 (m, 3H), 4.04-3.97 (m, 2H), 3.85-3.78 (m, 1H), 1.34 (d, J = 6.9 Hz, 3H), 1.19 (t, J = 7.2 Hz, 3H); MS (m/z) 289.1 [M+ Na]. Step 3: Synthesis of ethyl 2-((3-(4-(3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)propionate

2-((3-(4-Hydroxyphenyl)oxycyclobutane-3-yl)oxy)propanoate (compound of step 2, 0.9 gm, 3.38 mmol), 1-bromo-3-(bromo) methyl) benzene (commercial sources, 0.88 g, 3.52 mmol) and a mixture of _{K 2 CO 3 (0.7 g,} 5.07 mmol) of (7 ml) was stirred overnight at RT in dry DMF. The reaction mixture was diluted with EtOAc (EtOAc) (EtOAc)EtOAc. The filtrate was concentrated and purified by flash chromatography eluting elut elut Yield: 82%. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.62 (s, 1H), 7.494 (d, J = 4.5 Hz, 1H), 7.38 (d, J = 4.5 Hz, 1H), 7.34 (d, J = 5.1 Hz, 2H), 7.29 (m, 1H), 7.00 (d, J = 5.1 Hz, 2H), 5.07 (s, 2H), 5.055 (d, J = 4.2 Hz, 1H), 4.96 (d, J = 3.9 Hz, 1H), 4.93 (d, J = 3.9 Hz, 1H), 4.89 (d, J = 3.9 Hz, 1H), 4.02 (q, J = 4.2 Hz, 2H), 3.85 (q, J = 3.9 Hz, 1H), 1.34 (d, J = 4.2 Hz, 3H, 1.20 (t, J = 4.2 Hz, 3H); MS (m/z) 457.9 (M+Na). Step 4: Ethyl 2-((3- (4-((3'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)propane Acid ester synthesis

Ethyl 2-((3-(4-(3-bromobenzyl)oxy)phenyl)oxy) in a solvent mixture of 1,4-dioxane (10 ml) and water (3 ml) Cyclobutane-3-yl)oxy)propionate (compound of Step 3, 0.22 g, 0.505 mmol), (3-fluoro-2-methylphenyl)boronic acid (commercial source, 0.101 g, 0.657 mmol) A mixture of Na ₂ CO ₃ (0.127 g, 1.516 mmol) was degassed using an argon balloon and spun for 20 minutes with ultrasonic waves. Next, tetrakis(triphenylphosphine)palladium(0) (0.029 g, 0.101 mmol) was added and again blown with argon for 20 minutes. The reaction mixture was heated at 80 °C for 3 h. After the reaction was completed, the mixture was diluted with ethyl acetate (20 ml) and water (10 ml) and filtered through celite® filter pad. The organic layer and the aqueous layer were separated, and the aqueous layer was washed twice with ethyl acetate (10 ml). The organic layer was washed with EtOAcq. Yield: 70.7 %; ¹ H NMR (CDCl ₃ , 300 MHz): δ 1.17 (t, J = 6.9 Hz, 3H), 1.32 (d, J = 6.6 Hz, 3H), 2.16 (s, 3H), 3.82 (q, J = 6.6 Hz, 1H), 3.97 (q, J = 6.9 Hz, 2H), 4.86-5.05 (m, 4H), 5.14 (s, 2H), 7.00-7.05 (m, 4H), 7.12- 7.33 (m, 4H), 7.38 (s, 1H), 7.45-7.47 (m, 2H); MS (m/z) 487.4 (M+Na). Example 84 2-((3-(4-((3'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)propionic acid (compound 82)

Add NaOH (0.043 g, 1.076 mmol) to ethyl 2-((3-(4-((3'-fluoro-2'-methyl-[1,1') in THF:water (2.5:1) a solution of -biphenyl]-3-yl)methoxy)phenyl)oxocyclobutan-3-yl)oxy)propionate (Compound of Example 83, 0.1 g, 0.215 mmol), and the reaction mixture Stir at RT for 3 h. The solvent was removed, and the residue was crystalljjjjjjjjjj The organic layer was dried over Na ₂ SO _4, and concentrated to obtain the title compound (0.08 g). Yield: 85%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 1.11 (d, J = 6.6 Hz, 2H), 2.20 (s, 3H), 3.66 (q, J = 6.6 Hz, 1H), 4.67 ( d, J = 6.9 Hz, 1H), 4.77-4.80 (m, 2H), 4.77-4.80 (m, 2H), 4.87 (d, J = 6.9 Hz, 1H), 5.18 (s, 2H), 7.04-7.07 (m, 3H), 7.11-7.28 (m, 3H), 7.35-7.38 (m, 3H), 7.45 (s, 2H); MS (m/z) 459.6 (M + Na). Example 85 Ethyl 2-((3-(4-((2'-)-trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)propionate (compound 83)

Ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane) in a solvent mixture of dioxane (4 ml) and water (1 ml) 3-yl)oxy)propionate (compound of step 3 of Example 83, 100 mg, 0.230 mmol), (2-(trifluoromethyl)phenyl)boronic acid (commercial source, 387 mg, 2.035 mmol) A mixture of K ₂ CO ₃ (563 mg, 4.07 mmol) was degassed using an argon balloon for 20 min. Tetrakis(triphenylphosphine)palladium(0) (19.6 mg, 0.017 mmol) was added and the reaction mixture was again degassed for 5 min. The reaction mixture was heated at 65-70 °C for 3 h. After the reaction was completed, the reaction mixture was iced and the solvent was removed. The residue was extracted with ethyl acetate. The organic layer was dried with EtOAc EtOAc m. Yield: 73.17%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.76-7.74 (m, 1H), 7.60-7.55 (m, 1H), 7.50-7.43 (m, 3H), 7.40-7.36 (m , 2H), 7.33-7.29 (m, 3H), 7.01-6.96 (m, 2H), 5.13 (s, 2H), 5.05-5.02 (m, 1H), 4.95-4.85 (m, 3H), 4.02-3.95 (m, 2H), 3.82-3.76 (m, 1H), 1.32 (d, J = 6.9 Hz, 3H), 1.65 (t, J = 7.2 Hz, 3H); MS: (m/z) 501.1 [M+ H ]. Example 86 2-((3-(4-((2'-)(Trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)propionic acid (compound 84)

Add LiOH (32 mg, 0.74 mmol) to ethyl 2-((3-(4-2(4-(trifluoromethyl))-[1,1' in THF:MeOH (1:4) a solution of -biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionate (compound of Example 85, 75 mg, 0.150 mmol), and will react The mixture was stirred at RT for 2 to 3 h. The mixture was reacted with ice, concentrated and washed with diethyl ether. Ammonium chloride solution was added and the compound was extracted with ethyl acetate. The organic layer was washed with brine, dried over Na ₂ SO ₄ and concentrated to obtain the title compound of semi-solid (61mg). Yield: 86.15%; ¹ H NMR (DMSO, 300 MHz): δ 12.48 (br s, 1H), 7.84-7.81 (m, 1H), 7.74-7.61 (m, 2H), 7.50-7.41 (m, 2H) ), 7.39-7.33 (m, 4H), 7.28-7.26 (m, 1H), 7.06- 7.03 (m, 2H), 5.17 (s, 2H), 4.85-4.76 (m, 3H), 4.69-4.67 (m , 1H), 3.71-3.69 (m, 1H), 1.13 (d, J = 6.9 Hz, 3H); MS: m/z 471.0 [M-H]. Example 87 Ethyl 2-((3-(4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl) )oxy)propionate (compound 85)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)propionate with o-tolylboronic acid. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.47-7.40 (m, 4H), 7.32-7.29 (m, 4H), 7.26-7.24 (m, 2H), 7.02-6.99 (m, 2H), 5.13 ( s, 2H), 5.04-5.02 (m, 1H), 4.96-4.85 (m, 3H), 4.02-3.95 (m, 2H), 3.84-3.77 (m, 1H), 2.66 (s, 3H), 1.32 ( d, J = 6.6 Hz, 3H), 1.16 (t, J = 7.2 Hz, 3H); MS (m/z) 447.1 [M+ H]. Example 88 2-((3-(4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Propionate (compound 86)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 88 was obtained by hydrolysis of the compound of Example 87. ¹ H NMR (DMSO, 300 MHz): δ 12.48 (br s, 1H), 7.46-7.44 (m, 2H), 7.39-7.36 (m, 2H), 7.34-7.26 (m, 2H), 7.24-7.18 ( m, 4H), 7.01 (d, J = 8.7 Hz, 2H), 5.17 (s, 2H), 4.85-4.76 (m, 3H), 4.69 (d, J = 6.6 Hz, 1H), 3.73-3.67 (m , 1H), 2.19(s, 3H), 1.13 (d, J = 6.9 Hz, 3H); MS: (m/z) 417.0 [M-H]. Example 89 Ethyl 2-((3-(4-((2)-chloro-4'-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl) ]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)propionate (Compound 87) Step 1: Ethyl 2-((3-(4-((2') Synthesis of -Chloro-4'-hydroxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionate

Ethyl 2-((3-(4-(3-carboxybenzyl)oxy)phenyl)oxycyclobutan-3-yl) in a solvent mixture of dioxane and water (4:1) )oxy)propionate (compound of step 3 of Example 83, 1.2 g, 2.76 mmol), (2-chloro-4-hydroxyphenyl)boronic acid (commercial source, 0.713 g, 4.14 mmol) and K ₂ CO ₃ The reaction mixture (1.143 g, 8.27 mmol) was degassed by blowing argon for 25 min. Tetrakis(triphenylphosphine)palladium(0) (0.04 g, 0.138 mmol) was added to the reaction mixture and degassed again for 5 min. The reaction mixture was heated at 65-70 °C for 4 h. After completion of the reaction, the reaction mixture was taken from EtOAc EtOAc. The organic layer was dried with EtOAc EtOAc (EtOAc) Yield: 62.1 %; ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.48 (s, 1H), 7.46-7.42 (m, 2H), 7.41-7.40 (m, 1H), 7.33-7.30 (m, 2H ), 7.24-7.21 (m, 1H), 7.04-6.99 (m, 3H), 6.83-6.79 (m, 1H), 5.70 (s, 1H), 5.13 (s, 2H), 5.07 (d, J = 6.6 Hz, 1H), 4.90-4.89 (m, 3H), 4.02-3.95 (m, 2H), 3.85-3.78 (m, 1H), 1.32 (d, J = 6.9Hz, 3H), 1.27 (t, J= 4.5 Hz, 3H); MS: (m/z) 505.9 [M+H]. Step 2: Ethyl 2-((3-(4-((2)-chloro-4'-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-linked Synthesis of Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionate

Add Cs ₂ CO ₃ (313 mg, 0.961 mmol) to ethyl 2-((3-(4-((2'-chloro-4'-hydroxy-[1,1') in DMF (5 mL) a solution of -biphenyl]-3-yl)methoxy)phenyl)oxocyclobutan-3-yl)oxy)propionate (357 mg, 0.739 mmol), and the reaction mixture was stirred at RT After 10 minutes, the addition of (tetrahydro-2H-pyran-4-yl)methyl 4-methylbenzenesulfonate (commercial source, 200 mg, 0.739 mmol) was added. The reaction mixture was heated at 80 °C for 2 h. After the reaction was completed, the mixture was reacted with ice and concentrated. The residue was dissolved in ethyl acetate and washed with water. The organic layer was dried with EtOAc (EtOAc m. Yield: 61.93%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.48 (s, 1H), 7.45-7.41 (m, 3H), 7.32-7.24 (m, 3H), 7.02-6.99 (m, 3H) ), 6.88-6.84 (m, 1H), 5.13 (s, 2H), 5.04 (d, J = 6.6 Hz, 1H), 4.95-4.86 (m, 3H), 4.06-4.05 (m, 2H), 4.01- 3.94 (m, 2H), 3.85-3.77 (m, 3H), 3.50-3.42 (m, 2H), 2.07-2.09 (m, 1H), 1.79-1.75 (m, 2H), 1.50-1.46 (m, 2H) ), 1.32 (d, J = 6.9 Hz, 3H), 1.16 (t, J = 7.2 Hz, 3H); MS (m/z) 603.2 [M+ Na]. Example 90 2-((3-(4-((2H-Chloro-4-yl)methoxy)-[1,1'-biphenyl]- 3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propanoic acid (Compound 88)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 90 was obtained by hydrolysis of the compound of Example 89. ¹ H NMR (DMSO, 300 MHz): δ 12.46 (br s, 1H), 7.46 (d, J = 4.2 Hz, 3H), 7.37-7.29 (m, 4H), 7.13-7.12 (m, 1H), 7.06 -6.98 (m, 3H), 5.16 (s, 2H), 4.86-4.76 (m, 3H), 4.68 (d, J = 6.6 Hz, 1H), 3.90-3.85 (m, 4H), 3.70-3.67-4.05 (m, 1H), 3.35-3.27 (m, 2H), 1.97-1.96 (m, 1H), 1.68-1.64 (m, 2H), 1.36-1.29 (m, 2H), 1.13 (d, J = 6.9Hz , 3H); MS (m/z) 551.1 [M-2H]. Example 91 Ethyl 2-((3-(4-((2'-)-chloro-4'-((1,1-dioxo)-tetrahydrothiophen-3-yl)methoxy)-[1,1 '-Biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)propionate (Compound 89)

The title compound was prepared in a similar manner as Compound 87 of Example 89, which was taken to ethyl 2-((3-(4-((2'-chloro-4')-hydroxy-[1,1'-biphenyl]-3 -yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionate (258 mg, 0.534 mmol) with (1,1-dioxainyltetrahydrothiophen-3-yl) Reaction of methyl 4-methylbenzenesulfonate (commercial source, 170 mg, 0.559 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.49-7.47 (m, 3H), 7.45-7.41 (m, 1H), 7.34-7.31 (m, 3H), 7.03-7.00 (d, J = 10.2 Hz, (3, H) -3.95 (m, 2H), 3.83-3.78 (m, 1H), 3.38-3.26 (m, 2H), 3.20-3.17 (m, 1H), 3.14-3.07 (m, 2H), 3.03-2.97 (m, 1H), 2.47-2.46 (m, 1H), 2.23-2.15 (m, 1H), 1.34 (d, J = 6.6 Hz, 2H), 1.17 (t, J = 6.9 Hz, 3H); MS (m/z ) 638.2 [M+ Na]. Example 92 2-((3-(4-((2'-Chloro-4'-((1,1-dioxo)-tetrahydrothiophen-3-yl)methoxy)-[1,1'- Biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)propionic acid (compound 90)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 91 was obtained by hydrolysis of the compound of Example 91. ¹ H NMR (DMSO, 300 MHz): δ 12.53 (br s, 1H), 7.48 (d, J = 3.6 Hz, 3H), 7.38-7.30 (m, 4H), 7.18 (d, J = 2.4 Hz, 1H ), 7.08-7.01 (m, 3H), 5.18 (s, 2H), 4.86-4.77 (m, 3H), 4.71 (d, J = 6.9Hz, 1H), 4.13 (d, J = 6.0 Hz, 2H) , 3.72-3.70 (m, 1H), 3.23-3.17 (m, 2H), 3.14-3.10 (m, 1H), 2.92-2.84 (m, 2H), 2.35-2.29 (m, 1H), 1.99-1.92 ( m, 1H), 1.15 (d, J = 6.9 Hz, 3H); MS (m/z) 585.0 [MH]. Example 93 Ethyl 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl) Methoxy)phenyl)oxycyclobutan-3-yl)oxy)propionate (Compound 91)

The title compound was prepared in a similar manner as Compound 87 of Example 89, which was taken to ethyl 2-((3-(4-((2'-chloro-4')-hydroxy-[1,1'-biphenyl]-3 -yl)methoxy)phenyl)oxocyclobutan-3-yl)oxy)propionate (275 mg, 0.569 mmol) with 3-(methylsulfonyl)propyl 4-methylbenzenesulfonic acid Reaction of ester (commercial source, 174 mg, 0.595 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.49-7.47 (m, 1H), 7.45-7.42 (m, 2H), 7.33 (s, 2H), 7.30-7.28 (m, 2H), 7.03-7.00 ( m, 3H), 6.89-6.86 (m, 1H), 5.14(s, 2H), 5.05 (d, J = 6.9 Hz, 1H), 4.97-4.87 (m, 3H), 4.17 (t, J = 5.7 Hz , 2H), 4.02-3.95 (m, 2H), 3.83-3.81 (m, 1H), 3.29 (t, J = 7.2 Hz, 2H), 2.99 (s, 3H), 2.42-2.37 (m, 2H), 1.34 (d, J = 6.9 Hz, 3H), 1.17 (t, J = 7.2 Hz, 3H); MS (m/z) 603.1 [M+]. Example 94 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl) A Oxy)phenyl)oxycyclobutane-3-yl)oxy)propionic acid (compound 92)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 93 was obtained by hydrolysis of the compound of Example 93. ¹ H NMR (DMSO, 300 MHz): δ 12.05 (br s, 1H), 7.45 (d, J = 4.8 Hz, 3H), 7.35-7.30 (m, 4H), 7.14 (d, J = 2.4 Hz, 2H) , 7.05 (s, 2H), 7.02-6.98 (m, 1H), 5.73 (s, 3H), 5.15 (s, 3H), 4.84-4.75 (m, 3H), 4.68 (d, J = 6.6 Hz, 1H ), 4.13 (t, J = 6.3 Hz, 2H), 3.72-3.66 (m, 1H), 3.26-3.23 (m, 1H), 2.17-2.08 (m, 2H), 1.12 (d, J = 6.9 Hz, 3H); MS (m/z) 573.1 [MH]. Example 95 Ethyl 2-((3-(4-((2,1-dioxy)tetrahydro-2H-thiopyran-4-yl)methoxy)- [1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)propionate (Compound 93) Step 1:1, 1-dioxy ion Synthesis of tetrahydro-2H-thiopyran-4-yl)methyl 4-methylbenzenesulfonate

Add 4-toluenesulfonium chloride (52.2 g, 274 mmol) to 4-(hydroxymethyl)tetrahydro-2H-thiopyran-1,1-dioxide (compound of step 1, 30 g, 183 mmol) To the solution, triethylamine (76 ml, 548 mmol) and DMAP (2.232 g, 18.27 mmol) in DCM (300 ml) After the reaction was completed, the reaction mixture was diluted with DCM (300 ml) and washed twice with water (500 ml). The organic layer was dried over sodium sulfate and concentrated. The residue was dissolved in 10% ethyl acetate / petroleum ether (180 ml) and stirred for 2 h. The solid was filtered and washed with EtOAc EtOAc EtOAc EtOAc Yield: 99%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 7,80 (d, J = 8.1 Hz, 2H), 7.39 (d, J = 8.1 Hz, 2H), 3.91 (d, J = 6.0 Hz, 2H), 3.087-2.912 (m, 4H), 2.482 (s, 3H), 2.151 (d, J = 13.8 Hz, 2H), 2.022-1.794 (m, 3H); MS: (m/z) 341.1 (M+Na). Step 2: Ethyl 2-((3-(4-((2,1-dioxy)yltetrahydro-2H-thiopyran-4-yl)methoxy) Synthesis of -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionate

The title compound was prepared in a similar manner as Compound 87 of Example 89, which was taken to ethyl 2-((3-(4-((2'-chloro-4')-hydroxy-[1,1'-biphenyl]-3 -yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionate (95 mg, 0.196 mmol) with (1,1-dioxaionyltetrahydro-2H-thiopyran- Reaction of 4-yl)methyl 4-methylbenzenesulfonate (compound of Step 1, 65.77 mg, 0.206 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.62-7.56 (m, 3H), 7.49-7.45 (m, 1H), 7.33-7.30 (m, 3H), 7.03-7.00 (m, 3H), 6.89- 6.85 (m, 1H), 5.14 (s, 3H), 5.05 (d, J = 6.6 Hz, 1H), 4.97-4.91 (m, 3H), 4.15-4.10 (m, 1H), 4.02-3.95 (m, 2H), 3.92 (d, J = 4.8Hz, 2H), 3.85-3.78 (m, 1H), 3.19-3.07 (m, 3H), 2.31-2.30 (m, 1H), 2.08-2.06 (m, 3H) , 1.34 (d, J = 6.9 Hz, 3H), 1.17 (t, J = 6.9 Hz, 3H); MS (m/z) 630.2 [M+ H]. Example 96 2-((3-(4-((2,1-Dioxyindolyltetrahydro-2H-thiopyran-4-yl)methoxy)-[1 ,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)propionic acid (Compound 94)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 96 was obtained by hydrolysis of the compound of Example 96. ¹ H NMR (DMSO, 300 MHz): δ 12.51 (br, s, 1H) 7.47-7.46 (m, 3H), 7.38-7.32 (m, 4H), 7.17 (d, J = 2.4 Hz, 1H), 7.08 (s, 2H), 7.05-7.00 (m, 1H), 5.18 (s, 2H), 4.84-4.77 (m, 3H), 4.71 (d, J = 6.9 Hz, 1H), 3.98 (d, J = 5.7 Hz, 2H), 3.73-3.70 (m, 1H), 3.20-3.16 (m, 2H), 3.10-3.06 (m, 2H), 2.16-2.12 (m, 3H), 1.78-1.74 (m, 2H), 1.15 (d, J = 6.9 Hz, 3H); MS (m/z) 599.1 [MH]. Example 97 Ethyl 2-((3-(4-((4'-fluoro-2'-methyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxycyclobutane Alk-3-yl)oxy)acetate (compound 95)

Ethyl 2-((3-(4-(3-bromobenzyl)oxy)phenyl)oxycyclobutane in 1,4-dioxane (16 ml) and water (4 ml) 3-yl)oxy)acetate (compound prepared in a similar manner to the compound of Step 1 of Example 17) (1 g, 2.37 mmol), (4-fluoro-2-methylphenyl)boronic acid (0.731 The reaction mixture of g, 4.75 mmol) and K ₂ CO ₃ (0.984 g, 7.12 mmol) was vortexed for 5 min and then degassed under argon for 20 min. Tetrakis(triphenylphosphine)palladium(0) (0.128 g, 0.442 mmol) was added to the resulting solution, and the mixture was stirred at 80 ° C for 4 h. After the reaction was completed, the reaction mixture was diluted with ethyl acetate (30 ml) and water (25 ml) and filtered through celite® filter pad. The organic layer was dried over anhydrous sodium Yield: 72.0%; ¹ H NMR (CDCl ₃ , 300 MHz): δ ¹ H NMR (CDCl ₃ , 500 MHz): δ 1.26 (t, J = 7.0 Hz, 3H), 2.25 (s, 3H), 3.82 (s, 2H), 4.19 (q, J = 7.0 Hz, 2H), 4.88 (d, J = 7.0 Hz, 2H), 5.02 (d, J = 7.0 Hz, 2H), 5.147 (s, 2H), 6.91 -7.00 (m, 3H), 7.05 (d, J = 8.5 Hz, 2H), 7.20 (t, J = 8.0 Hz, 1H), 7.38-7.46 (m, 5H); MS: (m/z) 473.2 ( M+Na). Example 97a 2-((3-(4-((4'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- Calcium 3-yl)oxy)acetate (compound 95a)

The title compound was prepared via the general procedure for the preparation of the calcium salt as described in Method A, using Compound 95.

¹ H NMR (DMSOd ₆ , 300 MHz): δ 2.19 (s, 3H), 3.39 s, 2H), 4.65 (d, J = 6.5 Hz, 2H), 4.84 (d, J = 6.5 Hz, 2H), 5.16 (s, 2H), 7.04 (d, J = 8.5 Hz, 2H), 7.09 (d, J = 7.5 Hz, 2H), 7.16 (d, J = 9.5 Hz, 1H), 7.22 (t, J = 7.5 Hz , 1H), 7.28 (d, J = 5.5 Hz, 1H), 7.38 (s, 1H), 7.41-7.46 (m, 3H); MS: (m/z) 883.4 (M+H), 445 (M+ Na). Example 98 Ethyl 2-((3-(4-((3-(4-methylthiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy) Acid ester (compound 96)

The title compound was prepared in a similar manner as Compound 95 of Example 97, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (0.23 g, 0.55 mmol) with (4-methylthiophen-2-yl)boronic acid (commercial source, 0.16 g, 1.1 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 1.26 (t, J = 7.0 Hz, 3H), 2.31 (s, 3H), 3.84 (s, 2H), 4.19 (q, J = 7.0 Hz, 2H), 4.88 (d, J = 6.5 Hz, 2H), 5.02 (d, J = 6.5 Hz, 2H), 5.15 (s, 2H), 6.89 (s, 1H), 7.05 (d, J = 8.5 Hz, 2H), 7.16 (s, 1H), 7.35-7.43 (m, 4H), 7.57 (d, J = 7.5 Hz, 1H), 7.66 (s, 1H); MS (m/z) 461.3 (M+Na). Example 98a 2-((3-(4-((3-(4-methylthiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate) Compound 96a)

The title compound was prepared via the general procedure for the preparation of the calcium salt as described in Method A, using Compound 96. ¹ H NMR (DMSOd ₆ , 300 MHz): δ 2.23 (s, 3H), 3.39 (s, 2H), 4.66 (d, J = 6.5 Hz, 2H), 4.85 (d, J = 6.5 Hz, 2H), 5.15 (s, 2H), 7.05 (d, J = 8.0 Hz, 2H), 7.13 (s, 1H), 7.36-7.45 (m, 5H), 7.58 (d, J = 7.0 1H), 7.70 (s, 1H) Example 99 Ethyl 2-((3-(4-((3'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxy) Cyclobutane-3-yl)oxy)acetate (compound 97)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (400 mg, 0.949 mmol) and (3-fluoro-2-methylphenyl)boronic acid (commercial source, 220 mg, 1.429 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.49-7.44 (m, 2H), 7.39-7.36 (m, 3H), 7.30-7.29 (m, 1H) , 7.23-7.16 (m, 1H), 7.05-7.00 (m, 4H), 5.15 (s, 2H), 5.01 (d, J = 6.9 Hz, 2H), 4.87 (d, J = 6.9 Hz, 2H), 4.20 (m, 2H), 3.82 (s, 2H), 2.16 (d, J = 2.4, 3H), 1.24 (t, J = 7.2 Hz, 3H); MS (m/z) 473.1 [M+ Na]. Example 100 2-((3-(4-((3'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetic acid (compound 98)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 99 was obtained by hydrolysis of the compound of Example 99. ¹ H NMR (DMSO, 300 MHz): δ 12.62 (br s, 1H), 7.50-7.49 (m, 2H), 7.42 (s, 1H), 7.38 (d, J = 5.1 Hz, 2H), 7.32- 7.28 (m, 2H), 7.20-7.16 (m, 1H), 7.09 (d, J = 5.1 Hz, 3H), 5.20 (s, 2H), 4.81 (d, J = 4.2Hz, 2H), 4.75 (d, J = 4.2 Hz, 2H), 3.74 (s, 2H), 2.10 (s, 3H); MS (m/z) 445.4 [M+ Na]. Example 100a 2-((3-(4-((3'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane - Calcium 3-yl)oxy)acetate (compound 98a)

The title compound was prepared via the general procedure for the preparation of the calcium salt as described in Method A, using Compound 98. ¹ H NMR (DMSOd ₆ , 300 MHz): δ 2.50 (s, 3H), 3.35 (s, 2H), 4.64 (d, J = 6.0 Hz, 2H), 4.84 (d, J = 6.0 Hz, 2H), 5.17 (s, 2H), 7.03-7.07 (m, 3H), 7.17 (br s, 1H), 7.29 (br s, 2H), 7.42-7.47 (m, 5H); MS: (m/z) 445.1 ( M + Na). Example 101 Methyl 2-((3-(4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Alk-3-yl)oxy)acetate (compound 99)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (compound of Step 1 of Example 17, 150 mg, 0.368 mmol) with o-tolylboronic acid (75.04 mg, 0.552 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.46-7.38 (m, 4H), 7.36-7.33 (m, 2H), 7.27-7.10 (m, 4H), 7.05 (d, J = 8.7 Hz, 2H) , 5.15 (s, 2H), 5.02 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9 Hz 2H), 3.85 (s, 2H), 3.72 (s, 3H), 2.27 (s, 3H) ); MS (m/z): 441.2 [M+ Na]. Example 102 2-((3-(4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate (compound 100)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 101 was obtained by hydrolysis of the compound of Example 101. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.44-7.34 (m, 4H), 7.31-7.29 (m, 4H), 7.27-7.24 (m, 2H), 7.06 (d, J = 8.7 Hz, 2H) , 5.15 (s, 2H), 4.98-4.91 (m, 4H), 3.87 (s, 2H), 2.27 (s, 3H); MS (m/z): 405.2 [M+H]. Example 102a 2-((3-(4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Calcium acetate (compound 100a)

The title compound was prepared via the general procedure prepared according to the calcium salt as described in Method B, using Compound 100. Yield: 70%; ¹ H NMR (DMSOd ₆ , 300 MHz): δ 2.19 (s, 3H), 3.35 (s, 2H), 4.65 (d, J = 6.6 Hz, 2H), 4.84 (d, J = 6.6 Hz, 2H), 5.16 (s, 2H), 7.05 (d, J = 8.7 Hz, 2H), 7.17-7.29 (m, 5H), 7.40-7.46 (m, 5H); MS: (m/z) 403 [MH]. Example 103 Ethyl 2-((3-(4-((3'-chloro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Alk-3-yl)oxy)acetate (Compound 101)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (100 mg, 0.24 mmol) and (3-chloro-2-methylphenyl)boronic acid (commercial source, 62.5 mg, 0.36 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.50 (s, 2H), 7.40 (d, J = 8.7 Hz, 4H), 7.27 (s, 1H), 7.21-7.14 (m, 2H), 7.05 (d , J = 8.7 Hz, 2H), 5.15 (s, 2H), 5.03 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9 Hz, 2H), 4.14-4.21 (m, 2H), 3.83 (s, 2H), 2.27 (s, 3H), 1.27 (t, J = 7.2 Hz, 3H); MS (m/z): 489.2 [M+Na]. Example 104 2-((3-(4-((3'-Chloro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetic acid (compound 102)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 103 was obtained by hydrolysis of the compound of Example 103. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.45 -7.47 (m, 2H), 7.37-7.40 (m, 2H), 7.31 (s, 2H), 7.27 (s, 1H), 7.13-7.21 (m, 2H), 7.05 (d, J=8.4Hz, 2H), 5.14 (s, 2H), 4.91-4.99 (m, 4H), 3.88 (s, 3H), 2.88 (s, 3H); MS (m/z ) 437.1 [M-1]. Example 104a 2-((3-(4-((3'-Chloro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- Calcium 3-yl)oxy)acetate (compound 102a)

The title compound was prepared via the general procedure prepared according to the calcium salt as described in Method B, using Compound 102. ¹ H NMR (DMSOd ₆ , 300 MHz): δ 2.20 (s, 3H), 3.39 (s, 2H), 4.64 (d, J = 6.6 Hz, 2H), 4.84 (d, J = 6.6 Hz, 2H), 5.16 (s, 2H), 7.04 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 7.2 Hz, 1H), 7.28-7.30 (m, 3H), 7.39-7.48 (m, 5H); MS :(m/z) 437 [MH]. Example 105 Ethyl-2-((3-(4-((2,1-dioxy)yltetrahydro-2H-thiopyran-4-yl)methoxy) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound 103) Step 1: 4-(hydroxymethyl) Synthesis of tetrahydro-2H-thiopyran 1,1-dioxide

Add BH ₃ .DMS (27.8 ml, 293 mmol) to tetrahydro-2H-thiopyran-4-carboxylic acid 1,1-dioxide in DCM (450 ml) at 37 ° C for 50 min. (Commercial source, 43.5 g, 244 mmol) in a stirred solution and the reaction mixture was stirred at the same temperature for 2.5 h. Potassium fluoride (17.02 g, 293 mmol) in water (34 ml) was added over a 20 min period and the mixture was stirred at 37 ° C for 2 h. The organic layer was separated and the aqueous layer was washed with DCM. The organic layer was dried over sodium sulfate. The solvent was evaporated and the residue was crystalljjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjs The title compound (32.8 g, 200 mmol). Yield: 82%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 4.66 (t, J = 5.4 Hz, 1H), 3.28 (t, J = 5.4 Hz, 2H), 3.149-2.972 (m, 4H) , 2.01 (d, J = 12.9 Hz, 2H), 1.676-1.50 (m, 3H); MS: (m/z) 162.8 (MH), 187.1 (M+Na). Step 2: Ethyl 2-((3-(4-((2'-chloro-4'-hydroxy-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxycyclobutane Synthesis of alk-3-yl)oxy)acetate

Ethyl 2-((3-(4-(3-bromobenzyl)oxy)phenyl)oxy) in a solvent mixture of water (20 ml) and 1,4-dioxane (50 ml) Cyclobutane-3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (5 g, 11.87 mmol), (2-chloro-4-hydroxyphenyl) A mixture of boric acid (4.09 g, 23.74 mmol) and K ₂ CO ₃ (4.10 g, 29.7 mmol) was spun for 10 minutes at room temperature and degassed for 40 minutes in an argon balloon atmosphere. Tetrakis(triphenylphosphine)palladium(0) (2.74 g, 2.374 mmol) was added and the air was again blown with argon for 20 minutes. The reaction mixture was heated at 80 °C for 3 h. After the reaction was completed, the reaction mixture was filtered and evaporated from ethyl acetate (200 ml). The organic layer was washed with EtOAc EtOAc m. Yield: 91%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.52 (s, 1H), 7.49-7.41 (m, 3H), 7.39 (d, J = 8.7 Hz, 2H), 7.24 (d, J = 8.4 Hz, 1H), 7.06 (d, J = 8.7 Hz, 2H), 7.00 (d, J = 2.7 Hz, 1H), 6.84 (dd, J = 8.4 Hz, 1H), 5.14 (s, 2H) , 5.03 (d, J = 6.9 Hz, 2H), 4.90 (d, J = 6.9 Hz, 2H), 4.22 (q, J = 6.9 Hz, 2H), 3.83 (s, 2H), 1.28 (t, J = 6.9 Hz, 3H); MS: (m/z) 491.1 (M+Na). Step 3: Ethyl-2-((3-(4-((2'-chloro-4'-((1,1-dioxy)tetrahydro-2H-thiopyran-4-yl)methoxy) Synthesis of -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate

Ethyl 2-((3-(4-((2'-chloro-4'-hydroxy-[1,1'-biphenyl)-3-yl)methoxy)benzene in DMF (15 ml) Oxycyclobutane-3-yl)oxy)acetate (compound of step 3, 1.5 g, 3.20 mmol), (1,1-dioxyindolyltetrahydro-2H-thiopyran-4-yl) A mixture of methyl 4-methylbenzenesulfonate (Compound of Example 95 Step 1, 1.069 g, 3.36 mmol) and Cs ₂ CO ₃ (1.56 g, 4.80 mmol) was heated at 85 ° C for 1.5 h. After the reaction was completed, the reaction mixture was filtered thru EtOAc (EtOAc) pad. The filtrate was concentrated and dried with EtOAc EtOAc EtOAcjjjjjjjjjjj Yield: 85%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.492-7.453 (m, 3H), 7.396-7.367 (m, 3H), 7.305 (s, 1H), 7.058-7.017 (m, 3H) ), 6.899 (dd, J = 8.7 Hz, 1H), 5.147 (s, 2H), 5.026 (d, J = 6.9 Hz, 2H), 4.885 (d, J = 6.9 Hz, 2H), 4.217 (q, J = 6.9 Hz, 2H), 3.920 (d, J = 4.5 Hz, 2H), 3.834 (s, 2H), 3.192-3.030 (m, 4H), 2.339-2.303 (m, 2H), 2.080-2.063 (m, 3H), 1.280 (t, J = 6.9 Hz, 3H); MS (m/z) 616.3 (M+H), 614.4 (MH). Example 106 2-((3-(4-((2,1-Dioxy-4'-((1,1-dioxy)tetrahydro-2H-thiopyran-4-yl)methoxy)-[1 ,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (Compound 104)

A solution of NaOH (0.020 g, 0.512 mmol) in water (4 ml) was added to ethyl 2-((3-(4-(2)-chloro-4'-) in THF (10 ml) (1,1-dioxy-ionic tetrahydro-2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane To a solution of alkin-3-yl)oxy)acetate (Compound 103, 0.21 g, 0.341 mmol), followed by MeOH (2 mL). The reaction mixture was stirred for approximately 90 minutes. After the reaction was completed, the reaction mixture was concentrated, and the residue was suspended in water (10 ml), and the pH was acidified with 10% HCl. The residue was extracted with ethyl acetate and washed with water and brine. The organic layer was dried with EtOAc EtOAcjjjjjj Yield: 95%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 12.623 (s, 1H), 7.651-7.545 (m, 1H), 7.471-7.462 (m, 3H), 7.390-7.317 (m, 3H ), 7.166 (d, J = 2.4 Hz, 1H), 7.095 (d, J = 8.7 Hz, 2H), 7.039 (dd, J = 8.4 Hz, 1H), 5.188 (s, 2H), 4.819 (d, J = 8.7 Hz, 2H), 4.756 (d, J = 8.7 Hz, 2H), 3.984 (d, J = 6.0 Hz, 2H), 3.744 (s, 2H), 3.242-3.061 (m, 4H), 2.166-2.124 (m, 3H), 1.828-1.747 (m, 2H), MS (m/z) 637.4 (M+Na), 616.3 (M+H), 614.2 (MH). Example 106a 2-((3-(4) -((2'-chloro-4'-((1,1-dioxy)tetrahydro-2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl]-3- Calcium (meth)phenyl)oxycyclobutan-3-yl)oxy)acetate (compound 104a)

The title compound was prepared via the general procedure prepared according to the calcium salt as described in Method B, using Compound 104. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 7.458-7.410 (m, 5H), 7.331-7.302 (m, 2H), 7.159 (d, J = 2.1 Hz, 1H), 7.055-7.001 (m, 3H), 5.159 (s, 2H), 4.852 (d, J = 6.6 Hz, 2H), 4.659 (d, J = 6.6 Hz, 2H), 3.974 (d, J = 5.7 Hz, 2H), 3.392 (s, 2H), 3.243-3.055 (m, 4H), 2.160-2.118 (m, 3H), 1.823-1.742 (m, 2H); MS: (m/z) MH 585, M+Na 609.2. Example 107 Ethyl 2-((3-(4-(3-(3,5-dimethylisoxazol-4-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl) )oxy)acetate (compound 105)

Ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane) in a solvent mixture of dioxane (8 mL) and water (2 mL) 3-yl)oxy)acetate (compound prepared in a similar manner to the compound of Step 1 of Example 17) (0.250 g, 0.593 mmol), (3,5-dimethylisoxazole-4-yl) The reaction mixture of boric acid (commercial source, 0.100 g, 0.712 mmol) and sodium bicarbonate (0.100 g, 1.187 mmol) was degassed with argon gas for 20 minutes. Tetrakis(triphenylphosphine)palladium(0) (0.017 g, 0.059 mmol) was added and the reaction mixture was again degassed for 5 min. The reaction mixture was heated at 80 °C for 3 h. After the reaction was completed, the solvent was removed and the residue was extracted ethyl acetate. The organic layer was washed with EtOAc EtOAc m. Yield: 17.33%; ¹ H NMR (300 MHz, CDCl ₃ ): δ 7.51 (s, 1H), 7.49 (d, J = 7.5 Hz, 1H), 7.49 (d, J = 8.7 Hz, 2H), 7.32 (s, 1H), 7.27 (m, 1H), 7.04 (d, J = 8.7 Hz, 2H), 5.14 (s, 2H), 5.02 (d, J = 6.9 Hz, 2H), 4.87 (d, J = 6.9 Hz, 2H), 4.21 (q, J = 7.2 Hz, 2H), 3.82 (s, 2H), 2.40 (s, 3H), 2.27 (s, 3H), 1.27 (t, J = 7.2 Hz, 3H) ;MS: (m/z) (ESI) 460.9 [M+Na]. Example 107a 2-((3-(4-(3-(3,5-Dimethylisoxazol-4-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy Calcium acetate (compound 105a)

The title compound was prepared via the general procedure prepared according to the calcium salt as described in Method A, using Compound 105. ¹ H NMR (300 MHz, CDCl ₃ ): δ 7.49-7.40 (m, 5H), 7.35 (d, J = 6.9 Hz, 1H), 7.06 (d, J = 8.4 Hz, 2H), 5.18 (s, 2H) ), 4.85 (d, J = 6.6 Hz, 2H), 4.65 (d, J = 6.6 Hz, 2H), 3.35 (s, 2H), 2.37 (s, 3H), 2.19 (s, 3H); MS: ( m/z) 857.3 [M+H]. Example 108 Ethyl 2-((3-(4-((3-(5-(hydroxymethyl))thiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy Acetate (Compound 106) Step 1: Ethyl 2-((3-(4-((3-(4,4,5,5-tetramethyl-1,3,2-dioxaboron) Synthesis of cyclo-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate

The title compound was prepared in a similar manner as the compound of Step 1 of Example 51. Substitution with ethyl 2-((3-(4-(3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate was carried out via the procedure described in Example 17 Methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate was obtained. Step 2: Ethyl 2-((3-(4-((3-(5-(hydroxymethyl))thiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl) Synthesis of oxy)acetate

Ethyl 2-((3-(4-(4-(4,4,5,5-tetramethyl-1,3,2-)) in DMF (2 ml) and water (0.2 ml) Oxoborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (0.2 gm, 0.427 mmol), (5-bromothiophen-2-yl) A solution or suspension of methanol (0.1 g, 0.518 mmol) and NaHCO ₃ (0.108 g, 1.286 mmol) was degassed by ultrasonic vibration in an argon balloon atmosphere. Tetrakis (triphenylphosphine) palladium (0) (0.048 gm, 0.042 mmol) and the mixture was stirred at 100 ^o C 15 h. After the reaction was completed, the reaction mixture was taken up in ice and extracted with ethyl acetate. The organic layer was washed with EtOAc (EtOAc m. Yield: 26%; ¹ H NMR (300 MHz, CDCl ₃ ): δ 7.68 (m, 2H), 7.49 (m, 2H), 7.39 (d, J = 7.4 Hz, 2H), 7.20 (d, J = 3.3 Hz, 1H), 7.05 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 3.3 Hz, 1H), 5.11 (s, 2H), 5.01 (d, J = 6.9, Hz, 2H), 4.87 (m, 4H), 4.20 (q, J = 6.9 Hz, 2H), 3.82 (s, 2H), 1.26 (t, J = 6.9 Hz, 3H); MS: (m/z) 477.3 (M+Na ). Example 108a 2-((3-(4-((3-(5-(hydroxymethyl))thiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy) Calcium acetate (compound 106a)

Was prepared via the preparation of a calcium salt according to the general procedure as described in Method A of the title compound, using Compound ^{106. 1 H NMR (300 MHz,} CDCl 3): δ 7.67 (s, 1H), 7.60 (d, J = 7.2 Hz, 1H), 7.45 (m, 5H), 7.07 (d, J = 8.7 Hz, 2H), 6.96 (s, 1H), 5.70 (s, 2H), 5.17 (s, 2H), 4.85 (d, J = 6.6 Hz, 2H), 4.66 (m, 4H); MS: (m/z) 891.3 [M+H]. Example 109 Ethyl 2-((3-(4-(4-(4-(hydroxymethyl)thiazol-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy Acetate (Compound 107) Step 1: Ethyl 2-((3-(4-((3-(4,4,5,5-tetramethyl-1,3,2-dioxaboron) Synthesis of cyclo-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate

The title compound was prepared in a similar manner as the compound of Step 1 of Example 51. Substitution with ethyl 2-((3-(4-(3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate was carried out as described in Example 17 The procedure for obtaining methyl 2-((3-(4-(3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate. Step 2: Ethyl 2-((3-(4-(4-(4-(hydroxymethyl)thiazol-2-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl) Synthesis of oxy)acetate

Ethyl 2-((3-(4-((3-(4)4,5,5-tetramethyl-1) in a solvent mixture of dioxane (20 ml) and water (5 ml) 3,2-dioxaborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound of step 1, 10.25 g, 0.534 mmol) a solution of (2-bromothiazol-4-yl)methanol (commercial source, 0.104 g, 0.534 mmol) and K ₂ CO ₃ (0.148 g, 1.068 mmol) was spun for 30 minutes with an ultrasonic wave and was taken off under argon. Gas for 20 minutes. Tetrakis(triphenylphosphine)palladium(0) (10.79 mg, 0.037 mmol) was added and the reaction mixture was again degassed for 20 min. The reaction mixture was heated to 80 °C for 5 h. After the reaction was completed, the reaction mixture was diluted with ethyl acetate and water. The organic layer was washed with EtOAc EtOAc m. Yield: 22.62%. Example 109a 2-((3-(4-((3-(4-(hydroxymethyl)thiazol-2-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy) Calcium acetate (compound 107a)

The title compound was prepared via the general procedure as described for the calcium salt as described in Method A, using Compound 107. ¹ H NMR (300 MHz, CDCl ₃ ): δ 8.02 (s, 1H), 7.88 (d, J = 7.2 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.48 (s, 1H), 7.44 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7Hz, 2H), 5.46 (br s, 1H), 5.21 (s, 2H), 4.83 (d, J = 6.9 Hz, 2H) , 4.64 (d, J = 6.9 Hz, 2H), 4.62 (s, 2H), 3.24 (s, 2H); MS (m/z) 893.3 [M+H]. Example 110 Ethyl 2-((3-(4-((4-(hydroxymethyl))oxycyclobutane-3-yl)methoxy)-2'-(trifluoromethyl) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound 108) Step 1: 3-((4- Synthesis of bromo-3-(trifluoromethyl)phenoxy)methyl)oxocyclobutane-3-yl)methanol

4-Bromo-3-(trifluoromethyl)phenol (commercial source, 0.2 g, 0.83 mmol), (3-(bromomethyl)oxycyclobutane-3-yl)methanol (commercial source, 0.18 g, A mixture of 0.994 mmol) and potassium carbonate (0.115 g, 0.994 mmol) was stirred in anhydrous acetonitrile (4 ml) at 80 ° C for 4 h. The reaction mixture was diluted with EtOAc (20 mL). The solid was filtered and washed with EtOAc. The filtrate was concentrated and purified to a semi-solid (0.27 g) by flash column chromatography. Yield: 95%; ¹ H NMR (300 MHz, CDCl ₃ ) δ (ppm): 7.63 (d, J = 5.1 Hz, 1H), 7.29 (s, 1H), 7.0 (dd, J = 5.4 Hz, 1H ), 4.620 (m, 4H), 4.274 (s, 2H), 4.065 (d, J = 2.7 Hz, 2H); MS: m/z 341.2 [M+], 340.7 [MH]. Step 2: Ethyl 2-((3-(4-((4)-((3-(hydroxymethyl)oxycyclobutane-3-yl)methoxy)-2'-(trifluoromethyl) Synthesis of -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate

Ethyl 2-((3-(4-((3-(4,4,5,5,5-tetramethyl-1,3,3,5,5,5,5,5,5,5,5,5 2-Dioxaborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Example 109 Step 1 compound, 0.162 g, 0.346 mmol) (3-((4-bromo-3-(trifluoromethyl)phenoxy)methyl)oxycyclobutan-3-yl)methanol (compound of step 1, 0.13 g, 0.381 mmol) with K ₂ the reaction CO ₃ (0.144 g, 1.039 mmol) the mixture was shaken for 5 minutes to ultrasound and degassed with argon for 20 min. Tetrakis(triphenylphosphine)palladium(0) (10.01 mg, 0.035 mmol) was added and the mixture was heated at 80 °C for 2 h. After the reaction was completed, the reaction mixture was diluted with ethyl acetate and water and filtered thru EtOAc. The organic layer was separated, washed with EtOAc EtOAc m. Yield: 11%; ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.47 (m, 2H), 7.38 (m, 4H), 7.32 (m, 2H), 7.15 (d, J = 8 Hz, 1H), 7.04 (d, J = 8.5 Hz, 2H), 5.06 (s, 2H), 5.02 (d, J = 6.5Hz, 2H), 4.88 (d, J = 6.5Hz, 2H), 4.65 (q, 6.5Hz, 4H), 4.34 (s, 2H), 4.20 (q, J = 7Hz, 2H), 4.10 (s, 2H), 3.72 (s, 2H), 1.39 (t, J = 7Hz, 3H). Example 110a 2- ((3-(4-((4'-((3-(Hydroxymethyl)oxycyclobutane-3-yl)methoxy)-2'-(trifluoromethyl)-[1,1' -biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid calcium (compound 108a)

The title compound was prepared via the general procedure prepared according to the calcium salt as described in Method A, using Compound 108. ¹ H NMR (500 MHz, CDCl ₃ ): δ 7.48 (m, 2H), 7.42 (d, J = 8 Hz, 2H), 7.35 (d, J = 12 Hz, 4H), 7.25 (d, 1H), 7.04 (D, J = 8.5 Hz, 2H), 5.17 (s, 2H), 5.11 (t, 2H), 4.84 (d, J = 6.5 Hz, 2H), 4.63 (d, J = 6.5 Hz, 2H), 4.46 (d, J = 6Hz, 2H), 4.42 (d, J=6Hz, 2H), 4.27 (s, 2H), 3.74 (d, J = 4.5 Hz, 2H). Example 111 Ethyl 2-((3-(4-((2',6'-bis(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate (compound 109)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (100 mg, 0.24 mmol) and (2,6-bis(trifluoromethyl)phenyl)boronic acid (commercial source) , 25 mg, 0.36 mmol) of the reaction.

¹ H NMR (CDCl ₃ , 300 MHz): d 8.03 (s, 1H), 7.87 (d, J = 8.7 Hz, 1H), 7.32-7.52 (m, 7H) 7.04 (d, J = 8.7 Hz, 2H) , 5.15 (s, 2H), 5.03 (d, J = 7.2 Hz, 2H), 4.89 (d, J = 7.2Hz, 2H), 4.14-4.21 (m, 2H), 3.83 (s, 2H), 1.27 ( t, J = 7.2 Hz, 3H); MS: (m/z) 577.2 [M+Na] Example 112 2-((3-(4-((2',6'-bis(trifluoromethyl))- [1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (Compound 110)

Adding LiOH (27.2 mg, 0.64 mmol) to ethyl 2-((3-(4-((2',6'-bis(trifluoromethyl))-[1] in THF:MeOH (1:4) , a stirred solution of 1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound 109, 70 mg, 0.12 mmol), and The reaction mixture was stirred at RT for 3 h. The solvent was removed, the reaction mixture was acidified with saturated NH ₄ Cl solution (pH 6-6.5), and extracted with ethyl acetate. The organic layer was washed with EtOAc EtOAc m. Yield: 58.7 %; ¹ H NMR (CDCl ₃ , 300 MHz): d 8.02 (s, 1H), 7.87 (d, J = 7.8 Hz, 1H), 7.46-7.53 (m, 3H), 7.40 (s, 1H), 7.31-7.34 (m, 3H) , 7.07 (d, J=8.7 Hz, 2H), 5.16 (s, 2H), 4.91-4.99 (m, 4H), 3.87 (s, 2H); MS: ( m/z) 525.2 [M-1]. Example 112a 2-((3-(4-((2',6'-bis(trifluoromethyl)-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxycarbonyl Butane-3-yl)oxy)acetic acid calcium (compound 110a)

The title compound was prepared via the general procedure prepared according to the calcium salt as described in Method B, using Compound 110. ¹ H NMR (300 MHz, CDCl ₃ ): δ 8.13 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 7.8 Hz, 1H), 7.57 (m, 2H), 7.43 (d, J = 8.7 Hz, 2H), 7.33 (d, J = 7.2, Hz, 2H), 7.05 (d, J = 8.7Hz, 2H), 5.16 (s, 2H), 4.85 (d, J = 6.9Hz, 2H), 4.66 (d, J = 6.9 Hz, 2H), 3.41 (s, 2H); MS: (m/z) 549.1 [M+Na]. Example 113 Ethyl 2-((3-(4-((4'-cyano-2'-methyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxyl) Butan-3-yl)oxy)acetate (Compound 111) Step 1: Synthesis of 4-cyano-2-methylphenyltrifluoromethanesulfonate

Add aniline triflate (1.44 g, 4.03 mmol) to 4-hydroxy-3-methylbenzonitrile (commercial source, 0.45 g, 3.38 mmol) and triethylamine in anhydrous DCM (8 mL) (0.708 ml, 5.08 mmol) was stirred in a solution and the mixture was stirred overnight at RT. The reaction mixture was diluted with EtOAc EtOAc m. Yield: 48%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.655 (s, 1H), 7.62 (d, J = 8.7 Hz, 1H), 7.408 (d, J = 8.7 Hz, 1H), 2.445 (s, 3H); MS: (m/z) 265.9 (M+H). Step 2: Ethyl 2-((3-(4-((4')-cyano-2'-methyl-[1 Synthesis of 1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate

The title compound was prepared in a similar manner as Compound 107 of Example 109, which was taken to ethyl 2-((3-(4-((3)))) Dioxaborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (0.44 g, 0.943 mmol) with 4-cyano-2-yl Reaction of phenyltrifluoromethanesulfonate (compound of Step 1, 0.30 g, 1.13 mmol). Yield: 37%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.57-7.48 (m, 5H), 7.40-7.32 (m, 4H), 7.04 (d, J = 8.7 Hz, 2H), 5.14 ( s, J = 6.9 Hz, 2 H), 4.87 (d, J = 6.9 Hz, 2H), 4.21 (q, J = 7.3 Hz, 2H), 3.83 (s, 2H), 2.28 (s, 3H), 1.94 (s, 2H), 1.27 (t, J = 7.3 Hz, 3H); MS: (m/z) 480.1 [M+Na]. Example 113a 2-((3-(4-((4'-Cyano-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Calcium-3-yl)oxy)acetate (compound 111a)

The title compound was prepared via the general procedure for the preparation of the calcium salt as described in Method A, using Compound 111. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 7.80 (m, 2H), 7.495-7.334 (m, J = 7.5 Hz, 7H), 7.052 (d, J = 7.8 Hz, 2H), 5.17 (s , 2H), 4.84 (m, J = 6.3 Hz, 2H), 4.65 (m, J = 6 Hz, 2H), 2.23 (s, 2H), 2.18 (s, 3H). Example 114 Ethyl 2-(( 3-(4-((3-(5-(hydroxymethyl))-3-methylthiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy) Acid ester (compound 112)

The title compound was prepared in a similar manner as Compound 108 of Example 110, which was taken to ethyl 2-((3-(4-((3-(4,4,5,5,4-tetramethyl-1,3,2-) Oxoborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound of Example 1 of Example 109, 0.44 g, 0.943 mmol) Reaction of 5-bromo-4-methylthiophen-2-yl)methanol (commercial source, 0.290 g, 1.4 mmol). Yield: 53%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.95 (s, 1H), 7.65 (m, J = 18.6 Hz, 1H), 7.45-7.357 (m, J = 28 Hz, 6H) , 7.09 (d, J = 8.4 Hz, 1H), 6.8 (s, 1H), 5.48 (t, J = 11.4 Hz, 1H), 5.2 (s, 2H), 4.82-4.75 (m, J = 19.8 Hz, 4H), 4.59 (d, J = 5.4 Hz, 2H), 4.06-3.997 (m, J = 21.3 Hz, 2H), 3.8 (s, 1H), 2.3 (s, 3H), 1.17 (t, J = 20.7 Hz, 3H); MS: (m/z) 491.5 [M+Na]. Example 114a 2-((3-(4-((3-(5-(hydroxymethyl))-3-methylthiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3- Calcium acetate (compound 112a)

The title compound was prepared via the general procedure prepared according to the calcium salt as described in Method A, using Compound 112. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 7.48 (s, 2H), 7.43-7.413 (m, J = 7.8 Hz, 4H), 7.06 (d, J = 8 Hz, 2H), 6.88 (s , 1H), 5.56 (brs, 2H), 5.18 (s, 2H), 4.84 (d, J = 6.3 Hz, 2H), 4.66 (d, J = 6 Hz, 2H), 4.57 (s, 2H), 2.2 (s, 3H); MS: (m/z) 463.2 [M+Na] (mass of the parent acid). Example 115 Ethyl 2-((3-(4-(3-(5-methylthiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy) Acid ester (compound 113)

Ethyl 2-((3-(4-(3-bromobenzyl)oxy)phenyl)oxy) in a solvent mixture of 1,4-dioxane (20 ml) and water (5 ml) Cyclobutane-3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (1.11 g, 2.64 mmol), (5-methylthiophen-2-yl) A reaction mixture of boric acid (commercial source, 0.75 g, 5.28 mmol) and K ₂ CO ₃ (0.913 g, 6.6 mmol) was spun in an ultrasonic wave and degassed using an argon balloon for 20 minutes. Tetrakis(triphenylphosphine)palladium(0) (0.076 g, 0.264 mmol) was added and the reaction mixture was again degassed for 20 min. The reaction mixture was heated at 80 °C for 3 h. After the reaction was completed, the reaction mixture was diluted with ethyl acetate (50 ml) and water (20 ml) and filtered through celite® filter pad. The organic layer was washed with water, brine, dried over sodium sulfate, evaporated and evaporated. Example 115a 2-((3-(4-((3-(5-methylthiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate) Compound 113a)

The title compound was prepared via the general procedure for the preparation of the calcium salt as described in Method A, using Compound 113. ¹ H NMR (DMSOd ₆ , 300 MHz): δ 7.64 (s, 1H), 7.54 (d, J = 7.2 Hz, 1H), 7.44-7.31 (m, 5H), 7.06 (d, J = 7.8 Hz, 2H ), 6.82 (s, 1H), 5.13 (s, 2H), 4.85 (d, J = 6.3 Hz, 2H), 4.66 (d, J = 6 Hz, 2H), 3.38 (s, 2H), 2.49 (s , 3H); MS: (m/z) 859.4 (M+). Example 116 Ethyl 2-((3-(4-((2'-)difluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate (compound 114)

The title compound was prepared in a similar manner as Compound 107 of Example 109, which was taken to ethyl 2-((3-(4-((3-(4,4,5,5,4-tetramethyl-1,3,2-) Oxoborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (1 g, 2.13 mmol) with 1-bromo-2-(difluoro) Reaction of methyl)benzene (commercial source, 0.663 g, 3.2 mmol). Yield: 50%; ¹ H NMR (CDCl ₃ , 500 MHz): δ 7.81 (d, J = 7 Hz, 1H), 7.549-7.514 (m, J = 7 Hz, 4H), 7.45 (s, 1H) , 7.40 (d, J = 8.5 Hz, 2H), 7.37-7.359 (m, J = 5.5 Hz, 2H), 7.05 (d, J = 8.5 Hz, 2H), 6.521 (s, 1H), 5.16 (s, 2H), 5.02 (s, J = 6.5 Hz, 2H), 4.88 (s, J = 6.5 Hz, 2H), 4.19 (q, J = 7 Hz, 2H), 3.8 (s, 2H), 1.27 (t, J = 14 Hz, 3H); MS (m/z) 491.1 (M+Na). Example 116a 2-((3-(4-((2'-(Difluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)calcium acetate (compound 114a)

The title compound was prepared via the general procedure prepared according to the calcium salt as described in Method A, using Compound 114. ¹ H NMR (DMSO-d ₆ , 500 MHz): δ 7.75 (d, J = 7.5 Hz, 1H), 7.63 (s, 1H), 7.557 (s, 1H), 7.53 (d, J = 6.5 Hz, 2H ), 7.44-7.39 (m, 4H), 7.33 (d, J = 6.5 Hz, 1H), 7.06 (d, J = 8.5 Hz, 2H), 6.74 (s, 1H), 5.19 (s, 2H), 4.85 (d, J = 6.5 Hz, 2H), 4.66 (d, J = 6.5 Hz, 2H), 3.37 (s, 2H); MS (m/z) 439.1 (MH), 463.1 (M+Na). Example 117 Ethyl 2-((3-(4-((3-(3-methylthiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy) Acid ester (compound 115)

The title compound was prepared in a similar manner as Compound 113 of Example 115, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy Acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (100 mg, 0.24 mmol) and (2,6-bis(trifluoromethyl)phenyl)boronic acid (commercial source, 25 mg, 0.36 mmol) of the reaction.

Yield: 36%; ¹ H NMR (CDCl ₃ , 500 MHz): δ 7.54 (s, 1H), 7.46 (d, J = 4 Hz, 2H), 7.39 (d, J = 8.5 Hz, 3H), 7.24 (d, J = 5 Hz, 1H), 7.05 (d, J = 8.5 Hz, 2H), 6.95 (d, J = 5 Hz, 1H), 5.14 (s, 2H), 5.02 (s, J = 6.5 Hz , 2H), 4.88 (s, J = 7 Hz, 2H), 4.20 (q, J = 36 Hz, 2H), 3.83 (s, 2H), 2.33 (s, 3H), 1.27 (t, J = 14 Hz , 3H); MS (m/z) 461.1 (M+Na). Example 117a 2-((3-(4-((3-(3-methylthiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate) Compound 115a)

The title compound was prepared via the general procedure for the preparation of the calcium salt as described in Method A, using Compound 115. ¹ H NMR (DMSOd ₆ , 500 MHz): δ 7.53 (s, 1H), 7.48 (d, J = 6 Hz, 2H), 7.44 (d, J = 8.6 Hz, 4H), 7.06 (d, J = 8.5 Hz, 2H), 7.00 (d, J = 5 Hz, 1H), 5.19 (s, 2H), 4.85 (s, J = 6.5 Hz, 2H), 4.66 (s, J = 6.5 Hz, 2H), 3.33 ( s, 2H), 2.267 (s, 3H); MS: (m/z) M+Na 433. Example 118 Ethyl 2-((3-(4-((4'-(N,N-dimethylaminesulfonyl)-2'-methyl-[1,1'-biphenyl]-3- Methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate (Compound 116)

The title compound was prepared in a similar manner as Compound 107 of Example 109, which was taken to ethyl 2-((3-(4-((3-(4,4,5,5,4-tetramethyl-1,3,2-) Oxoborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (1 g, 2.13 mmol) with 4-bromo-N,N,3 - Reaction of trimethylbenzenesulfonamide (commercial source, 0.21 g, 0.755 mmol). Yield: 67.5%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.691-7.643 (m, 2H), 7.48 (s, 2H), 7.40-7.37 (d, J = 8.4 Hz, 4H), 7.271 ( s, 1H), 7.05 (d, J = 8.4 Hz, 2H), 5.15 (s, 2H), 5.02 (d, J = 6.9 Hz, 2H), 4.87 (d, J = 6.9 Hz, 2H), 4.21 ( q, J = 6.9 Hz, 2H), 3.83 (s, 2H), 2.77 (s, 6H), 2.33 (s, 3H), 1.27 (t, J = 6.9 Hz, 3H); MS: (m/z) 562.2 (M+Na). Example 118a 2-((3-(4-((4'-(N,N-dimethylaminesulfonyl)-2'-methyl-[1,1'-biphenyl]-3-yl) Calcium methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound 116a)

The title compound was prepared via the general procedure prepared according to the calcium salt as described in Method A, using Compound 116. ¹ H NMR (DMSOd ₆ , 300 MHz): δ 7.68 (s, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.51-7.40 (m, 6H), 7.36 (m, 1H), 7.06 (d , J = 8.4 Hz, 2H), 5.18 (s, 2H), 4.84 (d, J = 6.6 Hz, 2H), 4.65 (d, J = 6 Hz, 2H), 2.64 (s, 6H), 3.339 (s , 2H), 2.3 (s, 3H); MS: (m/z) 1060.4 (M+). Example 119 Ethyl 2-((3-(4-((2,1-dioxy-l-tetrahydro-2H-thiopyran-4-yl)oxy)-[ 1,1'-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound 117) Step 1:1, 1-dioxyl group Synthesis of tetrahydro-2H-thiopyran-4-yl 4-methylbenzenesulfonate

The title compound was prepared in a similar manner as the compound of Step 1 of Example 95, which was to react with 4-hydroxytetrahydro-2H-thiopyran 1,1-dioxide (commercial source) and 4-toluenesulfonium chloride. Step 2: Ethyl 2-((3-(4-((2,1-dioxy)yltetrahydro-2H-thiopyran-4-yl)oxy)- Synthesis of [1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate

The title compound was prepared in a similar manner to compound 105 as in Example 107, which was taken to ethyl 2-((3-(4-((2'))). -yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Example 105 Step 3 compound, 80 mg, 0.171 mmol) and 1,1-dioxy-ionic tetrahydrogen Reaction of -2H-thiopyran-4-yl 4-methylbenzenesulfonate (compound of Step 1, 51.9 mg, 0.171 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.48-7.46 (m, 3H), 7.40-7.37 (m, 3H), 7.33-7.30 (m, 1H), 7.08-7.06 (m, 1H), 7.03 ( s, 2H), 6.93-6.90 (m, 1H), 5.15 (s, 2H), 5.03 (d, J = 6.9 Hz, 2H), 4.88 (d, J = 6.9 Hz, 2H), 4.70-4.69 (m , 1H), 4.22-4.15 (m, 2H), 3.89 (s, 2H), 3.43-3.38 (m, 2H), 3.01-2.97 (m, 2H), 2.50-2.43 (m, 4H), 1.27 (t , J= Hz, 3H); MS: (m/z) 602.1 [M+H]. Example 120 2-((3-(4-((2,1-Dioxy-4'-((1,1-dioxy)tetrahydro-2H-thiopyran-4-yl)oxy)-[1, 1'-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (Compound 118)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 119 was obtained by hydrolysis of the compound of Example 119. ¹ H NMR (DMSO, 300 MHz): δ 12.62 (br s, 1H), 7.47 (d, J = 3.9 Hz, 3H), 7.39-7.34 (m, 4H), 7.30 (d, J = 2.4 Hz, 1H ), 7.13-7.06 (m, 3H), 5.18 (s, 2H), 4.81-4.79 (m, 3H), 4.75 (d, J = 6.9 Hz, 2H), 3.74 (s, 2H), 3.27 (m, 4H), 2.23-2.21 (m, 4H); MS (m/z): 572.1 [MH]. Example 121 Methyl 2-((3-(4-((4,1-dioxy)tetrahydro-2H-thiopyran-4-yl)methoxy)-2',6'-Dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound 119)

The title compound was prepared in a similar manner as Compound 87 of Example 89, which was taken to methyl 2-((3-(4-((4'-hydroxy-2',6'-dimethyl-[1,1'-) Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Example 51 Step 2 'Compound, 100 mg, 0.223 mmol) and (1,1 Reaction of 2-dioxyionic tetrahydro-2H-thiopyran-4-yl)methyl 4-methylbenzenesulfonate (Compound 95, Step 1 compound, 77.5 mg, 0.243 mmol). ¹ H NMR (CDCl3, 300 MHz): δ 7.48-7.42 (m, 2H), 7.39-7.34 (m, 2H), 7.19 (s, 1H), 7.11-7.09 (m, 1H), 7.03-7.00 (m , 2H), 6.65(s, 2H), 5.14 (s, 2H), 5.01 (d, J = 6.9 Hz, 2H), 4.87 (d, J = 6.9Hz, 2H), 3.90(d, J= 4.5Hz , 2H), 3.83(s, 2H), 3.72 (s, 3H), 3.19-3.06 (m, 4H), 2.31-2.19 (m, 2H), 2.06-2.05 (m, 3H), 2.00(s, 6H ); MS (m/z) 617.3 [M+ Na]. Example 122 2-((3-(4-((4)-((1,1-Dioxy)tetrahydro-2H-thiopyran-4-yl)methoxy)-2',6'-di Methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (Compound 120)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 121 was obtained by hydrolysis of the compound of Example 121. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.46-7.39 (m, 2H), 7.32-7.27 (m, 2H), 7.18 (s, 1H), 7.11-7.09 (m, 1H), 7.04 (d, J= 9.0, 2H), 6.65 (s, 2H), 5.15 (s, 2H), 4.98-4.90 (m, 4H), 3.90-3.87 (m, 2H), 3.85 (s, 2H), 3.19-3.14 ( m, 2H), 3.10- 3.06 (m, 2H), 2.30-2.19 (m, 3H), 2.11-2.06 (m, 2H), 1.99 (s, 6H); MS (m/z): 603.2 [M+ Na ]. Example 123 Methyl 2-((3-(4-((3-(2-fluoropyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid Ester (compound 121)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (Compound of Example 17 Step 1, 150 mg, 0.368 mmol) with (2-fluoropyridin-3-yl)boronic acid (commercial source, 77.78 mg, 0.552 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 8.24- 8.22 (m, 1H), 7.94-7.88 (m, 1H), 7.66 (s, 1H), 7.55 (s, 1H), 7.53-7.51 (m, 2H), 7.40 (d, J = 8.7 Hz, 2H), 7.33-7.31 (m, 1H), 7.06 (d, J = 8.7Hz, 2H), 5.16 (s, 2H), 5.02 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9Hz, 2H), 3.85 (s, 2H), 3.72(s, 3H); MS: (m/z) 446.1 [M+ Na]+. Example 124 2-((3-(4-(3-(2-Fluoropyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (Compound 122 )

The title compound was prepared in a similar manner as Compound 84 of Example 86. Compounds of Example 123 were obtained by hydrolysis of the compound of Example 124. ¹ H NMR (CDCl ₃ , 300 MHz): δ 8.24-8.22 (m, 1H), 7.94-7.88 (m, 1H), 7.65 (s, 1H), 7.55-7.51 (m, 3H), 7.36-7.32 ( m, 2H), 7.30-7.29 (m, 1H), 7.07 (d, J = 8.7 Hz, 2H). 5.17 (s, 2H), 4.99-4.91 (m, 4H), 3.88 (s, 2H); MS: (m/z) 410.2 [M+H]. Example 125 Methyl 2-((3-(4-((2'-chloro-4'-(isopentyloxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate (compound 123)

The title compound was prepared in a similar manner as Compound 87 of Example 89, which was taken to methyl 2-((3-(4-((2'))) -yl)methoxy)phenyl)oxocyclobutan-3-yl)oxy)acetate (Example 41 Step 1, Compound, 50 mg, 0.110 mmol) and isoamyl 4-methylbenzenesulfonic acid Reaction of ester (commercial source, 26.6 mg, 0.11 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.50 (s, 1H), 7.46-7.44 (m, 3H), 7.38-7.35 (m, 2H), 7.28-7.25 (m, 1H), 7.06- 7.03 ( m, 3H), 6.90- 6.86 (m, 1H), 5.14 (s, 2H), 5.02 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9Hz, 2H), 4.03 (t, J = 6.6Hz, 2H), 3.85 (s, 2H), 3.72 (s, 3H), 1.89-1.82 (m, 1H), 1.74-1.68 (m, 2H), 1.00 (d, J = 6.6 Hz, 6H) ;MS: (m/z) 547.3 [M+ Na]. Example 126 2-((3-(4-((2'-chloro-4'-(isopentyloxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxy Cyclobutane-3-yl)oxy)acetic acid (compound 124)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 125 was obtained by hydrolysis of the compound of Example 125. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.50 (s, 1H), 7.47-7.40 (m, 2H), 7.33 (s, 2H), 7.30 (s, 1H), 7.25 (s, 1H), 7.06 (s, 2H), 7.04-7.03 (m, 1H), 6.89-6.86 (m, 1H), 5.15 (s, 2H), 4.98-4.91 (m, 4H), 4.02 (t, J = 6.6 Hz, 2H ), 3.87 (s, 2H), 1.91-1.80 (m, 1H), 1.74- 1.67 (m, 2H), 1.00 (d, J = 6.6 Hz, 6H); MS (m/z) 533.2 [M+ Na] . Example 127 methyl 2-((3-(4-((2'-chloro-3'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Alk-3-yl)oxy)acetate (compound 125)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (Compound of Example 17 Step 1, 250 mg, 0.614 mmol) with (2-chloro-3-methylphenyl)boronic acid (commercial source, 157 mg, 0.921 mmol). ¹ H NMR (CDCl3, 300 MHz): δ 7.50-7.46 (m, 3H), 7.43-7.42 (m, 1H), 7.41-7.35 (m, 2H), 7.26-7.25 (m, 1H), 7.22- 7.17 (m, 2H), 7.06-7.03 (m, 2H), 5.15 (s, 2H), 5.02 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9 Hz, 2H), 3.85 (s, 2H), 3.72 (s, 3H), 2.47 (s, 3H); MS (m/z) 475.1 [M+ Na]. Example 128 2-((3-(4-((2'-Chloro-3'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetic acid (compound 126)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 128 was obtained by hydrolysis of the compound of Example 127. ¹ H NMR (DMSO, 300 MHz): δ 12.62 ( br, s, 1H), 7.49-7.47 (m, 3H), 7.39-7.36 (m, 4H), 7.34-7.28 (m, 1H), 7.22-7.20 (m, 1H), 7.09-7.06 (m, 2H), 5.19 (s, 2H), 4.81-4.73 (m, 4H), 3.74 (s, 2H), 2.40 (s, 3H); MS (m/z ): 437 [M- H]. Example 129

Methyl 2-((3-(4-((3'-chloro-2'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate (compound 127)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (Compound of Example 17 Step 1, 250 mg, 0.614 mmol) with (3-chloro-2-methoxyphenyl)boronic acid (commercial source, 685 mg, 3.68 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.66 (s, 1H), 7.55-7.51 (m, 1H), 7.48-7.47 (m, 2H), 7.42-7.41 (m, 1H), 7.39-7.36 ( m, 2H), 7.27- 7.26 (m, 1H), 7.16-7.10 (m, 1H), 7.06- 7.03 (m, 2H), 5.15 (s, 2H), 5.02 (d, J = 7.2Hz, 2H) , 4.88 (d, J = 6.9Hz, 2H), 3.85 (s, 2H), 3.72 (s, 3H), 3.51 (s, 3H); MS (m/z) 491.1 [M+ Na]+. Example 130 2 -((3-(4-((3'-Chloro-2'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3- Alkyloxyacetic acid (compound 128)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 130 was obtained by hydrolysis of the compound of Example 129. ¹ H NMR (DMSO, 300 MHz): δ 12.65 (br s, 1H), 7.62 (s, 1H), 7.52-7.49 (m, 4H), 7.39-7.33 (m, 3H), 7.26-7.21 (m, 1H), 7.10-7.07 (m, 2H), 5.20 (s, 2H), 4.81 (d, J = 7.2 Hz, 2H), 4.75 (d, J = 6.9 Hz, 2H), 3.73 (s, 2H), 3.41 (s, 3H); MS (m/z) 453 [MH]. Example 131 Ethyl 2-((3-(4-((2'-chloro-4'-methoxy-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxycarbonyl) Butan-3-yl)oxy)acetate (compound 129)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (100 mg, 0.24 mmol) and 4-methoxy-2-chlorophenyl)boronic acid (commercial source, 63.3 mg, 0.34 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.36-7.50 (m, 6H), 7.27-7.30 (m, 1H), 7.03-7.06 (m, 3H), 6.87-6.91 (m, 1H), 5.15 ( s, 2H), 5.02 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9Hz, 2H), 4.14-4.21 (m, 2H), 3.86 (s, 5H), 1.28(t, J = 6.9 Hz 3H). MS: (m/z) 505.2 [M+Na]. Example 132 2-((3-(4-((2'-Chloro-4'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid (compound 130)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 131 was obtained by hydrolysis of the compound of Example 131. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.34-7.40 (m, 3H), 7.27-7.29 (m, 4H), 6.90 (d, J = 2.4 Hz, 3H), 6.87-6.88 (m, 1H) , 5.15 (s, 2H), 4.91-4.99 (m, 4H), 3.88 (s, 5H); MS: m/z 454.9 [M-1]. Example 132a 2-((3-(4-((2'-Chloro-4'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Calcium-3-yl)oxy)acetate (compound 130a)

The title compound was prepared via the general procedure prepared according to the calcium salt as described in Method B, using Compound 22. ¹ H NMR (DMSO-d ₆ 300 MHz): δ 7.46-7.44 (m, 4H), 7.409 (s, 1H), 7.365-7.349 (m, 1H), 7.336 (d, J = 8.7 Hz, 1H), 7.140 (d, J = 2.4 Hz, 1H), 7.074 (d, J = 15 Hz, 2H), 6.992 (d, J = 2.7 Hz, 1H), 5.154 (s, 2H), 4.851 (d, J = 6.9 Hz, 2H), 4.657 (d, J = 6.9 Hz, 2H), 3.808 (s, 3H), 3.401 (s, 2H); MS (m/z) 477.1 [M+Na] (mass of parent acid). Example 133 methyl 2-((3-(4-((2'))-dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate (compound 131)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (compound of Example 17 Step 1, 100 mg, 0. 246 mmol) with (2,6-xylene)boronic acid (commercial source, 55.2 mg, 0.368 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): d 7.50 (d, J = 10.5 Hz, 4H), 7.00 (s, 1H), 7.13-7.18 (m, 4H), 7.03 (d, J = 8.4 Hz, 2H ), 5.15 (s, 2H), 5.02 (d, J = 6.6 Hz, 2H), 4.89 (d, J = 6.6Hz, 2H), 3.85 (s, 2H), 3.72 (s, 3H), 2.06 (s , 6H); MS: (m/z) 455.2 [M+Na]. Example 134 2-((3-(4-((2')-Dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid (compound 132)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 134 was obtained by hydrolysis of the compound of Example 134. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.34-7.40 (m, 5H), 7.22 (s, 1H), 7.11-7.19 (m, 4H), 7.05 (d, J = 8.4 Hz, 2H), 5.15 (s, 2H), 4.90-4.98 (m, 4H), 3.87 (s, 2H), 2.02 (s, 6H); MS: (m/z) 417.1 [M-1]. Example 134a 2-((3-(4-((2',6'-Dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 Metformin salts of the group -oxy)acetic acid (compound 132a)

The title compound was prepared via the general procedure as described for the metformin salt as described above, using compound 134. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.40-7.48 (m, 3H), 7.21-7.34 (m, 3H), 7.10-7.22 (m, 6H), 7.00 (d, J = 9.00 Hz, 2H) , 5.12 (s, 2H), 4.94 (d, J = 6.9 Hz, 2H), 4.86 (d, J = 6.9Hz, 2H), 4.14-4.21 (m, 2H), 3.64 (s, 2H), 3.00 ( s, 6H), 2.02 (s, 6H); MS: (m/z) 545.8 [M-1]. Example 135 Ethyl 2-((3-(4-((4'-propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3- Ethyl)acetate (compound 133)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (75 mg, 0. 017 mmol) and (4-propoxyphenyl)boronic acid (commercial source, 48.1 mg, 0.26 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.63 (s, 1H) 7.56 (d, J = 8.4 Hz, 3H), 7.43-7.48 (m, 1H), 7.40 (d, J = 8.7 Hz, 3H) , 7.07 (d, J=8.7Hz, 2H), 7.00 (d, J=8.0Hz, 2H), 5.15 (s, 2H), 5.03 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9Hz, 2H), 4.14-4.21 (m, 2H), 4.00 (t, J=6.6 Hz, 2H), 3.83 (s, 2H), 1.79-1.79 (m, 2H), 1.27 (t, J=7.2 Hz, 3H), 1.10 (t, J = 7.5 Hz, 3H); MS (m/z): 499.3 [M+Na]. Example 136 2-((3-(4-((4'-)-propoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetic acid (compound 134)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 136 was obtained by hydrolysis of the compound of Example 135. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.63 (s, 1H), 7.56 (d, J = 9.0 Hz, 3H), 7.31-7.48 (m, 4H), 7.07 (m, 4H), 5.14 (s , 2H), 4.91-4.99(m, 4H), 4.15 (t, J=6.6Hz, 2H), 3.88 (s, 2H), 1.79-1.91 (m, 2H), 1.09 (t, J=7.5 Hz, 3H); MS (m/z) 447.1 [M-1]. Example 137 Ethyl 2-((3-(4-((2'-chloro-4'-methyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)acetate (compound 135)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (100 mg, 0.24 mmol) and (2-chloro-4-methylphenyl)boronic acid (commercial source, 62.8 Mg, 0.36 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.63 (d, J = 10.5 Hz, 2H), 7.35-7.56 (m, 7H), 7.06 (d, J = 8.7 Hz, 2H), 5.15 (s, 2H) ), 5.03 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9Hz, 2H), 4.14-4.21 (m, 2H), 3.83 (s, 2H), 2.43 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H); MS (m/z): 466.9 [M+1]. Example 138 2-((3-(4-((2'-chloro-4'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetic acid (compound 136)

The title compound was prepared in a similar manner as Compound 84 of Example 86. Compounds of Example 138 were obtained by hydrolysis of the compound of Example 137. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.45- 7.47 (m, 2H), 7.37-7.40 (m, 2H), 7.31 (s, 2H), 7.27 (s, 1H), 7.13-7.21 (m, 2H), 7.05 (d, J = 8.4 Hz, 2H), 5.14 (s, 2H), 4.91-4.99 (m, 4H), 3.88 (s, 3H), 2.88 (s, 3H). Example 139 Ethyl 2-((3-(4-((4'-)-pentyloxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane - 3-yl)oxy)acetate (compound 137)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (100 mg, 0.23 mmol) and 3-(pentyloxy)phenyl)boronic acid (commercial source, 74.1 mg, 0.35) Mmmol) reaction. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.63 (s, 1H) 7.55 (d, J = 8.7 Hz, 3H), 7.43-7.48 (m, 1H), 7.37 (d, J = 8.4 Hz, 3H) , 7.07 (d, J=8.7Hz, 2H), 6.78 (d, J=8.4Hz, 2H), 5.15 (s, 2H), 5.03 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9Hz, 2H), 4.14-4.21 (m, 2H), 4.000 (t, J=6.6 Hz, 2H), 3.90 (s, 2H), 1.79-1.87 (m, 2H), 1.38-1.50 (m, 3H) ), 1.27 (t, J = 7.2 Hz, 4H), 0.98 (t, J = 6.5 Hz, 3H); MS: (m/z) 505.5 [M+1]. Example 140 2-((3-(4-((4'-)-Pentyloxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3- Alkyloxyacetic acid (compound 138)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 139 was obtained by hydrolysis of the compound of Example 139. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.63 (s, 1H), 7.56 (d, J = 8.7 Hz, 3H), 7.31-7.48 (m, 4H), 7.07 (d, J = 8.7 Hz, 2H ), 7.00 (d, J=8.7 Hz, 2H), 5.14 (s, 2H), 4.91-4.99 (m, 4H), 4.03 (t, J=6.6Hz, 2H), 2.08 (s, 2H), 1.79 -1.87 (m, 2H), 1.35-1.56 (m, 4H), 0.98 (t, J = 7.5 Hz, 3H); MS: (m/z) 474.9 [M-1]. Example 141 Ethyl 2-((3-(4-((4'-)-isobutoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetate (compound 139)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (100 mg, 0.23 mmol) and (3-isobutoxyphenyl)boronic acid (commercial source, 64.1 mg) , 0.35 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.63 (s, 1H) 7.56 (d, J = 8.4 Hz, 3H), 7.45-7.48 (m, 1H), 7.40 (d, J = 8.4 Hz, 3H) , 7.07 (d, J=8.7 Hz, 2H), 7.00 (d, J=8.7 Hz, 2H), 5.15 (s, 2H), 5.07 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9 Hz, 2H), 4.14-4.21 (m, 2H), 3.83 (s, 2H), 3.79 (d, J=6.6 Hz, 2H), 2.71-2.08 (m, 1H), 1.27(t, J=6.9 Hz, 3H), 1. 07 (d, J=6.6Hz, 6H); MS: (m/z) 489.3 [M-1]. Example 142 2-((3-(4-((4'-Biphenyl)-3-yl)methoxy)phenyl)oxycyclobutan-3-yl) )oxy)acetic acid (compound 140)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 141 was obtained by hydrolysis of the compound of Example 141. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.63 (s, 1H), 7.53-7.52 (m, 3H), 7.31-7.48 (m, 4H), 7.07 (d, J=8.7 Hz, 2H), 7.00 (J=6.3 Hz, 2H), 5.14 (s, 2H), 4.91-4.99 (m, 4H), 3.88 (s, 2H), 3.79 (d, J= 6.6 Hz, 2H), 2.06-2.19 (m, 1H), 1.04-1.07 (m, 6H); MS: (m/z) 485.2 [M+Na]. Example 143 Ethyl 2-((3-(4-((4'-(butylthio))-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane - 3-yl)oxy)acetate (compound 141)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (100 mg, 0.24 mmol) and (3-(butylthio)phenyl)boronic acid (commercial source, Reaction of 75.60 mg, 0.36 mmol) ¹ H NMR (CDCl ₃ , 300 MHz): d 7.65 (s, 1H) 7.38-7.56 (m, 9H), 7.06 (d, J = 8.7 Hz, 2H), 5.15 ( s, 2H), 5.03 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9 Hz, 2H), 4.14-4.21 (m, 2H), 3.83 (s, 2H), 3.00 (t, J =6.4 Hz, 2H), 1.66-1.71(m, 2H), 1.45-1.52(m, 2H), 1.27 (t, J=6.4Hz, 3H), 0.98 (t, J=7.5Hz, 3H);MS :(m/z) 529.3 [M+Na]. Example 144 2-((3-(4-((4'-(butylthio))-[1,1'-biphenyl]-3-yl)) Oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid (compound 142)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 144 was obtained by hydrolysis of the compound of Example 144. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.70 (s, 1H), 7.29-7.65 (m, 9H), 7.02 (d, J = 8.7 Hz, 2H), 5.18 (s, 2H), 4.91-5.03 (m, 4H), 3.88 (s, 2H), 3.00 (t, J=6.5 Hz, 2H), 1.64-1.73 (m, 3H), 1.547-1.55 (m, 2H), 098 (t, J=7.5 Hz, 3H); MS: (m/z) 479.3 [M+1]. Example 145 Ethyl 2-((3-(4-((4'-)-isopropyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate (compound 143)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (100 mg, 0.24 mmol) and (4-(isopropylthio)phenyl)boronic acid (commercial source, 72.2 mg, 0.36 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.66 (s, 1H) 7.2-7.56 (m, 9H), 7.07 (d, J=9Hz, 2H), 5.15 (s, 2H), 5.03 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9Hz, 2H), 4.14-4.21 (m, 2H), 3.83 (s, 2H), 3.40-3.49 (m, 1H), 1.36 (t, J= 9 Hz, 6H), 1.28 (t, J = 6 Hz, 3H); MS: (m/z) 514.8 [M+Na]. Example 146 2-((3-(4-((4'-(isopropylthio))-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid (compound 144)

The title compound was prepared in a similar manner as Compound 84 of Example 86. Compounds of Example 146 were obtained by hydrolysis of the compound of Example 145. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.76 (s, 1H), 7.32-7.56 (m, 7H), 7.48 (d, J = 9.0 Hz, 2H), 7.07 (d, J = 9 Hz, 2H) , 5.18(s, 2H), 4.91-4.99 (m, 4H), 3.88 (s, 2H), 3.40-3.49 (m, 1H), 1.25-1.44 (m, 6H); MS: m/z 487.2 [M +Na]. Example 147 Ethyl 2-((3-(4-((4'-)-trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate (compound 145)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (75 mg, 0.18 mmol) and (4-(trifluoromethyl)phenyl)boronic acid (commercial source, 52.5 mg, 0.27 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.69-7.72 (m, 5H) 7.53-7.60 (m, 3H), 7.41 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 5.17 (s, 2H), 4.89 (d, J = 6.9 Hz, 2H), 4.14-4.21 (m, 2H), 4.0 (t, J=6.6 Hz, 2H), 3.83 (s, 2H), 1.27 (t, J = 6.9 Hz, 3H); MS: (m/z) 487.5 [M+1]. Example 148 2-((3-(4-((4'-)(Trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid (compound 146)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 147 was obtained by hydrolysis of the compound of Example 147. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.58-7.69 (m, 5H), 7.48-7.56 (m, 3H), 7.48 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7 Hz , 2H), 5.17 (s, 2H), 4.91-4.99 (m, 4H), 3.89 (s, 2H); MS: (m/z) 458.4 [M-1]. Example 149 methyl 2-((3-(4-((2'-chloro-4'-propoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxy ring Butan-3-yl)oxy)acetate (compound 147)

The title compound was prepared in a similar manner as Compound 87 of Example 89, which was taken to methyl 2-((3-(4-((2'))) -yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Example 41 Step 1, Compound, 50 mg, 0.11 mmol) and 1-bromopropane (commercial source, 13.52 mg) , 0.11 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.50 (s, 1H), 7.46-7.42 (m, 3H), 7.38-7.35 (m, 2H), 7.25 (s, 1H), 7.06-7.03 (m, 3H), 6.90- 6.86 (m, 1H), 5.15 (s, 2H), 5.01 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9 Hz, 2H), 3.96 (t, J= 6.6 Hz, 2H), 3.85 (s, 2H), 3.72 (s, 3H), 1.88-1.81 (m, 2H), 1.07 (t, J = 7.2 Hz, 3H); MS: (m/z) 519.2 [M+ Na]. Example 150 2-((3-(4-((2'-Chloro-4'-propoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid (compound 148)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 150 was obtained by hydrolysis of the compound of Example 149. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.50 (s, 1H), 7.47-7.40 (m, 3H), 7.33-7.30 (m, 2H), 7.25 (s, 1H), 7.07-7.03 (m, 3H), 6.90-6.86 (m, 1H), 5.15 (s, 2H), 4.97-4.92 (m, 4H), 3.96 (t, J = 6.6 Hz, 2H), 3.87 (s, 2H), 1.90-1.79 (m, 2H), 1.07 (t, J = 7.2 Hz, 3H); MS: (m/z) 481.0 [MH]. Example 151 Ethyl 2-((3-(4-((3-(2-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy) Acid ester (compound 149)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (400 mg, 0.949 mmol) and (2-methylpyridin-3-yl)boronic acid (commercial source, 194 mg, 1.417 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ 8.52-8.50 (m, 1H), 7.55-7.52 (m, 1H), 7.48-7.46 (m, 2H), 7.39-7.36 (m, 3H), 7.31- 7.29 (m, 1H), 7.20-7.18 (m, 1H), 7.04 (d, J = 8.7Hz, 2H), 5.14 (s, 2H), 5.01 (d, J = 6.9Hz, 2H), 4.86 (d , J = 6.9Hz, 2H), 4.16 (q, J = 7.2Hz, 2H), 3.82 (s, 2H), 2.49(s, 3H), 1.24 (t, J= 7.2 Hz, 3H); MS: ( m/z) 434.4 [M+ H]. Example 152 2-((3-(4-((3-(2-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (compound) 150)

The title compound was prepared in a similar manner as Compound 84 of Example 86. Compounds of Example 152 were obtained by hydrolysis of the compound of Example 152. ¹ H NMR (DMSO, 300 MHz): δ 12.62 (br s, 1H), 8.54-8.53 (m, 1H), 7.78 (d, J = 6.9 Hz, 1H), 7.53-7.49 (m, 3H), 7.38 -7.36 (m, 4H), 7.09 (d, J = 8.7 Hz, 2H), 5.20 (s, 2H), 4.81 (d, J = 6.9Hz, 2H), 4.75 (d, J= 6.9Hz, 2H) , 3.74 (s, 2H), 2.43 (s, 3H); MS: (m/z) 406.1 [M+H]. Example 153 Ethyl 2-((3-(4-((4'-(methylsulfonyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate (compound 151)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (200 mg, 0.475 mmol) and (4-(methylsulfonyl)phenyl)boronic acid (commercial source, 142 mg) , 0.710 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ 8.03 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.69-7.64 (m, 2H), 7.53-7.49 (m , 2H), 7.40 (d, J = 8.7 Hz, 2H), 7.05 (d, J = 8.7Hz, 2H), 5.16 (s, 2H), 5.01 (d, J = 6.9Hz, 2H), 4.87 (d , J = 6.9Hz, 2H), 4.16 (q, J = 7.2Hz, 2H), 3.83 (s, 2H), 3.10 (s, 3H), 1.24 (t, J= 7.2 Hz, 3H); MS: ( m/z) 519.1 [M+Na]. Example 154 2-((3-(4-((4'-(Methanesulfonyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid (compound 152)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 153 was obtained by hydrolysis of the compound of Example 153. ¹ H NMR (DMSO, 300 MHz): δ 12.60 (br s, 1H), 8.03-7.94 (m, 4H), 7.85 (s, 1H), 7.73-7.71 (m, 1H), 7.55 (d, J = 4.5Hz, 2H), 7.39 (d, J = 8.7Hz, 2H), 7.11 (d, J = 8.7 Hz, 2H), 5.22 (s, 2H), 4.81 (d, J = 6.9Hz, 2H), 4.75 (d, J = 6.9 Hz, 2H), 3.74 (s, 2H), 3.25 (s, 3H); MS: (m/z) 491.1 [M+ Na]. Example 155 Ethyl 2-((3-(4-(3-(5-(1-cyanocyclopropyl))thiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3 -yl)oxy)acetate (compound 153)

The title compound was prepared in a similar manner to compound 107 as in Example 109, which was taken to ethyl 2-((3-(4-(4,4,5,5,5-tetramethyl-1,3,2-) Dioxaborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (0.44 g, 0.943 mmol) with 1-(5-bromothiophene- Reaction of 2-yl)cyclopropanecarbonitrile (commercial source, 41 mg, 0.18 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.61-7.60 (m, 1H), 7.52-7.50 (m, 1H), 7.43-7.36 (m, 4H), 7.16-7.15 (m, 1H), 7.04- 7.01 (m, 3H), 5.10 (s, 2H), 5.02 (d, J = 6.9Hz, 2H), 4.87 (d, J = 6.9Hz, 2H), 4.17 (q, J = 7.2Hz, 2H), 3.82 (s, 2H), 1.79-1.77 (m, 2H), 1.50-1.46 (m, 2H), 1.24 (t, J = 7.2 Hz, 3H); MS: (m/z) 512.3 [M+Na] . Example 156 2-((3-(4-(3-(5-(1-Cyanocyclopropyl))thiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl )oxy)acetic acid (compound 154)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 156 was obtained by hydrolysis of the compound of Example 155. ¹ H NMR (DMSO, 300 MHz): δ 12.58 (br s, 1H), 7.72-7.71 (m, 1H), 7.60-7.58 (m, 1H), 7.46-7.36 (m, 5H), 7.11-7.06 ( m, 3H), 5.16 (s, 2H), 4.81 (d, J = 6.9Hz, 2H), 4.75 (d, J= 6.9Hz, 2H), 3.74 (s, 2H), 1.86-1.82 (m, 2H) ), 1.58-1.53 (m, 2H); MS: (m/z) 484.4 [M+ Na]. Example 157 Ethyl 2-((3-(4-((4'-(methylsulfinyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Alk-3-yl)oxy)acetate (compound 155)

A solution of sodium periodate (149 mg, 0.697 mmol) in water (2 ml) was added dropwise at RT to ethyl 2-(3 in a mixture of ethanol (10 ml) and acetone (3.5 ml). -(4-((4'-(methylthio)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid The ester (the compound was prepared in a similar manner as Compound 31) (250 mg, 0.538 mmol) was stirred. The reaction mixture was stirred at RT for 12 h. After the reaction is completed, the reaction mixture is evaporated, mjjjjjjj 220 mg). Yield: 85.1%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.79-7.72 (m, 4H), 7.69 (s, 1H), 7.60-7.58 (m, 1H), 7.54-7.49 (m, 2H ), 7.41 (d, J = 8.7 Hz, 2H), 7.06 (d, J = 8.7Hz, 2H), 5.16 (s, 2H), 5.02 (d, J = 6.9Hz, 2H), 4.88 (d, J = 6.9Hz, 2H), 4.17 (q, J = 7.2Hz, 2H), 3.83 (s, 2H), 3.10 (s, 3H), 1.25 (t, J= 7.2 Hz, 3H); MS: (m/ z) 503.5 [M+Na]. Example 158 2-((3-(4-((4'-(methylsulfinyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetic acid (compound 156)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 157 was obtained by hydrolysis of the compound of Example 157. ¹ H NMR (DMSO, 300 MHz): δ 12.62 (br s, 1H), 7.89 (d, J = 8.4 Hz, 2H), 7.79 (t, J = 7.5 Hz, 3H), 7.70-7.68 (m, 1H) ), 7.55-7.51 (m, 2H), 7.39 (d, J = 8.4Hz, 2H), 7.11 (d, J = 8.4Hz, 2H), 5.21 (s, 2H), 4.81 (d, J = 6.9Hz , 2H), 4.75 (d, J = 6.9 Hz, 2H), 3.74 (s, 2H), 2.78 (s, 3H); MS (m/z): 475.3 [M+ Na]. Example 159 Ethyl 2-((3-(4-(3-(3-(trifluoromethyl)pyridin-4-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl) Oxy)acetate (compound 157)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner to the compound of Step 1 of Example 17) (300 mg, 0.712 mmol) and (3-(trifluoromethyl)pyridin-3-yl)boronic acid (commercial source) , 203 mg, 1.063 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ 8.81 (d, J = 5.1 Hz, 1H), 8.68 (s, 1H), 7.64 (d, J = 5.1 Hz, 1H), 7.55-7.47 (m, 2H ), 7.43-7.31 (m, 4H), 7.04 (d, J = 8.7 Hz, 2H), 5.15 (s, 2H), 5.02 (d, J = 6.9 Hz, 2H), 4.87 (d, J = 6.9 Hz) , 2H), 4.17 (q, J = 7.2 Hz, 2H), 3.82 (s, 2H), 1.24 (t, J = 7.2 Hz, 3H); MS: (m/z) 510.4 [M+ Na]. Example 160 2-((3-(4-(3-(3-(Trifluoromethyl)pyridin-4-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy ) acetic acid (compound 158)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 160 was obtained by hydrolysis of the compound of Example 159. ¹ H NMR (DMSO, 300 MHz): δ 12.61 (br s, 1H), 8.89 (d, J = 5.1 Hz, 1H), 8.70 (s, 1H), 7.86 (d, J = 5.1 Hz, 1H), 7.59-7.49 (m, 3H), 7.38 (d, J = 8.7 Hz, 3H), 7.08 (d, J = 8.7 Hz, 2H), 5.19 (s, 2H), 4.81 (d, J = 7.2 Hz, 2H ), 4.75 (d, J = 7.2 Hz, 2H), 3.73 (s, 2H); MS: (m/z) 460.1 [M+H]. Example 161 Ethyl 2-((3-(4-(3-(2-(trifluoromethyl)pyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl) Oxy)acetate (compound 159)

The title compound was prepared in a similar manner to compound 107 as in Example 109, which was taken to ethyl 2-((3-(4-(4,4,5,5,5-tetramethyl-1,3,2-) Dioxaborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (0.44 g, 0.943 mmol) with 3-bromo-2-(tris) Reaction of fluoromethyl)pyridine (96.5 mg, 0.427 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 8.75 (d, J = 4.5 Hz, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.51-7.46 (m, 3H), 7.41-7.36 (m , 4H), 7.04(d, J = 8.7 Hz, 2H), 5.15 (s, 2H), 5.02 (d, J = 6.9Hz, 2H), 4.87 (d, J = 6.9Hz, 2H), 4.17 (q , J = 7.2 Hz, 2H), 3.82 (s, 2H), 1.24 (t, J = 7.2 Hz, 3H); MS (m/z): 510.4 [M+ Na] ⁺ . Example 162 2-((3-(4-(3-(2-(Trifluoromethyl)pyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy ) acetic acid (compound 160)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 161 was obtained by hydrolysis of the compound of Example 161. ¹ H NMR (DMSO, 300 MHz): δ 12.61 (br s, 1H), 8.78 (d, J = 4.2 Hz, 2H), 7.99 (d, J = 7.8 Hz, 1H), 7.80-7.76 (m, 1H) ), 7.57-7.49 (m, 2H), 7.45 (s, 1H), 7.38-7.32 (m, 3H), 7.08 (d, J = 8.7 Hz, 2H), 5.19 (s, 2H), 4.81 (d, J = 7.2 Hz, 2H), 4.75 (d, J = 7.2 Hz, 2H), 3.73 (s, 2H); MS: (m/z) 482.1 [M+ Na]. Example 163 Ethyl 2-((3-(4-((3-(pyrimidin-5-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetate (Compound) 161)

The title compound was prepared in a similar manner to compound 107 as in Example 109, which was taken to ethyl 2-((3-(4-(4,4,5,5,5-tetramethyl-1,3,2-) Dioxaborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (300 mg, 0.638 mmol) with 5-bromopyrimidine (68 mg, 0.428 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ 9.23 (s, 1H), 8.98 (s, 2H), 7.71-7.64 (m, 2H), 7.57 (s, 2H), 7.41 (d, J = 8.7 Hz , 2H), 7.06(d, J =8.7Hz, 2H), 5.18 (s, 2H), 5.02 (d, J = 6.9Hz, 2H), 4.87 (d, J = 6.9Hz, 2H), 4.17 (q , J = 7.2 Hz, 2H), 3.82 (s, 2H), 1.24 (t, J = 7.2 Hz, 3H); MS: (m/z) 443.2 [M+ Na]. Example 164 2-((3-(4-((3-(pyrimidin-5-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (Compound 162)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 164 was obtained by hydrolysis of the compound of Example 164. ¹ H NMR (DMSO, 300 MHz): δ 12.63 (br s, 1H), 9.20 (s, 1H), 9.16 (s, 2H), 7.92 (s, 1H), 7.79-7.78 (m, 1H), 7.58 (d, J = 4.8 Hz, 2H), 7.39 (d, J = 8.7 Hz, 2H), 7.11 (d, J = 8.7 Hz, 2H), 5.20 (s, 2H), 4.81 (d, J = 6.9 Hz , 2H), 4.75 (d, J = 6.9 Hz, 2H), 3.74 (s, 2H); MS: (m/z) 392.9 [M+ H]. Example 165 Ethyl 2-((3-(4-((3-(4-methylpyrimidin-5-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy) Acid ester (compound 163)

The title compound was prepared in a similar manner to compound 107 as in Example 109, which was taken to ethyl 2-((3-(4-(4,4,5,5,5-tetramethyl-1,3,2-) Dioxaborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (300 mg, 0.638 mmol) with 5-bromo-4-methyl Reaction of pyrimidine (74 mg, 0.428 mmol). Yield semi-solid 180 mg, 64.7%. ¹ H NMR (CDCl ₃ , 300 MHz): δ 9.09 (s, 1H), 8.56 (s, 1H), 7.54-7.52 (m, 2H), 7.42-7.38 (m, 3H), 7.32-7.31 (m, 1H), 7.05 (d, J = 8.7 Hz, 2H), 5.16 (s, 2H), 5.02 (d, J = 6.9Hz, 2H), 4.87 (d, J = 6.9Hz, 2H), 4.17 (q, J = 7.2 Hz, 2H), 3.82 (s, 2H), 2.51 (s, 3H), 1.24 (t, J = 7.2 Hz, 3H); MS: (m/z) 457.1 [M+ Na] Example 166 2- ((3-(4-(3-(4-Methylpyrimidin-5-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid (Compound 164)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 166 was obtained by hydrolysis of the compound of Example 166. ¹ H NMR (DMSO, 300 MHz): δ 12.62 (br s, 1H), 9.04 (s, 1H), 8.61 (s, 1H), 7.56-7.54 (m, 3H), 7.46-7.44 (m, 1H) , 7.39 (d, J = 8.7Hz, 2H), 7.10 (d, J = 8.7Hz, 2H), 5.20 (s, 2H), 4.81 (d, J = 7.2Hz, 2H), 4.75 (d, J= 7.2 Hz, 2H), 3.74 (s, 2H), 2.42 (s, 3H); MS (m/z) 406.9 [M+ H]. Example 167 Ethyl 2-((3-(4-((3-(2-methoxypyrimidin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy) Acetate (compound 165)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (300 mg, 0.712 mmol) and (2-methoxypyrimidin-3-yl)boronic acid (commercial source, 164 mg) , 1.072 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ 8.19-8.17 (m, 1H), 7.65-7.62 (m, 2H), 7.55-7.53 (m, 1H), 7.49-7.44 (m, 2H), 7.39 ( d, J = 8.7 Hz, 2H), 7.05-6.97 (m, 3H), 5.14 (s, 2H), 5.02 (d, J = 6.9 Hz, 2H), 4.88 (d, J = 6.9 Hz, 2H), 4.17 (q, J = 7.2 Hz, 2H), 3.97 (s, 3H), 3.82 (s, 2H), 1.24 (t, J = 7.2 Hz, 3H); MS: (m/z) 450.1 [M+ H] . Example 168 2-((3-(4-(3-(2-Methoxypyrimidin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid ( Compound 166)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 167 was obtained by hydrolysis of the compound of Example 167. ¹ H NMR (DMSO, 300 MHz): δ 12.61 (br s, 1H), 8.18-8.17 (m, 1H), 7.76-7.74 (m, 1H), 7.62 (s, 1H), 7.49-7.44 (m, 3H), 7.39 (d, J = 8.7Hz, 2H), 7.12-7.06 (m, 3H), 5.17 (s, 2H), 4.81 (d, J = 7.2Hz, 2H), 4.75 (d, J= 7.2 Hz, 2H), 3.85 (s, 3H), 3.74 (s, 2H); MS: (m/z) 422.1 [M+H]. Example 169 Ethyl 2-((3-(4-((3-(pyrazin-2-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetate ( Compound 167)

The title compound was prepared in a similar manner to compound 107 as in Example 109, which was taken to ethyl 2-((3-(4-(4,4,5,5,5-tetramethyl-1,3,2-) Dioxaborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (300 mg, 0.638 mmol) with 2-bromopyrazine (68 mg , 0.428 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ 9.07 (s, 1H), 8.66 (s, 1H), 8.55 (d, J = 2.4 Hz, 1H), 8.12 (s, 1H), 7.99-7.89 (m , 1H), 7.58-7.56 (m, 2H), 7.39 (d, J = 8.7 Hz, 2H), 7.0 6 (d, J = 8.7 Hz, 2H), 5.19 (s, 2H), 5.02 (d, J = 6.9Hz, 2H), 4.88 (d, J = 6.9Hz, 2H), 4.17 (q, J = 7.2Hz, 2H), 3.82 (s, 2H), 1.24 (t, J= 7.2 Hz, 3H); MS: (m/z) 442.9. [M+ Na]. Example 170 2-((3-(4-((3-(pyrazin-2-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid (Compound 168)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 170 was obtained by hydrolysis of the compound of Example 170. ¹ H NMR (DMSO, 300 MHz): δ 12.63 (br s, 1H), 9.20 (s, 1H), 9.16 (s, 2H), 7.92 (s, 1H), 7.79-7.78 (m, 1H), 7.58 (d, J = 4.8 Hz, 2H), 7.39 (d, J = 8.7 Hz, 2H), 7.11 (d, J = 8.7 Hz, 2H), 5.23 (s, 2H), 4.81 (d, J = 6.9 Hz , 2H), 4.75 (d, J = 6.9 Hz, 2H), 3.74 (s, 2H); MS: (m/z) 393.4 [M+ Na]. Example 171 Ethyl 2-((3-(4-((3-(6-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy) Acid ester (compound 169)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (400 mg, 0.949 mmol) and (6-methylpyridin-3-yl)boronic acid (commercial source, 195.1 mg, 1.425 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 500 MHz): δ 8.57 (s, 1H), 7.82 (d, J = 4.8 Hz, 1H), 7.65 (s, 1H), 7.57-7.55 (m, 1H), 7.53-7.47 (m, 2H), 7.40 (d, J = 5.1Hz, 2H), 7.28-7.25 (m, 1H), 7.06 (d, J = 5.1Hz, 2H), 5.17 (s, 2H), 5.02 (d, J = 7.0Hz 2H), 4.88 (d, J = 7.0Hz, 2H), 4.18 (q, J = 7.0Hz, 2H), 3.84 (s, 2H), 2.63 (s, 3H), 1.25 (t, J = 7.0 Hz, 3H); MS: (m/z) 434.1 [M+H]. Example 172 2-((3-(4-(3-(6-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (compound) 170)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 171 was obtained by hydrolysis of the compound of Example 171. ¹ H NMR (DMSO, 500 MHz): δ 12.64 (br s, 1H), 8.70 (s, 1H), 7.98 (d, J = 4.8 Hz, 1H), 7.79 (s, 1H), 7.68 (d, J = 4.2Hz, 1H), 7.53-7.48 (m, 2H), 7.39-7.34 (m, 3H), 7.11 (d, J = 5.1Hz, 2H), 5.20 (s, 2H), 4.81 (d, J = </ RTI></RTI><RTIgt; Example 173 Ethyl 2-((3-(4-((2'-(cyanomethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate (compound 171)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner to the compound of Step 1 of Example 17) (400 mg, 0.949 mmol) and 2-(2-(4,4,5,5-tetramethyl-1) , 3,2-Dioxaborolan-2-yl)phenyl)acetonitrile (commercial source, 346 mg, 1.423 mmol). ¹ H NMR (CDCl ₃ , 500 MHz): δ 7.57-7.56 (m, 1H), 7.51-7.50 (m, 2H), 7.43-7.42 (m, 2H), 7.40-7.39 (m, 3H), 7.33- 7.32 (m, 2H), 7.05 (d, J = 5.1Hz, 2H), 5.16 (s, 2H), 5.03 (d, J = 7.0Hz 2H), 4.88 (d, J = 7.0Hz, 2H), 4.18 (q, J = 7.0 Hz, 2H), 3.84 (s, 2H), 3.63 (s, 2H), 1.26 (t, J = 7.0 Hz, 3H); MS (m/z) 480.3 [M+ Na]. Example 174 2-((3-(4-((2'-(Cyanomethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid (compound 172)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 174 was obtained by hydrolysis of the compound of Example 174. ¹ H NMR (DMSO, 500 MHz): δ 12.60 (br s, 1H), 7.54-7.51 (m, 3H), 7.45 (s, 3H), 7.39-7.37 (m, 1H), 7.33-7.32 (m, 3H), 7.10 (d, J = 8.5Hz, 2H), 5.20 (s, 2H), 4.81 (d, J = 7.0Hz 2H), 4.75 (d, J = 7 Hz, 2H), 3.89 (s, 2H) ), 3.74 (s, 2H); MS: (m/z) 452.1 [M+Na]. Example 175 Ethyl 2-((3-(4-((3-(pyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate (Compound) 173)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) The oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (400 mg, 0.949 mmol) was reacted with pyridin-3-ylboronic acid (commercial source, 175 mg, 1.424 mmol). ¹ H NMR (CDCl ₃ , 500 MHz): δ 8.88 (s, 1H), 8.63 (d, J = 4.0 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.70-7.66 (m, 2H ), 7.57-7.54 (m, 1H), 7.52-7.49 (m, 2H), 7.40 (d, J = 8.5Hz, 2H), 7.07 (d, J = 8.5 Hz, 2H), 5.18 (s, 2H) , 5.02 (d, J = 7.0 Hz 2H), 4.88 (d, J = 7.0Hz, 2H), 4.20-4.16 (m, 2H), 3.84 (s, 2H), 1.25 (t, J = 7.0 Hz, 3H MS: (m/z) 420.2 [M+H]. Example 176 2-((3-(4-((3-(pyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (Compound 174)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 175 was obtained by hydrolysis of the compound of Example 176. ¹ H NMR (DMSO, 300 MHz): δ 12.62 (br s, 1H), 8.91 (s, 1H), 8.59 (d, J = 3.9 Hz, 1H), 8.12 (d, J = 7.8 Hz, 1H), 7.82 (s, 1H), 7.69-7.62 (m, 2H), 7.56-7.49 (m, 2H), 7.39 (d, J = 8.7Hz, 2H), 7.11 (d, J = 8.7 Hz, 2H), 5.20 (s, 2H), 4.81 (d, J = 6.9 Hz 2H), 4.75 (d, J = 6.9 Hz, 2H), 3.74 (s, 2H); MS: (m/z) 392.1 [M+ H]. Example 177 Ethyl 2-((3-(4-((3-(pyridin-4-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate (Compound) 175)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) The oxy)acetate (compound prepared in a similar manner to the compound of Step 1 of Example 17) (400 mg, 0.949 mmol) was reacted with pyridin-4-ylboronic acid (commercial source, 175 mg, 1.424 mmol). ¹ H NMR (CDCl ₃ , 500 MHz): δ 8.69 (d, J = 5.0 Hz, 2H), 7.73 (s, 1H), 7.70-7.68 (m, 2H), 7.57-7.54 (m, 2H), 7.50 -7.48 (m, 1H), 7.41 (d, J = 8.5 Hz, 2H), 7.07 (d, J = 8.5 Hz, 2H), 5.18 (s, 2H), 5.03 (d, J = 7.0 Hz 2H), 4.88 (d, J = 7 Hz, 2H), 4.20-4.13 (m, 2H), 3.84 (s, 2H), 1.26 (t, J = 7.0 Hz, 3H); MS: (m/z) 420.2 [M+ H]. Example 178 2-((3-(4-((3-(pyridin-4-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (Compound 176)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 177 was obtained by hydrolysis of the compound of Example 178. ¹ H NMR (DMSO, 500 MHz): δ 12.59 (br s, 1H), 8.75 (s, 2H), 7.97 (s, 1H), 7.93 (s, 2H), 7.85-7.84 (m, 1H), 7.61 -7.59 (m, 2H), 7.40 (d, J = 8.0 Hz, 2H), 7.11 (d, J = 7.5 Hz, 2H), 5.23 (s, 2H), 4.81 (d, J = 7.0 Hz 2H), 4.75 (d, J = 7.0 Hz, 2H), 3.75 (s, 2H); MS: (m/z) 392.1 [M+H]. Example 179 methyl 2-((3-(4-((2'-)-trifluoromethoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Alk-3-yl)oxy)acetate (compound 177)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (compound of Example 17 Step 1, 250 mg, 0.614 mmol) with (2-(trifluoromethoxy)phenyl)boronic acid (commercial source, 189.4 mg, 0.920 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.54 (s, 1H), 7.46-7.44 (m, 4H), 7.38-7.34 (m, 5H), 7.04-7.01 (m, 2H), 5.30 (s, 2H), 5.00 (d, J = 6.9Hz, 2H), 4.87 (d, J = 6.9Hz, 2H), 3.83 (s, 2H), 3.70 (s, 3H); MS (m/z) 511.1 [M +Na]. Example 180 2-((3-(4-((2'-)(Trifluoromethoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetic acid (compound 178)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 180 was obtained by hydrolysis of the compound of Example 179. ¹ H NMR (DMSO, 300 MHz): δ 12.55 (br s, 1H), 7.54-7.52 (m, 2H), 7.50-7.49 (m, 5H), 7.43-7.42 (m, 1H), 7.37 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 5.18 (s, 2H), 4.80 (d, J = 6.9 Hz, 2H), 4.74 (d, J = 6.9 Hz, 2H) , 3.72 (s, 2H). MS (m/z): 473.0 [MH]. Example 181 Ethyl 2-((3-(4-((4'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Alk-3-yl)oxy)acetate (compound 179)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (400 mg, 0.949 mmol) and (4-fluoro-2-methylphenyl)boronic acid (commercial source, 220 mg, 1.429 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.45-7.42 (m, 2H), 7.38-7.35 (m, 4H), 7.21-7.16 (m, 1H), 7.04-6.99 (m, 1H), 6.96- 6.91 (m, 3H), 5.13 (s, 2H), 5.01 (d, J = 6.9Hz, 2H), 4.87 (d, J = 6.9Hz, 2H), 4.17 (q, J = 7.2Hz, 2H), 3.82 (s, 2H), 2.23 (s, 3H), 1.24 (t, J = 7.2 Hz, 3H); MS: (m/z) 473.3 [M+ Na]. Example 182 2-((3-(4-((4'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetic acid (compound 180)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 182 was obtained by hydrolysis of the compound of Example 181. ¹ H NMR (DMSO, 500 MHz): δ 12.63 (br s, 1H), 7.47-7.46 (m, 2H), 7.39-7.38 (m, 2H), 7.36 (s, 1H), 7.29-7.28 (m, 1H), 7.25-7.22 (m, 1H), 7.17 (d, J = 10.0Hz, 1H), 7.09 (d, J = 4.8Hz, 3H), 5.19 (s, 2H), 4.81 (d, J = 7.0 Hz, 2H), 4.75 (d, J = 7.0 Hz, 2H), 3.74 (s, 2H), 2.20 (s, 3H); MS (m/z) 445.3 [M+ Na]. Example 183 Ethyl 2-((3-(4-((5'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Alk-3-yl)oxy)acetate (compound 181)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (400 mg, 0.949 mmol) and (5-fluoro-2-methylphenyl)boronic acid (commercial source, 220 mg, 1.429 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 500 MHz): δ 7.49-7.44 (m, 2H), 7.39 (d, J = 8.0 Hz, 3H), 7.30-7.28 (m, 1H), 7.24-7.21 (m, 1H) , 7.05 (d, J = 8.5Hz, 2H), 6.99-6.96 (m, 2H), 5.15 (s, 2H), 5.02 (d, J = 7.0 Hz, 2H), 4.88 (d, J = 7.0 Hz, 2H), 4.17 (q, J = 7.5Hz, 2H), 3.82 (s, 2H), 2.21 (s, 3H), 1.26 (t, J = 7.5 Hz, 3H); MS: (m/z) 473.3 [ M+ Na]. Example 184 2-((3-(4-((5'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetic acid (compound 182)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 184 was obtained by hydrolysis of the compound of Example 183. ¹ H NMR (DMSO, 500 MHz): δ 12.63 (br s, 1H), 7.48 (s, 2H), 7.43 (s, 1H), 7.39 (d, J = 8.5 Hz, 2H), 7.33-7.32 (m , 2H), 7.14-7.12 (m, 1H), 7.09-7.04 (m, 3H), 5.20 (s, 2H), 4.81 (d, J = 7.0 Hz, 2H), 4.75 (d, J = 7.0 Hz, 2H), 3.74 (s, 2H), 2.16 (s, 3H); MS: (m/z) 445.2 [M+ Na]. Example 185 Ethyl 2-((3-(4-((2'-fluoro-6'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Alk-3-yl)oxy)acetate (compound 183)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (400 mg, 0.949 mmol) and (2-fluoro-6-methylphenyl)boronic acid (commercial source, 220 mg, 1.429 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 500 MHz): δ 7.49-7.47 (m, 2H), 7.38-7.36 (m, 3H), 7.26-7.23 (m, 2H), 7.09-6.99 (m, 4H), 5.15 ( s, 2H), 5.02 (d, J = 7.0 Hz, 2H), 4.88 (d, J = 7.0 Hz, 2H), 4.18 (q, J = 7.5Hz, 2H), 3.83 (s, 2H), 2.16 ( s, 3H), 1.26 (t, J = 7.5 Hz, 3H); MS: (m/z) 473.3 [M+ Na]. Example 186 2-((3-(4-((2'-Fluoro-6'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetic acid (compound 184)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 186 was obtained by hydrolysis of the compound of Example 186. ¹ H NMR (DMSO, 500 MHz): δ 12.63 (br s, 1H), 7.50 (s, 2H), 7.38 (d, J = 9.0 Hz, 3H), 7.26-7.23 (m, 2H), 7.16-7.11 (m, 2H), 7.09 (d, J = 9.0Hz, 2H), 5.19 (s, 2H), 4.81 (d, J = 7.0 Hz, 2H), 4.75 (d, J = 7.0 Hz, 2H), 3.74 (s, 2H), 2.08 (s, 3H). MS: (m/z) 445.4 [M+ Na]. Example 187 Ethyl 2-((3-(4-((2'-(methylthio))-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane - 3-yl)oxy)acetate (compound 185)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (1.5 g, 3.56 mmol) and (2-(methylthio)phenyl)boronic acid (commercial source, 0.898 g, 5.34 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 500 MHz): δ 7.51 (s, 1H), 7.48-7.47 (m, 2H), 7.44-7.41 (m, 1H), 7.38-7.37 (m, 3H), 7.31-7.30 ( m, 1H), 7.25-7.24 (m, 2H), 7.05 (d, J = 8.5Hz, 2H), 5.15 (s, 2H), 5.02 (d, J = 7.0 Hz, 2H), 4.88 (d, J = 7.0 Hz, 2H), 4.19-4.17 (m, 2H), 3.83 (s, 2H), 2.39 (s, 3H), 1.26 (t, J = 7.5 Hz, 3H); MS: (m/z) 487.4 [M+ Na]. Example 188 2-((3-(4-((2'-(methylthio))-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3- Alkyloxyacetic acid (compound 186)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 187 was obtained by hydrolysis of the compound of Example 187. ¹ H NMR (DMSO, 500 MHz): δ 12.62 (br s, 1H), 7.47-7.45 (m, 3H), 7.38 (d, J = 9.0 Hz, 3H), 7.35 (d, J = 8.0 Hz, 2H ), 7.24-7.19 (m, 2H), 7.09 (d, J = 8.5Hz, 2H), 5.18 (s, 2H), 4.81 (d, J = 7.0 Hz, 2H), 4.75 (d, J = 7.0 Hz) , 2H), 3.74 (s, 2H), 2.36 (s, 3H); MS: (m/z) 459.1 [M+ Na]. Example 189 Ethyl 2-((3-(4-((2'-(methylsulfonyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate (compound 187)

A solution of oxone (1.98 g, 3.24 mmol) in water was added dropwise at 0 °C to ethyl 2-((3-(4-((2'-)-methylthio) in THF. -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound 185, 400 mg, 0.861 mmol) stirred solution . The reaction mixture was stirred at RT for 48 h. After the reaction was completed, the reaction mixture was concentrated, and the residue was evaporated. The organic layer was washed with EtOAc (EtOAc m. Yield: 72.04%; ¹ H NMR (CDCl ₃ , 500 MHz): δ 8.26 (d, J = 8.0 Hz, 1H), 7.69-7.66 (m, 1H), 7.61-7.54 (m, 3H), 7.52- 7.49(m, 1H), 7.46-7.44 (m, 1H), 7.42-7.40 (m, 1H), 7.38-7.37 (m, 2H), 7.04 (d, J = 8.5Hz, 2H), 5.17 (s, 2H), 5.02 (d, J = 7.0 Hz, 2H), 4.87 (d, J = 7.0 Hz, 2H), 4.21-4.16 (m, 2H), 3.83 (s, 2H), 2.63 (s, 3H), 1.26 (t, J = 7 Hz, 3H); MS: (m/z) 519.5 [M+ Na]. Example 190 2-((3-(4-((2'-(Methanesulfonyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid (compound 188)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 190 was obtained by hydrolysis of the compound of Example 189. ¹ H NMR (DMSO, 500 MHz): δ 12.62 (br s, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.77 (t, J = 7.5 Hz, 1H), 7.69 (t, J = 7.5 Hz, 1H), 7.54-7.53 (m, 1H), 7.49-7.47 (m, 2H), 7.43 (d, J = 7.5Hz, 1H), 7.38-7.36 (m, 3H), 7.08 (d, J = 8.5Hz, 2H), 5.19 (s, 2H), 4.81 (d, J = 7.0 Hz, 2H), 4.75 (d, J = 7.0 Hz, 2H), 3.74 (s, 2H), 2.80 (s, 3H) ;MS: (m/z) 491.5 [M+ Na]. Example 191 Ethyl 2-((3-(4-((2'-(methylsulfinyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Alk-3-yl)oxy)acetate (compound 189)

A solution of sodium periodate (276.2 mg, 1.291 mmol) in water (2 ml) was added dropwise at RT to ethyl 2-(3 in a mixture of ethanol (10 ml) and acetone (3.5 ml). -(4-((2'-(methylthio)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid The ester (Compound 185, 400 mg, 0.861 mmol) was stirred. The reaction mixture was stirred at RT for 12 h. After the reaction was completed, the reaction mixture was concentrated, and the residue was dissolved in ethyl acetate. The organic layer was washed with EtOAc (EtOAc m. Yield: 46.0%. ¹ H NMR (CDCl ₃ , 500 MHz): δ 8.15 (d, J = 7.5 Hz, 1H), 7.65 (t, J = 7.5 Hz, 1H), 7.57 (t, J = 7.5 Hz, 1H), 7.51- 7.48 (m, 3H), 7.41-7.39 (m, 2H), 7.36-7.28 (m, 2H), 7.05 (d, J = 9.0 Hz, 2H), 5.16 (s, 2H), 5.03 (d, J = 7.0 Hz, 2H), 4.88 (d, J = 7.0 Hz, 2H), 4.21-4.17 (m, 2H), 3.84 (s, 2H), 2.37 (s, 3H), 1.26 (t, J = 7.0 Hz, 3H); MS: (m/z) 503.5 [M+ Na]. Example 192 2-((3-(4-((2'-(methylsulfinyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetic acid (compound 190)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 191 was obtained by hydrolysis of the compound of Example 191. ¹ H NMR (DMSO, 500 MHz): δ 12.60 (br s, 1H), 8.01 (d, J = 7.5 Hz, 1H), 7.71 (t, J = 7.0 Hz, 1H), 7.63 (t, J = 7.5 Hz, 1H), 7.53-7.50 (m, 2H), 7.47 (s, 1H), 7.40-7.37( m, 4H), 7.09 (d, J = 8.5Hz, 2H), 5.22 (s, 2H), 4.81 (d, J = 7.0 Hz, 2H), 4.75 (d, J = 7.0 Hz, 2H), 3.74 (s, 2H), 2.38 (s, 3H); MS: (m/z) 475.3 [M+ Na]. Example 193 Ethyl 2-((3-(4-((3-(5-methoxy-2-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3- Ethyl)acetate (compound 191)

The title compound was prepared in a similar manner to compound 107 as in Example 109, which was taken to ethyl 2-((3-(4-(4,4,5,5,5-tetramethyl-1,3,2-) Dioxaborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (150 mg, 0.32 mmol) with 3-bromo-5-methoxy Reaction of benzyl-2-methylpyridine (commercial source, 44 mg, 0.218 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 8.23 (d, J = 3.0 Hz, 1H), 7.49-7.47 (m, 3H), 7.40 (d, J = 8.7 Hz, 3H), 7.32-7.30 (m , 1H), 7.05 (d, J = 8.7 Hz, 2H), 5.15 (s, 2H), 5.02 (d, J = 6.9 Hz 2H), 4.87 (d, J = 6.9 Hz, 2H), 4.17 (q, J = 7.2 Hz, 2H), 3.87 (s, 3H), 3.82 (s, 2H), 2.42 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H); MS: (m/z) 464.1 [ M+H]. Example 194 2-((3-(4-((3-(5-Methoxy-2-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetic acid (compound 192)

The title compound was prepared in a similar manner as Compound 84 of Example 86. Compounds of Example 194 were obtained by hydrolysis of the compound of Example 193. ¹ H NMR (DMSO, 300 MHz): δ 12.62 (br s, 1H), 8.19 (d, J = 2.7 Hz, 1H), 7.51- 7.49 (m, 3H), 7.38 (d, J = 8.4 Hz, 3H ), 7.21 (d, J = 2.7 Hz, 1H), 7.09 (d, J = 8.7 Hz, 2H), 5.20 (s, 2H), 4.81 (d, J = 6.9 Hz 2H), 4.75 (d, J = 6.9 Hz, 2H), 3.82 (s, 3H), 3.73 (s, 2H). 2.31 (s, 3H); MS: (m/z) 436.2 [M+H]. Example 195 Methyl 2-((3-(4-((2'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3- Ethyl)acetate (compound 193)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to methyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (compound of Example 17 Step 1) (250 mg, 0.614 mmol) with (2-methoxyphenyl)boronic acid (commercial source, 139 mg, 0.915 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.59 (s, 1H), 7.52-7.50 (m, 1H), 7.46-7.44 (m, 1H), 7.41-7.40 (m, 1H), 7.37 (s, 1H), 7.34 (s, 2H), 7.31 (s, 1H), 7.06-6.98 (m, 4H), 5.13 (s, 2H), 5.00 (d, J = 6.9Hz 2H), 4.88 (d, J = 6.9 Hz, 2H), 3.89 (s, 2H), 3.83 (s, 3H), 3.70 (s, 3H); MS: (m/z) 457.1 [M+ Na]. Example 196 2-((3-(4-((2'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetic acid (compound 194)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 196 was obtained by hydrolysis of the compound of Example 195. ¹ H NMR (DMSO, 300 MHz): δ 12.57 (br s, 1H), 7.53 (s, 1H), 7.41-7.35 (m, 5H), 7.31-7.26 (m, 2H), 7.11-6.99 (m, 4H), 5.16 (s, 2H), 4.80 (d, J = 6.9Hz 2H), 4.74 (d, J = 6.9Hz, 2H), 3.72 (s, 2H), 3.71(s, 3H);MS:( m/z) 419.1 [M-H]. Example 197 Ethyl 2-((3-(4-((6-(2-(trifluoromethyl)phenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutan-3-yl) )oxy)acetate (compound 195)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((6-bromopyridin-2-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (150 mg, 0.355 mmol) and (2-(trifluoromethyl)phenyl)boronic acid (commercial Source, 101 mg, 0.532 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 500 MHz): δ 7.81-7.78 (m, 2H), 7.65-7.62 (m, 1H), 7.59-7.56 (m, 1H), 7.53-7.50 (m, 1H), 7.38- 7.36 (m, 2H), 7.27-7.24 (m, 2H), 7.05-7.03 (m, 2H), 5.29 (s, 2H), 5.01 (d, J = 6.9 Hz 2H), 4.87 (d, J = 6.9 Hz, 2H), 4.18-4.13 (m, 2H), 3.82 (s, 2H), 1.24 (t, J = 6.9 Hz, 3H); MS: (m/z) 488.2 [M+H]. Example 198 2-((3-(4-(6-(2-(Trifluoromethyl)phenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Base) acetic acid (compound 196)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 197 was obtained by hydrolysis of the compound of Example 197. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 10.56 (br s, 1H), 7.94 (t, J = 7.8 Hz, 1H), 7.87 (d, J = 7.8 Hz, 1H), 7.78-7.73 ( m, 1H), 7.69-7.64 (m, 1H), 7.57-7.54 (m, 2H), 7.46 (d, J = 7.5Hz, 1H), 7.37 (d, J = 8.4Hz, 2H), 7.08 (d , J = 8.7Hz, 2H), 5.21 (s, 2H), 4.80 (d, J = 7.2 Hz 2H), 4.73 (d, J = 7.2Hz, 2H), 3.73 (s, 2H); MS (m/ z): 460.2 [M+ H]. Example 199 Ethyl 2-((3-(4-((6-(2-chloro-4-methoxyphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutan-3-yl) )oxy)acetate (compound 197)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((6-bromopyridin-2-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (150 mg, 0.355 mmol) and (2-chloro-4-methoxyphenyl)boronic acid (commercial Source, 100 mg, 0.536 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 500 MHz): δ 7.80 (t, J = 8.0 Hz, 1H), 7.58 (t, J = 8.0 Hz, 2H), 7.52 (d, J = 8.0 Hz, 1H), 7.40 ( d, J = 8.5 Hz, 2H), 7.08-7.04 (m, 2H), 6.96-6.94 (m, 2H), 5.30 (s, 2H), 5.02 (d, J = 7.0 Hz 2H), 4.88 (d, J = 7.0 Hz, 2H), 4.18 (q, J = 7.0Hz, 2H), 3.87 (s, 3H), 3.84 (s, 2H), 1.26 (t, J = 7.0 Hz, 3H); MS: (m /z) 484.2 [M+ H]. Example 200 2-((3-(4-(6-(2-Chloro-4-methoxyphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate (compound 198)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 199 was obtained by hydrolysis of the compound of Example 199. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 10.56 (br s, 1H), 7.90 (t, J = 7.8 Hz, 1H), 7.59-7.48 (m, 3H), 7.38 (d, J = 8.4 Hz, 2H), 7.13-7.02 (m, 4H), 5.23 (s, 2H), 4.80 (d, J = 6.9 Hz 2H), 4.74 (d, J = 6.9 Hz, 2H), 3.82 (s, 3H) , 3.73 ( s, 2H); MS: (m/z) 456.2 [M+ H]. Example 201 Ethyl 2-((3-(4-((6-(2,4-dimethylphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy) Acetate (compound 199)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((6-bromopyridin-2-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (150 mg, 0.355 mmol) and (2,4-xylene)boronic acid (commercial source, 80 mg) , 0.533 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 500 MHz): δ 7.79 (t, J = 8.0 Hz, 1H), 7.49 (d, J = 7.5 Hz, 1H), 7.39 (d, J = 8.5 Hz, 2H), 7.33 ( t, J = 7.0 Hz, 2H), 7.13 (d, J = 9.5 Hz, 2H), 7.07 (d, J = 9.0 Hz, 2H), 5.30 (s, 2H), 5.02 (d, J = 7.0 Hz 2H ), 4.88 (d, J = 7.0 2H), 4.18 (q, J = 7.0 Hz 2H), 3.89 (s, 2H), 2.39 (s, 3H), 2.37 (s, 3H), 1.26 (t, J = 7.0 Hz, 3H); MS (m/z) 448.2 [M+ H]. Example 202 2-((3-(4-(6-(2,4-Dimethyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid ( Compound 200)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 201 was obtained by hydrolysis of the compound of Example 201. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.61 (br s, 1H), 7.90-7.85 (m, 1H), 7.46-7.41 (m, 2H), 7.37-7.35 (m, 2H), 7.30 -7.27 (m, 2H), 7.09-7.03 (m, 3H), 5.23 (s, 2H), 4.79 (d, J = 6.6 Hz 2H), 4.73 (d, J = 6.6Hz, 2H), 3.72 (s , 2H), 2.30 (s, 3H), 2.27 (s, 3H); MS: (m/z) 420.2 [M+H]. Example 203 Ethyl 2-((3-(4-((6-(3-fluoro-2-methylphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound 201)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((6-bromopyridin-2-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (150 mg, 0.355 mmol) and (3-fluoro-2-methylphenyl)boronic acid (commercial source) , 80 mg, 0.533 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 500 MHz): δ 7.83 (t, J = 8.0 Hz, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.40 (d, J = 9.0 Hz, 2H), 7.35 ( d, J = 7.5 Hz, 1H), 7.26-7.25 (m, 1H), 7.23 (d, J = 7.0Hz, 1H), 7.12-7.06 (m, 3H), 5.30 (s, 2H), 5.02 (d , J = 6.5 Hz 2H), 4.88 (d, J = 6.5Hz, 2H), 4.18 (q, J = 7.5 Hz 2H), 3.84 (s, 2H), 2.81 (s, 3H), 1.26 (t, J = 7.5 Hz, 3H); MS: (m/z) 452.2 [M+H]. Example 204 2-((3-(4-(6-(3-Fluoro-2-methylphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy ) acetic acid (compound 202)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 204 was obtained by hydrolysis of the compound of Example 203. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.61 (br s, 1H), 7.93 (t, J = 7.8 Hz, 1H), 7.49 (t, J = 11.1 Hz, 2H), 7.37-7.35 ( m, 2H), 7.30-7.28 (m, 1H), 7.25 (d, J = 8.1 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H), 5.24 (s, 2H), 4.79 (d, J = 6.6 Hz 2H), 4.73 (d, J = 6.6Hz, 2H), 3.72 (s, 2H), 2.18 (s, 3H); MS (m/z) 423.4 [M+]. Example 205 Ethyl 2-((3-(4-((5-(2-(trifluoromethyl)phenyl)thiophen-2-yl)methoxy)phenyl)oxycyclobutan-3-yl) )oxy)acetate (compound 203)

The title compound was prepared in a similar manner to compound 83 as in Example 85, which was taken to ethyl 2-((3-(4-((5-bromothiophen-2-yl)methoxy)phenyl)oxycyclobutane - 3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (150 mg, 0.351 mmol) and (2-(trifluoromethyl)phenyl)boronic acid (commercial Source, 99.7 mg, 0.525 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.78 (d, J = 7.5 Hz, 1H), 7.56-7.48 (m, 3H), 7.41 (d, J = 8.7 Hz, 2H), 7.09-7.04 (m , 4H), 5.25 (s, 2H), 5.02 (d, J = 7.2 Hz, 2H), 4.88 (d, J = 7.2 Hz, 2H), 4.18 (q, J = 7.2Hz, 2H), 3.83 (s , 2H), 1.25 (t, J = 7.2 Hz, 3H); MS: (m/z) 515.2 [M+ Na]. Example 206 2-((3-(4-((5-(2-(Trifluoromethyl)phenyl)thiophen-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate (compound 204)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 206 was obtained by hydrolysis of the compound of Example 206. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.62 (br s, 1H), 7.84-7.57 (m, 4H), 7.39 (d, J = 8.7 Hz, 2H), 7.23 (s, 1H), 7.10-7.05 (m, 3H), 5.33 (s, 2H), 4.81-4.75 (m, 4H), 3.74 (s, 2H); MS (m/z) 487.1 [M+ Na]. Example 207 Ethyl 2-((3-(4-((2-(3-)))))))))))) Oxy)acetate (compound 205)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((2-bromothiazol-4-yl)methoxy)phenyl)oxycyclobutane - 3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (150 mg, 0.350 mmol) and (3-fluoro-2-methylphenyl)boronic acid (commercial source) , 81 mg, 0.522 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.43-7.33 (m, 3H), 7.30-7.27 (m, 1H), 7.24-7.07 (m, 4H), 5.31 (s, 2H), 5.02 (d, J = 6.9 Hz, 2H), 4.88 (d, J = 6.9 Hz, 2H), 4.18 (q, J = 7.2Hz, 2H), 3.83 (s, 2H), 2.48 (s, 3H), 1.25 (t, J = 7.2 Hz, 3H); MS: (m/z) 458.2 [M+ Na]. Example 208 2-((3-(4-((2-(3-fluoro-2-methylphenyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy ) acetic acid (compound 206)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 208 was obtained by hydrolysis of the compound of Example 208. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.62 (br s, 1H), 7.91 (s, 1H), 7.57 (d, J = 7.2 Hz, 1H), 7.04-7.32 (m, 4H), 7.14 (d, J = 8.1 Hz, 2H), 5.28 (s, 2H), 4.82 (d, J = 6.9 Hz, 2H), 4.76 (d, J = 6.9 Hz, 2H), 3.75 (s, 2H), 2.43 (s, 3H); MS (m/z) 427.9 [M-H]. Example 209 Ethyl 2-((3-(4-((2-(o-to))thiazol-4-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid Ester (compound 207)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((2-bromothiazol-4-yl)methoxy)phenyl)oxycyclobutane - 3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (150 mg, 0.350 mmol) and o-tolylboronic acid (commercial source, 11 mg, 0.522 mmol) Reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.75-7.72 (m, 1H), 7.41-7.32 (m, 5H), 7.21-7.20 (m, 1H), 7.10 (d, J = 8.7 Hz, 2H) , 5.33 (s, 2H), 5.03 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9 Hz, 2H), 4.18 (q, J = 7.2Hz, 2H), 3.83 (s, 2H) , 2.60 (s, 3H), 1.25 (t, J = 7.2 Hz, 3H); MS: (m/z) 440.2 [M+H]. Example 210 2-((3-(4-((2-(o-tolyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (Compound 208 )

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 210 was obtained by hydrolysis of the compound of Example 209. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.62 (br s, 1H), 7.86 (s, 1H), 7.76 (d, J = 7.5 Hz, 1H), 7.40-7.33 (m, 4H), 7.15 (d, J = 8.4 Hz, 3H), 5.27 (s, 2H), 4.82 (d, J = 6.9 Hz, 2H), 4.76 (d, J = 6.9 Hz, 2H), 3.75 (s, 2H), 2.53 (s, 3H); MS: (m/z) 412.1 [M+H]. Example 211 Ethyl 2-((3-(4-(2-(2-(trifluoromethyl)phenyl)thiazol-5-yl)methoxy)phenyl)oxycyclobutan-3-yl) )oxy)acetate (compound 209)

The title compound was prepared in a similar manner to compound 83 as in Example 85, which was taken to ethyl 2-((3-(4-((2-bromothiazol-5-yl)methoxy)phenyl)oxycyclobutane - 3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (150 mg, 0.350 mmol) and (2-(trifluoromethyl)phenyl)boronic acid (commercial Source, 100 mg, 0.527 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.91 (s, 1H), 7.85-7.82 (m, 1H), 7.66-7.65 (m, 3H), 7.44 (d, J = 8.7 Hz, 2H), 7.07 (d, J = 8.7Hz, 2H), 5.34 (s, 2H), 5.04 (d, J = 7.2 Hz, 2H), 4.88 (d, J = 7.2 Hz, 2H), 4.19 (q, J = 7.2Hz , 2H), 3.84 (s, 2H), 1.26 (t, J = 7.2 Hz, 3H); MS (m/z) 494.1 [M+ H]. Example 212 2-((3-(4-(2-(2-(Trifluoromethyl)phenyl)thiazol-5-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate (compound 210)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 212 was obtained by hydrolysis of the compound of Example 211. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.63 (br s, 1H), 8.07 (s, 1H), 7.95-7.92 (m, 1H), 7.81-7.78 (m, 3H), 7.42 (d , J = 8.4 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 5.46 (s, 2H), 4.83 (d, J = 7.2 Hz, 2H), 4.76 (d, J = 7.2 Hz, 2H ), 3.75 (s, 2H); MS: (m/z) 466.1 [M+H]. Example 213 Ethyl 2-((3-(4-((5-(3-chloro-2-methylphenyl)thiophen-2-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound 211)

The title compound was prepared in a similar manner to compound 83 as in Example 85, which was taken to ethyl 2-((3-(4-((5-bromothiophen-2-yl)methoxy)phenyl)oxycyclobutane - 3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (150 mg, 0.351 mmol) and (3-chloro-2-methylphenyl)boronic acid (commercial source) , 90.0 mg, 0.528 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.41-7.36 (m, 3H), 7.29 (s, 1H), 7.17-7.15 (m, 2H), 7.11-7.04 (m, 2H), 6.93 (d, J = 3.6Hz, 1H), 5.24 (s, 2H), 5.02 (d, J = 6.9 Hz, 2H), 4.88 (d, J = 6.9 Hz, 2H), 4.18 (q, J = 7.2Hz, 2H) , 3.83 (s, 2H), 2.44 (s, 3H), 1.25 (t, J = 7.2 Hz, 3H); MS: (m/z) 495.2 [M+ Na]. Example 214 2-((3-(4-((5-(3-chloro-2-methylphenyl))thiophen-2-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy ) acetic acid (compound 212)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 213 was obtained by hydrolysis of the compound of Example 213. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.60 (br s, 1H), 7.48-7.45 (m, 1H), 7.40-7.34 (m, 2H), 7.32-7.29 (m, 1H), 7.26 -7.24 (m, 2H), 7.11-7.08 (m, 3H), 5.33 (s, 2H), 4.81 (d, J = 7.2 Hz, 2H), 4.75 (d, J = 7.2 Hz, 2H), 3.74 ( s, 2H), 2.38 (s, 3H); MS: (m/z) 467.1 [M+ Na]. Example 215 Ethyl 2-((3-(4-((6-(3-chloro-2-methylphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound 213)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((6-bromopyridin-2-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (150 mg, 0.355 mmol) and (3-chloro-2-methylphenyl)boronic acid (commercial source) , 90 mg, 0.528 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 500 MHz): δ 7.83 (t, J = 8.0 Hz, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.40 ( d, J = 9.0 Hz, 2H), 7.33-7.31 (m, 2H), 7.28-7.24(m, 1H), 7.07 (d, J = 8.5Hz, 2H), 5.30 (s, 2H), 5.02 (d , J = 7.0 Hz 2H), 4.88 (d, J = 7.0 Hz, 2H), 4.18 (q, J = 7.0 Hz, 2H), 3.84 (s, 2H), 2.36 (s, 3H), 1.26 (t, J = 7.0 Hz, 3H); MS: (m/z) 468.2 [M+ H]. Example 216 2-((3-(4-(6-(3-Chloro-2-methylphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy ) acetic acid (compound 214)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 215 was obtained by hydrolysis of the compound of Example 216. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.62 (br s, 1H), 7.93-7.91 (m, 1H), 7.53-7.44 (m, 4H), 7.38-7.32 (m, 4H), 7.09 (d, J = 8.4 Hz, 1H), 5.24 (s, 2H), 4.77-4.71 (m, 4H), 3.70 (s, 2H), 2.26 (s, 3H); MS: (m/z) 440.2 [ M+ H]. Example 217 Ethyl 2-((3-(4-(2-(2-(trifluoromethyl)phenyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutan-3-yl) )oxy)acetate (compound 215)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((2-bromothiazol-4-yl)methoxy)phenyl)oxycyclobutane - 3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (150 mg, 0.350 mmol) and (2-(trifluoromethyl)phenyl)boronic acid (commercial Source, 99.7 mg, 0.525 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.84-7.82 (m, 1H), 7.67-7.61 (m, 3H), 7.50 (s, 1H), 7.40 (d, J = 8.7 Hz, 2H), 7.09 (d, J = 8.7Hz, 2H), 5.33 (s, 2H), 5.03 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9 Hz, 2H), 4.18 (q, J = 7.2Hz) , 2H), 3.83 (s, 2H), 1.26 (t, J = 7.2 Hz, 3H); MS: (m/z) 494.1 [M+H]. Example 218 2-((3-(4-(2-(2-(Trifluoromethyl)phenyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate (compound 216)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 217 was obtained by hydrolysis of the compound of Example 217. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.62 (br s, 1H), 7.96-7.92 (m, 2H), 7.81-7.76 (m, 3H), 7.39 (d, J = 8.7 Hz, 2H ), 7.13 (d, J = 8.7 Hz, 2H), 5.26 (s, 2H), 4.82 (d, J = 6.9 Hz, 2H), 4.76 (d, J = 6.9 Hz, 2H), 3.75 (s, 2H) ); MS (m/z) 466.1 [M+ H]. Example 219 Ethyl 2-((3-(4-((2-(3-fluoro-3-methyl))thiazol-5-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound 217)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((2-bromothiazol-4-yl)methoxy)phenyl)oxycyclobutane - 3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (200 mg, 0.467 mmol) and (3-fluoro-2-methylphenyl)boronic acid (commercial source) , 108 mg, 0.702 mmol) of the reaction.

¹ H NMR (CDCl ₃ , 300 MHz): δ 7.90 (s, 1H), 7.58 (s, 1H), 7.51-7.46 (m, 1H), 7.44-7.40 (m, 2H), 7.24-7.19 (m, 1H), 7.07-6.98 (m, 2H), 5.29 (s, 2H), 5.03 (d, J = 7.2 Hz, 2H), 4.88- 4.84 (m, 2H), 4.18 (q, J = 7.2Hz, 2H ), 3.84 (s, 2H), 2.59 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H); MS: (m/z) 458.2 [M+ Na]. Example 220 2-((3-(4-((2-(3-fluoro-2-methylphenyl)thiazol-5-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy ) acetic acid (compound 218)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 220 was obtained by hydrolysis of the compound of Example 219. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.61 (br s, 1H), 8.08 (s, 1H), 7.56 (d, J = 7.2 Hz, 1H), 7.42-7.32 (m, 4H), 7.14-7.08 (m, 2H), 5.45 (s, 2H), 4.82 (d, J = 6.9 Hz, 2H), 4.76 (d, J = 6.9 Hz, 2H), 3.75 (s, 2H), 2.43 (s , 3H); MS (m/z) 454.1 [M+ Na]. Example 221 Methyl 2-((3-(4-((2'-)difluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate (compound 219)

The title compound was prepared in a similar manner to compound 107 as in Example 109, which was taken to methyl 2-((3-(4-(4,4,5,5,5-tetramethyl-1,3,2-) Dioxaborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (1 g, 2.13 mmol) with 1-bromo-2-(di) Reaction of fluoromethyl)benzene (commercial source, 69 mg, 0.333 mmol).

¹ H NMR (CDCl ₃ , 300 MHz): δ 7.80-7.78 (m, 1H), 7.53-7.48 (m, 4H), 7.46 (s, 2H), 7.43-7.36 (m, 4H), 7.04 (d, J = 8.7 Hz, 2H), 5.15 (s, 2H), 5.01 (d, J = 6.9 Hz, 2H), 4.87 (d, J = 6.9 Hz, 2H), 3.84 (s, 2H), 3.71 (s, 3H); MS: (m/z) 477.1 [M+ Na]. Example 222 2-((3-(4-((2'-(Difluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid (compound 220)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 221 was obtained by hydrolysis of the compound of Example 221. ¹ H NMR (DMSO, 300 MHz): δ 12.62 (br s, 1H), 7.76 (d, J = 7.5 Hz, 1H), 7.64-7.56 (m, 2H), 7.54-7.51 (m, 2H), 7.45 (s, 1H), 7.41-7.37 (s, 4H), 7.34 (d, J = 6.5Hz, 1H), 7.10 (d, J = 8.5Hz, 2H), 5.21 (s, 2H), 4.81 (d, J = 7.0 Hz, 2H), 4.75 (d, J = 7.0 Hz, 2H), 3.74 (s, 2H); MS: (m/z) 463.3 [M+Na]. Example 223 Ethyl 2-((3-(4-((4'-(3-(methylsulfonyl)propoxy)-2'-(trifluoromethyl)-[1,1'-biphenyl) ]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (compound 221) Step 1:1-bromo-4-(3-(methylsulfonyl) Synthesis of propoxy)-2-(trifluoromethyl)benzene

Addition of cesium carbonate (1926 mg, 5.91 mmol) to 4-bromo-3-(trifluoromethyl)phenol (commercial source, 570 mg, 2.365 mmol) and 3-(methylsulfonyl)propyl in anhydrous DMF A mixture of 4-methylbenzenesulfonate (commercial source, 691 mg, 2.365 mmol) was added and the reaction was stirred at RT overnight. After the reaction was completed, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic solvent was removed, and the residue was purified mjjjjjjjj Yield: 73.8 %; ¹ H NMR (CDCl ₃ , 300 MHZ): δ 7.62 (d, J = 8.2 Hz, 1H), 7.22 (d, J = 1.6 Hz, 1H), 6.91 (d, J = 8.2 Hz , 1H), 4.17 (t, J = 6.0 Hz, 2H), 3.28 (t, J = 7.5 Hz, 2H), 2.99 (s, 3H), 2.42 -2.37 (m, 2H); MS: (m/z ) 383.5 [M+ Na]. Step 2: Ethyl 2-((3-(4-((4'-(3-(methylsulfonyl))propoxy)-2'-(trifluoromethyl)-[1,1'-linked Synthesis of Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate

Add tetrakistriphenylphosphine palladium (0) (22.21 mg, 0.019 mmol) to dioxane (4 ml) and ethyl 2-((3-(4-((3-) 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy) Acid ester (Example 109 Step 1, compound 150 mg, 0.320 mmol), 1-bromo-4-(3-(methylsulfonyl)propoxy)-2-(trifluoromethyl)benzene (Step 1) The compound, 139 mg, 0.384 mmol) was taken in a degassed solution of sodium bicarbonate (67.3 mg, 0.801 mmol) and the mixture was heated in a microwave for 20 min. After the reaction was completed, the reaction mixture was diluted with ethyl acetate. The organic layer was washed with EtOAcq. Yield: 23.07%. Example 223a 2-((3-(4-((4'-(3-(methylsulfonyl)propoxy)-2'-(trifluoromethyl)-[1,1 '-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid calcium (compound 221a)

The title compound was prepared via the general procedure for the preparation of the calcium salt as described in Method A, using Compound 223. ¹ H NMR (500 MHz, DMSO-d ₆ ) δ: 7.48-7.45 (m, 2H), 7.41 (d, J = 6.4 Hz, 2H), 7.37-7.24 (m, 4H), 7.25 (d, J = 8 Hz, 1H ), 7.05 (d, J = 8 Hz, 2H), 5.16 (s, 2H), 4.83 (d, J = 6.4 Hz, 2H), 4.64 (d, J = 6.4 Hz, 2H), 4.22 (t, J = 6.2 Hz, 2H), 3.33-3.21 (m, 2H), 3.24 (s, 2H), 3.03 (s, 3H), 2.20-2.16 (m, 2H); MS: (m/z) 593 [MH] (mass of parent acid). Example 224 Ethyl 2-((3-(4-((3'-fluoro-2'-methyl-[1,1'-biphenyl)-3-yl)methoxy)-2-methylbenzene) Oxycyclobutane-3-yl)oxy)acetate (Compound 222) Step 1: Synthesis of 4-(benzyloxy)-1-bromo-2-methylbenzene

Potassium carbonate (3.33 g, 24.06 mmol) was added to a stirred solution of 4-bromo-3-methylphenol (commercial source, 3.0 g, 16.04 mmol) from acetonitrile at RT. The reaction mixture was stirred at RT for 10 min then bromobenzene (1.9 mL, 16.04 mmol). The reaction mixture was refluxed at 90 °C for 2 h. After the reaction was completed, the reaction mixture was filtered and washed with acetonitrile. The filtrate was concentrated, evaporated with EtOAc EtOAc m. Yield: 85.58%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.43-7.37 (m, 4H), 7.35-7.32 (m, 2H), 6.89 (d, J = 3.0 Hz, 1H), 6.71- 6.67 (m, 1H), 5.03 (s, 2H), 2.36 (s, 3H); MS: (m/z) 301.1 [M+ Na]. Step 2: Synthesis of 3-(4-(benzyloxy)-2-methylbenzene)oxycyclobutan-3-ol

The title compound was prepared in a similar manner as the compound of Example 1 Step 1. Substituting 4-(benzyloxy)-1-bromo-2-methylbenzene (compound of Step 1) for 1-(benzyloxy)-4-bromobenzene. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.46-7.35 (m, 5H), 7.11 (d, J = 8.4 Hz, 1H), 6.86-6.78 (m, 2H), 5.22 (d, J = 7.2 Hz , 2H), 5.08 (s, 2H), 4.90 (d, J = 7.2 Hz, 2H), 2.34 (s, 1H), 2.25 (s, 3H); MS (m/z) 293.1 [M+ Na]. Step 3: Synthesis of ethyl 2-((3-(4-(benzyloxy)-2-methylphenyl)oxycyclobutane-3-yl)oxy)acetate

The title compound was prepared in a similar manner as the compound of Example 1 Step 2. Substitution of 3-(4-(benzyloxy)phenyl)oxyl ring with 3-(4-(benzyloxy)-2-methylphenyl)oxycyclobutan-3-ol (compound of step 2) Butan-3-ol, and methyl 2-bromoacetate was replaced with ethyl 2-bromoacetate. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.44-7.35 (m, 5H), 7.09 (d, J = 8.4 Hz, 1H), 6.86-6.78 (m, 2H), 5.11 (d, J = 6.9 Hz , 2H), 5.07 (s, 2H), 5.00 (d, J = 6.9Hz, 2H), 4.09 (q, J = 7.2Hz, 2H), 3.77 (s, 2H), 2.23(s, 3H), 1.21 (t, J = 7.2 Hz, 3H); MS: (m/z) 379.2 [M+ Na]. Step 4: Synthesis of ethyl 2-((3-(4-hydroxy-2-methylphenyl)oxycyclobutane-3-yl)oxy)acetate

The title compound was prepared in a similar manner as the compound of Example 1 Step 3. Substituting methyl 2-((3-(4-(benzyloxy)-2-methylphenyl)oxycyclobutan-3-yl)oxy)acetate (compound of step 3) for methyl 2 -((3-(4-(Benzyloxy)phenyl)oxycyclobutane-3-yl)oxy)acetate. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.04 (d, J = 8.1 Hz, 1H), 6.69-6.65 (m, 2H), 5.32 (s, 1H), 5.11 (d, J = 6.9 Hz, 2H ), 5.00 (d, J = 6.9Hz, 2H), 4.10 (q, J = 7.2Hz, 2H), 3.70 (s, 2H), 2.20(s, 3H), 1.22 (t, J = 7.2Hz, 3H ); MS: (m/z) 289.1 [M+ Na]. Step 5: Ethyl 2-((3-(4-(3-bromobenzyl)oxy)-2-methylphenyl)oxycyclobutan-3-yl)oxy)acetate

Addition of cesium carbonate (789 mg, 2.422 mmol) to ethyl 2-((3-(4-hydroxy-2-methylphenyl)oxycyclobutane-3-yl)oxy) in DMF (5 ml) A stirred solution of acetate (compound of Step 4, 430 mg, 1.615 mmol). The reaction mixture was stirred at RT for 10 min then added 1-bromo-3-(bromomethyl)benzene ( commercial, 404 mg, 1.615 mmol). The reaction mixture was further stirred at 80 ° C for 2 h. After the reaction was completed, the reaction mixture was taken up in ice and concentrated. The residue was redissolved in EtOAc (EtOAc)EtOAc. Yield: 86.78%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.61 (s, 1H), 7.50 (m, 1H), 7.38-7.35 (m, 1H), 7.30- 7.25 (m, 1H), 7.10 (d, J = 8.4 Hz, 1H), 6.84 (d, J = 2.4 Hz, 1H), 6.79-6.76 (m, 1H), 5.11 (d, J = 6.9 Hz, 2H), 5.04 (s, 2H) ), 5.00 (d, J = 6.9Hz, 2H), 4.10 (q, J = 7.2Hz, 2H), 3.78 (s, 2H), 2.23 (s, 3H), 1.21 (t, J = 7.2Hz, 3H ); MS: (m/z) 459.1 [M+ Na]. Step 6: Ethyl 2-((3-(4-((3'-fluoro-2'-methyl-[1,1'-biphenyl)-3-yl)methoxy)-2-methyl) Synthesis of Phenyl)oxocyclobutane-3-yl)oxy)acetate

The title compound was prepared in a similar manner to compound 83 as in Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy))-2-methylphenyl)oxycyclobutane- Reaction of 3-yl)oxy)acetate (compound of Step 5, 100 mg, 0.230 mmol) with (3-fluoro-2-methylphenyl)boronic acid (commercial source, 53.4 mg, 0.347 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.48-7.45 (m, 2H), 7.39 (s, 1H), 7.33-7.31 (m, 1H), 7.23- 7.18 (m, 1H), 7.10-7.05 ( m, 3H), 6.89-6.86 (m, 1H), 6.82-6.79 (m, 1H), 5.12 (s, 2H), 5.09 (d, J= 7.2 Hz, 2H), 5.00 (d, J = 6.9Hz) , 2H), 4.10 (q, J = 7.2Hz, 2H), 3.77 (s, 2H), 2.23 (s, 3H), 2.18 (d, J = 2.1Hz, 3H), 1.21 (t, J = 7.2Hz , 3H); MS (m/z) 482.1 [M+NH ₄ ]. Example 225 2-((3-(4-((3'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)-2-methylphenyl)oxy Cyclobutane-3-yl)oxy)acetic acid (compound 223)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 225 was obtained by hydrolysis of the compound of Example 224. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.50 (br s, 1H), 7.48 (s, 2H), 7.42 (s, 1H), 7.31-7.27 (m, 2H), 7.21- 7.15 (m , 2H), 7.09 (d, J = 7.5Hz, 1H), 6.90-6.84 (m, 2H), 5.17 (s, 2H), 4.95 (d, J = 7.2 Hz, 2H), 4.79 (d, J = 7.2 Hz, 2H), 3.63 (s, 2H), 2.12 (d, J = 4.2 Hz, 3H), 1.23 (s, 3H); MS: (m/z) 459.1 [M+ Na]. Example 226 Ethyl 2-((3-(4-((3'-chloro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)-2-methylbenzene) Oxycyclobutane-3-yl)oxy)acetate (compound 224)

The title compound was prepared in a similar manner to compound 83 as in Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy))-2-methylphenyl)oxycyclobutane- Reaction of 3-yl)oxy)acetate (Example 224 Step 5 Compound, 100 mg, 0.230 mmol) with (3-chloro-2-methylphenyl)boronic acid (commercial source, 58.5 mg, 0.343 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.47-7.45 (m, 3H), 7.41-7.37 (m, 2H), 7.22-7.17 (m, 2H), 7.10- 7.07 (m, 1H), 6.86 ( s, 1H), 6.82-6.79 (m, 1H), 5.12 (s, 2H), 5.09 (d, J= 6.9 Hz, 2H), 5.00 (d, J = 6.9Hz, 2H), 4.10 (q, J = 7.2 Hz, 2H), 3.77 (s, 2H), 2.28 (s, 3H), 2.23 (s, 3H), 1.21 (t, J = 7.2 Hz, 3H); MS: (m/z) 503.2 [M+ Na]. Example 227 2-((3-(4-((3'-Chloro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)-2-methylphenyl)oxy Cyclobutane-3-yl)oxy)acetic acid (compound 225)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 226 was obtained by hydrolysis of the compound of Example 226. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.50 (br s, 1H), 7.48-7.45 (m, 2H), 7.40 (s, 2H), 7.31-7.26 (m, 2H), 7.20 (d , J = 7.8 Hz, 2H), 6.90-6.84 (m, 2H), 5.16 (s, 2H), 4.96 (d, J = 7.2 Hz, 2H), 4.79 (d, J = 7.2 Hz, 2H), 3.64 (s, 2H), 2.21 (s, 3H), 2.12 (s, 3H); MS (m/z) 475.1 [M+ Na]. Example 228 Ethyl 2-((3-(2-methyl-4-((2'-methyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxycyclobutane Alk-3-yl)oxy)acetate (compound 226)

The title compound was prepared in a similar manner to compound 83 as in Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy))-2-methylphenyl)oxycyclobutane- Reaction of 3-yl)oxy)acetate (Example 224 Step 5 Compound, 100 mg, 0.230 mmol) with o-tolylboronic acid (commercial source, 46.8 mg, 0.344 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.49-7.41 (m, 3H), 7.33-7.28 (m, 5H), 7.10 (d, J = 8.4 Hz, 1H), 6.86 (s, 1H), 6.82 -6.79 (m, 1H), 5.12 (s, 2H), 5.09 (d, J = 6.9 Hz, 2H), 5.00 (d, J = 6.9Hz, 2H), 4.10 (q, J = 7.2Hz, 2H) , 3.77 (s, 2H), 2.28 (s, 3H), 2.23 (s, 3H), 1.21 (t, J = 7.2 Hz, 3H); MS: (m/z) 469.2 [M+ Na]. Example 229 2-((3-(2-Methyl-4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-yl)oxy)acetic acid (compound 227)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 229 was obtained by hydrolysis of the compound of Example 228. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.44 (br s, 1H), 7.47-7.40 (m, 3H), 7.28-7.26 (m, 4H), 7.21-7.18 (m, 2H), 6.90 -6.84 (m, 2H), 5.17 (s, 2H), 4.96 (d, J = 7.2 Hz, 2H), 4.80 (d, J = 7.2 Hz, 2H), 3.64 (s, 2H), 2.20 (s, 3H), 2.12 (s, 3H); MS: (m/z) 441.1 [M+ Na]. Example 230 Ethyl 2-((3-(2-fluoro-4-((3'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate (Compound 228) Step 1: 4-(Benzyloxy)-1-bromo-2-fluorobenzene

Potassium carbonate (3.25 g, 23.56 mmol) was added to a stirred solution of 4-bromo-3-fluorophenol (commercial source, 3.0 g, 15.71 mmol) from acetonitrile at RT. The reaction mixture was stirred at RT for 10 min then bromobenzene (1. The reaction mixture was refluxed at RT for 10 min then bromobenzene (1.86 ml, 15.71 mmol). The reaction mixture was stirred at 90 °C for 2 h. After the reaction was completed, the reaction mixture was filtered and washed with acetonitrile. The filtrate was concentrated, redissolved in ethyl acetate, washed with water, brine and dried over anhydrous sodium sulfate. The organic solvent was removed, and the residue was purified by flash column chromatography toiel Yield: (88.43%); ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.44-7.35 (m, 6H), 6.80-6.75 (m, 1H), 6.70-6.67 (m, 1H), 5.04 (s , 2H); MS: (m/z) 280.1 [MH]. Step 2: Synthesis of 3-(4-(benzyloxy)-2-fluorophenyl)oxocyclobutane-3-ol

The title compound was prepared in a similar manner as the compound from step 1 of Example 1. Substituting 4-(benzyloxy)-1-bromo-2-fluorobenzene (the compound of Step 1) for 1-(benzyloxy)-4-bromobenzene. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.43-7.42 (m, 4H), 7.39-7.36 (m, 1H), 7.28-7.20 (m, 1H), 6.82-6.73 (m, 2H), 5.13 ( d, J = 6.9 Hz, 2H), 5.08 (s, 2H), 4.90 (d, J = 6.9 Hz, 2H), 2.63 (s, 1H); MS: (m/z) 275.1 [M+H]. Step 3: Synthesis of ethyl 2-((3-(4-(benzyloxy)-2-fluorophenyl)oxycyclobutane-3-yl)oxy)acetate

The title compound was prepared in a similar manner as the compound from step 2 of Example 1. Substituting 3-(4-(benzyloxy)phenyl)oxyl ring with 3-(4-(benzyloxy)-2-fluorophenyl)oxycyclobutan-3-ol (compound of step 2) Butan-3-ol, and methyl 2-bromoacetate was replaced with ethyl 2-bromoacetate. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.44-7.37 (m, 5H), 7.14 (t, J = 8.7 Hz, 1H), 6.82-6.70 (m, 2H), 5.08 (s, 2H), 5.06 -5.00 (m, 4H), 4.14 (q, J = 7.2Hz, 2H), 3.90 (s, 2H), 1.21 (t, J = 7.2Hz, 3H); MS (m/z) 383.2 [M+ Na] . Step 4: Synthesis of ethyl 2-((3-(2-fluoro-4-hydroxyphenyl)oxycyclobutane-3-yl)oxy)acetate

The title compound was prepared in a similar manner as the compound from step 3 of Example 1. Substituting methyl 2-((3-(4-(benzyloxy)-2-fluorophenyl)oxycyclobutan-3-yl)oxy)acetate (compound of step 3) for methyl 2 -((3-(4-(Benzyloxy)phenyl)oxycyclobutane-3-yl)oxy)acetate. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.07 (t, J = 8.1 Hz, 1H), 6.66-6.58 (m, 2H), 5.81 (s, 1H), 5.06-5.00 (m, 4H), 4.13 (q, J = 7.2 Hz, 2H), 3.92 (s, 2H), 1.24 (t, J = 7.2 Hz, 3H); MS: (m/z) 293.1 [M+ Na]. Step 5: Synthesis of ethyl 2-((3-(4-(3-bromobenzyl)oxy)-2-fluorophenyl)oxycyclobutane-3-yl)oxy)acetate

The title compound was prepared in a similar manner as the compound of Example 224 Step 5. Substituting ethyl 2-((3-(2-fluoro-4-hydroxyphenyl)oxycyclobutane-3-yl)oxy)acetate (compound of step 4) for ethyl 2-((3- (4-Hydroxy-2-methylphenyl)oxycyclobutane-3-yl)oxy)acetate. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.60 (s, 1H), 7.51-7.49 (d, J = 7.8 Hz, 1H), 7.37-7.34 (m, 1H), 7.31 (s, 1H), 7.16 (d, J = 8.4 Hz, 1H), 6.81-6.69 (m, 2H), 5.05-5.00 (m, 6H), 4.11 (q, J = 7.2 Hz, 2H), 3.90 (s, 2H), 1.28 ( t, J = 7.2 Hz, 3H); MS: (m/z) 462.2 [M+ Na]. Step 6: Ethyl 2-((3-(2-fluoro-4-((3'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)benzene) Synthesis of oxycyclobutane-3-yl)oxy)acetate

The title compound was prepared in a similar manner to compound 83 as in Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy))-2-fluorophenyl)oxycyclobutane- Reaction of 3-yl)oxy)acetate (compound of Step 5, 100 mg, 0.228 mmol) with (3-fluoro-2-methylphenyl)boronic acid (commercial source, 52.5 mg, 0.341 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.51-7.42 (m, 2H), 7.37 (s, 1H), 7.33 (s, 1H), 7.23- 7.12 (m, 2H), 7.08-7.03 (m, 2H), 6.84-6.72 (m, 2H), 5.32 (s, 2H), 5.06-5.00 (m, 4H), 4.11 (q, J = 7.2Hz, 2H), 3.90 (s, 2H), 2.18 (d , J = 2.4 Hz, 3H), 1.22 (t, J = 7.2 Hz, 3H); MS: (m/z) 491.4 [M+Na]. Example 231 2-((3-(2-Fluoro-4-((3'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxy Cyclobutane-3-yl)oxy)acetic acid (compound 229)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 230 was obtained by hydrolysis of the compound of Example 230. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.58 (br s, 1H), 7.49-7.43 (s, 2H), 7.37 (s, 1H), 7.34-7.27 (m, 3H), 7.18 (t , J = 9.3Hz, 1H), 7.09 (d, J = 7.5Hz, 1H), 7.01 (d, J = 12.6, 1H), 6.93 (d, J = 8.4Hz, 1H), 5.21 (s, 2H) , 4.89 (d, J = 7.2 Hz, 2H), 4.81 (d, J = 7.2 Hz, 2H), 3.76 (s, 2H), 2.10 (s, 3H); MS: (m/z) 463.2 [M+ Na ]. Example 232 Ethyl 2-((3-(4-((3'-chloro-2'-methyl-[1,1'-biphenyl)-3-yl)methoxy)-2-fluorophenyl) Oxycyclobutane-3-yl)oxy)acetate (compound 230)

The title compound was prepared in a similar manner to compound 83 as in Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy))-2-fluorophenyl)oxycyclobutane- Reaction of 3-yl)oxy)acetate (Example 230 Step 5 compound, 100 mg, 0.228 mmol) with (3-chloro-2-methylphenyl)boronic acid (commercial source, 58.1 mg, 0.341 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.51-7.35 (m, 5H), 7.22-7.12 (m, 3H), 6.83-6.72 (m, 2H), 5.12 (s, 2H), 5.06-5.00 ( m, 4H), 4.11 (q, J = 7.2Hz, 2H), 3.90 (s, 2H), 2.28 (s, 3H), 1.22 (t, J = 7.2Hz, 3H); MS: (m/z) 507.2 [M+ Na]. Example 233 2-((3-(4-((3'-Chloro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)-2-fluorophenyl)oxy) Cyclobutane-3-yl)oxy)acetic acid (compound 231)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 233 was obtained by hydrolysis of the compound of Example 232. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.59 (br s, 1H), 7.45-7.41 (m, 2H), 7.37 (s, 2H), 7.34-7.26 (m, 3H), 7.20 (d , J = 7.5Hz, 1H), 7.01-6.90 (m, 2H), 5.21 (s, 2H), 4.89 (d, J = 7.2 Hz, 2H), 4.81 (d, J = 7.2 Hz, 2H), 3.76 (s, 2H), 2.20 (s, 3H); MS: (m/z) 479.1 [M+ Na]. Example 234 Ethyl 2-((3-(2-fluoro-4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate (compound 232)

The title compound was prepared in a similar manner to compound 83 as in Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy))-2-fluorophenyl)oxycyclobutane- Reaction of 3-yl)oxy)acetate (Example 230 Step 5 compound, 100 mg, 0.228 mmol) with o-tolylboronic acid (commercial source, 46.4 mg, 0.341 mmol).

¹ H NMR (CDCl ₃ , 300 MHz): δ 7.50-7.45 (m, 3H), 7.42-7.39 (m, 1H), 7.35-7.32 (m, 2H), 7.18-7.12 (m, 2H), 6.83- 6.73 (m, 3H), 5.13 (s, 2H), 5.06-5.00 (m, 4H), 4.11 (q, J = 7.2Hz, 2H), 3.90 (s, 2H), 2.28 (s, 3H), 1.22 (t, J = 7.2 Hz, 3H); MS: (m/z) 473.2 [M+ Na]. Example 235 2-((3-(2-Fluoro-4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid (compound 233)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 234 was obtained by hydrolysis of the compound of Example 234. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 12.56 (br s, 1H), 7.48-7.41 (m, 3H), 7.29-7.27 (m, 4H), 7.21-7.20 (m, 2H), 7.00 -6.90 (m, 2H), 5.21 (s, 2H), 4.89 (d, J = 7.2 Hz, 2H), 4.81 (d, J = 7.2 Hz, 2H), 3.72 (s, 2H), 2.20 (s, 3H); MS (m/z) 423.4 [M+H]. Example 236 Ethyl 2-((3-(4-((2'-chloro-6'-(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate (compound 234)

The title compound was prepared in a similar manner as Compound 95 of Example 97, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (100 mg, 0.246 mmol) with (2-chloro-6-(trifluoromethyl)phenyl)boronic acid (commercial source, 55.1 mg, 0.246 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): d 7.76 (s, 1H), 7.51-7.61 (m, 4H), 7.38-7.48 (m, 4H), 7.00 (d, J = 8.7 Hz, 2H), 5.15 (s, 2H), 5.03 (d, J = 6.9 Hz, 2H), 4.86 (d, J = 6.9Hz, 2H), 4.19-4.21 (m, 2H), 3.81 (s, 2H), 1.23 (t, J = 7.2 Hz, 3H); MS: (m/z) 543.2 (M+Na). Example 237 2-((3-(4-((2'-chloro-6'-(trifluoromethyl))) [1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid (compound 235)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 236 was obtained by hydrolysis of the compound of Example 236. ¹ H NMR (CDCl ₃ , 300 MHz): d 7.99 (s, 1H), 7.82 (d, J = 8.7 Hz, 1H) 7.67 (d, J = 8.7 Hz, 1H), 7.37-7.55 (m, 6H) , 7.07 (d, J=8.7Hz, 2H), 5.20 (s, 2H), 4.82(d, J = 6.9 Hz, 2H), 4.70 (d, J = 6.9Hz, 2H), 3.54(s, 2H) ;MS: (m/z) 490.9 [M-1]. Example 238 Ethyl 2-((3-(4-((4'-propyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl) )oxy)acetate (compound 236)

The title compound was prepared in a similar manner to compound 83 as in Example 85, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy))-2-fluorophenyl)oxycyclobutane- Reaction of 3-yl)oxy)acetate (Example 230 Step 5 compound, 100 mg, 0.237 mmol) with (4-propylphenyl)boronic acid (commercial source, 58.4 mg, 0.356 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.66 (s, 1H), 7.37-7.59 (m, 7H), 7.26-7.29 (m, 2H), 7.06 (d, J = 8.7 Hz, 2H), 5.13 (s, 2H), 5.86-5.15 (m, 4H), 4.15-4.21 (m, 2H), 3.83 (s, 2H), 2.68 (m, 2H), 1.73 (m , 3H) 1.25 (t, J= 6.0 Hz, 4H), 1.0 (t, J = 5.4 Hz, 3H); MS: (m/z) 483.2 [M+ Na]. Example 239 2-((3-(4-((4'-propyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate (compound 237)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 239 was obtained by hydrolysis of the compound of Example 238. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.66 (s, 1H), 7.39-7.591 (m, 4H), 7.26-7.34 (m, 5H), , 7.00 (d, J = 8.7 Hz, 2H), 5.15 (s, 2H), 4.99-4.91 (m, 4H), 3.88 (s, 2H), 2.67 (t, J= 7.5 Hz, 2H) 1.63-1.76 (m, 2H) 1.00 (t, J=7.2 Hz , 3H); MS: (m/z) 431.1 [M-1]. Example 240 Ethyl 2-((3-(4-((2-(5,5-dimethylcyclopent-1-en-1-yl)-2'-fluoro-5'-methoxy-[ 1,1'-Biphenyl]-4-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (Compound 238) Step 1: 4-(Chloromethyl)- Synthesis of 2-(5,5-dimethylcyclopent-1-en-1-yl)-2'-fluoro-5'-methoxy-1,1'-biphenyl

The title compound was synthesized according to the procedure described in S. P. Brown et al. Medicinal Chemistry Letters, 2012, 3 (9), 726-730. Step 2: Ethyl 2-((3-(4-((2-(5,5-dimethylcyclopent-1-en-1-yl)-2'-fluoro-5'-methoxy-) Synthesis of [1,1'-biphenyl]-4-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate

Ethyl 2-((3-(4-hydroxyphenyl)oxycyclobutane-3-yl)oxy)acetate in DMF (5 ml) (compounds as in compound of step 1 of Example 1) Prepared in a similar manner) (0.149 g, 0.592 mmol), 4-(chloromethyl)-2-(5,5-dimethylcyclopent-1-en-1-yl)-2'-fluoro-5'- Methoxy-1,1'-biphenyl (compound of Step 1, 0.17 g, 0.493 mmol) was stirred with cesium carbonate (0.241 g, 0.739 mmol) at RT for 20 h. After the reaction was completed, the~~~~~~~~~~~~~ The organic layer was washed with EtOAc EtOAc m. Yield: 46%; ¹ H NMR (CDCl ₃ , 300 MHz): δ 0.84 (s, 6H), 1.24 (t, J = 7.2 Hz, 3H), 1.65 (t, J = 6.9 Hz, 2H), 2.25 (t, J = 6.9 Hz, 2H), 3.75 (s, 3H), 3.82 (s, 2H), 4.17 (q, J = 7.2 Hz, 2H), 4.87 (d, J = 6.9 Hz, 2H), 5.00 (d, J = 6.9 Hz, 2H), 5.12 (s, 2H), 5.52 (br s, 1H), 6.78-6.81 (m, 2H), 6.93 - 7.06 (m, 3H), 7.26-7.39 (m, 5H). Example 240a 2-((3-(4-((2-(5,5-Dimethylcyclopent-1-en-1-yl)-2'-fluoro-5'-methoxy-[1, 1'-Biphenyl]-4-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid calcium (compound 238a)

The title compound was prepared via the general procedure prepared according to the calcium salt as described in Method A, using compound 240. ¹ H NMR (DMSO-d ₆ , 300 MHz): δ 0.77 (s, 6H), 1.56 (t, J = 6.6 Hz, 2H), 2.17 (bs, 2H), 3.70 (s, 3H), 3.41 (s (2, H), 4. , 7.03-7.13 (m, 3H), 7.27-7.30 (m, 2H), 7.40-7.44 (m, 3H). Example 241 Ethyl 2-((3-(4-((2-(3-chloro-2-methylphenyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate (compound 239)

The title compound was prepared in a similar manner as Compound 83 of Example 85, which was taken to ethyl 2-((3-(4-((2-bromothiazol-4-yl)methoxy)phenyl)oxycyclobutane - 3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 17) (150 mg, 0.350 mmol) and (3-chloro-2-methylphenyl)boronic acid (commercial source) , 89.1 mg, 0.522 mmol) of the reaction. ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.46-7.44 (m, 1H), 7.42 (s, 1H), 7.41-7.38 (m, 3H), 7.22-7.14 (m, 1H), 7.09 (d, J = 8.7 Hz, 2H), 5.31 (s, 2H), 5.02 (d, J = 6.9 Hz, 2H), 4.88 (d, J = 6.9 Hz, 2H), 4.18 (q, J = 7.2 Hz, 2H) , 3.83 (s, 2H), 2.57 (s, 3H), 1.25 (t, J = 7.2 Hz, 3H); MS (m/z) 474.1 [M+ H]. Example 242 2-((3-(4-((2-(3-chloro-2-methylphenyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy ) acetic acid (compound 240)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 241 was obtained by hydrolysis of the compound of Example 241. ¹ H NMR (DMSO, 300 MHz): δ 12.62 (br s, 1H), 8.25 (s, 1H), 7.92 (d, J = 3.6 Hz, 1H), 7.61 (t, J = 6.6 Hz, 2H), 7.40-7.33 (m, 2H), 7.12 (t, J = 8.7Hz, 2H), 5.28 (s, 2H), 4.82 (d, J = 6.9 Hz 2H), 4.76 (d, J = 6.9Hz, 2H) , 3.76 (s, 2H). 2.39 (s, 3H); MS: (m/z) 444.0 [MH]. Example 243 Ethyl 2-((3-(4-(3-(4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)benzyl)oxy)phenyl)oxycarbonyl Butan-3-yl)oxy)acetate (compound 241)

The title compound was prepared in a similar manner to compound 107 as in Example 109, which was taken to ethyl 2-((3-(4-(4,4,5,5,5-tetramethyl-1,3,2-) Dioxaborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (150 mg, 0.320 mmol) with 2-bromo-4,5, Reaction of 6,7-tetrahydrobenzo[b]thiophene (104 mg, 0.480 mmol). ¹ H NMR (CDCl ₃ , 500 MHz): δ 7.62 (s, 1H), 7.53-7.48 (m, 1H), 7.38-7.37 (m, 3H), 7.32-7.31 (m, 1H), 7.05-7.01 ( m, 3H), 5.11 (s, 2H), 5.02 (d, J = 7.0 Hz, 2H), 4.88 (d, J = 7.0 Hz, 2H), 4.18 (q, J = 7.5Hz, 2H), 3.84 ( s, 2H), 2.80-2.79 (m, 2H), 2.64-2.62 (m, 2H), 1.89-1.83 ( m, 4H), 1.26 (t, J = 7.5 Hz, 3H); MS: (m/z ) 501.1 [M+Na]. Example 244 2-((3-(4-((3-(4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid (compound 242)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 244 was obtained by hydrolysis of the compound of Example 243. ¹ H NMR (DMSO, 300 MHz): δ 12.67 (br s, 1H), 7.66-7.64 (m, 1H), 7.54-7.52 (m, 1H), 7.40-7.37 (m, 4H), 7.20 (s, 1H), 7.10-7.07 (m, 2H), 5.14 (s, 2H), 4.80-4.73 (m, 4H), 3.75 (s, 2H), 2.74-2.72 (m, 2H). 2.57-2.55 (m, 2H), 1.79-1.75 (m, 4H). Example 245 Ethyl 2-((3-(4-(4-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)benzyl)oxy)phenyl)oxycarbonyl Butan-3-yl)oxy)acetate (compound 243)

The title compound was prepared in a similar manner to compound 107 as in Example 109, which was taken to ethyl 2-((3-(4-(4,4,5,5,5-tetramethyl-1,3,2-) Dioxaborolan-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate (150 mg, 0.320 mmol) with 2-bromo-4,5, Reaction of 6,7-tetrahydrobenzo[d]thiazole (46.4 mg, o.213 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.99 (s, 1H), 7.85 (d, J = 6.9 Hz, 1H), 7.47 (d, J = 7.2 Hz, 2H), 7.39 (d, J = 8.7 Hz, 2H), 7.05 (d, J = 8.7Hz, 2H), 5.14 (s, 2H), 5.03 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9 Hz, 2H), 4.18 ( q, J = 7.2 Hz, 2H), 3.83 (s, 2H), 2.86-2.84 (m, 4H), 1.96-1.92 (m, 4H), 1.26 (t, J = 7.2 Hz, 3H); MS: ( m/z) 480.2 [M+ H]. Example 246 2-((3-(4-((3-(4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl)benzyl)oxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid (compound 244)

The title compound was prepared in a similar manner as Compound 84 of Example 86. Compounds of Example 246 were obtained by hydrolysis of the compound of Example 245. ¹ H NMR (DMSO, 300 MHz): δ 12.64 (br s, 1H), 7.96 (s, 1H), 7.82 (d, J = 6.9 Hz, 1H), 7.51-7.49 (m, 2H), 7.40-7.37 (d, J = 8.4Hz, 2H), 7.10 (d, J = 8.4Hz, 2H), 5.12 (s, 2H), 4.82 (d, J = 7.2Hz, 2H), 4.76 (d, J = 7.2Hz , 2H), 3.75 (s, 2H), 2.80 (d, J = 15.6Hz, 4H), 1.82-1.80 (m, 4H). Example 247 Ethyl 2-((3-(4-((4'-cyclopropyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3- Ethyl)acetate (compound 245)

The title compound was prepared in a similar manner as Compound 95 of Example 97, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (150 mg, 0.356 mmol) with (4-cyclopropylphenyl)boronic acid (commercial source, 82.93 mg, 0.512 mmol). ¹ H NMR (CDCl ₃ , 500 MHz): δ 7.65 (s, 1H), 7.52 (d, J = 7.5 Hz, 1H), 7.52 (d, J = 7.5 Hz, 2H), 7.47 (t, J = 8.0 Hz, 1H), 7.39 (t, J =10.5Hz, 3H), 7.18 (d, J = 8.0Hz, 2H), 7.06(d, J = 8.0Hz, 2H), 5.15 (s, 2H), 5.02 ( d, J = 7.0 Hz, 2H), 4.89 (d, J = 7.0 Hz, 2H), 4.17 (q, J = 7.5Hz, 2H), 3.84 (s, 2H), 1.96-1.94 (m, 1H), 1.26 (t, J = 7.5 Hz, 3H), 1.03-1.01 (d, J = 8.0 Hz, 2H), 0.76 (d, J = 5.0 Hz, 2H); MS: (m/z) 459.5 [M+H ]. Example 248 2-((3-(4-((4'-cyclopropyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetic acid (compound 246)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 247 was obtained by hydrolysis of the compound of Example 247. ¹ H NMR (DMSO, 300 MHz): δ 12.64 (br s, 1H), 7.71 (s, 1H), 7.61 (s, 1H), 7.58-7.54 (m, 2H), 7.49-7.44 (m, 2H) , 7.43-7.36 (m, 2H), 7.18 (d, J = 8.4Hz, 2H), 7.10(d, J= 8.7Hz, 2H), 5.19 (s, 2H), 4.81 (d, J =6.9Hz, 2H), 4.76 (d, J = 6.9 Hz, 2H), 3.74 (s, 2H), 1.98-1.91 (m, 1H). 1.01 - 0.94 (m, 2H), 0.73-0.68 (m, 2H). Example 249 Ethyl 2-((3-(4-((3-(5,6,7,8-tetrahydronaphthalen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3- Ethyl)acetate (compound 247)

The title compound was prepared in a similar manner as Compound 95 of Example 97, which was taken to ethyl 2-((3-(4-((3-bromobenzyl)oxy)phenyl)oxycyclobutane-3-yl) Reaction of oxy)acetate (150 mg, 0.356 mmol) with (5,6,7,8-tetrahydronaphthalen-2-yl)boronic acid (commercial source, 94 mg, 0.534 mmol). ¹ H NMR (CDCl ₃ , 300 MHz): δ 7.65 (s, 1H), 7.58-7.55 (m, 1H), 7.49-7.33 (m, 6H), 7.18 (d, J = 7.5 Hz, 1H), 7.07 (d, J = 7.5 Hz, 2H), 5.15 (s, 2H), 5.03 (d, J = 6.9 Hz, 2H), 4.89 (d, J = 6.9 Hz, 2H), 4.18 (q, J = 7.2 Hz , 2H), 3.89 (s, 2H), 2.85-2.83 (m, 4H), 1.85-1.84 (m, 4H), 1.26 (t, J = 7.2 Hz, 3H); MS: (m/z) 495.3 [ M+ Na]. Example 250 2-((3-(4-(3-(5,6,7,8-tetrahydronaphthalen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetic acid (compound 248)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 250 was obtained by hydrolysis of the compound of Example 249. ¹ H NMR (DMSO, 300 MHz): δ 12.63 (br s, 1H), 7.71 (s, 1H), 7.60 (d, J = 7.2 Hz, 1H), 7.48-7.46 (m, 2H), 7.42-7.35 (m, 4H), 7.15-7.07 (m, 3H), 5.18 (s, 2H), 4.81 (d, J = 7.2 Hz, 2H), 4.76 (d, J = 7.2 Hz, 2H), 3.74 (s, 2H), 2.78-2.74 (m, 4H), 1.75-1.73 (m, 4H); MS: (m/z) 443.0 [MH]. Example 251 Ethyl 2-((3-(4-(4-(2-(methoxy)amino)-2-(p-tolyl)ethoxy)benzyl)oxy)phenyl)oxy Cyclobutane-3-yl)oxy)acetate (Compound 249) Step 1: Synthesis of 2-bromo-1-(p-tolyl)ethanone O-methylhydrazine

2-Bromo-1-(p-tolyl)ethanone (commercial source, 1 eq.) and sodium acetate (1.2 eq.) were dissolved in glacial acetic acid (10 mL) and the mixture was stirred for 10 min. O-methylhydroxylamine hydrochloride (commercial source, 0.96 equivalents) was added to the resulting solution, and the resulting mixture was heated at 100 °C for 3 to 4 h. After the reaction was completed, the reaction mixture was poured into water (20 mL) The organic layer was washed with EtOAc (EtOAc m.

¹ H NMR (CDCl ₃ , 300 MHz): δ 7.62 (d, J = 7.8 Hz, 2H), 7.23 (d, J = 8.1 Hz, 2H), 4.37 (s, 2H), 4.10 (s, 3H), 2.40 (s, 3H); MS (m/z): 242.0 [M+H]. Step 2: Synthesis of 2-(4-(hydroxymethyl)phenoxy)-1-(p-tolyl)ethanone O-methylhydrazine

Potassium carbonate (1.5 eq.) was added to a stirred solution of 4-hydroxybenzyl alcohol (1 eq.) in acetonitrile (30 mL), and the resulting mixture was stirred at RT for 10 min. (Z)-2-Bromo-1-(p-tolyl)ethanone O-methylindole (compound of step 1, 1 equivalent) was added to the stirred reaction mixture, and the reaction mixture was at 80 ° C - Heat at 100 °C for 4 to 5 h. After the reaction was completed, the reaction mixture was filtered, evaporated and evaporated The organic layer was washed with EtOAc (EtOAc m. ¹ H NMR (300 MHz, CDCl ₃ ): δ 7.59 (d, J = 9.0 Hz, 2H), 7.28 (d, J = 6.0 Hz, 2H), 7.18 (d, J = 7.8 Hz, 2H), 6.93 (d, J = 9.0 Hz, 2H), 5.24 (s, 2H), 4.62 (s, 2H), 4.13 (s, 3H), 2.36 (s, 3H); MS: (m/z) 286.0 [M +H], 308.0 [M+Na]. Step 3: Ethyl 2-((3-(4-(4-(2-(methoxy)amino)-2-(p-tolyl)ethoxy)benzyl)oxy)phenyl) Synthesis of Oxycyclobutane-3-yl)oxy)acetate

Ethyl 2-((3-(4-hydroxyphenyl)oxycyclobutane-3-yl)oxy)acetate (compound prepared in a similar manner as the compound of Step 1 of Example 1) was added to anhydrous a stirred solution of (Z)-2-(4-(hydroxymethyl)phenoxy)-1-(p-tolyl)ethanone O-methylhydrazine in THF, and the resulting solution is at 0 ^o C Cool down in a nitrogen atmosphere. Next, triphenylphosphine (1.5 eq.) was added and the reaction mixture was stirred for 15 min then diethyl azodicarboxylate (1.5 eq.). The reaction mixture was warmed to RT and stirred for 10 to 12 h. After the reaction was completed, the solvent was removed and the residue was extracted ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium The residue was purified by flash column chromatography (EtOAcEtOAcEtOAc LCMS: (m/z) 520.3 [M+H]. Example 252 2-((3-(4-(4-(2-(methoxy)amino)-2-(p-tolyl)ethoxy)benzyl)oxy)phenyl)oxycyclobutane Alk-3-yl)oxy)acetic acid (compound 250)

The title compound was prepared in a similar manner as Compound 84 of Example 86. The compound of Example 252 was obtained by hydrolysis of the compound of Example 251. LCMS: (m/z) 492.3 [M+H]. Pharmacological test

The pharmacological activity of a compound as a GPR40 agonist can be confirmed by several pharmacological tests known in the art. The exemplified pharmacological tests provided below have been carried out with the compounds of the present invention synthesized in the above examples. Example 253 Phosphoinositide Accumulation Test

A phosphoinositide accumulation assay is performed to characterize the GPR40 agonist activity of the compounds of the invention. The test was carried out according to the method substantially as described in Diabetes, 2008, 57(8): 2211-2219 and PLoS One, 2011, 6(11): e27270. a) Production of FFAR1 (GPR40) CHOK1

Stable FFAR1 (GPR40) CHOK1 strain was used to determine the GPR40 agonist activity of the test compound (the compound of the invention synthesized in the above examples). Stable FFAR1 (GPR40) CHOK1 strains expressing recombinant human GPR40 were generated according to the procedures described herein below.

The full-length human GPR40 cDNA (accession number: NM_005303) was colonized into a mammalian expression vector (pReceiver) and stably transfected into (Chinese hamster ovary) CHOK1 cells using Amaxa technology. 2 μg of pReceiver hGPR40 was transfected into 1×10 ⁶ CHOK1 cells in a 6-well plate. Cells were divided into three 100 mm cell culture dishes on the second day, and geneticin (800 μg/ml) was added to the cell culture on the third day. The selection medium containing Ham's F-12 K, supplemented with FBS (10%) and geneticin (800 μg/ml) was replaced every three days until colony formation. The isolated colonies were further purified (single cell colonization) after 14 days to obtain a homologous single cell homologous population expressing the pure GPR40 receptor protein on the cell surface. Cell surface GPR40 receptor expression was measured by flow cytometry. The created internal gene transfer cell line (strain) was labeled as FFAR1 (GPR40) CHOK1 strain. b) Determination of intracellular release of phosphoinositide

FFAR1 (GPR40) CHOK1 cells were suspended in medium supplemented with Ham's F-12 K supplemented with FBS (10%) and geneticin (800 μg/ml). The cells were seeded at a density of 2 x 10 ⁴ cells per well in a 384-well tissue culture dish and cultured overnight. The medium was discarded and the cells were further suspended at pH 7.6, including HEPES (10 mM), glucose (5.5 mM), CaCl ₂ (1 mM), NaCl (150 mM), KCl (4.2 mM), MgCl ₂ (0.5 mM). ) with LiCl (50 mM) stimulation buffer. A test compound (a representative compound of formula (I)) 10 mM stock was prepared in DMSO, and then a log-fold dilution of the test compound was performed with stimulation buffer. Various concentrations of test compound were added to each well in a standard DMSO solution. The plates were further incubated for 1 h at 37 ° C in a 5% CO ₂ incubator. The final concentration of test compound in each well varied from 1 pM to 10 μM. The DMSO concentration in the test was 0.1% or less. After incubation, the lysis reagent and anti-Tb conjugate were added to each well. The intracellular phosphoinositide release and accumulation of the test compound was measured by the binding ability of the anti-Tb conjugate to the internally produced phosphoinositide in each well compared to the phosphoinositide coupled to the dye d2 externally added to each well. . The disk was then read using a Perkin Elmer (Envision) disk reader and the fluorescent signal was acquired. The EC ₅₀ value of the test compound was calculated from a non linear regression sigmoidal curve graph plotted between the concentration of the test compound and the fluorescence intensity. The EC ₅₀ values of test compounds are provided in Table 1.

Indicated by the inositol phosphates accumulation test GPR40 agonist activity of the compounds of the present invention based on the EC ₅₀ values of the test compound is determined.

It must be noted that the singular forms "a" and "the" Thus, for example, reference to a composition includes "a compound" includes a mixture of two or more compounds.

It should be further noted that the term "or" is generally used to mean "and/or" unless the context clearly dictates otherwise.

Claims (19)

a compound of formula (I); Formula (I) wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl; R ₂ together with R ₃ forms a saturated or partially unsaturated a 3- to 9-membered heterocyclic group containing one or two heteroatoms independently selected from the group consisting of O, N and S; or R ₂ and R ₃ together forming a saturated or partially unsaturated (C ₄ -C ₈ )cycloalkyl; R _{4 is,} in each case, independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy , -O(C ₁ -C ₆ )alkyl, (C ₆ -C ₁₀ )aryl, amine, cyano, nitro, -C(O)R ₉ or -S(O) _p R ₆ Groups; R _v and R _w are independently selected from the group consisting of hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ a group consisting of an alkyl group, an amine group, a cyano group, a -C(O)R ₉ , a (C ₃ -C ₈ )cycloalkyl group, a (C ₆ -C ₁₀ )aryl group, a heterocyclic group and a heteroaryl group And R _x and R _y are independently selected from the group consisting of A-CH(R ₇ )-X, AX-CH(R ₇ ) and R ₅ ; at least one of R _x and R _y is defined as A-CH (R ₇₎ -X or _{AX-CH (R 7);} R 5 is hydrogen, (C ₁ -C ₆₎ alkyl, halo, haloalkyl (C ₁ -C ₆₎ alkyl, hydroxy, -O (C ₁ -C ₆₎ alkyl, (C ₆ -C ₁₀₎ aryl, amino, cyano, nitro, -C (O) R ₉ Or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkylamino or dialkylamino; R ₇ is hydrogen or (C ₁ -C ₆ ) alkyl; X is CR ₈ R ₈ , O, NR ₈ or S; Q is O, NR ₈ or S(O) _p ; R _{8 is} in each case independently selected from hydrogen, (C ₁ - C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, cyano, -C(O)(C ₁ -C ₆ ) a group consisting of an alkyl group, -C(O)O(C ₁ -C ₆ )alkyl, -C(O)NH ₂ and -S(O) _p R ₆ ; wherein R ₆ is as defined above ; R ₉ is (C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ An aryl group, a heterocyclic group, a heteroaryl group, R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ are independently selected from hydrogen and (C ₁ -C ₆ )alkyl; or R ₁₀ and R ₁₁ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₂ and R ₁₃ are hydrogen; or R ₁₂ and R ₁₃ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₀ and R ₁₁ are hydrogen; R _{14 is} in each case independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, -O(C ₃ -C ₈ )cycloalkyl , -O(C ₁ -C ₆ )alkylheterocyclyl, -O-heterocyclyl, halo(C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S ( O) _p R ₆ , (C ₆ -C ₁₀ ) aryl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ ) aryl, amine, cyano, nitro, -C(O a group consisting of R ₉ , -S(O) _p R ₆ , -(CH ₂ ) _s NR ₁₅ R ₁₆ and -X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X, R ₆ and R ₉ are R ₁₅ and R ₁₆ are independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3; m is an integer from 1 to 4; p is an integer from 0 to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is from 1 to 4 An integer * represents the point of X of -CH or -X-CH(R ₇ ) attached to CH(R ₇ )-X; wherein (C ₁ -C ₆ )alkyl is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O And one or more groups of R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ are substituted; wherein R ₆ , R ₉ and p are as described above Definitive; -O(C ₁ -C ₆ )alkyl is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ - C ₁₀ ) aryl, heterocyclic, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -S(O) _p R ₆ , -NR Substituting one or more groups of ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above; C ₆ -C ₁₀ ) aryl is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, halogen ,halogen (C ₁ -C ₆₎ alkyl, hydroxy, -O (C ₁ -C ₆₎ alkyl, halo (C ₁ -C ₆₎ alkoxy, (C ₃ -C ₈₎ cycloalkyl -alkyl, (C ₆ -C ₁₀ ) aryl, -O(C ₆ -C ₁₀ )aryl, (C ₁ -C ₆ )alkylheterocyclyl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ and -O(CH ₂ ) _s C[=NO(C ₁ -C ₆ )alkyl]R Substituting one or more groups of ₈ groups; wherein R ₆ , R ₈ , R ₉ , s and p are as defined above; the heterocyclic group is a 3- to 9-membered ring which is not Substituted or independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, halogen,halogen (C ₁ -C ₆ ) Alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl ,heterocyclyl,heteroaryl,amino,cyano,nitro,-(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ ) Substituted by one or more groups of alkyl, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined as above; heteroaryl is a 3-10 yuan ring, which is unsubstituted Unsubstituted or independently selected from the group consisting of (C ₁ -C ₆₎ alkyl, (C ₂ -C ₈₎ alkenyl, (C ₂ -C ₈₎ alkynyl, halogen, halo (C ₁ -C ₆₎ alkyl a group, a hydroxyl group, a -O(C ₁ -C ₆ )alkyl group, a halogenated (C ₁ -C ₆ )alkoxy group, a (C ₃ -C ₈ )cycloalkyl group, a (C ₆ -C ₁₀ )aryl group, a group consisting of a heterocyclic group, a heteroaryl group, an amine group, a cyano group, a nitro group, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ Substituted by one or more groups; wherein R ₆ , R ₉ and p are as defined above; halogen is chlorine, bromine, iodine or fluorine; or an isotopic form thereof, a stereoisomer, a tautomer And a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a prodrug, a polymorph, an N oxide, an S oxide or a monocarboxylic acid isoelectronic alignment. a compound of the formula (Ia) as described in claim 1 of the patent scope, Formula (Ia) wherein Q is selected from O, NR ₈ or S; Z, R _v , R _w , R ₂ , R ₃ , R ₄ , R ₇ , R _y , X, A, m and n are as applied Or as defined in the first paragraph of the patent; or a isotopic form thereof, a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a prodrug, A polymorph, an N oxide, an S oxide, or a monocarboxylic acid isoelectronic alignment. If the application or the compound of item 2 in item 1 patentable scope, wherein Z is -COOR ₁ or _{-CON (R 1) 2; R} 1 is hydrogen or (C ₁ -C ₆₎ alkyl; and R & lt ₂ R ₃ together form a ring comprising one or two saturated or partially unsaturated 3 to 9 membered heterocyclic groups independently selected from the group consisting of O, N and S; R ₄ in each In the case of being independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, —O(C ₁ -C ₆ )alkyl, amine, a group consisting of cyano, -C(O)R ₉ and -S(O) _p R ₆ ; R _v and R _w are independently selected from hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl , halogenated (C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, a group of (C ₆ -C ₁₀ ) aryl, heterocyclic and heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halogen (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkylamino or dialkylamino; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl X is CR ₈ R ₈ , O, NR ₈ or S; Q is O; R _{8 is} in each case selected from hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ - a group consisting of C ₆ )alkyl, -C(O)O(C ₁ -C ₆ )alkyl, -C(O)NH ₂ and -S(O) _p R ₆ wherein R ₆ is as described above As defined; R ₉ is (C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is (C ₆ -C ₁₀ )aryl, heteroaryl, R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ are independently selected from hydrogen and (C ₁ -C ₆ )alkyl; or R ₁₀ and R ₁₁ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₂ and R ₁₃ are hydrogen; or R ₁₂ and R ₁₃ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₀ and R ₁₁ are hydrogen; R _{14 is} in each case independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, -O(C ₃ -C ₈ )cycloalkyl , halogenated (C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₁ -C ₆ )alkyl-heterocyclyl, -O-heterocyclyl, (C ₆ -C ₁₀ )aryl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ ) aryl, amine, cyano, nitro, -C ( O) R ₉ , -S(O) _p R ₆ , -(CH ₂ ) _s NR ₁₅ R ₁₆ and -X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X, R ₆ and R ₉ R ₁ and R ₁₆ are independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3 m is an integer from 1 to 4; p is an integer from 0 to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is 1 to An integer of 4; * represents the point of X of -CH; or -X-CH(R ₇ ) attached to CH(R ₇ )-X; wherein (C ₁ -C ₆ )alkyl is unsubstituted or independently selected Free (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic, heteroaryl, amino, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O Substituting one or more groups consisting of _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above; -O(C ₁ -C ₆ )alkyl is unsubstituted Or independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic, hydroxy, halogen, amine, cyano a group consisting of -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ Substituted by one or more groups; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above; (C ₆ -C ₁₀ ) aryl is unsubstituted or independently selected from (C ₁ -C ₆₎ alkyl, halo, halo (C ₁ -C ₆₎ alkyl, hydroxy, -O (C ₁ -C ₆₎ alkyl, halo (C ₁ -C ₆₎ alkyl Group, (C ₆ -C ₁₀₎ aryl, (C ₁ -C ₆₎ alkyl heterocyclyl, heteroaryl, amino, cyano, nitro, -C (O) R ₉ and -O (C Substituted by one or more groups consisting of ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above; heterocyclyl is not Substituted or independently selected from (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo (C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, cyano, nitro, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl One of the group consisting of -O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ is substituted by one or more of the groups 3 to a 9-membered ring; wherein R ₆ and p are as defined above; a heteroaryl group is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ An alkyl group, a hydroxyl group, a -O(C ₁ -C ₆ )alkyl group, a halogenated (C ₁ -C ₆ )alkoxy group, a (C ₆ -C ₁₀ )aryl group, a heteroaryl group, a heterocyclic group, an amine Substituted by one or more groups consisting of a group consisting of a cyano group, a cyano group, a nitro group, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ One to three yuan ; Wherein R _6, R ₉ and p are as defined as above; and halo is chloro, bromo, iodo or fluoro; or a pharmaceutically on the isotopic form, stereoisomers, tautomers, acceptable salts, pharmaceutical Acceptable solvates, prodrugs, polymorphs, N oxides, S oxides or carboxylic acid isomers. The compound of any one of claims 1 to 3 wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a ring containing one or two oxygen atoms saturated or partially unsaturated 3 to 6 membered heterocyclic groups; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ and a group consisting of -S(O) _p R ₆ ; R _v is hydrogen and R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amino, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic Or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ An alkyl group, an amine group, a cyano group, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, an amine group, a monoalkylamino group or dialkylamino group; R ₇ is hydrogen or (C ₁ -C ₆₎ alkyl; X is _{CR 8 R 8, O, NR} 8 or S; Q is O; R ₈ in each case Lower tie independently selected from hydrogen, (C ₁ -C _{6) alkyl, -C (O) (C 1} -C 6) alkyl, -C (O) O (C 1 -C 6) alkyl, - a group consisting of C(O)NH ₂ and -S(O) _p R ₆ wherein R ₆ is as defined above; R ₉ is (C ₁ -C ₄ )alkyl, -O(C ₁ - C ₆ ) alkyl, hydroxy or amine; A is R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ are independently selected from hydrogen and (C ₁ -C ₆ )alkyl; or R ₁₀ and R ₁₁ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₂ and R ₁₃ are hydrogen; or R ₁₂ and R ₁₃ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₀ and R ₁₁ are hydrogen; R _{14 is} in each case independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, -O(C ₃ -C ₈ )cycloalkyl , halogenated (C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₁ -C ₆ )alkyl-heterocyclyl, -O-heterocyclyl, (C ₆ -C ₁₀ )aryl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ ) aryl, amine, cyano, nitro, -C ( O) R ₉ , -S(O) _p R ₆ , -(CH ₂ ) _s NR ₁₅ R ₁₆ and -X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X, R ₆ and R ₉ R ₁₅ and R ₁₆ are independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and (CH ₂ ) _t OH; n is an integer from 1 to 3; m is an integer from 1 to 4; p is an integer from 0 to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is from 1 to 4 An integer * represents a point of -CH attached to CH(R ₇ )-X; wherein, (C ₁ -C ₆ )alkyl is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, halogen , halogenated (C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic One or more groups consisting of heteroaryl, amine, cyano, nitro, C(O)R ₉ and O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ Substituted; wherein R ₆ , R ₉ and p are as defined above; -O(C ₁ -C ₆ )alkyl is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic, hydroxy, halogen, amine, cyano, (C ₁ -C ₆ )alkyl-S(O) Substituting one or more groups consisting of _p R ₆ , -S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above; (C ₆ -C ₁₀ ) aryl is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆₎ alkyl, hydroxy, O (C ₁ -C ₆₎ alkyl, halo (C ₁ -C ₆₎ alkoxy, (C ₆ -C ₁₀₎ aryl , (C ₁ -C ₆₎ alkyl heterocyclyl, heteroaryl, amino, cyano, _{nitro, -C (O) R 9,} -O (C 1 -C 6) alkyl -S (O a group of one or more groups consisting of _p R ₆ and -O(CH ₂ ) _s C[=NO(C ₁ -C ₆ )alkyl]R ₈ ; wherein R ₆ , R ₈ , R ₉ , s and p are as defined above; the heterocyclic group is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl , hydroxy, O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, cyano, nitro, (C ₁ - C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ One or more groups of the group are substituted with one of the 3 to 9 membered rings; wherein R ₆ and p are as defined above; the heteroaryl group is unsubstituted or independently selected from (C ₁ - C ₆ ) alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ - a group of C ₁₀ ) aryl, heteroaryl, amine, cyano, nitro, C(O)R ₉ and O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ Replaced by one or more groups a 3- to 10-membered ring; wherein R ₆ , R ₉ and p are as defined above; halogen is chlorine, bromine, iodine or fluorine; or an isotopic form thereof, a stereoisomer, a tautomer a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a prodrug, a polymorph, an N oxide, an S oxide or a monocarboxylic acid isoelectronic alignment. The compound of any one of clauses 1 to 4, wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a ring containing one or two oxygen atoms saturated or partially unsaturated 3 to 6 membered heterocyclic groups; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ and a group consisting of -S(O) _p R ₆ ; R _v is hydrogen and R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amino, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic Or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ An alkyl group, an amine group, a cyano group, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, an amine group, a monoalkylamino group Or a dialkylamino group; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X and Q are O; R ₉ is (C ₁ -C ₄ )alkyl, -O(C ₁ -C ₆ ) alkyl, Or amine groups; A is R ₁₀ , R ₁₁ , R ₁₂ and R ₁₃ are independently selected from hydrogen and (C ₁ -C ₆ )alkyl; or R ₁₀ and R ₁₁ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₂ and R ₁₃ are hydrogen; or R ₁₂ and R ₁₃ may together form a (C ₃ -C ₈ )cycloalkyl ring and R ₁₀ and R ₁₁ are hydrogen; R _{14 is} in each case independently selected from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, -O(C ₃ -C ₈ )cycloalkyl , halogenated (C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₁ -C ₆ )alkyl-heterocyclyl, -O-heterocyclyl, (C ₆ -C ₁₀ )aryl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ ) aryl, amine, cyano, nitro, -C ( a group of O)R ₉ , -S(O) _p R ₆ , -(CH ₂ ) _s NR ₁₅ R ₁₆ and -X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X, R ₆ and R ₉ R ₁₅ and R ₁₆ are independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and (CH ₂ ) _t OH; n is an integer from 1 to 3; m is an integer from 1 to 4; p is an integer from 0 to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is from 1 to 4 An integer * represents a point of -CH attached to CH(R ₇ )-X; wherein, (C ₁ -C ₆ )alkyl is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, halogen , halogenated (C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic One or more groups consisting of heteroaryl, amine, cyano, nitro, C(O)R ₉ and O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ Substituted; wherein R ₆ , R ₉ and p are as defined above; -O(C ₁ -C ₆ )alkyl is unsubstituted or is independently selected from (C ₁ -C ₆ )alkyl (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic, hydroxy, halogen, amine, cyano, (C ₁ -C ₆ )alkyl-S(O) Substituting one or more groups consisting of _p R ₆ , -S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above; (C ₆ -C ₁₀ ) aryl is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆₎ alkyl, hydroxy, O (C ₁ -C ₆₎ alkyl, halo (C ₁ -C ₆₎ alkoxy, (C ₆ -C ₁₀₎ Group, (C ₁ -C ₆₎ alkyl heterocyclyl, heteroaryl, amino, cyano, _{nitro, -C (O) R 9,} -O (C 1 -C 6) alkyl -S ( O) substituted with one or more groups consisting of _p R ₆ and -O(CH ₂ ) _s C[=NO(C ₁ -C ₆ )alkyl]R ₈ ; wherein R ₆ , R ₉ , s and p are as defined above; and R ₈ is selected from hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ -C ₆ )alkyl, -C(O)O a group consisting of (C ₁ -C ₆ )alkyl, -C(O)NH ₂ and -S(O) _p R ₆ wherein R ₆ is as defined above; heterocyclyl is unsubstituted Or independently selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) alkoxy, (C ₆ -C ₁₀ ) aryl, amine, cyano, nitro, (C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-( a 3- to 9-membered ring substituted with one or more groups of C ₁ -C ₆ )alkyl and O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; R ₆ and p are as defined above; heteroaryl is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy , O(C ₁ -C ₆ )alkyl , halogenated (C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, heteroaryl, amine, cyano, nitro, C(O)R ₉ and O(C ₁ -C ₆ ) A 3- to 10-membered ring substituted by one or more groups consisting of alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above; Is chlorine, bromine, iodine or fluorine; or a isotopic form thereof, a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a prodrug, a Polymorph, N-oxide, S-oxide or monocarboxylic acid isoelectronic alignment. The compound of any one of clauses 1 to 5, wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a ring containing one or two oxygen atoms saturated or partially unsaturated 3 to 6 membered heterocyclic groups; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ and a group consisting of -S(O) _p R ₆ ; R _v is hydrogen and R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amino, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic Or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ An alkyl group, an amine group, a cyano group, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, an amine group, a monoalkylamino group Or a dialkylamino group; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X and Q are O; R ₉ is (C ₁ -C ₆ )alkyl, O(C ₁ -C ₆ ) alkane base, Hydroxyl or amine group; A is R ₁₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ ) alkane , halo(C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R _{6 , -} O(C ₃ -C ₈ )cycloalkyl, -O (C ₁ -C ₆ )alkyl-heterocyclyl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ )aryl, -O-heterocyclyl, cyano, -S(O) _a group consisting of _p R ₆ , —(CH ₂ ) _s NR ₁₅ R ₁₆ and —X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X and R ₆ are as defined above; R ₁₅ and R ₁₆ are Independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3; m is an integer from 1 to 4; p is 0 An integer up to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is an integer from 1 to 4; 1 * indicates a connection to CH (R ₇ ) the point of -CH of -X; wherein, (C ₁ -C ₆ )alkyl is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ - C ₆ ) alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₆ -C ₁₀ ) aryl One or more groups consisting of a group consisting of an amino group, an amine group, a cyano group, a nitro group, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ Substituted; wherein R ₆ , R ₉ and p are as defined above; -O(C ₁ -C ₆ )alkyl is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic, hydroxy, halogen, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ Substituting one or more groups consisting of -S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ And p and s are as defined above; the heterocyclic group is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy , -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, cyano, nitro, -(C ₁ - C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ group one or more of the group consisting of substituted 3-9 yuan ring; wherein R ₆ and p are as defined as above; and halo is chloro, bromo, iodo or fluoro; or Isotope form, a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a prodrug, a polymorph, an N oxide, an S oxide or a Carboxylic acid is an electron alignment. The compound of any one of clauses 1 to 6, wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a ring containing one or two oxygen atoms saturated or partially unsaturated 3 to 6 membered heterocyclic group; R ₄ is hydrogen; R _v is hydrogen and R _w is hydrogen, halogen , hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl , halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkylamino, dialkylamino; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X and Q Is O; R ₉ is (C ₁ -C ₆ )alkyl, O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is R ₁₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, hydroxy, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ ) alkane , halo(C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₃ -C ₈ )cycloalkyl, -O (C ₁ -C ₆ )alkyl-heterocyclyl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ )aryl, -O-heterocyclyl, cyano, -S(O) _a group consisting of _p R ₆ , —(CH ₂ ) _s NR ₁₅ R ₁₆ and —X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X and R ₆ are as defined above; R ₁₅ and R ₁₆ are Independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3; m is an integer from 1 to 4; p is 0 An integer up to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is an integer from 1 to 4; * indicates a connection to CH (R ₇ a point of -CH of -X; wherein, (C ₁ -C ₆ )alkyl is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ ) alkyl, hydroxy, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ ) Substituting one or more groups consisting of alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above; -O(C ₁ -C ₆ An alkyl group is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, hydroxy , halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR Substituting one or more groups consisting of ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above; heterocyclyl is unsubstituted or independently Selected as (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) alkane Oxyl, (C ₆ -C ₁₀ )aryl, amine, -(C ₁ -C ₆ )alkyl-OH, -(C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ ) alkane One of the groups of 3 to 9-membered rings substituted with one or more groups consisting of -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ and p are as The above defined; halogen is chlorine, bromine, iodine or fluorine; or an isotopic form thereof, a stereoisomer, a tautomer a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a prodrug, a polymorph, an N oxide, an S oxide or a monocarboxylic acid isoelectronic alignment. The compound of any one of clauses 1 to 7 wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a ring containing one or two oxygen atoms saturated or partially unsaturated 3 to 6 membered heterocyclic group; R ₄ is hydrogen; R _v is hydrogen and R _w is hydrogen, halogen , hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl , halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, amine, monoalkylamino or dialkylamino; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X and Q Is O; R ₉ is (C ₁ -C ₆ )alkyl, O(C ₁ -C ₆ )alkyl, hydroxy or amine; A is R ₁₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ ) alkyl, halogen, hydroxy, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ ) alkane , halo(C ₁ -C ₆ )alkoxy, -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -O(C ₃ -C ₈ )cycloalkyl, -O (C ₁ -C ₆ )alkyl-heterocyclyl, -O(C ₁ -C ₆ )alkyl (C ₆ -C ₁₀ )aryl, -O-heterocyclyl, cyano, -S(O) _a group consisting of _p R ₆ , —(CH ₂ ) _s NR ₁₅ R ₁₆ and —X(CH ₂ ) _s NR ₁₅ R ₁₆ ; wherein X and R ₆ are as defined above; R ₁₅ and R ₁₆ are Independently selected from the group consisting of hydrogen, (C ₁ -C ₆ )alkyl and -(CH ₂ ) _t OH; n is an integer from 1 to 3; m is an integer from 1 to 4; p is 0 An integer up to 2; q is an integer from 1 to 4; r is an integer from 1 to 5; s is an integer from 1 to 4; t is an integer from 1 to 4; * indicates a connection to CH (R ₇ a point of -CH of -X; wherein, (C ₁ -C ₆ )alkyl is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ ) alkyl, hydroxy, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ - Substituting one or more groups of C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above; -O(C ₁ -C ₆ ) an alkyl group which is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclic, Hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s Substituted by one or more groups consisting of NR ₁₅ R ₁₆ ; wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined above; heterocyclyl is unsubstituted or independent Selected from (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) Alkoxy, (C ₆ -C ₁₀ )aryl, amine, -(C ₁ -C ₆ )alkyl-OH, -(C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ ) a 3- to 9-membered ring substituted with one or more groups of alkyl and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ and p are As defined above; halogen is chlorine, bromine, iodine or fluorine; or an isotopic form thereof, a stereoisomer, an interconversion Structure was acceptable salts thereof a pharmaceutically, of a pharmaceutically acceptable solvate thereof, a prodrug, a polymorph, N-oxide, S-oxide or a carboxylic acid isosteres thereof. The compound of any one of clauses 1 to 8, wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl R ₂ and R ₃ together form a ring containing one or two oxygen atoms saturated or partially unsaturated 3 to 6 membered heterocyclic groups; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, -C(O)R ₉ and a group consisting of -S(O) _p R ₆ ; R _v is hydrogen and R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amino, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic Or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ An alkyl group, an amine group, a cyano group, -C(O)R ₉ or -S(O) _p R ₆ ; R ₆ is hydrogen, (C ₁ -C ₆ )alkyl, an amine group, a monoalkylamino group Or a dialkylamino group; R ₇ is hydrogen or (C ₁ -C ₆ )alkyl; X and Q are O; R ₉ is (C ₁ -C ₄ )alkyl, -O(C ₁ -C ₆ ) alkyl, A hydroxy or amine group; A is a (C ₆ -C ₁₀ ) aryl or heteroaryl group; n is an integer from 1 to 3; m is an integer from 1 to 4; s is an integer from 1 to 4; p is An integer from 0 to 2; wherein (C ₁ -C ₆ )alkyl is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, halogen, halo (C ₁ -C ₆ ) One of a group consisting of an alkyl group, a hydroxyl group, an amine group, a cyano group, a nitro group, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ or more Substituted by a polygroup; wherein R ₆ , R ₉ and p are as defined above; -O(C ₁ -C ₆ )alkyl is unsubstituted or independently selected from (C ₁ -C ₆ ) Alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ )alkyl-S _{(O) p R 6, -S} (O) p R 6, -NR 15 R 16 and - one of a group (CH _{2) s} NR ₁₅ R ₁₆ composed of a group or more substituents; wherein R ₆ , p and s are as defined above; and R ₁₅ and R ₁₆ are as defined in the formula (I) in the first claim; (C ₆ -C ₁₀ ) aryl is unsubstituted or independently selected from the group consisting of (C ₁ -C ₆₎ alkyl, halo , Halo (C ₁ -C ₆₎ alkyl, hydroxy, -O (C ₁ -C ₆₎ alkyl, halo (C ₁ -C ₆₎ alkoxy, -O (C ₆ -C ₁₀₎ aryl , (C ₁ -C ₆ )alkylheterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ , -O(C ₁ -C ₆ )alkyl-S ( O) substituted with one or more groups consisting of _p R ₆ and -O(CH ₂ ) _s C[=NO(C ₁ -C ₆ )alkyl]R ₈ ; wherein R ₆ , R ₉ , s and p are as defined above, and R ₈ is selected from hydrogen, (C ₁ -C ₆ )alkyl, -C(O)(C ₁ -C ₆ )alkyl, -C(O)O a group consisting of (C ₁ -C ₆ )alkyl, -C(O)NH ₂ and -S(O) _p R ₆ wherein R ₆ is as defined above; heterocyclyl is unsubstituted Or independently selected from (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo (C ₁ - C ₆ ) alkoxy, (C ₆ -C ₁₀ )aryl, amine, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ ) one of the alkyl groups and one or more groups substituted by one or more groups consisting of -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ is p is as defined above; heteroaryl is unsubstituted or independently Selected as (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halogenated (C ₁ -C ₆ ) alkane Oxyl, amine, cyano, nitro, (C ₆ -C ₁₀ ) aryl, heterocyclic, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _a one or more 3- to 10-membered ring substituted by one or more groups consisting of _p R ₆ ; wherein R ₆ , R ₉ and p are as defined above; halogen is chlorine, bromine, iodine or fluorine; Or a isotopic form thereof, a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a prodrug, a polymorph, an N oxide, an S oxide Or a monocarboxylic acid isoelectronic alignment. A compound as described in claim 1 or 2, wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C ₆ )alkyl; R ₂ and R ₃ together form an oxycyclobutane ring; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy a group consisting of -O(C ₁ -C ₆ )alkyl, aminyl, cyano, nitro, -C(O)R ₉ and -S(O) _p R ₆ ; R _v and R _w Independently selected from the group consisting of hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, amine, cyano, a group consisting of -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl and heteroaryl; R _y is R ₅ ; R ₅ Is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, nitro, -C(O)R ₉ or -S(O) _p R ₆ ; X and Q are O; A is (C ₆ -C ₁₀ ) aryl, heteroaryl, m is 1; R ₆ , R ₇ , R ₉ , R ₁₀ , R ₁₁ , R ₁₂ , R ₁₃ , R ₁₄ , n, p, q and r are as in the formula (I) in the first item of the patent application scope a (C ₁ -C ₆ )alkyl group which is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ ) alkynyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ Aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ Substituted by one or more groups; wherein R ₆ , R ₉ and p are as defined in the formula (I) in the first item of the patent application; -O(C ₁ -C ₆ )alkyl Is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, hydroxy, halogen, Amino, cyano, -(C ₁ -C ₆ )alkyl-S(O) _p R ₆ , -S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ one or more of the group consisting of radicals substituted; wherein _{R 6, R 15, R 16} , p and s are as patent scope clause 1 Formula (I) are defined; (C ₆ -C ₁₀₎ aryl is unsubstituted or independently selected from the group consisting of (C ₁ -C ₆₎ alkyl, (C ₂ -C ₈₎ alkenyl, ( C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, ( C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, (C ₁ -C ₆ )alkylheterocyclyl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ and -O(CH ₂ ) _s C[=NO(C ₁ -C ₆ )alkyl]R Substituting one or more groups of ₈ groups; wherein R ₆ , R ₉ and p are as defined in the formula (I) in the first item of the patent application; the heterocyclic group is unsubstituted Or independently selected from (C ₁ -C ₆ )alkyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo (C ₁ - C ₆ ) alkoxy, (C ₆ -C ₁₀ ) aryl, amine, cyano, nitro, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O One of the group consisting of -(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ is substituted by one or more groups of 3 to 9 Ring; where R ₆ and p are as applied The one defined by the formula (I) in the first item; the heteroaryl group is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ )alkenyl, C ₂ -C ₈ )alkynyl, halogen, halo(C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C _a 3- to 10-membered ring substituted by one or more groups consisting of ₁ -C ₆ )alkyl-S(O) _p R ₆ ; wherein R ₆ , R ₉ and p are as claimed in the patent application a chemical formula (I) as defined in item 1; halogen is chlorine, bromine, iodine or fluorine; or an isotopic form thereof, a stereoisomer, a tautomer, a pharmaceutically acceptable salt, A pharmaceutically acceptable solvate, a prodrug, a polymorph, an N oxide, an S oxide or a monocarboxylic acid isoelectronic alignment. The compound of any one of the preceding claims, wherein Z is -COOR ₁ or -CON(R ₁ ) ₂ ; R ₁ is hydrogen or (C ₁ -C) ₆ ) an alkyl group; R ₂ together with R ₃ form an oxycyclobutane ring; R ₄ is independently selected in each case from hydrogen, (C ₁ -C ₆ )alkyl, halogen, halogen (C ₁ a group of -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, nitro, -C(O)R ₉ and -S(O) _p R ₆ Group; R _v is hydrogen and R _w is hydrogen, halogen, hydroxy, (C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkyl, -O(C ₁ -C ₆ )alkyl, Amino, cyano, -C(O)R ₉ , (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl or heteroaryl; R _y is R ₅ ; R ₅ is hydrogen, (C ₁ -C ₆ )alkyl, halogen, halogenated (C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, amine, cyano, nitro , -C(O)R ₉ or -S(O) _p R ₆ ; X and Q are O; A is m is 1; R ₆ , R ₇ , R ₉ , R ₁₄ , n, p, q and r are as defined in the formula (I) in the first item of the patent application; wherein (C ₁ -C ₆ ) alkane The group is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, halogen,halo (C1-C6 An alkyl group, a hydroxyl group, a -O(C ₁ -C ₆ )alkyl group, a (C ₃ -C ₈ )cycloalkyl group, a (C ₆ -C ₁₀ )aryl group, a heterocyclic group, a heteroaryl group, an amine group, Substituted by one or more groups consisting of cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ ; _6. R ₉ and p are as defined in the formula (I) in the first item of the patent application; -O(C ₁ -C ₆ )alkyl is unsubstituted or independently selected from (C ₁ - C ₆ )alkyl, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ )aryl, heterocyclyl, hydroxy, halogen, amine, cyano, -(C ₁ -C ₆ ) alkane Substituting one or more groups of the group consisting of _s -S(O) _p R ₆ , -S(O) _p R ₆ , -NR ₁₅ R ₁₆ and -(CH ₂ ) _s NR ₁₅ R ₁₆ ; Wherein R ₆ , R ₁₅ , R ₁₆ , p and s are as defined in the chemical formula (I) in the first item of the patent application; (C ₆ -C ₁₀ ) The aryl group is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, halogen, halogenated ( C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ ) aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R ₉ , -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ is substituted with one or more groups consisting of -O(CH ₂ ) _s C[=NO(C ₁ -C ₆ )alkyl]R ₈ ; wherein R ₆ , R ₈ , R ₉ , s and p are as defined in the formula (I) in claim 1 of the patent application; the heterocyclic group is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, halogen, halogen ( C ₁ -C ₆ )alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₆ -C ₁₀ )aryl, amine, cyanide Base, nitro, -(C ₁ -C ₆ )alkyl-OH, (C ₁ -C ₆ )alkyl-O-(C ₁ -C ₆ )alkyl and -O(C ₁ -C ₆ ) alkane One of the group consisting of one or more groups consisting of a group consisting of s-S(O) _p R ₆ is substituted with a 3- to 9-membered ring; wherein R ₆ and p are as in the formula (I) of claim 1 Defined; The group is unsubstituted or independently selected from (C ₁ -C ₆ )alkyl, (C ₂ -C ₈ )alkenyl, (C ₂ -C ₈ )alkynyl, halogen,halo (C ₁ - C ₆ ) alkyl, hydroxy, -O(C ₁ -C ₆ )alkyl, halo(C ₁ -C ₆ )alkoxy, (C ₃ -C ₈ )cycloalkyl, (C ₆ -C ₁₀ Aryl, heterocyclic, heteroaryl, amine, cyano, nitro, -C(O)R ₉ and -O(C ₁ -C ₆ )alkyl-S(O) _p R ₆ One or more groups of one or more groups are substituted by a 3- to 9-membered ring; wherein R ₆ , R ₉ and p are as defined in the chemical formula (I) in the first item of the patent application; halogen is chlorine, Bromine, iodine or fluorine; or a isotopic form thereof, a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a prodrug, a polymorph, N oxide, S oxide or monocarboxylic acid isoelectronic alignment. The compound of any one of clauses 1 to 11, wherein the compound is selected from the group consisting of: methyl 2-((3-(4-((2', 6') -Dimethyl-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3- Ethyl)oxy)acetate; 2-((3-(4-((2',6'-dimethyl-4'-(3-(methylsulfonyl)propoxy)-[1, 1'-Biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-([1,1'-) Biphenyl]-3-ylmethoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-([1,1'-biphenyl]-) 3-ylmethoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((4'-)-trifluoromethyl)-[1, 1'-Biphenyl]-4-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-) Fluoromethyl)-[1,1'-biphenyl]-4-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4) -((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy) Acetate; 2-((3-(4-((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy Acetic acid; methyl 2-((3-(4-(3-phenoxybenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-(( 3-(4-((3-phenoxybenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-(4-) Phenoxybenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-(4-phenoxybenzyl)oxy)) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2-phenoxybenzyl)oxy)phenyl)oxycyclobutane-3 -yl)oxy)acetate; 2-((3-(4-((2-phenoxybenzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; 2-((3-(4-(4-fluorophenoxy)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-( (3-(4-((3-(4-fluorophenoxy)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3- 4-((4'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-( (3-(4-((4'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-(4'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate ; 2-((3-(4-((4'-)-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate; methyl 2-((3-(4-((2',4'-dimethyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxy ring Butyl-3-yl)oxy)acetate; 2-((3-(4-((2')-)-dimethyl-[1,1'-biphenyl]-3-yl) Oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2'-chloro-[1,1'-biphenyl]-3-) Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-chloro-[1,1'-biphenyl]] 3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((4'-hydroxy-[1,1'-) Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-hydroxy-[1, 1'-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((3')-hydroxy-) [1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3') -hydroxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-( (2'-Fluoro-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid 2-((3-(4-((2'-fluoro-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy) Acetic acid; methyl 2-((3-(4-((4'-(methylthio))-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-(yl)oxy)acetate; 2-((3-(4-((4'-(methylthio))-[1,1'-biphenyl]-3-yl)methoxy)benzene Oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((3'-cyano)-[1,1'-biphenyl]-3-yl)) Oxy)phenyl)oxycyclobutan-3-yl)oxy)acetate; 2-((3-(4-((3'-cyano)-[1,1'-biphenyl]-3) -yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2')-fluoro-5'-(trifluoromethyl)) )-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-(( 2'-Fluoro-5'-(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; Ethyl 2-((3-(4-((2'-fluoro-4'-(trifluoromethyl)-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxy Cyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-fluoro-4'-(trifluoromethyl)-[1,1'-biphenyl]] 3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2'-)(trifluoromethyl))-[ 1,1 '-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-)) Methyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4- ((2'-Chloro-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-(yl)oxy)acetate; 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonyl)propoxy)-[1,1'- Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2'-chloro-4'-) ((3-(Hydroxymethyl)oxycyclobutane-3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetate; 2-((3-(4-((2'-chloro-4'-((3-(hydroxymethyl))oxycyclobutane-3-yl)methoxy) )-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-(( 2'-Chloro-4'-((1,1-dioxainyltetrahydrothiophen-3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)benzene Oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-chloro-4'-((1,1-dioxy)-tetrahydrothiophene) 3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl) Acetate; methyl 2-((3-(4-((2'-chloro-4'-((1,1-dioxy)tetrahydro-2H-thiopyran-4-yl)methoxy) )-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-(( 2'-Chloro-4'-((1,1-dioxoisotetrahydro-2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl) A Oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2'-chloro-4'-((tetrahydro-2H-pyran)) 4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-( (3-(4-((2'-chloro-4'-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)) Oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((4'-((3-(hydroxymethyl))oxycyclobutane) 3-yl)methoxy)-2',6'-dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy Acetate; 2-((3-(4-((4'-)(3-(hydroxymethyl))oxycyclobutane-3-yl)methoxy)-2',6'-di Methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-( (4'-((1,1-Dioxy)tetrahydrothiophen-3-yl)methoxy)-2',6'-dimethyl-[1,1'-biphenyl ]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-((1,1-) Oxygen-based tetrahydrothiophen-3-yl)methoxy)-2',6'-dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2',6'-dimethyl-4'-((tetrahydro-2H-pyran-4-yl)) Methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3- 4-((2',6'-Dimethyl-4'-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl) Methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((4'-((1,1-dioxy)-tetrahydro- 2H-thiopyran-4-yl)oxy)-2',6'-dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3 -yl)oxy)acetate; 2-((3-(4-((4)-((1,1-dioxy)tetrahydro-2H-thiopyran-4-yl)oxy)- 2',6'-Dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-( (3-(4-((4-(spiro[茚-1,4'-piperidine]-1'-ylmethyl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy Acetate; 2-((3-(4-((4-()))))) Phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((4-(()))) Piperidine]-1'-yl)methyl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4- ((1-Methylspiro[porphyrin-3,4'-piperidinyl]-1'-yl)methyl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy) Acetic acid; methyl 2-((3-(4-(4-fluoro-4'-methyl-[1,1'-biphenyl]-2-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetate; 2-((3-(4-((4-fluoro-4'-methyl-[1,1'-biphenyl]-2-yl)methoxy) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2'-(benzyloxy)-4-fluoro-[1,1') -biphenyl]-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-)) 4-fluoro-[1,1'-biphenyl]-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3- (4-((4-Fluoro-[1,1'-biphenyl]-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-(( 3-(4-((4-fluoro-[1,1'-biphenyl]-2-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; methyl 2- ((3-(4-((3',4-Difluoro-[1,1'-biphenyl]-2-yl)methoxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)acetate; 2-((3-(4-((3')4-difluoro-[1,1'-biphenyl]-2-yl)methoxy) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((4'-(3-(methylsulfonyl))propoxy)-[1, 1'-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-)) -(Methanesulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2 -((3-(4-((4'-((3-(hydroxymethyl))oxycyclobutane-3-yl)methoxy)-[1,1'-biphenyl]-3-yl) Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-)(3-(hydroxymethyl))oxycyclobutane) 3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-( (3-(4-((4'-((1,1-Dioxy)tetrahydrothiophen-3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy Phenyl)oxycyclobutan-3-yl)oxy)acetate; 2-((3-(4-((4'-)(1,1-dioxy)tetrahydrothiophene-3 -yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3) -(4-((4'-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl]-3- Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-((tetrahydro-2H-pyran-4-) Methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3- (4-((4-(o-tolyloxy)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-(( 4-(o-tolyloxy)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3'-fluoro-)- 2'-Methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionate; 2-((3- 4-((3'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)propionic acid ; ethyl 2-((3-(4-((2'-)-trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-(yl)oxy)propionate; 2-((3-(4-((2'-)(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)) Phenyl)oxycyclobutane-3-yl)oxy)propionic acid; ethyl 2-((3-(4-((2'-methyl-[1,1'-biphenyl]-3-yl) Methoxy)phenyl)oxycyclobutan-3-yl)oxy)propionate; 2-((3-(4-((2'-methyl-[1,1'-biphenyl]] 3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionic acid; ethyl 2-((3) -(4-((2'-chloro-4'-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy) Phenyl)oxycyclobutane-3-yl)oxy)propionate; 2-((3-(4-((2'-chloro-4'-((tetrahydro-2H-pyran-4) -yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionic acid; ethyl 2-(( 3-(4-((2'-chloro-4'-((1,1-dioxo)tetrahydrothiophen-3-yl)methoxy)-[1,1'-biphenyl]-3- Methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionate; 2-((3-(4-((2'-chloro-4'-((1,1-) Dioxyindolinotetrahydrothiophen-3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy) Propionic acid; ethyl 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3- Methoxy)phenyl)oxycyclobutan-3-yl)oxy)propionate; 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonate)) Mercapto)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionic acid; ethyl 2-(( 3-(4-((2'-chloro-4'-((1,1-dioxy)tetrahydro-2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl ]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)propionate; 2-((3-(4-((2'-chloro-4'-((2'))) 1,1- Oxygen-based tetrahydro-2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl) Oxy)propionic acid; ethyl 2-((3-(4-((4'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate; ethyl 2-((3-(4-((3-(4-)methylthiophen-2-yl)benzyl)oxy)benzene Oxycyclobutane-3-yl)oxy)acetate; ethyl 2-((3-(4-((3'-fluoro-2'-methyl-[1,1'-biphenyl) ]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3')-fluoro-2'-methyl) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2) '-Methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4) -((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-(( 3-(4-((3'-Chloro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy ) acetate; 2-((3-(4-((3'-chloro-2'-methyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxy ring Butyl-3-yl)oxy)acetic acid; ethyl-2-((3-(4-((2'-chloro-4'-((1,1-dioxo)) Tetrahydro-2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy ) acetate; 2-((3-(4-((2'-chloro-4'-((1,1-dioxo)-tetrahydro-2H-thiopyran-4-yl)methoxy) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3) -(3,5-dimethylisoxazol-4-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; ethyl 2-((3- (4-((3-(5-(hydroxymethyl))thiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; ethyl 2- ((3-(4-(4-(4-(hydroxymethyl)thiazol-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; Ethyl 2-((3-(4-((4)-((3-(hydroxymethyl)oxycyclobutane-3-yl)methoxy)-2'-(trifluoromethyl)-[ 1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; ethyl 2-((3-(4-((2) ',6'-bis(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2',6'-bis(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid; ethyl 2-((3-(4-((4'-cyanide)) -2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; ethyl 2-(( 3-(4-((3-(5-(hydroxymethyl))-3-methylthiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy) Ethyl ester; ethyl 2-((3-(4-((3-(5-methylthiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy) Acetate; ethyl 2-((3-(4-((2'-(difluoromethyl)-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxy ring Butane-3-yl)oxy)acetate; ethyl 2-((3-(4-(3-(3-methylthio)-2-yl)benzyl)oxy)phenyl)oxy Cyclobutane-3-yl)oxy) acetate; ethyl 2-((3-(4-((4'-(N,N-dimethylaminesulfonyl)-2'-methyl) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; ethyl 2-((3-(4-( (2'-Chloro-4'-((1,1-dioxoindolizhan-2H-thiopyran-4-yl)oxy)-[1,1'-biphenyl]-3-yl) A Oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-chloro-4'-((1,1-dioxy)) Tetrahydro-2H-thiopyran-4-yl)oxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy) Acetic acid; methyl 2-((3-(4-((4'-((1,1-dioxy)) Hydrogen-2H-thiopyran-4-yl)methoxy)-2',6'-dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)acetate; 2-((3-(4-((4'-((1,1-dioxo)-tetrahydro-2H-thiopyran-4-yl)) Oxy)-2',6'-dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-(3-(2-fluoropyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetate; -((3-(4-(3-(2-fluoropyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; methyl 2-( (3-(4-((2'-Chloro-4'-(isopentyloxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetate; 2-((3-(4-((2'-chloro-4'-(isopentyloxy)-[1,1'-biphenyl]-3-yl)) Methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2'-chloro-3'-methyl-[1,1') -biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-chloro-3') -methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4- ((3'-Chloro-2'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3 -yl)oxy)acetate; 2-((3-(4-((3'-chloro-2'-methoxy-[1,1'-biphenyl]-3-yl)methoxy) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2'-chloro-4'-methoxy-[1,1'-linked) Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-chloro-4'-) Oxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-( (2',6'-Dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2- ((3-(4-((2',6'-Dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate; ethyl 2-((3-(4-((4'-propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-(yl)oxy)acetate; 2-((3-(4-((4'-propoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2'-chloro-4'-methyl-[1,1'-biphenyl]-3-) Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-chloro-4'-methyl-[1, 1'-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((4'-)) —(1,1′-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-( (4'-(Pentyloxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-( (3-(4-((4'-isobutoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy) Acid ester; 2-((3-(4-((4'-biphenyloxy)-3-yl)methoxy)phenyl)oxycyclobutane-3- Ethyl)oxy)acetic acid; ethyl 2-((3-(4-((4'-(butylthio))-[1,1'-biphenyl)-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-(butylthio))-[1,1'-biphenyl]-3-yl)) Methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((4'-)-isopropylthio)-[1,1'- Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-)-isopropylthio) )-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-(( 4'-(Trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-( (3-(4-((4'-(Trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2'-chloro-4'-propoxy-[1,1'-biphenyl]-3-yl)) Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-chloro-4'-propoxy-[1,1] '-Biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3-(2-) Pyridin-3-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3-(2-methyl))) Pyridin-3-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((4'-))) )-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-(( 4'-(Methanesulfonyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-( (3-(4-(3-(5-(1-Cyanocyclopropyl)thiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy) Acid ester; 2-((3-(4-(3-(5-(1-cyanocyclopropyl))thiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3- Ethyl)oxy)acetic acid; ethyl 2-((3-(4-((4'-(methylsulfinyl)-[1,1'-biphenyl]-3-yl)methoxy)benzene Oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4) '-(Methanesulfinyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-( (3-(4-(3-(3-(Trifluoromethyl)pyridin-4-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetate; 2-((3-(4-(3-(3-(trifluoromethyl)pyridin-4-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid ; ethyl 2-((3-(4-(3-(2-(trifluoromethyl)pyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy Acetate; 2-((3-(4-((3-(2-(trifluoromethyl)pyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3- Ethyl)oxy)acetic acid; ethyl 2-((3-(4-(3-(pyrimidin-5-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy) Acetate; 2-((3-(4-(3-(pyrimidin-5-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; -((3-(4-(3-(4-methylpyrimidin-5-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetate; 2- ((3-(4-(3-(4-methylpyrimidin-5-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; ethyl 2-( (3-(4-((3-(2-methoxypyrimidin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-( (3-(4-( (3-(2-Methoxypyrimidin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-() (3-(Pyrazin-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3-) Pyrazin-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3-(6-methyl))) Pyridin-3-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3-(6-methylpyridine))) -3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2'-(cyanomethyl)))) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2) '-(Cyanomethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-(( 3-(4-((3-(pyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4- ((3-(pyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3-) Pyridin-4-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3-(pyridin-4-yl))) Benzyl)oxy)phenyl)oxetane Alkyl-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2'-)-trifluoromethoxy)-[1,1'-biphenyl]-3-yl)) Oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-)(trifluoromethoxy)-[1,1'-) Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((4'-fluoro-2'-) Methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-( (4'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2 -((3-(4-((5'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl) Oxy)acetate; 2-((3-(4-((5'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2'-fluoro-6'-methyl-[1,1'-biphenyl]-3) -yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2')-fluoro-6'-methyl-[1 , 1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2'-( Methylthio)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4) -((2'-(methylthio)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2 -((3-(4-((2'-(methylsulfonyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate; 2-((3-(4-((2'-(methylsulfonyl)-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxy Cyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2'-(methylsulfinyl)-[1,1'-biphenyl]-3-yl) Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-(methylsulfinyl))-[1,1 '-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3-(5-) Oxy-2-methylpyridin-3-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3) -(5-methoxy-2-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-) 4-((2'-Methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2- ((3-(4-((2'-Methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid ; ethyl 2-((3-(4-((6-(2-(trifluoromethyl)phenyl)pyridine-2-) Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-(6-(2-(trifluoromethyl)phenyl))) Pyridin-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((6-(2-chloro-4-)) Oxyphenyl)pyridin-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((6-(2-))) 4-methoxyphenyl)pyridin-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((6-) (2,4-xylene)pyridin-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((6-) (2,4-xylene)pyridin-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((6-) (3-fluoro-2-methylphenyl)pyridin-2-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-( (6-(3-Fluoro-2-methylphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-) 4-((5-(2-(Trifluoromethyl)phenyl)thiophen-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-( (3-(4-((5-(2-(Trifluoromethyl)phenyl)thiophen-2-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; 2-((3-(4-(2-(3-fluoro-2-methylphenyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy) Acid ester; 2-((3-(4-((2-(3-)))))))))))))) Acetate; ethyl 2-((3-(4-((2-(o-tolyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy) Acetate; 2-((3-(4-((2-(o)-yl)thiazol-4-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; Ethyl 2-((3-(4-(2-(2-(trifluoromethyl)phenyl)thiazol-5-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate; 2-((3-(4-((2-(2-(trifluoromethyl)phenyl)thiazol-5-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid; ethyl 2-((3-(4-((5-(3-chloro-2-methylphenyl)thiophen-2-yl)methoxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)acetate; 2-((3-(4-((5-(3-chloro-2-methylphenyl)thiophen-2-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((6-(3-chloro-2-methylphenyl)pyridin-2-yl)methoxy)) Phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((6-(3-chloro-2-methylphenyl)pyridin-2-yl))) Oxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2-(2-(trifluoromethyl)phenyl)thiazol-4-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2-(2-(trifluoromethyl)phenyl)thiazol-4-yl)methoxy) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2-(3-)))))) Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2-(3-fluoro-2-methylphenyl))) -yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; methyl 2-((3-(4-((2'-)-difluoromethyl)-[1, 1'-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2'-) Fluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4) -((4'-(3-(methylsulfonyl)propoxy)-2'-(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl Oxycyclobutane-3-yl)oxy)acetate; ethyl 2-((3-(4-((3'-fluoro-2'-methyl-[1,1'-biphenyl]] 3-yl)methoxy)-2-methylphenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3')-fluoro-2) '-Methyl-[1,1'-biphenyl]-3-yl)methoxy)-2-methylphenyl)oxy ring Butyl-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3'-chloro-2'-methyl-[1,1'-biphenyl]-3-yl)) Methoxy)-2-methylphenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3'-chloro-2'-methyl-[ 1,1'-biphenyl]-3-yl)methoxy)-2-methylbenzene)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(2-) 4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetate; -((3-(2-methyl-4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl) Ethyl)acetic acid; ethyl 2-((3-(2-fluoro-4-((3'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy) Phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(2-fluoro-4-((3'-fluoro-2'-methyl-[1, 1'-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3'-chloro-)- 2'-Methyl-[1,1'-biphenyl]-3-yl)methoxy)-2-fluorophenyl)oxocyclobutane-3-yl)oxy)acetate; 2-( (3-(4-((3'-Chloro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)-2-fluorophenyl)oxycyclobutane-3 -yl)oxy)acetic acid; ethyl 2-((3-(2-fluoro-4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)benzene) Oxygen ring 3-(yl)oxy)acetate; 2-((3-(2-fluoro-4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((2'-chloro-6'-(trifluoromethyl))-[1,1 '-Biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((2')-chloro-6) '-(Trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-(( 3-(4-((4'-propyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; 2-((3-(4-((4'-propyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy) Acetic acid; ethyl 2-((3-(4-((2-(5,5-dimethylcyclopent-1-en-1-yl)-2'-fluoro-5'-methoxy-[ 1,1'-biphenyl]-4-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; ethyl 2-((3-(4-((2) -(3-chloro-2-methylphenyl)thiazol-4-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4- ((2-(3-Chloro-2-methylphenyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3- (4-((3-(4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane -3-yl)oxy)acetate; 2-((3-(4-((3-(4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)benzyl) Oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4-((3-(4,5,6,7-tetrahydrobenzo[d][d Thiazol-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetate; 2-((3-(4-((3-(4,5, 6,7-tetrahydrobenzo[d]thiazol-2-yl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ethyl 2-((3-(4) -((4'-cyclopropyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetate; 2-( (3-(4-((4'-cyclopropyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; Ethyl 2-((3-(4-(3-(5,6,7,8-tetrahydronaphthalen-2-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl) Oxy)acetate; 2-((3-(4-((3-(5,6,7,8-tetrahydronaphthalen-2-yl)benzyl)oxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid; ethyl 2-((3-(4-(4-(2-(methoxy)))-2-(p-tolyl)ethoxy)benzyl Oxy)phenyl)oxycyclobutane-3-yl)oxy)acetate; and 2-((3-(4-(4-(2-(methoxyimino))-2-) (p-tolyl)ethoxy)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy Acetic acid; or an isotopic form, a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a pharmaceutically acceptable solvate, a prodrug, a polymorph, an N oxide, an S oxidation Or a carboxylic acid homo-array. The compound of any one of claims 1 to 12, wherein the compound is selected from the group consisting of 2-((3-(4-((2', 6') Methyl-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl) Oxy)acetic acid; 2-((3-(4-([1,1'-biphenyl]-3-ylmethoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; -((3-(4-((4'-)(trifluoromethyl)-[1,1'-biphenyl]-4-yl)methoxy)phenyl)oxycyclobutane-3-yl) Oxy) acetic acid; 2-((3-(4-((5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-(3-phenoxybenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy Acetate; 2-((3-(4-(4-phenoxybenzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; 2-((3- 4-((2-phenoxybenzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3-(4-)) Oxy)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4')-methyl-[1,1'-linked Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4')-methoxy-[1,1 '-Link Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2',4'-dimethyl-[ 1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2')-chloro-) [1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4')-hydroxy) -[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3'-) Hydroxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2') -fluoro-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4) '-(Methylthio)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3- 4-((3'-Cyano-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3 -(4-((2'-fluoro-5'-(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl Oxy)acetic acid; 2-((3-(4-((2'-fluoro-4'-(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-)(trifluoromethyl)-[1,1'-biphenyl]-3- Methoxy Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonyl))propoxy) )-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2') -Chloro-4'-((3-(hydroxymethyl)oxycyclobutane-3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-((1,1-dioxo)-tetrahydrothiophen-3-yl) Methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4- ((2'-Chloro-4'-((1,1-dioxo)tetrahydro-2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-((tetrahydro-2H-pyran)) 4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3 -(4-((4'-((3-(hydroxymethyl)oxycyclobutan-3-yl)methoxy)-2',6'-dimethyl-[1,1'-biphenyl ]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4'-((1,1-dioxy)) Tetrahydrothiophen-3-yl)methoxy)-2',6'-dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Cyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2',6'-dimethyl-4'-((tetrahydro-2H-pyran-4-yl)) Methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4- ((4'-((1,1-Dioxy)tetrahydro-2H-thiopyran-4-yl)oxy)-2',6'-dimethyl-[1,1'-biphenyl] -3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4-())) Acridine]-1'-ylmethyl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4-((1- Methylspiro[porphyrin-3,4'-piperidinyl]-1'-yl)methyl)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; ((3-(4-(4-fluoro-4'-methyl-[1,1'-biphenyl]-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy Acetate; 2-((3-(4-((2'-(benzyloxy)-4-fluoro-[1,1'-biphenyl)-2-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-(4-fluoro-[1,1'-biphenyl]-2-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3')4-difluoro-[1,1'-biphenyl]-2-yl)methoxy) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4'-(3-(methylsulfonyl))propoxy)-[1,1 '-Link ]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4'-((3-(hydroxymethyl)))) Oxycyclobutane-3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; -((3-(4-((4'-((1,1-dioxy)tetrahydrothiophen-3-yl)methoxy)-[1,1'-biphenyl]-3-yl) Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4)-((tetrahydro-2H-pyran-4-yl))) Oxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-(( 4-(o-tolyloxy)benzyl)oxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3')-fluoro-2') -methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)propionic acid; 2-((3-(4-( (2'-(Trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionic acid; 2-( (3-(4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)propanoic acid; 2-((3-(4-((2)-chloro-4'-((tetrahydro-2H-pyran-4-yl)methoxy)-[1,1'-biphenyl]-3- Methoxy)phenyl)oxycyclobutan-3-yl)oxy)propionic acid; 2-((3-(4-((2'-chloro-4'-((1,1-) Ionic tetrahydrothiophen-3-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propionic acid 2-((3-(4-((2'-chloro-4'-(3-(methylsulfonyl)propoxy)-[1,1'-biphenyl]-3-yl)methoxy Phenyl)oxycyclobutane-3-yl)oxy)propionic acid; 2-((3-(4-((2'-chloro-4'-((1,1-dioxy-4'-)) Hydrogen-2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)propane Acid; 2-((3-(4-((3'-fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-(yl)oxy)acetic acid; 2-((3-(4-((2'-methyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxycyclobutane Alkyl-3-yl)oxy)acetic acid; 2-((3-(4-((3'-chloro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy) Phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-((1,1-dioxy)-tetrahydro- 2H-thiopyran-4-yl)methoxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; -((3-(4-((2',6'-bis(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane- 3-(yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-((1,1-dioxo)-tetrahydro-2H-thiopyran-4 -yl)oxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4) -((4'-((1,1-dioxo)tetrahydro-2H-thiopyran-4-yl)methoxy)-2',6'-dimethyl-[1,1'-linked Benzyl-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3-(2-fluoropyridin-3-yl))) Benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-(isopentyloxy))-) [1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2')-) -3'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4) -((3'-Chloro-2'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-methoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid; 2-((3-(4-((2',6'-dimethyl-[1,1'-biphenyl)-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4'-propoxy-[1,1'-biphenyl]-3-yl)methoxy)) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-chloro-4'-methyl-[1,1'-biphenyl]-3) -基)甲甲Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4'-)-pentyloxy)-[1,1'-biphenyl]-3 -yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4'-isobutoxy-[1,1'-) Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4'-(butylthio))-[1 ,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((4'-)-isopropyl Thio)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-(( 4'-(Trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3 -(4-((2'-chloro-4'-propoxy-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy Acetic acid; 2-((3-(4-((3-(2-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; 2-((3-(4-((4'-(methylsulfonyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl Ethoxy)acetic acid; 2-((3-(4-(3-(5-(1-cyanocyclopropyl))thiophen-2-yl)benzyl)oxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid; 2-((3-(4-((4'-(methylsulfinyl)-[1,1'-biphenyl]-) 3-()-methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3-(3-(trifluoromethyl))) -yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3-(2-(trifluoromethyl))pyridine) 3-()-benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-(3-(pyrimidin-5-yl)benzyl)) Oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3-(4-methylpyrimidin-5-yl)benzyl)oxy)) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3-(2-methoxy))))) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-(3-(pyrazin-2-yl)benzyl)oxy)phenyl)oxycyclobutane- 3-()-oxy)acetic acid; 2-((3-(4-((3-(6-methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl) Ethoxy)acetic acid; 2-((3-(4-((2'-(cyanomethyl)-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxy ring Butyl-3-yl)oxy)acetic acid; 2-((3-(4-(3-(pyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl) Oxy)acetic acid; 2-((3-(4-((3-(pyridin-4-yl)benzyl)oxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; ((3-(4-((2'-)) Oxy)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-(( 4'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-(( 3-(4-((5'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy Acetic acid; 2-((3-(4-((2'-fluoro-6'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane -3-yl)oxy)acetic acid; 2-((3-(4-((2'-(methylthio))-[1,1'-biphenyl]-3-yl)methoxy)phenyl) Oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-(methylsulfonyl)-[1,1'-biphenyl]-3-yl)) Methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-(methylsulfinyl))-[1,1'-linked Benzyl-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3-(5-methoxy-2-) Methylpyridin-3-yl)benzyl)oxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2')-methoxy-[ 1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((6-(2-) (trifluoromethyl)phenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; 2-((3 -(4-((6-(2-chloro-4-methoxyphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-( (3-(4-((6-(2,4-Dimethyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; 2-((3 -(4-((6-(3-fluoro-2-methylphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-(( 3-(4-((5-(2-(Trifluoromethyl)phenyl)thiophen-2-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; ((3-(4-(2-(3-fluoro-2-methylphenyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; -((3-(4-((2-(o-tolyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; 2-((3 -(4-((2-(2-(trifluoromethyl)phenyl)thiazol-5-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; (3-(4-((5-(3-chloro-2-methylphenyl)thiophen-2-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2- ((3-(4-(6-(3-chloro-2-methylphenyl)pyridin-2-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid; -((3-(4-(2-(2-(trifluoromethyl)phenyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutan-3-yl)oxy)acetic acid ; 2-((3-(4-((2-(3-) -2-methylphenyl)thiazol-5-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((2'-) Fluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-( (3'-Fluoro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)-2-methylphenyl)oxocyclobutane-3-yl)oxy)acetic acid ; 2-((3-(4-((3'-Chloro-2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)-2-methylphenyl)oxy ring Butyl-3-yl)oxy)acetic acid; 2-((3-(2-methyl-4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy) Phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(2-fluoro-4-((3'-fluoro-2'-methyl-[1,1') -biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3-yl)oxy)acetic acid; 2-((3-(4-((3'-chloro-2'-) -[1,1'-biphenyl]-3-yl)methoxy)-2-fluorophenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-((3-(2- Fluoro-4-((2'-methyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxocyclobutane-3-yl)oxy)acetic acid; 2-( (3-(4-((2'-Chloro-6'-(trifluoromethyl)-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxycyclobutane-3 -yl)oxy)acetic acid; 2-((3-(4-((4'-propyl)-[1,1'-biphenyl)-3-yl)methoxy)phenyl)oxycyclobutane -3- base) Oxy)acetic acid; 2-((3-(4-((2-(3-chloro-2-methylphenyl)thiazol-4-yl)methoxy)phenyl)oxycyclobutan-3-yl) Ethyl)acetic acid; and 2-((3-(4-(4-(2-(2-(methoxy)))-2-(p-tolyl)ethoxy)benzyl)oxy)benzene Oxycyclobutane-3-yl)oxy)acetic acid; or a isotopic form thereof, a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a pharmaceutically acceptable solvent a compound, a prodrug, a polymorph, an N oxide, an S oxide or a monocarboxylic acid isoelectronic alignment. The compound of any one of claims 1 to 13, wherein the compound is a pharmaceutically acceptable salt. The compound of claim 14, wherein the pharmaceutically acceptable salt is a calcium salt. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) as defined in any one of claims 1 to 13 or a isotopic form thereof, a stereoisomer, A tautomer, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate, and a pharmaceutically acceptable carrier or excipient. A compound of the formula (I), or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof, according to any one of claims 1 to 13 Treatment of a disease or condition of the G protein coupled receptor-40 (GPR40) vector. A compound of formula (I) for use as claimed in claim 17, wherein the disease or symptom of the GPR40 vector is selected from the group consisting of diabetes, obesity, hyperglycemia, glucose intolerance, insulin resistance, hyperinsulinemia, Hypercholesterolemia, hypertension, hyperlipoproteinemia, hyperlipidemia, hypertriglyceridemia, dyslipidemia, metabolic syndrome, X syndrome, cardiovascular disease, atherosclerosis, kidney disease, polycystic Ovarian syndrome, ketoacidosis, thrombotic disorder, nephropathy, diabetic neuropathy, diabetic retinopathy, sexual dysfunction, fatty liver development, skin disease, dyspepsia, hypoglycemia, cancer, edema, and pancreatic β-cell regeneration Group of. A compound of formula (I) for use as described in claim 17 or claim 18, wherein the disease or symptom of the GPR40 vector is selected from the group consisting of diabetes, obesity, insulin resistance, hyperglycemia, glucose intolerance Symptoms, hypercholesterolemia, hypertriglyceridemia, dyslipidemia, hyperlipoproteinemia, hyperinsulinemia, atherosclerosis, diabetic neuropathy, diabetic retinopathy, metabolic syndrome, X syndrome, hypertension, and A group consisting of pancreatic beta cell regeneration.