US20230089073A1 - Gpcr receptor agonists, pharmaceutical compositions comprising the same, and methods for their use - Google Patents

Gpcr receptor agonists, pharmaceutical compositions comprising the same, and methods for their use Download PDF

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US20230089073A1
US20230089073A1 US17/586,751 US202217586751A US2023089073A1 US 20230089073 A1 US20230089073 A1 US 20230089073A1 US 202217586751 A US202217586751 A US 202217586751A US 2023089073 A1 US2023089073 A1 US 2023089073A1
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alkyl
certain embodiments
substituted
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Xiaohui Du
Ray FUCINI
Xu Ran
Chien-Hung Yeh
Xiang Zhou
Rui Gao
Joon Won Jeong
Li Liu
Subas Man Sakya
Xiaofang Wang
Hiroyuki Kawai
Craig Lee
David Lloyd
Stig Hansen
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Carmot Therapeutics Inc
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Carmot Therapeutics Inc
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Assigned to CARMOT THERAPEUTICS, INC. reassignment CARMOT THERAPEUTICS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: JEONG, JOON WON, LLOYD, DAVID, FUCINI, Ray, GAO, RUI, HANSEN, STIG, SAKYA, SUBAS MAN, ZHOU, XIANG, KAWAI, HIROYUKI, RAN, Xu, YEH, CHIEN-HUNG, DU, XIAOHUI, LEE, CRAIG, LIU, LI, WANG, XIAOFANG
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    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
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    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08—Bridged systems

Definitions

  • GLP-1 receptor modulator compounds are provided herein; pharmaceutical compositions comprising the compounds; methods of producing the compounds; and methods of using the compounds, and compositions for therapy.
  • the compounds, and compositions are useful, for instance, in methods of treatment, and prevention of metabolic diseases or conditions, methods of detection of metabolic diseases or conditions, and methods of diagnosis of metabolic diseases or conditions.
  • Diabetes is a serious chronic disease that occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces.
  • Complications of diabetes include, damage to the heart, blood vessels, eyes, kidneys, and nerves. Diabetes can increase risk of heart disease, and stroke. The results include serious effects on quality of life, health, and mortality. WHO Global Report on Diabetes, 2016, World Health Organization. As of 2017, approximately 462 million individuals worldwide, about 6.28% of the population was affected by type 2 diabetes, and this prevalence was increasing measurably. Khan et al., 2020 , J Epidemiol. Glob. Health 10(1):107-111. The global economic burden of diabetes in 2015 was estimated to be $1.3T, and estimated to increase to $2.1T by 2030.
  • GLP-1 receptor The glucagon-like peptide-1 receptor (GLP-1 receptor, or GLP1R) has emerged as a potential target for treating type 2 diabetes. Its ligand, glucagon-like peptide-1 (GLP-1) enhances glucose-induced insulin secretion, and increases insulin synthesis among many other effects. Doyle and Egan, 2007 , Pharmacol. Ther. 113(3):546-593. GLP-1 is known to delay gastric emptying, suppress food intake, increase satiety, and reduce weight in humans. Shah and Vella, 2014 Rev Endocr Metab Disord. 15(3): 181-187.
  • GLP-1 receptor Activating the GLP-1 receptor has been shown to have beneficial effects on insulin secretion and the maintenance of beta cell glucose sensing, transcription, synthesis, proliferation, and survival. Doyle and Egan, 2007, supra. While the GLP-1 receptor is a promising therapeutic target, only a handful of GLP-1 receptor drugs have been approved to date, and most, or all of these are peptide, or polypeptide drugs.
  • the compounds of Formula (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), and sub-formulas and embodiments thereof, are useful for modulating the activity of GLP-1 receptor.
  • the compounds can be used to agonize the activity of GLP-1 receptor.
  • the compounds can be used for treating diseases, or conditions modulated by GLP-1 receptor.
  • A is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, —NMe 2 , or —CF 3 ;
  • Ring B is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted bicyclic;
  • Ring C is substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heterocycloalkenyl, each comprising at least one N, linked to L 3 as depicted; zero, one, or two of D 1 , D 2 , and D 3 are N, and the rest are CH, or CR 6 ;
  • W is N, CR 14 , or C; when W is CR 4 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —, or —C(O)—;
  • L 4 is absent, or L 4 together with L 1 and Rings A and B form a fused tricycle, and L 5 is absent;
  • L 5 is absent, or L 5 together with L 2 and Rings B and C form a fused tricycle, and L 4 is absent;
  • R 4 is unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene;
  • R 5 is selected from the group consisting of —COOH, —COCF 3 , —C(OH)CF 3 , —CONHCN, —CONHOH, CONHOMe, —CONHS
  • each R 6 is independently selected from the group consisting of alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO—, and R 11 R 12 N—;
  • R 11 is hydrogen, or alkyl;
  • R 12 is hydrogen, or alkyl;
  • R 13 is hydrogen, or alkyl;
  • R 14 is hydrogen, cyano, halo, hydroxyl, alkyl, haloalklyl, methyl, CH 2 F, or CH 2 OH; wherein when L 1 is a —CH 2 O—, L 4 is absent, and L 5 is absent, then either L 2 is —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, or
  • L 3 is —C(O)—, or both.
  • A is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, —NMe 2 , or —CF 3 ;
  • Ring B is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
  • Ring C is further unsubstituted or further substituted, and/or bridged; zero, one, or two of D 1 , D 2 , and D 3 are N, and the rest are CH or CR 6 ;
  • W is N, CH, or C; when W is CH the adjacent dashed lines indicate single bonds;
  • L 3 is —CH 2 —, or —C(O)—;
  • L 4 is absent, or L 4 together with L 1 and Rings A and B form a fused tricycle, and L 5 is absent;
  • L 5 is absent, or L 5 together with L 2 and Rings B and C form a fused tricycle, and L 4 is absent;
  • R 4 is unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene;
  • R 5 is selected from the group consisting of —COOH, —COCF 3 , —C(OH)CF 3 , —CONHCN, —CONHOH, CONHOMe, —CONHS
  • each R 6 is independently selected from the group consisting of alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO—, and R 11 R 12 N—;
  • R 11 is hydrogen or alkyl;
  • R 12 is hydrogen or alkyl; and
  • R 13 is hydrogen or alkyl; wherein, when L 1 is —CH 2 O—, L 4 is absent, and L 5 is absent, then either L 2 is —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, or
  • L 3 is —C(O)—, or both.
  • W is N, CH, or C; when W is CH, the adjacent dashed lines indicate single bonds; when W is C, one adjacent dashed line indicates a double bond, for instance L 2 is —C(H) ⁇ ; zero, one, or two of A 1 , A 2 , A 3 , A 4 , and A 5 are N, and the rest are CH or CR 1 ; zero, one, or two of B 1 , B 2 , B 3 , and B 4 are N, and the rest are CH or CR 2 ; zero, one, or two of D 1 , D 2 , and D 3 are N, and the rest are CH or CR 6 ; L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—; L
  • each R 6 is independently selected from the group consisting of alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO—, and R 11 R 12 N—;
  • R 11 is hydrogen, or alkyl;
  • R 12 is hydrogen, or alkyl;
  • R 13 is hydrogen, or alkyl; and
  • o is an integer from 0 to 4.
  • W is N, CH, or C; when W is CH, the adjacent dashed lines indicate single; zero, one, or two of A 1 , A 2 , A 3 , A 4 , and A 5 are N, and the rest are CH, or CR 1 ; zero, one, or two of D 1 , D 2 , and D 3 are N, and the rest are CH, or CR 6 ; each R 1 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—; L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—; L 2 is selected from the group consisting of a bond
  • L 3 is —CH 2 —, or —C(O)—; each R 3 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—; R 4 is unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 is selected from the group consisting of —COOH, —COCF 3 , —C(OH)CF 3 , —CONHCN, —CONHOH, CONHOMe, —CONHSO 2 N(Me) 2 , —PO 3 H 2 , —PO(Me
  • each R 6 is independently selected from the group consisting of F, and methyl;
  • R 11 is hydrogen, or alkyl;
  • R 12 is hydrogen, or alkyl;
  • R 13 is hydrogen, or alkyl; and
  • o is 1, 2, 3, or 4.
  • the compounds are useful in methods of treatment and prevention of metabolic diseases, and conditions, methods of detection of metabolic diseases, and conditions, and methods of diagnosis of metabolic diseases, and conditions.
  • compositions comprising a compound of Formula (I), (Ia), (XXX), or (XXXI).
  • the compositions are pharmaceutical compositions. Any suitable pharmaceutical composition may be used.
  • a kit comprising the compound of Formula (I), (Ia), (XXX), or (XXXI), or embodiments thereof, or a pharmaceutical composition thereof.
  • kits for using the compounds or the compositions described herein are for treatment.
  • the methods are diagnostic methods.
  • the methods are analytical methods.
  • the compounds, or compositions described herein are used to treat a disease, or condition.
  • the disease, or condition is selected from metabolic diseases, or conditions.
  • the disease is type 2 diabetes.
  • FIG. 1 provides intravenous glucose tolerance test (IVGTT) in cynomolgus monkeys.
  • GLP-1 receptor compounds useful for treating metabolic diseases or conditions, such as type 2 diabetes.
  • the term “about” indicates and encompasses an indicated value, and a range above and below that value. In certain embodiments, the term “about” indicates the designated value ⁇ 10%, ⁇ 5%, or ⁇ 1%. In certain embodiments, the term “about” indicates the designated value ⁇ one standard deviation of that value. In certain embodiments, for example, logarithmic scales (e.g., pH), the term “about” indicates the designated value ⁇ 0.3, ⁇ 0.2, or ⁇ 0.1.
  • Alkoxy and “alkoxyl,” refer to the group —OR′′ where R′′ is alkyl or cycloalkyl. Alkoxy groups include, in certain embodiments, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, 1,2-dimethylbutoxy, and the like.
  • alkoxyamine refers to the group -alkylene-O—NH 2 , wherein alkylene is as defined herein.
  • alkoxyamine groups can react with aldehydes to form oxime residues.
  • alkoxyamine groups include —CH 2 CH 2 —O—NH 2 and —CH 2 —O—NH 2 .
  • alkyl refers to a saturated straight, or branched hydrocarbon.
  • the alkyl group is a primary, secondary, or tertiary hydrocarbon.
  • the alkyl group includes one to ten carbon atoms (i.e., C 1 to C 10 alkyl).
  • the alkyl is a lower alkyl, for example, C 1-6 alkyl, and the like.
  • the alkyl group is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secbutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, isohexyl, 3-methylpentyl, 2,2-dimethylbutyl, and 2,3-dimethylbutyl.
  • substituted alkyl refers to an alkyl substituted with one, two, or three groups independently selected from a halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, alkoxy, aryl, heteroaryl, cycloalkyl, cyano, oxo, alkyne, and heterocycloalkylalkylene. In some embodiments, alkyl is unsubstituted.
  • a halogen e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)
  • alkyl haloalkyl
  • hydroxyl amino, alkylamino, alkoxy, aryl, heteroaryl, cycloalkyl, cyano, oxo, alkyne, and heterocycloalkylal
  • alkylene refers to a divalent alkyl group, as defined herein. “Substituted alkylene” refers to an alkylene group substituted as described herein for alkyl. In some embodiments, alkylene is unsubstituted.
  • Alkenyl refers to an olefinically unsaturated hydrocarbon group, in certain embodiments, having up to about eleven carbon atoms, or from two to six carbon atoms (e.g., “lower alkenyl”), which can be straight-chained or branched, and having at least one, or from one to two sites of olefinic unsaturation. “Substituted alkenyl” refers to an alkenyl group substituted as described herein for alkyl.
  • Alkenylene refers to a divalent alkenyl as defined herein. Lower alkenylene is, for example, C 2 -C 6 -alkenylene.
  • Alkynyl refers to acetylenically unsaturated hydrocarbon groups, in certain embodiments, having up to about eleven carbon atoms, or from two to six carbon atoms (e.g., “lower alkynyl”), which can be straight-chained or branched, and having at least one, or from one to two sites of acetylenic unsaturation.
  • alkynyl groups include acetylene (—C ⁇ CH), propargyl (—CH 2 C ⁇ CH), and the like.
  • Substituted alkynyl refers to an alkynyl group substituted as described herein for alkyl.
  • Alkynylene refers to a divalent alkynyl as defined herein.
  • Lower alkynylene is, for example, C 2 -C 6 -alkynylene.
  • Amino refers to —NH 2 .
  • alkylamino refers to the group —NHR′′ where R′′ is, for example, C 1-10 alkyl, as defined herein. In certain embodiments, alkylamino is C 1-6 alkylamino.
  • dialkylamino refers to the group —NR′′R′′ where, each R′′ is independently C 1-10 alkyl, as defined herein. In certain embodiments, dialkylamino is di-C 1-6 alkylamino.
  • aryl refers to phenyl, biphenyl, or naphthyl.
  • the term includes both substituted and unsubstituted moieties.
  • An aryl group can be substituted with any described moiety including, but not limited to, one or more moieties (e.g., in some embodiments one, two, or three moieties) selected from the group consisting of halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, and phosphonate, wherein each moiety is independently either unprotected, or protected as necessary, as would be appreciated by those skilled in the art (e.g., Greene
  • arylamino refers to an —NR′R′′ group where R′ is hydrogen, or C 1 -C 6 -alkyl; and R′′ is aryl, as defined herein.
  • arylene refers to a divalent aryl group, as defined herein.
  • aryloxy refers to an —OR group where R is aryl, as defined herein.
  • Alkarylene refers to an arylene group, as defined herein, wherein the aryl ring is substituted with one or two alkyl groups. “Substituted alkarylene” refers to an alkarylene, as defined herein, where the arylene group is further substituted, as defined herein for aryl.
  • Alkylene refers to an -alkyl-arylene- or arylene-alkyl, for instance, a —C 1 -C 2 alkyl-arylene-, -arylene-C 1 -C 2 alkyl-, or —C 1 -C 2 alkyl-arylene-C 1 -C 2 alkyl- group, where arylene is as defined herein.
  • Substituted aralkylene refers to an aralkylene, as defined herein, where the aralkylene group is substituted, as defined herein for aryl.
  • Substituted C 1 -C 2 alkyl refers to a C 1 -C 2 alkyl group that is substituted as defined herein for an alkyl.
  • Arylalkylene refers to -alkyl-arylene- or arylene-alkyl, for instance, a —C 1 -C 2 alkyl-arylene-, -arylene-C 1 -C 2 alkyl-, or —C 1 -C 2 alkyl-arylene-C 1 -C 2 alkyl- group, where arylene is as defined herein.
  • “Substituted arylalkylene” refers to an arylalkylene, as defined herein, where the arylalkylene group is substituted, as defined herein for aryl.
  • “Substituted C 1 -C 2 alkyl” refers to a C 1 -C 2 alkyl group that is substituted as defined herein for an alkyl.
  • Carboxyl or “carboxy” refers to —C(O)OH or —COOH.
  • cycloalkyl refers to a saturated cyclic hydrocarbon.
  • the cycloalkyl group may be a saturated, and/or bridged, and/or non-bridged, and/or a fused bicyclic group.
  • the cycloalkyl group includes three to ten carbon atoms (i.e., C 3 to C 10 cycloalkyl).
  • the cycloalkyl has from three to fifteen carbons (C 3-15 ), from three to ten carbons (C 3-10 ), from three to seven carbons (C 3-7 ), or from three to six carbons (C 3 -C 6 ) (i.e., “lower cycloalkyl”).
  • the cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexylmethyl, cycloheptyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, decalinyl, or adamantyl.
  • cycloalkylene refers to a divalent cycloalkyl group, as defined herein.
  • the cycloalkylene group is cyclopropylene
  • Lower cycloalkylene refers to a C 3 -C 6 -cycloalkylene.
  • cycloalkylalkyl refers to an alkyl group, as defined herein, substituted with one or two cycloalkyl, as defined herein.
  • esters refers to —C(O)OR, or —COOR, where R is alkyl, as defined herein.
  • haloalkyl refers to an alkyl group, as defined herein, substituted with one, or more halogen atoms (e.g., in some embodiments one, two, three, four, or five) which are independently selected.
  • heteroalkyl refers to an alkyl, as defined herein, in which one or more carbon atoms are replaced by heteroatoms.
  • heteroalkenyl refers to an alkenyl, as defined herein, in which one, or more carbon atoms are replaced by heteroatoms.
  • heteroalkynyl refers to an alkynyl, as defined herein, in which one, or more carbon atoms are replaced by heteroatoms. Suitable heteroatoms include, but are not limited to, nitrogen (N), oxygen (O), and sulfur (S) atoms.
  • Heteroalkyl, heteroalkenyl, and heteroalkynyl are optionally substituted.
  • heteroalkyl moieties include, but are not limited to, aminoalkyl, sulfonylalkyl, and sulfinylalkyl.
  • heteroalkyl moieties also include, but are not limited to, methylamino, methylsulfonyl, and methylsulfinyl.
  • “Substituted heteroalkyl” refers to heteroalkyl substituted with one, two, or three groups independently selected from halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy.
  • a heteroalkyl group may comprise one, two, three, or four heteroatoms.
  • a 4-membered heteroalkyl may generally comprise one, or two heteroatoms
  • a 5- or 6-membered heteroalkyl may generally comprise one, two, or three heteroatoms
  • a 7- to 10-membered heteroalkyl may generally comprise one, two, three, or four heteroatoms.
  • heteroalkylene refers to a divalent heteroalkyl, as defined herein.
  • substituted heteroalkylene refers to a divalent heteroalkyl, as defined herein, substituted as described for heteroalkyl.
  • heterocycloalkyl refers to a monovalent, monocyclic, or multicyclic non-aromatic ring system, wherein one, or more of the ring atoms are heteroatoms independently selected from oxygen (O), sulfur (S), and nitrogen (N) (e.g., where the nitrogen, or sulfur atoms may be optionally oxidized, and the nitrogen atoms may be optionally quaternized) and the remaining ring atoms of the non-aromatic ring are carbon atoms.
  • heterocycloalkyl is a monovalent, monocyclic, or multicyclic fully-saturated ring system.
  • the heterocycloalkyl group has from three to twenty, from three to fifteen, from three to ten, from three to eight, from four to seven, from four to eleven, or from five to six ring atoms.
  • the heterocycloalkyl may be attached to a core structure at any heteroatom or carbon atom which results in the creation of a stable compound.
  • the heterocycloalkyl is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include a fused or bridged ring system and in which the nitrogen or sulfur atoms may be optionally oxidized, and/or the nitrogen atoms may be optionally quaternized.
  • heterocycloalkyl radicals include, but are not limited to, 2,5-diazabicyclo[2.2.2]octanyl, decahydroisoquinolinyl, dihydrobenzisoxazinyl, dihydrofuryl, dihydroisoindolyl, dihydropyranyl, dihydropyrazolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dioxolanyl, 1,4-dithianyl, furanonyl, imidazolidinyl, imidazolinyl, indolinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, oxazolidinonyl, oxazolidinyl, oxiranyl, piperaz
  • heterocycloalkyl may also be optionally substituted as described herein.
  • heterocycloalkyl is substituted with one, two, or three groups independently selected from halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, oxo, cyano, and alkoxy.
  • a heterocycloalkyl group may comprise one, two, three, or four heteroatoms.
  • a 4-membered heterocycloalkyl may generally comprise one or two heteroatoms
  • a 5 or 6-membered heterocycloalkyl may generally comprise one, two, or three heteroatoms
  • a 7- to 10-membered heterocycloalkyl may generally comprise one, two, three, or four heteroatoms.
  • Heterocycloalkylene refers to a divalent heterocycloalkyl as defined herein.
  • heteroaryl refers to a monovalent monocyclic aromatic group, and/or multicyclic aromatic group, wherein at least one aromatic ring contains one, or more heteroatoms independently selected from oxygen, sulfur, and nitrogen in the ring.
  • Each ring of a heteroaryl group can contain one, or two oxygen atoms, one, or two sulfur atoms, and/or one to four nitrogen atoms, provided that the total number of heteroatoms in each ring is four, or less and each ring contains at least one carbon atom.
  • the heteroaryl has from five to twenty, from five to fifteen, or from five to ten ring atoms.
  • a heteroaryl may be attached to the rest of the molecule via a nitrogen or a carbon atom.
  • monocyclic heteroaryl groups include, but are not limited to, furanyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, triazolyl, thiadiazolyl, thiazolyl, thienyl, tetrazolyl, and triazinyl.
  • bicyclic heteroaryl groups include, but are not limited to, benzofuranyl, benzimidazolyl, benzoisoxazolyl, benzopyranyl, benzothiadiazolyl, benzothiazolyl, benzothienyl, benzotriazolyl, benzoxazolyl, furopyridyl, imidazopyridinyl, imidazothiazolyl, indolizinyl, indolyl, indazolyl, isobenzofuranyl, isobenzothienyl, isoindolyl, isoquinolinyl, naphthyridinyl, oxazolopyridinyl, phthalazinyl, pteridinyl, purinyl, pyridopyridyl, pyrrolopyridyl, quinolinyl, quinoxalinyl, quinazolinyl, thiadiazolopyrimidyl, and thi
  • tricyclic heteroaryl groups include, but are not limited to, acridinyl, benzindolyl, carbazolyl, dibenzofuranyl, perimidinyl, phenanthrolinyl, phenanthridinyl, phenarsazinyl, phenazinyl, phenothiazinyl, phenoxazinyl, and xanthenyl.
  • heteroaryl may also be optionally substituted as described herein. “Substituted heteroaryl” is a heteroaryl substituted as defined for aryl.
  • heteroarylene refers to a divalent heteroaryl group, as defined herein. “Substituted heteroarylene” is a heteroarylene substituted as defined for aryl.
  • heteroarylalkylene refers to -alkyl-heteroarylene- or -heteroarylene-alkyl, for instance, a —C 1 -C 2 alkyl-heteroarylene-, -heteroarylene-C 1 -C 2 alkyl-, or —C 1 -C 2 alkyl-heteroarylene-C 1 -C 2 alkyl- group, where heteroarylene is as defined herein.
  • “Substituted heteroarylalkylene” refers to a heteroarylalkylene, as defined herein, where the heteroarylalkylene group is substituted, as defined herein for aryl.
  • “Substituted C 1 -C 2 alkyl” refers to a C 1 -C 2 alkyl group that is substituted as defined herein for an alkyl.
  • an “oxo” refers to ⁇ O.
  • protecting group refers to a group that is added to an oxygen, nitrogen, or phosphorus atom to prevent its further reaction, or for other purposes.
  • oxygen, and nitrogen protecting groups are known to those skilled in the art of organic synthesis. (See, e.g., Greene, et al., Protective Groups in Organic Synthesis, John Wiley and Sons, Fourth Edition, 2006, which is incorporated herein by reference).
  • “Pharmaceutically acceptable salt” refers to any salt of a compound provided herein which retains its biological properties, and which is not toxic or otherwise undesirable for pharmaceutical use. Such salts may be derived from a variety of organic, and inorganic counter-ions well known in the art.
  • Such salts include, but are not limited to (1) acid addition salts formed with organic, or inorganic acids such as hydrochloric, hydrobromic, sulfuric, nitric, phosphoric, sulfamic, acetic, trifluoroacetic, trichloroacetic, propionic, hexanoic, cyclopentylpropionic, glycolic, glutaric, pyruvic, lactic, malonic, succinic, sorbic, ascorbic, malic, maleic, fumaric, tartaric, citric, benzoic, 3-(4-hydroxybenzoyl)benzoic, picric, cinnamic, mandelic, phthalic, lauric, methanesulfonic, ethanesulfonic, 1,2-ethane-disulfonic, 2-hydroxyethanesulfonic, benzenesulfonic, 4-chlorobenzenesulfonic, 2-naphthalenesulfonic, 4-to
  • Pharmaceutically acceptable salts further include, by way of example and without limitation, sodium, potassium, calcium, magnesium, ammonium, and tetraalkylammonium salts, and the like, and when the compound contains a basic functionality, salts of non-toxic organic, or inorganic acids, such as hydrohalides, for example, hydrochloride and hydrobromide, sulfate, phosphate, sulfamate, nitrate, acetate, trifluoroacetate, trichloroacetate, propionate, hexanoate, cyclopentylpropionate, glycolate, glutarate, pyruvate, lactate, malonate, succinate, sorbate, ascorbate, malate, maleate, fumarate, tartarate, citrate, benzoate, 3-(4-hydroxybenzoyl)benzoate, picrate, cinnamate, mandelate, phthalate, laurate, methanesulfonate (mesylate), e
  • the term “substantially free of” or “substantially in the absence of” with respect to a composition refers to a composition that includes at least 85%, or 90% by weight, in certain embodiments 95%, 98%, 99%, or 100% by weight; or in certain embodiments, 95%, 98%, 99%, or 100% of the designated enantiomer or diastereomer of a compound.
  • the compounds are substantially free of one of two enantiomers.
  • the compounds are substantially free of one of two diastereomers.
  • the compounds are substantially free of enantiomers (i.e., a racemic, or 50:50 mixture of compounds).
  • the term “isolated” with respect to a composition refers to a composition that includes at least 85%, 90%, 95%, 98%, or 99% to 100% by weight, of the compound, the remainder comprising other chemical species, enantiomers or diastereomers.
  • Solidvate refers to a compound provided herein, or a salt thereof, that further includes a stoichiometric, or non-stoichiometric amount of solvent bound by non-covalent intermolecular forces. Where the solvent is water, the solvate is a hydrate.
  • “Isotopic composition” refers to the amount of each isotope present for a given atom
  • “natural isotopic composition” refers to the naturally occurring isotopic composition, or abundance for a given atom.
  • Atoms containing their natural isotopic composition may also be referred to herein as “non-enriched” atoms. Unless otherwise designated, the atoms of the compounds recited herein are meant to represent any stable isotope of that atom. For example, unless otherwise stated, when a position is designated specifically as hydrogen (H), the position is understood to have hydrogen at its natural isotopic composition.
  • “Isotopic enrichment” refers to the percentage of incorporation of an amount of a specific isotope at a given atom in a molecule in the place of that atom's natural isotopic abundance. For example, deuterium (D) enrichment of 1% at a given position means that 1% of the molecules in a given sample contain deuterium at the specified position. Because the naturally occurring distribution of deuterium is about 0.0156%, deuterium enrichment at any position in a compound synthesized using non-enriched starting materials is about 0.0156%.
  • the isotopic enrichment of the compounds provided herein can be determined using conventional analytical methods known to one of ordinary skill in the art, including mass spectrometry and nuclear magnetic resonance spectroscopy.
  • “Isotopically enriched” refers to an atom having an isotopic composition other than the natural isotopic composition of that atom. “Isotopically enriched” may also refer to a compound containing at least one atom having an isotopic composition other than the natural isotopic composition of that atom.
  • alkyl, “alkylene,” “alkylamino,” “dialkylamino,” “cycloalkyl,” “aryl,” “arylene,” “alkoxy,” “amino,” “carboxyl,” “heterocycloalkyl,” “heteroaryl,” “heteroarylene,” “carboxyl,” and “amino acid” groups optionally comprise deuterium (D) at one, or more positions where hydrogen (H) atoms are present, and wherein the deuterium composition of the atom or atoms is other than the natural isotopic composition.
  • alkyl optionally comprise carbon-13 ( 13 C) at an amount other than the natural isotopic composition.
  • EC 50 refers to a dosage, concentration, or amount of a particular test compound that elicits a dose-dependent response at 50% of maximal expression of a particular response that is induced, provoked, or potentiated by the particular test compound.
  • IC 50 refers to an amount, concentration, or dosage of a particular test compound that achieves a 50% inhibition of a maximal response in an assay that measures such response.
  • the terms “subject”, and “patient” are used interchangeably.
  • the terms “subject”, and “subjects” refer to an animal, such as a mammal including a non-primate (e.g., a cow, pig, horse, cat, dog, rat, and mouse), and a primate (e.g., a monkey, such as a cynomolgous monkey, a chimpanzee, and a human), and in certain embodiments, a human.
  • the subject is a farm animal (e.g., a horse, a cow, a pig, etc.), or a pet (e.g., a dog or a cat).
  • the subject is a human.
  • terapéutica agent refers to any agent(s) which can be used in the treatment, or prevention of a disorder, or one or more symptoms thereof.
  • therapeutic agent includes a compound provided herein.
  • a therapeutic agent is an agent which is known to be useful for, or has been, or is currently being used for the treatment, or prevention of a disorder, or one, or more symptoms thereof.
  • “Therapeutically effective amount” refers to an amount of a compound, or composition that, when administered to a subject for treating a condition, is sufficient to effect such treatment for the condition.
  • a “therapeutically effective amount” can vary depending on, inter alia, the compound, the disease or disorder, and its severity, and the age, weight, etc., of the subject to be treated.
  • Treating” or “treatment” of any disease, or disorder refers, in certain embodiments, to ameliorating a disease, or disorder that exists in a subject.
  • “treating”, or “treatment” includes ameliorating at least one physical parameter, which may be indiscernible by the subject.
  • “treating”, or “treatment” includes modulating the disease, or disorder, either physically (e.g., stabilization of a discernible symptom), or physiologically (e.g., stabilization of a physical parameter), or both.
  • “treating”, or “treatment” includes delaying, or preventing the onset of the disease, or disorder, or delaying, or preventing recurrence of the disease, or disorder.
  • treating includes the reduction or elimination of either the disease, or disorder, or retarding the progression of the disease, or disorder, or of one, or more symptoms of the disease, or disorder, or reducing the severity of the disease, or disorder, or of one, or more symptoms of the disease, or disorder.
  • prophylactic agent refers to any agent(s) which can be used in the prevention of a disorder, or one or more symptoms thereof.
  • the term “prophylactic agent” includes a compound provided herein.
  • the term “prophylactic agent” does not refer a compound provided herein.
  • a prophylactic agent is an agent which is known to be useful for, or has been or is currently being used to prevent, or impede the onset, development, progression, and/or severity of a disorder.
  • prophylactically effective amount refers to the amount of a therapy (e.g., prophylactic agent) which is sufficient to result in the prevention, or reduction of the development, recurrence, or onset of one or more symptoms associated with a disorder, or to enhance or improve the prophylactic effect(s) of another therapy (e.g., another prophylactic agent).
  • a therapy e.g., prophylactic agent
  • another therapy e.g., another prophylactic agent
  • GLP-1 receptor compounds useful for modulating one, or more properties of GLP-1 receptor.
  • the compounds can be prepared as described herein and used for therapy, or diagnosis.
  • the therapy is the treatment of a metabolic disease or condition.
  • the therapy is the treatment of type 2 diabetes.
  • the embodiments described herein include the recited compounds as well as pharmaceutically acceptable salts, hydrates, solvates, stereoisomers, tautomers, and/or mixtures thereof.
  • a compound of Formula (I), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof wherein A is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, —NMe 2 , or —CF 3 ; Ring B is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Ring C is further unsubstituted or further substituted, and/or bridged; zero, one, or two of D 1 , D 2 , and D 3 are N, and the rest are CH, or CR 6 ; L 1 is selected from the group consisting of a bond, —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-
  • L 3 is —CH 2 — or —C(O)—;
  • L 4 is absent, or L 4 together with L 1 and Rings A and B form a fused tricycle, and L 5 is absent;
  • L 5 is absent, or L 5 together with L 2 and Rings B and C form a fused tricycle, and L 4 is absent;
  • R 4 is unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene;
  • R 5 is selected from the group consisting of —COOH, —COCF 3 , —C(OH)CF 3 , —CONHCN, —CONHOH, CONHOMe, —CONHSO
  • each R 6 is independently selected from the group consisting of alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO—, and R 11 R 12 N—;
  • R 11 is hydrogen, or alkyl;
  • R 12 is hydrogen, or alkyl;
  • R 13 is hydrogen, or alkyl.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —CF 2 —, —SO 2 —, —O—, —CF 2 —.
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • L 1 when L 1 is —CH 2 O—, L 4 is absent, and L 5 is absent, then either L 2 is —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —, CHF—, —CHOH—, —NH—, —N(Me)-, or
  • L 3 is —C(O)—, or both.
  • L 1 is —CH 2 O—
  • L 4 is absent
  • L 5 is absent
  • L 2 is —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, or
  • L 3 is —C(O)—.
  • L 4 together with L 1 and Rings A and B form a fused tricycle.
  • L 5 together with L 2 and Rings B and C form a fused tricycle.
  • Ring C is substituted or unsubstituted azetidinyl, substituted or unsubstituted pyrrolidinyl, or substituted or unsubstituted piperidinyl.
  • A is a ring selected from phenyl and cyclohexyl.
  • Ring C is selected from piperidine and piperazine.
  • Ring B is selected from phenyl, furan, pyridine, pyrimidine, thiophene, oxazole, and benzofuran.
  • A is phenyl and Ring C is piperazine.
  • A is phenyl, and Ring C is piperidine.
  • A is phenyl, and Ring C is piperazine, and Ring B is phenyl.
  • A is phenyl, and Ring C is piperazine, and Ring B is furan.
  • A is phenyl, and Ring C is piperidine, and Ring B is phenyl.
  • A is phenyl, and Ring C is piperidine, and Ring B is phenyl.
  • A is phenyl, and Ring C is piperidine, and Ring B is phenyl.
  • A is phenyl, and Ring C is piper
  • A is a ring selected from phenyl and cyclohexyl.
  • Ring C is selected from substituted piperidine, azetidine, and pyrrolidine.
  • Ring B is selected from phenyl, furan, pyridine, pyrimidine, thiophene, oxazole, and benzofuran.
  • A is phenyl and Ring C is piperazine.
  • A is phenyl, and Ring C is piperidine.
  • A is phenyl, and Ring C is substituted piperidine.
  • A is phenyl, and Ring C is azetidine.
  • A is phenyl, and Ring C is pyrrolidine. In certain embodiments, A is phenyl, Ring C is piperazine, and Ring B is phenyl. In certain embodiments, A is phenyl, Ring C is piperazine, and Ring B is furan. In certain embodiments, A is phenyl, Ring C is piperidine, and Ring B is phenyl. In certain embodiments, A is phenyl, Ring C is piperidine, and Ring B is furan. In certain embodiments, A is phenyl, Ring C is substituted piperidine, and Ring B is phenyl. In certain embodiments, A is phenyl, Ring C is substituted piperidine, and Ring B is furan.
  • A is phenyl, Ring C is azetidine, and Ring B is phenyl. In certain embodiments, A is phenyl, Ring C is azetidine, and Ring B is furan. In certain embodiments, A is phenyl, Ring C is pyrrolidine, and Ring B is phenyl. In certain embodiments, A is phenyl, Ring C is pyrrolidine, and Ring B is furan.
  • a compound of Formula (Ta), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof wherein A is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, —NMe 2 , or —CF 3 ; Ring B is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Ring C is further unsubstituted or further substituted, and/or bridged; zero, one, or two of D 1 , D 2 , and D 3 are N, and the rest are CH, or CR 6 ; W is N, CH, or C; when W is CH, the adjacent dashed lines indicate single bonds; when W is C, one adjacent dashed line indicates a double bond, for instance L 2 is —C(H) ⁇ ; L 1 is selected from the group consisting of —
  • L 3 is —CH 2 — or —C(O)—;
  • L 4 is absent, or L 4 together with L 1 and Rings A and B form a fused tricycle, and L 5 is absent;
  • L 5 is absent, or L 5 together with L 2 and Rings B and C form a fused tricycle, and L 4 is absent;
  • R 4 is unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene;
  • R 5 is selected from the group consisting of —COOH, —COCF 3 , —C(OH)CF 3 , —CONHCN, —CONHOH, CONHOMe, —CONHSO
  • each R 6 is independently selected from the group consisting of alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO—, and R 11 R 12 N—;
  • R 11 is hydrogen, or alkyl;
  • R 12 is hydrogen, or alkyl;
  • R 13 is hydrogen, or alkyl.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —CF 2 —, —SO 2 —, —O—, —CF 2 —.
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • L 1 when L 1 is —CH 2 O—, L 4 is absent, and L 5 is absent, then either L 2 is —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, or
  • L 3 is —C(O)—, or both.
  • L 1 is —CH 2 O—
  • L 4 is absent
  • L 5 is absent
  • L 2 is —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, or
  • L 1 when L 1 is —CH 2 O—, L 4 is absent, and L 5 is absent, then L 2 is —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, or
  • L 3 is —C(O)—.
  • L 4 when L is —CH 2 O—, L 4 together with L 1 and Rings A and B form a fused tricycle.
  • L 5 when L 1 is —CH 2 O—, L 5 together with L 2 and Rings B and C form a fused tricycle.
  • A is a ring selected from phenyl, and cyclohexyl.
  • Ring C is selected from piperidine, and piperazine.
  • Ring B is selected from phenyl, furan, pyridine, pyrimidine, thiophene, oxazole, and benzofuran.
  • A is phenyl and Ring C is piperazine.
  • A is phenyl, and Ring C is piperidine.
  • A is phenyl, and Ring C is piperazine, and Ring B is phenyl.
  • A is phenyl, and Ring C is piperazine, and Ring B is furan.
  • A is phenyl, and Ring C is piperidine, and Ring B is phenyl.
  • A is phenyl, and Ring C is piperidine, and Ring B is phenyl.
  • A is phenyl, and Ring C is piperidine, and Ring B is phenyl.
  • A is phenyl, and Ring C is
  • a compound of Formula (XXX), or a pharmaceutically salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof wherein W is N, CH, or C; when W is CH, the adjacent dashed lines indicate single bonds; when W is C, one adjacent dashed line indicates a double bond, for instance L 2 is —C(H) ⁇ ; zero, one, or two of A 1 , A 2 , A 3 , A 4 , and A 5 are N, and the rest are CH, or CR 1 ; zero, one, or two of B 1 , B 2 , B 3 , and B 4 are N, and the rest are CH, or CR 2 ; zero, one, or two of D 1 , D 2 , and D 3 are N, and the rest are CH, or CR 6 ; L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)
  • each R 6 is independently selected from the group consisting of alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO—, and R 11 R 12 N—;
  • R 11 is hydrogen or alkyl;
  • R 12 is hydrogen, or alkyl;
  • R 13 is hydrogen, or alkyl; and
  • o is an integer from 0 to 4.
  • the compound of Formula (XXX) is selected from compounds 82, 83, 91, 92, and 110, in Table 1.
  • a compound of Formula (XXXI), or a pharmaceutically salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof wherein W is N, CH, or C; when W is CH, the adjacent dashed lines indicate single; zero, one, or two of A 1 , A 2 , A 3 , A 4 , and A 5 are N, and the rest are CH, or CR 1 ;
  • each R 1 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —. —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • L 3 is —CH 2 —, or —C(O)—; each R 3 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—; R 4 is unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 is selected from the group consisting of —COOH, —COCF 3 , —C(OH)CF 3 , —CONHCN, —CONHOH, CONHOMe, —CONHSO 2 N(Me) 2 , —PO 3 H 2 , —PO(Me
  • each R 6 is independently selected from the group consisting of F, and methyl;
  • R 11 is hydrogen, or alkyl;
  • R 12 is hydrogen, or alkyl;
  • R 13 is hydrogen, or alkyl; and
  • o is 1, 2, 3, or 4.
  • the compound of Formula (XXXI) is selected from compounds 97 and 107 in Table 1.
  • the compound of Formula (I) is according to Formula (IIa), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof:
  • each R 6 is independently selected from the group consisting of F, and methyl; each R 11 is hydrogen, or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; and o is 1, 2, 3, or 4.
  • the compound of Formula (I) is according to Formula (IIb), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof:
  • each R 6 is independently selected from the group consisting of F, and methyl; each R 11 is hydrogen, or alkyl; each R 12 is hydrogen, or alkyl; each R 13 is hydrogen, or alkyl; and o is 1, 2, 3, or 4.
  • the compound of Formula (I) is according to Formula (IIc), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof:
  • each R 6 is independently selected from the group consisting of F, and methyl; each R 11 is hydrogen, or alkyl; each R 12 is hydrogen, or alkyl; each R 13 is hydrogen, or alkyl; R 4 is hydrogen, cyano, halo, hydroxyl, or methyl; and o is 1, 2, 3, or 4.
  • the compound of Formula (I) is according to Formula (IId), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof:
  • each R 6 is independently selected from the group consisting of F, and methyl; each R 11 is hydrogen, or alkyl; each R 12 is hydrogen, or alkyl; each R 13 is hydrogen, or alkyl; R 14 is hydrogen, cyano, halo, hydroxyl, or methyl; and o is 1, 2, 3, or 4.
  • the compound of Formula (I) is according to Formula (IIg), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof:
  • each R 6 is independently selected from the group consisting of F, and methyl; each R 11 is hydrogen, or alkyl; each R 12 is hydrogen, or alkyl; each R 13 is hydrogen, or alkyl.
  • the compound of Formula (I) is according to Formula (IIh), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and/or mixture of stereoisomers thereof:
  • each R 6 is independently selected from the group consisting of F, and methyl; each R 11 is hydrogen, or alkyl; each R 12 is hydrogen, or alkyl; each R 13 is hydrogen, or alkyl.
  • W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —CF 2 —, —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen, or alkyl
  • each R 12 is hydrogen, or alkyl
  • each R 13 is hydrogen, or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-. In certain embodiments, L2 is O.
  • the compound of Formula (III) is selected from compounds 2, 3, 5-7, 10-18, 21-23, 25, 29, 32, 33, 35, 45, 46, 48, 50-52, 54, 56-58, 64-70, 75-80, 86, 89, 93, 95, 98, 100, 103-105, 111, 112, 115, 116, 122, 126, 130-133, 135, 137, 148, 149, 151, 157-159, 161, 162, 165, 166, 174, 187, 188, 202-208, 215-217, 221, 231, 232, 242, 243, 254, 255, 260, 263, 288, 294, 301, 318, 319, and 321 in Table 1.
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —.
  • R 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl;
  • R 5 is selected from the group consisting of —COOH, —COCF 3 , —C(OH)CF
  • each R 11 is hydrogen or alkyl
  • each R 12 is hydrogen or alkyl
  • each R 13 is hydrogen or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • L2 is O.
  • the compound of Formula (IIIa) is selected from compounds 103, 104, 111, 116, 126, 130-133, 135, 137, 148, 149, 151, 157-159, 161, 162, 165, 166, 174, 187, 188, 202-208, 215-217, 221, 231, 232, 242, 243, 254, 255, 260, 263, 288, 294, 301, 318, 319, and 321 in Table 1.
  • W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen or alkyl
  • each R 12 is hydrogen or alkyl
  • each R 13 is hydrogen or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • the compound of Formula (IV) is selected from compounds 8, 9, 19, 20, 24, 26, 30, 31, 36-43, 47, 49, 55, 59, 63, 72-74, 81, 84, 94, 96, 108, and 109 in Table 1.
  • W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • L 3 is —CH 2 —, or —C(O)— each R 1 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—; each R 2 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—; each R 3 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—; R 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkylene, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstitute
  • each R 11 is hydrogen, or alkyl
  • each R 12 is hydrogen, or alkyl
  • each R 13 is hydrogen, or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • the compound of Formula (V) is selected from compound 71 in Table 1.
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen, or alkyl
  • each R 12 is hydrogen, or alkyl
  • each R 13 is hydrogen, or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • the compound of Formula (VI) is selected from compounds 34, 62, and 331 in Table 1.
  • W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen, or alkyl
  • each R 12 is hydrogen, or alkyl
  • each R 13 is hydrogen or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • the compound of Formula (VII) is selected from compounds 60, 102, 113, 124, 136, 138, 141, 144, 154, 156, 160, 186, 214, 256, 278, and 279 in Table 1.
  • W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ; L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen or alkyl
  • each R 12 is hydrogen, or alkyl
  • each R 13 is hydrogen, or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • the compound of Formula (VIII) is selected from compound 44 in Table 1.
  • W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen or alkyl
  • each R 12 is hydrogen or alkyl
  • each R 13 is hydrogen or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • the compound of Formula (IX) is selected from compounds 27 and 28 in Table 1.
  • W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • L 3 is —CH 2 —, or —C(O)— each R 1 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—; each R 2 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—; each R 3 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—; R 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkylene, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstitute
  • each R 11 is hydrogen or alkyl
  • each R 12 is hydrogen or alkyl
  • each R 13 is hydrogen or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • the compound of Formula (X) is selected from compound 4, 272, and 284 in Table 1.
  • W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 3 is —CH 2 — or —C(O)—;
  • each R 1 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—;
  • each R 2 is independently selected from the group consisting of alky
  • each R 11 is hydrogen or alkyl
  • each R 12 is hydrogen or alkyl
  • each R 13 is hydrogen or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • the compound of Formula (XI) is selected from compounds 53, 90, 121, 142, and 143 in Table 1.
  • W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • L 3 is —CH 2 —, or —C(O)— each R 1 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—; each R 2 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—; each R 3 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—; R 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkylene, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstitute
  • each R 11 is hydrogen or alkyl
  • each R 12 is hydrogen or alkyl
  • each R 13 is hydrogen or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • the compound of Formula (XII) is compound 108 in Table 1.
  • W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • L 3 is —CH 2 —, or —C(O)— each R 1 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—; each R 2 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—; each R 3 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—; R 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkylene, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstitute
  • each R 11 is hydrogen or alkyl
  • each R 12 is hydrogen or alkyl
  • each R 13 is hydrogen or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • the compound of Formula (XIII) is selected from compounds 88, 178, and 179 in Table 1.
  • W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen or alkyl
  • each R 12 is hydrogen or alkyl
  • each R 13 is hydrogen or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • the compound of Formula (XIV) is selected from compounds 85, 139, and 220 in Table 1.
  • W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen or alkyl
  • each R 12 is hydrogen or alkyl
  • each R 13 is hydrogen or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-. In certain embodiments, L2 is O. In certain embodiments, the compound of Formula (XV) is selected from compounds 101, 114, 118, 120, 123, 140, 146, 152, 153, 198-200, 246-249, 251-253, 264, 268-271, 285, 290, 291, 330, and 347 in Table 1.
  • W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen or alkyl
  • each R 12 is hydrogen or alkyl
  • each R 3 is hydrogen or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • L2 is O.
  • R 14 is CH 2 F or CH 2 OH.
  • the compound of Formula (XVI) is selected from compounds 99, 128, 145, 150, 155, 163, 164, 168-171, 182, 183, 189, 227, 230, 239-241, 250, 257-259, 265-267, 274-277, 280, 283, 287, 292, 295, 297, 299, 308, 316, 321, 322, 333, 335, 337, 345, 346, 352, 354, 356-358, 362-364, 366-368, 378, and 380 in Table 1.
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —.
  • R 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl;
  • R 5 is selected from the group consisting of —COOH, —COCF 3 , —C(OH)CF
  • each R 11 is hydrogen or alkyl
  • each R 12 is hydrogen or alkyl
  • each R 13 is hydrogen or alkyl
  • R 4 is hydrogen, cyano, halo, hydroxyl, or methyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —CF 2 —, —SO 2 —, —O—, —CF 2 —.
  • L 2 is selected from the group consisting of —NH— and —N(Me)-. In certain embodiments, L2 is O. In certain embodiments, the compound of Formula (XVI) is selected from compounds 128, 145, 168-171, 182, 183, 227, 230, 239-241, 250, 257-259, 265-267, 274-277, 280, 283, 287, 292, 295, 297, 299, 302, 308, 316, 321, 322, 333, 335-337, 344-346, 352, 354, 356-359, 362-368, 378, and 380 in Table 1.
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 3 is —CH 2 —, or —C(O)—; each R 1 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—;
  • each R 2 is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO—;
  • each R 3 is independently selected from the group consisting of alkyl, substituted alkyl
  • each R 11 is hydrogen or alkyl
  • each R 12 is hydrogen or alkyl
  • each R 13 is hydrogen or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • the compound of Formula (XVII) is selected from compound 106 in Table 1.
  • W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen or alkyl
  • each R 12 is hydrogen or alkyl
  • each R 3 is hydrogen or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • the compound of Formula (XVIII) is compound 87 in Table 1.
  • W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —.
  • R 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl;
  • R 5 is selected from the group consisting of —COOH, —COCF 3 , —C(OH)CF
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —CF 2 —, —SO 2 —, —O—, —CF 2 —. —CHF—, —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-.
  • the compound of Formula (XXV) is compound 286 in Table 1.
  • W is N, CR 14 , or C; when W is CR 4 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ;
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen, or alkyl
  • each R 12 is hydrogen, or alkyl
  • each R 13 is hydrogen, or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is selected from the group consisting of —NH— and —N(Me)-. In certain embodiments, L2 is O.
  • the compound of Formula (XXVI) is selected from compounds 261, 262, 296, 304, 306, 307, 311, 313, 315, 325, 326, 331, 338, 340, 342, 343, 348, 353, 354, 355, 369, 374-, 376, 475-481, 483, 485, 489, 490, 492, 493, 495, 498, 504, 510, 512, 514, and 515 in Table 1.
  • A is —NMe 2 or —N(CH 3 )cylcohexane; L 1 is absent; W is N, CR 14 , or C; when W is CR 14 , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2 is —C(H) ⁇ ; L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen, or alkyl
  • each R 12 is hydrogen, or alkyl
  • each R 13 is hydrogen, or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • the compound of Formula (XXVII) is selected from compounds 1 and 62 in Table 1.
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 6 is independently selected from the group consisting of alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO—, and R 11 R 12 N—; each R 11 is hydrogen, or alkyl; each R 12 is hydrogen, or alkyl; each R 13 is hydrogen, or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; o is an integer from 0 to 4; and r is an integer from 0 to 3.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • each R 6 is independently selected from the group consisting of F, and methyl. In certain embodiments, each R 6 is F. In certain embodiments, the compound of Formula (XXXIX) is selected from compounds 224, 300, 303, 309, 310, 317, and 320 in Table 1.
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 6 is independently selected from the group consisting of alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO—, and R 11 R 12 N—; each R 11 is hydrogen, or alkyl; each R 12 is hydrogen, or alkyl; each R 13 is hydrogen, or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; o is an integer from 0 to 4; and r is an integer from 0 to 3.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • each R 6 is independently selected from the group consisting of F, and methyl. In certain embodiments, each R 6 is F. In certain embodiments, the compound of Formula (XL) is selected from compounds 302, 325, 336, 344, 359, and 365 in Table 1.
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 6 is independently selected from the group consisting of alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO—, and R 11 R 12 N—; each R 11 is hydrogen, or alkyl; each R 12 is hydrogen, or alkyl; each R 13 is hydrogen, or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; o is an integer from 0 to 4; and r is an integer from 0 to 3.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • each R 6 is independently selected from the group consisting of F, and methyl. In certain embodiments, each R 6 is F. In certain embodiments, each R 6 is methyl. In certain embodiments, the compound of Formula (XLI) is selected from compounds 302, 325, 336, 344, 359, 365, 478, 482, 484, 494, 496, 500-503, 505, 508, 509, and 511 in Table 1.
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen, or alkyl
  • each R 12 is hydrogen, or alkyl
  • each R 13 is hydrogen, or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is —O—.
  • the compound of Formula (XLII) is selected from compounds 370, 371, 373, 375, 377, 378, 486, and 513 in Table 1.
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 6 is independently selected from the group consisting of alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO—, and R 11 R 12 N—; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; o is an integer from 0 to 4; r is an integer from 0 to 3.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is —O—.
  • each R 6 is independently selected from the group consisting of F, and methyl. In certain embodiments, each R 6 is F. In certain embodiments, each R 6 is methyl. In certain embodiments, the compound of Formula (XLIII) is c selected from compounds 487 and 488 in Table 1.
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen, or alkyl
  • each R 12 is hydrogen, or alkyl
  • each R 13 is hydrogen, or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is —O—.
  • the compound of Formula (XLIV) is compound 372 in Table 1.
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen, or alkyl
  • each R 12 is hydrogen, or alkyl
  • each R 13 is hydrogen, or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is —O—.
  • the compound of Formula (XLV) is compound 379 in Table 1.
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 11 is hydrogen, or alkyl
  • each R 12 is hydrogen, or alkyl
  • each R 13 is hydrogen, or alkyl
  • n is an integer from 0 to 5
  • m is an integer from 0 to 4
  • o is an integer from 0 to 4.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • L 2 is —O—.
  • the compound of Formula (XLVI) is selected from compounds 125 and 129 in Table 1.
  • L 1 is selected from the group consisting of —O—, —CH 2 —, —NH—, —N(Me)-, —N(Et)-, —OCH 2 —, —OC(H,Me)-, —CH 2 O—, —NHCH 2 —, —N(Me)CH 2 —, and —SO 2 NH—;
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —NH—, —N(Me)-, and
  • each R 6 is independently selected from the group consisting of alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO—, and R 11 R 12 N—; each R 11 is hydrogen, or alkyl; each R 12 is hydrogen, or alkyl; each R 13 is hydrogen, or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; o is an integer from 0 to 4; and r is an integer from 0 to 3.
  • L 2 is selected from the group consisting of a bond, —C(O)—, —CH 2 —, —C(H) ⁇ , —SO 2 —, —O—, —CF 2 —. —CHF—, or —CH(OH)—, and
  • each R 6 is independently selected from the group consisting of F, and methyl. In certain embodiments, each R 6 is F. In certain embodiments, each R 6 is methyl. In certain embodiments, the compound of Formula (XLVII) is compound 491 in Table 1.
  • R 4 is selected from the group consisting of (S)-buta-4-yl-1,3-diol, butan-1-yl-one, 1-(cyanomethyl)-cycloprop-1-yl-methyl, 1-(Fluoromethyl)-cycloprop-1-yl-methyl, 1-hydroxyl-cycloprop-1-yl-methyl, isoxazol-5-yl-methyl, (1-methyl-1H-imidazol-5-yl)-methyl, 1-methoxy-cycloprop-1yl-methyl, methoxyethan-2-yl, 1-(2-methoxyethyl)-cycloprop-1-y
  • L 1 is —O—; and L 2 is —C(O)—.
  • L 1 is —O—; and L 2 is —CH 2 —.
  • L 1 is —O—; and L 2 is —C(H) ⁇ .
  • L 1 is —O—; and L 2 is —SO 2 —.
  • L 1 is —O—; and L 2 is —NH—.
  • L 1 is —O—; and L 2 is —N(Me)-.
  • L 1 is —O—; L 2 is —C(O)—; and L 3 is —CH 2 —.
  • L 1 is —O—; L 2 is —CH 2 —; and L 3 is —CH 2 —.
  • L 1 is —O—; L 2 is —C(H) ⁇ ; and L 3 is —CH 2 —.
  • L 1 is —O—; L 2 is —SO 2 —; and L 3 is —CH 2 —.
  • L 1 is —O—; L 2 is —NH—; and L 3 is —CH 2 —.
  • L 1 is —O—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —O—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —O—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —O—; L 2 is —SO 2 —; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —O—; L 2 is —NH—; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —O—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —O—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —O—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —O—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —O—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —O—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —O—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —O—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —O—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —O—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —O—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —O—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —O—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —O—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —O—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —O—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —O—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —O—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —O—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —O—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —O—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —O—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —O—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —O—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —O—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L is —O—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —O—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —O—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —O—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —O—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —O—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —O—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —O—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl
  • L 1 is —O—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1
  • L 1 is —O—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —O—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —O—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • R 1 can be selected from H, Cl, F, Me, —CF 3 , —OMe, —CN, —C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl.
  • R 4 is azetidine-3-yl-methyl.
  • R 4 is (3R)-azetidine-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (3S)-azetidine-3-yl-methyl.
  • R 4 is (S)-buta-4-yl-1,3-diol.
  • R 4 is butan-1-yl-one.
  • R 4 is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(Fluoromethyl)-cycloprop-1-yl-methyl.
  • R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazol-5-yl-methyl.
  • R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-methoxy-cycloprop-1yl-methyl.
  • R 4 is methoxyethan-2-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl.
  • R 4 is ⁇ [1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl.
  • R 4 is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl.
  • L is —CH 2 O—; and L 2 is —C(O)—.
  • L 1 is —CH 2 O—; and L 2 is —CH 2 —.
  • L 1 is —CH 2 O—; and L 2 is —C(H) ⁇ .
  • L 1 is —CH 2 O—; and L 2 is —SO 2 —.
  • L 1 is —CH 2 O—; and L 2 is —NH—.
  • L 1 is —CH 2 O—; and L 2 is —N(Me)-.
  • L 1 is —CH 2 O—; L 2 is —C(O)—; and L 3 is —CH 2 —.
  • L 1 is —CH 2 O—; L 2 is —CH 2 —; and L 3 is —CH 2 —.
  • L 1 is —CH 2 O—; L 2 is —C(H) ⁇ ; and L 3 is —CH 2 —.
  • L 1 is —CH 2 O—; L 2 is —SO 2 —; and L 3 is —CH 2 —.
  • L 1 is —CH 2 O—; L 2 is —NH—; and L 3 is —CH 2 —.
  • L 1 is —CH 2 O—; L 2 is —N(Me)-; and L 3 is —CH 2 —.
  • L 1 is —CH 2 O—; L 2 is —C(O)—; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —CH 2 O—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —CH 2 O—; L 2 is —C(H) ⁇ ; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —CH 2 O—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —CH 2 O—; L 2 is —NH—; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —CH 2 O—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —CH 2 O—; L 2 is —C(O)—; L 3 is —CH 2 —; R 2 and R 3 are each H; and R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —CH 2 O—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L is —CH 2 O—; L 2 is —C(H) ⁇ ; L 3 is —CH 2 —; R 2 and R 3 are each H; and R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —CH 2 O—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —CH 2 O—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —CH 2 O—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —CH 2 O—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —CH 2 O—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —CH 2 O—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —CH 2 O—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —CH 2 O—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —CH 2 O—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —CH 2 O—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —CH 2 O—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —CH 2 O—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —CH 2 O—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —CH 2 O—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —CH 2 O—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —CH 2 O—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —CH 2 O—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L is —CH 2 O—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —CH 2 O—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —CH 2 O—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —CH 2 O—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —CH 2 O—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —CH 2 O—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —CH 2 O—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —CH 2 O—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —CH 2 O—; L 2 is —NH—; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —CH 2 O—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —CH 2 O—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —CH 2 O—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —CH 2 O—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —; and
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —CH 2 O—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —; and
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —CH 2 O—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —CH 2 O—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • R 1 can be selected from H, Cl, F, Me, —CF 3 , —OMe, —CN, —C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl.
  • R 4 is azetidine-3-yl-methyl.
  • R 4 is (3R)-azetidine-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (3S)-azetidine-3-yl-methyl.
  • R 4 is (S)-buta-4-yl-1,3-diol. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), R 4 is butan-1-yl-one.
  • R 4 is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI) R 4 is 1-(Fluoromethyl)-cycloprop-1-yl-methyl.
  • R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazol-5-yl-methyl.
  • R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI) R 4 is 1-methoxy-cycloprop-1yl-methyl.
  • R 4 is methoxyethan-2-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl.
  • R 4 is ⁇ [1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl.
  • R 4 is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl.
  • L is —OCH 2 —; and L 2 is —C(O)—.
  • L 1 is —OCH 2 —; and L 2 is —CH 2 —.
  • L 1 is —OCH 2 —; and L 2 is —C(H) ⁇ .
  • L 1 is —OCH 2 —; and L 2 is —SO 2 —.
  • L 1 is —OCH 2 —; and L 2 is —NH—.
  • L 1 is —OCH 2 —; and L 2 is —N(Me)-.
  • L 1 is —OCH 2 —; L 2 is —C(O)—; and L 3 is —CH 2 —.
  • L 1 is —OCH 2 —; L 2 is —CH 2 —; and L 3 is —CH 2 —.
  • L 1 is —OCH 2 —; L 2 is —C(H) ⁇ ; and L 3 is —CH 2 —.
  • L 1 is —OCH 2 —; L 2 is —SO 2 —; and L 3 is —CH 2 —.
  • L 1 is —OCH 2 —; L 2 is —NH—; and L 3 is —CH 2 —.
  • L 1 is —OCH 2 —; L 2 is —N(Me)-; and L 3 is —CH 2 —.
  • L is —OCH 2 —;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —OCH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —OCH 2 —;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —OCH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —OCH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —; and
  • R 2 and R 3 are each H.
  • L 1 is —OCH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L is —OCH 2 —;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —OCH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —OCH 2 —;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —OCH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —OCH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L is —OCH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —OCH 2 —;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —OCH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —OCH 2 —;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —OCH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —OCH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —OCH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —OCH 2 —;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —OCH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —OCH 2 —;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —OCH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L is —OCH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —OCH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L is —OCH 2 —;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —OCH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —OCH 2 —;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —OCH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —OCH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —OCH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —OCH 2 —;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OCH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L is —OCH 2 —;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OCH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OCH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OCH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OCH 2 —;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OCH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl
  • L 1 is —OCH 2 —;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)
  • L 1 is —OCH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OCH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OCH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • R 1 can be selected from H, Cl, F, Me, —CF 3 , -OMe, —CN, —C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl.
  • R 4 is azetidine-3-yl-methyl.
  • R 4 is (3R)-azetidine-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (3S)-azetidine-3-yl-methyl.
  • R 4 is (S)-buta-4-yl-1,3-diol.
  • R 4 is butan-1-yl-one.
  • R 4 is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXIX), and (XL-XLIII), R 4 is 1-(Fluoromethyl)-cycloprop-1-yl-methyl.
  • R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXIX), and (XL-XLVII), R 4 is isoxazol-5-yl-methyl.
  • R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXIX), and (XL-XLVII), R 4 is 1-methoxy-cycloprop-1yl-methyl.
  • R 4 is methoxyethan-2-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl.
  • R 4 is ⁇ [1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl.
  • R 4 is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl.
  • L is —NH— and L 2 is —C(O)—.
  • L 1 is —NH— and L 2 is —CH 2 —.
  • L 1 is —NH—; and L 2 is —C(H) ⁇ .
  • L 1 is —NH—; and L 2 is —SO 2 —.
  • L 1 is —NH—; and L 2 is —NH—.
  • L 1 is —NH—; and L 2 is —N(Me)-.
  • L 1 is —NH—; L 2 is —C(O)—; and L 3 is —CH 2 —.
  • L 1 is —NH—; L 2 is —CH 2 —; and L 3 is —CH 2 —.
  • L 1 is —NH—; L 2 is —C(H) ⁇ ; and L 3 is —CH 2 —.
  • L 1 is —NH—; L 2 is —SO 2 —; and L 3 is —CH 2 —.
  • L 1 is —NH—; L 2 is —NH—; and L 3 is —CH 2 —.
  • L is —NH—; L 2 is —C(O)—; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L is —NH—; L 2 is —CH 2 —; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L is —NH—; L 2 is —C(H) ⁇ ; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —NH—; L 2 is —SO 2 —; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —NH—; L 2 is —NH—; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L is —NH—; L 2 is —N(Me)-; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L is —NH—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —NH—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —NH—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —NH—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —NH—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —NH—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —NH—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —NH—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —NH—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —NH—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —NH—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —NH—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —NH—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —NH—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —NH—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —NH—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —NH—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —NH—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —NH—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —NH—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —NH—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —NH—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —NH—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —NH—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —NH—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NH—;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NH—;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NH—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NH—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NH—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NH—;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NH—; L 2 is —CH 2 —; L 3 is —CH 2 —; R 2 and R 3 are each H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NH—; L 2 is —C(H) ⁇ ; L 3 is —CH 2 —; R 2 and R 3 are each H; R 4 is (1-ethyl-1
  • L 1 is —NH—;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NH—;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NH—;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • R 1 can be selected from H, Cl, F, Me, —CF 3 , —OMe, —CN, —C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl.
  • R 4 is azetidine-3-yl-methyl.
  • R 4 is (3R)-azetidine-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (3S)-azetidine-3-yl-methyl.
  • R 4 is (S)-buta-4-yl-1,3-diol.
  • R 4 is butan-1-yl-one.
  • R 4 is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(Fluoromethyl)-cycloprop-1-yl-methyl.
  • R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazol-5-yl-methyl.
  • R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-methoxy-cycloprop-1yl-methyl.
  • R 4 is methoxyethan-2-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl.
  • R 4 is ⁇ [1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl.
  • R 4 is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl.
  • L 1 is —N(Me)- and L 2 is —C(O)—.
  • L 1 is —N(Me)- and L 2 is —CH 2 —.
  • L 1 is —N(Me)- and L 2 is —SO 2 —.
  • L 1 is —N(Me)-; and L 2 is —NH—.
  • L 1 is —N(Me)-; and L 2 is —N(Me)-.
  • L 1 is —N(Me)-; and L 2 is —C(O)—; and L 3 is —CH 2 —.
  • L 1 is —N(Me)-; L 2 is —CH 2 —; and L 3 is —CH 2 —.
  • L 1 is —N(Me)-; L 2 is —C(H) ⁇ ; and L 3 is —CH 2 —.
  • L 1 is —N(Me)-; L 2 is —SO 2 —; and L 3 is —CH 2 —.
  • L 1 is —N(Me)-; L 2 is —NH—; and L 3 is —CH 2 —.
  • L is —N(Me)-; L 2 is —C(O)—; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —N(Me)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —N(Me)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —N(Me)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —N(Me)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —; and
  • R 2 and R 3 are each H.
  • L 1 is —N(Me)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —N(Me)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L is —N(Me)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Me)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Me)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Me)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Me)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Me)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Me)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Me)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Me)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Me)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Me)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Me)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl
  • L 1 is —N(Me)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl
  • L 1 is —N(Me)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • L 1 is —N(Me)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • R 1 can be selected from H, Cl, F, Me, —CF 3 , —OMe, —CN, —C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl.
  • R 4 is azetidine-3-yl-methyl.
  • R 4 is (3R)-azetidine-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (3S)-azetidine-3-yl-methyl.
  • R 4 is (S)-buta-4-yl-1,3-diol.
  • R 4 is butan-1-yl-one.
  • R 4 is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(Fluoromethyl)-cycloprop-1-yl-methyl.
  • R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazol-5-yl-methyl.
  • R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-methoxy-cycloprop-1yl-methyl.
  • R 4 is methoxyethan-2-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl.
  • R 4 is ⁇ [1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl.
  • R 4 is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl.
  • L 1 is —N(Et)-; and L 2 is —C(O)—.
  • L 1 is —N(Et)-; and L 2 is —CH 2 —.
  • L 1 is —N(Et)-; and L 2 is —C(H) ⁇ .
  • L 1 is —N(Et)-; and L 2 is —SO 2 —.
  • L 1 is —N(Et)-; and L 2 is —NH—.
  • L 1 is —N(Et)-; and L 2 is —N(Me)-.
  • L 1 is —N(Et)-; L 2 is —C(O)—; and L 3 is —CH 2 —.
  • L 1 is —N(Et)-; L 2 is —CH 2 —; and L 3 is —CH 2 —.
  • L 1 is —N(Et)-; L 2 is —C(H) ⁇ ; and L 3 is —CH 2 —.
  • L 1 is —N(Et)-; L 2 is —SO 2 —; and L 3 is —CH 2 —.
  • L is —N(Et)-; L 2 is —NH—; and L 3 is —CH 2 —.
  • L is —N(Et)-; L 2 is —N(Me)-; and L 3 is —CH 2 —.
  • L 1 is —N(Et)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —N(Et)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —N(Et)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —N(Et)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L is —N(Et)-; L 2 is —NH—; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L is —N(Et)-; L 2 is —N(Me)-; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L is —N(Et)-; L 2 is —C(O)—; L 3 is —CH 2 —; R 2 and R 3 are each H; and R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Et)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Et)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Et)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Et)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Et)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Et)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Et)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Et)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L is —N(Et)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Et)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Et)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Et)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L is —N(Et)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Et)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Et)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Et)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Et)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Et)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Et)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Et)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Et)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Et)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Et)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Et)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Et)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Et)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Et)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Et)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Et)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Et)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Et)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl
  • L 1 is —N(Et)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl
  • L 1 is —N(Et)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • L 1 is —N(Et)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Et)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Et)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • R 1 can be selected from H, Cl, F, Me, —CF 3 , —OMe, —CN, —C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl.
  • R 4 is azetidine-3-yl-methyl.
  • R 4 is (3R)-azetidine-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (3S)-azetidine-3-yl-methyl.
  • R 4 is (S)-buta-4-yl-1,3-diol. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI) R 4 is butan-1-yl-one.
  • R 4 is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI) R 4 is 1-(Fluoromethyl)-cycloprop-1-yl-methyl.
  • R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazol-5-yl-methyl.
  • R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXIX), and (XL-XLVII), R 4 is 1-methoxy-cycloprop-1yl-methyl.
  • R 4 is methoxyethan-2-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI) R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl.
  • R 4 is ⁇ [1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl.
  • R 4 is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl.
  • L 1 is —NHCH 2 —; and L 2 is —C(O)—.
  • L 1 is —NHCH 2 —; and L 2 is —CH 2 —.
  • L 1 is —NHCH 2 — and L 2 is —C(H) ⁇ .
  • L 1 is —NHCH 2 —; and L 2 is —SO 2 —.
  • L 1 is —NHCH 2 —; and L 2 is —NH—.
  • L 2 is —NHCH 2 —; and L 2 is —N(Me)-.
  • L 1 is —NHCH 2 —; L 2 is —C(O)—; and L 3 is —CH 2 —.
  • L 1 is —NHCH 2 —; L 2 is —CH 2 —; and L 3 is —CH 2 —.
  • L 1 is —NHCH 2 —; L 2 is —C(H) ⁇ ; and L 3 is —CH 2 —.
  • L 1 is —NHCH 2 —; L 2 is —SO 2 —; and L 3 is —CH 2 —.
  • L 1 is —NHCH 2 —; L 2 is —NH—; and L 3 is —CH 2 —.
  • L is —NHCH 2 —; L 2 is —N(Me)-; and L 3 is —CH 2 —.
  • L is —NHCH 2 —; L 2 is —C(O)—; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —NHCH 2 —; L 2 is —CH 2 —; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L is —NHCH 2 —; L 2 is —C(H) ⁇ ; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —NHCH 2 —; L 2 is —SO 2 —; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —NHCH 2 —; L 2 is —NH—; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L is —NHCH 2 —; L 2 is —N(Me)-; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —NHCH 2 —; L 2 is —C(O)—; L 3 is —CH 2 —; R 2 and R 3 are each H; and R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —NHCH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —NHCH 2 —; L 2 is —C(H) ⁇ ; L 3 is —CH 2 —; R 2 and R 3 are each H; and R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —NHCH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —NHCH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —NHCH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —NHCH 2 —;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —NHCH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —NHCH 2 —; L 2 is —C(H) ⁇ ; L 3 is —CH 2 —; R 2 and R 3 are each H; and R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —NHCH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —NHCH 2 —; L 2 is —NH—; L 3 is —CH 2 —; R 2 and R 3 are each H; and R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —NHCH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L is —NHCH 2 —;
  • L 2 is —C(O)-L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —NHCH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —NHCH 2 —;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —NHCH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —NHCH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —NHCH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —NHCH 2 —;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —NHCH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —NHCH 2 —;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —NHCH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —NHCH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —NHCH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —NHCH 2 —;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NHCH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NHCH 2 —;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NHCH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NHCH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L is —NHCH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NHCH 2 —;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L is —NHCH 2 —; L 2 is —CH 2 —; L 3 is —CH 2 —; R 2 and R 3 are each H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl
  • L 1 is —NHCH 2 —; L 2 is —C(H) ⁇ ; L 3 is —CH 2 —; R 2 and R 3 are each H; R 4 is (1-
  • L 1 is —NHCH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NHCH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —NHCH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • R 1 can be selected from H, Cl, F, Me, —CF 3 , —OMe, —CN, —C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl.
  • R 4 is azetidine-3-yl-methyl.
  • R 4 is (3R)-azetidine-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (3S)-azetidine-3-yl-methyl.
  • R 4 is (S)-buta-4-yl-1,3-diol.
  • R 4 is butan-1-yl-one.
  • R 4 is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(Fluoromethyl)-cycloprop-1-yl-methyl.
  • R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazol-5-yl-methyl.
  • R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-methoxy-cycloprop-1yl-methyl.
  • R 4 is methoxyethan-2-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl.
  • R 4 is ⁇ [1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl.
  • R 4 is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl.
  • L 1 is —N(Me)CH 2 —; and L 2 is —C(O)—.
  • L 1 is —N(Me)CH 2 —; and L 2 is —CH 2 —.
  • L 1 is —N(Me)CH 2 —; and L 2 is —C(H) ⁇ .
  • L 1 is —N(Me)CH 2 —; and L 2 is —SO 2 —.
  • L 1 is —N(Me)CH 2 —; and L 2 is —NH—.
  • L 1 is —N(Me)CH 2 —; and L 2 is —N(Me)-.
  • L 1 is —N(Me)CH 2 —; L 2 is —C(O)—; and L 3 is —CH 2 —.
  • L 1 is —N(Me)CH 2 —; L 2 is —CH 2 —; and L 3 is —CH 2 —.
  • L 1 is —N(Me)CH 2 —; L 2 is —C(H) ⁇ ; and L 3 is —CH 2 —.
  • L 1 is —N(Me)CH 2 —; L 2 is —SO 2 —; and L 3 is —CH 2 —.
  • L 1 is —N(Me)CH 2 —; L 2 is —NH—; and L 3 is —CH 2 —.
  • L 1 is —N(Me)CH 2 —; L 2 is —N(Me)-; and L 3 is —CH 2 —.
  • L 1 is —N(Me)CH 2 —; L 2 is —C(O)—; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —N(Me)CH 2 —; L 2 is —CH 2 —; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —N(Me)CH 2 —; L 2 is —C(H) ⁇ ; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —N(Me)CH 2 —; L 2 is —SO 2 —; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —N(Me)CH 2 —; L 2 is —NH—; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —N(Me)CH 2 —; L 2 is —N(Me)-; L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L is —N(Me)CH 2 —; L 2 is —C(O)—; L 3 is —CH 2 —; R 2 and R 3 are each H; and R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Me)CH 2 —; L 2 is —CH 2 —; L 3 is —CH 2 —; R 2 and R 3 are each H; and R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Me)CH 2 —; L 2 is —C(H) ⁇ ; L 3 is —CH 2 —; R 2 and R 3 are each H; and R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Me)CH 2 —; L 2 is —NH—; L 3 is —CH 2 —; R 2 and R 3 are each H; and R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Me)CH 2 —; L 2 is —N(Me)-; L 3 is —CH 2 —; R 2 and R 3 are each H; and R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —N(Me)CH 2 —; L 2 is —C(O)—; L 3 is —CH 2 —; R 2 and R 3 are each H; and R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Me)CH 2 —; L 2 is —C(H) ⁇ ; L 3 is —CH 2 —; R 2 and R 3 are each H; and R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Me)CH 2 —; L 2 is —NH—; L 3 is —CH 2 —; R 2 and R 3 are each H; and R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L is —N(Me)CH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L is —N(Me)CH 2 —; L 2 is —C(H) ⁇ ; L 3 is —CH 2 —; R 2 and R 3 are each H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is —COOH.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)CH 2 —; L 2 is —CH 2 —; L 3 is —CH 2 —; R 2 and R 3 are each H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl
  • L 1 is —N(Me)CH 2 —; L 2 is —C(H) ⁇ ; L 3 is —CH 2 —; R 2 and R 3
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —N(Me)CH 2 —;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • R 1 can be selected from H, Cl, F, Me, —CF 3 , —OMe, —CN, —C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl.
  • R 4 is azetidine-3-yl-methyl.
  • R 4 is (3R)-azetidine-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (3S)-azetidine-3-yl-methyl.
  • R 4 is (S)-buta-4-yl-1,3-diol.
  • R 4 is butan-1-yl-one.
  • R 4 is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(Fluoromethyl)-cycloprop-1-yl-methyl.
  • R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazol-5-yl-methyl.
  • R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-methoxy-cycloprop-1yl-methyl.
  • R 4 is methoxyethan-2-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl.
  • R 4 is ⁇ [1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl ⁇ .
  • R 4 is ⁇ [(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl.
  • R 4 is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl.
  • L 1 is —OC(H,Me)-; and L 2 is —C(O)—.
  • L 1 is —OC(H,Me)-; and L 2 is —CH 2 —.
  • L 1 is —OC(H,Me)-; and L 2 is —C(H) ⁇ .
  • L 1 is —OC(H,Me)- and L 2 is —SO 2 —.
  • L 1 is —OC(H,Me)-; and L 2 is —NH—.
  • L 1 is —OC(H,Me)-; and L 2 is —N(Me)-.
  • L 1 is —OC(H,Me)-; L 2 is —C(O)—; and L 3 is —CH 2 —.
  • L 1 is —OC(H,Me)-L 2 is —CH 2 —; and L 3 is —CH 2 —.
  • L 1 is —OC(H,Me)-; L 2 is —C(H) ⁇ ; and L 3 is —CH 2 —.
  • L 1 is —OC(H,Me)-; L 2 is —SO 2 —; and L 3 is —CH 2 —.
  • L 1 is —OC(H,Me)-; L 2 is —NH—; and L 3 is —CH 2 —.
  • L 1 is —OC(H,Me)-; L 2 is —N(Me)-; and L 3 is —CH 2 —.
  • L 1 is —OC(H,Me)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —OC(H,Me)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —OC(H,Me)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —OC(H,Me)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —OC(H,Me)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —; and
  • R 2 and R 3 are each H.
  • L 1 is —OC(H,Me)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —; and R 2 and R 3 are each H.
  • L 1 is —OC(H,Me)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —; R 2 and R 3 are each H; and
  • R 4 is (2S)-oxetan-2-yl-methyl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L is —OC(H,Me)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H; and
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —OC(H,Me)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —OC(H,Me)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —OC(H,Me)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —OC(H,Me)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L is —OC(H,Me)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl; and
  • R 5 is —COOH.
  • L 1 is —OC(H,Me)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —OC(H,Me)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —OC(H,Me)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —OC(H,Me)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —OC(H,Me)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —OC(H,Me)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and
  • R 5 is —COOH.
  • L 1 is —OC(H,Me)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (2S)-oxetan-2-yl-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —C(O)—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —CH 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl
  • L 1 is —OC(H,Me)-;
  • L 2 is —C(H) ⁇ ;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • L is —OC(H,Me)-;
  • L 2 is —SO 2 —;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L is —OC(H,Me)-;
  • L 2 is —NH—;
  • L 3 is —CH 2 —;
  • R 2 and R 3 are each H;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • L 1 is —OC(H,Me)-;
  • L 2 is —N(Me)-;
  • L 3 is —CH 2 —;
  • R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl;
  • R 5 is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl.
  • R 1 can be selected from H, Cl, F, Me, —CF 3 , —OMe, —CN, —C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl.
  • R 4 is azetidine-3-yl-methyl.

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  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Diabetes (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Epidemiology (AREA)
  • Endocrinology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
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MX2023001311A (es) 2020-08-06 2023-04-18 Gasherbrum Bio Inc Agonistas heterociclicos de glp-1.
EP4204415A1 (en) 2020-08-28 2023-07-05 Gasherbrum Bio, Inc. Heterocyclic glp-1 agonists
KR20240073108A (ko) 2021-10-05 2024-05-24 아스트라제네카 아베 Glp-1 수용체 조절제로서의 특정 2,5-디아자바이시클로[4.2.0]옥탄
WO2023057414A1 (en) 2021-10-05 2023-04-13 Astrazeneca Ab Certain octahydrofuro[3,4- b]pyrazines as glp-1 receptor modulators
WO2023057429A1 (en) 2021-10-05 2023-04-13 Astrazeneca Ab Certain 2,5-diazabicyclo[4.2.0]octanes and octahydrofuro[3,4- b]pyrazines as glp-1 receptor modulators
WO2023111144A1 (en) 2021-12-16 2023-06-22 Astrazeneca Ab Certain 3-azabicyclo[3.1.0]hexanes as glp-1 receptor modulators
WO2023111145A1 (en) 2021-12-16 2023-06-22 Astrazeneca Ab Certain 3-azabicyclo[3.1.0]hexanes as glp-1 receptor modulators
CN117362282A (zh) * 2022-07-07 2024-01-09 杭州德睿智药科技有限公司 Glp-1r激动剂的盐及其制备方法和应用
WO2024026338A1 (en) * 2022-07-27 2024-02-01 Carmot Therapeutics, Inc. N-heterocylic gpcr receptor agonists, pharmaceutical compositions comprising the same, and methods for their use
WO2024051700A1 (zh) * 2022-09-05 2024-03-14 德睿智药(苏州)新药研发有限公司 作为glp1r激动剂的新型芳基氘代苄醚取代杂环类化合物
WO2024051749A1 (zh) * 2022-09-06 2024-03-14 德睿智药(苏州)新药研发有限公司 一种glp-1r激动剂化合物的多晶型物及其制备方法与用途
WO2024102625A1 (en) 2022-11-11 2024-05-16 Eli Lilly And Company Glucagon-like peptide 1 receptor agonists
WO2024107781A1 (en) 2022-11-16 2024-05-23 Eli Lilly And Company Glucagon-like peptide 1 receptor agonists
WO2024138048A1 (en) * 2022-12-22 2024-06-27 Gasherbrum Bio, Inc. Heterocyclic glp-1 agonists

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JP2022508203A (ja) * 2018-11-22 2022-01-19 キル・レガー・セラピューティクス・インコーポレーテッド Ｇｌｐ－１ｒアゴニスト及びその使用
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KR20230152011A (ko) 2023-11-02
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