# US 8,785,468 B2 · Phenylalanine amide derivatives useful for treating insulin-related diseases and conditions

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- Number: US 8,785,468 B2
- Document ID: US8785468B2
- Status: Granted
- Kind: B2
- Application number: 13/148,296
- Filed: 2010-02-12
- Published: 2012-05-10
- Granted: 2014-07-22
- Earliest claimed: 2009-02-13
- Assignees: Amgen Inc.
- Applicants: Xiaohui Du; Zice Fu; Jonathan B. Houze; XianYun Jiao; Yong-Jae Kim; Leping Li; Jinqian Liu; Mike Elias Lizarzaburu; Julio C. Medina; Wang Shen; Simon Turcotte; Ming Yu
- Inventors: Xiaohui Du; Zice Fu; Jonathan B. Houze; XianYun Jiao; Yong-Jae Kim; Leping Li; Jinqian Liu; Mike Elias Lizarzaburu; Julio C. Medina; Wang Shen; Simon Turcotte; Ming Yu
- Web page: https://patentgrep.com/patent/US8785468B2

## CPC

- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 11/06: Antiasthmatics
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- C07D 401/14: containing three or more hetero rings
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 403/14: containing three or more hetero rings
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/14: containing three or more hetero rings
- C07D 417/04: directly linked by a ring-member-to-ring-member bond
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 417/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Provided herein are compounds of formula I: wherein A, B, X, R1, R2 and subscript n are as defined in the following disclosure. Compositions comprising the compounds are also provided, as well as methods for their use, for example, in treatment of type 2 diabetes and type 2 diabetes-related conditions.

## Claims

### Claim 1

A compound of formula V:
or pharmaceutically acceptable salt thereof, wherein
A is optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclyl;
B is optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl or optionally substituted heteroaryl;
R1a, R1b and R1c are each independently selected from —H, —Cl and —F; and
R6 is selected from amino or (C1-C5)alkyl.

### Claim 2

A compound of formula VI:
or pharmaceutically acceptable salt thereof, wherein
B is optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl or optionally substituted heteroaryl;
Z is amino, carboxy, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylamino, optionally substituted dialkylamino, optionally substituted cycloalkylamino, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —C(O)OR5 or —C(O)NR9R10, wherein
R5 is (C1-C5) alkyl; and
R9 and R10 are independently selected from H and (C1-C5)alkyl, or, optionally, R9 and R10 together with the nitrogen atom to which R9 and R10 are attached form a 5-membered ring;
R1a, R1b, R1c and R7b are each independently selected from —H, —Cl and —F; and
R7a is selected from the group consisting of amino, monosubstituted amino, halo and optionally substituted (C1-C5) alkyl.

### Claim 3

A compound of formula VIII:
or pharmaceutically acceptable salt thereof, wherein
A is optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocyclyl;
Z is amino, carboxy, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkylamino, optionally substituted dialkylamino, optionally substituted cycloalkylamino, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —C(O)OR5 or —C(O)NR9R10, wherein
R5 is (C1-C5)alkyl; and
R9 and R10 are independently selected from H and (C1-C5)alkyl, or, optionally, R9 and R10 together with the nitrogen atom to which R9 and R10 are attached form a 5-membered ring;
each R1 is independently halo;
subscript n is 0, 1, 2 or 3;
W1 selected from the group consisting of —CH═, —N═, —NH—, —O— and —S—;
W4 and W5 are independently selected from —C(R8)═, —C(O)—, —N═, —N(R8)—, —O— and
—S—, wherein
R8 is selected from the group consisting of hydrogen, acyl, amino, carboxy, carboxyalkyl, halo, hydroxy, hydroxyalkyl, monosubstituted amino, optionally substituted (C1-C5)alkyl, optionally substituted (C1-C5)alkylamino, optionally substituted (C1-C5)alkoxy, optionally substituted heteroaryl, optionally substituted halo(C1-C5)alkyl, optionally substituted heterocyclyl and optionally substituted heterocyclylalkyl; and
each bond is a single bond, double or π bond.

### Claim 4 (depends on 3)

The compound of claim 3, wherein A is selected from the group consisting of optionally substituted phenyl, optionally substituted pyrazol-3-yl, optionally substituted pyrazol-4-yl, optionally substituted pyridine-4-yl and optionally substituted thiazol-5-yl.

### Claim 5 (depends on 3)

The compound of claim 3, wherein Z is selected from the group consisting of pyridin-2-yl, thiazol-2-yl, thiazol-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, imidazol-2-yl, imidazol-4-yl, 1,2,3-triazol-4-yl, pyrazol-3-yl, tetrazol-5-yl, pyrazin-2-yl, 1,2,4-triazol-3-yl and isooxazol-3-yl, each of which is optionally substituted.

### Claim 6 (depends on 5)

The compound of claim 5, wherein R1 is fluoro and subscript n is 0 or 1.

### Claim 7

A compound or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:
(S)-2-((2-aminothiazol-4-yl)methylamino)-3-phenyl-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)propanamide,
(S)-3-phenyl-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)-2-((S)-1-(thiazol-4-yl)ethylamino)propanamide,
(S)-3-phenyl-N-5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(S)-3-(3-fluorophenyl)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(S)-3-Phenyl-N-(5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(S)-3-(4-Chlorophenyl)-N-(3-(pyridin-4-yl)isoxazol-5-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(S)-2-(3-(4-Fluorophenyl)-1-oxo-1-(3-(pyridin-4-yl)isoxazol-5-ylamino)propan-2-ylamino)acetic acid diTFA salt,
(S)-3-Phenyl-N-(3-(pyridin-4-yl)isoxazol-5-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(S)-3-Phenyl-N-(2-(pyridin-4-yl)thiazol-4-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(S)-tert-Butyl 1-oxo-3-phenyl-1-(2-(pyridin-4-yl)thiazol-4-ylamino)propan-2-ylcarbamate,
(S)-3-(4-Fluorophenyl)-N-(2-(pyridin-4-yl)thiazol-5-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(S)-3-Phenyl-N-(2-(pyridin-4-yl)thiazol-5-yl)-2-(thiazol-4-ylmethylamino)-propanamide,
(2S)—N-(5-(1H-Pyrazol-5-yl)pyridin-3-yl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(S)-3-Phenyl-N-(3-(pyridin-4-yl)-1H-pyrazol-5-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(2S)—N-(5-(2-methylamino)pyridine-4-yl)-1,3,4-thiadiazol-2-yl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(2S)-3-(4-fluorophenyl)-N-(5-(2-(methylamine)pyridine-4-yl)-1,3,4-thiadiazol-2-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(2S)-3-(4-fluorophenyl)-N-(1-methyl-3-(2-(methylamino)pyrimidin-4-yl)-1H-pyrazol-5-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(S)-3-phenyl-N-(4-(pyridin-4-yl)pyrimidin-2-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(S)—N-(2-methoxy-5-(pyridin-4-yl)pyridin-3-yl)-3-phenyl-2-(1-(pyridin-2-yl)cyclopropylamino)propanamide,
(2S)—N-(3-(1H-pyrazol-3-yl)phenyl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(S)—N-(2-hydroxy-5-(pyridin-4-yl)phenyl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(2S)—N-(2-methoxy-5-(1H-pyrazol-3-yl)-3-phenyl-2-(1-(thiazol-4-yl)cyclopropylamino)propanamide,
(2S)—N-(2-methoxy-5-(1H-pyrazol-3-yl)pyridin-3-yl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(2S)—N-(2-methoxy-5-(1H-pyrazol-4-yl)pyridin-3-yl)-3-phenyl-2-(pyridin-2-ylmethylamino)propanamide,
(2S)-3-(4-Fluorophenyl)-N-(1-methyl-3-(2-methylpyridin-4-yl)-1H-pyrazol-5-yl)-2-(thiazol-4-ylmethylamino)propanamide,
2-((S)-3-(4-Fluorophenyl)-1-(1-methyl-3-(2-methylpyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxopropan-2-ylamino)acetic acid dihydrochloride,
(S-tert-Butyl 1-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxo-3-phenylpropan-2-ylcarbamate,
(S)—N-(1-Methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)-3-phenyl-2-thiazol-4-ylmethylamino)propanamide,
(S)—N-(1-Methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)-3-phenyl-2-(pyridin-2-ylmethylamino)propanamide,
(S)-2-((5-Fluoropyridin-2-yl)methylamino)-N-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)-3-phenylpropanamide,
(S)-3-(4-Fluorophenyl)-N-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(S)-2-(Cyclopropylmethylamino)-N-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)-3-phenylpropanamide,
(S)-Ethyl 2-(1-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxo-3-phenylpropan-2-ylamino)acetate dihydrochloride,
(S)-2-(1-(1-Methyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxo-3-phenylpropan-2-ylamino)acetic acid dihydrochloride,
(2S)-3-(4-Fluorophenyl)-N-(3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(2S)-2-((1H-1,2,3-triazol-4-yl)methylamino)-3-(4-fluorophenyl)-N-(3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)propanamide,
(S)—N-(1-ethyl-3-(pyridine-4-yl)-1H-pyrazol-5-yl)-3-(4-fluorophenyl)-2-(thiazol-4-ylmethlamino)propanamide,
(R)-2-((S)-1-(1-Ethyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxo-3-phenylpropan-2-ylamino)propanoic acid,
(2S)-3-(4-Fluorophenyl)-N-(3-(2-methylpyridin-4-yl)-1H-pyrazol-5-yl)-2-(thiazol-4-ylmethylamino)propanamide dihydrochloride,
2-((S)-3-(4-Fluorophenyl)-1-(3-(2-methylpyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxopropan-2-ylamino)acetic acid dihydrochloride,
(2S)-3-(4-Fluorophenyl)-N-(4-methyl-2-(2-methylpyridin-4-yl)thiazol-5-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(2S)-2-((5-Fluoropyridin-2-yl)methylamino)-N-(1-methyl-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)-3-phenylpropanamide,
(2S)-2-((1H-Pyrazol-3-yl)methylamino)-3-(4-fluorophenyl)-N-(1-methyl-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)propanamide,
(2S)-2-(2-Ethoxyethylamino)-3-(4-fluorophenyl)-N-(1-methyl-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)propanamide,
(2S)-3-(4-Fluorophenyl)-2-((1-methyl-1H-pyrazol-3-yl)methylamino)-N-(1-methyl-3-(2-(methylamino)pyridin4-yl)-1H-pyrazol-5-yl)propanamide,
(2S)-3-(4-Fluorophenyl)-N-(1-methyl-3-(2-methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(2S)-3-(4-Fluorophenyl)-2-((5-fluoropyridin-2-yl)methylamino)-N-(1-methyl-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)propanamide,
(2S)-2-((1H-1-1,2,3-triazol-4-yl)methylamino)-3-(4-fluorophenyl)-N-(1-methyl-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)propanamide,
2-((S)-3-(4-Fluorophenyl)-1-(1-methyl-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxopropan-2-ylamino)acetic acid,
2-((S)-1-(1-Methyl-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxo-3-phenylpropan-2-ylamino)acetic acid,
(2S)—N-(1-methyl-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(2S)-2-((1H-tetrazol-5-yl)methylamino)-3-(4-fluorophenyl)-N-(1-methyl-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)propanamide,
(S)-2-(1-Oxo-3-phenyl-1-(3-(pyridin-4-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-ylamino)propan-2-ylamino)acetic acid,
(S)-3-(3Chlorophenyl)-N-(2-oxo-5-(pyridin-4-yl)-1,2-dihydropyridin-3-yl)-2-(thiazol-4-ylmethylamino)propanamide trifluoroacetate,
(S)-2-(5-(3-Phenyl-2-(thiazol-4-ylmethylamino)propanamido)-3-(pyridin-4-yl)-1H-pyrazol-1-yl)acetic acid,
(2S)—N-(3-(1-Methyl-1H-pyrazol-4-yl)phenyl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(2S)—N-(1-ethyl-3-(2-methylpyridin-4-yl)-1H-pyrazol-5-yl)-3-(4-fluorophenyl)-2-(thiazol-4-ylmethylamino)propanamide dihydrochloride,
(S)-2-(3-(4-Chlorophenyl)-1-(1-isopropyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxopropan-2-ylamino)acetic acid,
(2S)-3-(4-Fluorophenyl)-N-(1-(2-hydroxyethyl)-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(2S)—N-(1-Ethyl-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)-3-(4-fluorophenyl)-2-(thiazol-4-ylmethylamino)propanamide,
(2S)-2-((1H-1,2,3-triazol-4-yl)methylamino)-N-(1-ethyl-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)-3-(4-fluorophenyl)propanamide,
(2S)—N-(1-Ethyl-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)-3-(4-fluorophenyl)-2-((5-fluoropyridin-2-yl)methylamino)propanamide,
2-((S)-1-(1-Ethyl-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-ylamino)-3-(4-fluorophenyl)-1-oxopropan-2-ylamino)acetic acid,
(S)—N-(1-Methyl-5-(pyridin-4-yl)-1H-pyrazol-3-yl)-3-phenyl-2-(thiazol-5-ylmethylamino)propanamide,
(2S)—N-(3-(1H-Pyrazol-4-yl)phenyl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(S)-3-Phenyl-N-(3-(pyridin-4-yl)phenyl)-2-(2-(tetrahydro-2H-pyran-4-yl)ethylamino)propanamide,
(2S)-3-Phenyl-2-(1-(pyridin-2-yl)ethylamino)-N-(3-(pyridin-4-yl)phenyl)propanamide,
(2S)-3-Phenyl-2-(1-(pyridin-2-yl)propylamino)-N-(3-(pyridin-4-yl)phenyl)propanamide,
(R)-3-Phenyl-N-(3-(pyridin-4-yl)phenyl)-2-(thiazol-4-ylmethylamino)propanamide trifluoroacetate,
(R)-3-Phenyl-N-(3-(pyridin-4-yl)phenyl)-2-(thiazol-5-ylmethylamino)propanamide trifluoroacetate,
(R)-3-Phenyl-N-(3-(pyridin-4-yl)phenyl)-2-(thiazol-2-ylmethylamino)propanamide trifluoroacetate,
(2S)-3-Phenyl-2-(1-(pyrazin-2-yl)ethylamino)-N-(3-(pyridin-4-yl)phenyl)propanamide,
(2S)-3-Phenyl-N-(3-(pyridin-4-yl)phenyl)-2((tetrahydrofuran-3-yl)methylamino)propanamide,
(S)-2(Cyclopropylmethylamino)-3-(3-fluorophenyl)-N-(3-(pyridin-4-yl)phenyl)propanamide,
(S)-2-(Isopropylamino)-3-phenyl-N-(3-(pyridin-4-yl)phenyl)propanamide,
(S)-3-Phenyl-N-(3-(pyridin-4-yl)phenyl)-2-(thiazol-4-ylmethylamino)propanamide,
(S)-2-(Oxazol-5-ylmethylamino)-3-phenyl-N-(3-(pyridin-4-yl)phenyl)propanamide,
(S)-3-Phenyl-N-(3-(pyridin-4-yl)phenyl)-2-(thiazol-2-ylmethylamino)propanamide,
(S)-3-Phenyl-N-(3-(pyridin-4-yl)phenyl-2-(thiazol-5-ylmethylamino)propanamide,
(S)-2-((2-Methylthiazol-5-yl)methylamino)-3-phenyl-N-(3-(pyridin-4-yl)phenyl)propanamide,
(2S)-3-Phenyl-N-(3-(pyridin-4-yl)phenyl)-2-(1-(thiazol-4-yl)ethylamino)propanamide,
(S)-tert-Butyl 2-(1-oxo-3-phenyl-1-(3-(pyridin-4-yl)phenylamino)propan-2-ylamino)acetate,
(S)—N-Methyl-3-phenyl-N-(3-(pyridin-4-yl)phenyl)-2-(thiazol-4-ylmethylamino)propanamide,
(S)-2-(1-Oxo-3-phenyl-1-(3-(pyridin-4-yl)phenylamino)propan-2-ylamino)acetic acid,
(S)-2-((4-Methyl-4H-1,2,4-triazol-3-yl)methylamino)-3-phenyl-N-(3-(pyridin-4-yl)phenyl)propanamide,
(2S)—N-(3-(3-Fluoropyridin-4-yl)phenyl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(S)—N-(2-Oxo-5-(pyridin-4-yl)-1,2-dihydropyridin-3-yl)-3-phenyl-2-(1-(pyridin-2-yl)cyclopropylamino)propanamide,
(S)—N-(2-Methoxy-5-(pyridin-4-yl)pyridin-3-yl)-3-phenyl-2-((S)-1-(pyridin-2-yl)ethylamino)propanamide,
(S)—N-(2-Methoxy-5-(pyridin-4-yl)pyridin-3-yl)-2-(1-(2-methylthiazol-4-yl)cyclopropylamino)-3-phenylpropanamide,
(S)-2-(Isoxazol-3-ylmethylamino)-N-(2-methoxy-5-(pyridin-4-yl)pyridin-3-yl)-3-phenylpropanamide,
(S)—N-(2-Methoxy-5-(pyridin-4-yl)pyridin-3-yl)-3-phenyl-2-(1-(pyrimidin-2-yl)cyclopropylamino))propanamide,
(2S)-2-Amino-N-(2-methoxy-5-(2-methylpyridin-4-yl)pyridin-3-yl)-3-phenylpropanamide,
(2S)—N-(3-(2-Aminopyridin-4-yl)phenyl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(S)—N-(4-Methoxy-3-(pyridin-4-yl)phenyl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide1H,
(S)—N-(4-Methoxy-3-(pyridin-4-yl)phenyl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(2S)—N-(3-(2-methylpyridin-4-yl)phenyl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(S)—N-(3′-aminobiphenyl-3-yl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(2S)—N-(2-Methoxy-5-(2-methylpyridin-4-yl)pyridin-3-yl)-3-phenyl-2-(1-(pyridin-2-yl)cyclopropylamino)propanamide,
(S)—N-(2-Methoxy-5-(2-methylpyridin-4-yl)pyridin-3-yl)-3-phenyl-2-((S)-1-(pyridin-2-yl)ethylamino)propanamide,
(2S)—N-(2-Methoxy-5-(2-methylpyridin-4-yl)pyridin-3-yl)-3-phenyl-2-(pyridin-2-ylmethylamino)propanamide,
(2S)—N-(2-Methoxy-5-(2-methylpyridin-4-yl)pyridin-3-yl)-2-((1-methyl-1H-imidazol-4-yl)methylamino)-3-phenylpropanamide,
(2S)—N-(2-Methoxy-5-(2-methylpyridin-4-yl)pyridin-3-yl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(2S)—N-(2-Methoxy-6-(2-methylpyridin-4-yl)pyridin-4-yl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(2S)-3-(4-fluorophenyl)-N-(3-(2-(methylamino)pyridin-4-yl)-1-propyl-1H-pyrazol-5-yl)-2-(thiazol-4-ylmethylamino)propanamide,
(2S)-2-Amino-3-(4-fluorophenyl)-N-(1-isopropyl-3-(2-(methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)propanamide,
(2S)-3-(4-Fluorophenyl)-N-(1-isopropyl-3-(2-methylamino)pyridin-4-yl)-1H-pyrazol-5-yl)-2-(thiazol-4-ylmethylamino)propanamide,
N-(4′-fluoro-1,1′-biphenyl-3-yl)-N-(1,3-thiazol-4-ylmethyl)-L-phenylalaninamide,
(S)-3-(2-Amino-3-phenylpropanamido)-5-(pyridin-4-yl)benzoic acid,
(S)-3-(3-Phenyl-2-(thiazol-5-ylmethylamino)propanamido)-5-(pyridin-4-yl)benzoic acid,
(S)-3-(3-Phenyl-2-(thiazol-2-ylmethylamino)propanamido)-5-(pyridin-4-yl)benzoic acid,
(S)-3-(2-((1H-Pyrazol-4-yl)methylamino)-3-phenylpropanamido)-5-(pyridin-4-yl)benzoic acid,
(S)-3-(2-((1H-Pyrazol-3-yl)methylamino)-3-phenylpropanamido)-5-(pyridin-4-yl)benzoic acid,
(S)-3-(3-Phenyl-2-(pyridin-2-ylmethylamino)propanamido)-5-(pyridin-4-yl)benzoic acid,
(2S)—N-(3-chloro-5-(2-methylpyridin-4-yl)phenyl)-3-phenyl-2-(pyridin-2-ylmethylamino)propanamide,
(S)-3-(3-phenyl-2-(thiazol-4-ylmethylamino)propanamido)-5-(pyridin-4-yl)benzamide,
N-(4′-fluoro-1,1′-biphenyl-3-yl)-N-(1,3-thiazol-4-ylmethyl)-L-phenylalaninamide,
3-((S)-2-Amino-3-(2,4-dichlorophenyl)propanamido)-5-(2-methylpyridin-4-yl)benzoic acid,
3-(2-Methylpyridin-4-yl)-5-((S)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamido)benzoic acid,
3-(2-Methylpyridin-4-yl)-5-((S)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamido)benzoic acid,
(S)-3-Phenyl-2-(pyridin-2-ylmethylamino)-1-(6-(pyridin-4-yl)indolin-1-yl)propan-1-one,
(2S)—N-(3-(2-Methylpyridin-4-yl)-5-(methylsulfonamido)phenyl)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamide,
(2S)—N-(3-(2-Methylpyridin-4-yl)-5-(methylsulfonamido)phenyl)-3-phenyl-2-(pyridin-2-ylmethylamino)propanamide,
(S)-2,2-difluoro-2-(3-(3-phenyl-2-(thiazol-4-ylmethylamino)propanamido)-5-(pyridin-4-yl)phenyl)acetic acid,
(S)-1-(3-Phenyl-2-(thiazol-4-ylmethylamino)propanoyl)-6-(pyridin-4-yl)indoline-4-carbonitrile,
(S)-Methyl 1-(2-amino-3-phenylpropanoyl)-6-(pyridin-4-yl)indoline-4-carboxylate,
Methyl 1-((S)-3-phenyl-2-((S)-1-(pyridin-2-yl)ethylamino)propanoyl)-6-(pyridin-4-yl)indoline-4-carboxylate,
(S)-Methyl 1-(3-phenyl-2-(thiazol-4-ylmethylamino)propanoyl)-6-(pyridin-4-yl)indoline-4-carboxylate,
(S)-Methyl 1-(2-((1H-pyrazol-3-yl)methylamino)-3-phenylpropanoyl)-6-(pyridin-4-yl)indoline-4-carboxylate,
(S)-Methyl 1-(3-(4-fluorophenyl)-2-(thiazol-4-ylmethylamino)propanoyl)-6-(pyridin-4-yl)indoline-4-carboxylate,
(S)-Methyl 1-(2-((1H-pyrazol-3-yl)methylamino)-3-(4-fluorophenyl)propanoyl)-6-(pyridin-4-yl)indoline-4-carboxylate,
(S)-Methyl 1-(3-(4-fluorophenyl)-2-(pyridin-2-ylmethylamino)propanoyl)-6-(pyridin-4-yl)indoline-4-carboxylate,
Methyl 1-((S)-3-phenyl-2-((S)-1-(pyridin-2-yl)ethylamino)propanoyl)-6-(pyridin-4-yl)indoline-4-carboxylate,
(S)—N,N-Dimethyl-3-(3-phenyl-2-(thiazol-4-ylmethylamino)propanamido)-5-(pyridin-4-yl)benzamide,
(2S)-1-(6-(2-Methylpyridin-4-yl)indolin-1-yl)-3-phenyl-2-(thiazol-4-ylmethylamino)propan-1-one,
(S)-5-(1-(3-Phenyl-2-(thiazol-4-ylmethylamino)propanoyl)-6-(pyridin-4-yl)indolin-4-yl)-1,3,4-oxadiazol-2(3H)-one,
(S)-3-Phenyl-1-(6-(pyridin-4-yl)-4-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)indolin-1-yl)-2-(thiazol-4-ylmethylamino)propan-1-one,
(2S)-2-Amino-1-(4-(5-amino-1,3,4-oxadiazol-2-yl)-6-(pyridin-4-yl)indolin-1-yl)-3-phenylpropan-1-one,
(S)-1-(3-Phenyl-2-(thiazol-4-ylmethylamino)propanoyl)-6-(pyridin-4-yl)indoline-4-carboxamide,
(2S)-1-(4-(2-Methyl-2H-1,2,4-triazol-3-yl)-6-(pyridin-4-yl)indolin-1-yl)-3-phenyl-2-(thiazol-4-ylmethylamino)propan-1-one,
(S)—N-Methyl-1-(3-phenyl-2-(thiazol-4-ylmethylamino)propanoyl)-6-(pyridin-4-yl)indoline-4-carboxamide,
(S)-2-(3-(3-(4-Chlorophenyl)-2-(thiazol-4-ylmethylamino)propanamido)-5-(pyridin-4-yl)phenyl)-2-methylpropanoic acid,
Methyl 2-(4-(2-methylpyridin-4-yl)-2-((S)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamido)phenoxy)acetate,
Methyl 2-(3-(2-methylpyridin-4-yl)-5-((S)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamido)phenoxy)acetate,
(2S)-1-(6-(2-Methylpyridin-4-yl)-4-(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)indolin-1-yl)-3-phenyl-2-(thiazol-4-ylmethylamino)propan-1-one,
(2S)-1-(4-(5-Methyl-1,3,4-oxadiazol-2-yl)-6-(pyridin-4-yl)indolin-1-yl)-3-phenyl-2-(thiazol-4-ylmethylamino)propan-1-one,
(2S)-1-(4-(1,3,4-Oxadiazol-2-yl)-6-(pyridin-4-yl)indolin-1-yl)-3-phenyl-2-(thiazol-4-ylmethylamino)propan-1-one,
(2S)-1-(4-(5-Methyl-4H-1,2,4-triazol-3-yl)-6-(pyridin-4-yl)indolin-1-yl)-3-phenyl-2-(thiazol-4-ylmethylamino)propan-1-one,
(S)—N-(Cyclopropylmethyl)-3-(3-phenyl-2-(thiazol-4-ylmethylamino)propanamido)-5-(pyridin-4-yl)benzamide,
(S)—N-(2-Amino-2-oxoethyl)-1-(3-phenyl-2-(thiazol-4-ylmethylamino)propanoyl)-6-(pyridin-4-yl)indoline-4-carboxamide,
Methyl 6-(2-methylpyridine-4-yl)-1-((S)-3-phenyl-2-(pyridin-2-ylmethylamino)propanoyl)indoline-4-carboxylate,
(S)-tert-Butyl 3-(3-phenyl-2-(1-(pyridin-2-yl)cyclopropylamino)propanamido)-5-(pyridin-4-yl)benzoate,
(S)—N-(2-(dimethylamino)ethyl)-3-(3-phenyl-2-(thiazol-4-ylmethylamino)propanamido)-5-(pyridin-4-yl)benzamide bis trifluoroacetate salt,
(2S)—N-(2-(2-(Dimethylamino)ethoxy)-5-(2-methylpyridin-4-yl)phenyl)-3-phenyl-2(thiazol-4-ylmethylamino)propanamide trifluoroacetate,
(2S)—N-(3-(2-(Dimethylamino)ethoxy)-5-(2-methylpyridin-4-yl)phenyl)-3-phenyl-2-(pyridin-2-ylmethylamino)propanamide,
(S)-Methyl 2-(1-(3-phenyl-2-(thiazol-4-ylmethylamino)propanoyl)-6-(pyridin-4-yl)indoline-4-carboxamido)acetate,
tert-Butyl 2-(3-((S)-2-(benzyloxycarbonyl)-3-phenylpropanamido)-5-(2-methylpyridin-4-yl)pyridin-2-yloxy)acetate,
tert-Butyl 2-(5-(2-methylpyridin-4-yl)-3-((S)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamido)pyridin-2-yloxy)acetate,
Methyl 1-((16S)-3-(2-methylpyridin-4-yl)-5-((S)-3-phenyl-2-(thiazol-4-ylmethylamino)propanamido)benzyl)azetidine-3-carboxylate,
Methyl 1-((16S)-3-(2-methylpyridin-4-yl)-5-((S)-3-phenyl-2-(pyridin-2-ylmethylamino)propanamido)benzyl)azetidine-3-carboxylate,
(S)—N-(2-(2-Oxoimidazolidin-1-yl)ethyl)-1-(3-phenyl-2-(thiazol-4-ylmethylamino)propanoyl)-6-(pyridin-4-yl)indoline-4-carboxamide,
(S)-tert-Butyl 1-oxo-3-phenyl-1-(6-(pyrimidin-5-yl)indolin-1-yl)propan-2-ylcarbamate,
(S)-3-Phenyl-1-(6-(pyrimidin-5-yl)indolin-1-yl)-2-(thiazol-4-ylmethylamino)propan-1-one,
(S)-1-[6-(4-Fluoro-phenyl)-2,3-dihydro-indol-1-yl]-3-phenyl-2-[(thiazol-4-ylmethyl)-amino]-propan-1-one Trifluoroacetate,
(S)-2-methyl-2-(3-(3-phenyl-2-(thiazol-4-ylmethylamino)propanamido)-5-(pyridin-4-yl)phenyl)propanoic acid,
Ethyl 2-((S)-1-(1-ethyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxo-3-phenylpropan-2-ylamino)acetate dihydrochloride,
(S)-2-(1-(1-Ethyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxo-3-phenylpropan-2-ylamino)acetic acid,
(S)—N-(1-Ethyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)-2-(ethylcarbamoylmethylamino)-3-phenylpropanamide,
Ethyl 2-((S)-1-(1-ethyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-3-(1H-indol-3-yl)-1-oxopropan-2-ylamino)acetate dihydrochloride,
Ethyl 2-((S)-1-(1-ethyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-3-(3,4-difluorophenyl)-1-oxopropan-2-ylamino)acetate dihydrochloride,
(S)-2-(1-(1-Ethyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-3-(3,4-difluorophenyl)-1-oxopropan-2-ylamino)acetic acid,
Ethyl 2-((S)-1-(3-(2-chloropyridin-4-yl)-1-ethyl-1H-pyrazol-5-ylamino)-1-oxo-3-phenylpropan-2-ylamino)acetate dihydrochloride,
(S)-2-(1-(3-(2-Chloropyridin-4-yl)-1-ethyl-1H-pyrazol-5-ylamino)-1-oxo-3-phenylpropan-2-ylamino)acetic acid,
Ethyl 2-((S)-3-(4-fluorophenyl)-1-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxopropan-2-ylamino)acetate dihydrochloride,
2-((S)-3-(4-Fluorophenyl)-1-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxopropan-2-ylamino)acetic acid,
(S)-2-(Ethylcarbamoylmethylamino)-3-(4-fluorophenyl)-N-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)propanamide,
Ethyl 2-((S)-3-(3,4-difluorophenyl)-1-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxopropan-2-ylamino)acetate dihydrochloride,
(S)-2-(3-(3,4-difluorophenyl)-1-(1-ethyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxopropan-2-ylamino)acetic acid,
(S)-2-(Carbamoylmethylamino)-N-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-3-phenylpropanamide,
(S)-2-(Ethylcarbamoylmethylamino)-N-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)-3-phenylpropanamide,
(S)—N-(1-Methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)-2-(methylcarbamoylmethylamino)-3-phenylpropanamide,
(S)—N-(1-Methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)-2-(dimethylcarbamoylmethylamino)-3-phenylpropanamide,
(S)—N-(1-Methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)-3-phenyl-2-(propylcarbamoylmethylamino)propanamide,
(S)-2-(Isopropylcarbamoylmethylamino)-N-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)-3-phenylpropanamide,
(S)-2-(Cyclopropylcarbamoylmethylamino)-N-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)-3-phenylpropanamide,
(S)-2-(Ethylcarbamoylmethylamino)-N-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-yl)-3-phenylpropanamide dihydrochloride,
Ethyl 2-((S)-1-(3-(2-methoxypyridin-4-yl)-1-methyl-1H-pyrazol-5-ylamino)-1-oxo-3-phenylpropan-2-ylamino)acetate dihydrochloride,
(S)-2-(1-(3-(2-Methoxypyridin-4-yl)-1-methyl-1H-pyrazol-5-ylamino)-1-oxo-3-phenylpropan-2-ylamino)acetic acid,
(S)-2-(Carbamoylmethylamino)-N-(3-(2-methoxypyridin-4-yl)-1-methyl-1H-pyrazol-5-yl)-3-phenylpropanamide,
(S)-2-(Ethylcarbamoylmethylamino)-N-(3-(2-methoxypyridin-4-yl)-1-methyl-1H-pyrazol-5-yl)-3-phenylpropanamide,
(S)-2-(Diethylcarbamoylmethylamino)-N-(3-(2-methoxypyridin-4-yl)-1-methyl-1H-pyrazol-5-yl)-3-phenylpropanamide,
(S)—N-(1-Methyl-3-(2-methoxypyridin-4-yl)-1H-pyrazol-5-yl)-3-phenyl-2-(pyrrolidin-1-ylcarbonylmethylamino)propanamide,
Ethyl 2-((S)-1-oxo-3-phenyl-1-(3-(pyridin-4-yl)phenylamino)propan-2-ylamino)acetate dihydrochloride,
2-((S)-3-(3,4-Difluorophenyl)-1-oxo-1-(3-(pyridin-4-yl)phenylamino)propan-2-ylamino)acetic acid,
Ethyl 2-((S)-1-(2-fluoro-5-(pyridin-4-yl)phenylamino)-1-oxo-3-phenylpropan-2-ylamino)acetate dihydrochloride and
2-((S)-1-(2-fluoro-5-(pyridin-4-yl)phenylamino)-1-oxo-3-phenylpropan-2-ylamino)acetic acid.

### Claim 8 (depends on 1, 2)

A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and the compound as set forth in any of claims 1, 2, and 3.

### Claim 9 (depends on 1, 2, 3)

A method for treating a disease or condition, or symptom thereof, wherein the disease or condition is selected from the group consisting of type 2 diabetes, diabetic ketoacidosis, hyperglycemia, diabetic neuropathy, obesity, metabolic syndrome, inflammation, asthma, psoriasis, arthritis, rheumatoid arthritis, inflammatory bowel disease, cancer and neurologic disorder, the method comprising administering to a subject having the disease or condition a therapeutically effective amount of a compound according to any of claims 1, 2 and 3.