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

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.

Claims9

Dependent claims

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.

3 more elements

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.

11 more elements

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.

192 more elements

Dependencies are inferred from the claim text.

Facts

Application

13/148,296Filed 12 Feb 2010 · us provisional application

Priority

13 Feb 2009

Published

US 2012/0115811 A110 May 2012

Granted

22 Jul 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification21 codes

C07D 401/04
Containing two hetero rings: 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
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents

Phenylalanine amide derivatives useful for treating insulin-related diseases and conditions

Life of this patent

Phenylalanine amide derivatives useful for treating insulin-related diseases and conditions

Life of this patent

Abstract

Claims9