US 8,921,389 B2Granted

Naphthyridine derivatives as inhibitors of hypoxia inducible factor (HIF) hydroxylase

AssigneeFibroGen, Inc.

InventorsDanny Ng, Michael P. Arend, Lee A. Flippin

Life of this patent

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Abstract

The present disclosure relates to novel compounds, methods, and compositions capable of inhibiting HIF hydroxylase enzyme activity, thereby increasing the stability and/or activity of hypoxia inducible factor (HIF).

Claims26

Dependent claims

A compound of Formula Ia:

wherein
q is 0 or 1;
R1 is selected from the group consisting of hydrogen, cyano, halo, hydroxy, alkoxy, amino, acyloxy, aminoacyl, alkyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, heterocycloalkyl, heteroaryloxy, and heteroaryl;
one of Z1 or Z2 is —NR2— and the other of Z1 or Z2 is —C(O)—;
R2 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl;
R3 and R4 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, amino, acyloxy, aminoacyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, heterocycloalkyl, heteroaryloxy, and heteroaryl;
is a single or a double bond;
Y is —NR6— or —O—;
n is 1, 2, 3, 4, 5, or 6;
R5 is selected from the group consisting of hydrogen, acyl, sulfonyl, aminoacyl, oxycarbonyl, alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl;
R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl;
R7 and R8 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl;
or R7 and R8 together with the carbon atom to which they are attached form a cycloalkyl, or heterocycloalkyl;
W is selected from the group consisting of R9, —C(O)OR9, —C(O)NR6R9, —NR6C(O)R9, —NR6C(O)OR9, —NR6C(O)NR6R9, —NR6S(O)2R9, —S(O)2NR6R9, —NR6R9 and —OR9;
and
R9 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl;
and
further wherein each alkyl, alkoxy, amino, acyloxy, aminoacyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, heterocycloalkyl, heteroaryloxy, and heteroaryl described above for R1, R2, R3, R4, R6, R7, R8 and R9 can be optionally substituted with from 1 to 3 R10,
wherein each R10 is independently selected from the group consisting of alkyl, alkoxy, haloalkyl, haloalkoxy, acyl, acylamino, acyloxy, amino, aminoacyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aryl, aryloxy, aryloxyaryl, cyano, halogen, hydroxyl, nitro, oxo, thioxo, carboxyl, carboxyl ester, cycloalkyl, thio, alkylthio, arylthio, cycloalkylthio, heteroarylthio, heterocyclicthio, sulfonyl, heteroaryl, heterocyclic, cycloalkoxy, heteroaryloxy, heterocyclyloxy, oxycarbonylamino, oxythiocarbonylamino, —OS(O)2-alkyl, —OS(O)2-aryl, —OS(O)2-heteroaryl, —OS(O)2-heterocyclic, —OSO2—NR40R40, —NR40S(O)2—NR40-alkyl, —NR40S(O)2—NR40-aryl, —NR40S(O)2—NR40-heteroaryl, and —NR40S(O)2—NR40-heterocyclic, where each R40 is independently hydrogen or alkyl;
and further wherein each alkyl, alkoxy, aryl, aryloxy, aryloxyaryl, cycloalkyl, alkylthio, arylthio, cycloalkylthio, heteroarylthio, heterocyclicthio, heteroaryl, heterocyclic, cycloalkoxy, heteroaryloxy, or heterocyclyloxy may be additionally substituted with from 1-3 substituents independently alkyl, alkoxy, haloalkyl, haloalkoxy, or halogen;
or a pharmaceutically acceptable salt, single stereoisomer, mixture of stereoisomers, ester, tautomer or prodrug thereof.

18 more elements

A compound selected from the group consisting of [(1-benzyl-5-hydroxy-2-oxo-1,2,3,4-tetrahydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;

[(1-benzyl-5-hydroxy-3-methyl-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
[(1,3-dibenzyl-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
[(1-benzyl-5-hydroxy-3,8-dimethyl-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
[(1-benzyl-8-cyano-5-hydroxy-3-methyl-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
[(1-benzyl-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
[(1-benzyl-5-hydroxy-8-methyl-2-oxo-1,2,3,4-tetrahydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
[(1-benzyl-8-cyano-5-hydroxy-2-oxo-1,2,3,4-tetrahydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
[(1-benzyl-5-hydroxy-3-methyl-2-oxo-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
[(1-benzyl-5-hydroxy-2-oxo-3-phenethyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
[(1-benzyl-5-hydroxy-8-methyl-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
[(1-benzyl-5-hydroxy-2-oxo-3,8-diphenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
[(1-benzyl-8-cyano-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
3-[(1-benzyl-8-cyano-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
[(1,3-dibenzyl-8-cyano-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
3-[(1,3-dibenzyl-8-cyano-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
[(1,3-dibenzyl-5-hydroxy-8-methyl-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
3-[(1,3-dibenzyl-5-hydroxy-8-methyl-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
[(1,3-dibenzyl-5-hydroxy-2-oxo-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-acetic acid;
3-[(1,3-dibenzyl-5-hydroxy-2-oxo-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
4-[(1-benzyl-8-cyano-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-butyric acid;
5-[(1-benzyl-8-cyano-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-pentanoic acid;
3-[(1-benzyl-8-cyano-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-2,2-dimethyl-propionic acid;
[(7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-acetic acid;
3-[(7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-propionic acid;
3-[(7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-2,2-dimethyl-propionic acid;
4-[(7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-butyric acid;
5-[(7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-pentanoic acid;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid (pyridin-4-ylmethyl)-amide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methylamide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid dimethylamide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid amide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid propylamide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid cyclopropylamide;
1-benzyl-8-cyano-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid (pyridin-4-ylmethyl)-amide;
(R)-2-[(1-benzyl-8-cyano-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-3-phenyl-propionic acid;
(S)-2-[(1-benzyl-8-cyano-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-3-phenyl-propionic acid;
[(7-benzyl-4-hydroxy-1-methyl-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-acetic acid;
{[7-benzyl-1-(5-fluoro-pyridin-3-yl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl]-amino}-acetic acid;
[(7-benzyl-4-hydroxy-8-oxo-1-phenyl-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-acetic acid;
[(7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-acetic acid;
7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid (pyridin-4-ylmethyl)-amide;
3-[(7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-propionic acid;
3-[(7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-2,2-dimethyl-propionic acid;
(R)-2-[(7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-3-phenyl-propionic acid;
5-[(7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-pentanoic acid;
(S)-2-[(7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-3-phenyl-propionic acid;
(S)-2-[(7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-propionic acid;
(R)-2-[(7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-propionic acid;
7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid (2-morpholin-4-yl-ethyl)-amide;
7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid (pyridazin-4-ylmethyl)-amide;
{2-[(7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-ethoxy}-acetic acid;
1-{[(7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-methyl}-cyclobutanecarboxylic acid;
7-(2,4-dimethoxy-benzyl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methylamide;
{[7-(2,4-dimethoxy-benzyl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl]-amino}-acetic acid;
3-{[7-(2,4-benzyl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl]-amino}-propionic acid;
7-(2,4-dimethoxy-benzyl)-4-hydroxy-8-oxo-5,6,7,8-tetrahydro-[2,7]naphthyridine-3-carboxylic acid methylamide;
{[7-(2,4-dimethoxy-benzyl)-4-hydroxy-8-oxo-5,6,7,8-tetrahydro-[2,7]naphthyridine-3-carbonyl]-amino}-acetic acid;
3-{[7-(2,4-dimethoxy-benzyl)-4-hydroxy-8-oxo-5,6,7,8-tetrahydro-[2,7]naphthyridine-3-carbonyl]-amino}-propionic acid;
7 benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid (3-propylcarbamoyl-propyl)-amide;
3-[(4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-propionic acid;
7 (2,4-dimethoxy-benzyl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid phenethyl-amide;
7-(2,4-dimethoxy-benzyl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid (2-methoxy-ethyl)-amide;
7-(2,4-dimethoxy-benzyl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid 4-fluoro-benzylamide;
1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methylamide;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
{2-[(7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-ethoxy}-acetic acid;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid (1H-tetrazol-5-ylmethyl)-amide;
3-{[7-benzyl-1-(5-fluoro-pyridin-3-yl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl]-amino}-propionic acid;
3-{[7-benzyl-1-(5-fluoro-pyridin-3-yl)-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl]-amino}-2,2-dimethyl-propionic acid;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid [2-(3-isopropyl-ureido)-ethyl]-amide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid (2-sulfamoyl-ethyl)-amide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid [2-(2,2,2-trifluoro-acetylamino)-ethyl]-amide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid (2-acetylamino-ethyl)-amide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid {2-[methyl-(2,2,2-trifluoro-acetyl)-amino]-ethyl}-amide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid [2-(3-isopropyl-1-methyl-ureido)-ethyl]-amide;
{2-[(7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-ethyl}-methyl-carbamic acid methyl ester;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid [2-(methanesulfonyl-methyl-amino)-ethyl]-amide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid (2-methanesulfonylamino-ethyl)-amide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid [3-(2,2,2-trifluoro-acetylamino)-propyl]-amide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid [3-(3-isopropyl-ureido)-propyl]-amide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid (3-ureido-propyl)-amide;
1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid (2-acetylamino-ethyl)-amide;
1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid [2-(methanesulfonyl-methyl-amino)-ethyl]-amide;
1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid [2-(2,2,2-trifluoro-acetylamino)-ethyl]-amide;
1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid [2-(3-ethyl-ureido)-ethyl]-amide;
1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid (1H-tetrazol-5-ylmethyl)-amide;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-2,2-dimethyl-propionic acid;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid [2-(formyl-methyl-amino)-ethyl]-amide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid [2-(acetyl-methyl-amino)-ethyl]-amide;
1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid (2-formylamino-ethyl)-amide;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3,8-diphenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-8-methyl-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2,3,4-tetrahydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenethyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-pyridin-2-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
4-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-butyric acid;
3-[(1-benzyl-5-hydroxy-3-methyl-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-thiophen-2-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methylamide;
7-benzyl-1-cyano-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid cyclopropylamide;
1-benzyl-8-cyano-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methylamide;
3-[(1-benzyl-5-hydroxy-2-oxo-3-pyridin-4-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid (2-methanesulfonylamino-ethyl)-amide;
1-benzyl-8-cyano-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid [2-(methanesulfonyl-methyl-amino)-ethyl]-amide;
1-benzyl-5-hydroxy-8-methyl-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid [2-(methanesulfonyl-methyl-amino)-ethyl]-amide;
1-benzyl-5-hydroxy-2-oxo-3,8-diphenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid [2-(methanesulfonyl-methyl-amino)-ethyl]-amide;
1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid [2-(methanesulfonyl-methyl-amino)-ethyl]-amide;
3-[(5-hydroxy-2-oxo-1-phenethyl-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(5-hydroxy-2-oxo-1,3-diphenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(3-benzyl-5-hydroxy-2-oxo-1-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(5-hydroxy-1-methyl-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-{[1-benzyl-3-(4-cyano-phenyl)-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-benzyl-5-hydroxy-3-(4-methoxy-phenyl)-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-thiazol-2-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
(R)-3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-butyric acid;
3-{[5-hydroxy-1-(4-methoxy-benzyl)-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-(4-cyano-benzyl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-pyrazin-2-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-{[1-benzyl-5-hydroxy-3-(4-methanesulfonyl-phenyl)-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-benzyl-5-hydroxy-2-oxo-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-benzyl-5-hydroxy-3-(4-morpholin-4-yl-phenyl)-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-[(3-benzo[1,2,5]oxadiazol-5-yl-1-benzyl-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-{[1-benzyl-3-(5-fluoro-2-methoxy-phenyl)-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-benzyl-5-hydroxy-2-oxo-3-(4-trifluoromethoxy-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
(R)-2-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-3-phenyl-propionic acid;
3-{[1-benzyl-5-hydroxy-3-(1-methyl-1h-pyrazol-4-yl)-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-pyrimidin-5-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-{[1-benzyl-3-(2-dimethylamino-pyrimidin-5-yl)-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-[(1-cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-{[5-hydroxy-2-oxo-3-phenyl-1-(tetrahydro-pyran-4-ylmethyl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-[(5-hydroxy-2-oxo-3-phenyl-1-thiazol-2-ylmethyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyrimidin-5-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyrazin-2-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
5-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-pentanoic acid;
4-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-butyric acid;
5-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-pentanoic acid;
3-[(5-hydroxy-2-oxo-1,3-diphenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(5-hydroxy-1-methyl-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(5-hydroxy-2-oxo-1-phenethyl-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-4-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3,8-di-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
(R)-3-{[5-hydroxy-2-oxo-3-phenyl-1-(1-phenyl-ethyl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
(R)-4-{[5-hydroxy-2-oxo-3-phenyl-1-(1-phenyl-ethyl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-butyric acid;
3-{[1-benzyl-5-hydroxy-8-(5-methoxy-pyridin-3-yl)-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-benzyl-8-(5-chloro-pyridin-3-yl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
(S)-3-{[5-hydroxy-2-oxo-3-phenyl-1-(1-phenyl-ethyl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
(S)-4-{[5-hydroxy-2-oxo-3-phenyl-1-(1-phenyl-ethyl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-butyric acid;
(S)-3-{[5-hydroxy-2-oxo-3-phenyl-1-(1-phenyl-ethyl)-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
(R)-3-{[5-hydroxy-2-oxo-3-phenyl-1-(1-phenyl-ethyl)-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-benzyl-8-(5-fluoro-pyridin-3-yl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-benzyl-5-hydroxy-8-(2-methyl-pyridin-3-yl)-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-benzyl-5-hydroxy-8-(6-methyl-pyridin-3-yl)-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-(6-trifluoromethyl-pyridin-3-yl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-benzyl-5-hydroxy-8-(6-methoxy-pyridin-3-yl)-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1-(tetrahydro-pyran-4-ylmethyl)-1,2-dihydro[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-[(1-cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
4-[(1-cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-butyric acid;
3-{[1-benzyl-5-hydroxy-3-(4-methoxy-phenyl)-2-oxo-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
4-{[1-benzyl-5-hydroxy-3-(4-methoxy-phenyl)-2-oxo-1,2-dihydro[1,7]naphthyridine-6-carbonyl]-amino}-butyric acid;
3-{[1-benzyl-5-hydroxy-3-(3-methoxy-phenyl)-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
4-{[1-benzyl-5-hydroxy-3-(3-methoxy-phenyl)-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-butyric acid;
1-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-cyclopropanecarboxylic acid;
1-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-cyclopropanecarboxylic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-2,2-dimethyl-propionic acid;
3-{[1-benzyl-8-(2-ethoxy-pyrimidin-5-yl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-2-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridazin-4-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-thiazol-2-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid (3-formylamino-propyl)-amide;
7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid (3-acetylamino-propyl)-amide;
3-[(1-cyclohexylmethyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-4-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(5-hydroxy-2-oxo-1,3-diphenyl-8-pyridin-4-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-{[1-benzyl-5-hydroxy-8-(1-methyl-1h-pyrazol-4-yl)-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-thiazol-5-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-thiazol-4-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridazin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1-benzyl-5-hydroxy-2-oxo-3-phenethyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(1,3-dibenzyl-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
3-[(7-benzyl-4-hydroxy-8-oxo-1-pyridin-3-yl-7,8-dihydro-[2,7]naphthyridine-3-carbonyl)-amino]-propionic acid;
3-{[1-cyclohexylmethyl-8-(2-ethoxy-pyrimidin-5-yl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-benzyl-5-hydroxy-8-(2-methylsulfanyl-pyrimidin-5-yl)-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-benzyl-5-hydroxy-2-oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-benzyl-5-hydroxy-2-oxo-3-(2-trifluoromethyl-phenyl)-1,2-dihydro[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
4-{[1-benzyl-5-hydroxy-2-oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro[1,7]naphthyridine-6-carbonyl]-amino}-butyric acid;
4-{[1-benzyl-5-hydroxy-2-oxo-3-(3-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-butyric acid;
4-{[1-benzyl-5-hydroxy-2-oxo-3-(2-trifluoromethyl-phenyl)-1,2-dihydro[1,7]naphthyridine-6-carbonyl]-amino}-butyric acid;
3-{[1-benzyl-5-hydroxy-2-oxo-8-pyridin-3-yl-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-benzyl-5-hydroxy-2-oxo-8-pyridin-3-yl-3-(3-trifluoromethyl-phenyl)-1,2-dihydro[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-benzyl-5-hydroxy-2-oxo-8-pyridin-3-yl-3-(2-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-[(1-cyclopentylmethyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
4-[(1-cyclopentylmethyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl)-amino]-butyric acid;
3-[(1-cyclopentylmethyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro[1,7]naphthyridine-6-carbonyl)-amino]-propionic acid;
1-[(7-benzyl-4-hydroxy-8-oxo-7,8-dihydro[2,7]naphthyridine-3-carbonyl)-amino]-cyclopropanecarboxylic acid;
3-{[1-(2-ethyl-butyl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
4-{[1-(2-ethyl-butyl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro[1,7]naphthyridine-6-carbonyl]-amino}-butyric acid;
3-{[1-(2-ethyl-butyl)-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro-[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[1-(2-ethyl-butyl)-5-hydroxy-2-oxo-3-phenyl-8-pyridin-4-yl-1,2-dihydro[1,7]naphthyridine-6-carbonyl]-amino}-propionic acid;
3-{[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro[1,7]naphthyridine-6-carbonyl)-amino]-methyl}-benzoic acid;
and {1-[(1-benzyl-5-hydroxy-2-oxo-3-phenyl-8-pyridin-3-yl-1,2-dihydro[1,7]naphthyridine-6-carbonyl)-amino]-cyclopropyl}-acetic acid;
or a pharmaceutically acceptable salt, single stereoisomer, mixture of stereoisomers, ester, tautomer, or prodrug thereof.

203 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/983,025Filed 1 Feb 2012 · us provisional application
Priority: 2 Feb 2011
Published: US 2014/0088101 A127 Mar 2014
Granted: 30 Dec 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification17 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/4375
Ortho- or peri-condensed with heterocyclic ring systems: the heterocyclic ring system containing a six-membered ring having nitrogen as a ring…
A61K 31/444
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
A61K 31/497
Non-condensed pyrazines: containing further heterocyclic rings

Family

Application61/438,929Us provisional application · filed 2 Feb 2011
US 2014/0088101 A1Pre-grant publication · published 27 Mar 2014
US 8,921,389 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of Formula Ia:

wherein
q is 0 or 1;
R1 is selected from the group consisting of hydrogen, cyano, halo, hydroxy, alkoxy, amino, acyloxy, aminoacyl, alkyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, heterocycloalkyl, heteroaryloxy, and heteroaryl;
one of Z1 or Z2 is —NR2— and the other of Z1 or Z2 is —C(O)—;
R2 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl;
R3 and R4 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, amino, acyloxy, aminoacyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, heterocycloalkyl, heteroaryloxy, and heteroaryl;
is a single or a double bond;
Y is —NR6— or —O—;
n is 1, 2, 3, 4, 5, or 6;
R5 is selected from the group consisting of hydrogen, acyl, sulfonyl, aminoacyl, oxycarbonyl, alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl;
R6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl;
R7 and R8 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl;
or R7 and R8 together with the carbon atom to which they are attached form a cycloalkyl, or heterocycloalkyl;
W is selected from the group consisting of R9, —C(O)OR9, —C(O)NR6R9, —NR6C(O)R9, —NR6C(O)OR9, —NR6C(O)NR6R9, —NR6S(O)2R9, —S(O)2NR6R9, —NR6R9 and —OR9;
and
R9 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl;
and
further wherein each alkyl, alkoxy, amino, acyloxy, aminoacyl, cycloalkyl, cycloalkoxy, aryl, aryloxy, heterocycloalkyl, heteroaryloxy, and heteroaryl described above for R1, R2, R3, R4, R6, R7, R8 and R9 can be optionally substituted with from 1 to 3 R10,
wherein each R10 is independently selected from the group consisting of alkyl, alkoxy, haloalkyl, haloalkoxy, acyl, acylamino, acyloxy, amino, aminoacyl, aminocarbonylamino, aminothiocarbonylamino, aminocarbonyloxy, aryl, aryloxy, aryloxyaryl, cyano, halogen, hydroxyl, nitro, oxo, thioxo, carboxyl, carboxyl ester, cycloalkyl, thio, alkylthio, arylthio, cycloalkylthio, heteroarylthio, heterocyclicthio, sulfonyl, heteroaryl, heterocyclic, cycloalkoxy, heteroaryloxy, heterocyclyloxy, oxycarbonylamino, oxythiocarbonylamino, —OS(O)2-alkyl, —OS(O)2-aryl, —OS(O)2-heteroaryl, —OS(O)2-heterocyclic, —OSO2—NR40R40, —NR40S(O)2—NR40-alkyl, —NR40S(O)2—NR40-aryl, —NR40S(O)2—NR40-heteroaryl, and —NR40S(O)2—NR40-heterocyclic, where each R40 is independently hydrogen or alkyl;
and further wherein each alkyl, alkoxy, aryl, aryloxy, aryloxyaryl, cycloalkyl, alkylthio, arylthio, cycloalkylthio, heteroarylthio, heterocyclicthio, heteroaryl, heterocyclic, cycloalkoxy, heteroaryloxy, or heterocyclyloxy may be additionally substituted with from 1-3 substituents independently alkyl, alkoxy, haloalkyl, haloalkoxy, or halogen;
or a pharmaceutically acceptable salt, single stereoisomer, mixture of stereoisomers, ester, tautomer or prodrug thereof.

18 more elements

Facts

Application

13/983,025Filed 1 Feb 2012 · us provisional application

Priority

2 Feb 2011

Published

US 2014/0088101 A127 Mar 2014

Granted

30 Dec 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification17 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/4375
Ortho- or peri-condensed with heterocyclic ring systems: the heterocyclic ring system containing a six-membered ring having nitrogen as a ring…
A61K 31/444
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
A61K 31/497
Non-condensed pyrazines: containing further heterocyclic rings