US 12,715,856 B2Granted

Compounds useful as immunomodulators

AssigneeBristol-Myers Squibb Company

InventorsKap-Sun Yeung, Denis R. St. Laurent, Li-Qiang Sun, Zhiwei Yin, Katharine A. Grant-Young, Paul Michael Scola

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Abstract

The present disclosure generally relates to compounds useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases.

Claims2

Dependent claims

A compound which is

5-((2-(((1-(1H-Tetrazol-5-yl)ethyl)(methyl)amino)methyl)-4-chloro-5-((3′-(3-((R)-3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((2-(((2-(1H-Tetrazol-5-yl)propyl)(methyl)amino)methyl)-4-chloro-5-((3′-(3-((R)-3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((4-Chloro-5-((3′-(3-((R)-3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((2-(5-oxo-2,5-dihydro-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-methyl)phenoxy)methyl)nicotinonitrile,
5-((2-(((2-(1H-Tetrazol-5-yl)propyl)amino)methyl)-4-chloro-5-((3′-(3-((R)-3-hydroxy-pyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)-nicotinonitrile,
2-((5-Chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((5-cyanopyridin-3-yl)methoxy)benzyl)amino)-2-(3,5-dimethyl-1H-pyrazol-4-yl)acetic acid,
2-((5-Chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((5-cyanopyridin-3-yl)methoxy)benzyl)amino)-2-(1-methyl-1H-pyrazol-4-yl)acetic acid,
5-((4-Chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((3-(hydroxymethyl)-1-methyl-1,3a,4,6,7,7a-hexahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
5-((2-(((1-(1H-Tetrazol-5-yl)ethyl)(methyl)amino)methyl)-4-chloro-5-((3′-(3-(((S)-2,3-dihydroxypropyl)amino)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-phenoxy)methyl)nicotinonitrile,
5-((2-(((2-(1H-Tetrazol-5-yl)propyl)(methyl)amino)methyl)-4-chloro-5-((3′-(3-(((S)-2,3-dihydroxy-propyl)amino)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-phenoxy)methyl)nicotinonitrile,
5-((2-(((1-(1H-Tetrazol-5-yl)ethyl)(methyl)amino)methyl)-4-chloro-5-((2′-chloro-3′-(3-(((S)-2,3-dihydroxypropyl)amino)propoxy)-2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-phenoxy)methyl)-nicotinonitrile,
5-((2-(((2-(1H-Tetrazol-5-yl)propyl)(methyl)amino)methyl)-4-chloro-5-((2′-chloro-3′-(3-(((S)-2,3-dihydroxypropyl)amino)propoxy)-2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-phenoxy)methyl)nicotinonitrile,
N-(1-(3-((3′-((4-(((1-(1H-Tetrazol-5-yl)ethyl)(methyl)amino)methyl)-2-chloro-5-((5-cyanopyridin-3-yl)methoxy)phenoxy)methyl)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)oxy)-propyl)piperidin-4-yl)acetamide,
N-(1-(3-((3′-((4-(((1-(1H-Tetrazol-5-yl)ethyl)amino)methyl)-2-chloro-5-((5-cyanopyridin-3-yl)methoxy)phenoxy)methyl)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)oxy)propyl)piperidin-4-yl)acetamide,
N-(1-(3-((3′-((4-(((2-(2H-Tetrazol-5-yl)propyl)(methyl)amino)methyl)-2-chloro-5-((5-cyanopyridin-3-yl)methoxy)phenoxy)methyl)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)oxy)-propyl)piperidin-4-yl)acetamide,
(R)-4-(((5-chloro-4-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((5-methyl-1H-imidazol-4-yl)methoxy)benzyl)amino)methyl)pyrimidine-2-carbonitrile,
N-(1-(3-((3′-((4-(((2-(1H-Tetrazol-5-yl)propyl)amino)methyl)-2-chloro-5-((5-cyano-pyridin-3-yl)methoxy)phenoxy)methyl)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)oxy)propyl)-piperidin-4-yl)acetamide,
(R)-4-(((5-chloro-4-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((5-methyl-1-trityl-1H-imidazol-4-yl)methoxy)benzyl)amino)methyl)pyrimidine-2-carbonitrile,
(R)-1-(3-((3′-((4-((((1H-imidazol-2-yl)methyl)amino)methyl)-2-chloro-5-(pyrimidin-5-ylmethoxy)phenoxy)methyl)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)oxy)propyl)pyrrolidin-3-ol,
(R)-1-(3-((3′-((4-((((1H-pyrazol-4-yl)methyl)amino)methyl)-2-chloro-5-(pyrimidin-5-ylmethoxy)phenoxy)methyl)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)oxy)propyl)pyrrolidin-3-ol,
N-((1H-pyrazol-4-yl)methyl)-1-(5-chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-(pyridazin-3-ylmethoxy)phenyl)methanamine,
N-((1H-imidazol-2-yl)methyl)-1-(5-chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-(pyridazin-3-ylmethoxy)phenyl)methanamine,
N-((1H-pyrazol-4-yl)methyl)-1-(5-chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-methoxyphenyl)methanamine,
N-((1H-imidazol-2-yl)methyl)-1-(5-chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-methoxyphenyl)methanamine,
N-(5-chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-(pyrazin-2-ylmethoxy)benzyl)-1-(pyridazin-3-yl)methanamine,
N-(5-chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-(pyrazin-2-ylmethoxy)benzyl)-1-(pyrimidin-2-yl)methanamine,
N-((1H-imidazol-4-yl)methyl)-1-(5-chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-(pyrazin-2-ylmethoxy)phenyl)methanamine,
((R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((2-methyl-6,7-dihydrothiazolo[5,4-c]pyridin-5 (4H)yl)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-2-(((2-(5-chloro-1H-benzo[d]imidazol-2-yl)ethyl)amino)methyl)-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
(R)-5-((2-(((benzo[d]thiazol-2-ylmethyl)amino)methyl)-4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
(R)-5-((2-(((benzo[d]thiazol-2-ylmethyl)(methyl)amino)methyl)-4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((((1-methyl-1H-indazol-3-yl)methyl)amino)methyl)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((3′-(3-((R)-3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-(((4,5,6,7-tetrahydro-1H-indazol-5-yl)amino)methyl)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((3′-(3-((R)-3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((methyl (4,5,6,7-tetrahydro-1H-indazol-5-yl)amino)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-(((imidazo[1,5-a]pyridin-3-ylmethyl)amino)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((1-phenyl-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-2-((((4,5-diethyl-1H-imidazol-2-yl)methyl)(2-methoxyethyl)amino)methyl)-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl)methyl)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]12yridine-6-yl)methyl)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
5-((2-(((2-(1H-benzo[d]imidazol-2-yl)ethyl)amino)methyl)-4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((2-methyl-6,7-dihydrothiazolo[5,4-c]pyridin-5 (4H)-yl)methyl)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-(((4,5,6,7-tetrahydro-1H-indazol-5-yl)amino)methyl)phenoxy)methyl)nicotinonitrile,
5-((2-(((benzo[d]thiazol-2-ylmethyl)amino)methyl)-4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((((6-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)amino)methyl)phenoxy)methyl)nicotinonitrile,
5-((2-(((2-(1,2,4-oxadiazol-3-yl)propan-2-yl)amino)methyl)-4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-(((imidazo[1,5-a]pyridin-3-ylmethyl)amino)methyl)phenoxy)methyl)nicotinonitrile,
5-((2-(((2-(1,2,4-oxadiazol-3-yl)propan-2-yl-1,1,1,3,3,3-d6)amino)methyl)-4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((2-(((3-(benzyloxy)-1-(1,2,4-oxadiazol-3-yl)cyclobutyl)amino)methyl)-4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((2-((2-(1H-Pyrazol-4-yl)piperidin-1-yl)methyl)-4-chloro-5-((3′-(3-((R)-3-hydroxy-pyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)-nicotinonitrile,
5-((2-((2-(1H-Pyrazol-4-yl)piperidin-1-yl)methyl)-4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)-nicotinonitrile, or
5-((2-((2-(1H-Pyrazol-3-yl)piperidin-1-yl)methyl)-4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)-nicotinonitrile,
or a pharmaceutically acceptable salt thereof.

55 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/766,483Filed 1 Oct 2020 · us provisional application
Priority: 4 Oct 2019
Published: US 2024/0124417 A118 Apr 2024
Granted: 25 Aug 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61K 31/4439
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/4545
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/497
Non-condensed pyrazines: containing further heterocyclic rings

Family

Application62/910,721Us provisional application · filed 4 Oct 2019
US 2024/0124417 A1Pre-grant publication · published 18 Apr 2024
US 12,715,856 B2This patent

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

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Abstract

A compound which is

5-((2-(((1-(1H-Tetrazol-5-yl)ethyl)(methyl)amino)methyl)-4-chloro-5-((3′-(3-((R)-3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((2-(((2-(1H-Tetrazol-5-yl)propyl)(methyl)amino)methyl)-4-chloro-5-((3′-(3-((R)-3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((4-Chloro-5-((3′-(3-((R)-3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((2-(5-oxo-2,5-dihydro-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-methyl)phenoxy)methyl)nicotinonitrile,
5-((2-(((2-(1H-Tetrazol-5-yl)propyl)amino)methyl)-4-chloro-5-((3′-(3-((R)-3-hydroxy-pyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)-nicotinonitrile,
2-((5-Chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((5-cyanopyridin-3-yl)methoxy)benzyl)amino)-2-(3,5-dimethyl-1H-pyrazol-4-yl)acetic acid,
2-((5-Chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((5-cyanopyridin-3-yl)methoxy)benzyl)amino)-2-(1-methyl-1H-pyrazol-4-yl)acetic acid,
5-((4-Chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((3-(hydroxymethyl)-1-methyl-1,3a,4,6,7,7a-hexahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
5-((2-(((1-(1H-Tetrazol-5-yl)ethyl)(methyl)amino)methyl)-4-chloro-5-((3′-(3-(((S)-2,3-dihydroxypropyl)amino)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-phenoxy)methyl)nicotinonitrile,
5-((2-(((2-(1H-Tetrazol-5-yl)propyl)(methyl)amino)methyl)-4-chloro-5-((3′-(3-(((S)-2,3-dihydroxy-propyl)amino)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-phenoxy)methyl)nicotinonitrile,
5-((2-(((1-(1H-Tetrazol-5-yl)ethyl)(methyl)amino)methyl)-4-chloro-5-((2′-chloro-3′-(3-(((S)-2,3-dihydroxypropyl)amino)propoxy)-2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-phenoxy)methyl)-nicotinonitrile,
5-((2-(((2-(1H-Tetrazol-5-yl)propyl)(methyl)amino)methyl)-4-chloro-5-((2′-chloro-3′-(3-(((S)-2,3-dihydroxypropyl)amino)propoxy)-2-methyl-[1,1′-biphenyl]-3-yl)methoxy)-phenoxy)methyl)nicotinonitrile,
N-(1-(3-((3′-((4-(((1-(1H-Tetrazol-5-yl)ethyl)(methyl)amino)methyl)-2-chloro-5-((5-cyanopyridin-3-yl)methoxy)phenoxy)methyl)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)oxy)-propyl)piperidin-4-yl)acetamide,
N-(1-(3-((3′-((4-(((1-(1H-Tetrazol-5-yl)ethyl)amino)methyl)-2-chloro-5-((5-cyanopyridin-3-yl)methoxy)phenoxy)methyl)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)oxy)propyl)piperidin-4-yl)acetamide,
N-(1-(3-((3′-((4-(((2-(2H-Tetrazol-5-yl)propyl)(methyl)amino)methyl)-2-chloro-5-((5-cyanopyridin-3-yl)methoxy)phenoxy)methyl)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)oxy)-propyl)piperidin-4-yl)acetamide,
(R)-4-(((5-chloro-4-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((5-methyl-1H-imidazol-4-yl)methoxy)benzyl)amino)methyl)pyrimidine-2-carbonitrile,
N-(1-(3-((3′-((4-(((2-(1H-Tetrazol-5-yl)propyl)amino)methyl)-2-chloro-5-((5-cyano-pyridin-3-yl)methoxy)phenoxy)methyl)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)oxy)propyl)-piperidin-4-yl)acetamide,
(R)-4-(((5-chloro-4-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((5-methyl-1-trityl-1H-imidazol-4-yl)methoxy)benzyl)amino)methyl)pyrimidine-2-carbonitrile,
(R)-1-(3-((3′-((4-((((1H-imidazol-2-yl)methyl)amino)methyl)-2-chloro-5-(pyrimidin-5-ylmethoxy)phenoxy)methyl)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)oxy)propyl)pyrrolidin-3-ol,
(R)-1-(3-((3′-((4-((((1H-pyrazol-4-yl)methyl)amino)methyl)-2-chloro-5-(pyrimidin-5-ylmethoxy)phenoxy)methyl)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)oxy)propyl)pyrrolidin-3-ol,
N-((1H-pyrazol-4-yl)methyl)-1-(5-chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-(pyridazin-3-ylmethoxy)phenyl)methanamine,
N-((1H-imidazol-2-yl)methyl)-1-(5-chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-(pyridazin-3-ylmethoxy)phenyl)methanamine,
N-((1H-pyrazol-4-yl)methyl)-1-(5-chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-methoxyphenyl)methanamine,
N-((1H-imidazol-2-yl)methyl)-1-(5-chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-methoxyphenyl)methanamine,
N-(5-chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-(pyrazin-2-ylmethoxy)benzyl)-1-(pyridazin-3-yl)methanamine,
N-(5-chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-(pyrazin-2-ylmethoxy)benzyl)-1-(pyrimidin-2-yl)methanamine,
N-((1H-imidazol-4-yl)methyl)-1-(5-chloro-4-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-(pyrazin-2-ylmethoxy)phenyl)methanamine,
((R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((2-methyl-6,7-dihydrothiazolo[5,4-c]pyridin-5 (4H)yl)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-2-(((2-(5-chloro-1H-benzo[d]imidazol-2-yl)ethyl)amino)methyl)-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
(R)-5-((2-(((benzo[d]thiazol-2-ylmethyl)amino)methyl)-4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
(R)-5-((2-(((benzo[d]thiazol-2-ylmethyl)(methyl)amino)methyl)-4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((((1-methyl-1H-indazol-3-yl)methyl)amino)methyl)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((3′-(3-((R)-3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-(((4,5,6,7-tetrahydro-1H-indazol-5-yl)amino)methyl)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((3′-(3-((R)-3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((methyl (4,5,6,7-tetrahydro-1H-indazol-5-yl)amino)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-(((imidazo[1,5-a]pyridin-3-ylmethyl)amino)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((1-phenyl-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)-2-((1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl)methyl)phenoxy)methyl)nicotinonitrile,
(R)-5-((4-chloro-2-((((4,5-diethyl-1H-imidazol-2-yl)methyl)(2-methoxyethyl)amino)methyl)-5-((3′-(3-(3-hydroxypyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl)methyl)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]12yridine-6-yl)methyl)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridin-5-yl)methyl)phenoxy)methyl)nicotinonitrile,
5-((2-(((2-(1H-benzo[d]imidazol-2-yl)ethyl)amino)methyl)-4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((2-methyl-6,7-dihydrothiazolo[5,4-c]pyridin-5 (4H)-yl)methyl)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-(((4,5,6,7-tetrahydro-1H-indazol-5-yl)amino)methyl)phenoxy)methyl)nicotinonitrile,
5-((2-(((benzo[d]thiazol-2-ylmethyl)amino)methyl)-4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-((((6-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)amino)methyl)phenoxy)methyl)nicotinonitrile,
5-((2-(((2-(1,2,4-oxadiazol-3-yl)propan-2-yl)amino)methyl)-4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)-2-(((imidazo[1,5-a]pyridin-3-ylmethyl)amino)methyl)phenoxy)methyl)nicotinonitrile,
5-((2-(((2-(1,2,4-oxadiazol-3-yl)propan-2-yl-1,1,1,3,3,3-d6)amino)methyl)-4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((2-(((3-(benzyloxy)-1-(1,2,4-oxadiazol-3-yl)cyclobutyl)amino)methyl)-4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)nicotinonitrile,
5-((2-((2-(1H-Pyrazol-4-yl)piperidin-1-yl)methyl)-4-chloro-5-((3′-(3-((R)-3-hydroxy-pyrrolidin-1-yl)propoxy)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)-nicotinonitrile,
5-((2-((2-(1H-Pyrazol-4-yl)piperidin-1-yl)methyl)-4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)-nicotinonitrile, or
5-((2-((2-(1H-Pyrazol-3-yl)piperidin-1-yl)methyl)-4-chloro-5-((2′-chloro-2-methyl-3′-((1-methylpiperidin-3-yl)methoxy)-[1,1′-biphenyl]-3-yl)methoxy)phenoxy)methyl)-nicotinonitrile,
or a pharmaceutically acceptable salt thereof.

55 more elements

Facts

Application

17/766,483Filed 1 Oct 2020 · us provisional application

Priority

4 Oct 2019

Published

US 2024/0124417 A118 Apr 2024

Granted

25 Aug 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61K 31/4439
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/4545
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/497
Non-condensed pyrazines: containing further heterocyclic rings