	US 12,378,243 B2
	Quinoline compounds as inhibitors of KRAS
Qinda Ye, Claymont, DE (US); Matthew McCammant, West Chester, PA (US); Rocco Policarpo, Wilmington, DE (US); Artem Shvartsbart, Wilmington, DE (US); Wenyu Zhu, Wilmington, DE (US); Jeremy Roach, Philadelphia, PA (US); Gia Hoang, Wilmington, DE (US); Bin Hu, Garnet Valley, PA (US); Gencheng Li, Claymont, DE (US); Robert Susick, Wilmington, DE (US); Padmaja Polam, Kennett Square, PA (US); Fenglei Zhang, Berwyn, PA (US); Chao Qi, Wilmington, DE (US); Xiaozhao Wang, Mt. Laurel, NJ (US); Wenqing Yao, Wilmington, DE (US); Alexander Sokolsky, Wilmington, DE (US); Haolin Yin, Wilmington, DE (US); Le Zhao, Wilmington, DE (US); and Peter Carlsen, Wilmington, DE (US)
Assigned to Incyte Corporation, Wilmington, DE (US)
Filed by Incyte Corporation, Wilmington, DE (US)
Filed on Feb. 9, 2024, as Appl. No. 18/437,502.
Application 18/437,502 is a division of application No. 18/046,303, filed on Oct. 13, 2022, granted, now 11,939,328.
Claims priority of provisional application 63/368,563, filed on Jul. 15, 2022.
Claims priority of provisional application 63/363,270, filed on Apr. 20, 2022.
Claims priority of provisional application 63/279,464, filed on Nov. 15, 2021.
Claims priority of provisional application 63/255,610, filed on Oct. 14, 2021.
Prior Publication US 2024/0368152 A1, Nov. 7, 2024
Int. Cl. A61K 31/4745 (2006.01); A61P 35/00 (2006.01); C07D 471/04 (2006.01)

CPC C07D 471/04 (2013.01) [A61K 31/4745 (2013.01); A61P 35/00 (2018.01)]

34 Claims

1. A method of inhibiting KRAS activity, said method comprising contacting a compound selected from

3-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-2-((1R,3R,5R)-2-(cyclopropanecarbonyl)-2-azabicyclo[3.1.0]hexan-3-yl)-7-(2,3-dichlorophenyl)-6-fluoro-4-methyl-1H-pyrrolo[3,2-c]quinolin-8-yl)propanenitrile;

methyl (1S,3R,5S)-3-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-7-(2,3-dichlorophenyl)-4-(6-(dimethylcarbamoyl)pyridin-3-yl)-6-fluoro-1H-pyrrolo[3,2-c]quinolin-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate;

methyl (1R,3R,5R)-3-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-7-(2,3-dichlorophenyl)-4-(6-(dimethylcarbamoyl)pyridin-3-yl)-6-fluoro-1H-pyrrolo[3,2-c]quinolin-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate;

3-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(2,3-dichlorophenyl)-6-fluoro-4-(1-hydroxyethyl)-2-((1R,3R,5R)-2-(1-methylcyclopropane-1-carbonyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-pyrrolo[3,2-c]quinolin-8-yl)propanenitrile;

3-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(2,3-dichlorophenyl)-6-fluoro-2-((1R,3R,5R)-2-(1-fluorocyclopropane-1-carbonyl)-2-azabicyclo[3.1.0]hexan-3-yl)-4-(1-hydroxyethyl)-1H-pyrrolo[3,2-c]quinolin-8-yl)propanenitrile;

3-(1-((1R,4R,5S)-2-azabicyclo[2.1.1]hexan-5-yl)-7-(2,3-dichlorophenyl)-6-fluoro-2-((1R,3R,5R)-2-(1-fluorocyclopropane-1-carbonyl)-2-azabicyclo[3.1.0]hexan-3-yl)-4-methyl-1H-pyrrolo[3,2-c]quinolin-8-yl)propanenitrile;

or a pharmaceutically acceptable salt thereof;

with KRAS.