US 11,731,984 B2
KRas G12C inhibitors
Serge Louis Boulet, Fishers, IN (US); Kevin Charles Fortner, Indianapolis, IN (US); Deqi Guo, Carmel, IN (US); David Michael Hyman, Westport, CT (US); Sheng-Bin Peng, Carmel, IN (US); and Chong Si, Zionsville, IN (US)
Assigned to Eli LIlly and Company, Indianapolis, IN (US)
Filed by Eli Lilly and Company, Indianapolis, IN (US)
Filed on Dec. 4, 2020, as Appl. No. 17/111,676.
Claims priority of provisional application 62/946,586, filed on Dec. 11, 2019.
Prior Publication US 2021/0179633 A1, Jun. 17, 2021
Int. Cl. A61K 39/00 (2006.01); C07D 498/04 (2006.01); A61P 35/00 (2006.01); A61K 33/243 (2019.01); A61K 31/4985 (2006.01); A61K 31/506 (2006.01); A61K 31/517 (2006.01); A61K 31/519 (2006.01); A61K 31/5377 (2006.01); A61K 31/553 (2006.01); A61K 31/555 (2006.01); A61K 39/395 (2006.01); C07D 487/04 (2006.01)
CPC C07D 498/04 (2013.01) [A61K 31/4985 (2013.01); A61K 31/506 (2013.01); A61K 31/517 (2013.01); A61K 31/519 (2013.01); A61K 31/5377 (2013.01); A61K 31/553 (2013.01); A61K 31/555 (2013.01); A61K 33/243 (2019.01); A61K 39/3955 (2013.01); A61P 35/00 (2018.01); C07D 487/04 (2013.01)] 23 Claims
 
1. A compound of the formula:

OG Complex Work Unit Chemistry
wherein:
A is —OCH2—, —N(R6)CH2—, —OCH2CH2—, —N(R6)CH2CH2—, —CH2OCH2—, or —CH2N(R6)CH2—;
B is —CH2— or —C(O)—,
Y is —C(CN)— or —N—;
R1 is —CN, —C(O)C≡CR8, or a group of the formula

OG Complex Work Unit Chemistry
R2 is H, methyl, or —CH2CN;
R3 and R5 are each independently H, halogen, —C0-3 alkyl-cyclopropyl, —C1-6 alkyl optionally substituted 1-3 times with R10, or —O—C1-6 alkyl optionally substituted 1-3 times with R10;
R4 is H, halogen, or —C1-6 alkyl optionally substituted 1-3 times with R10;
R6 is H or —C1-6 alkyl optionally substituted 1-3 times with R10;
R7 is H, halogen, —NR11R12, —CH2NR11R12, —C1-6 alkyl optionally substituted 1-3 times with R10 or R13, —C0-3 alkyl cyclopropyl, or —O—C1-6 alkyl optionally substituted 1-3 times with R10 or R13;
R8 is H, —C1-4 alkyl optionally substituted 1-3 times with R10, or —C3-6 cycloalkyl optionally substituted 1-3 times with R10;
R9 is H, halogen, —CN, —C0-3 alkyl-C3-6 cycloalkyl, or —C1-6 alkyl optionally substituted 1-3 times with R10;
R10 is independently at each occurrence halogen, oxygen, hydroxy, —C1-4 alkyl, or —O—C1-4 alkyl;
R11 and R12 are each independently H, —C1-4 alkyl, or —C1-4 heteroalkyl, wherein R11 and R12 may combine to form a cycloheteroalkyl; and
R13 is independently at each occurrence —N—C1-4 alkyl,
or a pharmaceutically acceptable salt thereof.