US 12,403,135 B2
4H-pyrrolo[3,2-c]pyridin-4-one derivatives
Franziska Siegel, Cambridge, MA (US); Daniel Korr, Berlin (DE); Jens Schröder, Berlin (DE); Stephan Siegel, Berlin (DE); Heidi Greulich, Cambridge, MA (US); Bethany Kaplan, Cambridge, MA (US); and Matthew Meyerson, Boston, MA (US)
Assigned to Bayer Aktiengesellschaft, Leverkusen (DE); The Broad Institute, Inc., Cambridge, MA (US); and Dana-Farber Cancer Institute, Inc., Boston, MA (US)
Appl. No. 17/605,990
Filed by Bayer Aktiengesellschaft, Leverkusen (DE); The Broad Institute, Inc., Cambridge, MA (US); and Dana-Farber Cancer Institute, Inc., Boston, MA (US)
PCT Filed Apr. 22, 2020, PCT No. PCT/EP2020/061167
§ 371(c)(1), (2) Date Oct. 22, 2021,
PCT Pub. No. WO2020/216774, PCT Pub. Date Oct. 29, 2020.
Claims priority of provisional application 62/838,104, filed on Apr. 24, 2019.
Prior Publication US 2022/0378762 A1, Dec. 1, 2022
Int. Cl. A61P 35/00 (2006.01); A61K 31/444 (2006.01); A61K 31/4545 (2006.01); A61K 31/5377 (2006.01); A61K 38/17 (2006.01); A61K 45/06 (2006.01); C07D 471/04 (2006.01)
CPC A61K 31/444 (2013.01) [A61K 31/4545 (2013.01); A61K 31/5377 (2013.01); A61K 38/179 (2013.01); A61K 45/06 (2013.01); A61P 35/00 (2018.01); C07D 471/04 (2013.01)] 16 Claims
 
1. A method of treating cancer in a subject, wherein the cancer harbors a mutant EGFR with an exon 19 and/or 21 mutation, the method comprising administering to the subject an effective amount to a contact a cancer cell harboring the mutant EGFR with a compound of formula (I)

OG Complex Work Unit Chemistry
in which:
R1 represents methyl, ethyl, trifluoromethyl, 2,2-difluoroethyl, cyano, bromo, methoxy, or difluoromethoxy, or
with the proviso that when R1 is chloro, then R2 represents hydrogen or chloro and R3 and R4 represent hydrogen;
R2 represents hydrogen, methyl, fluoro, chloro or bromo;
R3 represents hydrogen or fluoro;
R4 represents hydrogen or fluoro, wherein at least one of R3 and R4 represents hydrogen;
R5 represents C2-C5-alkyl,
which is substituted once with hydroxy, C1-C4-alkoxy, R7R8N—, or phenyl, or R6—CH2—,
wherein said phenyl groups are optionally substituted one or more times, independently of each other, with R′;
R′ represents, independently of each other, hydroxy, halogen, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl or C1-C4-haloalkoxy;
R6 represents a group selected from the group:

OG Complex Work Unit Chemistry
wherein * indicates the point of attachment of said group with the rest of the molecule;
R7, R8 represent, independently of each other, C1-C3-alkyl, C1-C3-haloalkyl or
R7 and R8 together with the nitrogen atom to which they are attached form a 5- to 6-membered nitrogen containing heterocyclic ring, optionally containing one additional heteroatom or heteroatom containing group selected from O and NR10;
R9 represents hydrogen, C1-C3-alkyl or C1-C3-haloalkyl;
R10 represents hydrogen or C1-C3-alkyl;
or an N-oxide, a salt, a tautomer or a stereoisomer of said compound, or a salt of said N-oxide, tautomer or stereoisomer.