US 12,338,256 B2
Aza-tetracyclic oxazepine compounds and uses thereof
Matthew Leo Landry, South San Francisco, CA (US); Christian Nilewski, South San Francisco, CA (US); Michael Siu, South San Francisco, CA (US); Elisia Villemure, South San Francisco, CA (US); BinQing Wei, South San Francisco, CA (US); Steven Do, South San Francisco, CA (US); Lewis John Gazzard, South San Francisco, CA (US); and Samantha Alyson Green, South San Francisco, CA (US)
Assigned to GENENTECH, INC., South San Francisco, CA (US)
Filed by Genentech, Inc., South San Francisco, CA (US)
Filed on May 28, 2024, as Appl. No. 18/676,200.
Application 18/676,200 is a continuation of application No. PCT/US2023/022914, filed on May 19, 2023.
Claims priority of provisional application 63/343,959, filed on May 19, 2022.
Prior Publication US 2024/0368186 A1, Nov. 7, 2024
Int. Cl. C07D 519/00 (2006.01); A61K 31/553 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01); C07D 498/22 (2006.01)
CPC C07D 519/00 (2013.01) [A61K 31/553 (2013.01); A61K 45/06 (2013.01); A61P 35/00 (2018.01); C07D 498/22 (2013.01)] 28 Claims
 
1. A compound of formula (I):

OG Complex Work Unit Chemistry
or an atropisomer, or pharmaceutically acceptable salt thereof,
wherein:
X is NR6;
m is 1 or 2;
n is 1 or 2;
wherein n and m together make a 6- or 7-membered ring Ring A;
p is 0, 1, or 2;
R1 is (E2) or (E3)

OG Complex Work Unit Chemistry
each R7A is independently hydrogen, halogen, unsubstituted C1-3 alkyl or unsubstituted C1-3 haloalkyl; wherein at least one R7A is unsubstituted C1-3 haloalkyl;
L1 is RL1-substituted or unsubstituted C1-4 alkylene;
RL1 is halogen or unsubstituted C1-3 alkyl, or two RL1 together form an unsubstituted C3-4 cycloalkyl;
R2 is R9-substituted or unsubstituted 4-10 membered heterocycle comprising one or more heteroatoms selected from N, S, and O;
each R9 is independently halogen, CN, OH, OCF3, OCHF2, OCH2F, R10-substituted or unsubstituted C1-3 alkyl, R10-substituted or unsubstituted C1-3 haloalkyl, unsubstituted C1-3 alkoxy, R10-substituted or unsubstituted C1-3 alkylidene, R10-substituted or unsubstituted C3-4 cycloalkyl, or R10-substituted or unsubstituted 3 or 4-membered heterocycle;
or two R9 together form an R10-substituted or unsubstituted C3-5 cycloalkyl or an R10-substituted or unsubstituted C3-5 heterocycle comprising one or more oxygen atoms;
or two R9 together form a bridge between two carbon atoms of the heterocycle, wherein the bridge comprises 1-3 carbons;
each R10 is independently hydrogen, oxo, CN, halogen, or C1-3 unsubstituted alkyl;
R3 is hydrogen, —CN, halogen, unsubstituted C1-3 alkyl, or unsubstituted cyclopropyl;
one R4 is hydrogen and one R4 is methyl;
each R5 is independently halogen, oxo, unsubstituted C1-3 alkyl, or unsubstituted C1-3 haloalkyl;
or two R5 together form a bridge between two carbon atoms of Ring A, wherein the bridge comprises 1-3 carbons and optionally one heteroatom selected from O and N;
or two R5 together form a bridge between two carbon atoms of Ring A, wherein the bridge comprises one of O or NR11;
R11 is hydrogen, C(O)CH3, or unsubstituted C1-3 alkyl; and
R6 is hydrogen.