US 12,240,846 B2
5- and 6-azaindole compounds for inhibition of Bcr-Abl tyrosine kinases
Joseph P. Lyssikatos, Boulder, CO (US); Samuel Kintz, Boulder, CO (US); and Li Ren, Superior, CO (US)
Assigned to Enliven Inc., Boulder, CO (US)
Filed by Enliven Inc., Boulder, CO (US)
Filed on Aug. 11, 2023, as Appl. No. 18/233,259.
Application 18/233,259 is a continuation of application No. 18/080,641, filed on Dec. 13, 2022, granted, now 11,807,638.
Application 18/080,641 is a continuation of application No. 17/493,380, filed on Oct. 4, 2021, granted, now 11,767,321.
Claims priority of provisional application 63/224,236, filed on Jul. 21, 2021.
Claims priority of provisional application 63/087,763, filed on Oct. 5, 2020.
Prior Publication US 2023/0382907 A1, Nov. 30, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 471/04 (2006.01); C07D 519/00 (2006.01)
CPC C07D 471/04 (2013.01) [C07D 519/00 (2013.01)] 14 Claims
 
1. A compound of formula (I-A):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
X is NR3′ or CR3,
Y is NR2 or CR4,
wherein when X is NR3′, then Y is CR4, Y has a double bond to CR5, and X has a single bond to CR5; or when X is CR3, then Y is NR2, Y has a single bond to CR5, and X has a double bond to CR5;
m is an integer from 0 to 3;
each R1 is independently -D, —F, C1-C3 alkyl, C1-C3 alkylene-NR7R8, C1-C3 alkylene-NR7′R8′, C1-C3 alkylene-OH, C1-C3 alkylene-CN, C1-C2 alkylene-(C3-C6 cycloalkylene)-(C0-C2 alkylene)-NR7R8, C1-C2 alkylene-(C3-C6 cycloalkylene)-(C0-C2 alkylene)-NR7′R8′, C1-C2 alkylene-(C3-C6 cycloalkylene)-(C0-C2 alkylene)-OH, C1-C2 alkylene-(4 to 8-membered heterocycloalkylene)-(C0-C2 alkylene)-NR7R8, C1-C2 alkylene-(4 to 8-membered heterocycloalkylene)-(C0-C2 alkylene)-NR7′R8′, C1-C2 alkylene-(C3-C7 heterocycloalkylene)-(C0-C2 alkylene)-NR7R8, or C1-C2 alkylene-(C3-C7 heterocycloalkylene)-(C0-C2 alkylene)-NR7′R8′, wherein the alkyl, alkylene, cycloalkylene, and heterocycloalkylene moieties in R1 are optionally substituted with 1-3 fluorine atoms and/or 1-6 deuterium atoms, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3 alkyl, C3-C6 cycloalkyl, C2-C3 haloalkyl, C2-C3 alkylene-CN, or C2-C3 heteroalkyl;
R2 is C1-C3 alkyl or C3-C6 cycloalkyl, wherein said C1-C3 alkyl is optionally substituted with 1-3 fluorine atoms and/or 1-6 deuterium atoms;
R3 is —H, C3-C6 cycloalkyl, halogen, or —CN;
R3′ is —H, —C3-C6 cycloalkyl, or —CN;
R4 is —H, C1-C3 alkyl, or halogen, wherein said C1-C3 alkyl is optionally substituted with 1-3 fluorine atoms and/or 1-6 deuterium atoms;
R5 is C6-C14 aryl optionally substituted with 1-5 R9 groups;
each R7 is independently —H, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkylene-CN, or C1-C6 heteroalkyl;
each R8 is independently —H, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkylene-CN, or C1-C6 heteroalkyl;
each pair of R7 and R8′ taken together with the nitrogen atom to which they are attached independently form a 3- to 8-membered heterocyclic ring, wherein the heterocyclic ring optionally contains an additional 1-2 heteroatoms selected from the group consisting of N, O, and S, and wherein each heterocyclic nitrogen atom, if present, is independently optionally substituted with C1-C3 alkyl, C3-C6 cycloalkyl, C2-C3 haloalkyl, C2-C3 alkylene-CN, or C2-C3 heteroalkyl;
each R9 is independently halogen, —OR10, —NR7R8, C1-C3 alkyl, C1-C3 haloalkyl, C3-C6 cycloalkyl, —CN, S(O)nC1-C3 alkyl, or S(O)nC3-C6 cycloalkyl,
wherein n is an integer from 0 to 2; and
each R10 is independently —H, C1-C3 alkyl, C1-C3 haloalkyl, or C3-C6 cycloalkyl, wherein said C1-C3 alkyl is optionally substituted with hydroxyl, C1-C3 alkoxy, and/or 1-6 deuterium atoms.