US 12,421,197 B2
Aminopyrazine derivatives as PI3K-γ inhibitors
Brent Douty, Fallowfield, PA (US); Yanran Ai, West Chester, PA (US); David M. Burns, Plymouth Meeting, PA (US); Andrew P. Combs, Kennett Square, PA (US); Nikoo Falahatpisheh, Wilmington, DE (US); Daniel Levy, Philadelphia, PA (US); Padmaja Polam, Kennett Square, PA (US); Lixin Shao, Wilmington, DE (US); Stacey Shepard, Wilmington, DE (US); Artem Shvartsbart, Kennett Square, PA (US); Eddy W. Yue, Landenberg, PA (US); and Andrew W. Buesking, Wilmington, DE (US)
Assigned to Incyte Corporation, Wilmington, DE (US)
Filed by Incyte Corporation, Wilmington, DE (US)
Filed on May 24, 2021, as Appl. No. 17/328,240.
Application 17/328,240 is a continuation of application No. 16/458,530, filed on Jul. 1, 2019, granted, now 11,046,658.
Claims priority of provisional application 62/693,247, filed on Jul. 2, 2018.
Claims priority of provisional application 62/693,196, filed on Jul. 2, 2018.
Claims priority of provisional application 62/693,145, filed on Jul. 2, 2018.
Claims priority of provisional application 62/693,234, filed on Jul. 2, 2018.
Prior Publication US 2022/0411383 A1, Dec. 29, 2022
Int. Cl. C07D 241/20 (2006.01); C07D 401/04 (2006.01); C07D 401/14 (2006.01); C07D 403/04 (2006.01); C07D 403/06 (2006.01); C07D 403/12 (2006.01); C07D 403/14 (2006.01); C07D 405/12 (2006.01); C07D 413/04 (2006.01); C07D 417/04 (2006.01); C07D 471/04 (2006.01); C07D 471/06 (2006.01); C07D 487/04 (2006.01)
CPC C07D 241/20 (2013.01) [C07D 401/04 (2013.01); C07D 401/14 (2013.01); C07D 403/04 (2013.01); C07D 403/06 (2013.01); C07D 403/12 (2013.01); C07D 403/14 (2013.01); C07D 405/12 (2013.01); C07D 413/04 (2013.01); C07D 417/04 (2013.01); C07D 471/04 (2013.01); C07D 471/06 (2013.01); C07D 487/04 (2013.01)] 28 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof; wherein:
X1 is N or CR1;
R1 is selected from H, D, halo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 haloalkoxy, CN, OH and NH2;
R2 is a C1-6 haloalkyl, wherein each halogen is independently selected from F and Cl;
R3 is selected from H, D, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and NH2;
R3″ is selected from H, D, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and NH2;
or, alternatively, R3 and R3″ together form an oxo group;
R4, R5 and R6 are each independently selected from H, D, halo, CN, OH, NH2, and C1-6 alkyl;
R7 is selected from C6-14 aryl and 5-14 membered heteroaryl, wherein the C6-14 aryl and 5-14 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 independently selected R7A substituents;
R8 and R9 are each independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and;
provided that either: (a) R3 and R3″ together form an oxo group; or (b) R8 is C(O)Rb8;
each R7A is independently selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, NO2, ORa71, SRa71, NHORa71, C(O)Rb71, C(O)NRc71Rd71, and BRj71Rk71, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl, of R7A are each optionally substituted with 1, 2, 3 or 4 independently selected R7B substituents;
each Ra71, Rb71, Rc71, and Rd71 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl
each Rj71 and Rk71 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
or any Rj71 and Rk71 attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C1-6 alkyl and C1-6 haloalkyl;
each R7B is independently selected from D, halo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, NO2, ORa72, and SRa72;
each Ra72 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; and
each Rb8 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.
 
21. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.