US 12,201,636 B2
Heterocyclylamines as PI3K inhibitors
Yun-Long Li, Chadds Ford, PA (US); Wenqing Yao, Chadds Ford, PA (US); Andrew P. Combs, Kennett Square, PA (US); Eddy W. Yue, Landenberg, PA (US); Song Mei, Wilmington, DE (US); Joseph Glenn, Mount Royal, NJ (US); Thomas P. Maduskuie, Jr., Wilmington, DE (US); and Chunhong He, Boothwyn, PA (US)
Assigned to Incyte Corporation, Wilmington, DE (US); and Incyte Holdings Corporation, Wilmington, DE (US)
Filed by Incyte Corporation, Wilmington, DE (US); and Incyte Holdings Corporation, Wilmington, DE (US)
Filed on Oct. 3, 2023, as Appl. No. 18/376,346.
Application 18/376,346 is a continuation of application No. 17/866,942, filed on Jul. 18, 2022, granted, now 11,819,505.
Application 17/866,942 is a continuation of application No. 16/828,315, filed on Mar. 24, 2020, granted, now 11,433,071, issued on Sep. 6, 2022.
Application 16/828,315 is a continuation of application No. 16/446,098, filed on Jun. 19, 2019, granted, now 10,646,492, issued on May 12, 2020.
Application 16/446,098 is a continuation of application No. 16/112,160, filed on Aug. 24, 2018, granted, now 10,376,513, issued on Aug. 13, 2019.
Application 16/112,160 is a continuation of application No. 15/673,529, filed on Aug. 10, 2017, granted, now 10,092,570, issued on Oct. 9, 2018.
Application 15/673,529 is a continuation of application No. 14/872,881, filed on Oct. 1, 2015, granted, now 9,730,939, issued on Aug. 15, 2017.
Application 14/872,881 is a continuation of application No. 13/601,349, filed on Aug. 31, 2012, granted, now 9,199,982, issued on Dec. 1, 2015.
Claims priority of provisional application 61/677,445, filed on Jul. 30, 2012.
Claims priority of provisional application 61/594,882, filed on Feb. 3, 2012.
Claims priority of provisional application 61/530,866, filed on Sep. 2, 2011.
Prior Publication US 2024/0216377 A1, Jul. 4, 2024
Int. Cl. A61K 31/519 (2006.01); A61P 29/00 (2006.01); C07D 471/04 (2006.01); C07D 487/04 (2006.01); C07D 519/00 (2006.01)
CPC A61K 31/519 (2013.01) [A61P 29/00 (2018.01); C07D 471/04 (2013.01); C07D 487/04 (2013.01); C07D 519/00 (2013.01)] 8 Claims
 
1. A compound of the following formula:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
R2 is halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, phenyl, or 5-6 membered heteroaryl; wherein said phenyl and 5-6 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 substituents independently selected from halo, OH, CN, C1-4 alkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
R4 is H, halo, OH, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, or C1-4 haloalkoxy;
R5 is halo, OH, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, or cyclopropyl;
each R3b is independently selected from Cy1, —(C1-3 alkylene)-Cy1, halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, ORa1, SRa1, C(═O) Rb1, C(═O)NRc1Rd1, C(═O)ORa1, OC(═O)Rb1, OC(═O)NRc1Rd1, NRc1Rd1, NRc1C(═O)Rb1, NRc1C(═O)ORb1, NRc1C(═O)NRc1Rd1, C(═NRe)Rb1, C(═NRe)NRc1Rd1, NRc1C(═NRe)NRc1Rd1, NRc1S(═O)ORb1, NRc1S(═O)2NRc1Rd1, S(═O)Rb1, S(═O)2Rb1, and S(═O)2NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl are each optionally substituted with 1, 2, or 3 independently selected R11 groups;
each Re is independently selected from H, CN, OH, C1-4 alkyl, and C1-4 alkoxy;
each Cy1 is independently selected from C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl, each of which is optionally substituted with 1, 2, 3, or 4 independently selected R11 groups;
each Ra1, Rb1, Rc1, and Rd1 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl are each optionally substituted with 1, 2, or 3 independently selected R11 groups;
or Rc1 and Rd1 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7 membered heterocycloalkyl group, which is optionally substituted with —OH or C1-3 alkyl; and
each R11 is independently selected from OH, NO2, CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-C1-3 alkyl, HO—C1-3 alkyl, C1-3 alkoxy-C1-3 alkyl, C3-7 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(C1-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-4 alkoxycarbonyl, C1-3 alkylcarbonylamino, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(C1-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(C1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(C1-3 alkyl)aminocarbonylamino.