US 11,673,894 B2
Imidazopyrimidines and triazolopyrimidines as A2A / A2B inhibitors
Xiaozhao Wang, Mt. Laurel, NJ (US); Pei Gan, Claymont, DE (US); Taisheng Huang, Wilmington, DE (US); Chao Qi, Newark, DE (US); Ding-Quan Qian, Newark, DE (US); Liangxing Wu, Wilmington, DE (US); Wenqing Yao, Chadds Ford, PA (US); Zhiyong Yu, Wilmington, DE (US); Fenglei Zhang, Berwyn, PA (US); Le Zhao, Wilmington, DE (US); and Chunhong He, Wilmington, DE (US)
Assigned to Incyte Corporation, Wilmington, DE (US)
Filed by Incyte Corporation, Wilmington, DE (US)
Filed on Oct. 22, 2020, as Appl. No. 17/77,713.
Application 17/077,713 is a continuation of application No. 16/285,787, filed on Feb. 26, 2019, abandoned.
Claims priority of provisional application 62/793,015, filed on Jan. 16, 2019.
Claims priority of provisional application 62/721,312, filed on Aug. 22, 2018.
Claims priority of provisional application 62/718,216, filed on Aug. 13, 2018.
Claims priority of provisional application 62/635,926, filed on Feb. 27, 2018.
Prior Publication US 2021/0139485 A1, May 13, 2021
Int. Cl. C07D 497/04 (2006.01); C07D 487/04 (2006.01); C07D 491/056 (2006.01); C07D 519/00 (2006.01); A61P 35/00 (2006.01); A61P 25/00 (2006.01); A61P 9/00 (2006.01); A61P 29/00 (2006.01)
CPC C07D 487/04 (2013.01) [A61P 9/00 (2018.01); A61P 25/00 (2018.01); A61P 29/00 (2018.01); A61P 35/00 (2018.01); C07D 491/056 (2013.01); C07D 519/00 (2013.01)] 25 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof; wherein:
X is N;
R1 is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;
R2 is selected from C1-6 alkyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, (4-14 membered heterocycloalkyl)-C1-6 alkyl-, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, and NRc2Rd2, wherein the C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 independently selected RC substituents; and
wherein the C1-6 alkyl of R2 is substituted with 1, 2, 3, 4, or 5 independently selected RC substituent;
Cy1 is 3-cyanophenyl;
Cy2 is C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl, wherein the C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, or 4-14 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected RF substituents;
each Ra2, Rc2, and Rd2 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- of Ra2, Rc2, and Rd2 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected RG substituents;
or any Rc2 and Rd2 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected RG substituents;
each Rb2 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- of Rb2 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected RG substituents;
each RC, RF, and RG is independently selected from D, halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, (4-14 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa4, SRa4, NHORa4, C(O)Rb4, C(O)NRc4Rd4, C(O)NRc4(ORa4), C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4, NRc4NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4C(O)NRc4Rd4, C(═NRe4)Rb4, C(═NRe4)NRc4Rd4, NRc4C(═NRe4)NRc4Rd4, NRc4C(═NRe4)Rb4, NRc4S(O)Rb4, NRc4S(O)NRc4Rd4, NRc4S(O)2Rb4, NRc4S(O)(═NRe4)Rb4, NRc4S(O)2NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, S(O)2NRc4Rd4, OS(O)(═NRe4)Rb4, OS(O)2Rb4, SF5, P(O)Rf4Rg4, OP(O)(ORh4)(ORi4), P(O)(ORh4)(ORi4), and BRj4Rk4, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- of RC, RF, and RG are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected RH substituents;
each Ra4, Rc4, and Rd4 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- of Ra4, Rc4, and Rd4 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected RH substituents;
or, any Rc4 and Rd4 attached to the same N atom, together with the N atom to which they are attached, optionally form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected RH substituents;
each Rb4 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- of Rb4 are each optionally substituted with 1, 2, 3, 4, 5, 6, 7, or 8 independently selected RH substituents;
each Re4 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-;
each Rf4 and Rg4 is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-;
each Rh4 and Ri4 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-;
each Rj4 and Rk4 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
or, any Rj4 and Rk4 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 RH is independently selected from D, halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, (4-14 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa5, SRa5, NHORa5, C(O)Rb5, C(O)NRc5Rd5, C(O)NRc5(ORa5), C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, C(═NRe5)Rb5, C(═NRe5)NRc5Rd5, NRc5C(═NRe5)NRc5Rd5, NRc5C(═NRe5)Rb5, NRc5S(O)Rb5, NRc5S(O)NRc5Rd5, NRc5S(O)2Rb5, NRc5S(O)(═NRe5)Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, S(O)2NRc5Rd5, OS(O)(═NRe5)Rb5, OS(O)2Rb5, SF5, P(O)Rf5Rg5, OP(O)(ORh5)(ORi5), P(O)(ORh5)(ORi5), and BRj5Rk5, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- of RH are each optionally substituted with 1, 2, 3, or 4 independently selected RI substituents;
each Ra5, Rc5, and Rd5 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- of Ra5, Rc5, and Rd5 are each optionally substituted with 1, 2, 3, or 4 independently selected R substituents;
or any Rc5 and Rd5 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R substituents;
each Rb5 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- of Rb5 are each optionally substituted with 1, 2, 3, or 4 independently selected R substituents;
each Re5 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-;
each Rf5 and Rg5 is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-;
each Rh5 and Ri5 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-;
each Rj5 and Rk5 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
or, any Rj5 and Rk5 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 RI is independently selected from D, halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, (4-14 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa6, SRa6, NHORa6, C(O)Rb6, C(O)NRc6Rd6, C(O)NRc6(ORa6), C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6 NRc6NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)ORa6, NRc6C(O)NRc5Rd6, C(═NRe6)Rb6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, NRc6C(═NRe6)Rb6, NRc6S(O)Rb6, NRc6S(O)NRc6Rd6, NRc6S(O)2Rb6, NRc6S(O)(═NRe6)Rb6, NRc6S(O)2NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, S(O)2NRc6Rd6, OS(O)(═NRe6)Rb6, OS(O)2Rb6, SF5, P(O)Rf6Rg6, OP(O)(ORh6)(ORi6), P(O)(ORh6)(ORi6), and BRj6Rk6, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- of RI are each optionally substituted with 1, 2, 3, or 4 independently selected RJ substituents;
each Ra6, Rc6, and Rd6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- of Ra6, Rc6, and Rd6 are each optionally substituted with 1, 2, 3, or 4 independently selected R substituents;
or any Rc6 and Rd6 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R substituents;
each Rb6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- of Rb6 are each optionally substituted with 1, 2, 3, or 4 independently selected R substituents;
each Re6 is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-;
each Rf6 and Rg6 is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-;
each Rh6 and Ri6 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-;
each Rj6 and Rk6 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
or, any Rj6 and Rk6 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 RJ is independently selected from D, halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-, CN, NO2, ORa7, SRa7, NHORa7, C(O)Rb7, C(O)NRc7Rd7, C(O)NRc7(ORa7), C(O)ORa7, OC(O)Rb7, OC(O)NRc7Rd7, NRc7Rd7 NRc7NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)ORa7, NRc7C(O)NRc7Rd7, C(═NRe7)Rb7, C(═NRe7)NRc7Rd7, NRc7C(═NRe7)NRc7Rd7, NRc7C(═NRe7)Rb7, NRc7S(O)Rb7, NRc7S(O)NRc7Rd7, NRc7S(O)2Rb7, NRc7S(O)(═NRe7)Rb7, NRc7S(O)2NRc7Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, S(O)2NRc7Rd7, OS(O)(═NRe7)Rb7, OS(O)2Rb7, SF5, P(O)Rf7Rg7, OP(O)(ORh7)(ORi7), P(O)(ORh7)(ORi7), and BRj7Rk7, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- of RJ are each optionally substituted with 1, 2, 3, or 4 independently selected RK substituents;
each Ra7, Rc7, and Rd7 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- of Ra7, Rc7, and Rd7 are each optionally substituted with 1, 2, 3, or 4 independently selected RK substituents;
or any Rc7 and Rd7 attached to the same N atom, together with the N atom to which they are attached, form a 5- or 6-membered heteroaryl or a 4-14 membered heterocycloalkyl group, wherein the 5- or 6-membered heteroaryl or 4-14 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected RK substituents;
each Rb7 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl- of Rb7 are each optionally substituted with 1, 2, 3, or 4 independently selected RK substituents;
each Re7 is independently selected from H, OH, CN, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, and 4-14 membered heterocycloalkyl;
each Rf7 and Rg7 is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-;
each Rh7 and Ri7 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-;
each Rj7 and Rk7 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;
or, any Rj7 and Rk7 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 RK is independently selected from H, D, OH, halo, oxo, CN, C(O)OH, NH2, NO2, SF5, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-14 aryl, C3-14 cycloalkyl, 5-14 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-14 aryl-C1-6 alkyl-, C3-14 cycloalkyl-C1-6 alkyl-, (5-14 membered heteroaryl)-C1-6 alkyl-, and (4-14 membered heterocycloalkyl)-C1-6 alkyl-; and
wherein any heteroaryl group of any of the above-recited substituents optionally comprises an N-oxide on any ring-forming nitrogen.