	US 11,866,426 B2
	Benzothiazole compounds and uses thereof
Joshua Hummel, Hockessin, DE (US); Oleg Vechorkin, Wilmington, DE (US); Alexander Sokolsky, Philadelphia, PA (US); Qinda Ye, Claymont, DE (US); Kai Liu, Chadds Ford, PA (US); and Wenqing Yao, Chadds Ford, PA (US)
Assigned to Incyte Corporation, Wilmington, DE (US)
Filed by Incyte Corporation, Wilmington, DE (US)
Filed on Nov. 16, 2020, as Appl. No. 17/098,880.
Application 17/098,880 is a continuation of application No. 16/534,039, filed on Aug. 7, 2019, granted, now 10,899,755.
Claims priority of provisional application 62/839,230, filed on Apr. 26, 2019.
Claims priority of provisional application 62/715,890, filed on Aug. 8, 2018.
Prior Publication US 2021/0171518 A1, Jun. 10, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 417/14 (2006.01); A61P 35/00 (2006.01); C07D 487/08 (2006.01); C07D 498/08 (2006.01)

CPC C07D 417/14 (2013.01) [A61P 35/00 (2018.01); C07D 487/08 (2013.01); C07D 498/08 (2013.01)]

41 Claims

1. A method for treating a cancer in a patient, said method comprising: administering to the patient a therapeutically effective amount of a compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

A is N or CR^A;

Cy^Bis selected from C_5-10cycloalkyl, C_6-10aryl, and 5-6 membered heteroaryl; wherein the 5-6 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2 or 3 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-6 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the C_5-10cycloalkyl, C_6-10aryl and 5-6 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R⁷;

R¹is selected from Cy¹, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, CN, NO₂, SR^a1, C(O)R^b1, C(O)OR^a1, OC(O)R^b1, OC(O)NR^c1R^d1, NR^c1R^d1, NR^c1C(O)R^b1, NR^c1C(O)OR^a1, NR^c1C(O)NR^c1R^d1, C(═NR^e1)R^b1, C(═NOR^a1)R^b1, C(═NR^e1)NR^c1R^d1, NR^c1C(═NR^e1)NR^c1R^d1, NR^c1S(O)R^b1, NR^c1S(O)₂R^b1, NR^c1S(O)₂NR^c1R^d1, S(O)R^b1, S(O)NR^c1R^d1, S(O)₂R^b1, S(O)₂NR^c1R^d1, and BR^h1Rⁱ¹; wherein said C_2-6alkenyl and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R¹⁰;

R²is selected from H, D, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, halo, CN, NO₂, OR^f2, SR^f2, C(O)R^b2, C(O)NR^c2R^d2, C(O)OR^a2, OC(O)R^b2, OC(O)NR^c2R^d2, NR^j2R^k2, NR^c2C(O)R^b2, NR^c2C(O)OR^a2, NR^c2C(O)NR^c2R^d2, C(═NR^e2)R^b2, C(═NOR^a2)R^b2, C(═NR^e2)NR^c2R^d2, NR^c2C(═NR^e2)NR^c2R^d2, NR^c2S(O)R^b2, NR^c2S(O)₂R^b2, NR^c2S(O)₂NR^c2R^d2, S(O)R^b2, S(O)NR^c2R^d2, S(O)₂R^b2, S(O)₂NR^c2R^d2, and BR^h2Rⁱ²; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R¹³;

R³is selected from H, D, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-6cycloalkyl, 4-6 membered heterocycloalkyl, halo, CN, NO₂, OR^a3, SR^a3, C(O)R^b3, C(O)NR^c3R^d3, C(O)OR^a3, OC(O)R^b3, OC(O)NR^c3R^d3, NR^c3R^d3, NR^c3C(O)R^b3, NR^c3C(O)OR^a3, NR^c3C(O)NR^c3R^d3, NR^c3S(O)R^b3, NR^c3S(O)₂R^b3, NR^c3S(O)₂NR^c3R^d3, S(O)R^b3, S(O)NR^c3R^d3, S(O)₂R^b3, S(O)₂NR^c3R^d3, and BR^h3Rⁱ³; wherein said C_1-6alkyl, C_2-6alkenyl and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

R⁴is selected from H, D, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-6cycloalkyl, 4-6 membered heterocycloalkyl, halo, CN, NO₂, OR^a4, SR^a4, C(O)R^b4, C(O)NR^c4R^d4, C(O)OR^a4, OC(O)R^b4, OC(O)NR^c4R^d4, NR^c4R^d4, NR^c4C(O)R^b4, NR^c4C(O)OR^a4, NR^c4C(O)NR^c4R^d4, NR^c4S(O)R^b4, NR^c4S(O)₂R^b4, NR^c4S(O)₂NR^c4R^d4, S(O)R^b4, S(O)NR^c4R^d4, S(O)₂R^b4, S(O)₂NR^c4R^d4, and BR^h4Rⁱ⁴; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

R⁵is selected from H, D, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, halo, CN, NO₂, OR^a5, SR^a5, C(O)R^b5, C(O)NR^c5R^d5, C(O)OR^a5, OC(O)R^b5, OC(O)NR^c5R^d5, NR^c5R^d5, NR^c5C(O)R^b5, NR^c5C(O)OR^a5, NR^c5C(O)NR^c5R^d5, NR^c5S(O)R^b5, NR^c5S(O)₂R^b5, NR^c5S(O)₂NR^c5R^d5, S(O)R^b5, S(O)NR^c5R^d5, S(O)₂R^b5, S(O)₂NR^c5R^d5, and BR^h5Rⁱ⁵; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

R⁶is selected from H, D, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, CN, NO₂, OR^a6, C(O)R^b6, C(O)NR^c6R^d6, C(O)OR^a6, OC(O)R^b6, OC(O)NR^c6R^d6, NR^c6C(O)R^b6, NR^c6C(O)OR^a6, NR^c6C(O)NR^c6R^d6, NR^c6S(O)R^b6, NR^c6S(O)₂R^b6, NR^c6S(O)₂NR^c6R^d6, S(O)R^b6, S(O)NR^c6R^d6, S(O)₂R^b6, S(O)₂NR^c6R^d6, and BR^h6Rⁱ⁶; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R⁷is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, 5-10 membered heteroaryl, C_3-10cycloalkyl-C_1-3alkylene, 4-10 membered heterocycloalkyl-C_1-3alkylene, C_6-10aryl-C_1-3alkylene, 5-10 membered heteroaryl-C_1-3alkylene, halo, D, CN, NO₂, OR^a7, SR^a7, C(O)R^b7, C(O)NR^c7R^d7, C(O)OR^a7, OC(O)R^b7, OC(O)NR^c7R^d7, NR^c7R^d7, NR^c7C(O)R^b7, NR^c7C(O)OR^a7, NR^c7C(O)NR^c7R^d7, C(═NR^e7)R^b7, C(═NOR^a7)R^b7, C(═NR^e7)NR^c7R^d7, NR^c7C(═NR^e7)NR^c7R^d7, NR^c7S(O)R^b7, NR^c7S(O)₂R^b7, NR^c7S(O)₂NR^c7R^d7, S(O)R^b7, S(O)NR^c7R^d7, S(O)₂R^b7, S(O)₂NR^c7R^d7, and BR^h7Rⁱ⁷; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, 5-10 membered heteroaryl, C_3-10cycloalkyl-C_1-3alkylene, 4-10 membered heterocycloalkyl-C_1-3alkylene, C_6-10aryl-C_1-3alkylene, and 5-10 membered heteroaryl-C_1-3alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R⁸;

each R⁸is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, 5-10 membered heteroaryl, C_3-10cycloalkyl-C_1-3alkylene, 4-10 membered heterocycloalkyl-C_1-3alkylene, C_6-10aryl-C_1-3alkylene, 5-10 membered heteroaryl-C_1-3alkylene, halo, D, CN, OR^a8, SR^a8, C(O)R^b8, C(O)NR^c8R^d8, C(O)OR^a8, NR^c8R^d8, NR^c8C(O)R^b8, NR^c8C(O)OR^a8, NR^c8S(O)R^b8, NR^c8S(O)₂R^b8, NR^c8S(O)₂NR^c8R^d8, S(O)R^b8, S(O)NR^c8R^d8, S(O)₂R^b8, S(O)₂NR^c8R^d8, and BR^h8Rⁱ⁸; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, 5-10 membered heteroaryl, C_3-10cycloalkyl-C_1-3alkylene, 4-10 membered heterocycloalkyl-C_1-3alkylene, C_6-10aryl-C_1-3alkylene, and 5-10 membered heteroaryl-C_1-3alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R⁹;

each R⁹is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-6cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR^a9, SR^a9, C(O)R^b9, C(O)NR^c9R^d9, C(O)OR^a9, NR^c9R^d9, NR^c9C(O)R^b9, NR^c9C(O)OR^a9, NR^c9S(O)R^b9, NR^c9S(O)₂R^b9, NR^c9S(O)₂NR^c9R^d9, S(O)R^b9, S(O)NR^c9R^d9, S(O)₂R^b9, and S(O)₂NR^c9R^d9; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-6cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

Cy¹is selected from C_3-12cycloalkyl, 4-12 membered heterocycloalkyl, C_6-10aryl and 5-10 membered heteroaryl; wherein the 4-12 membered heterocycloalkyl and 5-10 membered heteroaryl each has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-12 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein said C_3-12cycloalkyl, 4-12 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R¹⁰;

each R¹⁰is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, 5-10 membered heteroaryl, C_3-10cycloalkyl-C_1-3alkylene, 4-10 membered heterocycloalkyl-C_1-3alkylene, C_6-10aryl-C_1-3alkylene, 5-10 membered heteroaryl-C_1-3alkylene, halo, D, CN, NO₂, OR^a10, SR^a10, C(O)R^b10, C(O)NR^c10R^d10, C(O)OR^a10, OC(O)R^b10, OC(O)NR^c10R^d10, NR^c10R^d10, NR^c10C(O)R^b10, NR^c10C(O)OR^a10, NR^c10C(O)NR^c10R^d10, C(═NR^e10)R^b10, C(═NOR^a10)R^b10, C(═NR^e10)NR^c10R^d10, NR^c10C(═NR^e10)NR^c10R^d10, NR^c10S(O)R^b10, NR^c10S(O)₂R^b10, NR^c10S(O)₂NR^c10R^d10, S(O)R^b10, S(O)NR^c10R^d10, S(O)₂R^b10, S(O)₂NR^c10R^d10, and BR^h10Rⁱ¹⁰; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, 5-10 membered heteroaryl, C_3-10cycloalkyl-C_1-3alkylene, 4-10 membered heterocycloalkyl-C_1-3alkylene, C_6-10aryl-C_1-3alkylene, and 5-10 membered heteroaryl-C_1-3alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R¹¹;

each R¹¹is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, 5-10 membered heteroaryl, C_3-10cycloalkyl-C_1-3alkylene, 4-10 membered heterocycloalkyl-C_1-3alkylene, C_6-10aryl-C_1-3alkylene, 5-10 membered heteroaryl-C_1-3alkylene, halo, D, CN, OR^a11, SR^a11, C(O)R^b11, C(O)NR^c11R^d11, C(O)OR^a11, NR^c11R^d11, NR^c11C(O)R^b11, NR^c11C(O)OR^a11, NR^c11S(O)R^b11, NR^c11S(O)₂R^b11, NR^c11S(O)₂NR^c11R^d11, S(O)R^b11, S(O)NR^c11R^d11, S(O)₂R^b11, S(O)₂NR^c11R^d11, and BR^h11Rⁱ¹¹; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, 5-10 membered heteroaryl, C_3-10cycloalkyl-C_1-3alkylene, 4-10 membered heterocycloalkyl-C_1-3alkylene, C_6-10aryl-C_1-3alkylene, and 5-10 membered heteroaryl-C_1-3alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R¹²;

each R¹²is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-6cycloalkyl, C_6-10aryl, 5-10 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR^a12, SR^a12, C(O)R^b12, C(O)NR^c12R^d12, C(O)OR^a12, NR^c12R^d12, NR^c12C(O)R^b12, NR^c12C(O)OR^a12, NR^c12S(O)R^b12, NR^c12S(O)₂R^b12, NR^c12S(O)₂NR^c12R^d12, S(O)R^b12, S(O)NR^c12R^d12, S(O)₂R^b12, S(O)₂NR^c12R^d12, and BR^h12Rⁱ¹²; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-6cycloalkyl, C_6-10aryl, 5-10 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R¹³is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, halo, D, CN, NO₂, OR^a13, SR^a13, C(O)R^b13, C(O)NR^c13R^d13, C(O)OR^a13, OC(O)R^b13, OC(O)NR^c13R^d13, NR^c13R^d13, NR^c13C(O)R^b13, NR^c13C(O)OR^a13, NR^c13C(O)NR^c13R^d13, C(═NR^e13)R^b13, C(═NOR^a13)R^b13, C(═NR^e13)NR^c13R^d13, NR^c13C(═NR^e13)NR^c13R^d13, NR^c13S(O)R^b13, NR^c13S(O)₂R^b13, NR^c13S(O)₂NR^c13R^d13, S(O)R^b13, S(O)NR^c13R^d13, S(O)₂R^b13, S(O)₂NR^c13R^d13, and BR^h13Rⁱ¹³; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g2;

each R^a1, R^c1, and R^d1is independently selected from H, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R¹⁰;

or any R^c1and R^d1attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from R¹⁰;

each R^b1is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R¹⁰;

each R^e1is independently selected from H, CN, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkylthio, C_1-6alkylsulfonyl, C_1-6alkylcarbonyl, C_1-6alkylaminosulfonyl, carbamyl, C_1-6alkylcarbamyl, di(C_1-6alkyl)carbamyl, aminosulfonyl, C_1-6alkylaminosulfonyl, and di(C_1-6alkyl)aminosulfonyl;

each R^h1and Rⁱ¹is independently selected from OH and C_1-6alkoxy;

or any R^h1and Rⁱ¹attached to the same B atom are C_2-3dialkoxy and 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 C_1-6alkyl;

each R^a2, R^c2, and R^d2is independently selected from H, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

or any R^c2and R^d2attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^b2is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^f2, R^j2, and R^k2is independently selected from H, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl and C_1-6haloalkyl; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g2;

each R^e2is independently selected from H, CN, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkylthio, C_1-6alkylsulfonyl, C_1-6alkylcarbonyl, C_1-6alkylaminosulfonyl, carbamyl, C_1-6alkylcarbamyl, di(C_1-6alkyl)carbamyl, aminosulfonyl, C_1-6alkylaminosulfonyl, and di(C_1-6alkyl)aminosulfonyl;

each R^h2and Rⁱ²is independently selected from OH and C_1-6alkoxy;

or any R^h2and Rⁱ²attached to the same B atom are C_2-3dialkoxy and 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 C_1-6alkyl;

each R^a3, R^c3, and R^d3is independently selected from H, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl and C_1-6haloalkyl; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^b3is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, and C_1-6haloalkyl; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^h3and Rⁱ³is independently selected from OH and C_1-6alkoxy;

or any R^h3and Rⁱ³attached to the same B atom are C_2-3dialkoxy and 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 C_1-6alkyl;

each R^a4, R^c4, and R^d4is independently selected from H, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, and C_1-6haloalkyl; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^b4is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, and C_1-6haloalkyl; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^h4and Rⁱ⁴is independently selected from OH and C_1-6alkoxy;

or any R^h4and Rⁱ⁴attached to the same B atom are C_2-3dialkoxy and 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 C_1-6alkyl;

each R^a5is independently selected from H, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, and C_1-6haloalkyl; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^c5and R^d5is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, and C_1-6haloalkyl; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^b5is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl and C_1-6haloalkyl; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^h5and Rⁱ⁵is independently selected from OH and C_1-6alkoxy;

or any R^h5and Rⁱ⁵attached to the same B atom are C_2-3dialkoxy and 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 C_1-6alkyl;

each R^a6, R^c6, and R^d6is independently selected from H, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl and C_1-6haloalkyl; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^b6is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl and C_1-6haloalkyl; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^h6and Rⁱ⁶is independently selected from OH and C_1-6alkoxy;

or any R^h6and Rⁱ⁶attached to the same B atom are C_2-3dialkoxy and 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 C_1-6alkyl;

each R^a7, R^c7, and R^d7is independently selected from H, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R⁸;

or any R^c7and R^d7attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from R⁸;

each R^b7is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R⁸;

each R^e7is independently selected from H, CN, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkylthio, C_1-6alkylsulfonyl, C_1-6alkylcarbonyl, C_1-6alkylaminosulfonyl, carbamyl, C_1-6alkylcarbamyl, di(C_1-6alkyl)carbamyl, aminosulfonyl, C_1-6alkylaminosulfonyl, and di(C_1-6alkyl)aminosulfonyl;

each R^h7and Rⁱ⁷is independently selected from OH and C_1-6alkoxy;

or any R^h7and Rⁱ⁷attached to the same B atom are C_2-3dialkoxy and 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 C_1-6alkyl;

each R^a8, R^c8, and R^d8is independently selected from H, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-6cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C_1-6alkyl C_2-6alkenyl, C_2-6alkynyl, C_3-6cycloalkyl, phenyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R⁹;

or any R^c8and R^d8attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 substituents independently selected from R⁹;

each R^b8is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-6cycloalkyl, phenyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl; wherein said C_1-6alkyl C_2-6alkenyl, C_2-6alkynyl, C_3-6cycloalkyl, phenyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R⁹;

each R^h8and Rⁱ⁸is independently selected from OH and C_1-6alkoxy;

or any R^h8and Rⁱ⁸attached to the same B atom are C_2-3dialkoxy and 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 C_1-6alkyl;

each R^a9, R^c9, and R^d9is independently selected from H, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, and C_1-6haloalkyl; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^b9is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, and C_1-6haloalkyl; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^a10, R^c10, and R^d10is independently selected from H, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R¹¹;

or any R^c10and R^d10attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from R¹¹;

each R^b10is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R¹¹;

each R^e10is independently selected from H, CN, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkylthio, C_1-6alkylsulfonyl, C_1-6alkylcarbonyl, C_1-6alkylaminosulfonyl, carbamyl, C_1-6alkylcarbamyl, di(C_1-6alkyl)carbamyl, aminosulfonyl, C_1-6alkylaminosulfonyl, and di(C_1-6alkyl)aminosulfonyl;

each R^h10and Rⁱ¹⁰is independently selected from OH and C_1-6alkoxy;

or any R^h10and Rⁱ¹⁰attached to the same B atom are C_2-3dialkoxy and 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 C_1-6alkyl;

each R^a11, R^c11, and R^d11is independently selected from H, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-6cycloalkyl, phenyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl; wherein said C_1-6alkyl C_2-6alkenyl, C_2-6alkynyl, C_3-6cycloalkyl, phenyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R¹²;

or any R^c11and R^d11attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2 or 3 substituents independently selected from R¹²;

each R^b11is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-6cycloalkyl, phenyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl; wherein said C_1-6alkyl C_2-6alkenyl, C_2-6alkynyl, C_3-6cycloalkyl, phenyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R¹²;

each R^h11and Rⁱ¹¹is independently selected from OH and C_1-6alkoxy;

or any R^h11and Rⁱ¹¹attached to the same B atom are C_2-3dialkoxy and 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 C_1-6alkyl;

each R^a12, R^c12and R^d12is independently selected from H, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, and C_1-6haloalkyl; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^b12is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl and C_1-6haloalkyl; wherein said C_1-6alkyl, C_2-6alkenyl, and C_2-6alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^h12and Rⁱ¹²is independently selected from OH and C_1-6alkoxy;

or any R^h12and Rⁱ¹²attached to the same B atom are C_2-3dialkoxy and 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 C_1-6alkyl;

each R^a13, R^c13, and R^d13is independently selected from H, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^b13is independently selected from C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl; wherein said C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_3-10cycloalkyl, 4-10 membered heterocycloalkyl, C_6-10aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R^g;

each R^e13is independently selected from H, CN, C_1-6alkyl, C_1-6haloalkyl, C_1-6alkylthio, C_1-6alkylsulfonyl, C_1-6alkylcarbonyl, C_1-6alkylaminosulfonyl, carbamyl, C_1-6alkylcarbamyl, di(C_1-6alkyl)carbamyl, aminosulfonyl, C_1-6alkylaminosulfonyl, and di(C_1-6alkyl)aminosulfonyl;

each R^h13and Rⁱ¹³is independently selected from OH and C_1-6alkoxy;

or any R^h13and Rⁱ¹³attached to the same B atom are C_2-3dialkoxy and 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 C_1-6alkyl;

each R^gis independently selected from OH, NO₂, CN, halo, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_3-6cycloalkyl, C_3-6cycloalkyl-C_1-2alkylene, C_1-6alkoxy, C_1-6haloalkoxy, C_1-3alkoxy-C_1-3alkyl, C_1-3alkoxy-C_1-3alkoxy, HO—C_1-3alkoxy, HO—C_1-3alkyl, cyano-C_1-3alkyl, H₂N—C_1-3alkyl, amino, C_1-6alkylamino, di(C_1-6alkyl)amino, thio, C_1-6alkylthio, C_1-6alkylsulfinyl, C_1-6alkylsulfonyl, carbamyl, C_1-6alkylcarbamyl, di(C_1-6alkyl)carbamyl, carboxy, C_1-6alkylcarbonyl, C_1-6alkoxycarbonyl, C_1-6alkylcarbonylamino, C_1-6alkylsulfonylamino, aminosulfonyl, C_1-6alkylaminosulfonyl, di(C_1-6alkyl)aminosulfonyl, aminosulfonylamino, C_1-6alkylaminosulfonylamino, di(C_1-6alkyl)aminosulfonylamino, aminocarbonylamino, C_1-6alkylaminocarbonylamino, and di(C_1-6alkyl)aminocarbonylamino; and

each R^g2is independently selected from OH, NO₂, CN, halo, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, C_1-6haloalkyl, C_1-6alkoxy, C_1-6haloalkoxy, C_1-3alkoxy-C_1-3alkyl, C_1-3alkoxy-C_1-3alkoxy, HO—C_1-3alkoxy, HO—C_1-3alkyl, cyano-C_1-3alkyl, H₂N—C_1-3alkyl, amino, C_1-6alkylamino, di(C_1-6alkyl)amino, thio, C_1-6alkylthio, C_1-6alkylsulfinyl, C_1-6alkylsulfonyl, carbamyl, C_1-6alkylcarbamyl, di(C_1-6alkyl)carbamyl, carboxy, C_1-6alkylcarbonyl, C_1-6alkoxycarbonyl, C_1-6alkylcarbonylamino, C_1-6alkylsulfonylamino, aminosulfonyl, C_1-6alkylaminosulfonyl, di(C_1-6alkyl)aminosulfonyl, aminosulfonylamino, C_1-6alkylaminosulfonylamino, di(C_1-6alkylaminosulfonylamino, aminocarbonylamino, C_1-6alkylaminocarbonylamino, and di(C_1-6alkyl)aminocarbonylamino; and

wherein the cancer is selected from breast cancer, colorectal cancer, lung cancer, ovarian cancer, pancreatic cancer, Burkitt's lymphoma, and acute promonocytic leukemia.