US 12,441,742 B2
Naphthyridine compounds as inhibitors of KRAS
Gencheng Li, Claymont, DE (US); Haolin Yin, Wilmington, DE (US); Chao Qi, Wilmington, DE (US); Xiaozhao Wang, Mt. Laurel, NJ (US); Wenqing Yao, Wilmington, DE (US); Bin Hu, Garnet Valley, PA (US); and Peter Carlsen, Wilmington, DE (US)
Assigned to Incyte Corporation, Wilmington, DE (US)
Filed by Incyte Corporation, Wilmington, DE (US)
Filed on Aug. 30, 2022, as Appl. No. 17/823,254.
Claims priority of provisional application 63/364,593, filed on May 12, 2022.
Claims priority of provisional application 63/239,152, filed on Aug. 31, 2021.
Prior Publication US 2023/0174555 A1, Jun. 8, 2023
Int. Cl. C07D 519/00 (2006.01); A61P 35/00 (2006.01); C07D 471/14 (2006.01)
CPC C07D 519/00 (2013.01) [A61P 35/00 (2018.01); C07D 471/14 (2013.01)] 28 Claims
 
1. A compound of Formula II:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
-AR1=BR2— is selected from —N═CR2— and —CR1═N—;
X is selected from N and CR5;
Y is selected from N and CR6;
R1 is selected from H, D, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, halo, CN, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, S(O)2NRc1Rd1, and BRh1Ri1; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
R2 is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, C(═NRe2)Rb2, C(═NORa2)Rb2, C(═NRe2)NRc2Rd2, NRc2C(═NRe2)NRc2Rd2, NRc2C(═NRe2)Rb2, NRc2S(O)Rb2, NRCS(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, S(O)2NRc2Rd2, and BRh2Ri2; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R23;
Cy1 is selected from C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 6-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 6-10 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 6-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 6-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R10;
R4 is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(═NRe3)Rb3, C(═NORa3)Rb3, C(═NRe3)NRc3Rd3, NRc3C(═NRe3)NRc3Rd3, NRc3C(═NRe3)Rb3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3, and BRh3Ri3; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R30;
R5 is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, C(═NRe5)Rb5, C(═NORa5)Rb5, C(═NRe5)NRc5Rd5, NRc5C(═NRe5)NRc5Rd5, NRc5C(═NRe5)Rb5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, S(O)2NRc5Rd5, and BRh5Ri5; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
R6 is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, [ORa6,] SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)ORa6, NRc6C(O)NRc6Rd6, C(═NRe6)Rb6, C(═NORa6)Rb6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, NRc6C(═NRe6)Rb6, NRc6S(O)Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, S(O)2NRc6Rd6, and BRh6Ri6; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R60;
R7 is selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, OC(O)Rb7, OC(O)NRc7Rd7, NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)ORa7, NRc7C(O)NRc7Rd7, C(═NRe7)Rb7, C(═NORa7)Rb7, C(═NRe7)NRc7Rd7, NRc7C(═NRe7)NRc7Rd7, NRc7C(═NRe7)Rb7, NRc7S(O)Rb7, NRc7S(O)2Rb7, NRc7S(O)2NRc7Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, S(O)2NRc7Rd7, and BRh7Ri7; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R70;
Cy2 is selected from C3-10 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein the 4-14 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 4-14 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C3-10 cycloalkyl, 4-14 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R20;
each R10 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa10, SRa10, C(O)Rb10, C(O)NRc10Rd10, C(O)ORa10, OC(O)Rb10, OC(O)NRc10Rd10, NRc10Rd10, NRc10C(O)Rb10, NRc10C(O)ORa10, NRc10C(O)NRc10Rd10, C(═NRe10)Rb10, C(═NORa10)Rb10, C(═NRe10)NRc10Rd10, NRc10C(═NRe10)NRc10Rd10, NRc10S(O)Rb10, NRc10S(O)2Rb10, NRc10S(O)2NRc10Rd10, S(O)Rb10, S(O)NRc10Rd10, S(O)2Rb10, S(O)2NRc10Rd10, and BRh10Ri10; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R11;
each R11 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NR11C(O)Rb11, NR11C(O)ORa11, NR11C(O)NRc11Rd11, NRc11S(O)Rb11, NRc11S(O)2Rb11, NRc11S(O)2NRc11Rd11, S(O)Rb11, S(O)NRc11Rd11, S(O)2Rb11, S(O)2NRc11Rd11, and BRh11Ri11; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R12;
each R12 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, ORa12, SRa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRc12Rd12, NRc12C(O)Rb12, NRc12C(O)ORa12, NRc12C(O)NRc12Rd12, NRc12S(O)Rb12, NRc12S(O)2Rb12, NRc12S(O)2NRc12Rd12, S(O)Rb12, S(O)NRc12Rd12, S(O)2Rb12, S(O)2NRc12Rd12, and BRh12Ri12; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each R20 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa20, SRa20, C(O)Rb20, C(O)NRc20Rd20, C(O)ORa20, OC(O)Rb20, OC(O)NRc20Rd20, NRc20Rd20, NRc20C(O)Rb20, NRc2C(O)ORa20, NRc20C(O)NRc20Rd20, C(═NRe20)Rb20, C(═NORa20)Rb20, C(═NRe20)NRc20Rd20, NRc20C(═NRe20)NRc20Rd20, NRc20S(O)Rb20, NRc20S(O)2Rb20, NRc20S(O)2NRc20Rd20, S(O)Rb20, S(O)NRc20Rd20, S(O)2Rb20, S(O)2NRc20Rd20, and BRh20Ri20; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21;
each R21 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, ORa21, SRa21, C(O)Rb21, C(O)NRc21Rd21, C(O)ORa21, OC(O)Rb21, OC(O)NRc21Rd21, NRc21Rd21, NR21C(O)Rb21, NRc21C(O)ORa21, NR21C(O)NRc21Rd21, NR21S(O)Rb21, NRc21S(O)2Rb21, NRc21S(O)2NRc21Rd21, S(O)Rb21, S(O)NRc21Rd21, S(O)2Rb21, S(O)2NRc21Rd21, and BRh21Ri21; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R22;
each R22 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, ORa22, SRa22, C(O)Rb22, C(O)NRc22Rd22, C(O)ORa22, OC(O)Rb22, OC(O)NRc22Rd22, NRc22Rd22, NRc22C(O)Rb22, NRc22C(O)ORa22, NRc22C(O)NRc22Rd22, NRc22S(O)Rb22, NR22S(O)2Rb22, NRc22S(O)2NRc22Rd22, S(O)Rb22, S(O)NRc22Rd22, S(O)2Rb22, S(O)2NRc22Rd22, and BRh22Ri22; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each R23 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa23, SRa23, C(O)Rb23, C(O)NRc23Rd23, C(O)ORa23, OC(O)Rb23, OC(O)NRc23Rd23, NRc23Rd23, NRc23C(O)Rb23, NRc23C(O)ORa23, NRc23C(O)NRc23Rd23, NRc23S(O)Rb23, NRc23S(O)2Rb23, NRc23S(O)2NRc23Rd23, S(O)Rb23, S(O)NRc23Rd23, S(O)2Rb23, S(O)2NRc23Rd23, and BRh23Ri23; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R24;
each R24 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, ORa24, SRa24, C(O)Rb24, C(O)NRc24Rd24, C(O)ORa24, OC(O)Rb24, OC(O)NRc24Rd24, NRc24Rd24, NRc24C(O)Rb24, NRc24C(O)ORa24, NRc24C(O)NRc24Rd24, NRc24S(O)Rb24, NRc24S(O)2Rb24, NRc24S(O)2NRc24Rd24, S(O)Rb24, S(O)NRc24Rd24, S(O)2Rb24, S(O)2NRc24Rd24, and BRh24Ri24; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each R30 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa30, SRa30, C(O)Rb30, C(O)NRc30Rd30, C(O)ORa30, OC(O)Rb30, OC(O)NRc30Rd30, NRc30Rd30, NRc30C(O)Rb30, NRc30C(O)ORa30, NRc30C(O)NRc30Rd30, NRc30S(O)Rb30, NRc30S(O)2Rb30, NRc30S(O)2NRc30Rd30, S(O)Rb30, S(O)NRc30Rd30, S(O)2Rb30, S(O)2NRc30Rd30, and BRh30Ri30; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R31;
each R31 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, ORa31, SRa31, C(O)Rb31, C(O)NRc31Rd31, C(O)ORa31, OC(O)Rb31, OC(O)NRc31Rd31, NRc31Rd31, NRc31C(O)Rb31, NRc31C(O)ORa31, NRc31C(O)NRc31Rd31, NRc31S(O)Rb31, NRc31S(O)2Rb31, NR31S(O)2NRc31Rd31, S(O)Rb31, S(O)NRc31Rd31, S(O)2Rb31, S(O)2NRc31Rd31, and BRh31Ri31; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R32;
each R32 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, ORa32, SRa32, C(O)Rb32, C(O)NRc32Rd32, C(O)ORa32, OC(O)Rb32, OC(O)NRc32Rd32, NRc32Rd32, NRc32C(O)Rb32, NRc32C(O)ORa32, NR32C(O)NRc32Rd32, NRc32S(O)Rb32, NRc32S(O)2Rb32, NRc32S(O)2NRc32Rd32, S(O)Rb32, S(O)NRc32Rd32, S(O)2Rb32, S(O)2NRc32Rd32, and BRh32Ri32; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each R60 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa60, SRa60, C(O)Rb60, C(O)NRc60Rd60, C(O)ORa60, OC(O)Rb60, OC(O)NRc60Rd60, NRc60Rd60, NRc60C(O)Rb60, NRc60C(O)ORa60, NRc60C(O)NRc60Rd60, NRc60S(O)Rb60, NRc60S(O)2Rb60, NRc60S(O)2NRc60Rd60, S(O)Rb60, S(O)NRc60Rd60, S(O)2Rb60, S(O)2NRc60Rd60, and BRh60Ri60; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R61;
each R61 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, ORa61, SRa61, C(O)Rb61, C(O)NRc61Rd61, C(O)ORa61, OC(O)Rb61, OC(O)NRc61Rd61, NRc61Rd61, NR61C(O)Rb61, NRc61C(O)ORa61, NRc61C(O)NRc61Rd61, NRc61S(O)Rb61, NRc61S(O)2Rb61, NRc61S(O)2NRc61Rd61, S(O)Rb61, S(O)NRc61Rd61, S(O)2Rb61, S(O)2NRc61Rd61, and BRh61Ri61; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R62;
each R62 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, ORa62, SRa62, C(O)Rb62, C(O)NRc62Rd62, C(O)ORa62, OC(O)Rb62, OC(O)NRc62Rd62, NRc62Rd62, NR62C(O)Rb62, NR62C(O)ORa62, NRc62C(O)NRc62Rd62, NRc62S(O)Rb62, NR62S(O)2Rb62, NR62S(O)2NRc62Rd62, S(O)Rb62, S(O)NRc62Rd62, S(O)2Rb62, S(O)2NRc62Rd62, and BRh62Ri62; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each R70 is independently selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, NO2, ORa70, SRa70, C(O)Rb70, C(O)NRc70Rd70, C(O)ORa70, OC(O)Rb70, OC(O)NRc70Rd70, NRc70Rd70, NRc70C(O)Rb70, NRc7C(O)ORa70, NRc70C(O)NRc70Rd70, NRc70S(O)Rb70, NRc70S(O)2Rb70, NRc70S(O)2NRc70Rd70, S(O)Rb70, S(O)NRc70Rd70, S(O)2Rb70, S(O)2NRc70Rd70, and BRh70Ri70; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-3 alkylene, 4-10 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene and 5-10 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Ra1, Rb1, Rc1, and Rd1 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
or any Rc1 and Rd1 attached 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 Rg;
each Rh1 and Ri1 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh1 and Ri1 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 Ra2, Rb2, Rc2 and Rd2 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R23;
or any Rc2 and Rd2 attached 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 R23;
each Re2 is independently selected from H, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl) carbamyl, aminosulfonyl, C1-6 alkylaminosulfonyl and di(C1-6 alkyl) aminosulfonyl;
each Rh2 and Ri2 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh2 and Ri2 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 Ra3, Rb3, Rc3 and Rd3 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R30;
or any Rc3 and Rd3 attached 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 R30;
each Re3 is independently selected from H, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl) carbamyl, aminosulfonyl, C1-6 alkylaminosulfonyl and di(C1-6 alkyl) aminosulfonyl;
each Rh3 and Ri3 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh3 and Ri3 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 Ra5, Rb5, Rc5, and Rd5 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
or any Rc5 and Rd5 attached 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 Rg;
each Re5 is independently selected from H, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl) carbamyl, aminosulfonyl, C1-6 alkylaminosulfonyl and di(C1-6 alkyl) aminosulfonyl;
each Rh5 and Ri5 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh5 and Ri5 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 Ra6, Rb6, Rc6, and Rd6 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R60;
or any Rc6 and Rd6 attached 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 R60;
each Re6 is independently selected from H, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl) carbamyl, aminosulfonyl, C1-6 alkylaminosulfonyl and di(C1-6 alkyl) aminosulfonyl;
each Rh6 and Ri6 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh6 and Ri6 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 Ra7, Rb7, Rc7 and Rd7 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R70;
or any Rc7 and Rd7 attached 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 R70;
each Re7 is independently selected from H, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl) carbamyl, aminosulfonyl, C1-6 alkylaminosulfonyl and di(C1-6 alkyl) aminosulfonyl;
each Rh7 and Ri7 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh7 and Ri7 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 Ra10, Rb10, Rc10 and Rd10 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R11;
or any Rc10 and Rd10 attached 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 Re10 is independently selected from H, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl) carbamyl, aminosulfonyl, C1-6 alkylaminosulfonyl and di(C1-6 alkyl) aminosulfonyl;
each Rh10 and Ri10 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh10 and Ri10 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 Ra11, Rb11, Rc11 and Rd11, is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C1-6 alkyl C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, 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 Rc11 and Rd11 attached 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 Rh11 and Ri11 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh11 and Ri11 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 Ra12, Rb12, Rc12 and Rd12, is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Rh12 and Ri12 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh12 and Ri12 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 Ra20, Rb20, Rc20 and Rd20 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R21;
or any Rc20 and Rd20 attached 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 R21;
each Re20 is independently selected from H, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl) carbamyl, aminosulfonyl, C1-6 alkylaminosulfonyl and di(C1-6 alkyl) aminosulfonyl;
each Rh20 and Ri20 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh20 and Ri20 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 Ra21, Rb21, Rc21 and Rd21, is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C1-6 alkyl C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R22;
or any Rc21 and Rd21 attached 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 R22;
each Rh21 and Ri21 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh21 and Ri21 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 Ra22, Rb22, Rc22 and Rd22, is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Rh22 and Ri22 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh22 and Ri22 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 Ra23, Rb23, Rc23 and Rd23, is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C1-6 alkyl C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R24;
or any Rc23 and Rd23 attached 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 R24;
each Rh23 and Ri23 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh23 and Ri23 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 Ra24, Rb24, Rc24 and Rd24, is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
each Rh24 and Ri24 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh24 and Ri24 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 Ra30, Rb30, Rc30 and Rd30 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R31;
or any Rc30 and Rd30 attached 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 R31;
each Rh30 and Ri30 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh30 and Ri30 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 Ra31, Rb31, Rc31 and Rd31, is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C1-6 alkyl C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R32;
or any Rc31 and Rd31 attached 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 R32;
each Rh31 and Ri31 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh31 and Ri31 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 Ra32, Rb32, Rc32 and Rd32, is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
or any Rc32 and Rd32 attached 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 Rg;
each Rh32 and Ri32 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh32 and Ri32 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 Ra60, Rb60, Rc60 and Rd60 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl, are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R61;
or any Rc60 and Rd60 attached 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 R61;
each Rh60 and Ri60 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh60 and Ri60 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 Ra61, Rb61, Rc61 and Rd61, is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C1-6 alkyl C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R62;
or any Rc61 and Rd61 attached 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 R62;
each Rh61 and Ri61 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh61 and Ri61 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 Ra62, Rb62, Rc62 and Rd62, is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and C1-6 haloalkyl; wherein said C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
or any Rc62 and Rd62 attached 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 Rg;
each Rh62 and Ri62 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh62 and Ri62 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 Ra70, Rb70, Rc70 and Rd70 is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
or any Rc70 and Rd70 attached 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 Rg;
each Rh70 and Ri70 is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or any Rh70 and Ri70 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; and
each Rg is independently selected from D, OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-2 alkylene, C1-6 alkoxy, C1-6 haloalkoxy, C1-3 alkoxy-C1-3 alkyl, C1-3 alkoxy-C1-3 alkoxy, HO-C1-3 alkoxy, HO-C1-3 alkyl, cyano-C1-3 alkyl, H2N-C1-3 alkyl, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkoxycarbonylamino, C1-6 alkylcarbonyloxy, aminocarbonyloxy, C1-6 alkylaminocarbonyloxy, di(C1-6 alkyl)aminocarbonyloxy, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino.