Bicyclic heterocycles as FGFR inhibitors

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• W is NR9;
• R1 is C1-6 alkyl, C1-6 haloalkyl, or C3-7 cycloalkyl;
• R3 is selected from H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, cyclopropyl, CN, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, C(═NRe)Rb, C(═NRe)NRcRd, NRcC(═NRe)NRcRd, NRcS(O)Rb, NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, and S(O)2NRcRd;
• R2 and R5 are each fluoro;
• R4 is H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 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, C(═NRe1)Rb1, C(═NRe1)NRc1Rd1, NRc1C(═NRe1)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, or S(O)2NRc1Rd1;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(═NRe1)NRc1Rd1, NRc1C(═NRe1)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, and S(O)2NRc1Rd1;
• R6 is halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CN, NO2, OR32, 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(═NRe2)NRc2Rd2, NRc2C(═NRe2)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, or S(O)2NRc2Rd2;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from R6a;
• each R6a is independently selected from Cy1, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRe2)NRc2Rd2, NRc2C(═NRe2)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Cy1, halo, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRe2)NRc2Rd2, NRc2C(═NRe2)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• R7 and R8 are each independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —C(O)RA, S(O)RA, S(O)2RA, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C i-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from R7a;
• each R7a is independently selected from Cy2, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(═NRe3)NRc3Rd3, NRc3C(═NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3, wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Cy2, halo, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(═NRe3)NRc3Rd3, NRc3C(═NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• R9 is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, or (4-10 membered heterocycloalkyl)-C1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from R9a;
• each R9a is independently selected from Cy3, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, C(═NRe4)NRc4Rd4, NRc4C(═NRe4)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4C(O)NRc4Rd4, NRc4S(O)Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, and S(O)2NRc4Rd4, wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Cy3, halo, CN, NO2, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, C(═NRe4)NRc4Rd4, NRc4C(═NRe4)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4C(O)NRc4Rd4, NRc4S(O)Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, and S(O)2NRc4Rd4;
• each RA is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl, wherein said C1-6 alkyl, C1-6 alkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R7a;
• Cy1, Cy2, and Cy3 are each independently selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, each of which is optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, 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(═NRe5)NRc5Rd5, NRc5C(═NRe5)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, CN, NO2, OR35, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, C(═NRe5)NRc5Rd5, NRc5C(═NRe5)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5;
• each Ra, Rb, Rc, and Rd is independently selected from H, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and cyclopropyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and cyclopropyl are each optionally substituted with 1, 2, or 3 substituents independently selected from CM alkyl, CM haloalkyl, halo, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)NRc6Rd6, NRc6C(O)ORa6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, and S(O)2NRc6Rd6;
• each Ra1, Rb1, Rc1, Rd1, Ra2, Rb2, Rc2, Rd2, Ra3, Rb3, Rc3, Rd3, Ra4, Rb4, Rc4, Rd4, Ra5, Rb5, Rc5, and Rd5 is independently selected from H, C1-6 alkyl, CM haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C1-4 alkyl, C1-4 haloalkyl, halo, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)NRc6Rd6, NRc6C(O)ORa6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, and S(O)2NRc6Rd6;
• or any Rc and Rd 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 C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, 5-6 membered heteroaryl, C1-6 haloalkyl, halo, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)NRc6Rd6, NRc6C(O)ORa6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, and S(O)2NRc6Rd6, wherein said C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, and 5-6 membered heteroaryl are optionally substituted by 1, 2, or 3 substituents independently selected from halo, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)NRc6Rd6, NRc6C(O)ORa6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, and S(O)2NRc6Rd6;
• or any Rc1 and Rd1 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 C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, 5-6 membered heteroaryl, C1-6 haloalkyl, halo, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)NRc6Rd6, NRc6C(O)ORa6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, and S(O)2NRc6Rd6, wherein said C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, and 5-6 membered heteroaryl are optionally substituted by 1, 2, or 3 substituents independently selected from halo, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)NRc6Rd6, NRc6C(O)ORa6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, and S(O)2NRc6Rd6;
• or any Rc2 and Rd2 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 C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, and 5-6 membered heteroaryl, C1-6 haloalkyl, halo, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)NRc6Rd6, NRc6C(O)ORa6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, and S(O)2NRc6Rd6, wherein said C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, and 5-6 membered heteroaryl are optionally substituted by 1, 2, or 3 substituents independently selected from halo, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)NRc6Rd6, NRc6C(O)ORa6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, and S(O)2NRc6Rd6;
• or any Rc3 and Rd3 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 C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, 5-6 membered heteroaryl, C1-6 haloalkyl, halo, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)NRc6Rd6, NRc6C(O)ORa6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, and S(O)2NRc6Rd6, wherein said C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, and 5-6 membered heteroaryl are optionally substituted by 1, 2, or 3 substituents independently selected from halo, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)NRc6Rd6, NRc6C(O)ORa6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, and S(O)2NRc6Rd6;
• or any Rc4 and Rd4 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 C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, 5-6 membered heteroaryl, C1-6 haloalkyl, halo, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)NRc6Rd6, NRc6C(O)ORa6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, and S(O)2NRc6Rd6, wherein said C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, and 5-6 membered heteroaryl are optionally substituted by 1, 2, or 3 substituents independently selected from halo, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)NRc6Rd6, NRc6C(O)ORa6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, and S(O)2NRc6Rd6;
• or any Rc5 and Rd5 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 C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, 5-6 membered heteroaryl, C1-6 haloalkyl, halo, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)NRc6Rd6, NRc6C(O)ORa6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, and S(O)2NRc6Rd6, wherein said C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, and 5-6 membered heteroaryl are optionally substituted by 1, 2, or 3 substituents independently selected from halo, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, OC(O)Rb6, OC(O)NRc6Rd6, NRc6Rd6, NRc6C(O)Rb6, NRc6C(O)NRc6Rd6, NRc6C(O)ORa6, C(═NRe6)NRc6Rd6, NRc6C(═NRe6)NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, and S(O)2NRc6Rd6;
• each Re, Re1, Re2, Re3, Re4, and Re5 is independently selected from H, C1-4 alkyl, CN, OR36, SRb6, S(O)2Rb6, C(O)Rb6, S(O)2NRc6Rd6, and C(O)NRc6Rd6;
• each Ra6, Rb6, Rc6, and Rd6 is independently selected from H, C1-4 alkyl, C1-4 haloalkyl, C2-4 alkenyl, and C2-4 alkynyl, wherein said C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylamino, di(C1-4 alkyl)amino, C1-4 haloalkyl, and C1-4 haloalkoxy;
• or any Rc6 and Rd6 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 OH, CN, amino, halo, C1-6 alkyl, C1-4alkoxy, C1-4 alkylthio, C1-4 alkylamino, di(C1-4 alkyl)amino, C1-4 haloalkyl, and C1-4 haloalkoxy;
• and
• each Re6 is independently selected from H, C1-4 alkyl, and CN.