Pyrazolopyrimidine compounds and uses thereof

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is selected from Cy1, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, halo, CN, NO2, 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(═NORa)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;
• wherein said C2-6 alkenyl and C2-6 alkynyl are each substituted with 1, 2, 3, or 4 substituents independently selected from R10;
• Cy1 is selected from C3-8 cycloalkyl, 4-12 membered heterocycloalkyl, C6-10 aryl 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 the C3-8 cycloalkyl, 4-12 membered heterocycloalkyl, C6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R10;
• Cy is 4-12 membered heterocycloalkyl;
• wherein the 4-12 membered heterocycloalkyl 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 4-12 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group;
• wherein when the 4-12 membered heterocycloalkyl of Cy has a fused aromatic ring, the 4-12 membered heterocycloalkyl is directly attached to the pyrazolopyrimidine core structure through a ring-forming atom of the saturated or partially saturated ring;
• and wherein the 4-12 membered heterocycloalkyl is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from R20;
• R2 is selected from H, D, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy and C1-4 haloalkoxy;
• 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, 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(═NORa1)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, and S(O)2NRc1Rd1;
• 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;
• or two R10 substituents taken together with the carbon atom to which they are attached form a spiro 4-7-membered heterocycloalkyl ring, or a spiro C3-6 cycloalkyl ring;
• wherein each spiro 4-7-membered heterocycloalkyl ring has at least one ring-forming carbon atom and 1, 2 or 3, ring-forming heteroatoms independently selected from N, O, and S;
• wherein a ring-forming carbon atom of each spiro 4-7-membered heterocycloalkyl ring is optionally substituted by oxo to form a carbonyl group;
• and wherein the spiro 4-7-membered heterocycloalkyl ring and spiro C3-6 cycloalkyl ring 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, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, NRc3Rd3 NRc3C(O)Rb3, NRc3C(O)ORa3, 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, 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, C6-10 aryl, 5-10 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, C6-10 aryl-C1-3 alkylene, 5-10 membered heteroaryl-C1-3 alkylene, halo, D, CN, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, 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, C3-6 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 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 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, 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, 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, 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, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, 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, 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, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, 5-6 membered heteroaryl-C1-3 alkylene, halo, D, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6Rd6 NRc6C(O)Rb6, NR6C(O)ORa6 NRc6S(O)Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6 S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, and S(O)2NRc6Rd6;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Rg;
• each Ra, Rc, and Rd 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, 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;
• 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 R10;
• or any Rc and Rd attached 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 Rb 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, and 5-10 membered heteroaryl-C1-3 alkylene;
• 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 R10;
• each Re is independently selected from H, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, aminosulfonyl, C1-6 alkylaminosulfonyl and di(C1-6 alkyl)aminosulfonyl;
• each Ra1, 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, 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;
• 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;
• or any Rc1 and Rd1 attached 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 R11;
• each Rb1 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, and 5-10 membered heteroaryl-C1-3 alkylene;
• 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 Re1 is independently selected from H, CN, C1-6 alkyl, 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, and di(C1-6 alkyl)aminosulfonyl;
• each Ra2, 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, 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;
• 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;
• or any Rc2 and Rd2 attached 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 R21;
• each Rb2 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, and 5-10 membered heteroaryl-C1-3 alkylene;
• 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 Re2 is independently selected from H, CN, C1-6 alkyl, 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, and di(C1-6 alkyl)aminosulfonyl;
• each Ra3, Rc3 and Rd3 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, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C13 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R12;
• 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 or 3 substituents independently selected from R12;
• each Rb3 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, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R12;
• each Ra4, Rc4 and Rd4 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, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R22;
• or any Rc4 and Rd4 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 Rb4 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, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, C3-6 cycloalkyl-C1-3 alkylene, 4-7 membered heterocycloalkyl-C1-3 alkylene, phenyl-C1-3 alkylene, and 5-6 membered heteroaryl-C1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R22;
• each Ra5, Rc5 and Rd5 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 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 Rb5 is independently selected from 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 Ra6, Rc6 and Rd6 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 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 Rg;
• each Rb6 is independently selected from 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;
• and
• each Rg is independently selected from 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 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.