Triazolotriazines as kinase inhibitors

A compound of Formula I:

• or pharmaceutically acceptable salt thereof, wherein:
• Cy1 is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, each optionally substituted by 1, 2, 3, 4, or 5 —W—X—Y-Z;
• Cy2 is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, each optionally substituted by 1, 2, 3, 4, or 5 —W′—X′—Y′-Z′;
• A is H, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, 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)NRCRD, NRCC(O)ORA, S(O)RB, S(O)NRCRD, S(O)2RB, NRCS(O)2RB, or S(O)2NRCRD;
• R1 and R2 together with the carbon atom to which they are attached form a 3- to 7-membered cycloalkyl group or 3- to 7-membered heterocycloalkyl group, each optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from Q, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, 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)NRcRd, NRcC(O)ORa, C(═NRg)NRcRd, NRcC(═NRg)NRcRd, P(Rf)2, P(ORe)2, P(O)ReRf, P(O)OReORf, S(O)Rb, S(O)NRcRd, S(O)2Rb, NRcS(O)2Rb, and S(O)2NRcRd, wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl is optionally substituted with 1, 2, or 3 substituents selected from Q, 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)NRcRd, NRcC(O)ORa, C(═NRg)NRcRd, NRcC(═NRg)NRcRd, P(Rf)2, P(O)ReRf, P(O)ReRf, P(O)OReORf, S(O)Rb, S(O)NRcRd, S(O)2Rb, NRcS(O)2Rb, and S(O)2NRcRd;
• Q is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, each 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, halosulfanyl, 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)NRc1Rd1, NRc1C(O)ORa1, C(═NRg1)NRc1Rd1, NRc1C(═NRg1)NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, NRc1S(O)2Rb1, and S(O)2NRc1Rd1;
• W and W′ are independently absent or independently selected from C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, O, S, NRh, CO, COO, CONRh, SO, SO2, SONRh and NRhCONRi, wherein each of the C1-6 alkylene, C2-6 alkenylene, and C2-6 alkynylene is optionally substituted by 1, 2 or 3 substituents independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, OH, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, and C2-8 dialkylamino;
• X and X′ are independently absent or independently selected from C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, arylene, cycloalkylene, heteroarylene, and heterocycloalkylene, wherein each of the C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, arylene, cycloalkylene, heteroarylene, and heterocycloalkylene is optionally substituted by 1, 2 or 3 substituents independently selected from halo, CN, NO2, OH, C1-6 alkyl, C1-6haloalkyl, C2-8 alkoxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C2-8 alkoxyalkoxy, cycloalkyl, heterocycloalkyl, C(O)ORj, C(O)NRhRi, amino, C1-6 alkylamino, and C2-8 dialkylamino;
• Y and Y′ are independently absent or independently selected from C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene, O, S, NRh, CO, COO, CONRh, SO, SO2, SONRh, and NRhCONRi, wherein each of the C1-6 alkylene, C2-6 alkenylene, and C2-6 alkynylene is optionally substituted by 1, 2 or 3 substituents independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, OH, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6 alkylamino, and C2-8 dialkylamino;
• Z and Z′ are independently selected from H, 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)b2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, C(═NRg2)NRc2Rd2, NRc2C(═NRg2)NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, NRc2S(O)2Rb2, S(O)2NRc2Rd2, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl are 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, halosulfanyl, 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)NRc2Rd2, NRc2C(O)ORa2, C(═NRg2)NRc2Rd2, NRc2C(═NRg2)NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, NRc2S(O)2Rb2, and S(O)2NRc2Rd2;
• wherein two adjacent —W—X—Y-Z, together with the atoms to which they are attached, optionally form a fused 4-, 5-, 6-, or 7-membered cycloalkyl ring or a fused 4-, 5-, 6-, or 7-membered heterocycloalkyl ring, each optionally substituted by 1, 2, or 3 substituents independently selected from 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, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, C(═NRg2)NRc2Rd2, NRc2C(═NRg2)NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, NRc2, S(O)2Rb2, S(O)2NRc2Rd2, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein two adjacent —W′—X′—Y′-Z′, together with the atoms to which they are attached, optionally form a fused 4-, 5-, 6-, or 7-membered cycloalkyl ring or a fused 4-, 5-, 6-, or 7-membered heterocycloalkyl ring, each optionally substituted by 1, 2, or 3 substituents independently selected from 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, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, C(═NRg2)NRc2Rd2, NRc2C(═NRg2)NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, NRc2S(O)2Rb2, S(O)2NRc2Rd2, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;
• RA is H, C1-4 alkyl, C2-4 alkenyl, or C2-4 alkynyl, wherein said C1-4 alkyl, C2-4 alkenyl, or C2-4 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, and C1-4 alkyl;
• RB is H, C1-4 alkyl, C2-4 alkenyl, or C2-4 alkynyl, wherein said C1-4 alkyl, C2-4 alkenyl, or C2-4 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, and C1-4 alkyl;
• RC and RD are independently selected from H, C1-4 alkyl, C2-4 alkenyl, or C2-4 alkynyl, wherein said C1-4 alkyl, C2-4 alkenyl, or C2-4 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, and C1-4 alkyl;
• or RC and RD together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, and C1-4 alkyl;
• Ra, Ra1, Ra2, are Ra3 are independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6haloalkoxy;
• Rb, Rb1, Rb2, are Rb3 are independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, and heterocycloalkylalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6haloalkoxy;
• Rc and Rd are independently selected from H, C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6haloalkoxy;
• or Rc and Rd together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6haloalkyl, and C1-6haloalkoxy;
• Rc1 and Rd1 are independently selected from H, C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, wherein said C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6haloalkoxy;
• or Rc1 and Rd1 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6haloalkyl, and C1-6haloalkoxy;
• Rc2 and Rd2 are independently selected from H, C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkyl, arylheterocycloalkyl, arylheteroaryl, biaryl, heteroarylcycloalkyl, heteroarylheterocycloalkyl, heteroarylaryl, and biheteroaryl, wherein said C1-10 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkyl, arylheterocycloalkyl, arylheteroaryl, biaryl, heteroarylcycloalkyl, heteroarylheterocycloalkyl, heteroarylaryl, and biheteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, hydroxyalkyl, cyanoalkyl, aryl, heteroaryl, C(O)ORa3, C(O)Rb3, S(O)2Rb3, alkoxyalkyl, and alkoxyalkoxy;
• or Rc2 and Rd2 together with the N atom to which they are attached form a 4-, 5-, 6- or 7-membered heterocycloalkyl group or heteroaryl group, each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, hydroxyalkyl, cyanoalkyl, aryl, heteroaryl, C(O)ORa3, C(O)Rb3, S(O)2Rb3, alkoxyalkyl, and alkoxyalkoxy;
• Re is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, (C1-6 alkoxy)-C1-6 alkyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocycloalkylalkyl;
• Rf is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl;
• Rg, Rg1, and Rg2 are independently selected from H, CN, and NO2;
• Rh and Ri are independently selected from H and C1-6 alkyl;
• and
• Rj is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl.