Pyridazino[4,5-D]pyrimidin-5(6H)-one inhibitors of kinases

A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof;

• B is
• (a) phenyl, naphthyl, tetrahydronaphthyl, indenyl, or dihydroindenyl;
• and m is 1, 2, or 3;
• R1 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
• wherein the R1 C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, CN, NO2, ORa, SRa, C(O)Ra, C(O)NRbRc, C(O)ORa, OC(O)Ra, OC(O)NRbRc, NRbRc, NRbC(O)Ra, S(O)Ra, S(O)NRbRc, S(O)2Ra, and NRbS(O)2Ra;
• wherein the R1 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl are optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, —C1-4alkyl-NReRf, CN, NO2, ORd, SRd, C(O)Rd, C(O)NReRf, C(O)ORd, OC(O)Rd, OC(O)NReRf, NReRf, NReC(O)Rd, S(O)Rd, S(O)NReRf, S(O)2Rd, NReS(O)2Rd, and S(O)2NReRf;
• R2, at each occurrence, is independently selected from the group consisting of halo, CN, C1-4 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4-haloalkyl, C1-4 hydroxyalkyl, C1-4 alkoxy, C1-4 haloalkoxy, C1-4-thioalkoxy, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, aryl-C1-6-alkyl-, cycloalkyl-C1-6-alkyl-, heteroaryl-C1-6-alkyl-, heterocycloalkyl-C1-6-alkyl-, NR6R7—C1-6-alkyl-, OR5, C(O)R5, C(O)NR6R7, C(O)OR5, OC(O)R5, OC(O)NR6R7, NR6R7, NR6C(O)R5, S(O)R5, S(O)NR6R7, S(O)2R5, NR6S(O)2R5, and S(O)2NR6R7, wherein the R2 cycloalkyl, aryl, heterocycloalkyl, and heteroaryl, alone or part of another group, are optionally substituted with one, two, or three R3;
• R3, at each occurrence, is independently selected from the group consisting of halo, C1-4 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, amino-C1-4-alkyl-, C1-4 alkylamino-C1-4 alkyl-, C1-4 dialkylamino-C1-4 alkyl-, hydroxy-C1-4-alkyl-, C1-4 alkyl-C1-4 alkoxy, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, aryl-(C1-4 alkyl)-, cycloalkyl-(C1-4 alkyl)-, heteroaryl-(C1-4 alkyl)-, heterocycloalkyl-(C1-4 alkyl)-, CN, NO2, ORn, SRn, C(O)Rn, C(O)NRoRp, C(O)ORn, OC(O)Rn, OC(O)NRoRp, NRoRp, NRoC(O)Rn, S(O)Rn, S(O)NRoRp, S(O)2Rn, NRoS(O)2Rn, and S(O)2NRoRp, wherein the R3 aryl, cycloalkyl, heteroaryl, and heterocycloalkyl, alone or as part of another group, are optionally substituted with one, two or three R8;
• R4 is hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy-C1-6-alkyl, C1-6 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, aryl-C1-6-alkyl-, cycloalkyl-C1-6-alkyl-, heteroaryl-C1-6-alkyl-, heterocycloalkyl-C1-6-alkyl-, wherein the R4 aryl, cycloalkyl, heteroaryl, and heterocycloalkyl, alone or part of another group, are optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, C1-6 alkyl, C2-6 alkenyl, C1-4 haloalkyl, alkoxy-C1-6-alkyl-, hydroxy-C1-6-alkyl-, heteroaryl, heterocycloalkyl, aryl-C1-6-alkyl-, cycloalkyl-C1-6-alkyl-, heteroaryl-C1-6-alkyl-, heterocycloalkyl-C1-6-alkyl-, Rm-heterocycloalkyl-C1-6-alkyl-, CN, NO2, ORg, SRg, C(O)Rg, C(O)NRhRi, C(O)ORg, OC(O)Rg, OC(O)NRhRi, —C1-6 alkyl-NRhRi, NRhRi, NRhC(O)Rg, NRhNRiRg, S(O)Rg, S(O)NRhRi, S(O)2Rg, NRhS(O)2Rg, and S(O)2NRhRi;
• wherein the R4 C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, alone or part of another group, are optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, CN, NO2, ORj, SRj, C(O)Rj, C(O)NRkRl, C(O)ORj, OC(O)Rj, OC(O)NRkRl, NRkRl, NRkC(O)Rj, S(O)Rj, S(O)NRkRl, S(O)2Rj, NRkS(O)2Rj, and S(O)2NRkRl;
• R5 is independently selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6-haloalkyl, heteroaryl-C1-6-alkyl-, heterocycloalkyl-C1-6-alkyl-, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl, wherein the R5 cycloalkyl, heteroaryl, and heterocycloalkyl, alone or as part of another group, are optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, CN, OH, C1-4 alkyl, C1-4-haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-4 alkylamino, C1-4 dialkylamino, C(O)OH, C(O)C1-4 alkyl, C(O)NH2, C(O)NH(C1-4 alkyl), or C(O)N(C1-4 alkyl)2;
• R6 and R7, at each occurrence, are independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6-haloalkyl, C1-6 hydroxyalkyl, C1-4 dialkylamino-C1-4 alkyl-, heteroaryl-C1-6-alkyl-, heterocycloalkyl-C1-6-alkyl-, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl, wherein the R6 and R7 aryl, cycloalkyl, heteroaryl, and heterocycloalkyl, alone or as part of another group, are optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, CN, OH, C1-4 alkyl, C1-4-haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-4 alkylamino, C1-4 dialkylamino, C(O)OH, C(O)C1-4 alkyl, C(O)NH2, C(O)NH(C1-4 alkyl), or C(O)N(C1-4 alkyl)2;
• R8 is independently selected from the group consisting of halo, C1-4 alkyl, C1-4alkylamino, C1-4 dialkylamino-C1-4 alkyl-, or 1-methylpiperazinyl;
• Ra, at each occurrence, is independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the Ra aryl, cycloalkyl, heteroaryl, and heterocycloalkyl alone or as part of another group, are optionally substituted with one, two or three substituents independently selected from the group consisting of halo and C1-4 alkyl;
• Rb and Rc, at each occurrence, are independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the Rb or Rc aryl, cycloalkyl, heteroaryl, and heterocycloalkyl alone or as part of another group, are optionally substituted with one, two or three substituents independently selected from the group consisting of halo and C1-4 alkyl;
• Rd, at each occurrence, is independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the Rd aryl, cycloalkyl, heteroaryl, and heterocycloalkyl, alone or part of another group, are optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo and C1-4 alkyl;
• Re and Rf, at each occurrence, are independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the Re or Rf aryl, cycloalkyl, heteroaryl, and heterocycloalkyl alone or as part of another group, are optionally substituted with one, two or three substituents independently selected from the group consisting of halo and C1-4 alkyl;
• Rg, at each occurrence, is independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the Rg aryl, cycloalkyl, heteroaryl, and heterocycloalkyl alone or as part of another group, are optionally substituted with one, two or three substituents independently selected from the group consisting of halo and C1-4 alkyl;
• Rh and Ri, at each occurrence, are independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the Rh or Ri aryl, cycloalkyl, heteroaryl, and heterocycloalkyl alone or as part of another group, are optionally substituted with one, two or three substituents independently selected from the group consisting of halo and C1-4 alkyl;
• Rj, at each occurrence, is independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the Rj aryl, cycloalkyl, heteroaryl, and heterocycloalkyl alone or as part of another group, are optionally substituted with one, two or three substituents independently selected from the group consisting of halo and C1-4 alkyl;
• Rk and Rl, at each occurrence, are independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the Rk or Rl aryl, cycloalkyl, heteroaryl, and heterocycloalkyl alone or as part of another group, are optionally substituted with one, two or three substituents independently selected from the group consisting of halo and C1-4 alkyl;
• Rn, at each occurrence, is independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the Rn aryl, cycloalkyl, heteroaryl, and heterocycloalkyl alone or as part of another group, are optionally substituted with one, two or three substituents independently selected from the group consisting of halo and C1-4 alkyl;
• Rm, at each occurrence, is independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —C(O)C1-6 alkyl, and C1-6 haloalkyl;
• and
• Ro and Rp, at each occurrence, are independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the Ro or Rp aryl, cycloalkyl, heteroaryl, and heterocycloalkyl alone or as part of another group, are optionally substituted with one, two or three substituents independently selected from the group consisting of halo and C1-4 alkyl.