Bicyclic heterocyclic derivatives and their use as pharmaceuticals

A compound of Formula I:

• or a pharmaceutically acceptable salt or solvate thereof;
• wherein
• W is N or CR;
• X is —CH2—, —NH— or —O—;
• Y is —NH— or —O—;
• A is N, or CR7;
• B is N, or CR8;
• L is (CR9R10)m, (CR9R10)pO(CR9R10)q, (CR9R10)pS(CR9R10)q, or (CR9R10)pNR11(CR9R10)q;
• Cy is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, each optionally substituted by 1, 2, 3, 4, or 5 R12;
• R is H, halo, C1-C6 alkyl, C1-C6 haloalkoxy;
• C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 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 is H, C1-C8 alkyl, aryl, heteroaryl, aryl-C1-C6 alkyl, or heteroaryl-C1-C6 alkyl, S(O)RB, S(O)NRCRD, S(O)2RB, or S(O)2NRCRD;
• each R2, R3, R4, R7 and R8 is independently selected from H, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, OH, 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;
• or R2 and R3, or R3 and R4 together with the carbon atom to which they are attached form a 4- to 7-membered cycloalkyl group or 5- to 7-membered heterocycloalkyl group, or heteroaryl group, each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, —C1-C6 alkyl NRcRd, —C1-C6 alkyl-Cy1, CN, NO2, Oxo, 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, P(O)ReRf, P(O)OReORf, S(O)Rb, S(O)NRcRd, S(O)2Rb, NRcS(O)2Rb, or S(O)2NRcRd;
• R5 is halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, CN, C(O)RB, C(O)NRCRD, S(O)RB, S(O)NRCRD, S(O)2RB, S(O)2NRCRD, (CR9R10)mCy1, C2-C6 alkenyl-Cy1, C2-C6 alkynyl-Cy1, C2-C6 alkynyl-O-Cy1, (CR9R10)pO(CR9R10)qCy1, (CR9R10)pS(CR9R10)qCy1, (CR9R10)pNR11(CR9R10)qCy1, Cy2(CR9R10)mCy1, Cy2(CR9R10)pO(CR9R10)qCy1, Cy2(CR9R10)pS(CR9R10)qCy1, or Cy2(CR9R10)pNR11(CR9R10)qCy1;
• R6 is H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, CN, NO2, C(O)ORA, C(O)RB, C(O)NRCRD, S(O)RB, S(O)NRCRD, S(O)2RB, or S(O)2NRCRD;
• each R9 and R10 is independently selected from H, halo, OH, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 alkoxy-C1-C6 alkyl, C1-C6 cyanoalkyl, heterocycloalkyl, cycloalkyl, C1-C6 haloalkyl, CN, or NO2;
• or R9 and R10 together with the C atom to which they are attached form a 3, 4, 5, 6, or 7-membered cycloalkyl or heterocycloalkyl ring, each optionally substituted by 1, 2, or 3 substituents independently selected from halo, OH, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 alkoxy-C1-C6 alkyl, C1-C6 cyanoalkyl, heterocycloalkyl, cycloalkyl, C1-C6 haloalkyl, CN, or NO2;
• R11 is H, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl;
• R12 is H, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, CN, NO2, N3, ORA, SRA, C(O)RB, C(O)NRCRD, C(O)ORA, OC(O)RB, OC(O)NRCRD, NRCRD, NRCC(O)RD, NRCC(O)NRcRD, NRCC(O)ORA, P(O)RERF, P(O)OREORF, S(O)RB, S(O)NRCRD, S(O)2RB, NRCS(O)2RB, S(O)2NRCRD, Cy3, OCy3, O—C1-C6 alkyl-Cy3, or O—C1-C6 alkyl-Cy3-C0-C6 alkyl-Cy4;
• wherein two adjacent R12, together with the atoms to which they are attached, optionally form a fused 4-10 membered cycloalkyl ring or a fused 4-10 membered heterocycloalkyl ring, each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, CN, NO2, Oxo, 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, OP(O)OReORf, P(O)OReORf, S(O)Rb, S(O)NRcRd, S(O)2Rb, NRcS(O)2Rb, S(O)2NRcRd, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;
• Cy1 is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, each optionally substituted by 1, 2, 3, 4, or 5 R13;
• each Cy2, Cy3, and Cy4 are independently selected from aryl, cycloalkyl, heteroaryl, or heteorcycloalkyl;
• R13 is H, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, CN, NO2, N3, ORA, SRA, C(O)RB, C(O)NRCRD, C(O)ORA, OC(O)RB, OC(O)NRCRD, NRCRD, NRCC(O)RD, NRCC(O)NRCRD, NRCC(O)ORD, P(O)RERF, P(O)OREORF, S(O)RB, S(O)NRCRD, S(O)2RB, NRCS(O)2RB, S(O)2NRCRD, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl;
• wherein two adjacent R13, together with the atoms to which they are attached, optionally form a fused 4-10 membered cycloalkyl ring or a fused 4-10 membered heterocycloalkyl ring, each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, halosulfanyl, CN, NO2, Oxo, 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, OP(O)OReORf, P(O)OReORf, S(O)Rb, S(O)NRcRd, S(O)2Rb, NRcS(O)2Rb, S(O)2NRcRd, aryl, cycloalkyl, heteroaryl, and heterocycloalkyl;
• wherein the alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy and alkoxy groups of any of the R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 substituents can be unsubstituted or substituted with 1, 2, or 3 R14 substituents independently selected from halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkylOH, C1-C6 alkyl-O—C1-C6 alkyl, CN, B(OH)2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)NRc1Rd1, NRc1C(O)ORa1, P(O)OReRf, OP(O)OReORf, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, NRc1S(O)2Rb1, S(O)2NRc1Rd1, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl;
• wherein the aryl, heteroaryl, cycloalkyl and heterocycloalkyl groups, arylalkyl and heteroarylalkyl groups of any of the R1, R9, R10, Cy2, Cy3 and Cy4 groups can be unsubstituted or substituted with 1, 2, 3 or 4 R15 substituents independently selected from halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkylOH, C1-C6 alkyl-O—C1-C6 alkyl, CN, NO2, N3, B(OH)2, 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, P(O)Re1Rf1, P(O)ORe1ORf1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, NRc1S(O)2Rb1, S(O)2NRc1Rd1, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl;
• RA is independently selected from H, C1-C6 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, cycloalkyl, cycloalkylalkyl, —C1-C6 alkyl-Cy3, heterocycloalkyl, heterocycloalkylalkyl, aryl, or heteroaryl, wherein said C1-C6 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl or heteroaryl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, halo, C1-C4 alkyl;
• NO2, Oxo, 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, OP(O)OReRf, P(O)OReORf, S(O)Rb, S(O)NRcRd, S(O)2Rb, NRcS(O)2Rb, S(O)2NRcRd;
• RB is independently selected from H, C1-C6 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, wherein said C1-C6 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, alkylamino, dialkylamino, halo, or C1-C4 alkyl;
• each RC and RD are independently selected from H, C1-C6 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, wherein said C1-C6 alkyl, C2-C4 alkenyl, C2-C4 alkynyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, alkylamino, dialkylamino, halo, or C1-C4 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, alkylamino, dialkylamino, halo, or C1-C4 alkyl;
• RE is independently H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, (C1-C4 alkoxy)-C1-C4 alkyl, C2-C4 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocycloalkylalkyl;
• RF is independently H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl;
• each Ra and Ra1 are independently selected from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl, wherein said C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4 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, alkylamino, dialkylamino, halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, or C1-C4 haloalkoxy;
• each Rb and Rb1 are independently selected from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkylalkyl, wherein said C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4 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, alkylamino, dialkylamino, halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, or C1-C4 haloalkoxy;
• each Rc and Rd are independently selected from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkyl, arylheterocycloalkyl, arylheteroaryl, biaryl, heteroarylcycloalkyl, heteroarylheterocycloalkyl, heteroarylaryl, or biheteroaryl, wherein said C1-4 alkyl, C1-4 haloalkyl, C2-4 alkenyl, C2-4 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkylalkyl, arylcycloalkyl, arylheterocycloalkyl, arylheteroaryl, biaryl, heteroarylcycloalkyl, heteroarylheterocycloalkyl, heteroarylaryl, or biheteroaryl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, alkylamino, dialkylamino, halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 hydroxyalkyl, C1-C4 cyanoalkyl, aryl, heteroaryl, C(O)ORa1, C(O)Rb1, S(O)2Rb1, alkoxyalkyl, and alkoxyalkoxy;
• 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, alkylamino, dialkylamino, halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, hydroxyalkyl, cyanoalkyl, aryl, heteroaryl, C(O)ORa1, C(O)Rb1, S(O)2Rb1, alkoxyalkyl, and alkoxyalkoxy;
• each Rc1 and Rd1 are independently selected from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl or heterocycloalkylalkyl, wherein said C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4 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, alkylamino, dialkylamino, halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, or C1-C4 haloalkoxy;
• 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, alkylamino, dialkylamino, halo, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, and C1-4 haloalkoxy;
• each Re and Re1 are independently selected from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, (C1-C4 alkoxy)-C1-C4 alkyl, C2-C4 alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, arylalkyl, cycloalkylalkyl, heteroarylalkyl, or heterocycloalkylalkyl;
• each Rf and Rf1 are independently selected from H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, aryl, cycloalkyl, heteroaryl, or heterocycloalkyl;
• each m is independently 0, 1, 2, 3, or 4;
• each p is independently 0, 1, 2, 3, or 4;
• and
• each q is independently 0, 1, 2, 3, or 4.