Bromodomain inhibitors

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

• wherein
• Rx is hydrogen or C1-C3 alkyl;
• Ry is C1-C3 alkyl, —(C2-C3 alkylenyl)-OH, or C1-C3 haloalkyl;
• X1 is N or CRx1 wherein
• Rx1 is hydrogen, C2-C6 alkenyl, C2-C6 alkynyl, —C(O)ORax1, —C(O)NRbx1Rcx1, —C(O)Rdx1, S(O)2Rdx1, —S(O)2NRbx1Rcx1, Gx1, C1-C6 haloalkyl, or C1-C6 alkyl;
• wherein the C1-C6 alkyl is optionally substituted with one substituent selected from the group consisting of ORax1, SRax1, S(O)Rdx1, S(O)2Rdx1, NRbx1Rcx1, —C(O)Rax1, —C(O)ORax1, —C(O)NRbx1Rcx1, —S(O)2NRbx1Rcx1, and Gx1;
• Rax1, Rbx1, and Rcx1, at each occurrence, are each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, Ga, or —(C1-C6 alkylenyl)-Ga;
• Rdx1, at each occurrence, are each independently C1-C6 alkyl, C1-C6 haloalkyl, Ga, or —(C1-C6 alkylenyl)-Ga;
• X2 is N or CRx2;
• wherein
• Rx2 is hydrogen, C2-C6 alkenyl, C2-C6 alkynyl, —C(O)ORax2, —C(O)NRbx2Rcx2, —C(O)Rdx2, —C(O)H, S(O)2Rdx2, —S(O)2NRbx2Rcx2, Gx2, C1-C6 haloalkyl, or C1-C6 alkyl;
• wherein the C1-C6 alkyl is optionally substituted with one substituent selected from the group consisting of ORax2, SRax2, S(O)Rdx2, S(O)2Rdx2, NRbx2Rcx2, —C(O)Rax2, —C(O)ORax2, —C(O)NRbx2Rcx2, —S(O)2NRbx2Rcx2, and Gx2;
• Rax2, Rbx2, and Rcx2, at each occurrence, are each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, Gb, or —(C1-C6 alkylenyl)-Gb;
• Rdx2, at each occurrence, is independently C1-C6 alkyl, C1-C6 haloalkyl, Gb, or —(C1-C6 alkylenyl)-Gb;
• Y1 is N or CRu;
• wherein Ru is hydrogen, C1-C6 alkyl, halogen, or C1-C6 haloalkyl;
• A1 is N or CR1, A2 is N or CR2, A3 is N or CR3;
• and A4 is N or CR4;
• with the proviso that zero, one, two, or three of A1, A2, A3, and A4 are N;
• R1, R3, and R4 are each independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, C1-C6 haloalkyl, CN, or NO2;
• R2 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, C1-C6 haloalkyl, —CN, NO2, G2a, —OR2a, —OC(O)R2d, —OC(O)NR2bR2c, —SR2a, —S(O)2R2d, —S(O)2NR2bR2c, —C(O) R2d, —C(O)OR2a, —C(O)NR2bR2c, —NR2bR2c, —N(R2e)C(O)R2d, —N(R2e)S(O)2R2d, —N(R2e)C(O)O(R2d), —N(R2e)C(O)NR2bR2c, —N(R2e)S(O)2NR2bR2c, —(C1-C6 alkylenyl)-G2a, —(C1-C6 alkylenyl)-OR2a, —(C1-C6 alkylenyl)-OC(O)R2d, —(C1-C6 alkylenyl)-OC(O)NR2bR2c, —(C1-C6 alkylenyl)-S(O)2R2d, —(C1-C6 alkylenyl)-S(O)2NR2bR2c, —(C1-C6 alkylenyl)-C(O)R2d, —(C1-C6 alkylenyl)-C(O)OR2a, —(C1-C6 alkylenyl)-C(O)NR2bR2c, —(C1-C6 alkylenyl)-NR2bR2c, —(C1-C6 alkylenyl)-N(R2e)C(O)R2d, —(C1-C6 alkylenyl)-N(R2e)S(O)2R2d, —(C1-C6 alkylenyl)-N(R2e)C(O)O(R2a), —(C1-C6 alkylenyl)-N(R2e)C(O)NR2bR2c, —(C1-C6 alkylenyl)-N(R2e)S(O)2NR2bR2c, and —(C1-C6 alkylenyl)-CN;
• R2a, R2b, R2c, and R2e, at each occurrence, are each independently hydrogen, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, G2b, or C1-C6 alkyl wherein the C1-C6 alkyl is optionally substituted with one substituent selected from the group consisting of —ORz1, NRz1Rz2, —C(O)ORz1, —C(O)NRz1Rz2, —S(O)2Rz1, —S(O)2NRz1Rz2 and G2b;
• R2d, at each occurrence, is independently C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, G2, or C1-C6 alkyl wherein the C1-C6 alkyl is optionally substituted with one substituent selected from the group consisting of —ORz1,
• NRz1Rz2, —C(O)ORz1, —C(O)NRz1Rz2, —S(O)2Rz1, —S(O)2NRz1Rz2, and G2b;
• Rz1 and Rz2, at each occurrence, are each independently hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl;
• Gx1, Gx2, Ga, Gb, G2a, and G2b, at each occurrence, are each independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl, and each of which is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 of Rw;
• L1 is absent, CH2, C(O), C(H)(OH), (CH2)mO, (CH2)mS(O)n wherein n is 0, 1, or 2;
• or (CH2)mN(Rz) wherein Rz is hydrogen, C1-C3 alkyl, C1-C3 haloalkyl, (C2-C3 alkylenyl)-OH, or unsubstituted cyclopropyl;
• m is 0 or 1;
• G1 is C1-C6 alkyl, alkoxyalkyl, G1a or —(C1-C6 alkylenyl)-G1a;
• wherein each G1a is independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl, and each G1a is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 of Rw;
• Rv and Rw, at each occurrence, are each independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, C1-C6 haloalkyl, —CN, oxo, —ORh, —OC(O)Ri, —OC(O)NRjRk, —SRh, —S(O)2Rh, —S(O)2NRjRk, —C(O)Rh, —C(O)-monocyclic heterocycle, —C(O)-monocyclic heteroaryl, —C(O)ORh, —C(O)NRjRk, —NRjRk, —N(Rh)C(O)Ri, —N(Rh)S(O)2Ri, —N(Rh) C(O)O(Ri), —N(Rh)C(O)NRjRk, —(C1-C6 alkylenyl)-ORh, —(C1-C6 alkylenyl)-OC(O)Ri, —(C1-C6 alkylenyl)-OC(O)NRjRk, —(C1-C6 alkylenyl)-S(O)2Rh, —(C1-C6 alkylenyl)-S(O)2NRjRk, —(C1-C6 alkylenyl)-C(O)Rh, —(C1-C6 alkylenyl)-C(O)ORh, —(C1-C6 alkylenyl)-C(O)NRjRk, —(C1-C6 alkylenyl)-NRjRk, —(C1-C6 alkylenyl)-N(Rh)C(O)Ri, —(C1-C6 alkylenyl)-N(Rh)S(O)2Ri, —(C1-C6 alkylenyl)-N(Rh)C(O)O(Ri), —(C1-C6 alkylenyl)-N(Rh)C(O)NRjRk, or —(C1-C6 alkylenyl)-CN;
• Rh, Rj, Rk, at each occurrence, are each independently hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl;
• and
• Ri, at each occurrence, is independently C1-C6 alkyl or C1-C6 haloalkyl.