Heterocyclic compounds and uses thereof

A method for treating a subject suffering from a disease or condition mediated by a bromodomain, said method comprising administering to the subject in need thereof an effective amount of a compound of formula (Va),

• wherein the disease or condition is breast cancer, midline carcinomas, acute myeloid leukemia, chronic lymphocytic leukemia, non-small cell lung cancer, prostate cancer, or uveal melanoma,
• wherein the compound of formula (Va) has the following structure:
• or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer, or a deuterated analog thereof,
• wherein:
• R2 is H;
• R4 is H;
• R6 is H;
• R7 is H, —OH, C1-6 alkyl, deuterated C1-6 alkyl, aryl, cycloalkyl, or heterocycloalkyl;
• R1 is heteroaryl optionally substituted with from 1-3 Rj groups;
• each Rj is independently halogen, —CN, —OH, —NH2, —NO2, —C(O)OH, —(S)OH, —C(O)NH2, —C(S)NH2, —S(O)2NH2, —NHC(O)NH2, —NHC(S)NH2, —NHS(O)2NH2, —C(NH)NH2, —CH═C(Rk)(Rk), —ORk, —SRk, OC(O)Rk, —OC(S)Rk, —P(=O)HRk, —P(═O)RkRk, —PH(═O)ORk, —P(═O)(ORk)2, —OP(═O)(ORk)2, —C(O)H, —O(CO)ORk, —C(O)Rk, —C(S)Rk, —C(O)ORk,—C(S)ORk, —S(O)Rk, —S(O)2Rk, —C(O)NHRk, —C(S)NHRk, —C(O)NRkRk, —C(S)NRkRk, —S(O)2NHRk, —S(O)2NRkRk, —C(NH)NHRk, —C(NH)NRkRk, —NHC(O)Rk, —NHC(S)Rk, —NRkC(O)Rk, —NRkC(S)Rk, —NHS(O)2Rk, —NRkS(O)2Rk, —NHC(O)NHRk, —NHC(S)NHRk, —NRkC(O)NH2, —NRkC(S)NH2, —NRkC(O)NHRk, —NRkC(S)NHRk, —NHC(O)NRkRk, —NHC(S)NRkRk, —NRkC(O)NRkRk, —NRkC(S)NRkRk, —NHS(O)2NHRk, —NRkS(O)2NH2,—NRkS(O)2NHRk, —NHS(O)2NRkRk, —NRkS(O)2NRkRk, —NHRk,or —NRkRk,
• each Rk is independently H, C1-6alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl, or cycloalkylalkyl;
• or
• two Rk groups when attached to the same carbon or nitrogen atom are taken together to form a 3- to 6-membered carbocyclic ring to 3- or 8-membered heterocyclic ring having from 1-2 heteroatoms as ring members selected from O, N, and S, wherein the nitrogen or sulfur ring atoms are optionally oxidized;
• R3 is deuterated C1-6alkyl, C1-6alkyl, aryl, heteroaryl, C3-8 cycloalkyl, or heterocycloalkyl, wherein each R3 is optionally substituted with from 1-3 substituents independently selected from CN, —OH, —NH2, —NO2, —C(O)OH, —C(S)OH, —C(O)NH2, —C(S)NH2, —S(O)2NH2, —NHC(O)NH2, —NHC(S)NH2, —NHS(O)2NH2, —C(NH)NH2, —B(OH)2, —Si(Rn)3, —CH═C(Rn)(Rn), —ORn, —SRn, —OC(O)Rn, —OC(S)Rn, —P(═O)HRn, —P(═O)RnRn, —PH(═O)ORn, —P(═O)(ORn)2, —OP(═O)(ORn)2, —C(O)H, —O(CO)ORn, —C(O)Rn, —C(S)Rn, —C(O)ORn, —C(S)ORn, —S(O)Rn, —S(O)2Rn, —C(O)NHRn, —C(S)NHRn, —C(O)NRnRn, —C(S)NRnRn, —S(O)2NHRn, —S(O)2NRnRn, —C(NH)NHRn, —C(NH)NRnRn, —NHC(O)Rn, —NHC(S)Rn, —NRnC(O)Rn, —NRnC(S)Rn, —NHS(O)2Rn, —NRnS(O)2Rn, —NHC(O)NHRn, —NHC(S)NHRn, —NRnC(O)NH2, —NRnC(S)NH2, —NRnC(O)NHRn, —NRnC(S)NHRn, —NHC(O)NRnRn, —NHC(S)NRnRn, —NRnC(O)NRnRn, —NRnC(S)NRnRn, —NHS(O)2NHRn, —NRnS(O)2NH2, —NRnS(O)2NHRn, —NHS(O)2NRnRn, —NRnS(O)2NRnRn, —NHRn, Rn, and —NRnRn, wherein each Rn is independently selected from H, C1-6alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl, and cycloalkylalkyl;
• or two Rn groups when attached to the same carbon or nitrogen atom are taken together to form a 3- to 6-membered carbocyclic ring or 3- to 8-membered heterocyclic ring having from 1-2 heteroatoms as ring members selected from O, N, and S, wherein the nitrogen or sulfur ring atoms are optionally oxidized;
• and
• R5 is
• optionally substituted with from 1 to 2 R11 groups independently selected from D, halogen, C1-6alkyl, deuterated C1-6alkyl, C1-4haloalkyl, C1-4, haloalkoxy, and —CN;
• wherein the wavy line indicates the point of attachment to the rest of molecule.

A method for treating a subject suffering from a disease or condition mediated by a bromodomain, said method comprising administering to the subject in need thereof an effective amount of a compound of formula (Va),

• wherein the disease or condition is breast cancer, midline carcinomas, acute myeloid leukemia, chronic lymphocytic leukemia, non-small cell lung cancer, prostate cancer, or uveal melanoma,
• wherein the compound of formula (Va) has the following structure:
• or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer, or a deuterated analog thereof,
• wherein:
• R2 is H;
• R4 is H;
• R6 is H;
• R7 is H, —OH, C1-6alkyl, deuterated C1-6alkyl, aryl, cycloalkyl, or heterocycloalkyl;
• R1 is heteroaryl optionally substituted with from 1-3 Rj groups;
• each Rj is independently halogen, —CN, —OH, —NH2, —NO2, —C(O)OH, —(S)OH, —C(O)NH2, —C(S)NH2, —S(O)2NH2, —NHC(O)NH2, —NHC(S)NH2, —NHS(O)2NH2, —C(NH)NH2, —CH═C(Rk)(Rk), —ORk, —SRk, OC(O)Rk, —OC(S)Rk, —P(═O)HRk, —P(═O)RkRk, —PH(═O)ORk, —P(═O)(ORk)2, —OP(═O)(ORk)2, —C(O)H, —O(CO)ORk, —C(O)Rk, —C(S)Rk, —C(O)ORk, —C(S)ORk, —S(O)Rk, —S(O)2Rk, —C(O)NHRk, —C(S)NHRk, —C(O)NRkRk, —C(S)NRkRk, —S(O)2NHRk, —S(O)2NRkRk, —C(NH)NHRk, —C(NH)NRkRk, —NHC(O)Rk, —NHC(S)Rk, —NRkC(O)Rk, —NRkC(S)Rk, —NHS(O)2Rk, —NRkS(O)2Rk, —NHC(O)NHRk, —NHC(S)NHRk, —NRkC(O)NH2, —NRkC(S)NH2, —NRkC(O)NHRk, —NRkC(S)NHRk, —NHC(O)NRkRk, —NHC(S)NRkRk, —NRkC(O)NRkRk, —NRkC(S)NRkRk, —NHS(O)2NHRk, —NRkS(O)2NH2, —NRkS(O)2NHRk, —NHS(O)2NRkRk, —NRkS(O)2NRkRk, —NHRk, or —NRkRk;
• each Rk is independently H, C1-6alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl, or cycloalkylalkyl;
• or
• two Rk groups when attached to the same carbon or nitrogen atom are taken together to form a 3- to 6-membered carbocyclic ring or 3- to 8-membered heterocyclic ring having 1-2 heteroatoms as ring members selected from O, N, and S, wherein the nitrogen or sulfur ring atoms are optionally oxidized;
• R3 is aryl or heteroaryl, wherein each R3 is optionally substituted with from 1-3 substituents independently selected from halogen, vinyl, C1-6alkyl, —OH, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy, —CN, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, C3-6cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
• and
• R5 is
• optionally substituted with from 1 to 2 R11 groups independently selected from D, halogen, C1-6alkyl, deuterated C1-6alkyl, C1-4haloalkyl, C1-4haloalkoxy, and —CN;
• wherein the wavy line indicates the point of attachment to the rest of molecule.

A method for treating a subject suffering from a disease or condition mediated by a bromodomain, said method comprising administering to the subject in need thereof an effective amount of a compound of formula (Va),

• wherein the disease or condition is breast cancer, midline carcinomas, acute myeloid leukemia, chronic lymphocytic leukemia, non-small cell lung cancer, prostate cancer, or uveal melanoma,
• wherein the compound of formula (Va) has the following structure:
• or a pharmaceutically acceptable salt, a solvate, a tautomer, a steroisomer, or a deuterated analog thereof,
• wherein:
• R2 is H;
• R4 is H;
• R6 is H;
• R7 is H, —OH, C1-6alkyl, deuterated C1-6alkyl, aryl, cycloalkyl, or heterocycloalkyl;
• R1 is heteroaryl optionally substituted with from 1-3 Rj groups;
• each Rj is independently halogen, —CN, —OH, —NH2, —NO2, —C(O)OH, —(S)OH, —C(O)NH2, —C(S)NH2, —S(O)2NH2, —NHC(O)NH2, —NHC(S)NH2, —NHS(O)2NH2, —C(NH)NH2, —CH═C(Rk)(Rk), —ORk, —SRk, OC(O)Rk, —OC(S)Rk, —P(═O)HRk, —P(═O)RkRk, —PH(═O)ORk, —P(═O)(ORk)2, —OP(═O)(ORk)2, —C(O)H, —O(CO)ORk, —C(O)Rk, —C(S)Rk, —C(O)ORk, —C(S)ORk, —S(O)Rk, —S(O)2Rk, —C(O)NHRk, —C(S)NHRk, —C(O)NRkRk, —C(S)NRkRk, —S(O)2NHRk, —S(O)2NRkRk, —C(NH)NHRk, —C(NH)NRkRk, —NHC(O)Rk, —NHC(S)Rk, —NRkC(O)Rk, —NRkC(S)Rk, —NHS(O)2Rk, —NRkS(O)2Rk, —NHC(O)NHRk, —NHC(S)NHRk, —NRkC(O)NH2, —NRkC(S)NH2, —NRkC(O)NHRk, —NRkC(S)NHRk, —NHC(O)NRkRk, —NHC(S)NRkRk, —NRkC(O)NRkRk, —NRkC(S)NRkRk, —NHS(O)2NHRk, —NRkS(O)2NH2, —NRkS(O)2NHRk, —NHS(O)2NRkRk, —NRkS(O)2NRkRk, —NHRk, or —NRkRk;
• each Rk is independently H, C1-6alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl, or cycloalkylalkyl;
• or
• two Rk groups when attached to the same carbon or nitrogen atom are taken together to form a 3- to 6-membered carbocyclic ring to 3- to 8-membered heterocyclic ring having from 1-2 heteroatoms as ring members selected from O, N, and S, wherein the nitrogen or sulfur ring atoms are optionally oxidized;
• R3 is aryl or heteroaryl, each of which is optionally substituted with from 1-5 substituents independently selected from halogen, —CN, —OH, —NH2, —NO2, —CH═C(Ri)(Ri), —C(O)OH, —C(S)OH, —C(O)NH2, —C(S)NH2, —S(O)2NH2, —NHC(O)NH2, —NHC(S)NH2, —NHS(O)2NH2, —C(NH)NH2, —ORi, —SRi, —OC(O)Ri, —OC(S)Ri, —P(═O)HRi, —P(═O)RiRi, —PH(═O)ORi, —P(═O)(OR)2, —OP(═O)(ORi)2, —C(O)H, —O(CO)ORi, —C(O)Ri, —C(S)Ri, —C(O)ORi, —C(S)ORi, —S(O)Ri, —S(O)2Ri, —C(O)NHRi, —C(S)NHRi, —C(O)NRiRi, —C(S)NRiRi, —S(O)2NHRi, —S(O)2NRiRi, —C(NH)NHRi, —C(NH)NRiRi, —NHC(O)Ri, —NHC(S)Ri, —NRiC(O)Ri, —NRiC(S)Ri, —NHS(O)2Ri, —NRiS(O)2Ri, —NHC(O)NHRi, —NHC(S)NHRi, —NRiC(O)NH2, —NRiC(S)NH2, —NRiC(O)NHRi, —NRiC(S)NHRi, —NHC(O)NRiRi, —NHC(S)NRiRi, —NRiC(O)NRiRi, —NRiC(S)NRiRi, —NHS(O)2NHRi, —NRiS(O)2NH2, —NRiS(O)2NHRi, —NHS(O)2NRiRi, —NRiS(O)2NRiRi, Ri, —NHRi, and —NRiRi, wherein each Ri is independently C1-6alkyl, aryl, aryl-C1-2alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, heteroaryl, heteroaryl-C1-4alkyl, heterocycloalkyl, or heterocycloalkyl-C1-4alkyl, wherein each Ri is further optionally substituted with from 1-3 Rp groups independently selected from halogen, CN, —OH, —NH2, —N(Rq)(Rq), —NO2, —C(O)OH, —C(O)NH2, —S(O)2NH2, —NHC(O)NH2, —C(NH)NH2, —P(═O)HRq, —P(═O)RqRq, —PH(═O)ORq, —P(═O)(ORq)2, —OP(═)(ORq)2, —OC(O)Rq, —OC(S)Rq, —C(O)Rq, —C(S)Rq, —C(O)ORq, —S(O)2Rq, —C(O)NHRq, C1-6alkyl, C1-6alkoxy, halogen, C1-6 haloalkyl, and C1-6 haloalkoxy, and wherein Rq is C1-6alkyl;
• and
• R5 is
• optionally substituted with from 1 to 2 R11 groups independently selected from D, halogen, C1-6alkyl, deuterated C1-6alkyl, C1-4haloalkyl, C1-4haloalkoxy, and —CN;
• wherein the wavy line indicates the point of attachment to the rest of molecule.