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 (III),

• wherein the disease or condition is breast cancer, midline carcinomas, acute myelogenous leukemia, chronic lymphocytic leukemia, non-small cell lung cancer, prostate cancer, or uveal melanoma,
• wherein the compound of formula (III) has the following structure:
• or a pharmaceutically acceptable salt, solvate, a tautomer, a stereoisomer, or a deuterated analog thereof,
• Y1 is N;
• R1 is deuterated C1-6alkyl, C1-6alkyl, aryl, aryl-C1-4alkyl, C3-6-cycloalkyl, C3-6- cycloalkylakyl, heteroaryl, heteroalkyl, heterocycloalkyl, heterocycloalkylalkyl, C2-6alkenyl, or C2-6alkynyl, each of which is optionally substituted with from 1-3 Rjgroups,
• R2 is H;
• R3 is deuterated C1-6alkyl, aryl, aryl-C1-4alkyl, heteroaryl, heteroaryl-C1-4alkyl, C3-8cycloalkyl, C3-8 cycloalkenyl, C3-8 cycloalkyl-C1-4alkyl, C2-6 alkynyl, heterocycloalkyl, or heterocycloalkyl-C1-4alkyl, wherein each R3 is optionally substituted with 1-3 substituents independently selected from CN, -OH, -NH2, -NO2, -C(O)OH, - C(S)OH,-C(O)NH2, -C(S)NH2, -NHC(O)NH2, -NHC(S)NH2, -NHS(O)2NH2, -C(NH)N H2, -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, -NRn, -NRnC(O)NH2, -NRnC(S)NH2, -NRnC(O)NHRn, -NRnC(S)NHRn, -NHC(O)NRnRn, -NHC(S)NRnRn, -NRC(O)NRRn, -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 H, C1-6alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl, or cyclaoalkylylalkyl;
• 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, wherein the aliphatic or aromatic portion of Rn is further optionally substituted with from 1-3 Rh;
• R4 is H;
• R5 is:
• each of which is optionally substituted with from 1-2 R11;
• wherein the wavy line indicates the point of attachment to the rest of molecule and each R11 is independently D, halogen, C1-6alkyl, deuterated C1-6alkyl, C1-4haloalkyl, C1-4haloalkoxy, or CN;
• L is —C(R6)(R7)—, —C(O)—, —S(O)—, —S—, —P(O)(Ra)—, —CH═C(Rb)—, or —Si(Rc)(Rc);
• R6 is H or D;
• R7 is H, D, halogen, —OH, C1-6alkyl, deuterated C1-6alkyl, C2-6alkenyl, C2-6alkynyl, aryl, aryl-C1-4 alkyl, C1-6alkoxy, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, heterocycloalkyl, heterocycloalkyl-C1-4alkyl, heteroaryl, heteroarylalkyl, C1-6haloalkyl, C1-6haloalkoxy, —ORd, —NRdRd, —C(O)ORd, —OC(O)Rd, —OC(O)ORd, —C(O)Rd, —NHC(O)Rd, —C(O)NRdRd, —SO2Rd, —NHSO2Rd, or —SO2NRdRd,
• wherein R7 is further optionally substituted with from 1-3 Rh groups;
• Ra is optionally substituted C1-6alkyl, optionally substituted aryl, or optionally substituted heteroaryl;
• Rb is H or C1-6alkyl;
• each Rc is independently C1-6alkyl or C1-6alkoxy;
• each Rd is independently H, C1-6alkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl, or aryl;
• each Rh is independently halogen, —CN, —OH, —NH2, —NO2, —CH═C(Rk)(Rk), —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)(ORi)2, —OP(═O)(ORi)2, —C(O)H, —O(CO)ORi, —C(O)Ri, —C(S)Ri, —C(O)ORi, —C(S)OR1, —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, or —NRiRi,
• 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;
• Rj is halogen, —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, —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;
• and
• 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 from 1-2 heteroatoms as ring members selected from O, N, and S, wherein the nitrogen or sulfur ring atoms are optionally oxidized, and wherein Rk is optionally substituted with from 1-3 Rh.