Compounds and methods for treating alcohol disorder

A compound having Formula (XII), Formula (XII-a), or Formula (XII-b), or a pharmaceutically acceptable salt or solvate thereof:

• wherein:
• X is O, S, or N—R4;
• Y is N;
• m and n are each independently 1-3, wherein the ring that m and n define form a 4-6 membered heterocycle;
• R1, R4, and R5 are each independently H, D, halo, oxo, alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, and NO2;
• wherein when R1, R4, or R5 is alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, then R1, R4, or R5 is optionally substituted with at least one Rb substituent;
• R9 and R10 are each independently H, D, halo, oxo, alkoxy, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, CN, NO2, ORa, and SRa;
• wherein when R9 or R10 is alkyl, alkoxy, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, then R9 or R10 is optionally substituted with at least one Rb substituent;
• each Ra is independently selected from H, D, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-14 membered heterocycloalkyl)-C1-4 alkyl;
• wherein when Ra is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl- or (4-14 membered heterocycloalkyl)-C1-4 alkyl, then Ra is optionally substituted with 1, 2, 3, 4, or 5 independently selected Rd substituents;
• each Rb substituent is independently selected from a bond, H, D, halo, oxo, C1-6 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C7-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, (4-14 membered heterocycloalkyl)-C1-4 alkyl, CN, OH, NH2, NO2, NHORc, ORc, SRc, C(O)Rc, C(O)NRcRc, C(O)ORc, OC(O)Rc, OC(O)NRcRc, C(═NRc)NRcRc, NRc(═NRc)NRcRc, NRc(═NOH)NRcRc, NRc(═NCN)NRcRc, SF5, P(O)RcRc, P(O)(ORc)(ORc), NHRc, NRcRc, NRc(O)Rc, NRcC(O)ORc, NRcC(O)NRcRc, NRcS(O)Rc, NRS(O)(═NRc)Rc, NRS(O)2Rc, NRcS(O)2NRcRc, S(O)Rc, S(O)NRcRc, S(O)2Rc or S(O)2NRcRc;
• wherein when Rb is C1-6 alkoxy, C1-4haloalkyl, C1-4 haloalkoxy, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-14 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl- or (4-14 membered heterocycloalkyl)-C1-4 alkyl, then Rb is optionally substituted with 1, 2, or 3 independently selected Rd substituents;
• each Rc is independently selected from H, D, OH, C1-6 alkyl, C1-6 alkoxy, C1-4 haloalkyl, C2-6alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl;
• wherein when Rc is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl- or (4-10 membered heterocycloalkyl)-C1-4 alkyl, then Rc is optionally substituted with 1, 2, 3, 4, or 5 independently selected Rf substituents;
• each Rf is independently selected from halogen, C1-1O alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl, halo, and CN;
• wherein when Rf is C1-4alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl, then Rf is optionally substituted with 1, 2, 3, 4, or 5 independently selected Rn substituents;
• each Rn is independently selected from C1-10 alkyl, C1-4 haloalkyl, halo, CN, Ro, NHORo, ORo, and SRo;
• each Rd is independently selected from D, oxo, C1-6 alkyl, C1-6 haloalkyl, halo, C3-10 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl, CN, NH2, NHORe, ORe, and SRe,
• wherein when Rd is C1-6alkyl, C3-10 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, or (4-10 membered heterocycloalkyl)-C1-4 alkyl, then Rd is optionally substituted with 1, 2, or 3 independently selected Rf substituents;
• each Re is independently selected from H, D, CN, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl,
• wherein when Re is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl- or (4-10 membered heterocycloalkyl)-C1-4 alkyl, then Re is optionally substituted with 1, 2 or 3 independently selected Rg substituents;
• each Rg is independently selected from H, D, C1-6 alkyl, C1-4 haloalkyl, C2-6alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl,
• wherein when Rg is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl- or (4-10 membered heterocycloalkyl)-C1-4 alkyl, then Rg is optionally substituted with 1, 2 or 3 independently selected RP substituents;
• each RP is independently selected from C1-10 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl, C3-10 cycloalkyl-C1-4 alkyl, (5-10 membered heteroaryl)-C1-4 alkyl, and (4-10 membered heterocycloalkyl)-C1-4 alkyl, halo, and CN;
• each Ro or Rr is independently selected from H, D, C1-10 alkyl, C3-6cycloalkyl, C6-10 aryl, 5 or 6-membered heteroaryl, C1-4 haloalkyl, C2-4alkenyl, and C2-4 alkynyl,
• wherein when Ro or Rr is C1-10 alkyl, C3-6 cycloalkyl, C6-10 aryl, 5 or 6-membered heteroaryl, C2-4 alkenyl, and C2-4 alkynyl, then Ro or Rr is optionally substituted with 1, 2 or 3 independently selected Rq substituents;
• each Rq is independently selected from D, OH, CN, —COOH, NH2, halo, C1-6alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-4 alkylthio, phenyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, —CONHR12, —NHC(O)R12, —OC(O)R12, —C(O)OR12, —C(O)R12, —SO2R12, —NHSO2R12, —SO2NHR12 and NR12R12,
• wherein when Rq is C1-6 alkyl, phenyl, 4-6 membered heterocycloalkyl or 5-6 membered heteroaryl, then Rg is optionally substituted with OH, CN, —COOH, NH2, C1-6 alkoxy, C3-6cycloalkyl or 4-6 membered heterocycloalkyl;
• and
• each R12 is independently C1-6 alkyl,
• and
• wherein when n and m together are 4 and Rb is H, R1 is not alkyl.