Dichlorophenol HSD17B13 inhibitors and uses thereof

A method of therapeutically treating a disease that is a liver disease associated with HSD17B13, a metabolic disease associated with HSD17B13, or a cardiovascular disease associated with HSD17B13, the method comprising administering a compound of Formula (Ia), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:

• wherein:
• Y is N or CR1;
• each R1 are independently hydrogen, deuterium, halogen, —CN, —OH, —ORa, —NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C1-C6deuteroalkyl;
• L is —C(═O) NR3—;
• R3 is hydrogen, C1-C6alkyl, C1-C6 haloalkyl, or C1-C6deuteroalkyl;
• R5a, R5b, R5c, and R5d are independently hydrogen, deuterium, halogen, —CN, —OH, —ORa, —SH, —SRa, —NRcRd, C1-C6 alkyl, C1-C6haloalkyl, or C1-C6deuteroalkyl;
• RA is —(C(R12)2)paryl or —(C(R12)2)pheteroaryl;
• wherein the aryl and heteroaryl is optionally and independently substituted with one or more RAb;
• each RAb are independently deuterium, halogen, —CN, —NO2, —OH, —ORa, —OC(═O)Ra, —OC(═O)ORb, —OC(═O) NRcRd, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —S(═O)2NRcRd, —NRcRd, —NRbC(═O) NRcRd, —NRbC(═O)Ra, —NRbC(═O)ORb, —NHS(═O)2Ra, —C(═O)Ra, —C(═O)C(═O)Ra, —C(═O)ORb, —C(═O) NRcRd, —C(═O)C(═O) NRcRd, C1-C6alkyl, C1-C6 haloalkyl, C1-C6deuteroalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally and independently substituted with one or more RAaa:
• each RAaa is independently deuterium, halogen, —CN, —NO2, —OH, —ORa, —OC(═O)Ra, —OC(═O)ORb, —OC(═O) NRcRd, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —S(═O)2NRcRd, —NRcRd, —NRbC(═O) NRcRd, —NRbC(═O)Ra, —NRbC(═O)ORb, —NHS(═O)2Ra, —C(═O)Ra, —C(═O)C(═O)Ra, —C(═O)ORb, —C(═O) NRcRd, —C(═O)C(═O) NRcRd, C1-C6alkyl, C1-C6 haloalkyl, C1-C6deuteroalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• each R12 is independently hydrogen, deuterium, halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6 deuteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• or two R12 on the same carbon are taken together to form a cycloalkyl or a heterocycloalkyl;
• wherein the cycloalkyl and heterocycloalkyl is optionally substituted with deuterium, halogen, —OH, —OCH3, —NH2, —NHCH3, —N(CH3)2, C1-C6alkyl, C1-C6haloalkyl, or C1-C6deuteroalkyl;
• p is 1;
• each Ra is independently C1-C6alkyl, C1-C6haloalkyl, C1-C6deuteroalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6 heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6alkyl(cycloalkyl), C1-C6alkyl(heterocycloalkyl), C1-C6alkyl(aryl), or C1-C6alkyl(heteroaryl);
• wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OCH3, —S(═O) CH3, —S(═O)2CH3, —S(═O)2NH2, —S(═O)2NHCH3, —S(═O)2N(CH3)2, —NH2, —NHCH3, —N(CH3)2, —C(═O) CH3, —C(═O) OH, —C(═O) OCH3, C1-C6alkyl, C1-C6haloalkyl, C1-C6deuteroalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl;
• each Rb is independently hydrogen, C1-C6alkyl, C1-C6 haloalkyl, C1-C6deuteroalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6alkyl(cycloalkyl), C1-C6alkyl(heterocycloalkyl), C1-C6alkyl(aryl), or C1-C6alkyl(heteroaryl);
• wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OCH3, —S(═O) CH3, —S(═O)2CH3, —S(═O)2NH2, —S(═O)2NHCH3, —S(═O)2N(CH3)2, —NH2, —NHCH3, —N(CH3)2, —C(═O) CH3, —C(═O) OH, —C(═O) OCH3, C1-C6alkyl, C1-C6haloalkyl, C1-C6 deuteroalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl;
• and
• each Rc and Rd are independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6deuteroalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6alkyl(cycloalkyl), C1-C6alkyl(heterocycloalkyl), C1-C6alkyl(aryl), or C1-C6alkyl(heteroaryl);
• wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OCH3, —S(═O) CH3, —S(═O)2CH3, —S(═O)2NH2, —S(═O)2NHCH3, —S(═O)2N(CH3)2, —NH2, —NHCH3, —N(CH3)2, —C(═O) CH3, —C(═O) OH, —C(═O) OCH3, C1-C6alkyl, C1-C6haloalkyl, C1-C6 deuteroalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl;
• or Rc and Rd are taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OCH3, —S(═O) CH3, —S(═O)2CH3, —S(═O)2NH2, —S(═O)2NHCH3, —S(═O)2N(CH3)2, —NH2, —NHCH3, —N(CH3)2, —C(═O) CH3, —C(═O) OH, —C(═O) OCH3, C1-C6alkyl, C1-C6haloalkyl, C1-C6 deuteroalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, or C1-C6heteroalkyl.