2-substituted thiazole hsd17b13 inhibitors and uses thereof

A compound of Formula (I), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:

• wherein:
• Ring A is thiazolyl;
• R1 is hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6deuteroalkyl, C1-C6hydroxyalkyl, or C1-C6aminoalkyl;
• R2 is hydrogen or C1-C6alkyl;
• R3 is C1-C10alkyl, C1-C10haloalkyl, C1-C10deuteroalkyl, C1-C10hydroxyalkyl, C1-C10aminoalkyl, C1-C10heteroalkyl, C2-C10alkenyl, C2-C10alkynyl, C1-C6alkylene(cycloalkyl), C1-C6alkylene(heterocycloalkyl), C1-C6alkylene(aryl), or C1-C6alkylene(heteroaryl);
• wherein the alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally and independently substituted with one or more R3a;
• each R3a 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-C6haloalkyl, C1-C6deuteroalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• or two R3a on the same atom are taken together to form an oxo;
• R4 is deuterium, halogen, C1-C6alkyl, C2-C6haloalkyl, C1-C6deuteroalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6alkylene(cycloalkyl), C1-C6alkylene(heterocycloalkyl), C1-C6alkylene(aryl), or C1-C6alkylene(heteroaryl);
• wherein the alkylene, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally substituted with one or more with one or more R4a;
• each R4a 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-C6haloalkyl, C1-C6deuteroalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6alkylene(cycloalkyl), C1-C6alkylene(heterocycloalkyl), C1-C6alkylene(aryl), or C1-C6alkylene(heteroaryl);
• wherein the alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is optionally and independently substituted with one or more R;
• or two R4a on the same atom are taken together to form an oxo;
• or two R4a on the same carbon are taken together to form a cycloalkyl or heterocycloalkyl;
• each optionally substituted with one or more R;
• or two R4a on the different atoms are taken together to form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• each optionally substituted with one or more R;
• X is N or CRX;
• RX is hydrogen, deuterium, halogen, —CN, —OH, —ORa, —NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C1-C6deuteroalkyl;
• R5 is hydrogen, deuterium, halogen, —CN, —OH, —ORa, —NRcRd, C1-C6alkyl, C1-C6haloalkyl, or C1-C6deuteroalkyl;
• each R6 is independently a halogen;
• each Ra is independently C1-C6alkyl, C1-C6haloalkyl, C1-C6deuteroalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6alkylene(cycloalkyl), C1-C6alkylene(heterocycloalkyl), C1-C6alkylene(aryl), or C1-C6alkylene(heteroaryl);
• wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;
• each Rb is independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6deuteroalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C1-C6heteroalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6alkylene(cycloalkyl), C1-C6alkylene(heterocycloalkyl), C1-C6alkylene(aryl), or C1-C6alkylene(heteroaryl);
• wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more with one or more R;
• 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-C6alkylene(cycloalkyl), C1-C6alkylene(heterocycloalkyl), C1-C6alkylene(aryl), or C1-C6alkylene(heteroaryl);
• wherein each alkyl, alkylene, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more R;
• 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 R;
• each R is independently halogen, —CN, —OH, —OC1-C3alkyl, —OC1-C3haloalkyl, —SC1-C3alkyl, —S(═O)C1-C3alkyl, —S(═O)2C1-C3alkyl, —S(═O)2NH2, —S(═O)2NHC1-C3alkyl, —S(═O)2N(C1-C3alkyl)2, —NH2, —NHC1-C3alkyl, —N(C1-C3alkyl)2, —C(═O)C1-C3alkyl, —C(═O)OH, —C(═O)OC1-C3alkyl, —C(═O)NH2, —C(═O)NHC1-C3alkyl, —C(═O)N(C1-C3alkyl)2, C1-C3alkyl, C1-C3haloalkyl, C1-C3deuteroalkyl, C1-C3hydroxyalkyl, C1-C3aminoalkyl, C1-C3heteroalkyl, or C3-C6cycloalkyl;
• or two R on the same atom form an oxo.