HSD17B13 inhibitors and uses thereof

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

• wherein:
• R1 is halogen;
• R2 is hydrogen;
• each R3 is independently hydrogen, deuterium, halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —NO2, —NRcRd, —NHS(═O)2Ra, —S(═O)2NRcRd, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRcRd, —OC(═O)NRcRd, —NRbC(═O)NRcRd, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, —C1-C6C(═O)ORb, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• L1 is —O;
• X1 is N or C—RX1;
• RX1 is deuterium, halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —NO2, —NRcRd, —NHS(═O)2Ra, —S(═O)2NRcRd, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRcRd, —OC(═O)NRcRd, —NRbC(═O)NRcRd, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, —C1-C6C(═O)ORb, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• X2 is N or C—RX2;
• RX2 is hydrogen, deuterium, halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —NO2, —NRcRd, —NHS(═O)2Ra, —S(═O)2NRcRd, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRcRd, —OC(═O)NRcRd, —NRbC(═O)NRcRd, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, —C1-C6C(═O)ORb, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• X3 is N or C—RX3;
• RX3 is hydrogen, deuterium, halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —NO2, —NRcRd, —NHS(═O)2Ra, —S(═O)2NRcRd, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRcRd, —OC(═O)NRcRd, —NRbC(═O)NRcRd, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, —C1-C6C(═O)ORb, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• X4 is N or C—RX4;
• RX4 is hydrogen, deuterium, halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —NO2, —NRcRd, —NHS(═O)2Ra, —S(═O)2NRcRd, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRcRd, —OC(═O)NRcRd, —NRbC(═O)NRcRd, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, —C1-C6C(═O)ORb, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• Ring A is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl;
• each RA is independently deuterium, halogen, —Y—CN, —Y—OH, —Y—ORa, —Y—SH, —Y—SRa, —Y—S(═O)Ra, —Y—S(═O)2Ra, —Y—NO2, —Y—NRcRd, —Y—NRbS(═O)2Ra, —Y—NRbS(═O)2NRcRd, —Y—S(═O)2NRcRd, —Y—C(═O)Ra, —Y—OC(═O)Ra, —Y—C(═O)ORb, —Y—OC(═O)ORb, —Y—C(═O)NRcRd, —Y—OC(═O)NRcRd, —Y—NRbC(═O)NRcRd, —Y—NRbC(═O)Ra, —Y—NRbC(═O)ORb, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, —C1-C6C(═O)ORb, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three deuterium, oxo, halogen, —CN, —OH, —OMe, —S(═O)Me, —S(═O)2Me, —NH2, —S(═O)2NH2, —C(═O)Me, —C(═O)OH, —C(═O)OMe, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, or C1-C6aminoalkyl;
• or
• two RA on the same carbon are taken together to form an oxo;
• each Y is independently a bond, C1-C6alkylene, or C1-C6haloalkylene;
• n is 0-4;
• each Ra is independently C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, 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, two, or three deuterium, oxo, halogen, —CN, —OH, —OMe, —S(═O)Me, —S(═O)2Me, —NH2, —S(═O)2NH2, —C(═O)Me, —C(═O)OH, —C(═O)OMe, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, or C1-C6aminoalkyl;
• each Rb is independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, 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, two, or three deuterium, oxo, halogen, —CN, —OH, —OMe, —S(═O)Me, —S(═O)2Me, —NH2, —S(═O)2NH2, —C(═O)Me, —C(═O)OH, —C(═O)OMe, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, or C1-C6aminoalkyl;
• and
• each Rc and Rd are independently hydrogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, 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, two, or three oxo, deuterium, halogen, —CN, —OH, —OMe, —S(═O)Me, —S(═O)2Me, —NH2, —S(═O)2NH2, —C(═O)Me, —C(═O)OH, —C(═O)OMe, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, or C1-C6aminoalkyl;
• or Rc and Rd are taken together with the atom to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three oxo, deuterium, halogen, —CN, —OH, —OMe, —S(═O)Me, —S(═O)2Me, —NH2, —S(═O)2NH2, —C(═O)Me, —C(═O)OH, —C(═O)OMe, C1-C6alkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, or C1-C6aminoalkyl;
• provided that the compound of Formula (I) is not