US 12,358,899 B2
Thyroid hormone receptor agonists and uses thereof
Bohan Jin, San Diego, CA (US); Qing Dong, San Diego, CA (US); and Gene Hung, San Diego, CA (US)
Assigned to XIZANG HAISCO PHARMACEUTICAL CO., LTD., Tibet (CN)
Filed by XIZANG HAISCO PHARMACEUTICAL CO., LTD., Tibet (CN)
Filed on Mar. 14, 2024, as Appl. No. 18/605,379.
Application 18/605,379 is a continuation of application No. 17/047,358, granted, now 11,964,964, previously published as PCT/US2019/034199, filed on May 28, 2019.
Claims priority of provisional application 62/767,402, filed on Nov. 14, 2018.
Claims priority of provisional application 62/731,364, filed on Sep. 14, 2018.
Claims priority of provisional application 62/684,113, filed on Jun. 12, 2018.
Prior Publication US 2024/0360106 A1, Oct. 31, 2024
Int. Cl. C07D 403/14 (2006.01); A61P 5/14 (2006.01); C07D 413/14 (2006.01)
CPC C07D 403/14 (2013.01) [A61P 5/14 (2018.01); C07D 413/14 (2013.01)] 13 Claims
 
1. A compound of Formula (IV), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof:

OG Complex Work Unit Chemistry
wherein:
R1 is hydrogen, deuterium, halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —NO2, —NRbRc, —NHS(═O)2Ra, —S(═O)2NRbRc, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRbRc, —OC(═O)NRbRc, —NRbC(═O)NRbRc, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —ORa, —NRbRc, —C(═O)Ra, —C(═O)ORb, —C(═O)NRbRe, C1-C6alkyl, or C1-C6haloalkyl;
R2 is hydrogen, halogen, —CN, —OH, —ORa, —S(═O)Ra, —S(═O)2Ra, —S(═O)2NRbRc, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —C(═O)NRbRc, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —ORa, —NRbRc, —C(═O)Ra, —C(═O)ORb, —C (═O)NRbRe, C1-C6alkyl, or C1-C6haloalkyl;
n is 2-4;
each R3 is independently hydrogen, deuterium, halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —NO2, —NRbRc, —NHS(═O)2Ra, —S(═O)2NRbRc, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRbRc, —OC(═O)NRbRc, —NRbC(═O)NRbRc, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —ORa, —NRbRc, —C(═O)Ra, —C(═O)ORb, —C(═O)NRbRe, C-C6alkyl, or C1-C6haloalkyl; and two R3 on adjacent carbons are taken together to form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OMe, —NH2, —C(═O)Me, —C(═O)OH, —C(═O)OMe, C1-C6alkyl, C1-C6deuteroalkyl, or C1-C6haloalkyl;
R4 is hydrogen, deuterium, halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —NO2, —NRbRc, —NHS(═O)2Ra, —S(═O)2NRbRc, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRbRc, —OC(═O)NRbRc, —NRbC(═O)NRbRc, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —ORa, —NRbRc, —C(═O)Ra, —C(═O)ORb, —C(═O)NRaRc, C1-C6alkyl, or C1-C6haloalkyl;
R5 is hydrogen, deuterium, halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —S(═O)2Ra, —NO2, —NRbRc, —NHS(═O)2Ra, —S(═O)2NRbRe, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRbRe, —OC(═O)NRbRc, —NRbC(═O)NRbRc, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6haloalkyl, C4-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —ORa, —NRbRc, —C(═O)Ra, —C(═O)ORb, —C(═O)NRbRe, C1-C6alkyl, or C1-C6haloalkyl;
R6 is hydrogen, —CN, —OH, —ORa, —S(═O)Ra, —S(═O)2Ra, —S(═O)2NRbRc, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —C(═O)NRbRc, C1-C6alkyl, C1-C6deuteroalkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —ORa, —NR Rc, −C(═O)Ra, —C(═O)ORb, —C(═O)NRbRc, C1-C6alkyl, or C1-C6haloalkyl;
each Ra is independently C1-C6alkyl, C1-C6deuteroalkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OMe, —NH2, —C(═O)Me, —C(═O)OH, —C(═O)OMe, C1-C6alkyl, or C1-C6haloalkyl; and
each Rb and Rc are independently hydrogen, deuterium, C1-C6alkyl, C-C6deuteroalkyl, C1-C6haloalkyl, C1-C6hydroxyalkyl, C1-C6aminoalkyl, C2-C6alkenyl, C2-C6alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OMe, —NH2, —C(═O)Me, —C(═O)OH, —C(═O)OMe, C1-C6alkyl, or C1-C6haloalkyl;
or Rb and Rc are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one or more oxo, deuterium, halogen, —CN, —OH, —OMe, —NH2, —C(═O)Me, —C(═O)OH, —C(═O)OMe, C1-C6alkyl, or C1-C6haloalkyl.