Triterpenoid compounds, pharmaceutical compositions thereof, and their use for treating a nuclear receptor subfamily 4 group a member 1-mediated disease

A compound of Formula (I):

• or a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof;
• or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof;
• wherein:
• R1 is (i) —C(O)NR1bR1c, —C(R1a)═NR1b, —C(R1a)═NOR1b, —C(O)R1a, —C(O)OR1a, —C(O)ONR1bR1c, —C(O)OP(OR1a)(OR1b), —C(O)N(CN)R1b, —C(O)N(R1b)OR1c, —C(O)SR1a, —C(═NR1a)NR1bR1c, —C(S)R1a, —C(S)OR1a, —C(S)NR1bR1c, —OR1a, —OC(O)R1a, —OC(O)OR1a, —OC(O)NR1bR1c, —OC(O)SR1a, —OC(═NR1a)NR1bR1c, —OC(S)R1a, —OC(S)OR1a, —OC(S)NR1bR1c, —OP(O)(OR1a)OR1d, —OS(O)R1a, —OS(O)2R1a, —OS(O)2OR1a, —OS(O)NR1bR1c, —OS(O)2NR1bR1c, —NR1bR1c, —NR1aC(O)R1d, —NR1aC(O)OR1d, —NR1aC(O)SR1d, —NR1aC(O)NR1bR1c, —NR1aC(═NR1d)R1b, —NR1aC(═NR1d)NR1bR1c, —NR1aC(S)R1d, —NR1aC(S)OR1d, —NR1aC(S)NR1bR1c, —NR1aS(O)R1d, —NRaS(O)2R1d, —NR1aS(O)NR1bR1c, —NR1aS(O)2NR1bR1c, —SR1a, —SC(O)R1a, —SC(O)NR1bR1c, —S(O)R1a, —S(O)2R1a, —S(O)2OR1a, —S(O)NR1bR1c, or —S(O)2NR1bR1c;
• (ii) hydrogen, deuterium, azido, cyano, halo, isocyanato, isothiocyanato, or nitro;
• or (iii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
• R2 is —OR1a, —OC(O)R1a, —OC(O)OR1a, —OC(O)NR1bR1c, —OC(O)SR1a, —OC(═NR1a)NR1bR1c, —OC(S)R1a, —OC(S)OR1a, —OC(S)NR1bR1c, —OP(O)(OR1a)OR1d, —OS(O)R1a, —OS(O)2R1a, —OS(O)2OR1a, —OS(O)NR1bR1c, —OS(O)2NR1bR1c, or heteroaryl;
• or R2 and R3 together with the carbon atoms to which they are attached form heterocyclylene;
• R3 and R4 together with the carbon atom to which they are attached form ═CO, ═CR1aR1c, ═CR1aCN, ═NR1b, ═NOR1b, ═NNR1aC(O)R1d, ═NNR1aC(O)NR1bR1c, or heterocyclylene;
• or R3 is C1-6 alkyl, —OR1a, —OC(O)R1a, —OC(O)OR1a, —OC(O)NR1bR1c, —OC(O)SR1a, —OC(═NR1a)NR1bR1c, —OC(S)R1a, —OC(S)OR1a, —OC(S)NR1bR1c, —OP(O)(OR1a)OR1d, —OS(O)R1a, —OS(O)2R1a, —OS(O)2OR1a, —OS(O)NR1bR1c, —OS(O)2NR1bR1c, —NR1bR1c, —NR1aC(O)R1d, —NR1aC(O)OR1d, —NR1aC(O)SR1d, —NR1aC(O)NR1bR1c, —NR1aC(═NR1d)R1b, —NR1aC(═NR1d)NR1bR1c, —NR1aC(S)R1d, —NR1aC(S)OR1d, —NR1aC(S)NR1bR1c, —NR1aS(O)R1d, —NR1aS(O)2R1d, —NR1aS(O)NR1bR1c, or —NR1aS(O)2NR1bR1c;
• and R4 is hydrogen or R3;
• or R3, R4, and R5 together with the carbon atoms to which they are attached form unsaturated heterocyclylene;
• or R3, R5, and R6 together with the carbon atoms to which they are attached form unsaturated heterocyclylene;
• R5 and R6 together with the carbon atom to which they are attached form ═CO, ═CR1aR1c, ═CR1aCN, ═NR1b, ═NOR1b, or heterocyclylene;
• or R5 is C1-6 alkyl, —OR1a, —OC(O)R1a, —OC(O)OR1a, —OC(O)NR1bR1c, —OC(O)SR1a, —OC(═NR1a)NR1bR1c, —OC(S)R1a, —OC(S)OR1a, —OC(S)NR1bR1c, —OP(O)(OR1a)OR1d, —OS(O)R1a, —OS(O)2R1a, —OS(O)2OR1a, —OS(O)NR1bR1c, —OS(O)2NR1bR1c, —NR1bR1c, —NR1aC(O)R1d, —NR1aC(O)OR1d, —NR1aC(O)SR1d, —NR1aC(O)NR1bR1c, —NR1aC(═NR1d)R1b, —NR1aC(═NR1d)R1bR1c, —NR1aC(S)R1d, —NR1aC(S)OR1d, —NR1aC(S)NR1bR1c, —NR1aS(O)R1d, —NR1aS(O)2R1d, —NR1aS(O)NR1bR1c, or —NR1aS(O)2NR1bR1c;
• and R6 is hydrogen or R5;
• and
• each R1a, R1b, R1c, and R1d is independently C1-6 alkyl, hydrogen, deuterium, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
• or R1a and R1c together with the C and N atoms to which they are attached form heterocyclyl;
• or R1b and R1c together with the N atom to which they are attached form heterocyclyl;
• wherein each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, and heterocyclylene is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Q, where each Q is independently selected from (a) deuterium, azido, cyano, halo, isocyanato, isothiocyanato, and nitro;
• (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl, each of which is further optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;
• and (c) —C(O)Ra, —C(O)ORa, —C(O)NRbRc, —C(O)SRa, —C(NRa)NRbRc, —C(S)Ra, —C(S)ORa, —C(S)NRbRc, —ORa, —OC(O)Ra, —OC(O)ORa, —OC(O)NRbRc, —OC(O)SRa, —OC(═NRa)NRbRc, —OC(S)Ra, —OC(S)ORa, —OC(S)NRbRc, —OPO3RaRd, —OS(O)Ra, —OS(O)2Ra, —OSO3Ra, —OS(O)NRbRc, —OS(O)2NRbRc, —NRbRc, —NRaC(O)Rd, —NRaC(O)ORd, —NRaC(O)NRbRc, —NRaC(O)SRd, —NRaC(═NRd)NRbRc, —NRaC(S)Rd, —NRaC(S)ORd, —NRaC(S)NRbRc, —NRaS(O)Rd, —NRaS(O)2Rd, —NRaS(O)NRbRc, —NRaS(O)2NRbRc, —SRa, —S(O)Ra, —S(O)2Ra, —S(O)NRbRc, and —S(O)2NRbRc, wherein each Ra, Rb, Rc, and Rd is independently (i) hydrogen or deuterium;
• (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl, each of which is optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;
• or (iii) Rb and Rc together with the N atom to which they are attached form heterocyclyl, optionally substituted with one or more, in one embodiment, one, two, three, or four, substituents Qa;
• wherein each Qa is independently selected from:
• (a) deuterium, azido, cyano, halo, isocyanato, isothiocyanato, and nitro;
• (b) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, and heterocyclyl;
• and (c) —C(O)Re, —C(O)ORe, —C(O)NRfRg, —C(O)SRe, —C(NRc)NRfRg, —C(S)Re, —C(S)ORe, —C(S)NRfRg, —ORe, —OC(O)Re, —OC(O)ORe, —OC(O)NRfRg, —OC(O)SRe, —OC(═NRe)NRfRg, —OC(S)Re, —OC(S)ORe, —OC(S)NRfRg, —OS(O)Re, —OS(O)2Re, —OS(O)NRfRg, —OS(O)2NRfRg, —NRfRg, —NReC(O)Rh, —NReC(O)ORf, —NReC(O)NRfRg, —NReC(O)SRf, —NReC(═NRh)NRfRg, —NReC(S)Rh, —NReC(S)ORf, —NReC(S)NRfRg, —NReS(O)Rh, —NReS(O)2Rh, —NReS(O)NRfRg, —NReS(O)2NRfRg, —SRe, —S(O)Re, —S(O)2Re, —S(O)NRfRg, and —S(O)2NRfRg;
• wherein each Re, Rf, Rg, and Rh is independently (i) hydrogen or deuterium;
• (ii) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C6-14 aryl, C7-15 aralkyl, heteroaryl, or heterocyclyl;
• or (iii) Rf and Rg together with the N atom to which they are attached form heterocyclyl.