Pantetheine derivatives and uses thereof

A compound of Formula (Iaa), (Iab), (Iac), (Iad), (Iae), (Iaf), (Iag), (Iah), (Iai), (Iaj), (Iba), (Ibj):

• or a pharmaceutically acceptable salt or solvate thereof,
• wherein:
• R1 is H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, —C(═O)R1b, —C(═O)R1c, —C(═O)R1z, —C(═O)—(CH═CH)n—R1a, —C(═O)CH2—[C(═O)CH2]p—[CH2]q—R1a, —C(═O)CH2—[CH(OR1c)—CH2]p—[CH2]q—R1a, —C(═O)CH2—[C(═O)CH2]p−[CH(OR1c)—CH2]r[CH2]q—R1a, —C(═O)—CH(C(═O)R1b)—[C(═O)CH2]p—[CH(OR1c)—CH2]r—[CH2]q—R1a, —C(═O)CH2—[CH(OR1c)CH2]r—[C(═O)CH2]p—[CH2]q—R1a, —C(═O)OR1c, —C(═O)N(R1c)2, —C(═O)—CH═CH—C(═O)OR1c, —C(═O)—[CH2]q—C(H)OR1c, —C(═O)—CH2CH2—C(═O)OR1c, —C(═O)CH2—[C(═O)CH2]p—[CH2]q—C(═O)OR1c, —C(═O)—[CH2]q—C(═O)R1a, —C(═O)—[CH2]q—C(═O)R1z, —[C(═O)CH2]q—C(═O)R1z, —C(═O)—CH2CH2—C(═O)R1z, —C(═O)—CH═CH—[C(═O)]pR1z, —C(═O)CH2—[C(═O)CH2]p—[CH2]q—C(═O)R1z, —SR1d,
• wherein the C1-C20 alkyl, C2-C20 alkenyl or C2-C20 alkynyl is optionally substituted with one or more R1a, and wherein one or more methylene moieties in the C1-C20 alkyl, C2-C20 alkenyl, or C2-C20 alkynyl are optionally replaced by one or more carbonyl moieties;
• each R1a is independently H, halogen, C1-C20 alkyl, C2-C20 alkenyl, —OR1c, —C(═O)OR1c, —C(═O)N(R1c)2, —N(R1c)2, —N(R1c)C(═O)R1b, —N(R1c)C(═O)R1z, —N(R1c)C(═O)OR1c, —OC(═O)R1b, —OC(═O)R1z, —OC(═O)OR1c, —OSi(R1g)3, —SC(═O)R1b, —SC(═O)R1z, —SC(═O)OR1c, —SC(═O)N(R1c)2, —C(═O)R1b, —C(═O)R1z, —SR1e, or R1, wherein the C1-C20 alkyl, C2-C20 alkenyl, or C2-C20 alkynyl is optionally substituted with one or more R1e;
• each R1b is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, —(CH2)q—C(═O)OR1c, —(CH2)q—C(═O)R1c, —CH2—C(═O)—(CH2)q—C(═O)OR1c, —CH2—[C(═O)CH2]p—[CH2]q—C(═O)OR1c, —CH═CH—C(═O)OR1c, —C(R1e)═C(R1e)—C(═O)OR1c, —C(═O)OR1c, —C(═O)N(R1c)2, or R1z, wherein the C1-C20 alkyl, C2-C20 alkenyl, or C2-C20 alkynyl is optionally substituted with one or more R1e;
• each R1c is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, —(C1-C20 alkyl)-(C3-C12 cycloalkyl), —(C1-C20 alkyl)-(C3-C12 heterocycloalkyl), —(C1-C20 alkyl)-(C3-C12 aryl), or —(C1-C20 alkyl)-(C3-C12 heteroaryl), wherein the C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, —(C1-C20 alkyl)-(C3-C12 cycloalkyl), —(C1-C20 alkyl)-(C3-C12 heterocycloalkyl), —(C1-C20 alkyl)-(C3-C12 aryl), or —(C1-C20 alkyl)-(C3-C12 heteroaryl) is optionally substituted with one or more R1e;
• or two R1c together with the one or more intervening atoms to which they are connected, form C3-C12 cycloalkyl or C3-C12 heterocycloalkyl, wherein the C3-C12 cycloalkyl or C3-C12 heterocycloalkyl is optionally substituted with one or more R1e;
• each R1d is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C10 cycloalkyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, —(C1-C20 alkyl)-(C3-C12 cycloalkyl), —(C1-C20 alkyl)-(C3-C12 heterocycloalkyl), —(C1-C20 alkyl)-(C3-C12 aryl), or —(C1-C20 alkyl)-(C3-C12 heteroaryl), wherein the C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, —(C1-C20 alkyl)-(C3-C12 cycloalkyl), —(C1-C20 alkyl)-(C3-C12 heterocycloalkyl), —(C1-C20 alkyl)-(C3-C12 aryl), or —(C1-C20 alkyl)-(C3-C12 heteroaryl) is optionally substituted with one or more R1e;
• each R1e is independently H, halogen, oxo, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, —OR1g, —C(═O)OR1g, —C(═O)N(R1g)2, —N(R1f)2, —N(R1g)2, —N(R1g)C(═O)R1f, —N(R1g)C(═NH)R1f, —N(R1g)C(═O)R1z, —N(R1g)C(═O)OR1g, —OC(═O)R1f, —OC(═O)R1z, —OC(═O)OR1g, —OSi(R1g)3, —SR1g, —N+(R1g)3, —SC(═O)R1f, —SC(═O)R1z, —SC(═O)OR1g, —SC(═O)N(R1g)2, —C(═O)R1f, —C(═O)R1z, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, or R1z, wherein the C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl is optionally substituted with one or more R1f or R1z;
• each R1f is independently H, oxo, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, —OSi(R1g)3, —OR1g, —CH2C(═O)OR1g, —CH═CH—C(═O)OR1g, —C(═O)OR1g, —C(═O)N(R1g)2, —N(R1g)2, or R1z, wherein the C1-C20 alkyl, C2-C20 alkenyl, or C2-C20 alkynyl is optionally substituted with one or more —OR1g or R1z;
• each R1g is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, —(C1-C20 alkyl)-(C3-C12 cycloalkyl), —(C1-C20 alkyl)-(C3-C12 heterocycloalkyl), —(C1-C20 alkyl)-(C3-C12 aryl), or —(C1-C20 alkyl)-(C3-C12 heteroaryl), wherein the C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, —(C1-C20 alkyl)-(C3-C12 cycloalkyl), —(C1-C20 alkyl)-(C3-C12 heterocycloalkyl), —(C1-C20 alkyl)-(C3-C12 aryl), or —(C1-C20 alkyl)-(C3-C12 heteroaryl) is optionally substituted with one or more R1z;
• each R1z is independently
• each n is independently an integer ranging from 0 to 20;
• each p is independently an integer ranging from 0 to 20;
• each q is independently an integer ranging from 0 to 20;
• each r is independently an integer ranging from 0 to 20;
• R2 and R3 are each independently H, —C(═O)R1b, —C(═O)OR1c, —C(═O)N(R1c)2, —C(═O)R1z, —C(═O)—CH═CH—C(═O)OR1c, —C(═O)—CH2—CH2—C(═O)OR1c,
• —C(═O)—CH═CH—C(═O)—R1z, —C(═O)—CH2—CH2—C(═O)—R1z, —Si(R1g)3,
• each X is independently —OR1c, —SR1c, —N(R1c)2,
• or R1z;
• or two X, together with the one or more intervening atoms to which they are connected, form C5-C12 heterocycloalkyl or C5-C12 heteroaryl, wherein the C5-C12 heterocycloalkyl or C5-C12 heteroaryl is optionally substituted with one or more R1a.

The compound of claim 1, wherein the compound is of Formula (Iaa), (Iab), (Iac), or (Iad), wherein:

• each R1a is independently H, halogen, C1-C20 alkyl, C2-C20 alkenyl, —OR1c, —C(═O)OR1c, —C(═O)N(R1c)2, —N(R1c)2, —N(R1c)C(═O)R1b, —N(R1c)C(═O)R1z, —N(R1c)C(═O)OR1c, —OC(═O)R1b, —OC(═O)R1z, —OC(═O)OR1c, —SC(═O)R1b, —SC(═O)R1z, —SC(═O)OR1c, —SC(═O)N(R1c)2, —C(═O)R1b, —C(═O)R1z, —SR1d, or R1z, wherein the C1-C20 alkyl, C2-C20 alkenyl, or C2-C20 alkynyl is optionally substituted with one or more R1e;
• each R1b is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, —(CH2)q—C(═O)OR1c, —(CH2)q—C(═O)R1c, —CH2—C(═O)—(CH2)q—C(═O)OR1c, —CH2—[C(═O)CH2]p—[CH2]q—C(═O)OR1c, —CH═CH—C(═O)OR1c, —C(R1e)═C(R1e)—C(═O)OR1c, —C(═O)OR1c, —C(═O)N(R1c)2, or R1z, wherein the C1-C20 alkyl, C2-C20 alkenyl, or C2-C20 alkynyl is optionally substituted with one or more R1e;
• each R1c is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, —(C1-C20 alkyl)-(C3-C12 cycloalkyl), —(C1-C20 alkyl)-(C3-C12 heterocycloalkyl), —(C1-C20 alkyl)-(C3-C12 aryl), or —(C1-C20 alkyl)-(C3-C12 heteroaryl), wherein the C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, —(C1-C20 alkyl)-(C3-C12 cycloalkyl), —(C1-C20 alkyl)-(C3-C12 heterocycloalkyl), —(C1-C20 alkyl)-(C3-C12 aryl), or —(C1-C20 alkyl)-(C3-C12 heteroaryl) is optionally substituted with one or more R1e;
• or two R1c together with the one or more intervening atoms to which they are connected, form C3-C12 cycloalkyl or C3-C12 heterocycloalkyl, wherein the C3-C12 cycloalkyl or C3-C12 heterocycloalkyl is optionally substituted with one or more R1e;
• each R1d is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C10 cycloalkyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, —(C1-C20 alkyl)-(C3-C12 cycloalkyl), —(C1-C20 alkyl)-(C3-C12 heterocycloalkyl), —(C1-C20 alkyl)-(C3-C12 aryl), or —(C1-C20 alkyl)-(C3-C12 heteroaryl), wherein the C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, —(C1-C20 alkyl)-(C3-C12 cycloalkyl), —(C1-C20 alkyl)-(C3-C12 heterocycloalkyl), —(C1-C20 alkyl)-(C3-C12 aryl), or —(C1-C20 alkyl)-(C3-C12 heteroaryl) is optionally substituted with one or more R1e;
• each R1e is independently H, halogen, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, —OR1g, —C(═O)OR1g, —C(═O)N(R1g)2, —N(R1g)2, —N(R1g)C(═O)R1f, —N(R1g)C(═NH)R1f, —N(R1g)C(═O)R1z, —N(R1g)C(═O)OR1g, —OC(═O)R1f, —OC(═O)R1z, —OC(═O)OR1g, —SR1g, —N+(R1g)3, —SC(═O)R1f, —SC(═O)R1z, —SC(═O)OR1g, —SC(═O)N(R1g)2, —C(═O)R1f, —C(═O)R1z, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, or R1z, wherein the C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl is optionally substituted with one or more R1f or R1z;
• each R1f is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, —OR1g, —CH2C(═O)OR1g, —CH═CH—C(═O)OR1g—C(═O)OR1g, —C(═O)N(R1g)2, —N(R1g)2, or R1z, wherein the C1-C20 alkyl, C2-C20 alkenyl, or C2-C20 alkynyl is optionally substituted with one or more —OR1g or R1z;
• each R1g is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, —(C1-C20 alkyl)-(C3-C12 cycloalkyl), —(C1-C20 alkyl)-(C3-C12 heterocycloalkyl), —(C1-C20 alkyl)-(C3-C12 aryl), or —(C1-C20 alkyl)-(C3-C12 heteroaryl), wherein the C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, —(C1-C20 alkyl)-(C3-C12 cycloalkyl), —(C1-C20 alkyl)-(C3-C12 heterocycloalkyl), —(C1-C20 alkyl)-(C3-C12 aryl), or —(C1-C20 alkyl)-(C3-C12 heteroaryl) is optionally substituted with one or more R1z;
• each R1z is independently
• each n is independently an integer ranging from 0 to 20;
• each p is independently an integer ranging from 0 to 20;
• each q is independently an integer ranging from 0 to 20;
• each r is independently an integer ranging from 0 to 20;
• R2 and R3 are independently H, —C(═O)R1b, —C(═O)OR1c, —C(═O)N(R1c)2, —C(═O)R1z, —C(═O)—CH═CH—C(═O)OR1c, —C(═O)—CH2—CH2—C(═O)OR1c,
• —C(═O)—CH═CH—C(═O)—R1z, —C(═O)—CH2—CH2—C(═O)—R1z,
• each X is independently —OR1c, —SR1c, —N(R1c)2,
• or R1z;
• or two X, together with the one or more intervening atoms to which they are connected, form C5-C12 heterocycloalkyl or C5-C12 heteroaryl, wherein the C5-C12 heterocycloalkyl or C5-C12 heteroaryl is optionally substituted with one or more R1a.