Back to results
US 2023/0093594 A1Published application
Pantethenoylcysteine derivatives and uses thereof
AssigneeComet Therapeutics, Inc.
InventorsArthur George Taveras, Angelina Roberta Sekirnik, Enej Kuscer
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to compounds of Formula (I) or (II): (Formulae (I), (II)), and pharmaceutically acceptable salts or solvates thereof. The present disclosure also relates to pharmaceutical compositions comprising the compounds and therapeutic and diagnostic uses of the compounds and pharmaceutical compositions.
Claims17
A compound of Formula (I) or (II):
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, —C(═O)R1b, —C(═O)R1c, —C(═O)R1z, —C(═O)—(CH═CH)nR1a, —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)CH2—[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(═O)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?]—C(═O)R1z, —C(═O)CHR1c—[C(═O)CHR1c]p—[CH2]q—R1a, —C(═O)CH2—[C(═O)CH2]p—[CH2]q—C(═O)R1a, —SR1d,
- 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 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(R1b)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, C1-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-C120 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, R1c, —C(═O)R1b, —C(═O)OR1e, —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;
- each R4 is independently H, —C(═O)OR4a, or —C(═O)N(R4a)2;
- each R4a is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl, 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 R4b;
- each R4b is independently H, halogen, —OR4c, —C(═O)OR4c, —C(═O)N(R4c)2, or —N(R4c)2;
- each R4c is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl;
- each R5 is independently H, —C(═O)OR5a, or —C(═O)N(R5a)2;
- each R5a is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl;
- each R6 is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl, 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 R6a;
- each R6a is independently halogen, —OR6b, —C(═O)OR6b, —C(═O)N(R6b)2, —N(R6b)2, N(R6b)C(═O)R1z, —N(R6b)C(═O)OR6b, —OC(═O)R1z, —OC(═O)OR6b, —SR6b, —N+(R6b)3, —SC(═O)R1z, —SC(═O)OR6b, —SC(═O)N(R6b)2, —C(═O)R1z, or R1z;
- each R6b is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl, 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 R1z;
- each R7 is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl, 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 R7a;
- each R7a is independently halogen, —OR7b, —C(═O)OR7b, —C(═O)N(R7b)2, —N(R7b)2, —N(R7b)C(═O)R1z, —N(R7b)C(═O)OR7b, —OC(═O)R1z, —OC(═O)OR7b, —SR7b, —N+(R7b)3, —SC(═O)R1z, —SC(═O)OR7b, —SC(═O)N(R7b)2, —C(═O)R1z, or R1z;
- each R7b is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl, 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 R1z;
- each R8 is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl, 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 R8a;
- each R8a is independently halogen, —OR8b, —C(═O)OR8b, —C(═O)N(R8b)2, —N(R8b)2, —N(R8b)C(═O)R1z, —N(R8b)C(═O)OR8b, —OC(═O)R1z, —OC(═O)OR8b, —SR8b, —N+(R8b)3, —SC(═O)R1z, —SC(═O)OR8b, —SC(═O)N(R8b)2, —C(═O)R1z, or R1z;
- each R8b is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl, 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 R1z;
- each R9 is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl, wherein the C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C2 heteroaryl is optionally substituted with one or more R9a;
- or two R9, together with the carbon atom 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 R9a;
- each R9a is independently halogen, —OR9b, —C(═O)OR9b, —C(═O)N(R9b)2, —N(R9b)2, —N(R9b)C(═O)R1z, —N(R9b)C(═O)OR9b, —OC(═O)R1z, —OC(═O)OR9b, —SR9b, —N+(R9b)3, —SC(═O)R1z, —SC(═O)OR9b, —SC(═O)N(R9b)2, —C(═O)R1z, or R1z;
- each R9b is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl, 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 R1z;
- each R10 is independently H, R10a, —OR10a, or —N(R10a)2;
- or two R10, together with the carbon atom 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 R10b;
- each R10a is independently C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, 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 R10b;
- each R10b is independently halogen, —OR10c, —C(═O)OR10c, —C(═CO)N(R10c)2, —N(R10c)2, —N(R10c)C(═O)R1z, —N(R10c)C(═O)OR10c, —OC(O)R1z, —OC(═O)OR10c, —SR10c, —N+(R10c)3, —SC(═O)R1z, —SC(═O)OR10c, —SC(═O)N(R10c)2, —C(═O)R1z, or R1z;
- each R10c is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl, 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 R1z;
- each R11 is independently H, R11a, —OR11a, or —N(R11a)2;
- or two R11, together with the carbon atom 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 R11b;
- each R11a is independently C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, 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 R11b;
- each R11b is independently halogen, —OR11c, —C(═O)OR11c, —C(═O)N(R11c)2, —N(R11c)2, —N(R11c)C(═O)R1z, —N(R11c)C(═O)OR11c, —OC(═O)R1z, —OC(═O)OR11c, —SR11c, —N+(R11c)3, —SC(═O)R1z, —SC(═O)OR11c, —SC(═O)N(R11c)2, —C(═O)R1z, or R1z;
- each R11c is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl, 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 R1z;
- T is a bond,
- C(═O)—(CH═CH)n—C(═O)—, —C(═O)—(CHR1b)n—C(═O)—, —C(═O)CH2—[C(═O)CH2]p—(CH2)q—C(═O)—, —C(═O)CH2—[CH(OR1c)—CH2]p—(CH2)q—C(═O)—, —C(═O)CH2—[C(═O)CH2]p—[CH(OR1c)—CH2]r—(CH2)q—C(═O)—, —C(═O)CH2—[CH(OR1c)—CH2]r—[C(═O)CH2]p—(CH2]q—C(═O)—, —C(═O)—(CHR1b)n—[C(═O)CH2]p—(CH2)q—C(O)—, —C(═O)CH2—[C(═O)—(CHR1b)n]p—(CH2)q—C(═O)—, —C(═O)CH2—[C(═O)CH2]p(CHR1b)q—C(═O)—, —C(═O)—(CHR1b)n—[C(═O)CH2]p—(CHR1b)q—C(═O)—, or C1-C20 alkyl optionally substituted with one or more R1e;
- each Rt is independently R1, R1a, or R1b;
- or
- two Rt, together with the one or more intervening atoms they are attached to, form a C3-C12 cycloalkyl or C3-C12 heterocycloalkyl, wherein C3-C12 cycloalkyl or C3-C12 heterocycloalkyl is optionally substituted with one or more R1a;
- and
- t is an integer ranging from 0 to 5.
54 more elements
A compound of Formula (I′) or (II′):
- or a pharmaceutically acceptable salt or solvate thereof, wherein:
- R1 is H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, C3-C12 heteroaryl, —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)CH2—[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(═O)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, —C(═O)CHR1c—[C(═O)CHR1c]p—[CH2]q—R1a, —C(═O)CH12—[C(═O)CH2)]p—[CH2]q—C(═O)R1a, —SR1d,
- 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 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(R1b)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)—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)1f, —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, R1c, —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;
- each R4 is independently H, —C(═O)OR4a, or —C(═O)N(R4a)2;
- each R4a is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C11 aryl, or C3-C12 heteroaryl, 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 R4b;
- each R4b is independently H, halogen, —OR4c, —C(═O)OR4c, —C(═O)N(R4c)2, or —N(R4c)2;
- each R4c is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl;
- each R5 is independently H, —C(═O)OR5a, or —C(═O)N(R5a)2;
- each R5a is independently H, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C3-C12 cycloalkyl, C3-C12 heterocycloalkyl, C3-C12 aryl, or C3-C12 heteroaryl;
- T is a bond,
- C(═O)—(CH═CH)n—C(═O)—, —C(═O)—(CHR1b)—C(═O)—, —C(═O)CH2—[C(═O)CH2]p—(CH2)q—C(═O)—, —C(═O)CH2—[CH(OR1c)—CH2]p—(CH2)q—C(═O)—, —C(═O)CH2—[C(═O)CH2]p—[CH(OR1c)—CH2]r—, (CH2)q—C(═O)—, —C(═O)CH2—[CH(OR1c)—CH2]r—[C(═O)CH2]p—(CH2]q—C(═O)—, —C(═O)—(CHR1b)n—[C(═O)CH2]p—(CH2)q—C(═O)—, —C(═O)CH2—[C(═O)—(CHR1b)n]p—(CH2)q—C(═O)—, —C(═O)CH2—[C(═O)CH2]p—(CHR1b)q—C(═O)—, —C(═O)—(CHR1b)n—[C(═O)CH2]p—(CHR1b)q—C(═O)—, or C1-C20 alkyl optionally substituted with one or more R1e;
- each Rt is independently R1, R1a, or R1b;
- or
- two Rt, together with the one or more intervening atoms they are attached to, form a C3-C12 cycloalkyl or C3-C12 heterocycloalkyl, wherein C3-C12 cycloalkyl or C3-C12 heterocycloalkyl is optionally substituted with one or more R1a;
- and
- t is an integer ranging from 0 to 5.
31 more elements
The compound of any one of the preceding claims, wherein R1 is —C(═O)CH2—[C(═O)CH2]p—[CH2]q—R1a and R3 is H.
The compound of any one of the preceding claims, wherein R3 is H, at least one R4;
- is H, and at least one R5 is H.
The compound of any one of the preceding claims, wherein R1 is —C(═O)CH2—[C(═O)CH2]p—[CH2]q—R1a and at least one of R2, R3, and R5 is H.
The compound of any one of the preceding claims, wherein the compound is of Formula (Iaa), (Iab), (Iac), or (Iad):
- or a pharmaceutically acceptable salt or solvate thereof.
The compound of any one of the preceding claims, wherein the compound is of Formula (Iaa-1), (Iab-1), (Iac-1), or (Iad-1):
- or a pharmaceutically acceptable salt or solvate thereof.
The compound of any one of the preceding claims, being selected from the compounds described in Table 1 and pharmaceutically acceptable salts thereof.
The compound of any one of the preceding claims, wherein the compound is not Compound No. 1 or any pharmaceutically acceptable salt thereof.
The compound of any one of the preceding claims, being selected from Compound No. 2-699 and pharmaceutically acceptable salts thereof.
The compound of any one of the preceding claims, being selected from Compound No. 2-699.
The compound of any one of the preceding claims, being selected from:
- Compound No.
- Structure
- 2
- 5
- 6
- 7
- 8
- 71
- 72
- 75
- 76
- 213
- 214
- 215
- 216
- 219
- 220
- 695
- 696
- 697
- 698
- 699
- and pharmaceutically acceptable salts thereof.
20 more elements
The compound of any one of the preceding claims, being selected from:
- Compound
- No.
- Structure
- 2
- 5
- 6
- 7
- 8
- 71
- 72
- 75
- 76
- 213
- 214
- 215
- 216
- 219
- 220
- 695
- 696
- 697
- 698
- 699
20 more elements
A pharmaceutical composition comprising the compound of any one of the preceding claims or a pharmaceutically acceptable salt thereof.
A method of treating or preventing a disease in a subject, comprising administering to the subject a therapeutically effective amount of a compound of any one of the preceding claims.
The compound of any one of the preceding claims for use in treating or preventing a disease in a subject, wherein the compound is for administration to the subject in at least one therapeutically effective amount.
A use of the compound of any one of the preceding claims for the manufacture of a medicament for treating or preventing a disease in a subject, wherein the compound is for administration to the subject in at least one therapeutically effective amount.
Dependencies are inferred from the claim text.