Sarm1 modulators, preparations, and uses thereof

A compound of the following structural Formula 1:

• a tautomer thereof, a solvate or stereoisomer of the compound or the tautomer, or a pharmaceutically acceptable salt of the foregoing, wherein:
• Ring A is phenyl, a 5- to 10-membered heteroaryl ring, a 5 to 10-membered carbocyclic ring or a 5 to 10-membered heterocyclic ring;
• Ring B is phenyl, a 9- to 11-membered aryl ring, a 9- to 11-membered heteroaryl ring, or a 9- to 11-membered heterocyclic ring;
• Ra is selected from ═O, C3-C6 cycloalkyl, —O(C1-C4 alkyl), COOH, CN, CONH2, —C(═O)NH(C1-C4 alkyl), —C(═O)N(C1-C4 alkyl)2, —C(═O)O(C1-C4 alkyl), halogen, and C1-C4 alkyl optionally substituted with 1 to 3 groups selected from halogen, —OH, cyclopropyl, oxetanyl, and azetidinyl;
• Rb is selected from ═O, OH, halogen, CN, —C(═O)NH2, —C(═O)NH(C1-C4 alkyl), —C(═O)O(C1-C4 alkyl), optionally substituted C3-C6 cycloalkyl, optionally substituted C3-C6 heterocyclyl, optionally substituted C5-C6 heteroaryl, —O(C1-C4 alkyl), —C(═O)(C1-C4 alkyl), —C(═O)(optionally substituted C3-C6 cycloalkyl), —C(═O)(optionally substituted 5- to 6-membered heterocyclyl), —C(═O)(optionally substituted 5- to 6-membered heteroaryl), —C(═O)(CH2)pC(═O)NH2, —NHC(═O)(C1-C4 alkyl), —C(═O)N(C1-C4 alkyl)2, —C(═O)NH(CH2)pOH, —S(═O)2NH2,
• C1-C4 alkyl optionally substituted with 1 to 3 groups selected from halogen, NH2, OH, OCH3, —C(═O)NH(C1-C4 alkyl), —C(═O)O(C1-C4 alkyl), —C(═O)N(C1-C4 alkyl)2, —COOH, —C(═O)NH2, CN, C3-C5 cycloalkyl, phenyl, —C(═O)(C1-C4 alkyl), —C(═O)(C3-C6 cycloalkyl), —C(═O)(5- to 6-membered heterocyclyl), —C(═O)(optionally substituted 5- to 6-membered heteroaryl), C(═O)NH(CH2)pOH, and 5- to 6-membered heteroaryl,
• 5- to 6-membered heteroaryl optionally substituted with 1 to 2 groups selected from C1-C3 alkyl, ═O, —NH2, —CN, —CONH2, halogen, and
• 4- to 6-membered heterocyclyl optionally substituted with 1 to 2 groups selected from ═O, —OH, —NH2, —CN, —CONH2, halogen, and C1-C3 alkyl, or two Rb attached to the same position on Ring B join to form a C3-C6 cycloalkyl, wherein R4 and R5 are each independently selected from H and C1 to C3 alkyl or R4 and R5 join to form a 3- to 5-membered cycloalkyl;
• L is selected from
• wherein
• R1 is H, D, or C1-C6 alkyl, and R2 is selected from CN, C1-C6 alkenyl, C3-C6 cycloalkyl, C3-C6 heterocyclyl, 5- or 6-membered heteroaryl,
• phenyl optionally substituted with 1 to 3 groups selected from C1-C4 alkyl and halogen, and
• C1-C6 alkyl optionally substituted with 1 to 3 groups selected from halogen, OH, CN, —SO2CH3, —NHSO2CH3, —CONH2, OCH3, and phenyl, or
• R1 and R2 join to form a 3- to 6-membered carbocyclyl or 3- to 6-membered heterocyclyl;
• R3 is C1-C4 alkyl optionally substituted with 1 to 3 groups selected from halogen, O(C1-C3 alkyl), OH, and NH2;
• m is an integer selected from 0, 1, 2, 3, and 4;
• n is an integer selected from 0, 1, 2, 3, and 4, and
• p is an integer selected from 1, 2, 3, and 4.
• provided that the compound is not any of Compound 1A to Compound 121A.