Substituted pyridine derivatives as SARM1 inhibitors

A compound of Formula Ia:

• or a pharmaceutically acceptable salt thereof, wherein:
• A is N or N+—O−;
• W is O, S, or NRN;
• ---- is a single, double, or triple bond;
• wherein when the ---- bond between X and Y is a single bond, then:
• X is CR5R6 and Y is O;
• or
• X is CR5R6 and Y is S, SO, or SO2;
• or
• X is O and Y is CR8R9;
• wherein when the ---- bond between X and Y is a double bond, then:
• X is CR5 and Y is CR8;
• and
• wherein when the ---- bond between X and Y is a triple bond, then:
• X is C and Y is C;
• Ring Z is C6-10 aryl, C3-7 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl;
• RN is H, C1-4 alkyl, or CN;
• R1 is halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, or C1-4 haloalkoxy;
• R2 is selected from H, halo, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C1-4 cyanoalkyl, C1-4 alkoxy, C1-4 alkoxy-C1-4 alkyl, C1-4 haloalkoxy, and C3-7 cycloalkyl;
• R3 is H, C1-4 alkyl, —C(═O)—(C1-6 alkyl), or —S(═O)2—(C1-6 alkyl);
• or
• R3 and R5, together with the atoms to which they are attached and together with any intervening atoms, form a C5-7 membered cycloalkyl ring or a 5-7 membered heterocycloalkyl ring, each optionally substituted by 1, 2, or 3 substituents independently selected from oxo, halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
• or
• R3 and R8, together with the atoms to which they are attached and together with any intervening atoms, form a C5-7 membered cycloalkyl ring or a 5-7 membered heterocycloalkyl ring, each optionally substituted by 1, 2, or 3 substituents independently selected from oxo, halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
• each R4 is independently F, Cl, nitro, cyano, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 alkoxy, or C1-4 haloalkoxy;
• or two adjacent R4 together with the atoms to which they are attached form a fused phenyl ring, C3-7cycloalkyl ring, 5-7 membered heteroaryl ring, or 4-7 membered heterocycloalkyl ring, each optionally substituted with 1, 2, or 3 substituents independently selected from oxo, halo, nitro, cyano, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
• or
• R4 and R9, together with the atoms to which they are attached and together with any intervening atoms, form a C5-7 membered cycloalkyl ring fused with ring Z or a 5-7 membered heterocycloalkyl ring fused with ring Z, each optionally substituted by 1, 2, or 3 substituents independently selected from oxo, halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
• R5, R6, R8, and R9 are each independently selected from H, halo, NH2, OH, C1-4 alkyl, C1-4 haloalkyl, C1-4 cyanoalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
• m is 0, 1, or 2;
• and
• n is 0, 1, 2, 3, 4, or 5.