US 12,404,265 B2
Substituted pyridine derivatives as SARM1 inhibitors
Jennifer Aiden Kozak, Pacifica, CA (US); Sean Pomeroy Brown, Half Moon Bay, CA (US); Christopher Michael Tegley, San Carlos, CA (US); Alexander Wayne Schammel, San Francisco, CA (US); Liusheng Zhu, Foster City, CA (US); Maximiliano De La Higuera Macias, San Francisco, CA (US); and Shilpa Sambashivan, Los Altos, CA (US)
Assigned to NURA BIO, INC., South San Francisco, CA (US)
Appl. No. 18/019,452
Filed by Nura Bio, Inc., South San Francisco, CA (US)
PCT Filed Aug. 3, 2021, PCT No. PCT/US2021/044389
§ 371(c)(1), (2) Date Sep. 1, 2023,
PCT Pub. No. WO2022/031736, PCT Pub. Date Feb. 10, 2022.
Claims priority of provisional application 63/060,790, filed on Aug. 4, 2020.
Prior Publication US 2023/0339913 A1, Oct. 26, 2023
Int. Cl. C07D 403/14 (2006.01); A61P 25/28 (2006.01); C07D 403/04 (2006.01)
CPC C07D 403/14 (2013.01) [A61P 25/28 (2018.01); C07D 403/04 (2013.01)] 16 Claims
 
1. A compound of Formula Ia:

OG Complex Work Unit Chemistry
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.