US 12,110,285 B2
Substituted pyridine derivatives as SARM1 inhibitors
Rao Kolluri, San Francisco, CA (US); Christopher Michael Tegley, San Carlos, CA (US); Liusheng Zhu, Foster City, CA (US); Sean Pomeroy Brown, Half Moon Bay, CA (US); Charles Howard Reynolds, Austin, TX (US); Andrew Stewart Tasker, Simi Valley, CA (US); and Cheryl A. Grice, Castle Rock, CO (US)
Assigned to NURA BIO, INC., South San Francisco, CA (US)
Filed by Nura Bio, Inc., South San Francisco, CA (US)
Filed on Mar. 3, 2023, as Appl. No. 18/178,325.
Application 18/178,325 is a division of application No. 17/875,301, filed on Jul. 27, 2022, granted, now 11,629,136.
Claims priority of provisional application 63/368,034, filed on Jul. 8, 2022.
Claims priority of provisional application 63/305,103, filed on Jan. 31, 2022.
Claims priority of provisional application 63/226,557, filed on Jul. 28, 2021.
Prior Publication US 2023/0286941 A1, Sep. 14, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 401/06 (2006.01); C07D 417/14 (2006.01)
CPC C07D 401/06 (2013.01) [C07D 417/14 (2013.01)] 19 Claims
 
1. A method of treating a neurological disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a compound of Formula IIa:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
Q is —Cy, —C1-4 alkyl-Cy, —CF3, or —C1-4 alkyl-CF3;
R1 is H;
R2 is H or C1-4 alkyl;
R4 and R4a are each independently selected from H, halo, and C1-4 alkyl;
each R5 is independently selected from halo and C1-4 alkyl, wherein R5 is attached to a carbon atom;
R6 and R7 are each independently selected from H, —ORa, —NRcRd, C1-4 alkyl, and C1-4 haloalkyl;
Cy is selected from C6-10 aryl, C3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, each optionally substituted by 1, 2, 3, 4, or 5 RCy substituents independently selected from halo, C1-4 alkyl, C1-4 haloalkyl, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, C(═NRe)Rb, C(═NRe)NRcRd, NRcC(═NRe)NRcRd, NRCS(O)Rb, NRCS(O)2Rb, NRCS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, and S(O)2NRcRd,
or two adjacent Roy substituents together with the atoms to which they are attached form a fused phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, or 4-7 membered heterocycloalkyl ring, each optionally substituted by 1, 2, 3, 4, or 5 substituents independently selected from halo, C1-4 alkyl, C1-4 haloalkyl, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, C(═NRe)Rb, C(═NRe)NRcRd, NRcC(═NRe)NRcRd, NRCS(O)Rb, NRCS(O)2Rb, NRCS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, and S(O)2NRcRd,
each Ra, Rb, Rc, and Rd is independently selected from H, C1-4 alkyl, and C1-4 haloalkyl, wherein said C1-4 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, and C1-4 haloalkoxy;
each Re is independently selected from H, C1-4 alkyl, and CN;
n is 0, 1, or 2; and
m is 1 or 2; wherein the neurological disorder is selected from amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), diabetic neuropathy, traumatic brain injury (TBI), ocular neuropathy, Parkinson's disease, Alzheimer's disease, and peripheral neuropathy.