US 11,945,796 B2
Substituted pyridine derivatives as SARM1 inhibitors
Sean Pomeroy Brown, Half Moon Bay, CA (US); Keira Garland, San Francisco, CA (US); Shilpa Sambashivan, Los Altos, CA (US); Christopher Michael Tegley, Daly City, CA (US); and Liusheng Zhu, Foster City, CA (US)
Assigned to NURA BIO, INC., South San Francisco, CA (US)
Filed by Nura Bio, Inc., South San Francisco, CA (US)
Filed on Sep. 15, 2021, as Appl. No. 17/475,896.
Claims priority of provisional application 63/079,279, filed on Sep. 16, 2020.
Prior Publication US 2022/0081417 A1, Mar. 17, 2022
Int. Cl. C07D 401/14 (2006.01); A61K 45/06 (2006.01); C07D 401/06 (2006.01); C07D 405/14 (2006.01); C07D 409/14 (2006.01); C07D 417/14 (2006.01)
CPC C07D 401/14 (2013.01) [A61K 45/06 (2013.01); C07D 401/06 (2013.01); C07D 405/14 (2013.01); C07D 409/14 (2013.01); C07D 417/14 (2013.01); C07B 2200/05 (2013.01)] 66 Claims
 
1. A compound of Formula Ib:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
X2 is —(CR6R7)m or —(CR6R7)p—C(═O)—(CR6R7)q—;
A is halo, CN, Cy, or C1-3 haloalkyl;
R1, R2, R3, R4, and R5 are each independently selected from H, D, halo, CH3, CH2CH3, CD3, CH2CD3, and CD2CD3;
R6 and R7 are each independently selected from H, D, halo, methyl, ethyl, and C1-3 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 RCy 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;
m is 1, 2, or 3;
n is 0, 1, or 2;
p is 0, 1, or 2; and
q is 0, 1, or 2.