US 11,806,335 B2
Heterocyclic carboxylate compounds as glycolate oxidase inhibitors
Hongyan Guo, San Mateo, CA (US); Amy S. Lee, Palo Alto, CA (US); Hyung-Jung Pyun, Fremont, CA (US); Devleena M. Shivakumar, Menlo Park, CA (US); Manoj C. Desai, Martinez, CA (US); Lianhong Xu, Palo Alto, CA (US); John E. Knox, Alameda, CA (US); and Zachary E R Newby, San Francisco, CA (US)
Assigned to Lilac Therapeutics, Inc., Walnut Creek, CA (US)
Filed by Lilac Therapeutics, Inc., Walnut Creek, CA (US)
Filed on Oct. 27, 2020, as Appl. No. 17/081,940.
Claims priority of provisional application 63/093,094, filed on Oct. 16, 2020.
Claims priority of provisional application 62/929,476, filed on Nov. 1, 2019.
Prior Publication US 2021/0128532 A1, May 6, 2021
Int. Cl. A61K 31/4192 (2006.01); A61K 31/19 (2006.01); A61K 31/194 (2006.01); A61K 31/351 (2006.01); A61K 31/381 (2006.01); A61K 31/382 (2006.01); A61K 31/415 (2006.01); A61K 31/4164 (2006.01); A61K 31/422 (2006.01); A61K 31/427 (2006.01); A61K 31/428 (2006.01); A61K 31/433 (2006.01); A61K 31/4439 (2006.01); A61K 31/454 (2006.01); A61K 31/4709 (2006.01); A61K 31/4725 (2006.01); A61K 31/497 (2006.01); A61K 31/501 (2006.01); A61K 31/506 (2006.01); A61K 31/5377 (2006.01); A61K 31/675 (2006.01); A61K 31/7048 (2006.01); A61K 38/51 (2006.01); A61K 45/06 (2006.01); C07D 231/14 (2006.01); C07D 233/90 (2006.01); C07D 249/06 (2006.01); C07D 401/04 (2006.01); C07D 401/10 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 403/04 (2006.01); C07D 403/10 (2006.01); C07D 403/14 (2006.01); C07D 405/04 (2006.01); C07D 405/10 (2006.01); C07D 405/14 (2006.01); C07D 413/10 (2006.01); C07D 417/04 (2006.01); C07D 417/10 (2006.01); C07F 9/6558 (2006.01); C12N 15/113 (2010.01)
CPC A61K 31/4192 (2013.01) [A61K 31/19 (2013.01); A61K 31/194 (2013.01); A61K 31/351 (2013.01); A61K 31/381 (2013.01); A61K 31/382 (2013.01); A61K 31/415 (2013.01); A61K 31/4164 (2013.01); A61K 31/422 (2013.01); A61K 31/427 (2013.01); A61K 31/428 (2013.01); A61K 31/433 (2013.01); A61K 31/4439 (2013.01); A61K 31/454 (2013.01); A61K 31/4709 (2013.01); A61K 31/4725 (2013.01); A61K 31/497 (2013.01); A61K 31/501 (2013.01); A61K 31/506 (2013.01); A61K 31/5377 (2013.01); A61K 31/675 (2013.01); A61K 31/7048 (2013.01); A61K 38/51 (2013.01); A61K 45/06 (2013.01); C07D 231/14 (2013.01); C07D 233/90 (2013.01); C07D 249/06 (2013.01); C07D 401/04 (2013.01); C07D 401/10 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/04 (2013.01); C07D 403/10 (2013.01); C07D 403/14 (2013.01); C07D 405/04 (2013.01); C07D 405/10 (2013.01); C07D 405/14 (2013.01); C07D 413/10 (2013.01); C07D 417/04 (2013.01); C07D 417/10 (2013.01); C07F 9/65583 (2013.01); C12N 15/113 (2013.01); C12N 2310/14 (2013.01)] 12 Claims
 
1. A compound of formula III:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, tautomer, stereoisomer, mixture of stereoisomers, or deuterated analog thereof, wherein:
R2 is hydrogen, —(CH2CH2O)1-9CH2CH2OCH3, C1-6 alkyl optionally substituted with one to three R4, cycloalkyl, or heteroaryl optionally substituted with one to three R5;
each R3 is independently aryl, heteroaryl, or heterocyclyl, wherein each R3 is optionally substituted with one to three R6;
each R4 is independently halo, hydroxy, —OC1-6alkyl, —NH2, —NHC1-6 alkyl, —N(C1-6alkyl)2, —OC(O)Ra, —OC(O)ORa, —OP(O)(ORb)2, or monocyclic heterocyclyl; wherein each is optionally substituted with one to three R5; provided only one R4 is heterocyclyl;
each R5 is independently cyano, halo, C1-4 alkyl, hydroxy, —OC1-4alkyl, C1-4 haloalkyl, or —OC1-4 haloalkyl;
each R6 is independently cyano, halo, —C(O)R7, —C(O)OR7, —C(O)NR7R8, —S(O)2NR7R8, —NR7C(O)R8, —OR7, C1-4 alkyl, —OC1-4alkyl, C1-4 haloalkyl, —OC1-4 haloalkyl, phenyl, heterocyclyl, or heteroaryl; wherein each is optionally substituted with one to three C1-4 alkyl, —C(O)OH or C1-4 haloalkyl;
R7 and R8 are each independently hydrogen, C1-4 alkyl or phenyl, pyridyl, or R7 and R8 together with the nitrogen atom to which they are attached form a heterocyclyl;
each Ra is independently C1-6 alkyl optionally substituted with —NH2, —NHC1-6 alkyl, —N(C1-6alkyl)2, or —OP(O)(ORb)2;
each Rb is independently hydrogen or C1-4 alkyl.