US 12,213,976 B2
Compounds and methods for treating oxalate-related diseases
Ayman Kabakibi, San Diego, CA (US); Mehmet Kahraman, La Jolla, CA (US); Michael Clare, Skokie, IL (US); and Thomas Leedom, Escondido, CA (US)
Assigned to OxaluRx, Inc., Saint Louis, MO (US)
Filed by OxaluRx, Inc., St. Louis, MO (US)
Filed on Oct. 12, 2022, as Appl. No. 18/046,064.
Application 18/046,064 is a division of application No. 17/000,301, filed on Aug. 22, 2020, granted, now 11,504,367.
Claims priority of provisional application 62/890,378, filed on Aug. 22, 2019.
Prior Publication US 2023/0110495 A1, Apr. 13, 2023
Int. Cl. A61K 31/506 (2006.01); A61K 31/4192 (2006.01); A61K 31/4439 (2006.01); A61K 31/454 (2006.01); A61K 31/497 (2006.01); A61K 31/501 (2006.01); C07D 249/04 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 405/12 (2006.01); C07D 405/14 (2006.01)
CPC A61K 31/506 (2013.01) [A61K 31/4192 (2013.01); A61K 31/4439 (2013.01); A61K 31/454 (2013.01); A61K 31/497 (2013.01); A61K 31/501 (2013.01); C07D 249/04 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 405/12 (2013.01); C07D 405/14 (2013.01)] 34 Claims
 
1. A method of inhibiting glycolate oxidase (GOX) activity in a biological sample comprising contacting the biological sample with a compound of Formula III,

OG Complex Work Unit Chemistry
or a salt, polymorph, or tautomer thereof, wherein:
R1 is chosen from hydrogen, C1-C6 alkyl, and C1-C6 cycloalkyl;
L is chosen from O, S, CH2, NH, NR4, S (O), SO2, and CR4═CR5;
each R2 is independently chosen from 5-10-membered heteroaryl, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylsulfonyl, C1-C6 alkylthio, C1-C6 haloalkoxy, C1-C6 haloalkyl, C6-C10 aryl, cyano, and halogen;
n is 0, 1, or 2;
R3 is chosen from 3-10-membered heterocycloalkyl, 5-10-membered heteroaryl, C1-C6 alkyl, C1-C6 sulfonyl, C3-C6 cycloalkyl, C3-C6 cycloalkylalkyl, C6-C10 aryl, and C6-C10 arylalkyl;
R4 and R5 are each independently chosen from hydrogen and C1-C6 alkyl, or R4 and R5, together with the atoms to which they are attached, form a cycloalkenyl; and
each R6 is independently chosen from 4-6-membered heterocycloalkyl, 5-10-membered heteroaryl, amino, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 alkylsulfonyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylalkyl, carboxyl, cyano, halogen, hydroxyl, methyl-4-6-membered heterocycloalkyl, and phenyl; and
m is 0, 1, 2, or 3.