US 12,391,703 B2
Aldoketo reductase inhibitors and uses thereof
William Greenlee, Shaker Heights, OH (US); Jonathan S. Stamler, Cleveland, OH (US); and Focco van den Akker, Shaker Heights, OH (US)
Assigned to CASE WESTERN RESERVE UNIVERSITY, Cleveland, OH (US); and UNIVERSITY HOSPITALS CLEVELAND MEDICAL CENTER, Cleveland, OH (US)
Appl. No. 17/762,793
Filed by CASE WESTERN RESERVE UNIVERSITY, Cleveland, OH (US)
PCT Filed Sep. 23, 2020, PCT No. PCT/US2020/052205
§ 371(c)(1), (2) Date Mar. 23, 2022,
PCT Pub. No. WO2021/061763, PCT Pub. Date Apr. 1, 2021.
Claims priority of provisional application 62/904,420, filed on Sep. 23, 2019.
Prior Publication US 2022/0251102 A1, Aug. 11, 2022
Int. Cl. C07D 491/107 (2006.01)
CPC C07D 491/107 (2013.01) 12 Claims
 
1. A method of increasing S-nitrosylation of proteins in a subject in need thereof, the method comprising: administering to the subject a compound having the following formula:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or tautomer thereof,
wherein R1, R2, R3, and R4 are each independently H, a halo group, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylsulfide, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, —CF3, —S—CF3, —SO2CF3, CO—N(Ra)—Rb, C1-C6 alkyl alcohol, C1-C6 alkyl ether, nitro, C1-C6 alkyl sulfide C1-C6 alkyl, C1-C6 alkylamine, C1-C6 alkyl esters, carboxylic acids, C1-C6 cycloalkyl, or C1-C6 heterocyclyl, Ra and Rb are each independently H or a C1-C6 alkyl, wherein at least one of R1, R2, R3, and R4 is not H, wherein the compound is administered to the subject at an amount effective to increase S-nitrosylation of proteins in the subject.