US 12,473,313 B2
Therapeutic compounds and methods of use thereof
Samuel Dudley, Minneapolis, MN (US); Gunda Ingrid Georg, Minneapolis, MN (US); Sudhakar Jakkaraj, Minneapolis, MN (US); and Narsihmulu Cheryala, Minneapolis, MN (US)
Assigned to REGENTS OF THE UNIVERSITY OF MINNESOTA, Minneapolis, MN (US)
Appl. No. 17/908,767
Filed by Regents of the University of Minnesota, Minneapolis, MN (US)
PCT Filed Mar. 4, 2021, PCT No. PCT/US2021/020907
§ 371(c)(1), (2) Date Sep. 1, 2022,
PCT Pub. No. WO2021/178690, PCT Pub. Date Sep. 10, 2021.
Claims priority of provisional application 62/985,769, filed on Mar. 5, 2020.
Prior Publication US 2023/0127371 A1, Apr. 27, 2023
Int. Cl. C07F 9/59 (2006.01); A61P 9/06 (2006.01); C07D 211/94 (2006.01)
CPC C07F 9/59 (2013.01) [A61P 9/06 (2018.01); C07D 211/94 (2013.01)] 18 Claims
 
1. A compound of formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
A is selected from —NRa—, —S—, —OC(—O)—, —NRaC(—O)—, —NRaC(═S)—, —NRaC(═O)O—, —NRaC(═NH)NRb—, —NRaC(═O)NRb—, —NRaC(═S)NRb—, —C(═O)O—, —C(═O)NRa— and —C(═O)NH(S(O)2)—;
B is (C1-C10)alkyl optionally substituted with one or more groups independently selected from the group consisting of halo and —OH;
X is a suitable counter anion;
R1 is aryl that is optionally substituted with one or more groups independently selected from the group consisting of nitro, carboxy, halo, cyano, heteroaryl, aryl, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkylthio, (C2-C6)alkanoyloxy, —OH, —NRaRb, —C(═O)NH(C1-C6 alkyl)(S(O)2Ra), —C(═O)NH(C1-C6 alkyl)(C(═O) ORa), —C(═O)NRaRb, —OS(O)3Ra, —C(═O)NH(S(O)2Ra), and —C(═O)(C1-C6 alkyl), wherein any heteroaryl, aryl, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkylthio and (C2-C6)alkanoyloxy is optionally substituted with one or more groups independently selected from the group consisting of halo, carboxy, —OH and cyano;
R2 is aryl that is optionally substituted with one or more groups independently selected from the group consisting of nitro, carboxy, halo, cyano, heteroaryl, aryl, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkylthio, (C2-C6)alkanoyloxy, —OH, —NRaRb, —C(═O)NH(C1-C6 alkyl)(S(O)2Ra), —C(═O)NH(C1-C6 alkyl)(C(═O) ORa), —C(═O)NRaRb, —OS(O)3Ra, —C(═O)NH(S(O)2Ra), and —C(═O)(C1-C6 alkyl), wherein any heteroaryl, aryl, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkylthio and (C2-C6)alkanoyloxy is optionally substituted with one or more groups independently selected from the group consisting of halo, carboxy, —OH and cyano;
R3 is aryl that is optionally substituted with one or more groups independently selected from the group consisting of nitro, carboxy, halo, cyano, heteroaryl, aryl, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkylthio, (C2-C6)alkanoyloxy, —OH, —NRaRb, —C(═O)NH(C1-C6 alkyl)(S(O)2Ra), —C(═O)NH(C1-C6 alkyl)(C(═O) ORa), —C(═O)NRaRb, —OS(O)3Ra, —C(═O)NH(S(O)2Ra), and —C(═O) (C1-C6 alkyl), wherein any heteroaryl, aryl, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkanoyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkylthio and (C2-C6)alkanoyloxy is optionally substituted with one or more groups independently selected from the group consisting of halo, carboxy, —OH and cyano; and
each Ra and Rb is independently selected from the group consisting of H, aryl, heteroaryl, (C1-C6)alkyl and (C3-C6)cycloalkyl wherein any aryl, heteroaryl, (C1-C6)alkyl, and (C3-C6)cycloalkyl, is optionally substituted with one or more groups independently selected from the group consisting of halo, nitro, —OH, cyano,; or Ra and Rb together with the nitrogen to which they are attached form a 4-10 membered ring heterocycle.