US 12,186,301 B2
Nitroxyl donors with improved therapeutic index
Vincent Jacob Kalish, Annapolis, MD (US); Frederick Arthur Brookfield, Abingdon (GB); Stephen Martin Courtney, Abingdon (GB); Lisa Marie Frost, Abingdon (GB); and John P. Toscano, Glen Arm, MD (US)
Assigned to Cardioxyl Pharmaceuticals, Inc., Chapel Hill, NC (US)
Filed by Cardioxyl Pharmaceuticals, Inc., Chapel Hill, NC (US)
Filed on Sep. 22, 2023, as Appl. No. 18/371,722.
Application 18/371,722 is a continuation of application No. 17/694,500, filed on Mar. 14, 2022, granted, now 11,786,501.
Application 17/694,500 is a continuation of application No. 17/063,372, filed on Oct. 5, 2020, granted, now 11,273,143, issued on Mar. 15, 2022.
Application 17/063,372 is a continuation of application No. 16/724,657, filed on Dec. 23, 2019, granted, now 10,792,273, issued on Oct. 6, 2020.
Application 16/724,657 is a continuation of application No. 16/242,139, filed on Jan. 8, 2019, granted, now 10,517,847, issued on Dec. 31, 2019.
Application 16/242,139 is a continuation of application No. 15/960,993, filed on Apr. 24, 2018, granted, now 10,213,408, issued on Feb. 26, 2019.
Application 15/960,993 is a continuation of application No. 15/430,946, filed on Feb. 13, 2017, granted, now 9,968,584, issued on May 15, 2018.
Application 15/430,946 is a continuation of application No. 14/880,173, filed on Oct. 9, 2015, granted, now 9,586,896, issued on Mar. 7, 2017.
Application 14/880,173 is a continuation of application No. 14/641,377, filed on Mar. 7, 2015, granted, now 9,156,804, issued on Oct. 13, 2015.
Application 14/641,377 is a continuation of application No. 14/158,456, filed on Jan. 17, 2014, granted, now 8,987,326, issued on Mar. 24, 2015.
Claims priority of provisional application 61/782,781, filed on Mar. 14, 2013.
Claims priority of provisional application 61/754,237, filed on Jan. 18, 2013.
Prior Publication US 2024/0066002 A1, Feb. 29, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/341 (2006.01); A61K 9/00 (2006.01); A61K 9/08 (2006.01); A61K 31/18 (2006.01); A61K 31/222 (2006.01); A61K 31/24 (2006.01); A61K 31/255 (2006.01); A61K 31/343 (2006.01); A61K 31/381 (2006.01); A61K 31/404 (2006.01); A61K 31/42 (2006.01); A61K 31/433 (2006.01); A61K 31/4436 (2006.01); A61K 31/5377 (2006.01); A61K 31/538 (2006.01); A61K 47/12 (2006.01); A61K 47/40 (2006.01); A61P 9/04 (2006.01); C07C 317/14 (2006.01); C07D 307/64 (2006.01)
CPC A61K 31/341 (2013.01) [A61K 9/0019 (2013.01); A61K 9/08 (2013.01); A61K 31/18 (2013.01); A61K 31/222 (2013.01); A61K 31/24 (2013.01); A61K 31/255 (2013.01); A61K 31/343 (2013.01); A61K 31/381 (2013.01); A61K 31/404 (2013.01); A61K 31/42 (2013.01); A61K 31/433 (2013.01); A61K 31/4436 (2013.01); A61K 31/5377 (2013.01); A61K 31/538 (2013.01); A61K 47/12 (2013.01); A61K 47/40 (2013.01); A61P 9/04 (2018.01); C07C 317/14 (2013.01); C07D 307/64 (2013.01)] 20 Claims
 
1. A method of treating ischemia/reperfusion injury, comprising administering an effective amount of a compound of formula (3), or a pharmaceutical composition comprising the compound of formula (3), to a patient in need thereof, wherein the compound of formula (3) is represented by formula:

OG Complex Work Unit Chemistry
wherein R is hydrogen, —(C1-C6)alkyl, —(C2-C4)alkenyl, phenyl, benzyl, cyclopentyl, cyclohexyl, —(C5-C7)heterocycloalkyl, benzyloxy, —O—(C1-C6)alkyl, —NH2, —NH—(C1-C4)alkyl, or —N((C1-C4)alkyl)2, wherein said —(C1-C6)alkyl, —(C2-C4)alkenyl, phenyl, benzyl, cyclopentyl, cyclohexyl, —(C5-C7)heterocycloalkyl, benzyloxy, —O—(C1-C6)alkyl, —NH—(C1-C4)alkyl, or —N((C1-C4)alkyl)2 can be unsubstituted or substituted with one or more substituents selected from halo, —(C1-C6)alkyl, —(C2-C4)alkenyl, —(C2-C3)alkynyl, -(5- or 6-membered)heteroaryl, —O—(C1-C6)alkyl, —S—(C1-C6)alkyl, —C(halo)3, —CH(halo)2, —CH2(halo), —CN, —NO2, —NH2, —NH—(C1-C4)alkyl, —N(—(C1-C4)alkyl)2, —C(═O)(C1-C4)alkyl, —C(═O)O(C1-C4)alkyl, —OC(═O)(C1-C4)alkyl, —OC(═O)NH2, —S(═O)(C1-C4)alkyl, or —S(═O)2(C1-C4)alkyl.