Nitroso compounds as nitroxyl donors and methods of use thereof

摘要

The invention relates to nitroso derivatives including carboxylic acid and phosphoric acid esters of hydroxy nitroso compounds that donate nitroxyl (HNO) under physiological conditions. The compounds and compositions of the invention are useful in treating and/or preventing the onset and/or development of diseases or conditions that are responsive to nitroxyl therapy, including heart failure, ischemia/reperfusion injury and cancer.

主权项

1. A compound of formula VII:or a pharmaceutically acceptable salt thereof, wherein
D is selected from alkyl-C(O)—, substituted alkyl-C(O)—, perhaloalkyl-C(O)—, alkenyl -C(O)—, substituted alkenyl-C(O)—, alkynyl-C(O)—, substituted alkynyl-C(O)—, aryl-C (O)—, substituted aryl-C(O)—, heteroaryl-C(O)—, substituted heteroaryl-C(O)—, heterocyclyl-C (O)— and -P(O)(OC1-C8alky)2; R4 is selected from H, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted acyl, alkoxycarbonyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, and sulfonyl; and each R11a, R11b, R12a, R12b, R13a, R13b, R14a, and R14b group is independently selected from H, substituted C1-C8 alkyl, unsubstituted C1-C8 alkyl, halo, hydroxyl, alkoxy, cyano, and nitro or two said groups attached to the same carbon atom together with that carbon atom form a carbonyl moiety or two said groups attached to adjacent carbon atoms together with those carbon atoms form a carbon-carbon double bond.