Nitroxyl donors with improved therapeutic index
AssigneeCardioxyl Pharmaceuticals, Inc.
InventorsVincent Jacob Kalish, Frederick Arthur Brookfield, Stephen Martin Courtney, Lisa Marie Frost, John P. Toscano
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Abstract
The disclosed subject matter provides N-substituted hydroxylamine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the disclosed subject matter provides methods of using such compounds or pharmaceutical compositions for treating heart failure.
Claims19
A method of treating a cardiovascular disease responsive to nitroxyl therapy, comprising intravenously 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:
- 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, —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;
- and
- wherein the compound or the pharmaceutical composition is administered at a dose of at least 1 μg/kg/min.
A method of treating heart failure, comprising intravenously 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:
- 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;
- and
- wherein the compound or the pharmaceutical composition is administered at a dose of at least 1 μg/kg/min.
Dependencies are inferred from the claim text.