Granted Patent
B2
US 12,186,301 · App. 18/371,722 · Granted Jan 7, 2025
Nitroxyl donors with improved therapeutic index
Inventors:
Vincent Jacob Kalish (Annapolis, MD); Frederick Arthur Brookfield (Abingdon, GB); Stephen Martin Courtney (Abingdon, GB); Lisa Marie Frost (Abingdon, GB); John P. Toscano (Glen Arm, MD)
Assignee:
Cardioxyl Pharmaceuticals, Inc.
A61K31/341A61K9/0019A61K9/08A61K31/18A61K31/222A61K31/24A61K31/255A61K31/343A61K31/381A61K31/404A61K31/42A61K31/433A61K31/4436A61K31/5377A61K31/538A61K47/12A61K47/40A61P9/04C07C317/14C07D307/64
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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.
Claims (21)
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:
wherein R is hydrogen, —(C 1 -C 6 )alkyl, —(C 2 -C 4 )alkenyl, phenyl, benzyl, cyclopentyl, cyclohexyl, —(C 5 -C 7 )heterocycloalkyl, benzyloxy, —O—(C 1 -C 6 )alkyl, —NH 2 , —NH—(C 1 -C 4 )alkyl, or —N((C 1 -C 4 )alkyl) 2 , wherein said —(C 1 -C 6 )alkyl, —(C 2 -C 4 )alkenyl, phenyl, benzyl, cyclopentyl, cyclohexyl, —(C 5 -C 7 )heterocycloalkyl, benzyloxy, —O—(C 1 -C 6 )alkyl, —NH—(C 1 -C 4 )alkyl, or —N((C 1 -C 4 )alkyl) 2 can be unsubstituted or substituted with one or more substituents selected from halo, —(C 1 -C 6 )alkyl, —(C 2 -C 4 )alkenyl, —(C 2 -C 3 )alkynyl, -(5- or 6-membered)heteroaryl, —O—(C 1 -C 6 )alkyl, —S—(C 1 -C 6 )alkyl, —C(halo) 3 , —CH(halo) 2 , —CH 2 (halo), —CN, —NO 2 , —NH 2 , —NH—(C 1 -C 4 )alkyl, —N(—(C 1 -C 4 )alkyl) 2 , —C(═O)(C 1 -C 4 )alkyl, —C(═O)O(C 1 -C 4 )alkyl, —OC(═O)(C 1 -C 4 )alkyl, —OC(═O)NH 2 , —S(═O)(C 1 -C 4 )alkyl, or —S(═O) 2 (C 1 -C 4 )alkyl.
2. The method of claim 1 , wherein R is methyl or ethyl.
3. The method of claim 1 , wherein R is methyl.
4. The method of claim 1 , wherein R is ethyl.
5. The method of claim 1 , wherein R is benzyl or phenyl.
6. The method of claim 1 , wherein R is phenyl.
7. The method of claim 1 , wherein R is benzyl.
8. The method of claim 1 , wherein R is-NH 2 .
9. The method of claim 1 , wherein R is unsubstituted.
10. The method of claim 1 , wherein R is substituted with a substituent selected from-halo, —NH 2 , —NHCH 3 , —CF 3 , or —OCH 3 .
11. The method of claim 1 , wherein the compound or the pharmaceutical composition is administered intravenously.
12. The method of claim 11 , wherein the compound or the pharmaceutical composition is administered in an amount of at least 1 μg/kg/min.
13. The method of claim 11 , wherein the compound or the pharmaceutical composition is administered in an amount of at least 2.5 μg/kg/min.
14. The method of claim 11 , wherein the compound or the pharmaceutical composition is administered in an amount of at least 5 μg/kg/min.
15. The method of claim 11 , wherein the compound or the pharmaceutical composition is administered in an amount of at least 7.5 μg/kg/min.
16. The method of claim 11 , wherein the compound or the pharmaceutical composition is administered in an amount of at least 12 μg/kg/min.
17. The method of claim 11 , wherein the compound or the pharmaceutical composition is administered in an amount of at least 15 μg/kg/min.
18. The method of claim 11 , wherein the compound or the pharmaceutical composition is administered in an amount of no more than about 30 μg/kg/min.
19. The method of claim 11 , wherein the compound or the pharmaceutical composition is administered in an amount of from about 1 μg/kg/min to about 100 μg/kg/min.
20. The method of claim 11 , wherein the compound or the pharmaceutical composition is administered in an amount of from about 2.5 μg/kg/min to about 100 μg/kg/min.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 17, 2023
From: KALISH, VINCENT JACOB; BROOKFIELD, FREDERICK ARTHUR; COURTNEY, STEPHEN MARTIN; FROST, LISA MARIE; TOSCANO, JOHN P.
To: CARDIOXYL PHARMACEUTICALS, INC.
Reel/Frame 065254/0908 →
Continuity (12)
Provisional Application
61782781
· Mar 14, 2013
Provisional Application
61754237
· Jan 18, 2013
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