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US 11,077,128 B2Granted
Selective inhibitors of Alpha2-containing isoforms of Na,K-ATPase and use thereof for reduction of intraocular pressure
AssigneeYeda Research and Development Co. Ltd.
InventorsSteven J. D. Karlish, Adriana Katz, Daniel M. Tal, Arie Marcovich
Life of this patent
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Abstract
Provided herein are alpha2-selective Na,K-ATPase inhibitors and prodrugs thereof, characterized by having a cyclic moiety attached to a digoxin or digitoxin derivative, as well as uses thereof in lowering intraocular pressure and in treating glaucoma and heart conditions.
Claims14
A pharmaceutical composition comprising as active ingredients:
- at least one ingredient selected from the group consisting of a prostaglandin analog, a β-blocker, an adrenergic agent, an α2-adrenergic receptor agonist, a miotic agent, a carbonic anhydrase inhibitor and a cholinergic agonist;
- and
- a compound represented by Formula III:
- including any pharmaceutically acceptable salt, hydrate, solvate, enantiomer and diastereomer thereof, and any mixtures thereof, and a pharmaceutically acceptable carrier, wherein:
- X is H or OH;
- R′ is selected from the group consisting of OH, C1-C6 alkyl, C1-C6 haloalkyl (C1-C6 alkyl substituted with at least one halo), —(CRbRc)nSi(Ra)3, —(CRbRc)n-C(═Y)—NR1R2, —(CRbRc)n-C(═Y)—NHOH, —(CRdRe)n-C(═Y)—COOR3, —NHC(═Y)NR1R2 and —(CRbRc)n-NH2;
- Y is O or S;
- R1, R2 and R3 are each independently H or a C1-C4 alkyl;
- Ra is a C1-C4 alkyl;
- Rb, Rc and Rd are each independently selected from H, a C1-C4 alkyl and a C1-C4 hydroxyalkyl;
- Re is selected from a C1-C4 alkyl and a C1-C4 hydroxyalkyl;
- and
- n is 0, 1 or 2.
10 more elements
A method of treating a heart condition in a subject in need thereof, comprising co-administering to the subject a therapeutically effective amount of:
- an agent selected from the group consisting of a β-blocker, an anticoagulation agent, an angiotensin-converting-enzyme inhibitor and an angiotensin II receptor antagonist;
- and
- a compound represented by Formula III:
- including any pharmaceutically acceptable salt, hydrate, solvate, enantiomer and diastereomer thereof, and any mixtures thereof, wherein:
- X is H or OH;
- R′ is selected from the group consisting of OH, C1-C6 alkyl, C1-C6 haloalkyl (C1-C6 alkyl substituted with at least one halo), —(CRbRc)nSi(Ra)3, —(CRbRc)n-C(═Y)—NR1R2, —(CRbRc)n-C(═Y)—NHOH, —(CRdRe)n-C(═Y)—COOR3, —NHC(═Y)NR1R2 and —(CRbRc)n—NH2;
- Y is O or S;
- R1, R2 and R3 are each independently H or a C1-C4 alkyl;
- Ra is a C1-C4 alkyl;
- Rb, Rc and Rd are each independently selected from H, a C1-C4 alkyl and a C1-C4 hydroxyalkyl;
- Re is selected from a C1-C4 alkyl and a C1-C4 hydroxyalkyl;
- and
- n is 0, 1 or 2.
10 more elements
Dependencies are inferred from the claim text.