Selective inhibitors of Alpha2-containing isoforms of Na,K-ATPase and use thereof for reduction of intraocular pressure

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 represented by general Formula II:
• A is —CH2—, —(CH2)2— or a covalent bond;
• and
• B is a cyclic moiety selected from the group consisting of an unsubstituted alicyclic moiety, a substituted alicyclic moiety, an unsubstituted heterocyclic moiety, a substituted heterocyclic moiety, an unsubstituted heteroaryl moiety and a substituted heteroaryl moiety, or B is selected from the group consisting of an alkylsulfonyl, an arylsulfonyl and a sulfonamide, or B is —N1R2, wherein R1 and R2 are each independently H or a C1-C4 alkyl provided that at least one of R1 and R2 is a C1-C4 alkyl, and a pharmaceutically acceptable carrier.

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 represented by general Formula II:
• A is a spacer moiety or a covalent bond;
• and
• B is a cyclic moiety, or B is selected from the group consisting of an alkylsulfonyl, an arylsulfonyl and a sulfonamide, or B is —N1R2, wherein R1 and R2 are each independently H or a C1-C4 alkyl provided that at least one of R1 and R2 is a C1-C4 alkyl.