SELECTIVE INHIBITORS OF ALPHA2 ISOFORM OF Na,K-ATPase AND USE FOR REDUCTION OF INTRA-OCULAR PRESSURE

摘要

The present invention relates to digoxin and digitoxin derivatives that are selective inhibitors of the α2 isoform of Na,K-ATPase, and that reduce intra-ocular pressure. The invention further relates to uses of these derivatives for treating disorders associated with elevated intraocular pressure, such as glaucomas, and/or as cardiotonic agents.

主权项

1. A compound represented by the structure of general formula (I): R is selected from the group consisting of OH, C1-C6 alkyl, C1-C6 haloalkyl, —(CRbRc)nSi(Ra)3, —(CRbRc)n—C(═Y)—NR1R2, —(CRbRc)n—C(═Y)—NHOH, —(CRdRe)n—C(═Y)—COOR3; and —NHC(═Y)NR1R2; Y is O or S; X is H or OH; 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 hydroxy alkyl; Re is selected from a C1-C4 alkyl and a C1-C4 hydroxyalkyl; and n is 0, 1 or 2; including salts, hydrates, solvates, polymorphs, geometrical isomers, optical isomers, enantiomers, diastereomers, and mixtures thereof.