Cyclosporin derivatives for treating ocular and dermal diseases and conditions

摘要

The present invention provides a method for the treatment of ocular or dermal diseases and/or conditions, e.g. an aqueous deficient dry eye state, uveitis or phacoanaphylactic endophthalmitis in an eye, or balanitis, psoriasis, or atopic dermatitis of the skin, said method comprising administering, topically to the eye or the skin, a therapeutically effective amount of a novel cyclosporin A derivative selected from the group consisting of compounds represented by the formula:; wherein R₁ is S-Alk-R wherein Alk is an alkylene linkage, preferably a methylene or poly methylene linkage, e.g. a C₂ to C₆ polymethylene linkage, or a polyalkenylene linkage, e.g. a C₃ to C₆ alkenylenyl linkage, R is R is —N═C(NR₃R₄)(NR₅R₆) or—NR₇[(NR₃R₄)C═NR₅], i.e. guanidines or—N═C(R₈)(NR₉R₁₀), i.e. amidines wherein R₃-R₁₀ is H, Alk, Ar or (CH₂)nAr wherein Ar is an aryl group and n is an integer of from 1 to 13 or R₃ and R₄ or R₄ and R₅ or R₅ and R₇ or R₃ and R₇, or R₉ and R₁₀, together may be —CH₂—CH₂— or —CH₂—CH₂—CH₂— and R₂ is selected from the group consisting of hydroxyl, lower alkyl and hydroxyl-substituted lower alkyl and R₂ is selected from the group consisting of hydroxy and lower alkyl.