Compounds and methods for delivery of prostacyclin analogs

摘要

This invention pertains generally to prostacyclin formulations and methods for their use in promoting vasodilation, inhibiting platelet aggregation and thrombus formation, stimulating thrombolysis, inhibiting cell proliferation (including vascular remodeling), providing cytoprotection, preventing atherogenesis and inducing angiogenesis.

主权项

1. A method of treating pulmonary hypertension comprising administering to a human subject with pulmonary hypertension an effective amount of a compound
of formulaor a pharmaceutically acceptable salt thereof, wherein R1 is a substituted or unsubstituted alkyl,R2 and R3 are the same or different and are independently selected from the group consisting of H, phosphate, and groups wherein OR2 and OR3 form esters of amino acids or proteins;wherein said unsubstituted alkyl is selected from the group consisting of:a) an unbranched alkyl selected from the group consisting of pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, and dodecyl;b) a branched alkyl selected from the group consisting of —CH(CH3)(CH2CH3), —CH(CH2CH3)2, —C(CH3)3, —C(CH2CH3)3, —CH2CH(CH3)2, —CH2CH(CH3)(CH2CH3), —CH2CH(CH2CH3)2, —CH2C(CH3)3, —CH2C(CH2CH3)3, —CH(CH3)CH(CH3)(CH2CH3), —CH2CH2CH(CH3)2, —CH2CH2CH(CH3)(CH2CH3), —CH2CH2CH(CH2CH3)2, —CH2CH2C(CH3)3, —CH2CH2C(CH2CH3)3, —CH(CH3)CH2CH(CH3)2, —CH(CH3)CH(CH3)CH(CH3)2, and —CH(CH2CH3)CH(CH3)CH(CH3)(CH2CH3);c) a cyclic alkyl selected from the group consisting of cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl; andd) a polycyclic alkyl group,wherein said substituted alkyl is an unsubstituted alkyl as defined above in which one or more bonds to one or more carbon or hydrogen atoms are replaced by a bond to an atom selected from F, Cl, Br, I, O, S, N and Si.