METHODS OF PREVENTING, REDUCING OR TREATING MACULAR DEGENERATION

摘要

The present invention is directed to selective adenosine A1 agonist compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat, reduce or prevent age-related macular degeneration.

主权项

1. A method of preventing age-related macular degeneration in a subject in need thereof, comprising the step of: applying an effective amount of an ophthalmic pharmaceutical composition comprising a compound according to Formula I to an eye of the subject,or a pharmaceutically acceptable salt thereof,
wherein
A is —CH2ONO2, —CH2OH, —CH2OSO3H;B and C are —OH;D is A and B are trans with respect to each other;B and C are cis with respect to each other;C and D are cis or trans with respect to each other;R1 is —C1-C10 alkyl, -aryl, -3- to 7-membered monocyclic heterocycle, -8- to 12-membered bicyclic heterocycle, —C3-C8 monocyclic cycloalkyl, —C3-C8 monocyclic cycloalkenyl, —C8-C12 bicyclic cycloalkyl, —C8-C12 bicyclic cycloalkenyl —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), or —(CH2)n-aryl;R2 is —H, halo, —CN, —NHR4, —NHC(O)R4, —NHC(O)OR4, —NHC(O)NHR4, —NHNHC(O)R4, —NHNHC(O)OR4, —NHNHC(O)NHR4, or —NH—N═C(R6)R7;R4 is —C1-C15 alkyl, -aryl, —(CH2)n-aryl, —(CH2)n-(3- to 7-membered monocyclic heterocycle), —(CH2)n-(8- to 12-membered bicyclic heterocycle), —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), —C≡C—(C1-C10 alkyl) or —C≡C-aryl;R6 is —C1-C10 alkyl, -aryl, —(CH2)n-aryl, —(CH2)n-(3- to 7-membered monocyclic heterocycle), —(CH2)n-(8- to 12-membered bicyclic heterocycle), —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl), —(CH2)n-(C3-C8 monocyclic cycloalkenyl), -phenylene-(CH2)nCOOH, or -phenylene-(CH2)nCOO—(C1-C10 alkyl);R7 is —H, —C1-C10 alkyl, -aryl, —(CH2)n-aryl, —(CH2)n-(3- to 7-membered monocyclic heterocycle), —(CH2)n-(8- to 12-membered bicyclic heterocycle), —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl) or —(CH2)n—(C8-C12 bicyclic cycloalkyl);and each n is independently an integer ranging from 1 to 5, and a pharmaceutically acceptable vehicle.