COMBINATION, KIT AND METHOD OF REDUCING INTRAOCULAR PRESSURE

摘要

The present invention is directed to a combination or a kit comprising a prostaglandin analog and an adenosine receptor A1 agonist and to a method of reducing intraocular pressure (IOP) in a subject using such combination or kit. The invention is particularly directed to a combination of latanoprost marketed under the brand Xalatan™ and Compound A.

主权项

1. An ophthalmic combination comprising i) an adenosine receptor A1 agonist and ii) a prostaglandin analog formulated for administration to an eye of a subject in an amount effective to reduce intraocular pressure, wherein the adenosine receptor A1 agonist is a compound of Formula (I)or a pharmaceutically acceptable salt thereof,wherein
A is —CH2OH, —CH2ONO2 or —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 —H, —C1-C10 alkyl, -aryl, -3- to 7-membered monocyclic heterocyclyl, -8- to 12-membered bicyclic heterocyclyl, —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 heterocyclyl), —(CH2)n-(8- to 12-membered bicyclic heterocyclyl), —(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl)n-(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl)n-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 heterocyclyl), —(CH2)n-(8- to 12-membered bicyclic heterocyclyl)n-(CH2)n—(C3-C8 monocyclic cycloalkyl), —(CH2)n—(C3-C8 monocyclic cycloalkenyl)n-(CH2)n—(C8-C12 bicyclic cycloalkyl), —(CH2)n—(C8-C12 bicyclic cycloalkenyl)n-(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 heterocyclyl), —(CH2)n-(8- to 12-membered bicyclic heterocyclyl), —(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.