Method for reducing intraocular pressure using indole derivatives

Abstract

The present invention provides a method of reducing intraocular pressure by administering pharmaceutical compositions comprising indole derivatives. The pharmaceutical compositions useful in this invention comprise indole derivatives and melatonin analogs of Formulae I-IV. A preferred embodiment is a method of lowering intraocular pressure using 5-(methoxycarbonylamino)-N-acetyltryptamine (5-MCA-NAT), also known as GR 135531, which has a prolonged duration of action and greater efficacy in lowering intraocular pressure compared to melatonin. The present invention further provides a method of treating disorders associated with ocular hypertension, and a method of treating various forms of glaucoma; the method comprises administering an effective dose of a pharmacuetical composition comprising an indole derivative with or without agents commonly used to treat such disorders.

What is claimed is:  
     
         1 . A compound selected from the group consisting of: [3-(2-acetylamino-ethyl)-2-methyl-1H-indol-5-yl]-carbamic acid methyl ester; [3-(2-acetylamino-ethyl)-2-phenyl-1H-indol-5-yl]-carbamic acid methyl ester; [3-(3-acetylamino-prop-1-yl)-1H-indol-5-yl]-carbamic acid methyl ester; N-[2-(5-methoxycarbonylamino-1H-indol-3-yl)-ethyl]-succinamic acid; [3-(2-acetylamino-ethyl)-1H-indol-5-yl]-carbamic acid allyl ester; [3-(2-acetylamino-ethyl)-1H-indol-5-yl]-carbamic acid 3-hydroxy-prop-1-yl ester; [3-(2-acetylamino-ethyl)-4-(1-methoxy-ethyl)-1-methyl-1H-indol-5-yl]-carbamic acid methyl ester; N-[3-(2-acetylamino-ethyl)-1H-indol-5-yl]-acetamide; [3-(2-acetylamino-ethyl)-1-benzyl-1H-indol-5-yl]-carbamic acid methyl ester; (1-oxo-2,3,4,9-tetrahydro-1H-β-carbolin-6-yl)-carbamic acid methyl ester; [3-(2-acetylamino-ethyl)-2-bromo-1H-indol-5-yl]-carbamic acid methyl ester; and [3-(2-propionylamino-ethyl)-1H-indol-5-yl]-carbamic acid methyl ester.  
     
     
         2 . The compound according to  claim 1 , wherein the compound is 3-(2-acetylamino-ethyl)-2-methyl-1H-indol-5-yl]-carbamic acid methyl ester.  
     
     
         3 . The compound according to  claim 1 , wherein the compound is [3-(2-acetylamino-ethyl)-1H-indol-5-yl]-carbamic acid allyl ester.  
     
     
         4 . The compound according to  claim 1 , wherein the compound is [3-(2-acetylamino-ethyl)-1-benzyl-1H-indol-5-yl]-carbamic acid methyl ester.  
     
     
         5 . The compound according to  claim 1 , wherein the compound is (1-oxo-2,3,4,9-tetrahydro-1H-β-carbolin-6-yl)-carbamic acid methyl ester.  
     
     
         6 . The compound according to  claim 1 , wherein the compound is [3-(2-acetylamino-ethyl)-2-bromo-1H-indol-5-yl]-carbamic acid methyl ester.  
     
     
         7 . The compound according to  claim 1 , wherein the compound is [3-(2-propionylamino-ethyl)-1H-indol-5-yl]-carbamic acid methyl ester.  
     
     
         8 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound selected from the group consisting of: [3-(2-acetylamino-ethyl)-2-methyl-1H-indol-5-yl]-carbamic acid methyl ester; [3-(2-acetylamino-ethyl)-2-phenyl-1H-indol-5-yl]-carbamic acid methyl ester; [3-(3-acetylamino-prop-1-yl)-1H-indol-5-yl]-carbamic acid methyl ester; N-[2-(5-methoxycarbonylamino-1H-indol-3-yl)-ethyl]-succinamic acid; [3-(2-acetylamino-ethyl)-1H-indol-5-yl]-carbamic acid allyl ester; [3-(2-acetylamino-ethyl)-1H-indol-5-yl]-carbamic acid 3-hydroxy-prop-1-yl ester; [3-(2-acetylamino-ethyl)-4-(1-methoxy-ethyl)-1-methyl-1H-indol-5-yl]-carbamic acid methyl ester; N-[3-(2-acetylamino-ethyl)-1H-indol-5-yl]-acetamide; [3-(2-acetylamino-ethyl)-1-benzyl-1H-indol-5-yl]-carbamic acid methyl ester; (1-oxo-2,3,4,9-tetrahydro-1H-β-carbolin-6-yl)-carbamic acid methyl ester; [3-(2-acetylamino-ethyl)-2-bromo-1H-indol-5-yl]-carbamic acid methyl ester; and [3-(2-propionylamino-ethyl)-1H-indol-5-yl]-carbamic acid methyl ester.  
     
     
         9 . The pharmaceutical composition according to  claim 8 , wherein the compound is 3-(2-acetylamino-ethyl)-2-methyl-1H-indol-5-yl]-carbamic acid methyl ester.  
     
     
         10 . The pharmaceutical composition according to  claim 8 , wherein the compound is [3-(2-acetylamino-ethyl)-1H-indol-5-yl]-carbamic acid allyl ester.  
     
     
         11 . The pharmaceutical composition according to  claim 8 , wherein the compound is [3-(2-acetylamino-ethyl)-1-benzyl-1H-indol-5-yl]-carbamic acid methyl ester.  
     
     
         12 . The pharmaceutical composition according to  claim 8 , wherein the compound is (1-oxo-2,3,4,9-tetrahydro-1H-β-carbolin-6-yl)-carbamic acid methyl ester.  
     
     
         13 . The pharmaceutical composition according to  claim 8 , wherein the compound is [3-(2-acetylamino-ethyl)-2-bromo-1H-indol-5-yl]-carbamic acid methyl ester.  
     
     
         14 . The pharmaceutical composition according to  claim 8 , wherein the compound is [3-(2-propionylamino-ethyl)-1H-indol-5-yl]-carbamic acid methyl ester.