Compositions and methods for reducing body fat

Abstract

The present invention relates to compositions, such as bimatoprost, latanoprost and travoprost, and methods to reduce fat in the body of an individual, for example, by topical administration, injection, and/or implantation of such compositions.

1 - 44 . (canceled) 
     
     
         45 . A pharmaceutical composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition is formulated for topical administration to the skin of a subject: 
       
         
           
           
               
               
           
         
       
       wherein:
 the dashed bonds represent a single or double bond which can be in the cis or trans configuration; 
 A is alkylene or alkenylene radical having from two to six carbon atoms, which radical may be interrupted by one or more oxide radicals and substituted with one or more hydroxy, oxo, alkyloxy, or alkylcarboxy groups, wherein the alkyl radical is from one to six carbon atoms; 
 B is a cycloalkyl radical having from three to seven carbon atoms or an aryl radical selected from the group consisting of hydrocarbyl aryl and heteroaryl radicals having from four to ten carbon atoms in which a heteroatom may be selected from the group consisting of nitrogen, oxygen, and sulfur atoms; 
 X is a radical selected from the group consisting of —OR 4  and —N(R 4 ) 2 , wherein R 4  is hydrogen, a lower alkyl radical having from one to six carbon atoms, 
 
       
         
           
           
               
               
           
         
         R 5  is a lower alkyl radical having from one to six carbon atoms; 
         Z is ═O or represents two hydrogen radicals; 
         one of R 1  and R 2  is ═O, —OH, or —O(CO)R 6 , and the other one is —OH or —O(CO)R 6 ; or R 1  is ═O and R 2  is H; and 
         R 6  is a saturated or unsaturated acyclic hydrocarbon group having from 1 to 20 carbon atoms, or —(CH 2 ) m R 7  in which m is 0-10 and R 7  is cycloalkyl radical having from three to seven carbon atoms, or a hydrocarbyl aryl or heteroaryl radical. 
       
     
     
         46 . The pharmaceutical composition of  claim 45 , wherein the compound is of Formula (II): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 y is 0 or 1; 
 x is 0 or 1; provided that x and y are not both 1; 
 Y is a radical selected from the group consisting of alkyl, halo, nitro, amino, thiol, hydroxy, alkyloxy, alkylcarboxy, and halo-substituted alkyl, wherein said alkyl radical comprises from one to six carbon atoms; 
 n is 0 or an integer from 1 to 3; and 
 R 3  is ═O, —OH, or —O(CO)R 6 . 
 
     
     
         47 . The pharmaceutical composition of  claim 46 , wherein the compound is of Formula (III): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         48 . The pharmaceutical composition of  claim 46 , wherein the compound is of Formula (V): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof;
 wherein Y 1  is —Cl or trifluoromethyl. 
 
     
     
         49 . The pharmaceutical composition of  claim 48 , wherein said compound is of Formula (VI): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         50 . The pharmaceutical composition of  claim 45 , provided that when B is not substituted with a pendant heteroatom-containing radical, and Z is ═O, then X is not —OR 4 . 
     
     
         51 . The pharmaceutical composition of  claim 45 , wherein Z is ═O; and X is —OR 4  or —N(R 4 ) 2 . 
     
     
         52 . The pharmaceutical composition of  claim 46 , wherein Z is ═O; and X is —OR 4  or —N(R 4 ) 2 . 
     
     
         53 . The pharmaceutical composition of  claim 46 , wherein R 1 , R 2 , and R 3  are —OH. 
     
     
         54 . The pharmaceutical composition of  claim 46 , wherein y is 0; and x is 1. 
     
     
         55 . The pharmaceutical composition of  claim 46 , wherein y is 1; and x is 0. 
     
     
         56 . The pharmaceutical composition of  claim 46 , wherein n is 0. 
     
     
         57 . The pharmaceutical composition of  claim 46 , wherein n is 1. 
     
     
         58 . The pharmaceutical composition of  claim 57 , wherein Y is trifluoromethyl. 
     
     
         59 . The pharmaceutical composition of  claim 45 , wherein the compound is selected from the group consisting of latanoprost, bimatoprost, and travoprost. 
     
     
         60 . The pharmaceutical composition of  claim 45 , wherein the compound is latanoprost. 
     
     
         61 . The pharmaceutical composition of  claim 45 , wherein the compound is bimatoprost. 
     
     
         62 . The pharmaceutical composition of  claim 45 , wherein the compound is travoprost. 
     
     
         63 . The pharmaceutical composition of  claim 45 , wherein the pharmaceutical composition is an ointment, lotion, or cream. 
     
     
         64 . The pharmaceutical composition of  claim 45  for reducing fat in the body of the subject. 
     
     
         65 . The pharmaceutical composition of  claim 45 , wherein the compound is present in the pharmaceutical composition in an amount effective for reducing fat in the body of the subject 
     
     
         66 . The pharmaceutical composition of  claim 65 , wherein the compound is present in the pharmaceutical composition in an amount from 0.001% to 1.0% (w/v), inclusive. 
     
     
         67 . The pharmaceutical composition of  claim 45 , wherein the pharmaceutical composition is a sustained-release formulation.