Methods of Treating an Overweight or Obese Subject

Abstract

The disclosure herein generally relates to methods of treating an overweight or obese condition, and overweight- or obesity-related conditions. In one embodiment, the disclosure provides a method of treating an overweight or obese condition involving administering to the subject in need thereof, an amount of a pharmaceutical composition including a MetAP-2 inhibitory compound, or a salt, ester, or prodrug thereof, effective to result in weight loss in the subject.

What is claimed is: 
     
         1 . A method of treating a subject having an overweight or obese condition, the method comprising: administering to the subject in need thereof, a therapeutically effective amount of a pharmaceutical composition comprising a compound of Formula III: 
       
         
           
           
               
               
           
         
       
       wherein:
 W is O or NR; 
 each R is, independently hydrogen or a C 1 -C 4 -alkyl; 
 Q is hydrogen, a linear, branched or cyclic C 1 -C 6 -alkyl; or aryl; 
 R 1  is hydroxy, C 1 -C 4 -alkoxy or halogen; and
 Z is —C(O)— or C 1 -C 4 -alkylene-C(O)—; and P is NHR, OR, or a peptide consisting of 1 to about 100 amino acid residues attached to Z at the N-terminus; 
 or Z is alkylene-O or alkylene-NR; and P is hydrogen or peptide comprising 1 to 100 amino acid residues attached to Z at the C-terminus; 
 
 or a pharmaceutically acceptable salt, ester, or prodrug thereof. 
 
     
     
         2 . A method of treating a subject having an overweight or obese condition, the method comprising: administering to the subject a therapeutically effective amount of a pharmaceutical composition comprises a compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         3 . The method of  claim 1 , wherein the subject has a Body Mass Index measurement selected from the group consisting of: at least about 25 kg/m 2 , at least about 30 kg/m 2 , and at least about 40 kg/m 2 . 
     
     
         4 .- 12 . (canceled) 
     
     
         13 . A method of improving exercise capacity in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a compound of Formula III: 
       
         
           
           
               
               
           
         
       
       wherein:
 W is O or NR; 
 each R is, independently hydrogen or a C 1 -C 4 -alkyl; 
 Q is hydrogen, a linear, branched or cyclic C 1 -C 6 -alkyl; or aryl; 
 R 1  is hydroxy, C 1 -C 4 -alkoxy or halogen; and
 Z is —C(O)— or C 1 -C 4 -alkylene-C(O)—; and P is NHR, OR, or a peptide consisting of 1 to about 100 amino acid residues attached to Z at the N-terminus; 
 or Z is alkylene-O or alkylene-NR; and P is hydrogen or peptide comprising 1 to 100 amino acid residues attached to Z at the C-terminus; 
 
 or a pharmaceutically acceptable salt, ester, or prodrug thereof. 
 
     
     
         14 . (canceled) 
     
     
         15 . A method of restoring normal metabolic action in an obese subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a compound of Formula III: 
       
         
           
           
               
               
           
         
       
       wherein:
 W is O or NR; 
 each R is, independently hydrogen or a C 1 -C 4 -alkyl; 
 Q is hydrogen, a linear, branched or cyclic C 1 -C 6 -alkyl; or aryl; 
 R 1  is hydroxy, C 1 -C 4 -alkoxy or halogen; and
 Z is —C(O)— or C 1 -C 4 -alkylene-C(O)—; and P is NHR, OR, or a peptide consisting of 1 to about 100 amino acid residues attached to Z at the N-terminus; 
 or Z is alkylene-O or alkylene-NR; and P is hydrogen or peptide comprising 1 to 100 amino acid residues attached to Z at the C-terminus; 
 
 or a pharmaceutically acceptable salt, ester, or prodrug thereof.