Alpha-amino esters of hydroxypropylthiazolidine carboxamide derivative and salt form, crystal polymorph thereof

Abstract

The invention provides α-amino esters of a hydroxypropylthiazolidine carboxamide derivative, (2S)-3-([1,1′-biphenyl]-4-ylsulfonyl)-N-[(1S)-3-hydroxy-1-phenylpropyl]-1,3-thiazolidine-2-carboxamide, as well as salts and crystal polymorph s thereof, that can be used to inhibit prostaglandin F receptor. The invention further encompasses methods of treating disorders such as pre-term labor at the early gestational stage by the administration of these substances to a patient in need of treatment.

1 - 26 . (canceled) 
     
     
         27 . A method of preventing labor prior to cesarean delivery in a human subject, the method comprising administering to the human subject a therapeutically effective amount of a compound represented by formula (III) 
       
         
           
           
               
               
           
         
       
     
     
         28 . The method of  claim 27 , wherein the human subject is characterized by a gestational age of from about 24 to about 34 weeks. 
     
     
         29 . The method of  claim 27 , wherein the compound is orally administered to the human subject. 
     
     
         30 . The method of  claim 27 , wherein the compound is intravenously administered to the human subject. 
     
     
         31 . The method of  claim 27 , wherein the compound is present within a pharmaceutical composition that further comprises one or more pharmaceutically acceptable excipients. 
     
     
         32 . The method of  claim 31 , wherein the pharmaceutical composition is a tablet, capsule, gel cap, powder, liquid solution, or liquid suspension. 
     
     
         33 . The method of  claim 27 , wherein the compound is in a crystalline state. 
     
     
         34 . The method of  claim 33 , wherein the compound exhibits characteristic X-ray powder diffraction peaks at about 7.0° 2θ, about 8.1° 2θ, about 10.0° 2θ, about 12.0° 2θ, about 13.1° 2θ, about 14.1° 2θ, about 16.4° 2θ, about 18.4° 2θ, about 20.1° 2θ, about 21.0° 2θ, about 23.5° 2θ, and about 29.5° 2θ. 
     
     
         35 . The method of  claim 34 , wherein the compound is characterized by an X-ray powder diffraction spectrum substantially as depicted in  FIG. 49 . 
     
     
         36 . The method of  claim 33 , wherein the compound exhibits  1 H nuclear magnetic resonance (NMR) peaks centered at about 1.1 ppm, about 3.3 ppm, about 4.9 ppm, about 5.4 ppm, about 7.1 ppm, about 7.7 ppm, about 7.9 ppm, and about 8.0 ppm. 
     
     
         37 . The method of  claim 36 , wherein the compound is characterized by a  1 H NMR spectrum substantially as depicted in  FIG. 21 . 
     
     
         38 . The method of  claim 33 , wherein the compound exhibits an endotherm at from about 145° C. to about 147° C. as measured by differential scanning calorimetry. 
     
     
         39 . The method of  claim 38 , wherein the compound is characterized by a differential scanning calorimetry curve substantially as depicted in  FIG. 20  or  FIG. 23 . 
     
     
         40 . The method of  claim 33 , wherein the compound exhibits a weight loss of from about 0.2% to about 0.6% when heated from 25° C. to 100° C. as measured by thermogravimetric analysis. 
     
     
         41 . The method of  claim 40 , wherein the compound exhibits a thermogravimetric analysis curve substantially as depicted in  FIG. 24 .