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 polymorphs thereof, that can be used to inhibit prostaglandin F receptor. The invention further encompasses methods of treating disorders such as preterm labor at the early gestational stage by the administration of these substances to a patient in need of treatment.

1 . A method of treating or preventing preterm labor in a human patient in need thereof, the method comprising providing to the patient a therapeutically effective amount of a compound represented by formula (II) 
       
         
           
           
               
               
           
         
         and an additional therapeutic agent. 
       
     
     
         2 . A method of delaying labor in a human patient in need thereof, the method comprising providing to the patient a therapeutically effective amount of a compound represented by formula (II) 
       
         
           
           
               
               
           
         
         and an additional therapeutic agent. 
       
     
     
         3 . A method of preventing labor prior to cesarean delivery in a human patient in need thereof, the method comprising providing to the patient a therapeutically effective amount of a compound represented by formula (II) 
       
         
           
           
               
               
           
         
         and an additional therapeutic agent. 
       
     
     
         4 . The method of  claim 1 , wherein the additional therapeutic agent is a tocolytic agent. 
     
     
         5 . The method of  claim 4 , wherein the tocolytic agent is an oxytocin receptor antagonist. 
     
     
         6 . The method of  claim 5 , wherein the oxytocin receptor antagonist is atosiban, retosiban, barusiban, epelsiban, or nolasiban. 
     
     
         7 . The method of  claim 6 , wherein the oxytocin receptor antagonist is atosiban. 
     
     
         8 . The method of  claim 4 , wherein the tocolytic agent is a calcium channel inhibitor. 
     
     
         9 . The method of  claim 8 , wherein the calcium channel inhibitor is nifedipine or nicardipine. 
     
     
         10 . The method of  claim 9 , wherein the calcium channel inhibitor is nifedipine. 
     
     
         11 . The method of  claim 1 , wherein the additional therapeutic agent is a betamimetic, a magnesium salt, a nitric oxide donor, progesterone or a variant thereof, or a corticosteroid. 
     
     
         12 . The method of  claim 11 , wherein the additional therapeutic agent is a betamimetic selected from the group consisting of terbutaline, ritodrine, hexoprenaline, albuterol, fenoterol, nylidrin, and orciprenaline. 
     
     
         13 . The method of  claim 11 , wherein the additional therapeutic agent is magnesium sulfate. 
     
     
         14 . The method of  claim 11 , wherein the additional therapeutic agent is nitroglycerine. 
     
     
         15 . The method of  claim 11 , wherein the additional therapeutic agent is progesterone or 17-α-hydroxyprogesterone caproate. 
     
     
         16 . The method of  claim 11 , wherein the additional therapeutic agent is a corticosteroid selected from the group consisting of betamethasone, dexamethasone, or hydrocortisone. 
     
     
         17 . The method of  claim 1 , wherein the patient is characterized by a gestational age of from about 24 weeks to about 34 weeks.