Therapeutic compounds

Abstract

Disclosed herein are compounds of the formula or salts or bioisosteres thereof. Therapeutic methods, medicaments, and compositions related thereto are also disclosed.

1 . A compound having a formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, or a prodrug thereof; 
       wherein a dashed line represents the presence or absence of a bond;
 Y is an organic acid functional group, or an amide or ester thereof comprising up to 14 carbon atoms; or Y is hydroxymethyl or an ether thereof comprising up to 14 carbon atoms; or Y is a tetrazolyl functional group; 
 A is —(CH 2 ) 6 —, cis —CH 2 CH═CH—(CH 2 ) 3 —, or —CH 2 C≡C—(CH 2 ) 3 —, wherein 1 or 2 carbon atoms may be replaced by S or O; or A is —(CH 2 ) m —Ar—(CH 2 ) o — wherein Ar is interarylene or heterointerarylene, the sum of m and o is 1, 2, 3, or 4, and wherein one CH 2  may be replaced by S or O; 
 U 1  is independently O; S; F; Cl; Br; I; CN; or O-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms ; 
 J 1  and J 2  are independently hydrogen; F; Cl, Br; I; O; OH; CN; O-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms; 
 alkyl having 1, 2, 3, 4, 5, or 6 carbon atoms; or CF 3 ; and 
 B is aryl or heteroaryl. 
 
     
     
         2 . A compound which is a carboxylic acid or a bioisostere thereof, said carboxylic acid having a structure 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, or a prodrug thereof; 
       wherein a dashed line represents the presence or absence of a bond;
 A is —(CH 2 ) 6 —, cis —CH 2 CH═CH—(CH 2 ) 3 —, or —CH 2 C≡C—(CH 2 ) 3 —, wherein 1 or 2 carbon atoms may be replaced by S or O; or A is —(CH 2 ) m —Ar—(CH 2 ) o — wherein Ar is interarylene or heterointerarylene, the sum of m and o is 1, 2, 3, or 4, and wherein one CH 2  may be replaced by S or O; 
 U 1  is independently O; S; F; Cl; Br; I; CN; or O-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms; 
 J 1  and J 2  are independently hydrogen; F; Cl, Br; I; O; OH; CN; O-alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms; 
 alkyl having 1, 2, 3, 4, 5, or 6 carbon atoms; or CF 3 ; and 
 B is aryl or heteroaryl. 
 
     
     
         3 . The compound according to  claim 1  wherein Y is selected from CO 2 R 2 , CON(R 2 ) 2 , CON(OR 2 )R 2 , CON(CH 2 CH 2 OH) 2 , CONH(CH 2 CH 2 OH), CH 2 OH, P(O)(OH) 2 , CONHSO 2 R 2 , SO 2 N(R 2 ) 2 , SO 2 NHR 2 , 
       
         
           
           
               
               
           
         
       
       wherein R 2  is independently H, C 1 -C 6  alkyl, unsubstituted phenyl, or unsubstituted biphenyl. 
     
     
         4 . The compound of  claim 3 , wherein said compound has a formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, or a prodrug thereof. 
     
     
         5 . The compound of  claim 3 , wherein said compound has a formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, or a prodrug thereof. 
     
     
         6 . The compound of  claim 3  wherein A is —(CH 2 ) 3 Ar—, —O(CH 2 ) 2 Ar—, —CH 2 OCH 2 Ar—, —(CH 2 ) 2 OAr, —O(CH 2 ) 2 Ar—, —CH 2 OCH 2 Ar—, or —(CH 2 ) 2 OAr, wherein Ar is monocyclic interheteroarylene. 
     
     
         7 . The compound of  claim 6  wherein Ar is interthienylene. 
     
     
         8 . The compound of  claim 6  wherein Ar is interthiazolylene. 
     
     
         9 . The compound of  claim 6  wherein Ar is interoxazolylene. 
     
     
         10 . The compound of  claim 7  wherein A is 5-(3-propyl)thiophen-2-yl. 
     
     
         11 . The compound of  claim 3  wherein A is 6-hexyl. 
     
     
         12 . The compound of  claim 3  wherein A is (Z)-6-hex-4-enyl. 
     
     
         13 . The compound of  claim 3  having the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof or a prodrug thereof. 
     
     
         14 . The compound of  claim 3  having the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof or a prodrug thereof. 
     
     
         15 . The compound of  claim 3  having the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof or a prodrug thereof. 
     
     
         16 . The compound of  claim 3  having the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof or a prodrug thereof. 
     
     
         17 . The compound of  claim 3  having the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof or a prodrug thereof. 
     
     
         18 . The compound of  claim 3  having the formulala 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof or a prodrug thereof. 
     
     
         19 . The compound of  claim 3  having the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof or a prodrug thereof. 
     
     
         20 . The compound of  claim 3  having the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof or a prodrug thereof. 
     
     
         21 . The compound of  claim 6  wherein B is substituted or unsubstituted phenyl. 
     
     
         22 . The compound of  claim 21  wherein B has 1, 2, 3, 4, or 5 substituents, wherein each substituent has one or more carbon, fluorine, chlorine, bromine, or oxygen atoms; and wherein all substituents taken together consist of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms; 0, 1, 2, 3, 4, 5, 6, 7, 8 or 9 fluorine atoms; 0, 1, 2 or 3 chlorine atoms, 0, 1, 2 or 3 bromine atoms, and 0, 1, 2 or 3 oxygen atoms. 
     
     
         23 . The compound of  claim 22  selected from
 5-{3-[(1S,5S)-5-(3-Chloro-5-hydroxymethyl-phenoxymethyl)-4-oxo-cyclopent-2-enyl]-propyl}-phiophene-2-carboxylic acid; and 
 5-{3-[(1S,2S)-2-(3-Chloro-5-hydroxymethyl-phenoxymethyl)-3-oxo-cyclopentyl]-propyl}-phiophene-2-carboxylic acid. 
 
     
     
         24 . A method of reducing intraocular pressure or treating glaucoma comprising administering a compound according to  claim 1  to a mammal in need thereof. 
     
     
         25 . The compound of  claim 3 , wherein said compound has a formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, or a prodrug thereof.