Antiangiogenic agents

Abstract

Compositions and methods for treating mammalian disease characterized by undesirable angiogenesis by administering derivatives of 2-methoxyestradiol of the general formula: wherein the variables are defined in the specification.

1 - 2 . (canceled)  
     
     
         3 . The method of  claim 10 , wherein: 
 R h1  and R h2  are independently H and Et.    
     
     
         4 . The method of  claim 10 , wherein: 
 R h1  and R h2  are independently H and n-Pr.    
     
     
         5 . The method of  claim 10 , wherein: 
 R h1  and R h2  are independently H and i-Bu.    
     
     
         6 . The method of  claim 10 , wherein: 
 R h1  and R h2  are independently H and CH 2 OH.    
     
     
         7 . The compound method of  claim 10 , wherein: 
 R h1  and R h2  are independently H and n-Bu.    
     
     
         8 . The method of  claim 10 , wherein: 
 R h1  and R h2  are independently H and Me.    
     
     
         9 . The method of  claim 10 , wherein: 
 R h1  and R h2  are independently H and (CH 2 ) n —C(Me) 2 .    
     
     
         10 . A method of inhibiting angiogenesis in a human or an animal comprising administering to the human or animal an angiogenesis inhibiting amount of a compound of the formula:  
       
         
           
           
               
               
           
         
       
       wherein: 
 a) R a  is —N 3 , —C≡N, —C≡C—R, —C═CH—R, —R—C═CH 2 , —C≡CH, —O—R, —R—R 1 , or —O—R—R 1  where R is a straight or branched alkyl with up to 10 carbons or aralkyl, and R 1  is —OH, —NH 2 , —Cl, —Br, —I, —F or CF 3 ;  
 b) Z′ is >CH or >C—R 2 —OH, where R 2  is an alkyl or branched alkyl with up to 10 carbons or aralkyl;  
 c) >C—R g  is >CH 2 , >C(H)—OH, >C═O, >C═N—OH, >C(R 3 )OH, >C═N—OR 3 , >C(H)—NH 2 , >C(H)—NHR 3 , >C(H)—NR 3 R 4 , or >C(H)—C(O)—R 3 , where each R 3  and R 4  is independently an alkyl or branched alkyl with up to 10 carbons or aralkyl;  
 d) R h1  and R h2  are independently H, or a straight or branched chain alkyl, alkenyl or alkynyl with up to 6 carbons that is unsubstituted, or substituted with one or more groups selected from a hetero functionality (O—Y, N—Y or S—Y) where Y is H, Me or an alkyl chain up to 6 carbons; a halo functionality (F, Cl, Br or I); an aromatic group optionally substituted with hetero, halo or alkyl; or R h1  and R h2  are independently an aromatic group optionally substituted with hetero, halo or alkyl, provided that both R h1  and R h2  are not H; and  
 wherein all monosubstituted substituents have either an α or β configuration.