Compositions and therapeutic methods involving isoflavones and analogues thereof

Abstract

Isoflavone compounds and analogues thereof, compositions containing same and therapeutic methods of treatment involving same are described.

1 .- 11 . (canceled)  
   
   
       12 . An isoflavone compound or analogue thereof of the general formula I:  
     
       
         
         
             
             
         
       
     
     in which 
 Z is chosen from hydrogen and Za,  
 Z A  is chosen from OR 9 , OC(O)R 10 , OS(O)R 10 , CHO, C(O)R 10 , COOH, CO 2 R 10 , CONR 3 R 4 , alkyl, haloalkyl, aryl, arylalkyl, thio, alkylthio, amino, alkylamino, dialkylamino, nitro, and halo,  
 W is chosen from hydrogen, hydroxy, OR 9 , OC(O)R 10 , OS(O)R 10 , CHO, C(O)R 10 , COOH, CO 2 R 10 , C 1-6  alkyl, haloC 1-6  alkyl, aryl, arylC 1-6  alkyl, thio, C 1-6  alkylthio, amino, C 1-6  alkylamino, diC 1-6  alkylamino, nitro, and halo,  
 X is chosen from O and S,  
 Y is  
                     
 R 1  and R 2  are independently hydrogen, hydroxy, OR 9 , OC(O)R 10 , OS(O)R 10 , CHO, C(O)R 10 , COOH, CO 2 R 10 , C 1-6  alkyl, haloC 1-6  alkyl, aryl, arylC 1-6  alkyl, thio, C 1-6  alkylthio, amino, C 1-6  alkylamino, diC 1-6  alkylamino, nitro, and halo,  
 R 3  is chosen from hydrogen, alkyl, aryl, arylalkyl, an amino acid, C(O)R 11  where R 11  is hydrogen, alkyl, aryl, arylalkyl or an amino acid, or CO 2 R 12  where R 12  is hydrogen, alkyl, haloalkyl, aryl, and arylalkyl,  
 R 4  is chosen from hydrogen, alkyl, and aryl,  
 or R 3  and R 4  taken together with the nitrogen to which they are attached comprise pyrrolidinyl or piperidinyl,  
 R 6  is chosen from hydrogen, hydroxy, C 1-6  alkyl, aryl, amino, thio, COR 11 , and CO 2 R 12 ,  
 R 7  is chosen from hydrogen, C(O)R 11 , C 1-6  alkyl, haloC 1-6  alkyl, aryl, arylC 1-6  alkyl, or Si(R 13 ) 3  where each R 13  is independently hydrogen, C 1-6  alkyl, and aryl,  
 R 9  is chosen from C 1-6  alkyl, haloC 1-6 alkyl, aryl, arylC 1-6 alkyl, C(O)R 11 , and Si(R 13 ) 3 ,  
 R 10  is chosen from hydrogen, C 1-6  alkyl, haloC 1-6  alkyl, amino, aryl, arylC 1-6  alkyl, an amino acid, C 1-6  alkylamino, and diC 1-6  alkylamino,  
 R 11  is chosen from hydrogen, C 1-6  alkyl, aryl, arylC 1-6  alkyl, and an amino acid,  
 R 12  is chosen from hydrogen, C 1-6  alkyl, haloC 1-6  alkyl, aryl, and arylC 1-6  alkyl,  
 R 14 , R 15  and R 16  are independently chosen from hydrogen, hydroxy, OR 9 , OC(O)R 10 , OS(O)R 10 , CHO, C(O)R 10 , COOH, CO 2 R 10 , C 1-6  alkyl, haloC 1-6  alkyl, aryl, arylC 1-6  alkyl, thio, C 1-6  alkylthio, amino, C 1-6  alkylamino, diC 1-6  alkylamino, nitro, and halo, and  
  aryl is chosen from phenyl and naphthyl, either of which is optionally substituted by one or more of C 1-4  alkyl, hydroxy, C 1-4  alkoxy, carbonyl, C 1-4  alkoxycarbonyl, C 1-4  alkylcarbonyloxy and halo, and with the proviso that:  
 when  
 R 1  is hydroxy, or OC(O)R A  where R A  is alkyl or an amino acid,  
 R 2  is hydrogen, hydroxy, OR B  where R B  is an amino acid or C(O)R A    
 Z is hydrogen, and  
 W is hydrogen, then  
 Y is not 4-hydroxyphenyl or 4-alkylphenyl;  
 when  
 R 1  is hydroxy, or OC(O)R A  where R A  is alkyl or an amino acid,  
 R 2  is hydrogen, hydroxy, OR B  where R B  is an amino acid or C(O)R A ,  
 Z is hydrogen, and  
 Y is 4-hydroxyphenyl or 4-alkylphenyl, then  
 W is not hydrogen;  
 when  
 R 1  is hydroxy, or OC(O)R A  where R A  is alkyl or an amino acid, and  
 Z is hydrogen,  
 W is hydrogen, and  
 Y is 4-hydroxyphenyl or 4-alkylphenyl, then  
 R 2  is not hydrogen, hydroxy, OR B  where R B  is an amino acid or C(O)R A ,  
 when  
 R 2  is hydrogen, hydroxy, OR B  where R B  is an amino acid or C(O)R A ,  
 Z is hydrogen,  
 W is hydrogen, and  
 Y is 4-hydroxyphenyl or 4-alkylphenyl, then  
 R 1  is not hydroxy, or OC(O)R A  where R A  is alkyl or an amino acid; and  
 when  
 R 1  is hydroxy, or OC(O)R A  where R A  is alkyl or an amino acid,  
 R 2  is hydrogen, hydroxy, OR B  where R B  is an amino acid or C(O)R A ,  
 W is hydrogen, and  
 Y is 4-hydroxyphenyl or 4-alkylphenyl; then  
 Z is not hydrogen.  
 
   
   
       13 . A compound according to  claim 12  having the formula:  
     
       
         
         
             
             
         
       
     
   
   
       14 . A therapeutic composition comprising one or more compounds selected from formula (I) as defined in  claim 12  in association with one or more pharmaceutical carriers and/or excipients.  
   
   
       15 . A compound of formula (I) as defined in  claim 12  for use in treatment, defense against, prophylaxis and or prevention of one or more therapeutic indications.  
   
   
       16 . Use of one or more compounds selected from formula (I) as defined in  claim 12  for the manufacture of a medicament for the treatment, amelioration, defense against, prophylaxis and/or prevention of one or more therapeutic indications selected from coronary artery spasm; hypertension; inflammatory diseases.  
   
   
       17 . Use according to  claim 16  wherein the inflammatory disease is inflammatory bowel disease, ulcerative colitis or Crohn's disease.