Beta-lactams having an alkyl-substituted side chain

Abstract

Taxane derivatives having an alkyl substituted C13 side chain.

What I claim is:  
     
         1 . A taxane derivative having the formula  
       
         
           
           
               
               
           
         
       
       wherein 
 X 1  is —OX 6 , —SX 7 , or —NX 8 X 9 ;  
 X 2  is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl;  
 X 3  is alkyl;  
 X 4  is hydrogen;  
 X 5  is —COX 10 , —COOX 10 , —COSX 10 , —CONX 8 X 10 , or —SO 2 X 11 ;  
 X 6  is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, hydroxy protecting group, or a functional group which increases the water solubility of the taxane derivative;  
 X 7  is alkyl, alkenyl, alkynyl, aryl, heteroaryl, or sulfhydryl protecting group;  
 X 8  is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterosubstituted alkyl, alkenyl, alkynyl, aryl or heteroaryl;  
 X 9  is an amino protecting group;  
 X 10  is alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterosubstituted alkyl, alkenyl alkynyl, aryl or heteroaryl;  
 X 11  is alkyl, alkenyl, alkynyl, aryl, heteroaryl, —OX 10 , or —NX 8 X 14 ;  
 X 14  is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl;  
 R 1  is hydrogen, hydroxy, protected hydroxy or together with R 14  forms a carbonate;  
 R 2  is hydrogen, hydroxy, —OCOR 31  together with R 2a  forms an oxo;  
 R 2a  is hydrogen or taken together with R 2  forms an oxo or;  
 R 4  is hydrogen, together with R 4a  forms an oxo, oxirane or methylene, or together with R 5a  and the carbon atoms to which they are attached form an oxetane ring;  
 R 4a  is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyano, hydroxy, —OCOR 30 , or together with R 4  forms an oxo, oxirane or methylene;  
 R 5  is hydrogen or together with R 5a  forms an oxo,  
 R 5a  is hydrogen, hydroxy, protected hydroxy, acyloxy, together with R 5  forms an oxo, or together with R 4  and the carbon atoms to which they are attached form an oxetane ring;  
 R 6  is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl, hydroxy, protected hydroxy or together with R 6a  forms an oxo;  
 R 6a  is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl, hydroxy, protected hydroxy or together with R 6  forms an oxo;  
 R 7  is hydrogen or together with R 7a  forms an oxo,  
 R 7a  is hydrogen, halogen, protected hydroxy, —OR 28 , or together with R 7  forms an oxo;  
 R 9  is hydrogen or together with R 9a  forms an oxo,  
 R 9a  is hydrogen, hydroxy, protected hydroxy, acyloxy, or together with R 9  forms an oxo;  
 R 10  is hydrogen or together with R 10a  forms an oxo,  
 R 10a  is hydrogen, —OCOR 29 , hydroxy, or protected hydroxy, or together with R 10  forms an oxo;  
 R 14  is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, hydroxy, protected hydroxy or together with R 1  forms a carbonate;  
 R 14a  is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl;  
 R 28  is hydrogen, acyl, hydroxy protecting group or a functional group which increases the solubility of the taxane derivative; and  
 R 29 , R 30 , and R 31  are independently hydrogen, alkyl, alkenyl, alkynyl, monocyclic aryl or monocyclic heteroaryl.  
 
     
     
         2 . The taxane derivative of  claim 1  wherein X 3  is cyclohexyl, cyclopropyl, cyclopentyl, cyclobutyl, propyl, or butyl.  
     
     
         3 . The taxane derivative of  claim 2  wherein X 5  is —COX 10  and X 10  is furyl or thienyl.  
     
     
         4 . The taxane derivative of  claim 2  wherein X 5  is —COOX 10 , and X 10  is alkyl R 9  is hydrogen and R 9a  is hydroxy.  
     
     
         5 . The taxane derivative of  claim 1  wherein X 5  is —COX 10 , X 10  is as defined in  claim 1 , X 3  is —CH 3 OH.  
     
     
         6 . The taxane derivative of  claim 2  wherein 
 R 10  is hydrogen or together with R 10a  forms an oxo,  
 R 10a  is hydrogen, hydroxy, protected hydroxy or —OCOR 29 , or together with R 10  forms an oxo;  
 R 9  is hydrogen or together with R 9a  forms an oxo;  
 R 9a  is hydrogen, acyloxy or together with R 9  forms an oxo;  
 R 7  is hydrogen, R 7a  is hydrogen, halogen or —OR 28 ;  
 R 5  is hydrogen;  
 R 5a  together with R 4  and the carbon atoms to which they are attached form an oxetane ring;  
 R 4a  is hydrogen, hydroxy, acetoxy or —OCOR 30 ,  
 R 2  is hydrogen, hydroxy, —OCOR 31  or taken together with R 2a  forms an oxo;  
 R 2a  is hydrogen or taken together with R 2  forms an oxo;  
 R 1  is hydrogen, hydroxy, protected hydroxy;  
 R 28  is hydrogen, acyl, hydroxy protecting group or a functional group which increases the water solubility of the taxane derivative; and  
 R 29 , R 30 , and R 31  are independently hydrogen, alkyl, alkenyl, alkynyl, monocyclic aryl or monocyclic heteroaryl.  
 
     
     
         7 . A pharmaceutical composition which contains the taxane derivative of  claim 1  and one or more pharmacologically acceptable, inert or physiologically active diluents or adjuvants.  
     
     
         8 . A β-lactam of the formula  
       
         
           
           
               
               
           
         
       
       wherein 
 X 1  is —OX 6 , —SX 7 , or —NX 8 X 9 ;  
 X 2  is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl;  
 X 3  is alkyl;  
 X 4  is hydrogen;  
 X 5  is —COX 10 , —COOX 10 , —COSX 10 , —CONX 8 X 10 , or -SO 2 X 11 ;  
 X 6  is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, hydroxy protecting group, or a functional group which increases the water solubility of the taxane derivative;  
 X 7  is alkyl, alkenyl, alkynyl, aryl, heteroaryl, or sulfhydryl protecting group;  
 X 8  is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterosubstituted alkyl, alkenyl, alkynyl, aryl or heteroaryl;  
 X 9  is an amino protecting group;  
 X 10  is alkyl, alkenyl, alkynyl, aryl, heteroaryl, or heterosubstituted alkyl, alkenyl alkynyl, aryl or heteroaryl;  
 X 11  is alkyl, alkenyl, alkynyl, aryl, heteroaryl, —OX 10 , or —NX 8 X 14 ; and  
 X 14  is hydrogen, alkyl, alkenyl, alkynyl, aryl, or heteroaryl.