Noscapine derivatives as adjuvant compositions and methods of use thereof

Abstract

An adjuvant composition comprising noscapine and its derivatives, for use in the treatment of tumors, cancer, as an adjuvant for vaccines.

1 - 14 . (canceled)  
   
   
       15 . A method of enhancing a mammal's protective immune response to a vaccine antigen, comprising the steps of administering to such mammal an immunogenic amount of the vaccine antigen and an immunogenicity-augmenting amount of noscapine in concurrent or sequential combination with such vaccine antigen.  
   
   
       16 . A method of enhancing a mammal's protective immune response to a vaccine antigen, the method comprising administering to a mammal an immunogenic amount of the vaccine antigen and an immunogenicity-augmenting amount of a noscapine compound of the following formula:  
     
       
         
         
             
             
         
       
       wherein: A is  
       
         
           
           
               
               
           
         
       
       and W is C 1-6  alkyl; or  
       
         
           
           
               
               
           
         
       
       and forms a six membered ring with B, said ring containing one nitrogen;  
       Y is  
       (a) C 1-6  alkyl, or H;  
       (b) C(O)—C 1-6 alkyl;  
       
         
           
           
               
               
           
         
       
       wherein Z is C 1-6  alkyl or O—C 1-6  alkyl;  
       (d) aryl; or  
       (e) heterocycle selected from the group consisting of piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, 2-oxoazepinyl, azepinyl, pyrrolyl, 4-piperidonyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, quinuclidinyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, thiadiazoyl, benzopyranyl, benzothiazolyl, benzoxazolyl, furyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, benzothienyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, and oxadiazolyl;  
       B is a single bond, OH or halo;  
       C is —OH, or —CH 2 — and  
       D is: (i) —OH, —CH 2 -halo, —CH(O)—, —COOH, —C(O)—O—C 1-6  alkyl, —(CH 2 ) n —, —CHOH—, wherein n is an integer and is 1, 2, or 3;  
       or wherein C and D form a 5-membered lactone or lactam ring;  
       E is —H or —CH 3 ; and  
       F is —OH or —OCH 3 , or pharmaceutically acceptable salts thereof, in concurrent or sequential combination with said vaccine antigen.