Enzyme-directed immunostimulant and uses thereof cross-reference to related application(s)

Abstract

The disclosed invention relates to the novel composition of matter that allows for the controlled release of highly active compounds to be delivered to a desired site. This novel composition utilizes the immune system to allow for the controlled release of desired compounds. The present invention can utilize a plurality of highly active compounds, with one embodiment being the use of chemotherapeutics for the treatment of cancer.

We/I claim: 
     
         1 . A compound of the formula (II), 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein 
         R is an enzyme substrate; 
         R1 is an immune-modulator; 
         X is O, S, N, or CH 2 ; and 
         Y is —OH, —OR 7 , —OCOR 7  and −NO 2 , wherein R 7  is an alkyl or substituted alkyl. 
       
     
     
         2 . A compound of  claim 1 , wherein
 R is selected from the group consisting of   
       
         
           
           
               
               
           
         
       
     
     
         3 . A compound of  claim 1 , wherein
 R is   
       
         
           
           
               
               
           
         
       
     
     
         4 . A compound of  claim 1 , wherein
 R1 is   
       
         
           
           
               
               
           
         
         wherein, R 2  is alkyl, substituted alkyl, alkenyl, alkynyl, and substituted alkynyl. 
       
     
     
         5 . A compound of  claim 1 , wherein R1 is a pharmaceutically acceptable salt of pyranoside, serine, glutamate, or phosphor containing peptide. 
     
     
         6 . The compound of  claim 1  wherein the compound has the formula, 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         7 . The compound of  claim 1  wherein the compound has the formula, 
       
         
           
           
               
               
           
         
       
     
     
         8 . A method of treating a patient that would benefit from the controlled release of immunomodulator for the treatment of a disease state comprising administering to a patient a therapeutically effective dose of a compound of Formula (II), 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein 
         R is an enzyme substrate; 
         R1 is an immune-modulator; 
         X is O, S, N, or CH2; and 
         Y is —OH, —OR7, —OCOR7 and —NO 2 , wherein R7 is an alkyl or substituted alkyl or a pharmaceutically acceptable salt thereof. 
       
     
     
         9 . The method of  claim 8  further comprising the step of monitoring the patient disease state progress to inform further treatment or prevention options. 
     
     
         10 . A method of  claim 8 , wherein the compound is administered in the presence of a parenteral carrier system. 
     
     
         11 . A method of  claim 8 , wherein said patient is suffering from a disease state of condition selected from at least one of: cancer, multidrug-resistant cancer, multidrug resistant pathogen infection, or comparable disease state resulting from underactivation of the immune system; or asthma, Crohn's disease, or comparable disease state resulting from over-activation of the immune system. 
     
     
         12 . A method of  claim 8 , wherein administration of the compound is sufficient to stimulate enzyme-directed activation of immune cells. 
     
     
         13 . A method of  claim 8 , wherein administration of the compound is sufficient to allow for release of the immunomodulator by enzymes in/on cancer cells or upregulated within the microenvironment of solid tumors. 
     
     
         14 . A method of  claim 8 , wherein administration of the compound avoids systemic inflammatory toxicity. 
     
     
         15 . A compound of the formula (I), 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein 
         R is an enzyme substrate; 
         R1 is an immune-modulator; 
         X is O, S, N, or CH 2 ; and 
         Y is one or more electron density modifying groups which may be the same or different if more than one Y is present on the benzene ring, and where the electron density modifying groups are selected from —OH, —OR 7 , —OCOR 7  and —NO 2 , wherein R 7  is an alkyl or substituted alkyl. 
       
     
     
         16 . The compound of  claim 15  wherein the enzyme substrate is selected from the group consisting of pyranosides, furanosides, and manosides. 
     
     
         17 . The compound of  claim 15  wherein the immune-modulator is selected from the group consisting of