Substituted pyrimidine compounds and methods of use and manufacture

Abstract

wherein X is absent, CH2, S, or O, and R is an alkyl group having from one to ten carbon atoms, and optionally salts, hydrates, or solvates thereof, that are useful in treating a patient having a disease or cancer. The compounds of this invention are useful as multi-enzyme antifolates selectively targeting the folate receptor (FR). Further, a method of making 5- and 6-substituted cyclopenta[d]pyrimidine for nonclassical and classical antifolates as TS and DHFR inhibitors is provided.

What is claimed is: 
     
         1 . A method of treating a patient having cancer comprising administering to a patient an effective amount of a compound comprising formula: 
       
         
           
           
               
               
           
         
       
       wherein X is S and n is an integer ranging from one to three, and optionally comprising a pharmaceutically acceptable salt, hydrate, or solvate thereof, and including optionally administering an effective amount of said salt, hydrate, or solvate of said compound to said patient. 
     
     
         2 . A method of treating a patient having cancer comprising administering to a patient an effective amount of a compound comprising formula: 
       
         
           
           
               
               
           
         
       
       wherein X is absent, CH 2 , O, or S, and R is an alkyl group having from one to ten carbon atoms or a hydrogen, and optionally comprising a pharmaceutically acceptable salt, hydrate, or solvate thereof, and including optionally administering an effective amount of said salt, hydrate, or solvate of said compound to said patient. 
     
     
         3 . A method of treating a patient having cancer comprising administering to a patient an effective amount of a compound comprising formula: 
       
         
           
           
               
               
           
         
       
       wherein X is absent, CH 2 , O, or S, and R is an alkyl group having from one to ten carbon atoms, and optionally comprising a pharmaceutically acceptable salt, hydrate, or solvate thereof, and including optionally administering an effective amount of said salt, hydrate, or solvate of said compound to said patient.