[Synthesis and antimalarial as well as antitumor activities of 2,4-diamino-6-(N-methyl-substituted benzylamino) quinazolines].

ABSTRACT

Sixteen 2,4-diamino-6-(N-methyl-substituted benzylamino) quinazolines (I) were synthesized by two different methods. 2-Nitro-5-chloro-benzonitrile was treated with the appropriate N-methyl-substituted benzylamines and I was formed after reduction and cyclization. Another method was reductive methylation, i.e., 2,4-diamino-6-substituted benzylaminoquinazolines reacted with formaldehyde and sodium cyanoborohydride at pH 6.3. Suppressive therapeutic tests in mice infected with Plasmodium berghei showed that four (I6,7,10,16) out of these compounds suppressed all the parasites when administered orally at the dose of 5 mg/kg and produced more than 99% suppression at 2.5 mg/kg. Eight compounds (I1,2,4,5,8-10,15) were found to have antitumor effects against Leukemia cells in culture comparable with or superior to those of the positive control methotrexate.