FUSED PYRIMIDINES .5. PYRIMIDO[4,5-D]PYRIMIDINE ANALOGS OF FOLIC-ACID

Pyrimido[4,5-d]pyrimidine analogues of folic acid have been prepared a nd tested for antitumor activity. Using Mannich reaction conditions, 2 ,4,6-triaminopyrimidine (12) or 2,4-diamino-6-oxopyrimidine (13) was t reated with formaldehyde and either diethyl N-[4-(2-aminoethyl)benzoyl ]-L-glutamate (18) or diethyl N-[4-(2-aminopropyl)benzoyl]-L-glutamate (24). The corresponding diester products (19, 20 and 25, 26) were con verted to the diacids (5, 6 and 7, 8) by treatment with aqueous ethano lic sodium hydroxide. Compounds(5, 6, and 7) were screened against CCR F-CEM leukemic cells and found to be significantly less active than DD ATHF, one of the most active compounds for this system.