SYNTHESIS AND ANTIVIRAL ACTIVITY OF NEW 3,4-DIHYDRO-2-ALKOXY-6-BENZYL-4-OXOPYRIMIDINES (DABOS), SPECIFIC INHIBITORS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

3,4-Dihydro-2-alkoxy-6-benzyl-4-oxopyrimidines (DABOs) have emerged as non-nucleoside inhibitors of human immunodeficiency virus type 1 [Art ico et al. (1993), Antiviral Chem Chemother 4: 361-368]. With a view t o increasing their potency, a new series of DABO derivatives, differen tly substituted at positions C-2 and/or C-5 of the pyrimidine ring and 3' or 3',5' of the benzyl moiety, have been synthesized. DABOs were p repared by reacting O-methylisourea with the appropriate methyl 2-alky l-4-phenylacetylacetate, with formation of ,4-dihydro-2-methoxy-6-aryl methyl-4-oxoprimidines. Subsequent displacement of the methoxy group l inked at the 2-position of the pyrimidine ring by treatment with alkox y and cycloalkoxy potassium salts led to the required derivatives. In vitro, the most potent compounds were 12e and 12p, which had an EC(50) of 0.8 mu M and a selective index of 400.