Reactions with pyrrolidine-2,4-diones, Part 4: Synthesis of some 3-substituted 1,5-diphenylpyrrolidine-2,4-diones as potential antimicrobial, anti-HIV-1 and antineoplastic agents.

The condensation of 1,5-dipheiiylpyrrolidine-2,4-dione (1) with ethyl orthoformate yielded 3-ethoxymethylene-1,5-diphenylpyrrolidinc-2,4-dione (2). Reaction of the latter with hydrazine hydrate, secondary amines 7a-c or urea afforded the corresponding 3-substituted aminomethylene-1,5-diphenylpyrrolidene-2,4-diones 3, 8a-c or 9. On the other hand, condensation of 3 With veratraldehyde (5a) yielded 3-[(3,4-dimethoxybenzylidene)hydrazinomethylene]-1,5-diphenylpyrrolidine-24-dione (6). Whereas, cyclization of 9 with the reactive malonate ester 11 produced 3-[(5-butyl-4-hydroxy-2,6dioxo- 1,2,3,6- tetralhydropyrimidin-1-yl) methylene]-1,5-diphenylpyrrolidine-2,4-dione (12). The condensation of some selected aromatic aldehydes 5a-c and addition of morpholine (7c) or piperidine (7d) to some of the resulting 3-arylidene,1,5-diphenylpyrrolidine-2,4-diones 13b, e gave the respective 3-substituted methyl-4-hydroxy-1,5-diphenyl-Delta (3)-pyrrolin-2-ones 14a-c. Selected members of the new series were screened for their in vitro antimicrobial, anti-HIV-1 and antineoplastic activities. Two compounds 14a, b showed pronounced inhibitory activities against Gram-positive bacteria; whereas, in the in vitro anti-HIV-1 screening, only one compound Be displayed a moderate activity. However, in the antineoplastic screening protocol, the tested compounds were devoid of activity.