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-diphenylpyrrolidine-2,4-dione (1) with ethyl orthoformate yielded 3-ethoxymethylene-1,5-diphenylpyrrolidine-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- 2,4-dione (6). Whereas, cyclization of 9 with the reactive malonate ester 11 produced 3-[(5-butyl-4-hydroxy-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-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, c 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 13c displayed a moderate activity. However, in the antineoplastic screening protocol, the tested compounds were devoid of activity.
Shams el-Dine
S A
SA
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Egypt.
Soliman
F S
FS
Ashour
F A
FA
Saudi
M N
MN
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004354:Drug Screening Assays, Antitumor; D005658:Fungi / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D011760:Pyrrolidinones