Synthesis and docking study of some pyrazolo [3, 4-d] pyrimidin -4 [5H]-one derivatives as phosphodiesterase-5 inhibitors

Twelve new pyrazolo [3, 4-d] pyriniidin-4-[5H]-one derivatives 13a-g, 14-17 and 24 were synthesized as inhibitors of phosphodiesterase enzyme type 5 [PDE5]. All intermediates and final compounds were analyzed by IR, H-NMR, mass spectra and elemental analysis. The title compounds were evaluated for their inhibitory activity toward PDE5 in comparison with sildenafil using anaesthetized normotensive rabbits. Eleven of the final compounds 13 a-g, 14, 16 and 24 were subjected to biological screening using animal model and nine of these compounds were subjected to molecular modeling study in order to investigate their binding mode. Most of the explored tested compounds showed the same binding mechanism as vardenafil and some of these compounds showed promising activity in comparison to sildenafil in the pharmacological studies. The results indicated that compound 24 is the most active member of the investigated series

Synthesis of new 4[3H]-quinazolinone derivatives of potential antimicrobial activity

A new series of quinazoline-4[3H]-one derivatives containing hydrazone, thiosemicarbazide, pyrazole moiety and 1,2,4-triazolo[4,3-a]quinazolin-5-[4H]-one derivatives, were prepared in order to study the effect of such combinations on the expected antimicrobial activity. Synthesis of target compounds [3-8] has been achieved through an interaction of the starting 2a or 2b with different alkyl or aryl isothiocyanate. Condensation of 2a or 2b with various aromatic aldehydes or ketones afforded the corresponding hydrazones 9-12. 1- [4-Pyridinyl]-l,2-dihydro-4-phenyl [allyl]-l, 2,4-triazolo [4t 3-a] quinazolin-5- [4H]-one derivatives 13, 14 have been synthesized through reflux of compound 9 or 10 in glacial acetic acid. On the other hand, 1-[3-substituted-3,4-dihydro-4-quinazolinon-2-yl]-3-[4-chlorophenyl] pyrazole-4-car-baldehyde 15 or 16 has also been synthesized through interaction of compounds 11 or 12 with Vilsmeier-Haack reagent. The structures of the new compounds were assigned by spectral and elemental methods of analysis. The synthesized compounds were tested for their in vitro antibacterial and antifungal activities. The tested compounds showed moderate antibacterial activity and weak or no antifungal activity

Synthesis and quantitative structure activity relationship [QSAR] study of new 3-allyl-5-substituted-3,4,5,6-tetrahydro-2H-l,3,5-thiadiazine-2-thiones of a potential antimicrobial activity

Fifteen new 3-allyl-5-substituted-3,4,5,6-tetrahydro-2H-l,3,5-thia diazine-2-thiones were synthesized by the reaction of allylamine with carbon disulfide and potassium hydroxide, followed by formaldehyde and appropriate primary amine such as alkyl, aralkylamines, glycine, L-alanine or ethyl glycine ester. The title compounds were tested, in vitro, for antimicrobial activity against gram-positive bacteria [Bacillus cereus, Staphylococcus aureus, Micrococcus leuteus], Gram-negative bacteria [Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa], and some fungi [Aspergillus flavus, Aspergillus niger, Candida albicans, Geotrichum candidum, Scopulariopsis brevicaulis and Tricho-phyton rubrum], using agar disc method. Quantitative structure activity relationship study was performed using the log form of MIC against Scopulariopsis brevicaulis fungi and some physico-chemical descriptors [MR, L, and Fr] of substituents at N-5 position. The log MIC were found to be negatively linearly correlated with MR and L and positively linearly correlated with Fr