We synthesized 2-(4-(4-fluorobenzylidene)-2-(4-fluorophenyl) 5-oxo-4,5-dihydroimidazol-1-yl) acetic acid 3. Chlorination afforded the chloro derivative 4, which reacted with different amines and hydrazine to afford compounds 5-8. Pyrazole, pyrazolone, and thiazolidinone derivatives were also synthesized from Imidazol-1-ylacetic acid hydrazide 8 to give compounds 9-12. Compounds were then evaluated for their anti-inflammatory activity against carrageenan-induced rat paw edema and their analgesic activity using the writhing test in albino mice. Compounds 5, 9, 10, 12 exhibited maximum anti-inflammatory activity, and all the compounds inhibited writhing, with 10 and 12 being two times more effective than the reference standard.
Three novel series of 2-(substituted phenyl)-4-(substituted arylidene)-imidazolone-5-(4H)-ones were derived from the corresponding oxazolones by condensation with different arylamines. Eleven of the synthesized compounds were selected and evaluated for their effect on carrageenan-induced rat paw edema. Compound 4b had the same efficacy as the reference standard (indomethacin), and compounds 3b, 3c, 4a, 4d and 9a showed good to excellent activities, with other compounds only weakly active. The potent compounds were evaluated for their inhibitory activities against COX-2-catalyzed PGE(2) production, with 4a, 4b and 3c showing strong inhibitory activity.
Novel pyrrolo[2,3-d]pyrimidines 5a-j, 6a-j and pyrrolo[2,3-b]pyridines 7a-h; incorporating the common vicinal diaryl motif of tumor necrosis factor-a (TNF-a) inhibitors, were synthesized starting from 2-amino-pyrrole-3-carbonitriles 1a-h. The structures of synthesized compounds were elucidated by spectral data (IR, NMR, and MS) and elemental analyses. Representative compounds were evaluated for their ability to inhibit lipopolysaccharideinduced TNF-a production in vivo in rat at 25 mg/kg p.o. Structure activity relationships are described. The pyrrolo[2,3-d]pyrimidines displayed better inhibitory activity than the pyrrolo[2,3-b]pyridines. The most potent among the biologically tested compounds was the pyrrolopyrimidine 5h (N-(4-ethoxyphenyl)-2-(4-oxo-6-phenyl-7-(pyridine-4-yl)-4H-pyrrolo[2,3-d]pyrimidin-3(7H)-yl)acetamide),showing TNF-a inhibitory activity (96 %) comparable to that of dexamethasone (91 %).
Trifluoperaizne (TFP) is an antipsychotic medication with limited oral bioavailability due to extensive first-pass metabolism; consequently, the goal of this project was to develop Leciplex nanoparticles to improve the bioavailability of TFP and to prolong its nasal residence time for treatment of the depression. Leciplex NPs were prepared using negatively charged phospholipid, cationic surfactant and biocompatible solvent and optimized using the 21 31 full factorial statistical design using various surfactants and different phospholipid to surfactant ratios. Design Expert® software was employed to select the optimum formula. The formulae were characterized regarding their particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency percentages (EE %), amount of drug released after 6 hours (Q6h), transmission electron microscopy analysis, fourier transform infrared ray spectroscopy (FT-IR) and stability for six months. Optimized formula was contained dimethyldidodecylammonium bromide as surfactant and had a
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