Synthesis and biological evaluation of novel pyrazole derivatives as urease inhibitors

Studies on enzyme inhibition remain an important area of pharmaceutical research since these studies have led to the discoveries of drugs useful in a variety of physiological conditions. The enzyme inhibitors can interact with enzymes and block their activity towards natural substrates. Urease inhibitors have recently attracted much attention as potential new anti-ulcer drugs. A series of novel substituted pyrazoles 8(a-j) has been synthesized by diazotization of fluoro chloro aniline (1) and the reaction of the corresponding diazonium salt solution (2) with ethyl cyanoacetate (3) to give the intermediate, ethyl 2-((3-chloro-4-fluorophenyl) diazenyl-2- cyanoacetate (4). The intermediate is then cyclised with chloroacetonitrile (5) using triethyl amine as the base to give the final compound, ethyl 4-amino-1-(3-chloro-4-flurophenyl)-5- cyano-1H-pyrazole-3-carboxylate (6). Nucleophilic substitution group is removed from the final compound and 8(a-j) derivatives have been synthesized. All the synthesized compounds were characterized by physical data (M.P. & TLC) and spectral Data (IR & 1H NMR). The synthesized compounds were evaluated for urease-inhibition activity. Molecular docking studies were carried out for these compounds with the enzyme urease. From the observations it has been noticed that some of the compounds possesses remarkable urease-inhibitory effect

RP-HPLC METHOD FOR ESTIMATION OF AN ANTIPSYCHOTIC DRUG - PIMOZIDE

Objective – To develop and validate RP-HPLC method for estimation of Pimozide in bulk and its tablet dosage form. Method- Chromatographic separation was carried out on Grace Smart RP-18 column (250 mm X 4.6 mm inner diameter; 5µm particle size) using a mobile phase consisted of Acetonitrile: 50 mM Disodium hydrogen phosphate buffer (pH 6.2, adjusted by 1 % ortho phosphoric acid) in the ratio of 60: 40 %v/v. The flow rate was maintained at 1 ml/min and UV detection was measured at 280 nm. Propyphenazone was used as an internal standard. Results-The calibration curve of Pimozide was linear in range of 5- 100 µg/ml. The mean % assay of marketed formulation was found to be 101.02 % and % recovery was observed in the range of 99.23- 101.91 %. Relative standard deviation for precision study was found less than 2 %. The LOD and LOQ values were found to be 0.553 µg/ml and 1.678 µg/ml respectively. Conclusion- The developed method is simple rapid and easy to apply, making it suitable for routine analysis of Pimozide in bulk and tablet dosage form. KEYWORDS- Pimozide, RP-HPLC, Validatio

Synthesis, In- vivo and In-silico anti-inflammatory studies of substituted fluoro pyrazole

N-phenyl-5-substituted -aryl-3-p-(fluorophenyl) pyrazoles have been synthesized from cyclization of 4-fluoroacetophenone (1) with various benzaldehydes (2) to give 4-fluorophenylstyrylketone (3) followed by treatment with phenyl hydrazine. The title compounds and their derivatives have been characterized by their elemental and spectral analysis. The newly synthesized compounds are screened for anti-inflammatory activity. All substituted 4-fluorophenylstyrylketones (250mg/kg orally p.o.) possessed anti-inflammatory activity against carrageenan-induced paw oedema in rat. Indomethacin (10mg/kg) was used as standard drug. And all compounds (0.20mM) showed ability to denature bovine serum albumin as observed in vitro inhibition studies. No correlation was found between the anti inflammatory activity and inhibition of bovine serum albumin denaturation. The docking studies were carried out for these compounds against the protein NFκB which is involved in inflammation signal cascade. Some of them showed good activity and molecular binding. Compounds such as 3b, 5b and 5e have exhibited comparative results in both in vivo and in silico studies