Synthesis, Anticonvulsant Activity and In silco Studies of Schiff Bases of 2-Aminothiophenes via Guanidine- Catalyzed Gewald Reaction

Purpose: To synthesize Schiff bases of 2-aminothiophenes and evaluate their anticonvulsant activity and in silco propertiesMethods: 2-Amino-N-o-tolyl-5,6-dihydro-4H-cylcopenta[b]thiophene-3-carboxamide was synthesized using 1,1,3,3-tetramethylguanidine lactate as a basic catalyst and by microwave irradiation. 2- substitued-o-tolyl-5,6-dihyro-4H-cylcopenta[b]thiophene-3-carboxamide was prepared by reacting with different substituted aromatic aldehydes. The synthesized compounds were characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (1H NMR) and mass spectrometry (MS) while their anticonvulsant activity was screened against maximum electroshockinduced seizure (MES), and pentylenetetrazole-induced seizure (PTZ) against phenytoin and diazepam as reference standards. Molecular docking (in silico) studies were performed using 4-aminobutyrateaminotransferase in order to predict possible protein-ligand interactions.Results: Among the 21 synthesized compounds, 2b, 2d, 2f, 2k, 2m, 2n and 2o showed good to moderate activity against MES and PTZ-induced convulsions. Compounds 2b, 2d, 2f, 2k and 2m exhibited lower activity against PTZ than against MES model while compounds 2n and 2o afforded greater protection against PTZ than against MES model. In silico results also revealed maximum binding affinity to GABA-AT protein which was higher than other compoundsConclusion: The synthesized compounds showed potent anticonvulsant activity. Molecular docking results should give an insight into how further modification of lead compound can be carried out for higher inhibitory activity.Keywords: Ionic liquid, 2-Aminothiophenes, Anticonvulsant, In silco studies, Molecular docking

Enantioselective Synthesis of Antiepileptic Drug: (-)-Levetiracetam-Synthetic Applications of the Versatile New Chiral N-Sul�nimine

We report an asymmetric synthesis of (-)-Levetiracetam (1) in six steps starting from versatile new chiral N-sul�nimine (3). e key step, stereoselective 1,2-addition of ethylmagnesium bromide (EtMgBr) to chiral N-sul�nimine derived from (R)-glyceraldehyde acetonide and (S)-t-BSA, gave the corresponding sulfonamide (2) in high diastereoselectivity. Simultaneous deprotection and deacetylation followed by NaIO 4 cleavage and reduction gave -amino alcohol (6). Subsequent reactions yielded the targeted compound levetiracetam (1)

Synthesis of N-(3-arylprop-2-ynyl)substituted olanzapine derivatives as potential inhibitors of PDE4B

The linkage between dopamine D2 receptors and PDE activity via cAMP prompted us to design a series of novel N-(3-arylprop-2-ynyl)substituted olanzapine derivatives as potential inhibitors of PDE4B. The target compounds were conveniently prepared by using a simple and inexpensive method involving Pd/C-mediated CC bond forming reaction under Sonogashira conditions. A number of compounds were synthesized by using this strategy in good yields. Some of the compounds showed promising inhibition of PDE4B when tested in vitro that was supported by the docking studies

A Validated RP-HPLC Method for the Determination of Impurities in Montelukast Sodium

Abstract: The present paper describes the development of a reverse phase chromatographic (RPLC) method for montelukast sodium in the presence of its impurities and degradation products generated from forced degradation studies. The drug substance was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. The degradation of montelukast sodium was observed under acid and oxidative environment. The drug was found to be stable in other stress conditions studied. Successful separation of the drug from the process impurities and degradation products formed under stress conditions were achieved on an Atlantis dC18 (250 x 4.6 mm) 5 µm column. The gradient LC method employs solution A and solution B as mobile phase. The solution A contains aqueous 0.1% OPA and solution B contains a mixture of water, acetonitrile (5:95 v/v). The HPLC method was developed and validated with respect to linearity, accuracy, precision, specificity and ruggedness

GASTRO-FLOATING TABLETS OF REPAGLINIDE: PREPARATION AND IN VIVO EVALUATION

Objective: Current research concerns the expansion of repaglinide matrix floating tablets, which are designed to prolong the gastric residence time, increase the drug bioavailability, and diminish the side effects.Methods: Different formulations of repaglinide floating tablets were prepared with different grades of hydroxypropyl methylcellulose (HPMC) and other agents. Evaluation parameters and in vivo bioavailability studies were conducted in the suitable model.Results: Among all the formulations, F21 containing HPMC K1500 PH PRM, Polyox WSR 303, and sodium bicarbonate, as gas generating agent was selected as optimized formulation based on physicochemical properties, floating lag time (36 s), and total floating time (>24 h). From in vitro dissolution studies, the optimized formulation F21 showed drug release of 98.92±5.19% within 24 h whereas 95.09±5.01% of the drug was released from the marketed product within 1 h.Conclusion: From in vitro and in vivo bioavailability studies repaglinide floating tablets expected to give a new choice for safe, economical, and increased bioavailability for effective management of diabetes mellitus

Palladium(II) Complexes of Thiosemicarbazones of 2-Furfuraldehyde & Thiophene-2-carboxaldehyde

277-27

Synthesis & Characterization of Nickel(II) Complexes with Thiophene-2-Carboxyaldehyde Thiosemicarbazone

641-64

Simultaneous HPLC Determination of Butenafine Hydrochloride and Betamethasone in a Cream Formulation

A fast, specific, accurate and precise reverse phase high performance liquid chromatographic method was developed for the simultaneous determination of butenafine hydrochloride and betamethasone in cream formulation. The determination was carried out on licrocart licrosphere RP-select B (250×4.6 mm, 5 μ) column in isocratic mode, the mobile phase consisting of 50 mM ammonium acetate buffer and acetonitrile in the ratio of 60:40, adjusted to pH 4.5 ± 0.1 with glacial acetic acid. The flow rate was 2.0 ml/min and eluent was monitored at 254 nm. The retention times of butenafine hydrochloride and betamethasone were 4.70 min and 7.76 min, respectively, and the resolution factor was greater than 4.0. Linearity of butenafine hydrochloride and betamethasone were in the range of 100-300 μg/ml and 5-15 μg/ml, respectively. The proposed method is also found to be precise and robust for the simultaneous determination of butenafine hydrochloride and betamethasone in cream formulation