A Novel and Efficient One Pot Synthesis of 2,4‐Disubstituted Thiazoles and Oxazoles Using Phenyltrimethylammoniumtribromide in Ionic Liquid

A novel and efficient one‐pot procedure has been described for synthesis of 2,4‐disubstituted thiazoles and oxazoles from substituted ketones using phenyltrimethylammoniumtribromide as in situ brominating agent followed by reaction with thioamide/thiourea and amides/ureas, respectively in [bmim][BF₄] ionicliquid. The advantages of the procedure include avoiding the handling of lacrymetric compounds, hazardous and toxic organic solvents along with good to excellent yield of the products.     

Iodine-catalyzed three-component one-pot synthesis of naphthopyranopyrimidines under solvent-free conditions

Iodine is found to be a highly efficient catalyst for the three-component coupling (3CC) of aldehydes, β-naphthol, and 1,3-dimethylbarbituric acid under solvent-free conditions to afford the corresponding 8,10-dimethyl-12-aryl-12H-naphtho[1′,2′5,6]pyrano[2,3-d]pyrimidine-9,11-diones in good yields with high selectivity. The use of readily available iodine makes this method very simple, convenient, and cost-effective.     

Concurrent determination of olanzapine,risperidone and 9‐hydroxyrisperidone in human plasma by ultra performance liquid chromatography with diode array detection method: application to pharmacokinetic study

A simple and sensitive ultra‐performance liquid chromatography (UPLC) method has been developed and validated for simultaneous estimation of olanzapine (OLZ), risperidone (RIS) and 9‐hydroxyrisperidone (9‐OHRIS) in human plasma in vitro. The sample preparation was performed by simple liquid–liquid extraction technique. The analytes were chromatographed on a Waters Acquity H class UPLC system using isocratic mobile phase conditions at a flow rate of 0.3 mL/min and Acquity UPLC BEH shield RP₁₈ column maintained at 40°C. Quantification was performed on a photodiode array detector set at 277 nm and clozapine was used as internal standard (IS). OLZ, RIS, 9‐OHRIS and IS retention times were found to be 0.9, 1.4, .1.8 and 3.1 min, respectively, and the total run time was 4 min. The method was validated for selectivity, specificity, recovery, linearity, accuracy, precision and sample stability. The calibration curve was linear over the concentration range 1–100 ng/mL for OLZ, RIS and 9‐OHRIS. Intra‐ and inter‐day precisions for OLZ, RIS and 9‐OHRIS were found to be good with the coefficient of variation <6.96%, and the accuracy ranging from 97.55 to 105.41%, in human plasma. The validated UPLC method was successfully applied to the pharmacokinetic study of RIS and 9‐OHRIS in human plasma. Copyright © 2015 John Wiley & Sons, Ltd.     

Structural investigations of anthranilimide derivatives by CoMFA and CoMSIA 3D-QSAR studies reveal novel insight into their structures toward glycogen phosphorylase inhibition

In the present work, three-dimensional quantitative structure–activity relationship (3-D QSAR) studies on a set of 70 anthranilimide compounds has been performed using docking-based as well as substructure-based molecular alignments. This resulted in the selection of more statistically relevant substructure-based alignment for further studies. Further, molecular models with good predictive power were derived using CoMFA (r ^2?=?0.997; Q ^2?=?0.578) and CoMSIA (r ^2?=?0.976; Q ^2?=?0.506), for predicting the biological activity of new compounds. The so-developed contour plots identified several key features of the compounds explaining wide activity ranges. Based on the information derived from the CoMFA contour maps, novel leads were proposed which showed better predicted activity with respect to the already reported systems. Thus, the present study not only offers a highly significant predictive QSAR model for anthranilimide derivatives as glycogen phosphorylase (GP) inhibitors which can eventually assist and complement the rational drug-design attempts, but also proposes a highly predictive pharmacophore model as a guide for further development of selective and more potent GP inhibitors as anti-diabetic agents.