Nucleophilic Functionalization of the Calix[6]arene Para- and Meta-Position via p‑Bromodienone Route

It is here demonstrated that the p-bromodienone route, previously reported for calix[4]arenes, is also effective for the functionalization of the calix[6]arene macrocycle. Thus, alcoholic O-nucleophiles can be introduced at the calix[6]arene exo rim. In addition, the reaction of a calix[6]arene p-bromodienone derivative with an actived aromatic substrate, such as resorcinol, led to the first example of a meta-functionalized, inherently chiral calix[6]arene derivativ

QSAR studies of 1,2,5-thiadiazole derivatives analogues of aceclidine as potent M1 muscarinic agonists

International audienceIn the present study, Quantitative structure-activity relationship (QSAR) study have been performed on twenty molecules of 1,2,5-thiadiazole derivatives. The compounds studied are the analogues of aceclidine as potent M1 muscarinic agonists. A multiple linear regression (MLR) procedure was used to design the relationships between molecular descriptors and biological activity of the 1,2,5- thiadiazole derivatives. The predictivity of the model was estimated by cross-validation with the leave-one-outmethod. Our results suggest a QSAR model based on the following descriptors Log P , HE, Pol, MR, MV, and MW, SAG, and Etotal. High correlation between experimental and predicted activity values was observed, indicating the validation and the good quality of the established QSAR models. © 2018 American Scientific Publishers

Quantitative structure anti-proliferative activity against HEPG2 and SW1116 relationships in a series of Pyrazine Derivatives

International audienceQuantitative structure activity relationship (QSAR) methods have been applied in several scientific studies including chemistry, biology and toxicology and drug discovery to predict and classify biological activities of virtual or newly-synthesized compounds. QSAR models can also be used in designing new chemical entities and are now regarded as essential tools in pharmaceutical industries to identify promising hits and generate high quality leads in the early stages of drug discovery. QSAR studies were performed on a series of pyrazine as anti-proliferative agents. A multiple linear regression (MLR) procedure was used to envisage the relationships between molecular descriptors and the activity of pyrazine derivatives. The predictivity of the model was estimated by cross-validation with the leave-one-out method. Our results suggest a QSAR model based of the following descriptors: logP, HE, SAG, Pol, qC3 for the anti-proliferative activity against the HEPG2 (human liver cancer cell) and logP, HE, MR, SAG, Vol, qC2, qC5, qC6, LUMO for the anti-proliferative activity against the SW1116 (human colorectal carcinoma cell). To confirm the predictive power of the models, an external set of molecules was used. High correlation between experimental and predicted activity values was observed, indicating the validation and the good quality of the derived QSAR models. Copyright © 2017 American Scientific Publishers All rights reserved

Property/activity relationships and drug likeness for pyrimidine derivatives as serine/threonine protein Kinase B inhibitors

International audienceThe equilibrium geometry and electronic structures of the pyrimidine, were determined and analyzed with ab initio/HF, and DFT method. In the present work, the calculated values, namely net charges, MESP contours/surfaces has also been drawn to explain the electronic activity of Pyrimidine. QSAR properties, Lipinski's parameters, Lipophilic Efficiency (LipE), are reported and discussed to understand the biological activity of the Pyrimidine Derivatives. © 2017 American Scientific Publishers