Pyridine Carboxamides: Potent Palm Site Inhibitors of HCV NS5B Polymerase

نویسندگان
چکیده

برای دانلود باید عضویت طلایی داشته باشید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Classification of HCV NS5B Polymerase Inhibitors Using Support Vector Machine

Using a support vector machine (SVM), three classification models were built to predict whether a compound is an active or weakly active inhibitor based on a dataset of 386 hepatitis C virus (HCV) NS5B polymerase NNIs (non-nucleoside analogue inhibitors) fitting into the pocket of the NNI III binding site. For each molecule, global descriptors, 2D and 3D property autocorrelation descriptors wer...

متن کامل

New Pyrazolobenzothiazine Derivatives as Hepatitis C Virus NS5B Polymerase Palm Site I Inhibitors

We have previously identified the pyrazolobenzothiazine scaffold as a promising chemotype against hepatitis C virus (HCV) NS5B polymerase, a validated and promising anti-HCV target. Herein we describe the design, synthesis, enzymatic, and cellular characterization of new pyrazolobenzothiazines as anti-HCV inhibitors. The binding site for a representative derivative was mapped to NS5B palm site ...

متن کامل

Non-nucleoside analogue inhibitors bind to an allosteric site on HCV NS5B polymerase. Crystal structures and mechanism of inhibition.

X-ray crystal structures of two non-nucleoside analogue inhibitors bound to hepatitis C virus NS5B RNA-dependent RNA polymerase have been determined to 2.0 and 2.9 A resolution. These noncompetitive inhibitors bind to the same site on the protein, approximately 35 A from the active site. The common features of binding include a large hydrophobic region and two hydrogen bonds between both oxygen...

متن کامل

Discovery of a novel series of non-nucleoside thumb pocket 2 HCV NS5B polymerase inhibitors.

A novel series of non-nucleoside thumb pocket 2 HCV NS5B polymerase inhibitors were derived from a fragment-based approach using information from X-ray crystallographic analysis of NS5B-inhibitor complexes and iterative rounds of parallel synthesis. Structure-based drug design strategies led to the discovery of potent sub-micromolar inhibitors 11a-c and 12a-c from a weak-binding fragment-like s...

متن کامل

QSAR study of HCV NS5B polymerase inhibitors using the genetic algorithm-multiple linear regression (GA-MLR)

Quantitative structure-activity relationship (QSAR) study has been employed for predicting the inhibitory activities of the Hepatitis C virus (HCV) NS5B polymerase inhibitors . A data set consisted of 72 compounds was selected, and then different types of molecular descriptors were calculated. The whole data set was split into a training set (80 % of the dataset) and a test set (20 % of the dat...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

ژورنال

عنوان ژورنال: ACS Medicinal Chemistry Letters

سال: 2010

ISSN: 1948-5875,1948-5875

DOI: 10.1021/ml100128h