Search

Your search keyword '"Baez-Santos YM"' showing total 2 results
Start Over Author "Baez-Santos YM" Topic severe acute respiratory syndrome
2 results on '"Baez-Santos YM"'

1. Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl) carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro inhibitors: identification of ML300 and noncovalent nanomolar inhibitors with an induced-fit binding.

Author

Turlington M, Chun A, Tomar S, Eggler A, Grum-Tokars V, Jacobs J, Daniels JS, Dawson E, Saldanha A, Chase P, Baez-Santos YM, Lindsley CW, Hodder P, Mesecar AD, and Stauffer SR

Subjects
Acetamides chemical synthesis, Antiviral Agents chemical synthesis, Humans, Models, Molecular, Severe Acute Respiratory Syndrome virology, Structure-Activity Relationship, Acetamides chemistry, Acetamides pharmacology, Antiviral Agents chemistry, Antiviral Agents pharmacology, Severe acute respiratory syndrome-related coronavirus drug effects, Severe Acute Respiratory Syndrome drug therapy
Abstract

Herein we report the discovery and SAR of a novel series of SARS-CoV 3CLpro inhibitors identified through the NIH Molecular Libraries Probe Production Centers Network (MLPCN). In addition to ML188, ML300 represents the second probe declared for 3CLpro from this collaborative effort. The X-ray structure of SARS-CoV 3CLpro bound with a ML300 analog highlights a unique induced-fit reorganization of the S2-S4 binding pockets leading to the first sub-micromolar noncovalent 3CLpro inhibitors retaining a single amide bond., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Published
2013
Full Text
View/download PDF

2. Discovery, synthesis, and structure-based optimization of a series of N-(tert-butyl)-2-(N-arylamido)-2-(pyridin-3-yl) acetamides (ML188) as potent noncovalent small molecule inhibitors of the severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL protease.

Author

Jacobs J, Grum-Tokars V, Zhou Y, Turlington M, Saldanha SA, Chase P, Eggler A, Dawson ES, Baez-Santos YM, Tomar S, Mielech AM, Baker SC, Lindsley CW, Hodder P, Mesecar A, and Stauffer SR

Subjects
Acetamides chemical synthesis, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Structure, Protease Inhibitors chemical synthesis, Small Molecule Libraries, Structure-Activity Relationship, Acetamides chemistry, Acetamides pharmacology, Drug Discovery, Protease Inhibitors chemistry, Protease Inhibitors pharmacology, Severe acute respiratory syndrome-related coronavirus enzymology, Severe Acute Respiratory Syndrome virology
Abstract

A high-throughput screen of the NIH molecular libraries sample collection and subsequent optimization of a lead dipeptide-like series of severe acute respiratory syndrome (SARS) main protease (3CLpro) inhibitors led to the identification of probe compound ML188 (16-(R), (R)-N-(4-(tert-butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide, Pubchem CID: 46897844). Unlike the majority of reported coronavirus 3CLpro inhibitors that act via covalent modification of the enzyme, 16-(R) is a noncovalent SARS-CoV 3CLpro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity. A multicomponent Ugi reaction was utilized to rapidly explore structure-activity relationships within S(1'), S(1), and S(2) enzyme binding pockets. The X-ray structure of SARS-CoV 3CLpro bound with 16-(R) was instrumental in guiding subsequent rounds of chemistry optimization. 16-(R) provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a noncovalent mechanism of action.

Published
2013
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results