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Literature DB >> 11844705

A designed P1 cysteine mimetic for covalent and non-covalent inhibitors of HCV NS3 protease.

Frank Narjes¹, Konrad F Koehler, Uwe Koch, Benjamin Gerlach, Stefania Colarusso, Christian Steinkühler, Mirko Brunetti, Sergio Altamura, Raffaele De Francesco, Victor G Matassa.

Abstract

The difluoromethyl group was designed by computational chemistry methods as a mimetic of the canonical P1 cysteine thiol for inhibitors of the hepatitis C virus NS3 protease. This modification led to the development of competitive, non-covalent inhibitor 4 (K(i) 30 nM) and reversible covalent inhibitors (6, K(i) 0.5 nM; and 8 K*(i) 10 pM).

Entities: Chemical Gene Species

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Year: 2002 PMID： 11844705 DOI： 10.1016/s0960-894x(01)00842-3

Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823

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Cited

11 in total

1. Regio- and Enantioselective Bromocyclization of Difluoroalkenes as a Strategy to Access Tetrasubstituted Difluoromethylene-Containing Stereocenters.

Authors: Edward Miller; Suhong Kim; Katarina Gibson; Jeffrey S Derrick; F Dean Toste
Journal: J Am Chem Soc Date: 2020-04-30 Impact factor: 15.419

2. A new reagent for direct difluoromethylation.

Authors: Yuta Fujiwara; Janice A Dixon; Rodrigo A Rodriguez; Ryan D Baxter; Darryl D Dixon; Michael R Collins; Donna G Blackmond; Phil S Baran
Journal: J Am Chem Soc Date: 2012-01-13 Impact factor: 15.419

3. In vitro selection and characterization of hepatitis C virus serine protease variants resistant to an active-site peptide inhibitor.

Authors: Caterina Trozzi; Linda Bartholomew; Alessandra Ceccacci; Gabriella Biasiol; Laura Pacini; Sergio Altamura; Frank Narjes; Ester Muraglia; Giacomo Paonessa; Uwe Koch; Raffaele De Francesco; Christian Steinkuhler; Giovanni Migliaccio
Journal: J Virol Date: 2003-03 Impact factor: 5.103

4. Photocatalytic Reductive Olefin Hydrodifluoroalkylation Enabled by Tertiary Amine Reductants Compatible with Complex Systems.

Authors: Jonathan D Ellefsen; Scott J Miller
Journal: J Org Chem Date: 2022-07-13 Impact factor: 4.198

5. Potent Inhibitors of Hepatitis C Virus NS3 Protease: Employment of a Difluoromethyl Group as a Hydrogen-Bond Donor.

Authors: Barbara Zheng; Stanley V D'Andrea; Li-Qiang Sun; Alan Xiangdong Wang; Yan Chen; Peter Hrnciar; Jacques Friborg; Paul Falk; Dennis Hernandez; Fei Yu; Amy K Sheaffer; Jay O Knipe; Kathy Mosure; Ramkumar Rajamani; Andrew C Good; Kevin Kish; Jeffrey Tredup; Herbert E Klei; Manjula Paruchuri; Alicia Ng; Qi Gao; Richard A Rampulla; Arvind Mathur; Nicholas A Meanwell; Fiona McPhee; Paul M Scola
Journal: ACS Med Chem Lett Date: 2018-01-19 Impact factor: 4.345

A designed P1 cysteine mimetic for covalent and non-covalent inhibitors of HCV NS3 protease.

1. Regio- and Enantioselective Bromocyclization of Difluoroalkenes as a Strategy to Access Tetrasubstituted Difluoromethylene-Containing Stereocenters.

2. A new reagent for direct difluoromethylation.

3. In vitro selection and characterization of hepatitis C virus serine protease variants resistant to an active-site peptide inhibitor.

4. Photocatalytic Reductive Olefin Hydrodifluoroalkylation Enabled by Tertiary Amine Reductants Compatible with Complex Systems.

5. Potent Inhibitors of Hepatitis C Virus NS3 Protease: Employment of a Difluoromethyl Group as a Hydrogen-Bond Donor.

6. CF₂H, a Hydrogen Bond Donor.

7. Biocatalytic Strategy for the Highly Stereoselective Synthesis of CHF₂ -Containing Trisubstituted Cyclopropanes.

8. Mild silver-mediated geminal difluorination of styrenes using an air- and moisture-stable fluoroiodane reagent.

9. Palladium-catalyzed difluoromethylation of heteroaryl chlorides, bromides and iodides.

10. Harnessing Fluorine-Sulfur Contacts and Multipolar Interactions for the Design of p53 Mutant Y220C Rescue Drugs.