Literature DB >> 12408705

Discovery of gamma-lactam hydroxamic acids as selective inhibitors of tumor necrosis factor alpha converting enzyme: design, synthesis, and structure-activity relationships.

James J-W Duan1, Lihua Chen, Zelda R Wasserman, Zhonghui Lu, Rui-Qin Liu, Maryanne B Covington, Mingxin Qian, Karl D Hardman, Ronald L Magolda, Robert C Newton, David D Christ, Ruth R Wexler, Carl P Decicco.   

Abstract

New gamma-lactam TACE inhibitors were designed from known MMP inhibitors. A homology model of TACE was built and examined to identify the S1' site as the key area for TACE selectivity over MMPs. Rational exploration of the P1'-S1' interactions resulted in the discovery of the 3,5-disubstituted benzyl ether as a TACE-selective P1' group. Further optimization led to the discovery of IK682 as a selective and orally bioavailable TACE inhibitor.

Entities:  

Mesh：

Substances：

Year:  2002        PMID： 12408705     DOI： 10.1021/jm0255670

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  8 in total

1.  Development of predictive pharmacophore model for in silico screening, and 3D QSAR CoMFA and CoMSIA studies for lead optimization, for designing of potent tumor necrosis factor alpha converting enzyme inhibitors.

Authors:  Prashant Revan Murumkar; Vishal Prakash Zambre; Mange Ram Yadav
Journal:  J Comput Aided Mol Des       Date:  2010-02-24       Impact factor: 3.686

Review 2.  Application of structural dynamic approaches provide novel insights into the enzymatic mechanism of the tumor necrosis factor-alpha-converting enzyme.

Authors:  Irit Sagi; Marcos E Milla
Journal:  Anal Biochem       Date:  2007-09-26       Impact factor: 3.365

Review 3.  ADAM-17: the enzyme that does it all.

Authors:  Monika Gooz
Journal:  Crit Rev Biochem Mol Biol       Date:  2010-04       Impact factor: 8.250

Review 4.  Rational approaches to improving selectivity in drug design.

Authors:  David J Huggins; Woody Sherman; Bruce Tidor
Journal:  J Med Chem       Date:  2012-01-12       Impact factor: 7.446

5.  Ginger components as new leads for the design and development of novel multi-targeted anti-Alzheimer's drugs: a computational investigation.

Authors:  Faizul Azam; Abdualrahman M Amer; Abdullah R Abulifa; Mustafa M Elzwawi
Journal:  Drug Des Devel Ther       Date:  2014-10-23       Impact factor: 4.162

6.  Molecular mechanisms and design principles for promiscuous inhibitors to avoid drug resistance: lessons learned from HIV-1 protease inhibition.

Authors:  Yang Shen; Mala L Radhakrishnan; Bruce Tidor
Journal:  Proteins       Date:  2015-02

Review 7.  Recyclization of Maleimides by Binucleophiles as a General Approach for Building Hydrogenated Heterocyclic Systems.

Authors:  Dmitriy Yu Vandyshev; Khidmet S Shikhaliev
Journal:  Molecules       Date:  2022-08-18       Impact factor: 4.927

8.  Prediction of an MMP-1 inhibitor activity cliff using the SAR matrix approach and its experimental validation.

Authors:  Yasunobu Asawa; Atsushi Yoshimori; Jürgen Bajorath; Hiroyuki Nakamura
Journal:  Sci Rep       Date:  2020-09-07       Impact factor: 4.379
  8 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.