Synthesis and structure-activity relationship of a novel, achiral series of TNF-alpha converting enzyme inhibitors

Bioorganic & Medicinal Chemistry Letters
John L GilmoreJames J-W Duan

Abstract

A novel series of achiral TNF-alpha converting enzyme (TACE) inhibitors has been discovered. These compounds exhibited activities from 0.35 to 11nM in a porcine TACE assay and inhibited TNF-alpha production in an LPS-stimulated whole blood assay with an IC(50) value of 23nM for the most potent one. They also have excellent selectivities over related metalloproteases including aggrecanases.

References

Nov 14, 1997·Immunology Today·A EiglerS Endres
Jun 17, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·S Wojtowicz-PragaM J Hawkins
Jul 8, 1999·Journal of Medicinal Chemistry·R C Newton, C P Decicco
Nov 30, 2000·The New England Journal of Medicine·P E LipskyUNKNOWN Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group
Oct 26, 2001·Bioorganic & Medicinal Chemistry Letters·J HolmsS Davidsen
Nov 16, 2001·Journal of Medicinal Chemistry·M H RabinowitzM C Rizzolio
Apr 6, 2002·Bioorganic & Medicinal Chemistry Letters·James M ChenJeremy I Levin
Apr 6, 2002·Bioorganic & Medicinal Chemistry Letters·J I LevinJ S Skotnicki
Apr 19, 2002·The Journal of Pharmacology and Experimental Therapeutics·Bernie ScallonCarrie Wagner
May 7, 2002·Bioorganic & Medicinal Chemistry Letters·Michael A LetavicChul H Yu
Jul 12, 2002·Arthritis Research·Ravinder N Maini, Marc Feldmann
Jun 5, 2003·Bioorganic & Medicinal Chemistry Letters·Masaaki SawaKohichiro Yoshino
Jul 23, 2003·Bioorganic & Medicinal Chemistry Letters·J I LevinJ S Skotnicki
May 6, 2004·Bioorganic & Medicinal Chemistry Letters·Noriyuki KameiMasanao Shimano
Jul 21, 2004·Bioorganic & Medicinal Chemistry Letters·Jeremy I LevinDauphine Barone
Jul 5, 2005·Expert Opinion on Investigational Drugs·F C Nelson, A Zask

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Citations

Jun 20, 2007·Bioorganic & Medicinal Chemistry Letters·John L GilmoreJames J-W Duan
Sep 13, 2011·Clinical Proteomics·Michael J DuffyPatricia M McGowan
Dec 13, 2012·Expert Opinion on Drug Discovery·Prashant R MurumkarMange Ram Yadav
May 2, 2009·Clinica Chimica Acta; International Journal of Clinical Chemistry·Michael J DuffyPatricia M McGowan
Nov 6, 2007·Bioorganic & Medicinal Chemistry·Sara Källström, Reko Leino
May 22, 2010·Chemical Biology & Drug Design·Malkeet S Bahia, Om Silakari
Nov 20, 2012·Drug Discovery Today·Soumita Mukherjee, Manojit Pal
Jul 28, 2016·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Cemal OrhanKazim Sahin
May 29, 2007·Bioorganic & Medicinal Chemistry Letters·Henry-Georges LombartJeremy Levin
Sep 16, 2008·Bioorganic & Medicinal Chemistry·Dimitris Georgiadis, Athanasios Yiotakis
Feb 27, 2010·Critical Reviews in Biochemistry and Molecular Biology·Monika Gooz
Apr 18, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Patricia M McGowanMichael J Duffy
Feb 21, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael J DuffyPatricia M McGowan
Oct 14, 2009·Journal of Medicinal Chemistry·Marion FlipoRebecca Deprez-Poulain
Feb 2, 2008·Annals of Oncology : Official Journal of the European Society for Medical Oncology·P M McGowanM J Duffy
Dec 20, 2008·Bioorganic & Medicinal Chemistry·Shirshendu DasGuptaMange Ram Yadav
Nov 13, 2021·Journal of the American Chemical Society·Julia R DorsheimerTomislav Rovis

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