Indole inhibitors of human nonpancreatic secretory phospholipase A2. 3. Indole-3-glyoxamides

Journal of Medicinal Chemistry
S E DraheimJ P Wery

Abstract

The preceding papers of this series detail the development of functionalized indole-3-acetamides as inhibitors of hnps-PLA2. We describe here the extension of the structure-activity relationship to include a series of indole-3-glyoxamide derivatives. Functionalized indole-3-glyoxamides with an acidic substituent appended to the 4- or 5-position of the indole ring were prepared and tested as inhibitors of hnps-PLA2. It was found that the indole-3-glyoxamides with a 4-oxyacetic acid substituent had optimal inhibitory activity. These inhibitors exhibited an improvement in potency over the best of the indole-3-acetamides, and LY315920 (6m) was selected for evaluation clinically as an hnps-PLA2 inhibitor.

Citations

Jun 24, 2010·Journal of Molecular Modeling·Preethi BadrinarayanG Narahari Sastry
Jan 15, 2013·Journal of Molecular Modeling·Kalarickal Vijayan DileepChittalakkottu Sadasivan
Jul 16, 2003·European Journal of Pharmacology·Yasuhiko TomitaYozo Hori
Mar 7, 2001·European Journal of Medicinal Chemistry·M PintoreJ R Chrétien
Jul 9, 2008·Journal of Medicinal Chemistry·Rob C OslundMichael H Gelb
Apr 15, 2008·Annual Review of Biochemistry·Gérard Lambeau, Michael H Gelb
Oct 6, 1999·American Journal of Respiratory and Critical Care Medicine·S FurueH Obara
Feb 19, 2009·BMC Cardiovascular Disorders·Jose O LeiteMaria Luz Fernandez
Sep 3, 2010·Expert Opinion on Investigational Drugs·Robert S RosensonColin Hislop
Oct 11, 2016·Expert Opinion on Therapeutic Patents·Maroula G KokotouGeorge Kokotos
Dec 26, 2018·Chemical Biology & Drug Design·Shengde ZhangAixia Yan
Feb 22, 2000·The Journal of Biological Chemistry·N SuzukiK Hanasaki
Jun 2, 2011·Chemical & Pharmaceutical Bulletin·Hitoshi NakayamaJun'ichi Uenishi
Oct 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ryung Rae KimW Bret Church
Mar 22, 2002·Journal of Medicinal Chemistry·Albert PalomerAntonio Espinosa
Jun 9, 2009·Journal of Chemical Information and Modeling·Bo LiLihe Zhang
Jun 19, 2021·Expert Opinion on Drug Discovery·Charikleia S BatsikaGeorge Kokotos
Sep 27, 2008·Bioorganic & Medicinal Chemistry Letters·Rob C OslundMichael H Gelb
Mar 29, 2000·Journal of Medicinal Chemistry·K SenoM Ohtani

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