Discovery of a Series of Indole-2 Carboxamides as Selective Secreted Phospholipase A2 Type X (sPLA2-X) Inhibitors

  • ACS Med Chem Lett. 2018 Jun 23;9(7):594-599. doi: 10.1021/acsmedchemlett.7b00505.
Laurent Knerr  1 ,  Fabrizio Giordanetto  1 ,  Peter Nordberg  1 ,  Daniel Pettersen  1 ,  Nidhal Selmi  1 ,  Hans-Georg Beisel  1 ,  Hannah de la Motte  1 ,  Thomas Olsson  1 ,  Tim D J Perkins  1 ,  Margareta Herslöf  1 ,  Åsa Månsson  1 ,  Mikael Dahlström  1 ,  Ingemar Starke  1 ,  Johan Broddefalk  1 ,  Gabrielle Saarinen  1 ,  Fredrik Klingegård  1 ,  Eva Hurt-Camejo  1 ,  Birgitta Rosengren  1 ,  Johan Brengdahl  2 ,  Frank Jansen  2 ,  Mattias Rohman  2 ,  Jenny Sandmark  2 ,  Kenth Hallberg  2 ,  Tomas Åkerud  2 ,  Robert G Roth  2 ,  Marie Ahlqvist  1
Affiliations
  • 1. Medicinal Chemistry, Translational Sciences, Bioscience and Drug Metabolism and Pharmacokinetics, Cardiovascular and Metabolic Diseases, IMED Biotech Unit, AstraZeneca, Gothenburg SE-431 89, Sweden.
  • 2. Reagents and Assay Development, Mechanistic Biology and Profiling, and Structure and Biophysics, Discovery Sciences, IMED Biotech Unit, AstraZeneca, Gothenburg SE-431 89, Sweden.
PMID: 30034585 DOI: 10.1021/acsmedchemlett.7b00505
Abstract

In order to assess the potential of sPLA2-X as a therapeutic target for atherosclerosis, novel sPLA2 inhibitors with improved type X selectivity are required. To achieve the objective of identifying such compounds, we embarked on a lead generation effort that resulted in the identification of a novel series of indole-2-carboxamides as selective sPLA2-X inhibitors with excellent potential for further optimization.

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