Design and synthesis of a series of glycerol-derived receptor mediated calcium entry (RMCE) blockers

W. Howson, WP Armstrong, K. Cassidy, R. Novelli, MA Tchorzewska, A. Jaxa-Chamiec, RE Dolle, TJ Hallam, BK Leigh, JE Merritt, KE Moores, TJ Rink

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Receptor mediated calcium entry (RMCE) is a now recognised mechanism by which the influx of Ca2+ into cells can occur. Agents which antagonise or block this mechanism are expected to possess anti-platelet aggregation and anti-inflammatory activities. The first series of RMCE blockers based upon the lead compound SC 38249, has been prepared. Their synthesis, activity against ADP evoked Ca2+ signals in human platelets and their anti-platelet aggregation activity is described. A trend between the c log P of these compounds and their activity as inhibitors of Ca2+ influx into human platelets stimulated by ADP was observed. This SAR study led to a 40-fold increase in activity over the initial lead compound.

Original languageEnglish
Pages (from-to)595-602
Number of pages8
JournalEuropean Journal of Medicinal Chemistry
Volume25
Issue number7
DOIs
StatePublished - Sep 1990

Keywords

  • Ca influx
  • anti-platelet aggregation
  • c log P
  • receptor mediated calcium entry

Fingerprint

Dive into the research topics of 'Design and synthesis of a series of glycerol-derived receptor mediated calcium entry (RMCE) blockers'. Together they form a unique fingerprint.

Cite this