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

Article abstract of DOI:10.1016/0223-5234(90)90184-5

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.