Discovery and Preliminary SAR of 5-Arylidene-2,2-Dimethyl-1,3-Dioxane- 4,6-Diones as Platelet Aggregation Inhibitors

Abdelaziz      El Maatougui; JhonnyAzuaje; Alberto      Coelho; Ernesto      Cano; Matilde      Yanez; Carmen      Lopez; Vicente      Yaziji; Carlos      Carbajales; Eddy      Sotelo

doi:10.2174/138620712801619122

Abstract

We herein document the discovery of 5-arylidene-2,2-dimethyl-1,3-dioxane-4,6-diones as a novel family of platelet aggregation inhibitors. The preliminary optimization study enabled us to establish the most salient features of the structure-activity relationships in this series as well as to identify novel derivatives that are upto 60 times more potent than the hit structure 1 and slightly superior to the reference drug Milrinone.

Keywords: Antiplatelet agents, Meldrum´s acid, platelet aggregation inhibitors, SAR, 5-Arylidene-2, 2-Dimethyl-1, 3-Dioxane-4, 6-Diones, Milrinone, antithrombotic agents, novel chemotypes, chemical genomics, signal transduction