Characterization of a unique dihydropyrimidinone, ethyl 4-(4′-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate, as an effective antithrombotic agent in a rat experimental model

Abstract

H-DHPM has the attributes of a promising potent antiplatelet candidate molecule that should attract further study. H-DHPM displayed antiplatelet activity both in vivo and in vitro, which was due partially by lowering the intraplatelet calcium concentration.

Ethyl 4-(4′-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate Prevents Progression of Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

“…This mechanism influences smooth muscle cell proliferation, hypertrophy, contraction and platelet aggregation related PAH pathogenesis 33 . H-DHPM, arrests biphasic calcium entry, thereby eliminating calcium cross talk and suggesting the direct stimulatory action of Ca 2+ -channel blockers on endothelial NO production 17,18 . Further, these studies have proven that H-DHPM improves balance between eNOS/iNOS in both preclinical and translational studies.…”

“…Consequently, it can be interpreted that Ca 2+ channels play important role in pathogenesis of MCT induced PAH. Recently, H-DHPM has been discovered as a versatile L-type CCB capable of antiplatelet and antithrombotic activity, owing to single acyl (heptanoyl) group at the C4′ position of DHPM molecule 17,18 . In the current study we used 30mg/kg dose of H-DHPM to evaluate its effect on PAH pathogenesis.…”

“…H-DHPM was synthesised as described previously at Department of Chemistry, university of Delhi, Delhi, India. The physical and chemical characteristics of the H-DHMP have been previously explained and were reproduced for present study 16,18 .…”

“…Dihydropyrimidinone (DHPM), a derivative of dihydropyrimidine and class of CCBs have antihypertensive effects; however, no established data is available on its use in treating PAH 17 . Of note, the structural modifications greatly influence function of pyrimidinones and recently, Munral 16,18 , et al synthesised a novel CCB, a modified DHPM, namely ethyl 4-(4′-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2one-5-carboxylate (H-DHPM). H-DHPM, a versatile CCB, has been reported to have better functional efficacy as compared to parent moiety OH-DHPM 16,18 .…”

“…Of note, the structural modifications greatly influence function of pyrimidinones and recently, Munral 16,18 , et al synthesised a novel CCB, a modified DHPM, namely ethyl 4-(4′-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2one-5-carboxylate (H-DHPM). H-DHPM, a versatile CCB, has been reported to have better functional efficacy as compared to parent moiety OH-DHPM 16,18 . The activity of H-DHPM in blocking Ca 2+ activity has been attributed by the authors to an acyl (heptonyl) group at C-4' position of the compound.…”