ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Preparation and antiplatelet activity of glycidic acid derivatives

Josef Jampílek, Eliška Brojerová, Martin Doležal, Jiří Kuneš, and Daniel Jun

Zentiva, a.s., U Kabelovny 130, CZ-102 37 Prague, Czech Republic

E-mail: josef.jampilek@zentiva.cz

Received: 2 July 2007  Revised: 12 October 2007  Accepted: 12 November 2007

Abstract: Arylalkanoic acid derivatives exhibit a variety of biological effects. In the current publication some of new glycidic acid derivatives were prepared via the Darzens condensation. The synthetic approach, analytical and spectroscopic data of all newly synthesized compounds are presented. The prepared compounds were evaluated as potential inhibitors of arachidonic acid-induced platelet aggregation and their activity was compared with that of acetylsalicylic acid as the standard. (±)-Ethyl 3-{4-[(4-methoxyphenyl)sulfanyl]phenyl}-3-methyl-cis-oxirane-2-carboxylate (IC₅₀ = 0.07 mmol L⁻¹) and (±)-3-{4-[(4-methoxyphenyl)sulfanyl]phenyl}-3-methyl-cis-oxirane-2-carboxylic acid (IC₅₀ = 0.06 mmol L⁻¹) showed the highest antiplatelet activity against arachidonic acid-induced platelet aggregation comparable with the standard. Structure-activity relationships between the chemical structure, lipophilicity, and the antiplatelet activity of the evaluated compounds are discussed.

Keywords: glycidic acid derivatives - Darzens condensation - geometric isomerism - in vitro antiplatelet activity - lipophilicity - structure-activity relationships

Full paper is available at www.springerlink.com.

DOI: 10.2478/s11696-008-0024-0

Chemical Papers 62 (3) 281–287 (2008)