作为维生素K拮抗剂的C-3脂肪族香豆素的合成及生物学评价

Synthesis and biological evaluation of C-3 aliphatic coumarins as vitamin K antagonists.

作者信息

Montagut-Romans Adrien, Boulven Manon, Jacolot Maïwenn, Moebs-Sanchez Sylvie, Hascoët Claire, Hammed Abdessalem, Besse Stéphane, Lemaire Marc, Benoit Etienne, Lattard Virginie, Popowycz Florence

机构信息

Univ Lyon, Université Claude Bernard Lyon 1, Laboratoire de Catalyse, Synthèse et Environnement, Institut de Chimie et de Biochimie Moléculaires et Supramoléculaires, ICBMS-CNRS-UMR 5246, F-69622 Villeurbanne Cedex, France; USC 1233 RS2GP, VetAgro Sup, INRA, Univ Lyon, F-69280 Marcy l'Etoile, France.

Univ Lyon, Institut National des Sciences Appliquées (INSA-Lyon), Laboratoire de Chimie Organique et Bioorganique, ICBMS-CNRS-UMR 5246, F-69621 Villeurbanne Cedex, France.

出版信息

Bioorg Med Chem Lett. 2017 Apr 1;27(7):1598-1601. doi: 10.1016/j.bmcl.2017.02.017. Epub 2017 Feb 11.

DOI:10.1016/j.bmcl.2017.02.017

PMID:28254487

Abstract

Since the discovery of Warfarin in the 1940s, the design of new warfarin-derived anticoagulants for rodent management has been challenging, with mainly structural modifications performed on the C3 position of the coumarin skeleton. In order to better understand the pharmacomodulation of such derivatives, we have synthesized a family of C3 (linear and branched) alkyl-4-hydroxycoumarins, which led to the identification of compounds 5e and 5f as potential short-term active anticoagulants.

摘要

自20世纪40年代发现华法林以来，设计用于灭鼠的新型华法林衍生抗凝剂一直具有挑战性，主要是在香豆素骨架的C3位进行结构修饰。为了更好地理解此类衍生物的药效调节作用，我们合成了一系列C3（直链和支链）烷基-4-羟基香豆素，从而确定化合物5e和5f为潜在的短期活性抗凝剂。