Synthesis and biological evaluation of direct thrombin inhibitors bearing 4-(piperidin-1-yl) pyridine at the P1 position with potent anticoagulant activity

M de Candia, F Fiorella, G Lopopolo…

文献索引：De Candia, Modesto; Fiorella, Filomena; Lopopolo, Gianfranco; Carotti, Andrea; Romano, Maria Rosaria; Lograno, Marcello Diego; Martel, Sophie; Carrupt, Pierre-Alain; Belviso, Benny D.; Caliandro, Rocco; Altomare, Cosimo Journal of Medicinal Chemistry, 2013 , vol. 56, # 21 p. 8696 - 8711

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被引用次数: 8

摘要

The design and synthesis of a new class of nonpeptide direct thrombin inhibitors, built on the structure of 1-(pyridin-4-yl) piperidine-4-carboxamide, are described. Starting from a strongly basic 1-amidinopiperidine derivative (6) showing poor thrombin (fIIa) and factor Xa (fXa) inhibition activities, anti-fIIa activity and artificial membrane permeability were considerably improved by optimizing the basic P1 and the X-substituted phenyl P4 binding moieties. ...