Article ID Journal Published Year Pages File Type
1397879 European Journal of Medicinal Chemistry 2009 16 Pages PDF
Abstract

To find new anti-thrombotic agents, a natural amino acid was introduced into the 3-position of anti-platelet aggregation active 3S-tetrahydroisoquinoline-3-carboxylic acid (THIQA), and 20 novel dipeptide derivatives, 3S-tetrahydroisoquinoline-3-carboxyamino acids (6a–t), targeting the intestinal peptide transport system were provided. In vitro anti-platelet aggregation assay of 6a–t indicated that their potencies of inhibiting adenosine diphosphate (ADP), arachidonic acid (AA), platelet-activating factor (PAF), and thrombin (TH) induced platelet aggregations were higher than that of THIQA, and the in vivo anti-thrombotic assay of 6a–t indicated that their potencies of inhibiting thrombogenesis in rats were also higher than that of THIQA. According to MFA based Cerius2 QSAR module, using training/test set of 6a,b,d,g–p/6c,e,f,q and training/test set of 6a–p/6q–t, two equations (r, 0.984 and 0.996) correlating the structures with in vitro or in vivo activity of 6a–t were established.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

Related Topics
Physical Sciences and Engineering Chemistry Organic Chemistry
Authors
, , , , , , , ,