摘要：

Based on ticlopidine active as an ADP receptor antagonist for inhibiting platelet aggregation in clinical test, and upon finding (±)-1,2-substituted-7-sulfonylamide/amide-1,2,3,4-tetrahydroisoquinoline (–) inhibited of platelet aggregation, a series of (±)-1--chlorophenyl-2-substituted-tetrahydroisoquinoline derivatives was designed and synthesized. Four analogs proved to be potential antiplatelet aggregation agents, and compound (TQP-3, applying for patent) which inhibits ADP-induced human platelet aggregation with IC values of approximately 0.206nM was the most active. Compound is more active than compound , which (Type I) is similar to ticlopidine. This is because there is a spacial hindrance in compound , and the -chloro group of compound may play the same a role as -chloro group of ticlopidine. On the other hand, with the different substitutions at different positions on the 2-substituted phenylacyl group, their inhibition of platelet aggregation differs. These compounds with -substituted group (, , ) showed a higher IC value for inhibiting ADP-induced human platelet aggregation than those with -substituted group (, ) or -substituted group (, ). It was observed that their inhibition is bromine-substituted derivative (), chlorine-substituted derivative (), and nitro-substituted derivative () in turn. Moreover, these compounds (Type II) may be more similar to clopidogrel than to ticlopidine due to the acyl group at 2 position of the nucleus playing a role as the ester group of clopidogrel. It was conjectured that these analogs function as a potential antiplatelet aggregation role by acting as ADP receptor antagonists.Graphical abstractFour analogs proved to be potential antiplatelet aggregation agents, and compound (TQP-3, applying for patent), which inhibits ADP-induced human platelet aggregation with IC values of approximately 0.206nM was the most active.

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