Synthesis and Antiaggregating Activity of Nonpeptide Fibrinogen Receptor Antagonists (Ⅱ): N-Substituted-O-(4-Amidinophenoxy) Ethyl-L-Tyrosine Methyl Ester

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Synthesis and Antiaggregating Activity of Nonpeptide Fibrinogen Receptor Antagonists (Ⅱ): N-Substituted-O-(4-Amidinophenoxy) Ethyl-L-Tyrosine Methyl Ester

Xu Tianlin^*, Jiang Xuntian^**, Hua Weiyi, Ni Peizhou, Pei Yongmei^*

Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009

Received:1998-11-10 Revised:1999-06-01 Online:1999-12-15 Published:1999-12-15
Contact: Xu Tianlin*, Jiang Xuntian**, Pei Yongmei*

Abstract

Abstract:

A series of nonpeptide fibrinogen receptor antagonists were designed andsynthesized by mimicking the structure of Arg-Gly-Asp (RGD) sequences in fibrinogen. In order toexplore the effect of spacer polarity on inhibitory activity, 12 N-substituted-O-(4-amidinophenoxy) ethyl-L-tyrosine methyl esters have been synthesized with the less polar dioxyethylene spacer insteadof the aminocarbonyl methyl in our previous report. The inhibitory effects of 12 target compoundscontaining tyrosine skeleton for adenosine 5-diphosphate (ADP) induced platelet aggregation inrabbit platelet-rich plasma were evaluated utilizing a turbidometric technique and 9 compoundsshowed inhibitory action at the concentration as low as 1×10^-6 mol·L^-1, of which Ii has the bestactivity.

Key words: Nonpeptide fibrinogen receptor antagonists, Nonpeptide fibrinogen receptor antagonists, Structure design, Structure design, Synthesis, Synthesis, Tyrosine, Tyrosine, Antiaggregating activity, Antiaggregating activity

Supporting:

Xu Tianlin^*, Jiang Xuntian^**, Hua Weiyi, Ni Peizhou, Pei Yongmei^*. Synthesis and Antiaggregating Activity of Nonpeptide Fibrinogen Receptor Antagonists (Ⅱ): N-Substituted-O-(4-Amidinophenoxy) Ethyl-L-Tyrosine Methyl Ester[J]. .

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Synthesis and Antiaggregating Activity of Nonpeptide Fibrinogen Receptor Antagonists (Ⅱ): N-Substituted-O-(4-Amidinophenoxy) Ethyl-L-Tyrosine Methyl Ester

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