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Design, synthesis, and structure-activity relationships of potent GPIIb/IIIa antagonists: discovery of FK419.

Abstract：

:The discovery of the non-peptide antiplatelet injectable agent FK419 is reported. Based on the beta-turn structure of RGD peptide sequences in the alpha chain of fibrinogen, which binds the glycoprotein IIb/IIIa (GPIIb/IIIa) on the surface of platelets to induce platelet aggregation, the prototype 2 was designed. After further substituent effects were investigated at the alpha-position of the carboxylic acid in 2, we enhanced platelet aggregation inhibition, and discovered the useful feature of reduced prolongation of bleeding time. Finally, the potent platelet aggregation inhibitor FK419 (3) could be discovered. FK419 shows a safe feature of reduced prolongation of bleeding time, as well as potent inhibition of platelet aggregation.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Yamanaka T,Ohkubo M,Kuroda S,Nakamura H,Takahashi F,Aoki T,Mihara K,Seki J,Kato M

doi

10.1016/j.bmc.2005.03.056

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

4343-52

issue

13

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(05)00281-6

journal_volume

13

pub_type

杂志文章

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