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Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists.

Abstract：

:To develop nonprostanoid prostacyclin receptor agonists with a high degree of metabolic resistance and an extended duration of action, a novel series of diphenylpyrazine derivatives was synthesized and evaluated for their inhibition of ADP-induced human platelet aggregation. Structure-activity relationship studies on the side chain containing the carboxylic acid moiety of the lead compound 5c showed that the length of the linker and the presence of the concatenating nitrogen atom adjacent to the pyrazine ring are critical for the antiaggregatory activity. This study led to the discovery of 2-amino-5,6-diphenylpyrazine derivatives 8c, 15a, and 15b, which showed potent inhibition of platelet aggregation with IC(50) values of 0.2 microM. Among these compounds, 15b is an orally available and long-lasting prostacyclin receptor agonist which is promising for the treatment of various vascular diseases.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Asaki T,Hamamoto T,Sugiyama Y,Kuwano K,Kuwabara K

doi

10.1016/j.bmc.2007.08.010

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

6692-704

issue

21

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(07)00699-2

journal_volume

15

pub_type

杂志文章

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