volume 15 issue 21 pages 6692-6704

Structure–activity studies on diphenylpyrazine derivatives: A novel class of prostacyclin receptor agonists

Tetsuo Asaki 1
Taisuke Hamamoto 1
Yukiteru Sugiyama 1
Keiichi Kuwano 1
Kenji Kuwabara 1
1
 
Discovery Research Laboratories, Nippon Shinyaku Co., Ltd, 14 Nishinosho-Monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan
Publication typeJournal Article
Publication date2007-11-01
scimago Q2
wos Q1
SJR0.608
CiteScore6.7
Impact factor3.0
ISSN09680896, 14643391
Organic Chemistry
Drug Discovery
Biochemistry
Molecular Biology
Pharmaceutical Science
Clinical Biochemistry
Molecular Medicine
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.
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GOST |
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GOST Copy
Asaki T. et al. Structure–activity studies on diphenylpyrazine derivatives: A novel class of prostacyclin receptor agonists // Bioorganic and Medicinal Chemistry. 2007. Vol. 15. No. 21. pp. 6692-6704.
GOST all authors (up to 50) Copy
Asaki T., Hamamoto T., Sugiyama Y., Kuwano K., Kuwabara K. Structure–activity studies on diphenylpyrazine derivatives: A novel class of prostacyclin receptor agonists // Bioorganic and Medicinal Chemistry. 2007. Vol. 15. No. 21. pp. 6692-6704.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.1016/j.bmc.2007.08.010
UR - https://doi.org/10.1016/j.bmc.2007.08.010
TI - Structure–activity studies on diphenylpyrazine derivatives: A novel class of prostacyclin receptor agonists
T2 - Bioorganic and Medicinal Chemistry
AU - Asaki, Tetsuo
AU - Hamamoto, Taisuke
AU - Sugiyama, Yukiteru
AU - Kuwano, Keiichi
AU - Kuwabara, Kenji
PY - 2007
DA - 2007/11/01
PB - Elsevier
SP - 6692-6704
IS - 21
VL - 15
PMID - 17764960
SN - 0968-0896
SN - 1464-3391
ER -
BibTex |
Cite this
BibTex (up to 50 authors) Copy
@article{2007_Asaki,
author = {Tetsuo Asaki and Taisuke Hamamoto and Yukiteru Sugiyama and Keiichi Kuwano and Kenji Kuwabara},
title = {Structure–activity studies on diphenylpyrazine derivatives: A novel class of prostacyclin receptor agonists},
journal = {Bioorganic and Medicinal Chemistry},
year = {2007},
volume = {15},
publisher = {Elsevier},
month = {nov},
url = {https://doi.org/10.1016/j.bmc.2007.08.010},
number = {21},
pages = {6692--6704},
doi = {10.1016/j.bmc.2007.08.010}
}
MLA
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MLA Copy
Asaki, Tetsuo, et al. “Structure–activity studies on diphenylpyrazine derivatives: A novel class of prostacyclin receptor agonists.” Bioorganic and Medicinal Chemistry, vol. 15, no. 21, Nov. 2007, pp. 6692-6704. https://doi.org/10.1016/j.bmc.2007.08.010.