Orally Active GPIIb/IIIa Antagonists : Synthesis and Biological Activities of Masked Amidines as Prodrugs of 2-[(3S)-4-[(2S)-2-(4-Amidinobenzoylamino)-3-(4-methoxyphenyl)propanoyl]-3-(2-methoxy-2-oxoethyl)-2-oxopiperazinyl]acetic Acid
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概要
- 論文の詳細を見る
To improve the in vivo potency of the potent GPIIb/IIIa antagonist 2-[(3S)-4-[(2S)-2-(4-amidinobenzoylamino)-3-(4-methoxyphenyl)propanoyl]-3-(2-methoxy-2-oxoethyl)-2-oxopiperazinyl]acetic acid (4), the amidino group was converted to an oxadiazole ring, thiadiazole ring or substituted amidoxime group. These groups were expected to be metabolized to an amidino group in vivo. The compounds synthesized were evaluated for their potency to inhibit the ex vivo adenosine 5'-diphosphate(ADP)-induced aggregation of guinea pig platelets. Among the compounds examined, the methoxycarbonyloxyamidine 8a exhibited the most potent ex vivo inhibitory activity with a fast onset and prolonged duration of action after oral administration.
- 社団法人日本薬学会の論文
- 2001-03-01
著者
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Miyawaki T
Department Of Dermatology Graduate School Of Medicine University Of Toyama
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Miyawaki Toshio
Medicinal Chemistry Research Laboratories Takeda Chemical Industries Ltd.
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Kawamura M
New Generation Research Laboratory Takeda Chemical Industries Ltd.
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KITAMURA Shuji
Medical Chemistry Research Laboratories, Takeda Chemical Industries, Ltd.
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FUKUSHI Hideto
Discovery Research Laboratories V, Takeda Chemical Industries, Ltd.
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KAWAMURA Masaki
Pharmacology Research Laboratories I, Takeda Chemical Industries, Ltd.
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TERASHITA Zen-ichi
Pharmacology Research Laboratories I, Takeda Chemical Industries, Ltd.
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NAKA Takehiko
Medical Chemistry Research Laboratories, Takeda Chemical Industries, Ltd.
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Naka T
Medicinal Chemistry Research Laboratories Takeda Chemical Industries Ltd.
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Kitamura S
Fujisawa Pharmaceutical Co. Ltd. Osaka Jpn
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Fukushi H
Discovery Research Laboratories V Takeda Chemical Industries Ltd.
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Kawamura Masaki
Department Of Physics Biology And Informatics Faculty Of Science Yamaguchi University
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Terashita Z
New Generation Research Laboratory Takeda Chemical Industries Ltd.
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Terashita Zen-ichi
Pharmaceutical Research Laboratories Ii Takeda Chemical Industries Ltd.
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