Agents for the Treatment of Overactive Detrusor. V. Synthesis and Inhibitory Activity on Detrusor Contraction of N-tert-Butyl-4,4-diphenyl-2-cyclopentenylamine
スポンサーリンク
概要
- 論文の詳細を見る
N-tert-Butyl-4,4-diphenyl-2-cyclopentenylamine ((±)-3) was designed to restrict the conformation of terodiline 1 and was synthesized in a 6-step approach starting with diphenylacetaldehyde (10) or in a 4-step approach starting with 2,2-diphenyl-4-pentenoic acid (17). Using di-p-toluoyltartaric acid as a resolving agent, the synthetic (±)-3 was resolved into its optically pure forms, (-)- and (+)-3. The (-)-enantiomer (-)-3・HCl (FK584) showed about ten times more potent inhibitory acitivity on urinary bladder rhythmic contraction in rats (ED_<30> =0.18 mg/kg, i.v.)than terodiline (ED_<30>=1.9 mg/kg, i.v), while the (+)-enantiomer (+)-3・HCl showed no inhibitory activity at 1.0 mg/kg i.v.Compound (-)-3・HCl (FK584) has pharmacological properties similar to those of terodiline, as evaluated by in vitro assay and is currently in clinical development for the treatment of overactive detrusor.
- 公益社団法人日本薬学会の論文
- 1996-10-15
著者
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Kinoshita T
Exploratory Research Laboratoeis Fujisawa Pharmaceutical Co. Ltd.
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寺井 孝雄
New Drug Research Laboratories Fujisawa Pharmaceutical Co., Ltd.,
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Tsubaki K
Institute For Chemical Research Kyoto University
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Terai T
New Drug Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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TANIGUCHI Kiyoshi
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.,
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TERAI Takao
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.,
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TSUBAKI Kazunori
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.,
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SHIOKAWA Youichi
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.,
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嶽 一彦
New Drug Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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TAKE Kazuhiko
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.,
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OKUMURA Kazuo
New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.,
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Shiokawa Y
Medicinal Chemistry Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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