Pyrazole derivatives as new potent and selective 20-hydroxy-5,8,11,14-eicosatetraenoic acid synthase inhibitors

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• 作者：Nakamura ; Toshio ; Kakinuma ; Hiroyuki ; Amada ; Hideaki ; Miyata ; Noriyuki ; Taniguchi ; Kazuo ; Koda ; Ayumi ; et. al.
• 关键词：20-HETE ; Pyrazole
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2004
• 出版时间：December 1, 2004
• 年：2004
• 卷：12
• 期：23
• 页码：6209-6219
• 全文大小：369 K

文摘

Improvement of the physical properties of pyrazole derivative 1, which we reported previously as a potent and selective 20-HETE synthase inhibitor (IC₅₀ 5.7nM), is described. Introduction of a sufficient substituted-amino group on the side chain enhanced the water-solubility of 1 (0.014mg/mL at pH6.8). Among the products, 2-piperazinoethoxy derivatives 3e and 6b showed solubility suitable for injection and potent inhibitory activity toward 20-HETE synthase (IC₅₀ 21.2 and 14.0nM, respectively).