Synthesis and antimuscarinic activity of a series of 4-(1-Imidazolyl)-2,2-diphenylbutyramides: Discovery of potent and subtype-selective antimuscarinic agents

Hiroyuki Miyachi, Hiromi Kiyota, Hideharu Uchiki, Mitsuru Segawa

研究成果査読

25 被引用数 (Scopus)

抄録

In a study directed toward the development of new, selective agents with potential utility in the treatment of altered smooth muscle contractility and tone, for example, as seen in urinary incontinence associated with bladder muscle instability, a series of 4-(1-imidazolyl)-2,2-diphenylbutyramide derivatives was prepared. These compounds were examined for M1, M2, and M3 muscarinic receptor subtype selectivity in isolated tissue assays. The compounds that showed potency and/or selectivity in these tests were further evaluated for in vivo anticholinergic effects on various organs and tissues, including urinary bladder, salivary gland, and eye in rats. The structure-activity relationships for the series of 4-(1-imidazolyl)-2,2-diphenylbutyramide derivatives are also discussed. This study led to the identification of 4-(2-methyl-1-imidazolyl)-2,2-diphenylbutyramide (KRP-197) as a candidate drug for the treatment of urinary bladder dysfunction. Copyright (C) 1999 Elsevier Science Ltd.

本文言語English
ページ(範囲)1151-1161
ページ数11
ジャーナルBioorganic and Medicinal Chemistry
7
6
DOI
出版ステータスPublished - 6月 1999
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

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