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

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25 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1151-1161
Number of pages11
JournalBioorganic and Medicinal Chemistry
Issue number6
Publication statusPublished - Jun 1999
Externally publishedYes



  • Antagonists
  • Anticholinergics
  • Molecular modelling/mechanics
  • Receptors

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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