Abstract
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 language | English |
|---|---|
| Pages (from-to) | 1151-1161 |
| Number of pages | 11 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 7 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1999 |
| Externally published | Yes |
Fingerprint
Keywords
- Antagonists
- Anticholinergics
- Molecular modelling/mechanics
- Receptors
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Organic Chemistry
- Drug Discovery
- Pharmaceutical Science
Cite this
Synthesis and antimuscarinic activity of a series of 4-(1-Imidazolyl)-2,2-diphenylbutyramides : Discovery of potent and subtype-selective antimuscarinic agents. / Miyachi, Hiroyuki; Kiyota, Hiromi; Uchiki, Hideharu; Segawa, Mitsuru.
In: Bioorganic and Medicinal Chemistry, Vol. 7, No. 6, 06.1999, p. 1151-1161.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synthesis and antimuscarinic activity of a series of 4-(1-Imidazolyl)-2,2-diphenylbutyramides
T2 - Discovery of potent and subtype-selective antimuscarinic agents
AU - Miyachi, Hiroyuki
AU - Kiyota, Hiromi
AU - Uchiki, Hideharu
AU - Segawa, Mitsuru
PY - 1999/6
Y1 - 1999/6
N2 - 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.
AB - 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.
KW - Antagonists
KW - Anticholinergics
KW - Molecular modelling/mechanics
KW - Receptors
UR - http://www.scopus.com/inward/record.url?scp=0033012210&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033012210&partnerID=8YFLogxK
U2 - 10.1016/S0968-0896(99)00003-6
DO - 10.1016/S0968-0896(99)00003-6
M3 - Article
C2 - 10428387
AN - SCOPUS:0033012210
VL - 7
SP - 1151
EP - 1161
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 6
ER -