Discovery of novel motilin antagonists: Conversion of tetrapeptide leads to orally available peptidomimetics

Peptidomimetic motilin antagonists ( 17c and 17d) were identified. Both compounds dose-dependently suppressed motilin-induced colonic and gastric motility in conscious dogs. We successfully discovered peptidomimetic motilin antagonists ( 17c and 17d) through the improvement of physicochemical proper...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2009-07, Vol.19 (13), p.3426-3429
Main Authors: Taka, Naoki, Matsuoka, Hiroharu, Sato, Tsutomu, Yoshino, Hitoshi, Imaoka, Ikuhiro, Sato, Haruhiko, Kotake, Ken-ichiro, Kumagai, Yoshikazu, Kamei, Kenshi, Ozaki, Ken-ichi, Higashida, Atsuko, Kuroki, Toshio
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Caco-2 Cells
Cell Line
Digestive system
Drug Discovery
Gastrointestinal Agents - antagonists & inhibitors
Gastrointestinal Agents - metabolism
GM-109
Humans
Medical sciences
Motilin
Motilin - antagonists & inhibitors
Motilin - metabolism
Motilin receptor antagonist
Oligopeptides - chemical synthesis
Oligopeptides - chemistry
Oligopeptides - pharmacology
Peptides - chemical synthesis
Peptides - chemistry
Peptidomimetics
Permeability
Pharmacology. Drug treatments
Rabbits
Rats
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Summary:Peptidomimetic motilin antagonists ( 17c and 17d) were identified. Both compounds dose-dependently suppressed motilin-induced colonic and gastric motility in conscious dogs. We successfully discovered peptidomimetic motilin antagonists ( 17c and 17d) through the improvement of physicochemical properties of a tetrapeptide antagonist ( 2). Furthermore, with oral administration and based on motilin antagonistic activity, both compounds suppressed motilin-induced colonic and gastric motility in conscious dogs.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.05.059