Discovery of novel motilin antagonists: Conversion of tetrapeptide leads to orally available peptidomimetics.
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.
Taka
Naoki
N
Chemistry Research Dept. 1, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd, 1-135 Komakado Gotemba City, Shizuoka 412-8513, Japan. takanok@chugai-pharm.co.jp
Matsuoka
Hiroharu
H
Sato
Tsutomu
T
Yoshino
Hitoshi
H
Imaoka
Ikuhiro
I
Sato
Haruhiko
H
Kotake
Ken-ichiro
K
Kumagai
Yoshikazu
Y
Kamei
Kenshi
K
Ozaki
Ken-ichi
K
Higashida
Atsuko
A
Kuroki
Toshio
T
D000818:Animals; D018938:Caco-2 Cells; D002460:Cell Line; D055808:Drug Discovery; D005765:Gastrointestinal Agents / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D009037:Motilin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D010539:Permeability; D011817:Rabbits; D051381:Rats
D005765:Gastrointestinal Agents; D009842:Oligopeptides; D010455:Peptides; D009037:Motilin