title: Discovery of novel motilin antagonists: Conversion of tetrapeptide leads to orally available peptidomimetics.
abstract: 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.
authors.affiliation: 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
authors.forename: Naoki
authors.initials: N
authors.lastname: Taka
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshino
authors.forename: Ikuhiro
authors.initials: I
authors.lastname: Imaoka
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sato
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Kotake
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Kenshi
authors.initials: K
authors.lastname: Kamei
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ozaki
authors.forename: Atsuko
authors.initials: A
authors.lastname: Higashida
authors.forename: Toshio
authors.initials: T
authors.lastname: Kuroki
mesh_terms: 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
chemical_list: D005765:Gastrointestinal Agents; D009842:Oligopeptides; D010455:Peptides; D009037:Motilin