title: New mu-opioid receptor agonists with phenoxyacetic acid moiety.
abstract: New muq-opioid receptor (MOR) agonists containing 4-hydroxypiperidine, piperidine and piperazine moieties were synthesized and evaluated to find a peripheral opioid analgesic. Among the synthesized compounds, 12-[1-[3-(N,N-dimethylcarbamoyl)-3,3-diphenylpropyl]-4-hydroxypiperidin-4-yl]phenoxy]acetic acid (8: SS620) having phenoxyacetic acid and 4-hydroxypiperidine moieties showed the highest agonist potency on the MOR in an isolated guinea-pig ileum preparation, and it also had selectivity to the human MOR expressed in Chinese hamster ovary (CHO)-K1 cells compared with the same types of delta- and kappa-opioid receptors (DOR and KOR). In addition, compound 8 showed a 10 times more potent MOR agonist activity than loperamide. Furthermore, compound 8 showed a peripheral analgesic activity in vivo screening on rat.
authors.affiliation: Central Research Laboratories SSP Co, Ltd, Narita, Chiba, Japan. Susumu.Sato@ssp.co.jp
authors.forename: Susumu
authors.initials: S
authors.lastname: Sato
authors.forename: Teruo
authors.initials: T
authors.lastname: Komoto
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kanamaru
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kawamoto
authors.forename: Tomomi
authors.initials: T
authors.lastname: Okada
authors.forename: Terumitsu
authors.initials: T
authors.lastname: Kaiho
authors.forename: Kinichi
authors.initials: K
authors.lastname: Mogi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Morimoto
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Umehara
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Koda
authors.forename: Akira
authors.initials: A
authors.lastname: Miyashita
authors.forename: Takao
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Niino
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Oka
mesh_terms: D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists*
chemical_list: D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu