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Sato S, Komoto T, Kanamaru Y, Kawamoto N, Okada T, Kaiho T, Mogi K, Morimoto S, Umehara N, Koda T, Miyashita A, Sakamoto T, Niino Y, Oka T: New mu-opioid receptor agonists with phenoxyacetic acid moiety. Chem Pharm Bull. 2002 Feb;50(2):292-7.
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. |
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