Synthesis of pyrrolomorphinan derivatives as κ opioid agonists

✍ Scribed by Hideaki Fujii; Yoshihiro Ida; Shinichi Hanamura; Yumiko Osa; Toru Nemoto; Mayumi Nakajima; Ko Hasebe; Kaoru Nakao; Hidenori Mochizuki; Hiroshi Nagase

• Book ID: 104004645
• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 576 KB
• Volume: 20
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.07.035

✦ Synopsis

We synthesized pyrrolomorphinan derivatives 6, 7, and 9 to examine whether the pyrrole ring would be an accessory site in the j opioid receptor selective antagonist, nor-binaltorphimine. Derivative 6 had an a,b-unsaturated ketone substituent that strongly bound to the j receptor. The compound with the highest j receptor selectivity, 6e, produced a dose-dependent antinociceptive effect in the mouse acetic acid writhing test. However, derivatives 7 and 9, which did not have a,b-unsaturated ketone substituents, showed less j receptor selectivity than compound 6. Based on structure-activity relationships, we proposed that these compounds adopted active structures for j selective agonist activity. The pyrrole ring