Synthesis and analgesic activity of stereoisomers of cis-fluoro-ohmefentanyl.
Four stereoisomers 1a-d of cis-fluoro-ohmefentanyl have been synthesized. Their absolute configurations were determined by X-ray analysis of (3S,4R,2'S)-(-)-cis-I d. The analgesic activity (mice, sc, hot plate) revealed extreme stereodifferences. The ED50 value of (3R,4S,2'S)-(+)-cis-I (1a) was 0.000774 mg/kg (17958 times more potent than that of morphine), while the corresponding antipode 1c was almost inactive.
Yong
Zou
Z
Shanghai Institute of Materia Medical, Chinese Academy of Sciences, Shanghai, Guangzhou, Guangdon, PR China. zouyong@gic.ac.cn
Hao
Wu
W
Weifang
Yuan
Y
Qiyuan
Dai
D
Xinjian
Chen
C
Wenqiao
Jin
J
Youcheng
Zhu
Z
D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D005283:Fentanyl / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008968:Molecular Conformation; D009020:Morphine / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000701:Analgesics, Opioid; D007202:Indicators and Reagents; C483144:cis-fluoro-ohmefentanyl; D009020:Morphine; D005283:Fentanyl