Synthesis and antinociceptive activity of chimonanthines and pyrrolidinoindoline-type alkaloids.

Abstract

Hodgkinsine, a trimeric pyrrolidinoindoline type alkaloid, present as a major constituent of Psychotria spp. (Rubiaceae), has shown to produce dose-dependent, naloxone reversible, analgesic effect in thermal models of nociception and in the capsaicin-induced pain. SAR studies have been initiated by synthesizing the three diastereomeric dimers (chimonanthines) (11-13) which were evaluated in vitro and in vivo along with the synthetic intermediates. Strong binding affinities for mu opioid receptors were found for (-)- and (+)-chimonanthine monourethanes (9 and 10), whereas (-)-, (+)- and (meso)-chimonanthine (11-13) and hodgkinsine displayed low affinity. In vivo data have shown that only (+)-chimonanthine (12) and calycosidine resemble the analgesic profile found for hodgkinsine.

• Authors: L Verotta, F Orsini, M Sbacchi, M A Scheildler, T A Amador, E Elisabetsky
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 10 Issue 7 Pg. 2133-42 (Jul 2002) ISSN: 0968-0896 [Print] England
• PMID: 11983509 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Analgesics
• Pyrroles

Topics

• Alkaloids (chemical synthesis, chemistry, pharmacology)
• Analgesics (chemical synthesis, chemistry, pharmacology)
• Pyrroles (chemistry)