Synthesis and antinociceptive activity of chimonanthines and pyrrolidinoindoline-Type alkaloids Original Research Article

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 μ 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.