Fig. 1: Oxa-iboga is a distinct class of iboga alkaloids discovered by structural editing of ibogaine, enabled by efficient de novo chemical synthesis.
From: Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models
a Ibogaine is a substance with broad therapeutic effects and complex pharmacology, that is distinct from classical psychedelic tryptamines. Relative potencies at known molecular targets are shown. b Oxa-iboga analogs are defined by the replacement of indole with benzofuran, resulting in accentuation of the KOR activity on the iboga pharmacological background. c De novo synthesis of iboga molecular framework rests on the catalytic union of the two main structural components of oxa-iboga skeleton, the isoquinuclidine and benzofuran ring systems. d Docking pose of noribogaine (carbon frame in green) in sticks representation inside KOR structure (active receptor state). Hydrogen bonding near the C10 phenol and tertiary amine are highlighted by yellow dashed lines. KOR (kappa opioid receptor), α3β4 (α3β4 nicotinic acetylcholine receptors), SERT (serotonin transporter), 5-HT (serotonin), NMDAR (N-methyl-D-aspartate receptor).
