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Axially Chiral Cannabinols: A New Platform for Cannabinoid‐Inspired Drug Discovery
Author(s) -
Navaratne Primali V.,
Wilkerson Jenny L.,
Ranasinghe Kavindri D.,
Semenova Evgeniya,
Felix Jasmine S.,
Ghiviriga Ion,
Roitberg Adrian,
McMahon Lance R.,
Grenning Alexander J.
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000025
Subject(s) - cannabinol , drug discovery , cannabinoid , chemistry , cannabinoid receptor , metabolic stability , computational biology , combinatorial chemistry , nanotechnology , receptor , materials science , biology , biochemistry , antagonist , in vitro
Phytocannabinoids (and synthetic analogs thereof) are gaining significant attention as promising leads in modern medicine. Considering this, new directions for the design of phytocannabinoid‐inspired molecules is of immediate interest. In this regard, we have hypothesized that axially‐chiral‐cannabinols (ax‐CBNs), unnatural and unknown isomers of cannabinol (CBN) may be valuable scaffolds for cannabinoid‐inspired drug discovery. There are two main factors directing our interest to these scaffolds: (a) ax‐CBNs would have ground‐state three‐dimensionality; ligand‐receptor interactions can be more significant with complimentary 3D‐topology, and (b) ax‐CBNs at their core structure are biaryl molecules, generally attractive platforms for pharmaceutical development due to their ease of functionalization and stability. Herein we report a synthesis of ax‐CBNs, examine physical properties experimentally and computationally, and perform a comparative analysis of ax‐CBN and THC in mice behavioral studies.