The role of fluorine substitution in the structure-activity relationships (SAR) of classical cannabinoids
Crocker, P. J., Mahadevan, A., Wiley, J., Martin, B. R., & Razdan, R. K. (2007). The role of fluorine substitution in the structure-activity relationships (SAR) of classical cannabinoids. Bioorganic and Medicinal Chemistry Letters, 17(6), 1504-1507.
A facile synthesis of 1-fluoro-1-deoxy-Delta(8)-THC analogs with side chains seven carbons in length, in the alkane/ene/yneseries (6, 5, and 4), was achieved from 1-fluoro-3,5-dimethoxybenzene (1). In vitro studies show that substitution by a fluorine has a significant detrimental effect on CB1 binding which is supported by in vivo testing. The implications of these results on the SAR of classical cannabinoids are discussed. (c) 2007 Published by Elsevier Ltd