3-(1',1'-Dimethylbutyl)-1-deoxy-delta8-THC and related compounds: synthesis of selective ligands for the CB2 receptor

Bioorg Med Chem. 1999 Dec;7(12):2905-14. doi: 10.1016/s0968-0896(99)00219-9.

Abstract

The synthesis and pharmacology of 15 1-deoxy-delta8-THC analogues, several of which have high affinity for the CB2 receptor, are described. The deoxy cannabinoids include 1-deoxy-11-hydroxy-delta8-THC (5), 1-deoxy-delta8-THC (6), 1-deoxy-3-butyl-delta8-THC (7), 1-deoxy-3-hexyl-delta8-THC (8) and a series of 3-(1',1'-dimethylalkyl)-1-deoxy-delta8-THC analogues (2, n = 0-4, 6, 7, where n = the number of carbon atoms in the side chain-2). Three derivatives (17-19) of deoxynabilone (16) were also prepared. The affinities of each compound for the CB1 and CB2 receptors were determined employing previously described procedures. Five of the 3-(1',1'-dimethylalkyl)-1-deoxy-delta8-THC analogues (2, n = 1-5) have high affinity (Ki = < 20 nM) for the CB2 receptor. Four of them (2, n = 1-4) also have little affinity for the CB1 receptor (Ki = > 295 nM). 3-(1',1'-Dimethylbutyl)-1-deoxy-delta8-THC (2, n = 2) has very high affinity for the CB2 receptor (Ki = 3.4 +/- 1.0 nM) and little affinity for the CB1 receptor (Ki = 677 +/- 132 nM).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cannabinoids / metabolism*
  • Cell Line
  • Dronabinol / analogs & derivatives*
  • Dronabinol / chemical synthesis
  • Dronabinol / chemistry
  • Dronabinol / metabolism
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Receptors, Cannabinoid
  • Receptors, Drug / metabolism*
  • Structure-Activity Relationship

Substances

  • 3-(1',1'-dimethylbutyl)-1-deoxy-delta(8)-tetrahydrocannabinol
  • Cannabinoids
  • Ligands
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Dronabinol