Synthesis and cannabinoid-1 receptor binding affinity of conformationally constrained analogs of taranabant

The design, synthesis, and binding activity of ring constrained analogs of the acyclic cannabinoid-1 receptor (CB1R) inverse agonist taranabant 1 are described. The initial inspiration for these taranabant derivatives was its conformation 1a, determined by 1H NMR, X-ray, and molecular modeling. The constrained analogs were all much less potent than their acyclic parent structure. The results obtained are discussed in the context of a predicted binding of 1 to a homology model of CB1R.

Graphical abstractThe design, synthesis, and binding activity of ring constrained analogs of the acyclic cannabinoid-1 receptor (CB1R) inverse agonist taranabant 1 are described. The initial inspiration for these taranabant derivatives was its conformation 1a, determined by 1H NMR, X-ray, and molecular modeling. The constrained analogs were all much less potent than their acyclic parent structure.Figure optionsDownload full-size imageDownload as PowerPoint slide