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

  • Bioorg Med Chem Lett. 2010 Aug 15;20(16):4757-61. doi: 10.1016/j.bmcl.2010.06.127.
Ihor E Kopka  1 ,  Linus S Lin ,  James P Jewell ,  Thomas J Lanza ,  Tung M Fong ,  Chun-Pyn Shen ,  Zhege J Lao ,  Sookhee Ha ,  Laurie G Castonguay ,  Lex Van der Ploeg ,  Mark T Goulet ,  William K Hagmann
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
PMID: 20643546 DOI: 10.1016/j.bmcl.2010.06.127
Abstract

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 (1)H 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.