Synthesis and cannabinoid-1 receptor binding affinity of conformationally constrained analogs of taranabant.
Bioorganic & medicinal chemistry letters 2010 Jul 1; In press
Kopka I IE, Lin L LS, Jewell J JP, Lanza T TJ, Fong T TM, Shen C CP, Lao Z ZJ, Ha S, Castonguay L LG, Van der Ploeg L, Goulet M MT, Hagmann W WK
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
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.
Keywords: cannabinoid taranabant
