Substituted acyclic sulfonamides as human cannabinoid-1 receptor inverse agonists

  • Bioorg Med Chem Lett. 2007 Apr 15;17(8):2184-7. doi: 10.1016/j.bmcl.2007.01.087.
Helen E Armstrong  1 ,  Amy Galka ,  Linus S Lin ,  Thomas J Lanza Jr ,  James P Jewell ,  Shrenik K Shah ,  Ravi Guthikonda ,  Quang Truong ,  Linda L Chang ,  Grace Quaker ,  Vincent J Colandrea ,  Xinchun Tong ,  Junying Wang ,  Sherry Xu ,  Tung M Fong ,  Chun-Pyn Shen ,  Julie Lao ,  Jing Chen ,  Lauren P Shearman ,  D Sloan Stribling ,  Kimberly Rosko ,  Alison Strack ,  Sookhee Ha ,  Lex Van der Ploeg ,  Mark T Goulet ,  William K Hagmann
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
PMID: 17293109 DOI: 10.1016/j.bmcl.2007.01.087
Abstract

Sulfonamide analogues of the potent CB1R inverse agonist taranabant were prepared and optimized for potency and selectivity for CB1R. They were variably more potent than the corresponding amide analogues. The most potent representative 22 had good pharmacokinetic and brain levels, but was modestly active in blocking CB1R agonist-mediated hypothermia.