Synthesis of functionalized 1,8-naphthyridinones and their evaluation as novel, orally active CB1 receptor inverse agonists

  • Bioorg Med Chem Lett. 2006 Feb;16(3):681-5. doi: 10.1016/j.bmcl.2005.10.028.
John S Debenham  1 ,  Christina B Madsen-Duggan ,  Thomas F Walsh ,  Junying Wang ,  Xinchun Tong ,  George A Doss ,  Julie Lao ,  Tung M Fong ,  Marie-Therese Schaeffer ,  Jing Chen Xiao ,  Cathy R-R C Huang ,  Chun-Pyn Shen ,  Yue Feng ,  Donald J Marsh ,  D Sloan Stribling ,  Lauren P Shearman ,  Alison M Strack ,  D Euan MacIntyre ,  Lex H T Van der Ploeg ,  Mark T Goulet
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. [email protected]
PMID: 16263284 DOI: 10.1016/j.bmcl.2005.10.028
Abstract

Synthesis, SAR, and binding affinities are described for a new class of 1,8-naphthyridinone CB1 receptor specific inverse agonists. Food intake, knockout mouse, and pharmacokinetic evaluation of 14 indicate that this compound is an effective orally active modulator of CB1.

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