Dihydro-pyrano[2,3-b]pyridines and tetrahydro-1,8-naphthyridines as CB1 receptor inverse agonists: synthesis, SAR and biological evaluation.

Christina B Madsen-Duggan,John S Debenham,Thomas F Walsh,Lin Yan,Pei Huo,Junying Wang,Xinchun Tong,Julie Lao,Tung M Fong,Jing Chen Xiao,Cathy R-R C Huang,Chun-Pyn Shen,D Sloan Stribling,Lauren P Shearman,Alison M Strack,Mark T Goulet,Jeffrey J Hale

Bioorganic & Medicinal Chemistry Letters（2010）

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摘要

Synthesis and structure-activity relationships of cannabinoid-1 receptor (CB1R) inverse agonists based on dihydro-pyrano[2,3-b] pyridine and tetrahydro-1,8-naphtyridine scaffolds are presented. Rat food intake and pharmacokinetic evaluation of 13g, 13i, 13k and 17a revealed these compounds to be highly efficacious orally active modulators of CB1R.

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关键词

Cannabinoid,CB1R,Inverse agonist,Dihydro-pyrano[2,3-b] pyridine,Tetrahydro-1,8-naphthyridine,Obesity

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