Furo[2,3-b]pyridine-based cannabinoid-1 receptor inverse agonists: synthesis and biological evaluation. Part 1.
The synthesis, SAR and binding affinities of cannabinoid-1 receptor (CB1R) inverse agonists based on furo[2,3-b]pyridine scaffolds are described. Food intake, mechanism specific efficacy, pharmacokinetic, and metabolic evaluation of several of these compounds indicate that they are effective orally active modulators of CB1R.
Debenham
John S
JS
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. john_debenham@merck.com
Madsen-Duggan
Christina B
CB
Toupence
Richard B
RB
Walsh
Thomas F
TF
Wang
Junying
J
Tong
Xinchun
X
Kumar
Sanjeev
S
Lao
Julie
J
Fong
Tung M
TM
Xiao
Jing Chen
JC
Huang
Cathy R-R C
CR
Shen
Chun-Pyn
CP
Feng
Yue
Y
Marsh
Donald J
DJ
Stribling
D Sloan
DS
Shearman
Lauren P
LP
Strack
Alison M
AM
Goulet
Mark T
MT
D000818:Animals; D001578:Benzopyrans; D004285:Dogs; D015195:Drug Design; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000882:Haplorhini; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000235:genetics; D013329:Structure-Activity Relationship
D001578:Benzopyrans; D005663:Furans; D011725:Pyridines; D043884:Receptor, Cannabinoid, CB1; C493951:furobenzopyranone