Synthesis of functionalized 1,8-naphthyridinones and their evaluation as novel, orally active CB1 receptor inverse agonists.
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.
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
Walsh
Thomas F
TF
Wang
Junying
J
Tong
Xinchun
X
Doss
George A
GA
Lao
Julie
J
Fong
Tung M
TM
Schaeffer
Marie-Therese
MT
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
MacIntyre
D Euan
DE
Van der Ploeg
Lex H T
LH
Goulet
Mark T
MT
D000284:Administration, Oral; D000818:Animals; D001665:Binding Sites; D004435:Eating / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D008956:Models, Chemical; D009287:Naphthyridines / Q000138:chemical synthesis; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors*
D009287:Naphthyridines; D043884:Receptor, Cannabinoid, CB1