Dihydro-pyrano[2,3-b]pyridines and tetrahydro-1,8-naphthyridines as CB1 receptor inverse agonists: synthesis, SAR and biological evaluation.
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.
Madsen-Duggan
Christina B
CB
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Debenham
John S
JS
Walsh
Thomas F
TF
Yan
Lin
L
Huo
Pei
P
Wang
Junying
J
Tong
Xinchun
X
Lao
Julie
J
Fong
Tung M
TM
Xiao
Jing Chen
JC
Huang
Cathy R-R C
CR
Shen
Chun-Pyn
CP
Stribling
D Sloan
DS
Shearman
Lauren P
LP
Strack
Alison M
AM
Goulet
Mark T
MT
Hale
Jeffrey J
JJ
D000284:Administration, Oral; D000818:Animals; D004435:Eating; D006801:Humans; D009287:Naphthyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010599:Pharmacokinetics; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000187:drug effects; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000187:drug effects; D013329:Structure-Activity Relationship; D015431:Weight Loss / Q000187:drug effects*
D009287:Naphthyridines; D011725:Pyridines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2