Lead optimization of 5,6-diarylpyridines as CB1 receptor inverse agonists.
Optimization of the biological activity for 5,6-diarylpyridines as CB1 receptor inverse agonists is described. Food intake and pharmacokinetic evaluation of 3f and 15c indicate that these compounds are effective orally active modulators of CB1.
Madsen-Duggan
Christina B
CB
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. christina_madsen_duggan@merck.com
Debenham
John S
JS
Walsh
Thomas F
TF
Toupence
Richard B
RB
Huang
Song X
SX
Wang
Junying
J
Tong
Xinchun
X
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
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
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D005247:Feeding Behavior / Q000187:drug effects; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008968:Molecular Conformation; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D013329:Structure-Activity Relationship; D013696:Temperature; D014050:Toluene / Q000737:chemistry
D011725:Pyridines; D043884:Receptor, Cannabinoid, CB1; D014050:Toluene