Substituted acyclic sulfonamides as human cannabinoid-1 receptor inverse agonists.
Sulfonamide analogues of the potent CB1R inverse agonist taranabant were prepared and optimized for potency and selectivity for CB1R. They were variably more potent than the corresponding amide analogues. The most potent representative 22 had good pharmacokinetic and brain levels, but was modestly active in blocking CB1R agonist-mediated hypothermia.
Armstrong
Helen E
HE
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
Galka
Amy
A
Lin
Linus S
LS
Lanza
Thomas J
TJ
Jewell
James P
JP
Shah
Shrenik K
SK
Guthikonda
Ravi
R
Truong
Quang
Q
Chang
Linda L
LL
Quaker
Grace
G
Colandrea
Vincent J
VJ
Tong
Xinchun
X
Wang
Junying
J
Xu
Sherry
S
Fong
Tung M
TM
Shen
Chun-Pyn
CP
Lao
Julie
J
Chen
Jing
J
Shearman
Lauren P
LP
Stribling
D Sloan
DS
Rosko
Kimberly
K
Strack
Alison
A
Ha
Sookhee
S
Van der Ploeg
Lex
L
Goulet
Mark T
MT
Hagmann
William K
WK
D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001923:Brain Chemistry; D063385:Cannabinoid Receptor Modulators / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007035:Hypothermia / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D010599:Pharmacokinetics; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
D019440:Anti-Obesity Agents; D063385:Cannabinoid Receptor Modulators; D043884:Receptor, Cannabinoid, CB1; D013449:Sulfonamides