Potent, selective 3-pyridylethanolamine beta3 adrenergic receptor agonists possessing a thiazole benzenesulfonamide pharmacophore.
A series of thiazole benzenesulfonamide-substituted 3-pyridylethanolamines was prepared and evaluated for their human beta3 adrenergic receptor agonist activity. Incorporation of aryl and heteroaryl substitution in the 4-position of the thiazole ring resulted in a number of highly potent and selective beta3 agonists. Results of preliminary in vivo evaluation of several of these compounds is described.
Mathvink
R J
RJ
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. robert_mathvink@merck.com
Tolman
J S
JS
Chitty
D
D
Candelore
M R
MR
Cascieri
M A
MA
Colwell
L F
LF
Deng
L
L
Feeney
W P
WP
Forrest
M J
MJ
Hom
G J
GJ
MacIntyre
D E
DE
Tota
L
L
Wyvratt
M J
MJ
Fisher
M H
MH
Weber
A E
AE
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004983:Ethanolamines / Q000138:chemical synthesis*; D006801:Humans; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis*; D013844:Thiazoles / Q000138:chemical synthesis*; D000096926:Benzenesulfonamides
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D013449:Sulfonamides; D013844:Thiazoles; D000096926:Benzenesulfonamides