4-Aminopiperidine ureas as potent selective agonists of the human beta(3)-adrenergic receptor.
The preparation and structure-activity relationships (SARs) of potent agonists of the human beta(3)-adrenergic receptor (AR) derived from a 4-aminopiperidine scaffold are described. Examples combine human beta(3)-AR potency with selectivity over human beta(1)-AR and/or human beta(2)-AR agonism. Compound 29s was identified as a potent (EC(50)=1nM) and selective (greater than 400-fold over beta(1)- with no beta(2)-AR agonism) full beta(3)-AR agonist with in vivo activity in a transgenic mouse model of thermogenesis.
Ashwell
M A
MA
Chemical Sciences, Wyeth-Ayerst Research, PO Box CN-8000, USA. mashwell@arqule.com
Solvibile
W R
WR
Han
S
S
Largis
E
E
Mulvey
R
R
Tillet
J
J
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D014508:Urea / Q000737:chemistry / Q000494:pharmacology*
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D010880:Piperidines; D014508:Urea