Potent, elective human beta3 adrenergic receptor agonists containing a substituted indoline-5-sulfonamide pharmacophore.
A series of compounds possessing an N-substituted indoline-5-sulfonamide pharmacophore was prepared and evaluated for their human beta3 adrenergic receptor agonist activity. The SAR of a wide range of urea and heterocyclic substituents is discussed. 4-Octyl thiazole compound 8c was the most potent and selective compound in the series, with 2800-fold selectivity over beta1 binding and 1400-fold selectivity over beta2 binding.
Department of Medicinal Chemistry and Biochemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.
R J
RJ
Mathvink
A M
AM
Barritta
M R
MR
Candelore
M A
MA
Cascieri
L
L
Deng
L
L
Tota
C D
CD
Strader
M J
MJ
Wyvratt
M H
MH
Fisher
A E
AE
Weber
D000322:Adrenergic Agonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D008956:Models, Chemical; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*
D000322:Adrenergic Agonists; D007211:Indoles; D013449:Sulfonamides