Human beta3 adrenergic receptor agonists containing cyanoguanidine and nitroethylenediamine moieties.
Pyridineethanolamine derivatives containing cyanoguanidine or nitroethylenediamine moieties were examined as human beta3 adrenergic receptor (AR) agonists. Notably, indoline derivatives 6a and 11 were potent beta3 AR agonists (beta3 EC50 = 13 and 19 nM, respectively), which showed good selectivity over binding to and minimal activation of the beta1 and beta2 ARs.
Brockunier
L L
LL
Department of Medicinal Chemistry, Biochemistry and Physiology, Merck Research Laboratories, Rahway, NJ 07065, USA.
Candelore
M R
MR
Cascieri
M A
MA
Liu
Y
Y
Tota
L
L
Wyvratt
M J
MJ
Fisher
M H
MH
Weber
A E
AE
Parmee
E R
ER
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D006224:Cricetinae; D003959:Diamines / Q000737:chemistry; D004980:Ethane / Q000031:analogs & derivatives / Q000737:chemistry; D006146:Guanidines / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D009595:Nitroparaffins / Q000737:chemistry; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D013329:Structure-Activity Relationship
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D003959:Diamines; D006146:Guanidines; D009595:Nitroparaffins; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; C014705:nitroethane; D000262:Adenylyl Cyclases; D004980:Ethane; C004711:dicyandiamido