New oxadiazolidinedione derivatives as potent and selective human beta3 agonists.
As part of our investigation into the development of potent and selective human beta3 agonists, a series of thiazolidinedione analogues was prepared and evaluated for their biological activity on the human beta3-adrenergic receptor. The oxadiazolidinedione derivative 17 was found to be the most potent and selective compound in this study, with an EC50 value of 0.02 microM at the beta3 receptor, 259-fold selectivity over the beta1 receptor, and 745-fold selectivity over the beta2 receptor.
Hu
B
B
Chemical Sciences, Wyeth-Ayerst Research, Pearl River, NY 10965, USA. hub@war.wyeth.com
Malamas
M
M
Ellingboe
J
J
Largis
E
E
Han
S
S
Mulvey
R
R
Tillett
J
J
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000819:agonists*; D006801:Humans; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology; D045162:Thiazolidinediones
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D010069:Oxadiazoles; D013844:Thiazoles; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione; D000242:Cyclic AMP