3-PYRIDYLOXYPROPANOLAMINE AGONISTS OF THE BETA(3) ADRENERGIC-RECEPTORWITH IMPROVED PHARMACOKINETIC PROPERTIES

Authors
WEBER AE OK HO ALVARO RF CANDELORE MR CASCIERI MA CHIU SHL DENG LP FORREST MJ HOM GJ HUTCHINS JE KAO J MACINTYRE DE MATHVINK RJ MCLOUGHLIN D MILLER RR NEWBOLD RC OLAH TV PARMEE ER PERKINS L STEARNS RA STRADER CD SZUMILOSKI J TANG YS TOTA L VICARIO PP WYVRATT MJ FISHER MH
Citation
Ae. Weber et al., 3-PYRIDYLOXYPROPANOLAMINE AGONISTS OF THE BETA(3) ADRENERGIC-RECEPTORWITH IMPROVED PHARMACOKINETIC PROPERTIES, Bioorganic & medicinal chemistry letters, 8(16), 1998, pp. 2111-2116
Citations number
13
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
8
Issue
16
Year of publication
1998
Pages
2111 - 2116
Database
ISI
SICI code
0960-894X(1998)8:16<2111:3AOTBA>2.0.ZU;2-0
Abstract
Pyridyloxypropanolamines L-749,372 (8, beta(3) EC50 = 3.6 nM) and L-75 0,355 (29, beta(3) EC50 = 13 nM) are selective partial agonists of the human receptor, with 33% and 49% activation, respectively. Both stimu late lipolysis in rhesus monkeys (ED50 = 2 and 0.8 mg/kg, respectively ), with minimal effects on heart rate. Oral bioavailability in dogs, 4 1% for L-749,372 and 47% for L-750,355, is improved relative to phenol analogs. (C) 1998 Elsevier Science Ltd. All rights reserved.