The synthesis and characterization of BMS-204352 (MaxiPost) and related 3-fluorooxindoles as openers of maxi-K potassium channels

3-Aryl-3-fluorooxindoles can be efficiently synthesized in two steps by the addition of an aryl Grignard to an isatin, followed by treatment with DAST. Oxindole 1 (BMS-204352; MaxiPost) can be isolated using chiral HPLC or prepared by employing chiral resolution. Cloned maxi-K channels are opened by...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2002-04, Vol.12 (7), p.1023-1026
Hauptverfasser:	HEWAWASAM, Piyasena, GRIBKOFF, Valentin K, PAJOR, Lorraine M, KNIPE, Jay, QI GAO, PERRONE, Robert, STARRETT, John E, PENDRI, Yadagiri, DWORETZKY, Steven I, MEANWELL, Nicholas A, MARTINEZ, Eduardo, BOISSARD, Christopher G, POST-MUNSON, Debra J, TROJNACKI, Joanne T, YELESWARAM, Krishnaswamy
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Biological and medical sciences Brain - drug effects Brain - metabolism Calcium - metabolism Cells, Cultured - drug effects Diazonium Compounds Humans Indoles - blood Indoles - chemical synthesis Indoles - pharmacology Large-Conductance Calcium-Activated Potassium Channels Male Medical sciences Microinjections Miscellaneous Oocytes - drug effects Oocytes - physiology Patch-Clamp Techniques Pharmacology. Drug treatments Potassium Channels, Calcium-Activated - drug effects Potassium Channels, Calcium-Activated - genetics Potassium Channels, Calcium-Activated - metabolism Rats Rats, Sprague-Dawley RNA, Messenger - metabolism Xenopus
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	3-Aryl-3-fluorooxindoles can be efficiently synthesized in two steps by the addition of an aryl Grignard to an isatin, followed by treatment with DAST. Oxindole 1 (BMS-204352; MaxiPost) can be isolated using chiral HPLC or prepared by employing chiral resolution. Cloned maxi-K channels are opened by 1, which demonstrates a brain/plasma ratio >9 in rats.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/s0960-894x(02)00101-4