Oxadiazolone bioisosteres of pregabalin and gabapentin

A series of oxadiazolone bioisosteres of pregabalin 1 and gabapentin 2 were prepared, and several were found to exhibit similar potency for the α 2-δ subunit of voltage-gated calcium channels. Oxadiazolone 9 derived from 2 achieved low brain uptake but was nevertheless active in models of osteoarthr...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2009, Vol.19 (1), p.247-250
Hauptverfasser:	Wustrow, David J., Belliotti, Thomas R., Capiris, Thomas, Kneen, Clare O., Bryans, Justin S., Field, Mark J., Williams, Dic, El-Kattan, Ayman, Buchholz, Lisa, Kinsora, Jack J., Lotarski, Susan M., Vartanian, Mark G., Taylor, Charles P., Donevan, Sean D., Thorpe, Andrew J., Schwarz, Jacob B.
Format:	Artikel
Sprache:	eng
Schlagworte:	Acid bioisostere Amines Animals Biological and medical sciences Brain - metabolism Cyclohexanecarboxylic Acids Drug Interactions Drug Therapy, Combination Gabapentin gamma-Aminobutyric Acid - analogs & derivatives Medical sciences Miscellaneous Neuropharmacology Octamer Transcription Factors Organic Anion Transporters Osteoarthritis - drug therapy Oxadiazoles - chemistry Oxadiazoles - pharmacology Oxadiazoles - therapeutic use Oxadiazolone Pharmacology. Drug treatments Pregabalin Rats α 2-δ
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	A series of oxadiazolone bioisosteres of pregabalin 1 and gabapentin 2 were prepared, and several were found to exhibit similar potency for the α 2-δ subunit of voltage-gated calcium channels. Oxadiazolone 9 derived from 2 achieved low brain uptake but was nevertheless active in models of osteoarthritis. The high clearance associated with compound 9 was postulated to be a consequence of efflux by OAT and/or OCT, and was attenuated on co-administration with cimetidine or probenecid.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2008.10.101