Oxadiazolone bioisosteres of pregabalin and gabapentin

Autor:	Thomas Richard Belliotti, Susan M. Lotarski, Justin Stephen Bryans, Dic Williams, Jack J. Kinsora, Clare O. Kneen, Andrew John Thorpe, David J. Wustrow, Jacob Bradley Schwarz, Ayman El-Kattan, Charles Taylor, Sean D. Donevan, Lisa Buchholz, Thomas Capiris, Mark G. Vartanian, Mark J. Field
Rok vydání:	2008
Předmět:	Gabapentin Cyclohexanecarboxylic Acids Protein subunit Clinical Biochemistry Pregabalin Pharmaceutical Science Organic Anion Transporters Pharmacology Biochemistry Drug Discovery Osteoarthritis medicine Potency Animals Drug Interactions Cimetidine Amines Molecular Biology gamma-Aminobutyric Acid Oxadiazoles Voltage-dependent calcium channel Chemistry Organic Chemistry Brain Rats Probenecid Molecular Medicine Octamer Transcription Factors Drug Therapy Combination Efflux medicine.drug
Zdroj:	Bioorganicmedicinal chemistry letters. 19(1)
ISSN:	1464-3405
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88d9b90cc172e35df292897ac3bce3f6 https://pubmed.ncbi.nlm.nih.gov/19010672 Zobrazit plný text záznamu Full Text from ScienceDirect