A new class of bradykinin B1 receptor antagonists with high oral bioavailability and minimal PXR activity

The design and synthesis of a novel class of human bradykinin B1 antagonists featuring difluoroethyl ether and isoxazole carboxamide moieties are disclosed. Compound 7g displayed excellent pharmacokinetic properties, efficient ex vivo receptor occupancy, and low potential for P450 induction via PXR...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2008-01, Vol.18 (2), p.682-687
Hauptverfasser:	FENG, Dong-Mei, DIPARDO, Robert M, PETTIBONE, Douglas J, BOCK, Mark G, KUDUK, Scott D, WAI, Jenny M, CHANG, Ronald K, DI MARCO, Christina N, MURPHY, Kathy L, RANSOM, Richard W, REISS, Duane R, CUYUE TANG, PRUEKSARITANONT, Thomayant
Format:	Artikel
Sprache:	eng
Schlagworte:	Administration, Oral Analgesics Animals Biological and medical sciences Biological Availability Bradykinin B1 Receptor Antagonists Dogs Humans Isoxazoles - pharmacokinetics Isoxazoles - pharmacology Macaca mulatta Medical sciences Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems Pharmacology. Drug treatments Pregnane X Receptor Rats Rats, Sprague-Dawley Receptors, Steroid - drug effects
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	The design and synthesis of a novel class of human bradykinin B1 antagonists featuring difluoroethyl ether and isoxazole carboxamide moieties are disclosed. Compound 7g displayed excellent pharmacokinetic properties, efficient ex vivo receptor occupancy, and low potential for P450 induction via PXR activation.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2007.11.057