title: A new class of bradykinin B1 receptor antagonists with high oral bioavailability and minimal PXR activity.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Feng
authors.forename: Robert M
authors.initials: RM
authors.lastname: DiPardo
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Wai
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Chang
authors.forename: Christina N
authors.initials: CN
authors.lastname: Di Marco
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Murphy
authors.forename: Richard W
authors.initials: RW
authors.lastname: Ransom
authors.forename: Duane R
authors.initials: DR
authors.lastname: Reiss
authors.forename: Cuyue
authors.initials: C
authors.lastname: Tang
authors.forename: Thomayant
authors.initials: T
authors.lastname: Prueksaritanont
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Pettibone
authors.forename: Mark G
authors.initials: MG
authors.lastname: Bock
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kuduk
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D065169:Bradykinin B1 Receptor Antagonists; D004285:Dogs; D006801:Humans; D007555:Isoxazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D008253:Macaca mulatta; D000077297:Pregnane X Receptor; D051381:Rats; D017207:Rats, Sprague-Dawley; D011987:Receptors, Steroid / Q000187:drug effects*
chemical_list: D065169:Bradykinin B1 Receptor Antagonists; D007555:Isoxazoles; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid