title: Potent and orally bioavailable non-peptide antagonists at the human bradykinin B(1) receptor based on a 2-alkylamino-5-sulfamoylbenzamide core.
abstract: The bradykinin B(1) receptor is rapidly induced after inflammation or tissue trauma and appears to play an important role in the maintenance of hyperalgesia in inflammatory conditions. Here, we describe the optimization process to identify novel, potent non-peptide human B(1) receptor antagonists based on a 2-alkylamino-5-sulfamoylbenzamide core. Optimized derivatives are selective, functional B(1) antagonists with low nanomolar affinity and exhibit oral bioavailability in animals.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Ritchie
authors.forename: Edward K
authors.initials: EK
authors.lastname: Dziadulewicz
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Culshaw
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Burgess
authors.forename: Graham C
authors.initials: GC
authors.lastname: Bloomfield
authors.forename: Gillian S
authors.initials: GS
authors.lastname: Drake
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Dunstan
authors.forename: David
authors.initials: D
authors.lastname: Beattie
authors.forename: Glyn A
authors.initials: GA
authors.lastname: Hughes
authors.forename: Pam
authors.initials: P
authors.lastname: Ganju
authors.forename: Peter
authors.initials: P
authors.lastname: McIntyre
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Bevan
authors.forename: Clare
authors.initials: C
authors.lastname: Davis
authors.forename: Mohammed
authors.initials: M
authors.lastname: Yaqoob
mesh_terms: D000284:Administration, Oral; D000588:Amines / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D001682:Biological Availability; D065169:Bradykinin B1 Receptor Antagonists; D002264:Carboxylic Acids / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000588:Amines; D000596:Amino Acids; D065169:Bradykinin B1 Receptor Antagonists; D002264:Carboxylic Acids; D010455:Peptides; D062367:ortho-Aminobenzoates; C000219:anthranilamide