title: Discovery of dehydro-oxopiperazine acetamides as novel bradykinin B1 receptor antagonists with enhanced in vitro potency.
abstract: In a series of bradykinin B1 antagonists, we discovered that replacement of oxopiperazine acetamides with dehydro-oxopiperazine acetamides provided compounds with enhanced activity against the B1 receptor. The synthesis and SAR leading to potent analogs with reduced molecular weight will be discussed.
authors.affiliation: Department of Chemistry Research and Discovery, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, United States. wqian@amgen.com
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Qian
authors.forename: Jian Jeffrey
authors.initials: JJ
authors.lastname: Chen
authors.forename: Jason
authors.initials: J
authors.lastname: Human
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Aya
authors.forename: Jiawang
authors.initials: J
authors.lastname: Zhu
authors.forename: Kaustav
authors.initials: K
authors.lastname: Biswas
authors.forename: Tanya
authors.initials: T
authors.lastname: Peterkin
authors.forename: Randall W
authors.initials: RW
authors.lastname: Hungate
authors.forename: Leyla
authors.initials: L
authors.lastname: Arik
authors.forename: Eileen
authors.initials: E
authors.lastname: Johnson
authors.forename: Gondi
authors.initials: G
authors.lastname: Kumar
authors.forename: Smriti
authors.initials: S
authors.lastname: Joseph
authors.forename: Janan
authors.initials: J
authors.lastname: Jona
authors.forename: Hong-Xun
authors.initials: HX
authors.lastname: Guo
authors.forename: Zufan
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D065169:Bradykinin B1 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D065169:Bradykinin B1 Receptor Antagonists; D010879:Piperazines