title: A new class of bradykinin 1 receptor antagonists containing the piperidine acetic acid tetralin core.
abstract: The bradykinin 1 (B1) receptor is upregulated during times of inflammation and is important for maintaining inflamed and chronic pain states. Blocking this receptor has been shown to reverse and/or ameliorate pain and inflammation in animal models. In this report, we describe a new class of B1 receptor antagonists that contain the piperidine acetic acid tetralin core. A structure-activity relationship for these analogs is described in this paper. The most potent compounds from this class have IC50s<20 nM in a B1 receptor functional assay. One of these compounds, 13g, shows modest oral bioavailability in rats.
authors.affiliation: Amgen Inc., Department of Chemistry Research and Development, One Amgen Center Drive, Thousand Oaks, CA 91360, USA. cfotsch@amgen.com
authors.forename: Christopher
authors.initials: C
authors.lastname: Fotsch
authors.forename: Gloria
authors.initials: G
authors.lastname: Biddlecome
authors.forename: Kaustav
authors.initials: K
authors.lastname: Biswas
authors.forename: Jian Jeff
authors.initials: JJ
authors.lastname: Chen
authors.forename: Derin C
authors.initials: DC
authors.lastname: D'Amico
authors.forename: Robert D
authors.initials: RD
authors.lastname: Groneberg
authors.forename: Nianhe Bruce
authors.initials: NB
authors.lastname: Han
authors.forename: Feng-Yin
authors.initials: FY
authors.lastname: Hsieh
authors.forename: Augustus
authors.initials: A
authors.lastname: Kamassah
authors.forename: Gondi
authors.initials: G
authors.lastname: Kumar
authors.forename: Dianna
authors.initials: D
authors.lastname: Lester-Zeiner
authors.forename: Qingyian
authors.initials: Q
authors.lastname: Liu
authors.forename: David A
authors.initials: DA
authors.lastname: Mareska
authors.forename: Babak Bobby
authors.initials: BB
authors.lastname: Riahi
authors.forename: Yueh-Ju Judy
authors.initials: YJ
authors.lastname: Wang
authors.forename: Kevin
authors.initials: K
authors.lastname: Yang
authors.forename: James
authors.initials: J
authors.lastname: Zhan
authors.forename: Joe
authors.initials: J
authors.lastname: Zhu
authors.forename: Eileen
authors.initials: E
authors.lastname: Johnson
authors.forename: Gordon
authors.initials: G
authors.lastname: Ng
authors.forename: Benny C
authors.initials: BC
authors.lastname: Askew
mesh_terms: D019342:Acetic Acid / Q000737:chemistry; D000284:Administration, Oral; D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D001682:Biological Availability; D065169:Bradykinin B1 Receptor Antagonists; D020128:Inhibitory Concentration 50; D010880:Piperidines / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000737:chemistry*
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D065169:Bradykinin B1 Receptor Antagonists; D010880:Piperidines; D013764:Tetrahydronaphthalenes; C032727:piperidine; C095210:tetralin; D019342:Acetic Acid