title: Discovery of 2-substituted benzoxazole carboxamides as 5-HT3 receptor antagonists.
abstract: A new class of 2-substituted benzoxazole carboxamides are presented as potent functional 5-HT(3) receptor antagonists. The chemical series possesses nanomolar in vitro activity against human 5-HT(3)A receptors. A chemistry optimization program was conducted and identified 2-aminobenzoxazoles as orally active 5-HT(3) receptor antagonists with good metabolic stability. These novel analogues possess drug-like characteristics and have potential utility for the treatment of diseases attributable to improper 5-HT(3) receptor function, especially diarrhea predominant irritable bowel syndrome (IBS-D).
authors.affiliation: Discovery R&D AMRI, 26 Corporate Circle, PO Box 15098, Albany, NY 12212-5098, USA.
authors.forename: Zhicai
authors.initials: Z
authors.lastname: Yang
authors.forename: David J
authors.initials: DJ
authors.lastname: Fairfax
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Maeng
authors.forename: Liaqat
authors.initials: L
authors.lastname: Masih
authors.forename: Alexander
authors.initials: A
authors.lastname: Usyatinsky
authors.forename: Carla
authors.initials: C
authors.lastname: Hassler
authors.forename: Soshanna
authors.initials: S
authors.lastname: Isaacson
authors.forename: Kevin
authors.initials: K
authors.lastname: Fitzpatrick
authors.forename: Russell J
authors.initials: RJ
authors.lastname: DeOrazio
authors.forename: Jianqing
authors.initials: J
authors.lastname: Chen
authors.forename: James P
authors.initials: JP
authors.lastname: Harding
authors.forename: Matthew
authors.initials: M
authors.lastname: Isherwood
authors.forename: Svetlana
authors.initials: S
authors.lastname: Dobritsa
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Christensen
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Wierschke
authors.forename: Brian I
authors.initials: BI
authors.lastname: Bliss
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Peterson
authors.forename: Cathy M
authors.initials: CM
authors.lastname: Beer
authors.forename: Christopher
authors.initials: C
authors.lastname: Cioffi
authors.forename: Michael
authors.initials: M
authors.lastname: Lynch
authors.forename: W Martin
authors.initials: WM
authors.lastname: Rennells
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Richards
authors.forename: Timothy
authors.initials: T
authors.lastname: Rust
authors.forename: Yuri L
authors.initials: YL
authors.lastname: Khmelnitsky
authors.forename: Marlene L
authors.initials: ML
authors.lastname: Cohen
authors.forename: David D
authors.initials: DD
authors.lastname: Manning
mesh_terms: D001583:Benzoxazoles / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001583:Benzoxazoles; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists