title: Novel benzamide-based histamine h3 receptor antagonists: the identification of two candidates for clinical development.
abstract: The preclinical characterization of novel phenyl(piperazin-1-yl)methanones that are histamine H3 receptor antagonists is described. The compounds described are high affinity histamine H3 antagonists. Optimization of the physical properties of these histamine H3 antagonists led to the discovery of several promising lead compounds, and extensive preclinical profiling aided in the identification of compounds with optimal duration of action for wake promoting activity. This led to the discovery of two development candidates for Phase I and Phase II clinical trials.
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Letavic
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Leah
authors.initials: L
authors.lastname: Aluisio
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Apodaca
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Manoj
authors.initials: M
authors.lastname: Bajpai
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Barbier
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Anne
authors.initials: A
authors.lastname: Bonneville
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Pascal
authors.initials: P
authors.lastname: Bonaventure
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Carruthers
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Christine
authors.initials: C
authors.lastname: Dugovic
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Fraser
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Kramer
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Lord
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Lovenberg
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Lilian Y
authors.initials: LY
authors.lastname: Li
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Kiev S
authors.initials: KS
authors.lastname: Ly
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Heather
authors.initials: H
authors.lastname: Mcallister
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Neelakandha S
authors.initials: NS
authors.lastname: Mani
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: Morton
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Anthony
authors.initials: A
authors.lastname: Ndifor
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: S Diane
authors.initials: SD
authors.lastname: Nepomuceno
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Chennagiri R
authors.initials: CR
authors.lastname: Pandit
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Sands
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Chandra R
authors.initials: CR
authors.lastname: Shah
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Shelton
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Snook
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Devin M
authors.initials: DM
authors.lastname: Swanson
authors.affiliation: Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
keywords: Histamine H3 antagonists; histamine; phenyl(piperazin-1-yl)methanones