title: Identification of a series of substituted 2-piperazinyl-5-pyrimidylhydroxamic acids as potent histone deacetylase inhibitors.
abstract: Pursuing our efforts in designing 5-pyrimidylhydroxamic acid anti-cancer agents, we have identified a new series of potent histone deacetylase (HDAC) inhibitors. These compounds exhibit enzymatic HDAC inhibiting properties with IC(50) values in the nanomolar range and inhibit tumor cell proliferation at similar levels. Good solubility, moderate bioavailability, and promising in vivo activity in xenograft model made this series of compounds interesting starting points to design new potent HDAC inhibitors.
authors.affiliation: Ortho-Biotech Oncology Research & Development, Department of Medicinal Chemistry, campus de Maigremont BP615, 27106, Val de Reuil, France. pangibau@prdfr.jnj.com
authors.forename: Patrick
authors.initials: P
authors.lastname: Angibaud
authors.forename: Kristof
authors.initials: K
authors.lastname: Van Emelen
authors.forename: Laurence
authors.initials: L
authors.lastname: Decrane
authors.forename: Sven
authors.initials: S
authors.lastname: van Brandt
authors.forename: Peter
authors.initials: P
authors.lastname: Ten Holte
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pilatte
authors.forename: Bruno
authors.initials: B
authors.lastname: Roux
authors.forename: Virginie
authors.initials: V
authors.lastname: Poncelet
authors.forename: David
authors.initials: D
authors.lastname: Speybrouck
authors.forename: Laurence
authors.initials: L
authors.lastname: Queguiner
authors.forename: Sandrine
authors.initials: S
authors.lastname: Gaurrand
authors.forename: Ann
authors.initials: A
authors.lastname: Mariën
authors.forename: Wim
authors.initials: W
authors.lastname: Floren
authors.forename: Lut
authors.initials: L
authors.lastname: Janssen
authors.forename: Marc
authors.initials: M
authors.lastname: Verdonck
authors.forename: Jacky
authors.initials: J
authors.lastname: van Dun
authors.forename: Jacky
authors.initials: J
authors.lastname: van Gompel
authors.forename: Ron
authors.initials: R
authors.lastname: Gilissen
authors.forename: Claire
authors.initials: C
authors.lastname: Mackie
authors.forename: Marc
authors.initials: M
authors.lastname: Du Jardin
authors.forename: Jozef
authors.initials: J
authors.lastname: Peeters
authors.forename: Marc
authors.initials: M
authors.lastname: Noppe
authors.forename: Luc
authors.initials: L
authors.lastname: Van Hijfte
authors.forename: Eddy
authors.initials: E
authors.lastname: Freyne
authors.forename: Martin
authors.initials: M
authors.lastname: Page
authors.forename: Michel
authors.initials: M
authors.lastname: Janicot
authors.forename: Janine
authors.initials: J
authors.lastname: Arts
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015195:Drug Design; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D006655:Histone Deacetylases