title: 5-Aminomethyl-1H-benzimidazoles as orally active inhibitors of inducible T-cell kinase (Itk).
abstract: A series of novel 5-aminomethyl-1H-benzimidazole based inhibitors of Itk were prepared. Structure-activity relationships, selectivity and cell activity are reported for this series. Compound 2, a potent and selective antagonist of Itk, inhibited anti-CD3 antibody induced IL-2 production in vivo in mice.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, 665 Stockton Drive, Exton, PA 19341, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Winters
authors.forename: Darius J
authors.initials: DJ
authors.lastname: Robinson
authors.forename: Hnin Hnin
authors.initials: HH
authors.lastname: Khine
authors.forename: Steven S
authors.initials: SS
authors.lastname: Pullen
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Woska
authors.forename: Ernest L
authors.initials: EL
authors.lastname: Raymond
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Sellati
authors.forename: Charles L
authors.initials: CL
authors.lastname: Cywin
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Snow
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Kashem
authors.forename: John P
authors.initials: JP
authors.lastname: Wolak
authors.forename: Josephine
authors.initials: J
authors.lastname: King
authors.forename: Paul V
authors.initials: PV
authors.lastname: Kaplita
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Liu
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Farrell
authors.forename: Renee
authors.initials: R
authors.lastname: DesJarlais
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Roth
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Moriarty
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D017252:CD3 Complex / Q000096:biosynthesis; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008956:Models, Chemical; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology
chemical_list: D001562:Benzimidazoles; D017252:CD3 Complex; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase