title: Itk kinase inhibitors: initial efforts to improve the metabolical stability and the cell activity of the benzimidazole lead.
abstract: Previously, we reported a series of novel benzimidazole based Itk inhibitors that exhibited excellent enzymatic potency and selectivity but low microsomal stability. Employing a structure based approach a new series of inhibitors with comparable potency and selectivity to the original series and with a potential for improved microsome stability was identified.
authors.affiliation: Johnson & Johnson, PRDUS, Springhouse, PA 19477, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Moriarty
authors.forename: Michael
authors.initials: M
authors.lastname: Winters
authors.forename: Lei
authors.initials: L
authors.lastname: Qiao
authors.forename: Declan
authors.initials: D
authors.lastname: Ryan
authors.forename: Renee
authors.initials: R
authors.lastname: DesJarlis
authors.forename: Darius
authors.initials: D
authors.lastname: Robinson
authors.forename: Brian N
authors.initials: BN
authors.lastname: Cook
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Kashem
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: Hnin Hnin
authors.initials: HH
authors.lastname: Khine
authors.forename: Josephine
authors.initials: J
authors.lastname: King
authors.forename: Steven S
authors.initials: SS
authors.lastname: Pullen
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Roth
authors.forename: Ronald
authors.initials: R
authors.lastname: Magolda
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000284:Administration, Oral; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D001665:Binding Sites; D017252:CD3 Complex / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D017252:CD3 Complex; D004791:Enzyme Inhibitors; D000255:Adenosine Triphosphate; C031000:benzimidazole; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase