title: Discovery, SAR and X-ray structure of 1H-benzimidazole-5-carboxylic acid cyclohexyl-methyl-amides as inhibitors of inducible T-cell kinase (Itk).
abstract: A series of novel potent benzimidazole based inhibitors of interleukin-2 T-cell kinase (Itk) were prepared. In this report, we discuss the structure-activity relationship (SAR), selectivity, and cell-based activity for the series. We also discuss the SAR associated with an X-ray structure of one of the small-molecule inhibitors bound to ITK.
authors.affiliation: Johnson & Johnson, PRDUS, LLC, Springhouse, PA 19477, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Moriarty
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
authors.forename: Steven S
authors.initials: SS
authors.lastname: Pullen
authors.forename: Hnin Hnin
authors.initials: HH
authors.lastname: Khine
authors.forename: Rosemarie H
authors.initials: RH
authors.lastname: Sallati
authors.forename: Ernest L
authors.initials: EL
authors.lastname: Raymond
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Woska
authors.forename: Deborah D
authors.initials: DD
authors.lastname: Jeanfavre
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Roth
authors.forename: Michael P
authors.initials: MP
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: DesJarlais
authors.forename: Darius
authors.initials: D
authors.lastname: Robinson
authors.forename: Matthew
authors.initials: M
authors.lastname: Wilson
authors.forename: Mark
authors.initials: M
authors.lastname: Bobko
authors.forename: Brian N
authors.initials: BN
authors.lastname: Cook
authors.forename: Ho Yin
authors.initials: HY
authors.lastname: Lo
authors.forename: Peter A
authors.initials: PA
authors.lastname: Nemoto
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Kashem
authors.forename: John P
authors.initials: JP
authors.lastname: Wolak
authors.forename: André
authors.initials: A
authors.lastname: White
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Magolda
authors.forename: Bruce
authors.initials: B
authors.lastname: Tomczuk
mesh_terms: D000577:Amides / Q000737:chemistry*; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D008956:Models, Chemical; D008968:Molecular Conformation; D011505:Protein-Tyrosine Kinases / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: C470231:5-benzimidazolecarboxylic acid; D000577:Amides; D001562:Benzimidazoles; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase