title: Synthesis and biological evaluation of novel (4 or 5-aryl)pyrazolyl-indoles as inhibitors of interleukin-2 inducible T-cell kinase (ITK).
abstract: Interleukin-2 inducible T-cell kinase (ITK) is one of five kinases that belong to the Tec kinase family that plays an important role in T-cell and mast cell signaling. Various reports point to a role of ITK in the treatment of allergic asthma. For example, it was shown that mice lacking ITK have reduced airway hyperresponsiveness, inflammation and tracheal responses in an allergic asthma model. In this article, we disclose novel ITK inhibitors based on (4 or 5-aryl)pyrazolyl-indole scaffold that were also found to be selective for ITK over other kinases like IRK, CDK2, GSK3ss and PKA.
authors.affiliation: Global Discovery, Nycomed Pharma Pvt. Ltd, Andheri (East), Mumbai, Maharashtra, India. avdhoot.velankar@nycomed.com
authors.forename: Avdhoot D
authors.initials: AD
authors.lastname: Velankar
authors.forename: Gianluca
authors.initials: G
authors.lastname: Quintini
authors.forename: Arati
authors.initials: A
authors.lastname: Prabhu
authors.forename: Alexander
authors.initials: A
authors.lastname: Weber
authors.forename: Gundula
authors.initials: G
authors.lastname: Hunaeus
authors.forename: Britta
authors.initials: B
authors.lastname: Voland
authors.forename: Monika
authors.initials: M
authors.lastname: Wuest
authors.forename: Christian
authors.initials: C
authors.lastname: Orjeda
authors.forename: Dipak
authors.initials: D
authors.lastname: Harel
authors.forename: Shaji
authors.initials: S
authors.lastname: Varghese
authors.forename: Vikas
authors.initials: V
authors.lastname: Gore
authors.forename: Meenal
authors.initials: M
authors.lastname: Patil
authors.forename: Deepak
authors.initials: D
authors.lastname: Gayke
authors.forename: Matthias
authors.initials: M
authors.lastname: Herdemann
authors.forename: Isabelle
authors.initials: I
authors.lastname: Heit
authors.forename: Andrea
authors.initials: A
authors.lastname: Zaliani
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy; D001665:Binding Sites; D003198:Computer Simulation; D004195:Disease Models, Animal; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D051379:Mice; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase