Bioorganic & Medicinal Chemistry Letters 2010-01-01

Identification of potent ITK inhibitors through focused compound library design including structural information

Matthias Herdemann, Isabelle Heit, Frank-Uwe Bosch, Gianluca Quintini, Claudia Scheipers, Alexander Weber

Index: Bioorg. Med. Chem. Lett. 20 , 6998, (2010)

Full Text: HTML

Abstract

A series of novel compound libraries inhibiting interleukin-2 inducible T cell kinase (ITK) were designed, synthesized and evaluated. In the first design cycle two library scaffolds were identified showing low micromolar inhibition of ITK. Further iterative design cycles including crystal structure information of ITK and structurally related kinases led to the identification of indolylindazole and indolylpyrazolopyridine compounds with low nanomolar ITK inhibition.Copyright © 2010 Elsevier Ltd. All rights reserved.