Substituted 4-amino-1H-pyrazolo[3,4-d]pyrimidines as multi-targeted inhibitors of insulin-like growth factor-1 receptor (IGF1R) and members of ErbB-family receptor kinases

Abstract This Letter describes the lead discovery, optimization, and biological characterization of a series of substituted 4-amino-1 H -pyrazolo[3,4- d ]pyrimidines as potent inhibitors of IGF1R, EGFR, and ErbB2. The leading compound 11 showed an IGF1R IC 50 of 12 nM, an EGFR (L858R) IC 50 of 31 nM, and an ErbB2 IC 50 of 11 nM, potent activity in cellular functional and anti-proliferation assays, as well as activity in an in vivo pharmacodynamic assay.