1383679-60-4Relevant academic research and scientific papers
Discovery of novel amino-pyrimidine inhibitors of the insulin-like growth factor 1 (IGF1R) and insulin receptor (INSR) kinases; parallel optimization of cell potency and hERG inhibition
Tye, Heather,Guertler, Ulrich,Hofmann, Marco H.,Mayer, Moriz,Pal, Sandeep,Rast, Georg,Sanderson, Michael P.,Schaaf, Otmar,Treu, Matthias,Zahn, Stephan K.
, p. 1244 - 1251 (2015/07/15)
The insulin-like growth factor-1 receptor (IGF1R) and closely related insulin receptor (INSR) are receptor tyrosine kinases which have been postulated to play a role in the tumorigenesis of certain cancers. Strategies for inhibiting oncogenic signaling via the IGF1R and INSR include IGF1R antibodies, IGF1/2 antibodies and dual IGF1R/INSR tyrosine kinase inhibitors (TKIs). IGF1R/INSR TKIs linsitinib (OSI-906) and BMS-754807 have progressed to phase II/III clinical studies in cancer patients. We describe here our efforts to develop small molecule dual inhibitors of the IGF1R/INSR receptor kinases based on an amino-pyrimidine structural class. Our main focus was the parallel optimization of cellular potency and off target activity (principally hERG inhibition) through modulation of physicochemical properties and introduction of key structural motifs using a matched molecular pairs approach and hERG homology model.
OXINDOLOPYRIMIDINE AS IGF1R RECEPTOR INHIBITORS
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Page/Page column 89; 98, (2012/07/13)
The present invention encompasses compounds of general formula (I) wherein the groups R5 to R10, A, L1, B, m and p are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, pharmaceutical preparations which contain such compounds and their use as medicaments.
