22908-25-4Relevant academic research and scientific papers
Discovery and Optimization of Dibenzodiazepinones as Allosteric Mutant-Selective EGFR Inhibitors
De Clercq, Dries J. H.,Heppner, David E.,To, Ciric,Jang, Jaebong,Park, Eunyoung,Yun, Cai-Hong,Mushajiang, Mierzhati,Shin, Bo Hee,Gero, Thomas W.,Scott, David A.,J?nne, Pasi A.,Eck, Michael J.,Gray, Nathanael S.
, p. 1549 - 1553 (2019)
Allosteric kinase inhibitors represent a promising new therapeutic strategy for targeting kinases harboring oncogenic driver mutations in cancers. Here, we report the discovery, optimization, and structural characterization of allosteric mutant-selective EGFR inhibitors comprising a 5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one scaffold. Our structure-based medicinal chemistry effort yielded an inhibitor (3) of the EGFR(L858R/T790M) and EGFR(L858R/T790M/C797S) mutants with an IC50 of a?10 nM and high selectivity, as assessed by kinome profiling. Further efforts to develop allosteric dibenzodiazepinone inhibitors may serve as the basis for new therapeutic options for targeting drug-resistant EGFR mutations.
HETEROCYCLIC COMPOUNDS AS AUTOTAXIN INHIBITORS
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Page/Page column 44-45, (2012/05/20)
Compounds of the formula (I), in which R, R1, R2, X, X1, Y, Y1, Q, E, n1 and n2 have the meanings indicated in claim 1, are autotaxin inhibitors and can be employed for the treatment of tumours.
UREA AND CARBAMATE COMPOUNDS AND ANALOGS AS KINASE INHIBITORS
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Page/Page column 108, (2010/04/27)
The invention is directed to compounds that can inhibit the bioactivity of one or more kinases such as any of Rho kinases, PKB (Akt) kinases, p70S6K kinase, LIM kinases, or IKK kinases, to methods of use of those compounds, and to methods of preparation of those compounds The inventive compounds can be used In the treatment of a variety of medical malconditions.
