25208-32-6Relevant articles and documents
Discovery of novel dual inhibitors of receptor tyrosine kinases EGFR and IGF-1R
Hempel, Cornelius,Totzke, Frank,Sch?chtele, Christoph,Najjar, Abdulkarim,Sippl, Wolfgang,Ritter, Christoph,Hilgeroth, Andreas
, p. 271 - 276 (2017/11/10)
Novel 4-benzylamino benzo-anellated pyrrolo[2,3-b]pyridines have been synthesized with varied substitution patterns both at the molecular scaffold of the benzo-anellated ring and at the 4-benzylamino residue. With a structural similarity to substituted thieno[2,3-d]pyrimidines as epidermal growth factor receptor (EGFR) inhibitors, we characterized the inhibition of EGFR for our novel compounds. As receptor heterodimerization gained certain interest as mechanism of cancer cells to become resistant against novel protein kinase inhibitors, we additionally measured the inhibition of insulin-like growth factor receptor IGF-1R which is a prominent receptor for such heterodimerizations with EGFR. Structure–activity relationships are discussed for both kinase inhibitions depending on the varied substitution patterns. We discovered novel dual inhibitors of both receptor tyrosine kinases with interest for further studies to reduce inhibitor resistance developments in cancer treatment.
Discovery of dually acting small-molecule inhibitors of cancer-resistance relevant receptor tyrosine kinases EGFR and IGF-1R
Hempel, Cornelius,Najjar, Abdulkarim,Totzke, Frank,Sch?chtele, Christoph,Sippl, Wolfgang,Ritter, Christoph,Hilgeroth, Andreas
supporting information, p. 2159 - 2166 (2016/11/17)
Novel benzo-anellated furo- and pyrrolo[2,3-b]pyridines with a 4-benzylamine substitution have been evaluated as inhibitors of the epidermal growth factor receptor (EGFR). Substituent effects on the determined protein kinase affinity have been discussed based on varied benzylamine residues at the differently substituted molecular scaffolds. Docking studies were carried out in order to explore the potential binding modes of the novel inhibitors. The observed activity data encouraged the measurement of the inhibition of the insulin-like growth factor receptor (IGF-1R), which is known to play an important role in the cancer-resistance development against EGFR inhibitors via receptor heterodimerizations with IGF-1R. We identified novel dual inhibitors of both kinases and report their first cancer cell growth inhibition data.
Discovery of 4-anilino α-carbolines as novel Brk inhibitors
Mahmoud, Kazem Ahmed,Krug, Martin,Wersig, Tom,Slynko, Inna,Sch?chtele, Christoph,Totzke, Frank,Sippl, Wolfgang,Hilgeroth, Andreas
, p. 1948 - 1951 (2014/04/17)
Dysregulation of cell signalling processes caused by an enhanced activity of protein kinases mainly contributes to cancer progression. Protein kinase inhibitors have been established as promising drugs that inhibit such overactive protein kinases in cancer cells. The formation of metastases, which makes a therapy difficult, remains a great challenge for cancer treatment. Recently, breast tumor kinase (Brk) was discovered as novel and interesting target for a cancer therapy because Brk participates in both cell dysregulation and metastasis. We discovered 4-anilino substituted α-carboline compounds as a novel class of highly active Brk inhibitors. In the current work, structure-activity relationships are discussed including docking results obtained for 4-anilino α-carbolines. A first profiling of selective kinase inhibition and a proof of concept for the antiproliferative effects is demonstrated. These results qualify the compounds as a promising class of novel antitumor agents.
Novel inhibitors of breast cancer relevant kinases Brk and HER2
Mahmoud, Kazem Ahmed,Wersig, Tom,Slynko, Inna,Totzke, Frank,Sch?chtele, Christoph,Oelze, Markus,Sippl, Wolfgang,Ritter, Christoph,Hilgeroth, Andreas
supporting information, p. 659 - 664 (2014/05/06)
Novel 4-anilino pyrido[2,3-b]indoles have been discovered as inhibitors of the breast cancer relevant protein kinase Brk. Within this first series favourable aniline substituents have been characterized. Combinations with substituents of the molecular scaffold have been further investigated and led to additional nanomolar Brk inhibitors. Due to the reported role of Brk in breast cancer progression via HER2 activation we determined the inhibition profile of our novel Brk inhibitors to additionally inhibit HER2. These studies characterized the first dually acting Brk and HER2 inhibitor and the first exclusive HER2 inhibitors. This journal is the Partner Organisations 2014.
N-Alkyl-5H-pyrido[4,3-b]indol-1-amines and derivatives as novel urotensin-II receptor antagonists
Wang, Yonghui,Wu, Zining,Guida, Brian F.,Lawrence, Sarah K.,Neeb, Michael J.,Rivero, Ralph A.,Douglas, Stephen A.,Jin, Jian
scheme or table, p. 4936 - 4939 (2009/04/16)
High throughput screening of our compound collection led to the discovery of a novel series of N-alkyl-5H-pyrido[4,3-b]indol-1-amines as urotensin-II receptor antagonists. Synthesis, initial structure and activity relationships, functional and animal ortholog activities of the series are described.
