1250296-92-4Relevant articles and documents
Discovery of 4-amino-1H-pyrazolo[3,4-d]pyrimidin derivatives as novel discoidin domain receptor 1 (DDR1) inhibitors
Dong, Ru,Zhou, Xin,Wang, Min,Li, Wen,Zhang, Jin-Yang,Zheng, Xin,Tang, Kai-Xiang,Sun, Li-Ping
, (2021)
DDR1 is a receptor tyrosine kinase that is activated by triple-helical collagens and has become an attractive target for anticancer therapy given its involvement in tumor growth, metastasis development, and tumor dormancy. Several drugs on the market, such as dasatinib and nilotinib, were reported to potently suppress the function of DDR1 and show significant therapeutic benefits in a variety of preclinical tumor models. Whereas only a few selective DDR1 inhibitors were disclosed in recent years. A series of 4-amino-1H-pyrazolo[3,4-d]pyrimidin derivatives were designed and synthesized. All compounds were evaluated via DDR1 kinase inhibition assay and cell anti-proliferative assay. One of the representative compounds, 6c, suppressed DDR1 kinase activity with an IC50 value of 44 nM and potently inhibited cell proliferation in DDR1-overexpressing cell lines HCT-116 and MDA-MB-231 with IC50 value of 4.00 and 3.36 μM respectively. Further molecular docking study revealed that 6c fitted ideally into DDR1 binding pocket and maintained the crucial hydrogen bonds with DDR1 kinase domain. Overall, these results suggest that the compound 6c is a potential DDR1 inhibitor deserving further investigation for cancer treatment.
Novel highly potent and selective nonsteroidal aromatase inhibitors: Synthesis, biological evaluation and structure-activity relationships investigation
Gobbi, Silvia,Zimmer, Christina,Belluti, Federica,Rampa, Angela,Hartmann, Rolf W.,Recanatini, Maurizio,Bisi, Alessandra
supporting information; experimental part, p. 5347 - 5351 (2010/10/21)
In further pursuing our search for potent and selective aromatase inhibitors, a new series of molecules was designed and synthesized, exploring possible structural modifications of a previously identified xanthone scaffold. Among them, highly potent compounds, with inhibitory activity in the low nanomolar range, were found. In particular, substitution of the heterocyclic oxygen atom in the xanthone core by a sulfur atom and/or increase in structure flexibility seemed to be favorable for the interaction with the enzyme.
