18880-07-4Relevant academic research and scientific papers
Development of Novel Inhibitors for Histone Methyltransferase SET7/9 based on Cyproheptadine
Hirano, Tomoya,Fujiwara, Takashi,Niwa, Hideaki,Hirano, Michitake,Ohira, Kasumi,Okazaki, Yusuke,Sato, Shin,Umehara, Takashi,Maemoto, Yuki,Ito, Akihiro,Yoshida, Minoru,Kagechika, Hiroyuki
, p. 1530 - 1540 (2018/08/01)
The histone methyltransferase SET7/9 methylates not only histone but also non-histone proteins as substrates, and therefore, SET7/9 inhibitors are considered candidates for the treatment of diseases. Previously, our group identified cyproheptadine, used clinically as a serotonin receptor antagonist and histamine receptor (H1) antagonist, as a novel scaffold of the SET7/9 inhibitor. In this work, we focused on dibenzosuberene as a substructure of cyproheptadine and synthesized derivatives with various functional groups. Among them, the compound bearing a 2-hydroxy group showed the most potent activity. On the other hand, a 3-hydroxy group or another hydrophilic functional group such as acetamide decreased the activity. Structural analysis clarified a rationale for the improved potency only by tightly restricted location and type of the hydrophilic group. In addition, a SET7/9 loop, which was only partially visible in the complex with cyproheptadine, became more clearly visible in the complex with 2-hydroxycyproheptadine. These results are expected to be helpful for further structure-based development of SET7/9 inhibitors.
FUSED RING HETEROCYCLE KINASE MODULATORS
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Page/Page column 116-117, (2008/12/04)
The present invention provides fused ring heterocycles as kinase modulators, pharmaceutical compositions containing these modulators, and methods of using these modulators to treat diseases mediated by kinase activity.
Evidence for Bromine-Lithium Exchange in a Local High Concentration Gradient
Beak, Peter,Liu, Chao
, p. 5999 - 6004 (2007/10/02)
The product ratios for bromine-lithium exchange of 3,3'-dibromostilbene (6) with one equivalent of n-butyl lithium, s-butyl lithium or t-butyl lithium in THF and in Et2O to give after quenching with methanol 3-bromostilbene (7) and stilbene (8), have been investigated.In the reactive cases the ratio of 8:7 is significantly greater than expected for a statistical reaction.The apparently accelerated exchange of 7-Li relative to 6 is attributed to reaction in a high local concentration of the butyl lithium reagent.
