- Discovery of 3,5-dimethylisoxazole derivatives as novel, potent inhibitors for bromodomain and extraterminal domain (BET) family
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Bromodomain and extra-terminal (BET) is a promising therapeutic target for various hematologic cancers. We used the BRD4 inhibitor compound 13 as a lead compound to develop a variety of compounds, and we introduced diverse groups into the position of the compound 13 orienting toward the ZA channel. A series of compounds (14–23, 38–41, 43, 47–49) bearing triazolopyridazine motif exhibited remarkable BRD4 protein inhibitory activities. Among them, compound 39 inhibited BRD4(BD1) protein with an IC50 of 0.003 μM was superior to lead compound 13. Meanwhile, compound 39 possess activity, IC50 = 2.1 μM, in antiproliferation activity against U266 cancer cells. On the other hand, compound 39 could arrest tumor cells into the G0/G1 phase and induce apoptosis, which was consistent with its results in inhibiting cell proliferation. Biological and biochemical data suggest that BRD4 protein might be a therapeutic target and that compound 39 is an excellent lead compound for further development.
- Fang, Lincheng,Hu, Zhaoxue,Yang, Yifei,Chen, Pan,Zhou, Jinpei,Zhang, Huibin
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- Medicine composition for treating knee osteoarthritis and preparation method thereof
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The invention relates to a medical composition for treating knee osteoarthritis. According to the medical composition, through restraining iNOS expression, the NO content is reduced, the chondrocyte apoptosis is reduced, synthesis of cartilage matrix is promoted, decomposition of cartilage matrix is restrained, the synovitis is restrained, the articular cartilage degrading is delayed, and articular cartilage repairing is promoted. The structure of the medical composition is shown in the description.
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Paragraph 0022; 0023; 0024; 0025
(2018/09/26)
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- HETEROAROMATIC COMPOUNDS AS PI3 KINASE MODULATORS AND METHODS OF USE
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The present invention provides heteroaromatic derivatives and pharmaceutical acceptable salts and formulations thereof useful in modulating the protein kinase activity, especially phosphatidylinositol 3-kinases (PI3 kinases) and mTOR, and in modulating inter- and/or intra-cellular signaling activities such as proliferation, differentiation, apoptosis, migration and invasion. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.
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Paragraph 0366
(2014/05/20)
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- DERIVATIVES OF 6-SUBSTITUTED TRIAZOLOPYRIDAZINES AS REV-ERB AGONISTS
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The present invention provides novel 6-substituted [1,2,4]triazolo[4,3-b]pyridazines that are agonists of Rev-Erb. These compounds, and pharmaceutical compositions comprising the same, are suitable means for treating any disease wherein the activation of Rev-Erb has therapeutic effects, for instance in inflammatory and circadian rhythm-related disorders or cardiometabolic diseases.
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Page/Page column 42
(2013/04/13)
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- AMINOPIPERIDINES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to novel substituted aminopiperidines which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DPP-IV inhibitors") and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
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Page/Page column 44
(2010/10/20)
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- BICYCLIC TRIAZOLONE DERIVATIVES AND HERBICIDES CONTAINING THE SAME
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The present invention provides a bicyclic triazolone derivative represented by the formula:J-Ar [wherein, J is and Ar is ], which has excellent selective weeding activity and weed killer containing the said bicyclic triazolone derivative.
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- 1,2,4-Triazolo (4,3-b) pyridazin-3-ones
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The new derivatives of 1,2,4-triazolo[4,3-b]pyridazin-3-ones and their salts which have the general formula SPC1 Wherein R1 represents hydrogen or lower alkyl, and R2 represents acyclic or cyclic amine groups, Are useful as psychotropic, anti-inflammatory and hypotensive agents.
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