- COMPOUNDS AND THEIR USES AS SPLEEN TYROSINE KINASE INHIBITORS
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Provided are compounds of Formula (I) which can be used as Syk inhibitors and potently as therapeutic agents against diseases mediated by Syk.
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Paragraph 0111
(2021/12/28)
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- Development of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates bearing sulfonylpiperazine as antitumor inhibitors targeting PI3Kα
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PI3K signal pathway plays a vital role in cellular functions and becomes an attractive approach for cancer therapy. Herein, a new series of novel chromeno[4,3-c]pyrazol-4(2H)-one derivatives bearing sulfonylpiperazine based on the PI3K inhibitors and our previous research. They were screened for their PI3K inhibitory activities and anticancer effects in vitro. Biological studies indicated that compound 7m revealed the remarkable antiproliferative activity (IC50 ranging from 0.03 to 0.09 μM) against four cancer cell lines (A549, Huh7, HL60 and HCT-116). Besides, compound 7m displayed a certain selective for PI3Kα (IC50 = 0.009 μM) over PI3Kβ, γ and δ, and meanwhile, it can remarkable decreased the expression level of p-Akt (Ser473) and p-S6K. In addition, compound 7m could not only induce HCT-116 cell arrest at G1 phase in a dose-dependent manner, but also induce cell apoptosis via upregulation of Bax and cleaved-caspase 3/9, and downregulation of Bcl-2. Besides, compound 7m can remarkably inhibit the growth of tumor in vivo. The above results suggested that compound 7m could be considered as a promising PI3Kα inhibitor.
- Yin, Yong,Sha, Shao,Wu, Xun,Wang, She-Feng,Qiao, Fang,Song, Zhong-Cheng,Zhu, Hai-Liang
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- NOVEL TETRAHYDROPYRIDOPYRIMIDINES FOR THE TREATMENT AND PROPHYLAXIS OF HBV INFECTION
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The present invention provides novel compounds having general formula (I), wherein R1 to R4, A, W, Q and Y are as described herein, compositions including the compounds and methods of using the compounds.
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Page/Page column 110; 111
(2018/09/25)
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- Structure-Activity Relationships of Potent, Targeted Covalent Inhibitors That Abolish Both the Transamidation and GTP Binding Activities of Human Tissue Transglutaminase
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Human tissue transglutaminase (hTG2) is a multifunctional enzyme. It is primarily known for its calcium-dependent transamidation activity that leads to formation of an isopeptide bond between glutamine and lysine residues found on the surface of proteins, but it is also a GTP binding protein. Overexpression and unregulated hTG2 activity have been associated with numerous human diseases, including cancer stem cell survival and metastatic phenotype. Herein, we present a series of targeted covalent inhibitors (TCIs) based on our previously reported Cbz-Lys scaffold. From this structure-activity relationship (SAR) study, novel irreversible inhibitors were identified that block the transamidation activity of hTG2 and allosterically abolish its GTP binding ability with a high degree of selectivity and efficiency (kinact/KI > 105 M-1 min-1). One optimized inhibitor (VA4) was also shown to inhibit epidermal cancer stem cell invasion with an EC50 of 3.9 μM, representing a significant improvement over our previously reported "hit" NC9.
- Akbar, Abdullah,McNeil, Nicole M. R.,Albert, Marie R.,Ta, Viviane,Adhikary, Gautam,Bourgeois, Karine,Eckert, Richard L.,Keillor, Jeffrey W.
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supporting information
p. 7910 - 7927
(2017/10/06)
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- 2,5-Disubstituted pyridines as potent GPR119 agonists
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A series of 2-piperazinyl-5-alkoxypyridines were synthesized and screened against human GPR119 receptor. Through SAR analysis, compounds containing 2-alkylsulfonylpiperazinyl-5-alkoxypyridines were discovered and found to be potent agonists of the human GPR119 receptor.
- Wu, Yulin,Kuntz, Judith D.,Carpenter, Andrew J.,Fang, Jing,Sauls, Howard R.,Gomez, Daniel J.,Ammala, Carina,Xu, Yun,Hart, Shane,Tadepalli, Sarva
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scheme or table
p. 2577 - 2581
(2010/06/19)
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- Cis-imidazolines
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There are provided compounds of the formula I wherein R, V1, V2 and Ring A are described herein. The compounds exhibit anticancer activity.
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Page/Page column 20
(2010/11/27)
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