- Design, synthesis, and structure-activity relationship studies of novel diaryl ether amides as potential antitumor agents
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Sorafenib is a drug that has been verified to be effective on hepatoma cells. Three series of diaryl ethers have been designed and synthesized based on the structure of sorafenib. The 5m compound shows better inhibitory potency against HepG2 cells (IC50 = 1.96 μM) than sorafenib (IC50 = 9.61μM). These results have been verified with MTT assay and colony-forming assay. Moreover, compound 5m exhibits good antitumor activities against PLC/PRF5, HeLa, A549, and HT-29 cell lines. The excellent bioactivity of compound 5m confirms that a single optical conformation is superior to the racemate. A western blotting analysis indicates that compound 5m induces the apoptosis of HepG2 cells by enhancing the protein levels of p21 and Cl-caspase3.
- Zheng, Man-Yi,Huang, Zhi-Ning,Yang, Shao-Mei,Han-Liang,Lu-Xu,Wang, Bao-Rui,Wang, Li-Juan,Wang, Hai-Li,Li, Shan-Hua,Li, Fu-Nan
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p. 727 - 736
(2019/05/22)
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- Synthesis and structure–activity relationship of N-(piperidin-4-yl)benzamide derivatives as activators of hypoxia-inducible factor 1 pathways
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Guided by bioisosterism and pharmacokinetic parameters, we designed and synthesized a series of novel benzamide derivatives. Preliminary in vitro studies indicated that compounds 10b and 10j show significant inhibitory bioactivity in HepG2 cells (IC50 values of 0.12 and 0.13?μM, respectively). Compounds 10b and 10j induced the expression of HIF-1α protein and downstream target gene p21, and upregulated the expression of cleaved caspase-3 to promote tumor cells apoptosis.
- Huang, Zhi-Ning,Liang, Han,Qiao, Hong,Wang, Bao-Rui,Qu, Ning,Li, Hua,Zhou, Run-Run,Wang, Li-Juan,Li, Shan-Hua,Li, Fu-Nan
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p. 1149 - 1161
(2018/07/21)
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- Substituted-aryl 7-aza[2.2.1]bicycloheptanes for the treatment of disease
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The invention provides compounds of Formula I: wherein the stereochemistry of the of the 7-azabicyclo[2.2.1]heptane ring is 1S, 2R, 4R and the nitrogen substituent at the C-2 carbon has the exo orientation; W is -Q, —C═C-Q, or —C≡C-Q; and Q is as defined
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- Substituted-aryl compounds for treatment of disease
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The invention provides compounds of Formula I: These compounds may be in the form of pharmaceutical salts or compositions, racemic mixtures, or pure enantiomers thereof. The compounds of Formula I are useful in pharmaceuticals to treat diseases or conditions in which α7 is known to be involved.
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- Quinuclidine-substituted aryl compounds for treatment of disease
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The invention provides compounds of Formula I: These compounds may be in the form of pharmaceutical salts or compositions, and racemic mixtures or pure enantiomers thereof. The compounds of Formula I are useful in pharmaceuticals in which α7 is known to be involved.
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- Aryl substituted pyrazoles, and pyrroles, and the use thereof
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This invention relates to compounds having the Formula I: or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein Het and R5-R13are set in the specification. The invention also is directed to the use of compounds of Formula I for the treatment of neuronal damage following global and focal ischemia, for the treatment or prevention of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), and for the treatment, prevention or amelioration of both acute or chronic pain, as antitinnitus agents, as anticonvulsants, and as antimanic depressants, as local anesthetics, as antiarrhythmics and for the treatment or prevention of diabetic neuropathy.
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- Isolation and identification of the major urinary metabolite of 4-(4- fluorophenoxy)benzaldehyde semicarbazone after oral dosing to rats
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4-(4-Fluorophenoxy)benzaldehyde semicarbazone (1) is a novel anticonvulsant affording excellent protection in the rat oral maximal electroshock (MES) screen as well as having an apparent protection index of over 300. The metabolism of this compound was st
- Dimmock,Semple,John,Beazely,Abrams
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p. 260 - 262
(2007/10/03)
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