1570-05-4Relevant articles and documents
Discovery and evaluation of the hybrid of bromophenol and saccharide as potent and selective protein tyrosine phosphatase 1B inhibitors
Zhang, Renshuai,Yu, Rilei,Xu, Qi,Li, Xiangqian,Luo, Jiao,Jiang, Bo,Wang, Lijun,Guo, Shuju,Wu, Ning,Shi, Dayong
, p. 24 - 33 (2017)
Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin signaling pathway. Inhibition of PTP1B is expected to improve insulin action. Appropriate selectivity and permeability are the gold standard for excellent PTP1B inhibitors. In this work, molecular hybridization-based screening identified a selective competitive PTP1B inhibitor. Compound 10a has IC50 values of 199?nM against PTP1B, and shows 32-fold selectivity for PTP1B over the closely related phosphatase TCPTP. Molecule docking and molecular dynamics studies reveal the reason of selectivity for PTP1B over TCPTP. Moreover, the cell permeability and cellular activity of compound 10a are demonstrated respectively.
Cannabidiol derivative, preparation method and application thereof
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, (2021/07/28)
The invention discloses a cannabidiol derivative, a preparation method and application thereof, and belongs to the technical field of medicinal chemistry, wherein the cannabidiol derivative is obtained by taking cannabidiol as a main body through a synthesis means, and an anti-tumor activity determination result shows that the cannabidiol derivative prepared by the invention has an inhibition effect on lung cancer cell strains, human breast cancer cell strains, nasopharynx cancer and drug-resistant strains thereof.
Synthesis and evaluation of new sesamol-based phenolic acid derivatives with hypolipidemic, antioxidant, and hepatoprotective effects
Xie, Yundong,Liu, Jiping,Shi, Yongheng,Bin Wang,Wang, Xiaoping,Wang, Wei,Sun, Meng,Xu, Xinya,He, Shipeng
, p. 1688 - 1702 (2021/07/26)
The objective of this study is to synthesize a series of sesamol-based phenolic acid derivatives, which were designed by combination principle. The hypolipidemic activity of all these compounds was preliminarily screened by acute hyperlipidemic mice model induced by Triton WR 1339, in which compound T6 exhibited more significant reducing plasma TG and TC than fenofibrate. Compound T6 was also found to obviously decrease TG and TC both in the plasma and hepatic tissue of high-fat-diet-induced hyperlipidemic mice. Moreover, T6 showed hepatoprotective effects, which remarkable amelioration in characteristic liver enzymes was examined and the histopathological observation displayed that compound T6 inhibited lipids accumulation in the hepatic. The levels of PPAR-α receptor related to lipids metabolism in hepatic tissue were upregulated after T6 treatment. Other potent effects of T6 such as antioxidant and anti-inflammatory activity were also observed. On the bases of these findings, compound T6 may serve as an effective hypolipidemic and hepatoprotective agent. [Figure not available: see fulltext.]
Biological Characterization, Mechanistic Investigation and Structure-Activity Relationships of Chemically Stable TLR2 Antagonists
Bermudez, Marcel,Grabowski, Maria,Murgueitio, Manuela S.,Rademann, J?rg,Rudolf, Thomas,Tiemann, Markus,Varga, Péter,Weindl, Günther,Wolber, Gerhard
, (2020/06/08)
Toll-like receptors (TLRs) build the first barrier in the innate immune response and therefore represent promising targets for the modulation of inflammatory processes. Recently, the pyrogallol-containing TLR2 antagonists CU-CPT22 and MMG-11 were reported; however, their 1,2,3-triphenol motif renders them highly susceptible to oxidation and excludes them from use in extended experiments under aerobic conditions. Therefore, we have developed a set of novel TLR2 antagonists (1–9) based on the systematic variation of substructures, linker elements, and the hydrogen-bonding pattern of the pyrogallol precursors by using chemically robust building blocks. The novel series of chemically stable and synthetically accessible TLR2 antagonists (1–9) was pharmacologically characterized, and the potential binding modes of the active compounds were evaluated structurally. Our results provide new insights into structure-activity relationships and allow rationalization of structural binding characteristics. Moreover, they support the hypothesis that this class of TLR ligands bind solely to TLR2 and do not directly interact with TLR1 or TLR6 of the functional heterodimer. The most active compound from this series (6), is chemically stable, nontoxic, TLR2-selective, and shows a similar activity with regard to the pyrogallol starting points, thus indicating the variability of the hydrogen bonding pattern.
Synthesis and comparative structure-activity study of carbohydrate-based phenolic compounds as α-glucosidase inhibitors and antioxidants
MacHida, Shota,Mukai, Saki,Kono, Rina,Funato, Megumi,Saito, Hiroaki,Uchiyama, Taketo
, (2019/12/04)
Twenty-one natural and unnatural phenolic compounds containing a carbohydrate moiety were synthesized and their structure-activity relationship (SAR) was evaluated for α-glucosidase inhibition and antioxidative activity. Varying the position of the galloyl unit on the 1,5-anhydro -D-glucitol (1,5-AG) core resulted in changes in the α-glucosidase inhibitory activity and notably, particularly strong activity was demonstrated when the galloyl unit was present at the C-2 position. Furthermore, increasing the number of the galloyl units significantly affected the α-glucosidase inhibition, and 2,3,4,6-tetra-galloyl-1,5-AG (54) and 2,3,4,6-tetra-galloyl-d-glucopyranose (61) exhibited excellent activities, which were more than 13-fold higher than the α-glucosidase inhibitory activity of acertannin (37). Moreover, a comparative structure-activity study suggested that a hemiacetal hydroxyl functionality in the carbohydrate core and a biaryl bond of the 4,6-O-hexahydroxydiphenoyl (HHDP) group, which are components of ellagitannins including tellimagrandin I, are not necessary for the α-glucosidase inhibitory activity. Lastly, the antioxidant activity increased proportionally with the number of galloyl units.
New uses of tetramethylpyrazine derivative in biological nerve protection
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, (2016/10/10)
The present invention provides applications of a tetramethylpyrazine derivative having a structure represented by a formula 1, or a salt thereof, or a composition containing a tetramethylpyrazine derivative having a structure represented by the formula 1 or a salt thereof in preparation of drugs for prevention or treatment of nervous system diseases, wherein R1 is any one selected from -H, -OCH3 and -OH, R2 is any one selected from -H, -OCH3 and -OH, R3 is any one selected from -H, -OCH3, -OH and -CH3, and R4 is any one selected from -H and -OCH3. The present invention further provides a tetramethylpyrazine derivative having a structure represented by a formula 2, or a salt thereof, or a composition containing a tetramethylpyrazine derivative having a structure represented by the formula 2 or a salt thereof in preparation of drugs for prevention or treatment of nervous system diseases, wherein R1 is any one selected from -H, -OH and -OCOCH3, R2 is any one selected from -H, -OCH3 and -OH, and R3 is any one selected from -H and -OH. The formulas 1 and 2 are defined in the specification.
The polyfunctional polymerizable compound
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Paragraph 0070; 0071, (2019/09/07)
PROBLEM TO BE SOLVED: To provide a polymerizable compound that exhibits excellent dissolvability with other liquid crystal compounds when it constitutes a polymerizable liquid crystal composition and that exhibits excellent heat resistance and mechanical strength when the polymerizable liquid crystal composition is cured. SOLUTION: The compound represented by general formula (I) is useful as a constituting member of a polymerizable composition as it has excellent dissolvability with other liquid crystal compounds. The polymerizable liquid crystal composition comprising the polymerizable compound has a wide liquid crystal phase temperature range. The optical anisotropic body obtained by using the polymerizable composition exhibits high heat resistance and is useful for applications such as a polarizing plate, a retardation plate and the like. COPYRIGHT: (C)2010,JPOandINPIT
ANTIMICROBIAL CATIONIC POLYAMINES
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Paragraph 0175, (2015/12/23)
Antimicrobial, non-hemolytic cationic polyamines were prepared by treating partially N-acylated polyethylenimines and/or partially oxidized polyethylenimines with a protic acid. The cationic polyamines can have a linear or branched polyethylenimine backbone structure. Preferably, the cationic polyamines comprise pendant urea groups, which can be introduced via a cyclic carbonate comprising a pendant urea group. The cationic polyamines can be active against a tuberculosis mycobacterium at low concentration. The cationic polyamines are also effective against Gram-negative Escherichia coli and Pseudomonas aeruginosa, Gram-positive Staphylococcus aureus, and fungus Candida albicans in solution and in the form of a film.
Synthetic studies of fisetin, myricetin and nobiletin analogs and related probe molecules
Hiza, Aiki,Tsukaguchi, Yuta,Ogawa, Takahiro,Inai, Makoto,Asakawa, Tomohiro,Hamashima, Yoshitaka,Kan, Toshiyuki
, p. 1371 - 1396 (2016/10/12)
We synthesized a series of analogs of fisetin, myricetin and nobiletin, as well as related fluorescein- and biotin-based flavone-probe molecules, on a suitable scale for biological and structure-activity relationship studies.
Indole derivatives as dual-effective agents for the treatment of neurodegenerative diseases: Synthesis, biological evaluation, and molecular modeling studies
Buemi, Maria Rosa,De Luca, Laura,Chimirri, Alba,Ferro, Stefania,Gitto, Rosaria,Alvarez-Builla, Julio,Alajarin, Ramon
, p. 4575 - 4580 (2013/07/26)
Several indole derivatives, that were highly potent ligands of GluN2B-subunit-containing N-methyl-d-aspartate (NMDA) receptor, also demonstrated antioxidant properties in ABTS method. In particular, the 2-(4-benzylpiperidin-1-yl)-1-(5-hydroxy-1H-indol-3-yl)ethanone (1) proved to be a dual-effective neuroprotective agent. With the aim to increase the antioxidant properties we added a catechol moiety onto piperidine moiety. The designed hybrid derivative 3,4-dihydroxy-N-[1-[2-(5-hydroxy-1H-indol-3-yl)-2-oxoethyl] piperidin-4-yl]benzamide (10) was the most effective antioxidant agent (>94.1 ± 0.1% of inhibition at 17 μM) and showed GluN2B/NMDA receptor affinity at low micromolar concentration (IC50 0.66 μM). By means of computational studies we explored the effect of the presence of this antioxidant fragment during the recognition process to binding pocket.
