20628-06-2Relevant articles and documents
Synthesis, structure-activity relationship studies and evaluation of a TLR 3/8/9 agonist and its analogues
Sarkar, Anindya,Kankanamalage, Anushka C. Galasiti,Zhang, Qian,Cheng, Heng,Sivaprakasam, Prasanna,Naglich, Joseph,Xie, Chunshan,Gangwar, Sanjeev,Boger, Dale L.
, p. 1377 - 1385 (2021)
A comprehensive SAR study of a putative TLR 3/8/9 agonist was conducted. Despite the excitement surrounding the potential of the first small molecule TLR3 agonist with a compound that additionally displayed agonist activity for TLR8 and TLR9, compound 1 displayed disappointing activity in our hands, failing to match the potency (EC50) reported and displaying only a low efficacy for the extent of stimulated NF-κB activation and release. The evaluation of >75 analogs of 1, many of which constitute minor modifications in the structure, failed to identify any that displayed significant activity and none that exceeded the modest activity found for 1. [Figure not available: see fulltext.].
Synthesis and biological evaluation of novel chromonyl enaminones as α-glucosidase inhibitors
Mendieta-Moctezuma, Aarón,Rugerio-Escalona, Catalina,Villa-Ruano, Nemesio,Gutierrez, Rsuini U.,Jiménez-Montejo, Fabiola E.,Fragoso-Vázquez, M. Jonathan,Correa-Basurto, José,Cruz-López, María C.,Delgado, Francisco,Tamariz, Joaquín
, p. 831 - 848 (2019/04/25)
Series of novel chromonyl enaminones 1a–e and 2a–e and 3-alkylated chromones 3a–e were synthesized and evaluated in vitro as α-glucosidase inhibitors as well as antioxidant and antifungal agents. Antifungal activity was tested on strains of Candida albicans. Compounds 2a and 2d–e showed good inhibition of the α-glucosidase enzyme (IC50 = 5.5, 0.9, and 1.5 mM, respectively), their effect being better than that of 1a–e, 3a–e, and acarbose (the standard, IC50 = 7.73 ± 0.9 mM). The structure–activity relationship suggests that the phenyl group at the C-3 position of the chromone ring system and the 4-chlorophenyl group at the enaminone moiety (derivatives 2) increased the inhibition of α-glucosidase. Compounds 2a–e exhibited a slight antioxidant effect, and compounds 3a–e a moderate antifungal activity against C. albicans (IC50 70.5–83.1 μg/mL). Docking studies revealed that compounds 2 interact with the α-glucosidase residues of the binding pocket. Therefore, these chromone derivatives may be considered as potential α-glucosidase inhibitors, as well as antifungal agents against some Candida strains of yeast.
PYRIMIDINES AND VARIANTS THEREOF, AND USES THEREFOR
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Paragraph 00384; 00385, (2017/10/13)
The present disclosure provides pyrimidine compounds and uses thereof, for example, for the treatment of diseases associated with P2X purinergic receptors. In certain aspects, the present disclosure provides P2X3 and/or P2X2/3 antagonists which are useful, for example, for the treatment of visceral organ, cardiovascular and pain-related diseases, conditions and disorders.
Divergent Total Syntheses of Flavonoid Natural Products Isolated from Rosa rugosa and Citrus unshiu
Sum, Tze Jing,Sum, Tze Han,Galloway, Warren R. J. D.,Spring, David R.
supporting information, p. 1725 - 1727 (2016/07/06)
The concise and step-economical total syntheses of three hydroxyaurones and one polymethoxyflavone from readily available starting materials is described. A divergent synthetic strategy is employed, which centres on a common chalcone scaffold from which both the aurone and flavone frameworks can be accessed through the use of different oxidative cyclisation methods. These are the first reported total syntheses of these biologically interesting compounds.
ANALOGS OF VINAXANTHONE AND XANTHOFULVIN, METHODS OF SYNTHESIS, AND METHODS OF TREATMENTS THEREOF
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Page/Page column 74, (2015/02/25)
The present invention relates generally to methods of synthesis of vinaxanthone and xanthofulvin, novel analogs, and methods of use thereof.
Synthesis and highly potent hypolipidemic activity of alpha-asarone- and fibrate-based 2-acyl and 2-alkyl phenols as HMG-CoA reductase inhibitors
Mendieta, Aarn,Jimnez, Fabiola,Garduo-Siciliano, Leticia,Mojica-Villegas, Anglica,Rosales-Acosta, Blanca,Villa-Tanaca, Lourdes,Chamorro-Cevallos, Germn,Medina-Franco, Jos L.,Meurice, Nathalie,Gutirrez, Rsuini U.,Montiel, Luisa E.,Cruz, Mara Del Carmen,Tamariz, Joaqun
, p. 5871 - 5882 (2015/01/08)
In the search for new potential hypolipidemic agents, the present study focused on the synthesis of 2-acyl phenols (6a-c and 7a-c) and their saturated side-chain alkyl phenols (4a-c and 5a-c), and on the evaluation of their hypolipidemic activity using a
Synthesis and agonistic activity at the GPR35 of 5,6-dihydroxyindole-2- carboxylic acid analogues
Deng, Huayun,Fang, Ye
scheme or table, p. 550 - 554 (2012/09/05)
5,6-Dihydroxyindole-2-carboxylic acid (DHICA), an intermediate of melanin synthesis and an eumelanin building block, was recently discovered to be a GPR35 agonist with moderate potency. Here, we report the synthesis and pharmacological characterization of a series of DHICA analogues against GPR35 using both label-free dynamic mass redistribution and Tango β-arrestin translocation assays. This led to identification of novel GPR35 agonists with improved potency and/or having biased agonism.
Inhibitors for expression of IgE receptor on human mast cell from Puerariae Flos
Tamura, Satoru,Yoshihira, Kunichika,Tokumaru, Mariko,Zisheng, Xu,Murakami, Nobutoshi
scheme or table, p. 3872 - 3875 (2010/08/19)
Bioassay-guided separation of the extract of the medicinal plant, Puerariae Flos, disclosed the two isoflavones tectorigenin (1) and genistein (2) as the inhibitors for expression of IgE receptor (FcRI), the key molecule triggering the allergic reactions, on human mast cells. As a result of analysis of structure-activity relationship of the naturally occurring and synthesized isoflavones, 7-O-methyl glycitein (11) was disclosed as the more potent inhibitor than tectorigenin (1). These isoflavone ingredients suppressed expression of FcRI more potently than the active flavonoids found previously. In addition, tectorigenin (1) was clarified to particularly reduce generation of γ-chain subunit to suppress expression of FcRI among the three subunits.
Synthesis and biological evaluation of coumarin-based inhibitors of NAD(P)H: Quinone oxidoreductase-1 (NQO1)
Nolan, Karen A.,Doncaster, Jeremy R.,Dunstan, Mark S.,Scott, Katherine A.,Frenkel, A. David,Siegel, David,Ross, David,Barnes, John,Levy, Colin,Leys, David,Whitehead, Roger C.,Stratford, Ian J.,Bryce, Richard A.
experimental part, p. 7142 - 7156 (2010/07/20)
The synthesis is reported here of two novel series of inhibitors of human NAD(P)H quinone oxidoreductase-1 (NQO1), an enzyme overexpressed in several types of tumor cell. The first series comprises substituted symmetric dicoumarol analogues; the second series contains hybrid compounds where one 4-hydroxycoumarin systemis replaced by a different aromatic moiety. Several compounds show equivalent or improved NQO1 inhibition over dicoumarol, both in the presence and in the absence of added protein. Further, correlation is demonstrated between the ability of these agents to inhibit NQO1 and computed binding affinity. We have solved the crystal structure of NQO1 complexed to a hybrid compound and find good agreement with the in silico model. For both MIA PaCa-2 pancreatic tumor cells and HCT116 colon cancer cells, dicoumarol shows the greatest toxicity of all compounds. Thus, we provide a computational, synthetic, and biological platform to generate competitive NQO1 inhibitors with superior pharmacological properties to dicoumarol. This will allow a more definitive study of NQO1 activity in cells, in particular, its drug activating/detoxifying properties and ability to modulate oncoprotein stability. 2009 American Chemical Society.
Design, synthesis and evaluation of flavonoid derivatives as potent AChE inhibitors
Sheng, Rong,Lin, Xiao,Zhang, Jing,Chol, Kim Sun,Huang, Wenhai,Yang, Bo,He, Qiaojun,Hu, Yongzhou
experimental part, p. 6692 - 6698 (2010/01/06)
A new series of flavonoid derivatives have been designed, synthesized and evaluated as potent AChE inhibitors. Most of them showed more potent inhibitory activities to AChE than rivastigmine. The most potent inhibitor isoflavone derivative 10d inhibit ACh
