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Compounds of a compound of compound of general formula (I) wherein X1, X2, A, R1R2, R3 and R4 are as defined herein; are useful as anti-mycobacterial agents, especially agents for the treatment of tuberculosis.

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The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain amino-ethyl-amino-aryl (AEAA) compounds which, inter alia, inhibit protein kinase D (PKD) (e.g., PKD1, PKD2, PKD3). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PKD, and in the treatment of diseases and conditions that are mediated by PKD, that are ameliorated by the inhibition of PKD, etc., including proliferative conditions such as cancer, etc.

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Screening of the Roche compound library led to the identification of 4-aminoquinoline 4 as structurally novel NR1/2B subtype selective NMDA receptor antagonist. The SAR which was developed in this series resulted in the discovery of highly potent and in vivo active blockers.

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The reaction of various substituted 2, 4-dichloroquinolines with ethyl 4-(3-hydroxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate was carried out in the presence of K2CO3 as a mild and efficient base at controlled temperature leading to novel 2-chloroquinoline based polyhydroquinoline with high regioselectivity. All the synthesized compounds were characterized using IR, NMR, Mass spectral data and then subjected to an in-silico analysis against P. falciparum lactate dehydrogenase.

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A series of novel 4-anilinoquinoline derivatives were synthesized and evaluated for their antiproliferative activities. Among them, 14h exhibited the most potent cytotoxic activity with IC50 values ranging from 1.5 to 3.9 nM against all tested cancer cell lines, and showed promising efficacy in multidrug resistant cancer cells. Flow cytometry assay, immune-fluorescence staining, microtubule dynamics assays and competition assays with EBI identified that 14h was a novel tubulin depolymerization agent by binding to the colchicine site. Importantly, in vivo efficacy evaluation of HCT116 xenograft model, 14h showed efficient antitumor activity without significant loss in body weight. All the results indicated that 14h could be a promising candidate for the treatment of cancer.

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The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain amino-ethyl-amino-aryl (AEAA) compounds which, inter alia, inhibit protein kinase D (PKD) (e.g., PKD1, PKD2, PKD3). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PKD, and in the treatment of diseases and conditions that are mediated by PKD, that are ameliorated by the inhibition of PKD, etc., including proliferative conditions such as cancer, etc.

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Mass spectral fragmentation of quinoline alkaloids of significance in plants has been investigated using electrospray ionisation ion trap mass spectrometry (ESI-MSn) with a view to characterisation of molecules of unknown structure isolated from these natural sources. This investigation has led to the generation of an appropriate database incorporating data from ESI-MSn and also from gas liquid chromatography (GLC) and liquid chromatography (HPLC) for these low molecular mass quinolines. This has been put to practical application in the identification of quinoline alkaloids in a plant extract. Thus, an acid extraction of the leaves of Choisya ternata containing such tertiary alkaloids was analysed by liquid chromatography-electrospray ionisation mass spectrometry (HPLC-ESI-MS) and the resulting behaviour of the quinolines was compared with that of the quinoline alkaloids in the database.

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New Advances in Chemical Research, May 2021. Application In Synthesis of 4-(4-((2,4-Dioxothiazolidin-5-ylidene)methyl)-2-methoxyphenoxy)-3-(trifluoromethyl)benzonitrile, Having gained chemical understanding at molecular level, chemistry graduates may choose to apply this knowledge in almost unlimited ways, as it can be used to analyze all matter and therefore our entire environment. In a document type is Article, and a compound is mentioned, 1055361-35-7, 4-(4-((2,4-Dioxothiazolidin-5-ylidene)methyl)-2-methoxyphenoxy)-3-(trifluoromethyl)benzonitrile, introducing its new discovery.

A series of piperidine-based derivatives were identified as novel and potent inhibitors of the influenza virus through structural modification of a compound that was selected from a high-throughput screen. Various analogues were synthesized and confirmed as inhibitors. The structure-activity relationship (SAR) studies suggested that the ether linkage between the quinoline and piperidine is critical for the inhibitory activity. The optimized compound tert-butyl 4-(quinolin-4-yloxy)piperidine-1-carboxylate 11e had an excellent inhibitory activity against influenza virus infection from a variety of influenza virus strains, with EC50values as low as 0.05 muM. The selectivity index value (SI = MLD50/EC50) of 11e is over 160 000 based on cytotoxicity, measured by MTT assays of three cell lines. We carried out a time-of-addition experiment to delineate the mechanism of inhibition. The result indicates that 11e interferes with the early to middle stage of influenza virus replication.

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A novel method for the regioselective C2-chlorination of heterocyclic N-oxides has been developed. PPh3/Cl3CCN were used as chlorinating reagents and the desired N-heterocyclic chlorides were obtained smoothly in satisfactory yields. The reactions proceeded in a highly efficient and selective manner across a broad range of substrates demonstrating excellent functional group tolerance. In addition, this chlorination reaction can be used for the modification of N-heterocyclic scaffolds of appealing ligands and pharmaceuticals.

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Optimisation of the left-hand-side aryl moiety of a file compound screening hit against Staphylococcus aureus methionyl tRNA synthetase led to the identification of a series of potent nanomolar inhibitors. The best compounds showed excellent antibacterial activity against staphylococcal and enterococcal pathogens, including strains resistant to clinical antibiotics.

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