84228-44-4Relevant articles and documents
HALOALLYLAMINE PYRAZOLE DERIVATIVE INHIBITORS OF LYSYL OXIDASES AND USES THEREOF
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Paragraph 0337, (2018/09/20)
The present invention relates to novel compounds which are capable of inhibiting certain amine oxidase enzymes. These compounds are useful for treatment of a variety of indications, e.g., fibrosis, cancer and/or angiogenesis in human subjects as well as i
Structure-Guided Synthesis and Mechanistic Studies Reveal Sweetspots on Naphthyl Salicyl Hydrazone Scaffold as Non-Nucleosidic Competitive, Reversible Inhibitors of Human Ribonucleotide Reductase
Huff, Sarah E.,Mohammed, Faiz Ahmad,Yang, Mu,Agrawal, Prashansa,Pink, John,Harris, Michael E.,Dealwis, Chris G.,Viswanathan, Rajesh
supporting information, p. 666 - 680 (2018/02/16)
Ribonucleotide reductase (RR), an established cancer target, is usually inhibited by antimetabolites, which display multiple cross-reactive effects. Recently, we discovered a naphthyl salicyl acyl hydrazone-based inhibitor (NSAH or E-3a) of human RR (hRR) binding at the catalytic site (C-site) and inhibiting hRR reversibly. We herein report the synthesis and biochemical characterization of 25 distinct analogs. We designed each analog through docking to the C-site of hRR based on our 2.7 ? X-ray crystal structure (PDB ID: 5TUS). Broad tolerance to minor structural variations preserving inhibitory potency is observed. E-3f (82% yield) displayed an in vitro IC50 of 5.3 ± 1.8 μM against hRR, making it the most potent in this series. Kinetic assays reveal that E-3a, E-3c, E-3t, and E-3w bind and inhibit hRR through a reversible and competitive mode. Target selectivity toward the R1 subunit of hRR is established, providing a novel way of inhibition of this crucial enzyme.
SELECTIVE CYSTEINE PROTEASE INHIBITORS AND USES THEREOF
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Paragraph 0262; 0263, (2018/03/25)
The present invention relates to compounds of Formula I, II, IA-VA, IVA1-IVA5, IIIA1-IIIA5 and their pharmaceutical uses. Particular aspects of the invention relate to the use of those compounds for the selective inhibition of one or more cysteine proteas
Copper-Mediated monochlorination of anilines and nitrogen-containing heterocycles
Yang, Xue-Yan,Zhao, Hong-Yi,Mao, Shuai,Zhang, San-Qi
supporting information, p. 2708 - 2714 (2018/10/15)
A simple and selective copper(II) chloride-mediated monochlorination of anilines and nitrogen-containing heterocycles has been developed. Stirring a mixture of aniline, copper(II) chloride, lithium chloride in EtOH under reflux condition produced 4-chloroaniline with high yield. Eighteen substrates including substituted anilines, N-substituted anilines, N,N-disubstituted anilines, 5-nitroindole and carbazole were all reactive and afforded desired products in moderate to excellent yields (52%–98%).
2-Trifluoromethyl-2-Hydroxypropionamide Derivatives as Novel Reversal Agents of ABCG2 (BCRP)-Mediated Multidrug Resistance: Synthesis and Biological Evaluations
Kathawala, Rishil J.,Li, Tianwen,Yang, Danwen,Guo, Hui-Qin,Yang, Dong-Hua,Chen, Xiang,Cheng, Changmei,Chen, Zhe-Sheng
, p. 2420 - 2429 (2017/06/13)
It has been postulated that one of the biggest impediments to a successful chemotherapy is the phenomena of multidrug resistance (MDR) in cancer cells. One of the main mechanisms of MDR is overexpression of the ATP-binding cassette (ABC) transporters in c
NOVEL 3,3-DIMETHYL TETRAHYDROQUINOLINE DERIVATIVES
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Page/Page column 203, (2011/11/01)
A compound of formula (I) as well as pharmaceutically acceptable salt thereof, wherein R1 to R5 have the significance given in claim 1, can be used as a medicament.
NOVEL 3,3-DIMETHYL TETRAHYDROQUINOLINE DERIVATIVES
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Page/Page column 75, (2011/10/31)
A compound of formula (I) as well as pharmaceutically acceptable salt thereof, wherein R1 to R5 have the significance given in claim 1, can be used as a medicament.
Synthesis and biological evaluation of novel prodrugs of anthracyclines for selective activation by the tumor-associated protease plasmin
De Groot, Franciscus M. H.,De Bart, Anton C. W.,Verheijen, Jan H.,Scheeren, Hans W.
, p. 5277 - 5283 (2007/10/03)
New prodrugs of daunorubicin and doxorubicin designed for selective activation by the serine protease plasmin are described. The low toxic prodrugs 3, 4, and 5 are converted to the corresponding cytotoxic drugs upon proteolysis by the tumor-associated protease plasmin. Application of a self- eliminating spacer was essential for enzyme activation. A prodrug containing a chloro-substituted spacer was synthesized with the aim of enhancing the rate of conversion by plasmin. All prodrugs were highly stable in buffer solution and in serum and on the average 15-fold less cytotoxic than the parent drugs in seven human tumor cell lines. A marked in vitro selectivity was demonstrated by incubation of the doxorubicin prodrugs with a plasmin generating MCF-7 breast cancer cell line transfected with urokinase-type plasminogen activator (u-PA) in comparison with the nontransfected nonplasmin generating cell line. Prodrugs 4 and 5 showed the same cytotoxic effect as the free parent drug doxorubicin in the u-PA transfected cells, indicating complete conversion of the prodrug by plasmin. Addition of the plasmin inhibitor Trasylol drastically increased the ID50 values in the u-PA transfected MCF-7 cells for both prodrugs 4 and 5.
Practical and efficient chlorination of deactivated anilines and anilides with NCS in 2-propanol
Zanka, Atsuhiko,Kubota, Ariyoshi
, p. 1984 - 1986 (2007/10/03)
Deactivated anilines and anilides were efficiently monochlorinated with NCS in 2-propanol. The described method was applicable to a large scale synthesis.
