- Quinoline-4-carboxamide skeleton derivative and application thereof
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The invention discloses a quinoline-4-formamide skeleton derivative and application thereof, belonging to the field of chemical medicines. The invention provides a compound as shown in a formula I or pharmaceutically acceptable salt thereof. The invention
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Paragraph 0048-0051; 0068-0071
(2021/06/09)
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- 2-furanyl-quinoline-4-formamide compound and application thereof
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The invention discloses a 2-furanyl-quinoline-4-formamide compound and application thereof, and the structural formula of the 2-furanyl-quinoline-4-formamide compound is shown as a formula (4) in thespecification, wherein R1 is selected from H, halogen or
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Paragraph 0018-0020; 0033-0035
(2021/02/06)
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- Discovery of Potent Small-Molecule SIRT6 Activators: Structure-Activity Relationship and Anti-Pancreatic Ductal Adenocarcinoma Activity
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SIRT6 activation is thought to be a promising target for the treatment of many diseases, particularly cancer. Herein, we report the discovery of a series of new small-molecule SIRT6 activators. Structure-activity relationship analyses led to the identific
- Chen, Xiuli,Sun, Weining,Huang, Shenzhen,Zhang, Hailin,Lin, Guifeng,Li, Hui,Qiao, Jingxin,Li, Linli,Yang, Shengyong
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p. 10474 - 10495
(2020/11/02)
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- Development of broad-spectrum enterovirus antivirals based on quinoline scaffold
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Non-polio enteroviruses such as enterovirus A71 (EV-A71), EV-D68, and coxsackievirus B3 (CVB3) are significant human pathogens with disease manifestations ranging from mild flu-like symptoms to more severe encephalitis, myocarditis, acute flaccid paralysis/myelitis, and even death. There is currently no effective antivirals to prevent or treat non-polio enterovirus infection. In this study, we report our progress in developing potent and broad-spectrum antivirals against these non-polio enteroviruses. Starting from our previously developed lead compounds that had potent antiviral activity against EV-D68, we synthesized 43 analogs and profiled their broad-spectrum antiviral activity against additional EV-D68, EV-A71, and CVB3 viruses. Promising candidates were also selected for mouse microsomal stability test to prioritize lead compounds for future in vivo mouse model studies. Collectively, this multi-parameter optimization process revealed a promising lead compound 6aw that showed single-digit to submicromolar EC50 values against two EV-D68 strains (US/KY and US/MO), two EV-A71 strains (Tainan and US/AK), and one CVB3 strain, with a high selectivity index. Encouragingly, 6aw was stable in mouse microsomes with a half-life of 114.7 min. Overall, 6aw represents one of the most potent broad-spectrum antiviral against non-polio enteroviruses, rendering it a promising lead candidate for non-polio enteroviruses with translational potential.
- Musharrafieh, Rami,Kitamura, Naoya,Hu, Yanmei,Wang, Jun
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supporting information
(2020/06/22)
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- CHROMOBOX PROTEIN INHIBITORS AND USES THEREOF
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Provided herein are compounds useful as inhibitors of CBX. Also described are pharmaceutical compositions and medical uses of these compounds.
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Page/Page column 64-65
(2018/04/20)
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- Synthesis and structure-activity relationship of disubstituted benzamides as a novel class of antimalarial agents
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Malaria is a devastating world health problem. Using a compound library screening approach, we identified a novel series of disubstituted benzamide compounds with significant activity against malaria strains 3D7 and K1. These compounds represent a new antimalarial molecular scaffold exemplified by compound 1, which demonstrated EC50 values of 60 and 430 nM against strains 3D7 and K1, respectively. Herein we report our findings on the efficient synthesis, structure-activity relationships, and biological activity of this new class of antimalarial agents.
- Mitachi, Katsuhiko,Salinas, Yandira G.,Connelly, Michele,Jensen, Nicholas,Ling, Taotao,Rivas, Fatima
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experimental part
p. 4536 - 4539
(2012/08/07)
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- Synthesis, characterization and antibacterial activities of some N-bridged heterocycles containing triazole, quinoline and nitrofuran moieties
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A series of 2-(2-furyl)4-quinolinecarboxylic acids (3), 2-(5-nitro-2-furyl)4-quinolinecarboxylic acids (6), 4-(3-aryloxymethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazolo-6-yl)-2- (furyl)quinolines (5) and 4-(3-aryloxymethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazolo-6-yl)-2- (5-nitro-2-furyl)quinolines (7) were synthesized. The structures of the newly synthesized compounds are confirmed on the basis of elemental analysis, IR, 1H-NMR and mass spectral data. The newly synthesized compounds are evaluated for their antibacterial activities. Compounds containing nitrofuran moiety showed excellent antibacterial activity. Results of such studies are disscussed in this paper.
- Holla, B. Shivarama,Shridhara,Rao, B. Sooryanarayana,Poojary, K. Narayana
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p. 105 - 109
(2007/10/03)
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- A series of quinoline analogues as potent inhibitors of C. albicans prolyl tRNA synthetase
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A series of quinoline inhibitors of C. albicans prolyl tRNA synthetase was identified. The most potent analogue, 2-(4bromo-phenyl)-6-chloro-8-methyl-4-quinolinecarboxylic acid, showed IC50=5 nM (Ca. ProRS) with high selectivity over the human enzyme.
- Yu, Xiang Y.,Hill, Jason M.,Yu, Guixue,Yang, Yifeng,Kluge, Arthur F.,Keith, Dennis,Finn, John,Gallant, Paul,Silverman, Jared,Lim, Audrey
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p. 541 - 544
(2007/10/03)
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- Discovery of a novel class of selective non-peptide antagonists for the human neurokinin-3 receptor. 1. Identification of the 4-quinolinecarboxamide framework
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A novel class of potent and selective non-peptide neurokinin-3 (NK-3) receptor antagonists, featuring the 4-quinolinecarboxamide framework, has been designed based upon chemically diverse NK-1 receptor antagonists. The novel compounds 33-76, prompted by chemical modifications of the prototype 4, have been characterized by binding analysis using a membrane preparation of chinese hamster ovary (CHO) cells expressing the human neurokinin-3 receptors (hNK-3-CHO), and clear structure-activity relationships (SARs) have been established. From SARs, (R)-N-[α-(methoxycarbonyl)benzyl]-2- phenylquinoline-4-carboxamide (65, SB 218795, hNK-3-CHO binding K(i) = 13 nM) emerged as one of the most potent compounds of this novel class. Selectivity studies versus the other neurokinin receptors (hNK-2-CHO and hNK-1-CHO) revealed that 65 is about 90-fold selective for hNK-3 versus hNK-2 receptors (hNK-2-CHO binding K(i) = 1221 nM) and over 7000-fold selective versus hNK-1 receptors (hNK-1-CHO binding K(i) = >100 μM). In vitro functional studies in rabbit isolated iris sphincter muscle preparation demonstrated that 65 is a competitive antagonist of the contractile response induced by the potent and selective NK-3 receptor agonist senktide with a K(b) = 43 nM. Overall, the data indicate that 65 is a potent and selective hNK-3 receptor antagonist and a useful lead for further chemical optimization.
- Giardina, Giuseppe A. M.,Sarau, Henry M.,Farina, Carlo,Medhurst, Andrew D.,Grugni, Mario,Raveglia, Luca F.,Schmidt, Dulcie B.,Rigolio, Roberto,Luttmann, Mark,Vecchietti, Vittorio,Hay, Douglas W. P.
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p. 1794 - 1807
(2007/10/03)
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