- Discovery of SARS-CoV-2 main protease inhibitors using a synthesis-directed: De novo design model
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The SARS-CoV-2 main viral protease (Mpro) is an attractive target for antivirals given its distinctiveness from host proteases, essentiality in the viral life cycle and conservation across coronaviridae. We launched the COVID Moonshot initiative to rapidly develop patent-free antivirals with open science and open data. Here we report the use of machine learning for de novo design, coupled with synthesis route prediction, in our campaign. We discover novel chemical scaffolds active in biochemical and live virus assays, synthesized with model generated routes. This journal is
- Morris, Aaron,McCorkindale, William,Drayman, Nir,Chodera, John D.,Tay, Sava?,London, Nir,Lee, Alpha A.
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p. 5909 - 5912
(2021/06/27)
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- Syntheses of novel 2-oxo-1,2-dihydroquinoline derivatives: Molecular and crystal structures, spectroscopic characterizations, Hirshfeld surface analyses, molecular docking studies and density functional theory calculations
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Sixteen new quinoline derivatives (3–18) have been synthesized through cyclocondensation, nucleophilic substitution and alkylation reactions. All the obtained compounds have been characterized using 1H-, 13C and 19F NMR spectroscopic measurements. The molecular and crystal structures of four of these compounds (10, 11, 15 and 18) have also been further examined by single crystal X-ray crystallography. The predicted spectral data were also obtained and compared to the experimental results using density functional theory (DFT). in order to understand the non-bonding intermolecular interactions in solid phase crystal packing. The closest contacts between active atoms of the four studied molecules were identified through both 2D and 3D Hirshfeld surface analyses. The different structures of the four compounds are optimized and their both energies highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO), as well as their clouds are evaluated. The obtained experimental results are correlated to the calculated ones and showed great compatibility. Finally, molecular docking studies are performed to investigate the binding patterns of the title compounds with the Protein Data Bank (PDB: 1M17) inhibitor targets and showed good insights on the possible interactions using the Auto-Dock Vina program.
- Baba, Yassir Filali,Boukir, Abdellatif,Chahdi, Fouad Ouazzani,Essassi, El Mokhtar,G?kce, Halil,H?kelek, Tuncer,Hayani, Sonia,Jasinski, Jerry P.,Kaur, Manpreet,Rodi, Youssef Kandri,Sebbar, Nada Kheira
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- Discovery, synthesis and molecular substantiation of N-(benzo[d]thiazol-2-yl)-2-hydroxyquinoline-4-carboxamides as anticancer agents
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The effort was taken to develop a series of benzothiazole and quinoline fused bioactive compounds obtained through a four-step synthetic route using a range of substituted acetoacetanilides. Achieved N-(benzo[d]thiazol-2-yl)-2-hydroxyquinoline-4-carboxamides (6a-l) were produced up to 96% of yield while the eco-friendly p-TSA used as a catalyst. Further, the anticancer activity of these compounds was determined using a range of cancer cell lines starting from MCF-7 (Breast cancer), HCT-116 (Colon cancer), PC-3 & LNCaP (Prostate) and SK-HEP-1 (Liver cancer). Present study compounds were also testified for antioxidant properties prior to anticancer studies since the Reactive Oxygen Species (ROS) being vital in cancer development. To determine the cell membrane stability effects of the compounds, human red blood cells (HRBC) based membrane protection assay was determined. In the results, compounds 6a-l were able to produce a dominated result values over PC3 cell lines (Prostate cancer) than the other cell lines used in this study. Since the connectivity of human germ cell alkaline phosphatase (hGC-ALP) in the development of prostate cancer is known, the most active compounds were evaluated for the hGC-ALP inhibition in order to ensure a mechanism of anticancer action of these compounds. The mode of interaction and binding affinity of these compounds was also investigated by a molecular docking study. In the results, 6d, 6i, 6k, and 6l were found with least IC50 values 0.075 μM and highest relative activity of 92%, 90%, and 96% respectively. The need for further animal model evaluation and pre-clinical studies recognized.
- Bindu,Vijayalakshmi,Manikandan
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- nitrogen-containing polycyclic compound and an organic electroluminescent device including the same
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Disclosed are a nitrogen-containing polycyclic compound and an organic electroluminescent device including the same.
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Paragraph 0270; 0271
(2016/10/09)
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- Scouting human A3 adenosine receptor antagonist binding mode using a molecular simplification approach: From triazoloquinoxaline to a pyrimidine skeleton as a key study
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The concept of molecular simplification as a drug design strategy to shorten synthetic routes, while keeping or enhancing the biological activity of the lead drug, has been applied to design new classes of human A3 adenosine receptor (AR) antag
- Morizzo, Erika,Capelli, Francesca,Lenzi, Ombretta,Catarzi, Daniela,Varano, Flavia,Filacchioni, Guido,Vincenzi, Fabrizio,Varani, Katia,Borea, Pier Andrea,Colotta, Vittoria,Moro, Stefano
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p. 6596 - 6606
(2008/09/16)
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- Use of imidazo?1,5-a!quinolones as neuroprotective agents
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The imidazo?1,5-a!quinolines (I) are useful in treating neurological diseases/conditions or chronic neurodegenerative diseases/conditions.
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- Imidazo[1,5-A]quinolines for treatment of anxiety and sleep disorders
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Imidazo[1,5-a]quinolines of formula (I) which are useful pharmaceutical agents for the treatment of anxiety, sleep disorders, panic states, convulsions and muscle disorders. STR1
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- 5-HT3 Receptor Antagonists. 1. New Quinoline Derivatives
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A series of esters and amides of 1-alkyl-2-oxo-1,2-dihydroquinoline-4-carboxylic acid or 2-alkoxyquinoline-4-carboxylic acid containing a basic azabicycloalkyl moiety has been synthesized and evaluated for affinity for the 3H>quipazine-labeled
- Hayashi, Hiroaki,Miwa, Yoshikazu,Miki, Ichiro,Ichikawa, Shunji,Yoda, Noboyuki,et al.
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p. 4893 - 4902
(2007/10/02)
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