118807-82-2Relevant academic research and scientific papers
X-ray Crystallography-Guided Design, Antitumor Efficacy, and QSAR Analysis of Metabolically Stable Cyclopenta-Pyrimidinyl Dihydroquinoxalinone as a Potent Tubulin Polymerization Inhibitor
Arnst, Kinsie E.,Banerjee, Souvik,Chen, Hao,Deng, Shanshan,Fakayode, Sayo O.,Li, Wei,Lukka, Pradeep B.,Ma, Lingling,Mahmud, Foyez,Meibohm, Bernd,Miller, Duane D.,Parmar, Keyur,Wang, Yuxi,White, Stephen W.,Wu, Zhongzhi,Yang, Lei,Yun, Mi-Kyung
, p. 13072 - 13095 (2021/09/07)
Small molecules that interact with the colchicine binding site in tubulin have demonstrated therapeutic efficacy in treating cancers. We report the design, syntheses, and antitumor efficacies of new analogues of pyridopyrimidine and hydroquinoxalinone compounds with improved drug-like characteristics. Eight analogues, 5j, 5k, 5l, 5m, 5n, 5r, 5t, and 5u, showed significant improvement in metabolic stability and demonstrated strong antiproliferative potency in a panel of human cancer cell lines, including melanoma, lung cancer, and breast cancer. We report crystal structures of tubulin in complex with five representative compounds, 5j, 5k, 5l, 5m, and 5t, providing direct confirmation for their binding to the colchicine site in tubulin. A quantitative structure-activity relationship analysis of the synthesized analogues showed strong ability to predict potency. In vivo, 5m (4 mg/kg) and 5t (5 mg/kg) significantly inhibited tumor growth as well as melanoma spontaneous metastasis into the lung and liver against a highly paclitaxel-resistant A375/TxR xenograft model.
TYPE II TOPOISOMERASE INHIBITORS AND METHODS OF MAKING AND USING THEREOF
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Page/Page column 38; 39, (2018/11/22)
Disclosed are Type II Topoisomerase Inhibitors, analogs thereof, pharmaceutical compositions thereof, and methods of making and using these compounds and compositions. Methods of using the disclosed compounds to treat infections, such as MRSA, MDR P. aeruginosa, and other pathogens are also described.
Synthesis of [18F]Fluoroarenes by Nucleophilic Radiofluorination of N-Arylsydnones
Narayanam, Maruthi Kumar,Ma, Gaoyuan,Champagne, Pier Alexandre,Houk, Kendall N.,Murphy, Jennifer M.
supporting information, p. 13006 - 13010 (2017/09/28)
A practical method for radiofluorination of anilines with [18F]fluoride via N-arylsydnone intermediates is described. These precursors are stable, easy to handle and facilitate direct and regioselective 18F-labeling to prepare [
INHIBITORS OF DNA GYRASE FOR THE TREATMENT OF BACTERIAL INFECTIONS
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Page/Page column 34-35, (2014/05/07)
The present invention relates to compounds which specifically inhibit bacterial DNA Gyrase and can be used for the treatment of respiratory tract infections.
Novel N-linked aminopiperidine inhibitors of bacterial topoisomerase type II: Broad-spectrum antibacterial agents with reduced hERG activity
Reck, Folkert,Alm, Richard,Brassil, Patrick,Newman, Joseph,Dejonge, Boudewijn,Eyermann, Charles J.,Breault, Gloria,Breen, John,Comita-Prevoir, Janelle,Cronin, Mark,Davis, Hajnalka,Ehmann, David,Galullo, Vincent,Geng, Bolin,Grebe, Tyler,Morningstar, Marshall,Walker, Phil,Hayter, Barry,Fisher, Stewart
experimental part, p. 7834 - 7847 (2012/01/06)
Novel non-fluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) are of interest for the development of new antibacterial agents that are not impacted by target-mediated cross-resistance with fluoroquinolones. Aminopiperidines that have a bicyclic aromatic moiety linked through a carbon to an ethyl bridge, such as 1, generally show potent broad-spectrum antibacterial activity, including quinolone-resistant isolates, but suffer from potent hERG inhibition (IC50= 3 M for 1). We now disclose the finding that new analogues of 1 with an N-linked cyclic amide moiety attached to the ethyl bridge, such as 24m, retain the broad-spectrum antibacterial activity of 1 but show significantly less hERG inhibition (IC 50= 31 M for 24m) and higher free fraction than 1. One optimized analogue, compound 24l, showed moderate clearance in the dog and promising efficacy against Staphylococcus aureus in a mouse thigh infection model.
SUBSTITUTED PIPERIDINE DERIVATIVES AND THEIR USE AS ANTIBATERIAL AGENTS
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Page/Page column 75, (2009/03/07)
The present invention relates to compounds of Formula (I):and pharmaceutically acceptable salts thereof, and to their use in the treatment of bacterial infections.
PIPERIDINES FOR THE TREATMENT OF BACTERIAL INFECTIONS
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Page/Page column 50, (2008/12/06)
The present invention relates to compounds of Formula (I), and pharmaceutically acceptable salts thereof, to their use in the treatment of bacterial infections, and to their methods preparation.
2-QUINOLINONE AND 2-QUINOXALINONE- DERIVATIVES AND THEIR USE AS ANTIBACTERIAL AGENTS
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Page/Page column 92-93, (2008/12/06)
The present invention relates to compounds of Formula (I) : and pharmaceutically acceptable salts thereof, to their use in the treatment of bacterial infections, and to their methods of preparation.
o-Nitroaniline Derivatives. Part 9. Benzimidazole N-Oxides Unsubstituted at N-1 and C-2
Harvey, Ian W.,McFarlane, Michael D.,Moody, David J.,Smith, David M.
, p. 681 - 690 (2007/10/02)
Since previous routes to the title compounds (1) have proved unsatisfactory as general methods, a simple new synthesis has been devised.N-Cyanomethyl-o-nitroanilines (5) are cyclised in basic media, giving 2-cyanobenzimidazole N-oxides (12) in good yield.Hydrolysis of these products with hydrochloric acid gives, directly, the title compounds as their hydrochloride salts (13), which may be isolated and purified, and which give the free N-oxides (1) by treatment with aqueous ammonia followed by evaporation. o-Nitrophenylglycine esters (4) may satisfactorily replace the nitriles (5) in certain cases.A modification of this kind in the related nitropyridylglycine series leads to 3H-imidazolpyridine 1-oxide (20).
