216883-22-6Relevant academic research and scientific papers
Synthesis of 7-amino-6-halogeno-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides: A way forward for targeting hypoxia and drug resistance of cancer cells
Buravchenko, Galina I.,Dezhenkova, Lyubov G.,Monzote, Lianet,Scherbakov, Alexander M.,Shchekotikhin, Andrey E.
, p. 38782 - 38795 (2021/12/20)
To establish a new approach for the synthesis of quinoxaline 1,4-dioxides as hypoxia-selective cytotoxic agents, an original multi-step preparation of derivatives possessing the diamine moiety at position 7 was evaluated. Herein, we present the synthesis of a series of novel 7-amino-6-halogeno-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides 13a-h, 14a,b,g based on the regioselective Beirut reaction. Comparison of antitumor properties of derivatives possessing the diamine moiety at position 7 with structurally close congeners possessing the corresponding amino groups at position 6 revealed key differences in the cytotoxicity profiles and HIF-1α inhibition. All the synthesized 7-amino-6-halogeno derivatives 13a-h, 14a,b,g demonstrated significant cytotoxic activities against breast cancer cell lines (MCF7, MDA-MB-231) in normoxia and hypoxia with IC50 values ranging from 0.1 to 7.6 μM. Most of these novel derivatives can circumvent the multidrug resistance of tumor cells caused by P-glycoprotein over expression. The lead compounds 13a, 14a and 14b can suppress the expression of HIF-1α at low micromolar concentrations and induce apoptosis in breast cancer MCF7 cells. In addition, compound 14b effectively inhibits BCL2 and ERα expression in MCF7 cells. The current research opens a new direction for targeting hypoxia and drug resistance of cancer cells. This journal is
PYRAZOLYLBENZIMIDAZOLE DERIVATIVES, COMPOSITIONS CONTAINING THEM AND USE THEREOF
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Page/Page column 27, (2009/08/16)
The disclosure relates to compounds of formula (I): wherein R1, R2, R3, R4, and R5 are as defined in the disclosure, to the compositions containing them and to the use thereof as medicaments, in particular as anticancer agents. The disclosure also relates to the process for preparing the compounds of formula (I) and to reaction intermediates.
Identification of novel benzimidazole series of potent and selective ORL1 antagonists
Okamoto, Osamu,Kobayashi, Kensuke,Kawamoto, Hiroshi,Ito, Satoru,Satoh, Atsushi,Kato, Tetsuya,Yamamoto, Izumi,Mizutani, Sayaka,Hashimoto, Masaya,Shimizu, Atsushi,Sakoh, Hiroki,Nagatomi, Yasushi,Iwasawa, Yoshikazu,Takahashi, Hiroyuki,Ishii, Yasuyuki,Ozaki, Satoshi,Ohta, Hisashi
scheme or table, p. 3278 - 3281 (2009/04/05)
Structure-activity studies on benzimidazole lead 1 obtained from library screening led to the discovery of potent and selective ORL1 antagonist 28, 5-chloro-2-[(1-ethyl-1-methylpropyl)thio]-6-[4-(2-hydroxyethyl)piperazin-1-yl]-1H-benzimidazole, which is s
