39067-28-2Relevant academic research and scientific papers
Discovery of Novel Aryl Carboxamide Derivatives as Hypoxia-Inducible Factor 1α Signaling Inhibitors with Potent Activities of Anticancer Metastasis
Liu, Mingming,Liang, Yuru,Zhu, Zhongzhen,Wang, Jin,Cheng, Xingxing,Cheng, Jiayi,Xu, Binpeng,Li, Rong,Liu, Xinhua,Wang, Yang
supporting information, p. 9299 - 9314 (2019/10/16)
In order to discover novel hypoxia-inducible factor 1 (HIF-1) inhibitors for the cancer metastasis treatment, 68 new aryl carboxamide compounds were synthesized and evaluated for their inhibitory effect by dual luciferase-reporter assay. Based on five rounds of investigation on structure-activity relationships step by step, compound 30m was discovered as the most active inhibitor (IC50 = 0.32 μM) with no obvious cytotoxicity (CC50 > 50 μM). It effectively attenuated hypoxia-induced HIF-1α protein accumulation and reduced transcription of vascular epidermal growth factor in a dose-dependent manner, which was further demonstrated by its inhibitory potency on capillary-like tube formation, angiogenesis of zebrafish as well as cellular migration and invasion. Importantly, compound 30m exhibited antimetastatic potency in breast cancer lung metastasis in the mice model, indicating its promising therapeutic potential for prevention and treatment of tumor metastasis. These results definitely merit attention for further rational design of more efficient HIF-1 inhibitors in the future.
OXAZEPINONE DERIVATIVE, AGRICULTURAL AND HORTICULTURAL INSECTICIDE CONTAINING THE DERIVATIVE, AND APPLICATION METHOD THEREOF
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Paragraph 0127, (2017/10/25)
PROBLEM TO BE SOLVED: To develop a novel agricultural and horticultural insecticide for overcoming factor of generation of insect pests having resistance to existing agents because damages caused by insect pests are still large in crop production such as
Process for the preparation of thiazole derivatives
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Paragraph 0227-0228, (2015/11/09)
This document discloses a process for the preparation of a synthetic intermediate in the synthesis of molecules having the following formula (I):
2-pyridyl P1'-substituted symmetry-based human immunodeficiency virus protease inhibitors (A-792611 and A-790742) with potential for convenient dosing and reduced side effects
DeGoey, David A.,Grampovnik, David J.,Flentge, Charles A.,Flosi, William J.,Chen,Yeung, Clinton M.,Randolph, John T.,Klein, Larry L.,Dekhtyar, Tatyana,Colletti, Lynn,Marsh, Kennan C.,Stoll, Vincent,Mamo, Mulugeta,Morfitt, David C.,Nguyen, Bach,Schmidt, James M.,Swanson, Sue J.,Mo, Hongmei,Kati, Warren M.,Molla, Akhteruzzaman,Kempf, Dale J.
experimental part, p. 2571 - 2586 (2010/02/28)
A series of symmetry-based HIV protease inhibitors was designed and synthesized. Modification of the core regiochemistry and stereochemistry significantly affected the potency, metabolic stability, and oral bioavailability of the inhibitors, as did the variation of a pendent arylmethyl P3 group. Optimization led to the selection of two compounds, 10c (A-790742) and 9d (A-792611), for advancement to preclinical studies. Both compounds displayed low nanomolar potency against wild type HIV in the presence of human serum, low rates of metabolism in human liver microsomes, and high oral bioavailability in animal models. The compounds were examined in a preclinical model for the hyperbilirubinemia observed with some HIV PIs, and both exhibited less bilirubin elevation than comparator compounds. X-ray crystallographic analyses of the new cores were used to examine differences in their binding modes. The antiviral activity of the compounds against protease inhibitor resistant strains of HIV was also determined.
PYRIDINE THIAZOLE CARBOXAMIDE DERIVATIVES, THE PREPARATION METHOD THEREOF, AND THE COMPOSITION FOR SKIN WHITENING CONTAINING THE SAME
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Page/Page column 11, (2010/11/27)
Disclosed are a pyridine thiazole carboxamide derivative expressed by a following chemistry figure 1 or pharmaceutically acceptable salt thereof, a method for preparing the same and a composition for suppressing c-kit activation or composition for skin wh
HIV protease inhibiting compounds
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Page/Page column 107, (2010/02/12)
A compound of the formula is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.
