62290-40-8Relevant academic research and scientific papers
Synthesis and structure-activity relationship of new chalcone linked 5-phenyl-3-isoxazolecarboxylic acid methyl esters potentially active against drug resistant Mycobacterium tuberculosis
Sahoo, Santosh Kumar,Rani, Bandela,Gaikwad, Nikhil Baliram,Ahmad, Mohammad Naiyaz,Kaul, Grace,Shukla, Manjulika,Nanduri, Srinivas,Dasgupta, Arunava,Chopra, Sidharth,Yaddanapudi, Venkata Madhavi
supporting information, (2021/06/14)
In search of novel therapeutic agents active against emerging drug-resistant Mycobacterium tuberculosis and to counter the long treatment protocol of existing drugs, herein we present synthesis and biological evaluation of a new series of 5-phenyl-3-isoxazolecarboxylic acid methyl ester-chalcone hybrids. Among 35 synthesized compounds, 32 analogues displayed potent in-vitro activity against Mycobacterium tuberculosis H37Rv with MIC 0.12–16 μg/mL. Cell viability test against Vero cells indicated 29 compounds to be non-cytotoxic (CC50 > 20 μg/mL & SI > 10). Most potent compounds with MIC 0.12 μg/mL (7 b, 7j, 7 ab) exhibited selectivity index (SI) in excess of 320. Further studies on activity against drug-resistant Mycobacterium tuberculosis revealed 7j as the most potent compound with MIC 0.03–0.5 μg/mL. Time-kill kinetic study suggested compound 7j displaying concentration-dependent bactericidal killing activity with relatively comparable potency to that of current first-line anti-TB drugs. Taken together, 7j presents a novel hit with potential to be translated into a potent antimycobacterial.
Discovery of benzamide-hydroxypyridinone hybrids as potent multi-targeting agents for the treatment of Alzheimer's disease
Bai, Renren,Gu, Jinping,Guo, Jianan,Jiang, Xiaoying,Xie, Yuanyuan,Zhang, Changjun,Zhou, Tao
, p. 2045 - 2054 (2021/10/08)
A novel class of benzamide-hydroxypyridinone (HPO) derivatives were innovatively designed, synthesised, and biologically evaluated as potential multitargeting candidates for the treatment of Alzheimer's disease (AD) through pharmacophores-merged approaches based on lead compounds 18d, benzyloxy phenyl analogs, and deferiprone (DFP). These hybrids possessed potent Monoamine oxidase B (MAO-B) inhibition as well as excellent iron chelation, with pFe3+ values ranging from 18.13 to 19.39. Among all the compounds, 8g exhibited the most potent selective MAO-B inhibitor (IC50 = 68.4 nM, SI = 213). Moreover, 8g showed favourable pharmacokinetic properties and had great potential to penetrate the BBB in silico and PAMPA-BBB assay. Molecular modelling showed that 8g could adopt an extended conformation and have more enhanced interactions with MAO-B than 18d. In vitro and in vivo assays demonstrated that 8g remarkably resisted Aβ-induced oxidation and ameliorated cognitive impairment induced by scopolamine. Taken collectively, these results suggest that compound 8g is a potential multifunctional candidate for anti-AD treatment.
Formamide pyridone iron chelating agent derivative with potential multi-target anti-AD activity as well as preparation method and application thereof
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Paragraph 0176-0177; 0180, (2020/12/10)
The invention provides a formamide pyridone iron chelating agent derivative shown as a formula (I) or a formula (II) which is described in the specification and a preparation method and application thereof. The formamide pyridone iron chelating agent derivative shown in the formula (I) or the formula (II) and the pharmaceutically acceptable salt thereof have the effects of inhibiting monoamine oxidase, chelating metal iron ions, resisting A beta and resisting oxidation activity. The derivative can be used for preparing medicines for resisting Alzheimer's disease, Parkinson's disease or other diseases treated by inhibiting monoamine oxidase, chelating metal iron ions, resisting A beta and resisting oxidation.
A New Class of Dengue and West Nile Virus Protease Inhibitors with Submicromolar Activity in Reporter Gene DENV-2 Protease and Viral Replication Assays
Kühl, Nikos,Graf, Dominik,Bock, Josephine,Behnam, Mira A. M.,Leuthold, Mila-Mareen,Klein, Christian D.
supporting information, p. 8179 - 8197 (2020/09/21)
Dengue and West Nile virus are rapidly spreading global pathogens for which no specific therapeutic treatments are available. One of the promising targets for drug discovery against dengue and other flaviviruses is the viral serine protease NS2B-NS3. We present the design, synthesis, and in vitro and cellular characterization of a novel chemotype of potent small-molecule non-peptidic dengue protease inhibitors derived from 4-benzyloxyphenylglycine. A newly developed luciferase-based DENV-2 protease reporter system in HeLa cells (DENV2proHeLa) was employed to determine the activity of the compounds in a cellular environment. Specificity and selectivity of the DENV2proHeLa system were confirmed by viral titer reduction assays. The compounds reach low micromolar to upper nanomolar inhibitory potency in cell-based assays, are selective against other serine proteases, and do not show relevant cytotoxicity. An extensive structure-activity relationship study provides a perspective for further drug development against flaviviral infections.
Benzylamine derivatives
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, (2008/06/13)
A benzylamine derivative or salt thereof having antidepressant and antianxiety activities having the general formula: STR1 wherein R1 is a lower alkyl group; R2 is a cycloalkyl group; and R3 is a halogen atom; or salt ther
