168253-03-0Relevant articles and documents
Design, molecular Docking, synthesis and evaluation of xanthoxylin hybrids as dual inhibitors of IL-6 and acetylcholinesterase for Alzheimer's disease
Bansal, Yogita,Kaur, Sukhvir
, (2022/02/22)
Interleukin-6 (IL-6) and acetylcholinesterase (AChE) are two important targets implicated in progression of Alzheimer's Disease (AD). Simultaneous inhibition of both IL-6 and AChE by a molecule presents an effective strategy for the treatment of AD. In this study, the pharmacophores for inhibition of IL-6 and AChE are identified, and coupled to design novel molecules capable of acting as dual inhibitors of IL-6 and AChE. Literature review reveals that xanthoxylin and a disubstituted or a carbamoyl amine are pharmacophore for IL-6 and AChE inhibition, respectively. Therefore, xanthoxylin is coupled with various disubstituted amines or carbamoyl amines through alkyl linkers of different lengths (1–4 carbon atoms) to design two series of 80 compounds. All designed compounds are docked in AChE. Based on their docking score, 15 compounds are selected for synthesis and evaluation of AChE inhibitory activity. The compounds showing > 45% inhibition of EeAChE are selected for evaluation of IL-6 and butyrylcholinesterase (BuChE) inhibitory activities. Compound Y13g is found to be the most potent inhibitor of EeAChE, BuChE and IL-6. It is further evaluated in vivo using STZ-induced amnesia model in mice at three doses (0.2, 0.4 and 0.8 mg/kg), wherein it shows dose-dependent effects. At 0.8 mg/kg, it reverses the STZ-induced memory deficit, and shows histopathology similarly as in normal animals. The findings suggest that compounds derived from coupling of xanthoxylin with piperazine through a 3-carbon chain provides a useful template for the development of new chemical entities effective against AD.
Dual inhibitors of Interleukin-6 and acetylcholinesterase for treatment of Alzheimer's disease: Design, docking, synthesis and biological evaluation
Bansal, Yogita,Kaur, Sukhvir
, (2021/11/13)
Multitarget compounds intercept two or more functionally complementary pathways simultaneously, and are therefore considered to have potential in effectively treating complex multifactorial diseases like Alzheimer's disease (AD). In the present study, novel molecules are designed by coupling a chromone and a N,N-disubstituted carbamoyl amine as pharmacophore for interleukin-6 (IL-6) and acetylcholinesterase (AChE) inhibition, respectively. Four series (Y1–Y4) of 40 compounds are designed by using alkyl linkers of different lengths (1–4 carbon atoms) for the coupling of the two selected pharmacophore. Docking of all designed compounds in AChE leads to the identification of twelve best fit compounds (Docking score >8.3). The data suggests that a 1- or 2-carbon atom linker is the most conducive to orient the pharmacophore for optimum binding with AChE active site. The predicted ADME properties of the 12 selected compounds suggest that these can cross the blood brain barrier (BBB) with good oral bioavailability. These compounds are synthesised and evaluated for anti-AChE activity. Five compounds, showing >45% inhibition of AChE, are further evaluated for IL-6 inhibitory activity. Compound Y1f is found to be the most potent inhibitor of both AChE and IL-6 (IC50 0.7 and 0.8 ?μM, respectively). It suggests that a chromone moiety connected to a piperidine ring through a 1-carbon atom linker may provide a useful template to medical chemists for the development of new chemical entities effective against AD.
BICYCLIC NITROGENATED HETEROCYCLIC COMPOUND
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Paragraph 1698, (2019/07/03)
The present invention provides: a novel use of a specific bicyclic nitrogen-containing heterocyclic compound as a PDE7 inhibitor; a novel bicyclic nitrogen-containing heterocyclic compound having a PDE7 inhibitory effect, a method for producing the compound, a use of the compound, and a pharmaceutical composition containing the PDE7 inhibitor or the compound; and others. More specifically, the present invention provides a PDE7 inhibitor containing the compound represented by the formula (I): [wherein the symbols have the same meanings as those described in the description] or a pharmaceutically acceptable salt thereof as an active ingredient.
Synthesis of 3- and 29-substituted celastrol derivatives and structure-activity relationship studies of their cytotoxic activities
Shan, Wei-Guang,Wang, Han-Guang,Chen, Yan,Wu, Rui,Wen, Yan-Tao,Zhang, Li-Wen,Ying, You-Min,Wang, Jian-Wei,Zhan, Zha-Jun
supporting information, p. 3450 - 3453 (2017/07/07)
A series of 3-carbamate and 29-ester celastrol derivatives (compounds 1–26) were designed and synthesized. These analogues were evaluated for their cytotoxic activities against several cancer cell lines. Cytotoxicity data revealed that the properties of substituents and substitution position had important influence on cytotoxic activity. Modification of C-3 hydroxyl with size-limited groups did not reduce the activity obviously. The introduction of polarity group like piperazine could improve the solubility. Compound 23 was chosen to further evaluate anti-tumor efficacy in vivo. It showed higher inhibition rate and better safety than celastrol during in vivo experiment by intragastric administration. The preliminary antitumor studies of compound 23 in vivo showed that it might be promising for the development of new antitumor agents.
DERIVATIVES OF [1, 2, 4] TRIAZOLO [4, 3 - A] PYRIDINE AS P38 - MAP KINASE INHIBITORS
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, (2016/10/10)
Mitogen activated protein kinase (MAPK) inhibitors disclosed herein are useful for the treatment of diseases of the respiratory tract, such as chronic eosinophilic pneumonia, asthma, COPD, adult respiratory distress syndrome (ARDS), exacerbation of airways hyper-reactivity consequent to other drug therapy, and airways disease that is associated with pulmonary hypertension.
KINASE INHIBITORS
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Paragraph 0433; 0434; 0435, (2015/01/06)
Compounds of formula (I) described herein are p38 MAPK inhibitors and are useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract
KINASE INHIBITORS
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Paragraph 0407; 0408, (2015/01/06)
Compounds of formula (I) described herein are p38 MAPK inhibitors and are useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract.
DERIVATIVES OF [1, 2, 4] TRIAZOLO [4, 3 - A] PYRIDINE AS P38 - MAP KINASE INHIBITORS
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Page/Page column 34, (2015/01/06)
This invention relates to compounds selected in the group consisting of compounds of formula (la) to (Id) and compositions, that are p38 MAPK inhibitors, useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract.
KINASE INHIBITORS
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Page/Page column 86, (2015/01/06)
This invention relates to compounds and compositions that are p38 MAPK inhibitors, useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract.
KINASE INHIBITORS
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Page/Page column 90; 91, (2015/01/06)
This invention relates to compounds and compositions that are p38 MAPK inhibitors, useful as anti-inflammatory agents in the treatment of, inter alia, diseases of the respiratory tract.
