- Novel BuChE-IDO1 inhibitors from sertaconazole: Virtual screening, chemical optimization and molecular modeling studies
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In our effort towards the identification of novel BuChE-IDO1 dual-targeted inhibitor for the treatment of Alzheimer's disease (AD), sertaconazole was identified through a combination of structure-based virtual screening followed by MM-GBSA rescoring. Preliminary chemical optimization was performed to develop more potent and selective sertaconazole analogues. In consideration of the selectivity and the inhibitory activity against target proteins, compounds 5c and 5d were selected for the next study. Further modification of compound 5c led to the generation of compound 10g with notably improved selectivity towards BuChE versus AChE. The present study provided us with a good starting point to further design potent and selective BuChE-IDO1 inhibitors, which may benefit the treatment of late stage AD.
- Zhou, You,Lu, Xin,Du, Chenxi,Liu, Yijun,Wang, Yifan,Hong, Kwon Ho,Chen, Yao,Sun, Haopeng
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- BuChE-IDO1 inhibitor as well as preparation method and application thereof
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The invention relates to the field of medicines, and particularly discloses a BuChE-IDO1 inhibitor as well as a preparation method and application thereof. The 7-chlorine-3-substituted benzothiophene part of sertaconazole is chemically modified, the influence of the 7-chlorine-3-substituted benzothiophene part of sertaconazole on the in-vitro inhibitory activity of AChE, BuChE and IDO1 is explored, the target compound is further optimized, and the technical problems that an existing BuChE-IDO1 inhibitor is poor in pertinence and safety are solved. What is explored is that an appropriate substituent group introduced to a 2-benzothiazole ring can form additional interaction with surrounding amino acids and heme iron, so that the binding affinity of the analogue with BuChE and IDO1 is increased, and a new idea is broadened for more efficient and targeted treatment of advanced AD diseases.
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- Diaryl-containing imidazole compound and preparation method and medical application thereof
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The invention discloses a diaryl-containing imidazole compound. The invention further discloses application of the diaryl-containing imidazole compound to preparation of drugs for preventing or treating Alzheimer's disease. The inventor screens butyrylcholine esterase and IDO1 as carriers for inhibiting the activity to evaluate the effect of the diaryl imidazole compound to treat Alzheimer's disease, and finds that the diaryl imidazole compound has good in vitro activity, and can be further developed as a precursor substance for performing the Alzheimer's disease resistant effect by inhibitingthe activity of cholinesterase. (The formula is shown in the description).
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- Substituted imidazole-1-vinyl compound and use thereof
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The invention relates to a substituted imidazole-1-ethylene compound as well as a preparation and an application thereof. The substituted imidazole-1-ethylene compound is a compound shown as a formula I, or salts thereof formed with medicinal acids or bases. According to the antifungal activity test performed on eight clinical fungi by the compound provided in the invention, a good fungus killing effect is achieved. The compound can serve as a novel broad-spectrum antifungal activity compound and is developed into antifungal medicines, disinfectants or feed additives.
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Paragraph 0056; 0108-0111
(2016/10/27)
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- ACETYLENIC MICROBIOCIDES
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Compounds of formula (I), wherein the other substituents HetAr, A', R1, R2, R3, R4, R5, R6, R7, R8 and R9 are as defined in claim 1, and their use in compositions and methods for the control and/or prevention of microbial infection, particularly fungal infection, in plants and to processes for the preparation of these compounds.
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Page/Page column 29-30
(2013/10/21)
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- Imidazole incorporated semicarbazone derivatives as a new class of anticonvulsants: Design, synthesis and in-vivo screening
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A series of novel imidazole incorporated semicarbazones was synthesized using an appropriate synthetic route and characterized by spectral analysis (IR, 1H NMR, 13C NMR and Mass). The anticonvulsant activity of the synthesized compounds was determined using doses of 30, 100, and 300 mg kg-1 against maximal electroshock seizure (MES), subcutaneous pentylenetetrazole (scPTZ) induced seizure and minimal neurotoxicity test. Six compounds exhibited protection in both models and 2-(1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethylidene)-N-p- tolylsemicarbazone emerged as the most active compound of the series without any neurotoxicity and significant CNS depressant effect. Liver enzyme estimations (SGOT, SGPT, Alkaline phosphatase) of the compound also showed no significant change in the enzymes levels. Moreover, it caused 80% elevation of γ-amino butyric acid (GABA) levels in the whole mice brain, thus indicating that it could be a promising candidate in designing of a potent anticonvulsant drug.
- Amir, Mohammad,Ali, Israr,Hassan, Mohd. Zaheen
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p. 571 - 580
(2013/07/28)
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- 2-Aryl-3-(1H-azol-1-yl)-1H-indole derivatives: A new class of antimycobacterial compounds - Conventional heating in comparison with MW-assisted synthesis
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2-Aryl-3-(1H-imidazol-1-yl and 1H-1,2,4-triazol-1-yl)-1H-indole derivatives were synthesized and tested for their in-vitro antifungal and antimycobacterial activities. These indole derivatives were devoid of antifungal activity against the tested strains of Candida spp. Yet, they exhibited an interesting antitubercular activity against Mycobacterium tuberculosis reference strain H37Rv.
- Zampieri, Daniele,Mamolo, Maria Grazia,Laurini, Erik,Scialino, Giuditta,Banfi, Elena,Vio, Luciano
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scheme or table
p. 716 - 722
(2010/07/04)
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- Antifungal and antimycobacterial activity of 1-(3,5-diaryl-4,5-dihydro-1H-pyrazol-4-yl)-1H-imidazole derivatives
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1-(3,5-Diaryl-4,5-dihydro-1H-pyrazol-4-yl)-1H-imidazole derivatives were synthesized and tested for their in vitro antifungal and antimycobacterial activities. These imidazole derivatives showed an excellent antifungal activity against a clinical strain of Candida albicans and an interesting antitubercular activity againstMycobacterium tuberculosis H37Rv reference strain.
- Zampieri, Daniele,Mamolo, Maria Grazia,Laurini, Erik,Scialino, Giuditta,Banfi, Elena,Vio, Luciano
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p. 4516 - 4522
(2008/09/21)
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- Research on antibacterial and antifungal agents. X. Synthesis and antimicrobial activities of 1-phenyl-2-(1H-azol-1-yl) ethane derivatives. Anticonvulsant activity of 1-(4-methylphenyl)-2-(1H-imidazol-1-yl) ethanol.
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The synthesis and antimicrobial activity of new phenylazolylethane derivatives are reported.Antimicrobial data in comparison with those obtained with miconazole, fluconazole, enilconazole, imazalil sulfate, pipemidic acid and minocycline showed that tested compounds generally possessed poor or weak activity.Toxicity and anticonvulsant activity of 1-(4-methylphenyl)-2-(1H-imidazol-1-yl)ethanol and structural likeness to Denzimol were also tested.The obtained results showed interesting anticonvulsant activity but only on the supraspinal region. azoles / antifungal / anticonvulsant agent
- Porretta, G. C.,Fioravanti, R.,Biava, M.,Cirilli, R.,Simonetti, N.,et al.
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p. 749 - 760
(2007/10/02)
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- Synthesis and 13C NMR Spectra of cis- and trans-methyl>>-1,3-dioxolane-4-methanols
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Syntheses and 13C nmr spectra of a number of cis and trans 2-(haloaryl)-2--4-(hydroxymethyl)-1,3-dioxolanes are described.The haloaryl groups are 2,4-dichloro, 2,4-difluoro-, 4-chloro- and 4-bromophenyl.In these series, some of the cis compounds become available through crystalline bromo benzoates 5.Separations of some trans isomers are achieved through fractional crystallizations of imidazolyl benzoate nitrates 6.Stereochemical assignments are based primarily on one major 13C chemical shift difference, namely that of C-4 of the 1,3-dioxolane ring, the chemical shift of the trans isomers being 1.0-2.5 ppm downfield from that of the cis isomers.
- Chapman, David R.,Bauer, Ludwig
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p. 2053 - 2061
(2007/10/02)
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