189005-44-5Relevant articles and documents
A novel formulation of zolpidem for direct nose-to-brain delivery: synthesis, encapsulation and intranasal administration to mice
Borodina, Tatiana,Marchenko, Irina,Trushina, Daria,Volkova, Yulia,Shirinian, Valerii,Zavarzin, Igor,Kondrakhin, Evgeny,Kovalev, Georgy,Kovalchuk, Mikhail,Bukreeva, Tatiana
, p. 1164 - 1173 (2018)
Objectives: Anxiolytic drug zolpidem was incorporated into the microcontainers based on mesoporous calcium carbonate particles modified by diethylaminoethyl-dextran/hyaluronic acid shell. The release of zolpidem in saline solution and in polymer film modelling nasal mucosa was investigated. The anxiolytic effect of zolpidem upon intranasal administration of microcontainers and free medicine was determined by in?vivo experiments on mice. Methods: The structures of all compounds during zolpidem synthesis were established using nuclear magnetic resonance spectroscopy. The loading efficacy and release kinetics of zolpidem were analysed by spectrophotometry. Surface morphology of formulation was investigated by scanning electron microscopy. To determine the effect of zolpidem-loaded containers administration by the intranasal route in?vivo experiments was carried out applying the open field test. Key findings: Nasal administration of zolpidem in the form of the microcontainers based on mesoporous calcium carbonate particles modified by diethylaminoethyl-dextran/hyaluronic acid shell has a pronounced anxiolytic effect on the behaviour of the animals in the open field test. Conclusions: The polyelectrolyte shell deposited together with zolpidem enhances the loading efficacy of the microcontainers. In vivo experiments on mice demonstrate increase in anxiolytic effect of zolpidem in microcontainers compared with upon intranasal administration of free medicine.
Structure-based discovery of potent and selective small-molecule inhibitors targeting signal transducer and activator of transcription 3 (STAT3)
Huang, Qiuyao,Zhong, Yan,Li, Bingbing,Ouyang, Shumin,Deng, Lin,Mo, Jianshan,Shi, Shuo,Lv, Nan,Wu, Ruibo,Liu, Peiqing,Hu, Wenhao,Zhang, Xiaolei,Wang, Yuanxiang
, (2021/05/17)
STAT3 has been validated as an attractive anticancer target due to its important roles in cancer initiation and progression. However, discovery of potent and selective STAT3 small-molecule inhibitors with druglike properties is still challenging. In this study, two series of substituted 2-phenylquinolines and 2-arylimidazo[1,2-a]pyridines were designed through structure-based drug discovery approach by condensing the privileged structures of STX-119 and SH4-54. Our study has resulted in the discovery of a number of highly potent and selective STAT3 inhibitors, exemplified by compound 39 with the privileged structure of 2-phenylimidazo[1,2-a]pyridine, which selectively inhibits phosphorylation of STAT3 and suppresses subsequent signaling pathway. Moreover, 39 inhibits cell growth, migration and invasion of human triple negative breast cancer (TNBC) cells lines. Consistently, it achieves significant and dose-dependent tumor growth inhibition in both cell line-derived and patient-derived xenograft tumor models in mice. These results clearly indicate that 39 is a highly potent and selective STAT3 inhibitor.
Synthesis of Substituted Imidazo[1,2-a]Pyridin-3-yl-Acetic Acids by Multicomponent Condensation of 2-Aminopyridines with Arylglyoxals and Meldrum’s Acid
Lichitsky, Boris V.,Tretyakov, Аleksander D.,Komogortsev, Andrey N.,Mityanov, Vitaly S.,Dudinov, Arkady А.,Krayushkin, Mikhail M.
, p. 156 - 159 (2019/03/23)
[Figure not available: see fulltext.] A simple and effective method for the synthesis of substituted imidazo[1,2-a]pyridin-3-yl-acetic acids has been developed based on the multicomponent condensation of 2-aminopyridines with arylglyoxals and Meldrum's acid.
A method for preparing [...] (by machine translation)
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, (2019/01/13)
The invention discloses a method for synthesizing [...], existing technology with the different is, first of all the toluene with maleic anhydride Friedel-crafts reaction to obtain the 4 - oxo - 4 - (4 - methyl phenyl) - 2 - butenoic, then the same halogen addition to obtain the 3 - halo - 4 - oxo - 4 - (4 - methyl phenyl) - butyric acid, the esterification reaction, the ring, to obtain 2 - (6 - methyl - 2 - P-imidazole [1, 2 - α] pyridine - 3 - yl) acetate, the hydrolysis, acidifying the resulting [...]. The method of the invention, obtaining the high-purity [...], the whole synthetic route less steps, high yield, low cost, less impurities, is suitable for industrial production. (by machine translation)
Preparation method of 6-methyl-2-(4-methyl phenyl) imidazo [1,2-a] pyridine-3-acetic acid
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Paragraph 0064; 0065; 0066; 0067; 0068; 0069, (2017/12/27)
The invention relates to a preparation method of 6-methyl-2-(4-methyl phenyl) imidazo [1,2-a] pyridine-3-acetic acid. The preparation method comprises the following steps: reacting 3-halogenated-4-(4-methyl phenyl)-4-ketobutyric acid (2) with 2-amino-5-methylpyridine (3) under the effect of a condensing agent to obtain the 6-methyl-2-(4-methyl phenyl) imidazo [1,2-a] pyridine-3-acetic acid (1). According to the method provided by the invention, the purity of the product reaches up to 99%. The preparation method is an environmentally-friendly method which is mild in reaction conditions, simple in operation, convenient for product purification, relatively low in cost, easy for impurity removal and little in three wastes, is applicable for laboratory synthesis, is applicable for large-scale industrial production, and can overcome the defects such as relatively long synthetic procedure, high cost, high product purification difficulty and serious environment pollution in the prior art.
Preparation method of zolpidem tartrate and intermediate thereof
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Paragraph 0046-0096, (2017/07/20)
The invention relates to a preparation method of zolpidem tartrate and an intermediate thereof. According to the preparation method, the ratio of starting materials is adjusted, solvent screening is carried out, investment on raw materials is low, the cost is reduced, the yield is improved, impurity contents of prepared zolpidic acid and the prepared zolpidem tartrate are low, purification can be avoided, organic solvents and excessive raw materials in a reaction process can be recycled, and therefore, the preparation method is suitable for industrial production and is considerable in application prospect.
Iron-Catalyzed Dehydrogenative sp3-sp2 Coupling via Direct Oxidative C-H Activation of Acetonitrile
Su, Huimin,Wang, Luyao,Rao, Honghua,Xu, Hao
, p. 2226 - 2229 (2017/05/12)
An iron-catalyzed dehydrogenative sp3-sp2 coupling of acetonitrile and 2-arylimidazo[1,2-a]pyridine has been realized, which can serve as a novel approach toward heteroarylacetonitriles. The merit of this strategy is illustrated by the breadth of functional groups tolerated in the transformation and the fast access to pharmaceuticals (such as zolpidem) directly from the heteroarylacetonitriles.
Flow chemistry synthesis of zolpidem, alpidem and other GABAA agonists and their biological evaluation through the use of in-line frontal affinity chromatography
Guetzoyan, Lucie,Nikbin, Nikzad,Baxendale, Ian R.,Ley, Steven V.
, p. 764 - 769 (2013/03/14)
The flow of information between chemical and biological research can present a bottleneck in pharmaceutical research. Tools that bridge these disciplines and aid information exchange have therefore clear value. Over the last few years, both synthetic chemistry and biological screening have benefited from automation, and a seamless chemistry-biology interface is now possible. We report here on the use of flow processes to perform synthesis and biological evaluation in an integrated manner. As proof of concept, a flow synthesis of a series of imidazo[1,2-a]pyridines, including zolpidem and alpidem, was developed and connected to a Frontal Affinity Chromatography screening assay to investigate their interaction with Human Serum Albumin (HSA). The Royal Society of Chemistry 2013.
2-ARYL IMIDAZO[1,2-A]PYRIDINE-3-ACETAMIDE DERIVATIVES, PREPARATION METHODS AND USE THEREOF
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Paragraph 0057, (2013/05/09)
Disclosed are 2-arylimidazo[1,2-a]pyridine-3-acetamide derivatives represented by formula I, their tautomer, racemate or optical isomer, their pharmaceutically acceptable salt, or their solvates, wherein R1, R2, R3 and R4 are defined as in the specification. Preparation methods of said compounds and use of said compounds in treating and/or preventing central nervous system disease associated with TSPO functional disorder
