- A novel formulation of zolpidem for direct nose-to-brain delivery: synthesis, encapsulation and intranasal administration to mice
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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.
- Borodina, Tatiana,Marchenko, Irina,Trushina, Daria,Volkova, Yulia,Shirinian, Valerii,Zavarzin, Igor,Kondrakhin, Evgeny,Kovalev, Georgy,Kovalchuk, Mikhail,Bukreeva, Tatiana
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- Structure-based discovery of potent and selective small-molecule inhibitors targeting signal transducer and activator of transcription 3 (STAT3)
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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.
- 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
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- Synthesis of Substituted Imidazo[1,2-a]Pyridin-3-yl-Acetic Acids by Multicomponent Condensation of 2-Aminopyridines with Arylglyoxals and Meldrum’s Acid
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[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.
- Lichitsky, Boris V.,Tretyakov, Аleksander D.,Komogortsev, Andrey N.,Mityanov, Vitaly S.,Dudinov, Arkady А.,Krayushkin, Mikhail M.
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p. 156 - 159
(2019/03/23)
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- A method for preparing [...] (by machine translation)
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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)
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- Preparation method of 6-methyl-2-(4-methyl phenyl) imidazo [1,2-a] pyridine-3-acetic acid
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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.
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Paragraph 0064; 0065; 0066; 0067; 0068; 0069
(2017/12/27)
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- Preparation method of zolpidem tartrate and intermediate thereof
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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.
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Paragraph 0046-0096
(2017/07/20)
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- Iron-Catalyzed Dehydrogenative sp3-sp2 Coupling via Direct Oxidative C-H Activation of Acetonitrile
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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.
- Su, Huimin,Wang, Luyao,Rao, Honghua,Xu, Hao
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p. 2226 - 2229
(2017/05/12)
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- Flow chemistry synthesis of zolpidem, alpidem and other GABAA agonists and their biological evaluation through the use of in-line frontal affinity chromatography
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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.
- Guetzoyan, Lucie,Nikbin, Nikzad,Baxendale, Ian R.,Ley, Steven V.
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p. 764 - 769
(2013/03/14)
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- 2-ARYL IMIDAZO[1,2-A]PYRIDINE-3-ACETAMIDE DERIVATIVES, PREPARATION METHODS AND USE THEREOF
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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
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Paragraph 0057
(2013/05/09)
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- 2-Aryl Imidazo[1,2-a]Pyridine-3-Acetamide Derivatives, Preparation Methods and Uses Thereof
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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
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Paragraph 0114; 0115; 0116; 0120
(2013/08/15)
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- Synthesis of imidazopyridines from the Morita-Baylis-Hillman acetates of nitroalkenes and convenient access to alpidem and zolpidem
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A variety of functionalized imidazo[1,2-a]pyridines have been synthesized through a one-pot, room temperature, and reagent-free reaction between MBH acetates of nitroalkenes and 2-aminopyridines. The reaction involves a cascade inter-intramolecular double aza-Michael addition of 2-aminopyridines to MBH acetates. Our methodology is marked by excellent yield, regioselectivity and, above all, adaptability to synthesize imidazopyridine-based drug molecules such as Alpidem and Zolpidem.
- Nair, Divya K.,Mobin, Shaikh M.,Namboothiri, Irishi N.N.
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p. 4580 - 4583
(2012/11/06)
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- PROCESS FOR PREPARING ZOLPIDEM AND ITS INTERMEDIATE
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The present invention relates to an improved process for the preparation of 6- methyl-2-[4-methylphenyl]imidazo[l,2-a]pyridine-3-N,N-dimethyl acetamide having formula (1). The compound of formula (1) has adopted name "Zolpidem". The present invention also relates to novel intermediate of the formula (2) and a process for its preparation.Wherein R represents methyl, ethyl, propyl, butyl, isopropyl, isobutyl or tertiary butyl group. The novel intermediate of formula (2) is used in preparation of Zolpidem having formula (1). Zolpidem is useful in the treatment of anxiety, sleep disorders and convulsion.
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Page/Page column 11; 15-17
(2009/03/07)
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- PROCESS FOR THE PREPARATION OF IMIDAZOPYRIDINES
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A process for the preparation of imidazopyridines of formula (I), comprising reacting 6-methyl-2-(4-methylphenyl)imidazo[l,2-a]pyridine with oxalyl chloride, followed by conversion of the chloride to oxoacetic acid, and further to compound of Formula (I).
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Page/Page column 7-8
(2008/06/13)
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- PROCESS FOR PREPARING ZOLPIDEM
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A process for preparing zolpidem.
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Page/Page column title page; sheet 1; 6
(2010/11/25)
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- IMIDAZO[1,2-A]PYRIDINE ANXIOLYTICS
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Imidazo[1,2-a]apyridines of the formulae I and II: are disclosed. The compounds are useful to treat anxiety and insomnia. Pharmaceutical compositions and methods are also disclosed. A representative compound of the invention is:
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Page/Page column 18
(2008/06/13)
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- PROCESS FOR THE PREPARATION OF N,N,6-TRIMETHYL-2-(4-METHYLPHENYL)-IMIDAZO[1,2-A]PYRIDINE-3-ACETAMIDE
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A process for the preparation of N,N,6-trimethyl-2-(4-methylphenyl)-imidazo [1,2-a]pyridine-3-acetamide, compound of formula (I), comprising reacting mixed anhydride, compound of formula (III), with dimethylamine; wherein R is selected from C1 to C6 linear or branched alkyl groups and substituted phenyl groups.
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- Process for the preparation of 2-phenyl-imidazo [1, 2-a] pyridine-3-acetamides
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A process for the preparation of 2-phenyl-imidazo[1,2-a]pyridine-3 -acetamides comprises the reaction of a 2-phenyl-imidazo[1,2-a]pyridine with an oxalic ester reactive derivative, followed by reduction of the carbonyl group and reaction with an amine.
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- A process for the preparation of 2-phenyl-imidazo[1,2-A]pyridine-3-acetamides
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A process for the preparation of 2-phenyl-imidazo[1,2-a]pyridine-3-acetamides comprises the reaction of a 2-phenyl-imidazo[1,2-a]pyridine with an oxalic ester reactive derivative, followed by reduction of the carbonyl group and reaction with an amine.
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- A structure-activity relationship study of the affinity of selected imidazo[1,2-a]pyridine derivatives, congeners of zolpidem, for the ω1-subtype of the benzodiazepine receptor
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A series of 6-substituted 2-aryl-N,N-dimethylimidazol [1,2-a]pyridine-3-acetamides, congeners of zolpidem and alpidem, was synthesized and tested in vitro for binding with the benzodiazepine receptor in the competition with 3H-zolpidem as an ω1-selective radioligand. Molecular electrostatic potential (MEP) and the HOMO and LUMO energies were calculated for the compounds by semi-empirical quantum chemistry methods. The lipophilicity parameter of the compounds, expressed as the logarithm of the octanol-water partition coefficient (log P), was calculated; alternatively, standard values of the Hansch hydrophobic substituent constants π were used. In agreement with earlier investigations on the benzodiazepine receptor ligands with a high preference for the ω1-subtype, a quantitative correlation of the biological data with molecular parameters has revealed a significant dependence (r=0.954) of the binding affinity (IC50) on the deepest MEP minimum, in this case associated with the amide carbonyl oxygen atom. The lipophilicity parameters were found to be of lower significance.
- Lange,Karolak-Wojciechowska,Wejroch,Rump
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