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.
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)
