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Information × Registration Number 0220U103536, 0115U002146 , R & D reports Title Ligands of benzodiazepine, serotonin, dopamine, and fibrinogen receptors. Synthesis, "structure-property" relationship, selectivity and bi(poly)modality of action popup.stage_title Head Andronati Sergey A., Доктор хімічних наук Registration Date 22-10-2020 Organization Physico-Chemical Institute O. Bogatsky National Academy of Sciences of Ukraine popup.description2  Objective of the study: Molecular design, synthesis, study of the structure of potential ligands of central and peripheral benzodiazepine receptors of the CNS - new derivatives of dihydro-1,4-benzodiazepine. The synthesis of new 3-phthalimidoacyl-1,2-dihydro-3H-1,4-benzodiazepin-2-ones, which were obtained by condensation of 3-hydroxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones or 3-ethoxyhydroxy-1,2-dihydro-3H-1,4-benzdiazepin-2-ones with corresponding phthalimido acid chlorides. It was found that the optimal conditions for acylation is the use of a 1.1-fold excess of the carboxylic acid chloride, the synthesis is carried out in chloroform at 0 °C in the presence of pyridine as a base. The structure of the obtained compounds was confirmed by IR spectroscopy, 1H-NMR spectroscopy and mass spectrometry. By studying the affinity of 3-phthalimidoacyl-1,2-dihydro-3H-1,4-benzodiazepin-2-ones to the CNS CBDD, it was found that the compounds MX-1870, MX-1936, MX-2003 and MX-2000 have an affinity with Ki = 6.6 ± 0.5, 15.5 ± 1.3, 24.7 ± 2.5 and 47.2 ± 4.5 nM, respectively. When studying the effect of derivatives of 3-aminoacylox-1,2-dihydro-3H-1,4-benzodiazepines on the appetite of rats using the "Anorexia" method, it was shown that some compounds (MX-1855, MX-1878, MX-1934) exhibit anorexigenic action and reduce appetite and body weight of research rats. Among the studied substances, a compound (MX-1934) was found, which contains at the third position as a linker the remainder of ethylene glycol and a phthalimidoamino acid fragment, at a dose of 0.1 mg / kg has the most expressive anorexigenic effect and reduces food intake by experimental animals by 60% compared to control. The nature of the manifestation of the anorexigenic action of compound MX-1934 is similar to the action of the saturation hormone leptin (20 nM). Compounds MX-1855 and MX-1870 with a short ether chain of a phthalimidoamino acid fragment at a dose of 0.1 mg/kg exhibit low anorexigenic activity and only by 15 Product Description popup.authors Illyushko Natalia О. Andronati Sergey A. Kabanova Tetyana A Karaseva Tamara L. Kryvenko Yana R. Krysko Andrei А. Krysko Olga L. Pavlovskyi Viktor I Polishchuk Pavlo G. popup.nrat_date 2021-03-17 Close