Synthesis, structure and affinity of novel 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones for CNS central and peripheral benzodiazepine receptors

Andronati Sergei; Semenishyna Ekaterina; Pavlovsky Victor; Simonov Yurii A.; Makan Svetlana; Boiko Iryna; Burenkova Natalya; Gdaniec Maria; Cardinael Pascal; Bouillon Jean-Philippe; Mazepa Aleksandr

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ANDRONATI, Sergei, SEMENISHYNA, Ekaterina, PAVLOVSKY, Victor, SIMONOV, Yurii A., MAKAN, Svetlana, BOIKO, Iryna, BURENKOVA, Natalya, GDANIEC, Maria, CARDINAEL, Pascal, BOUILLON, Jean-Philippe, MAZEPA, Aleksandr. Synthesis, structure and affinity of novel 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones for CNS central and peripheral benzodiazepine receptors. In: European Journal of Medicinal Chemistry, 2010, vol. 45, pp. 1346-1351. ISSN 0223-5234. DOI: https://doi.org/10.1016/j.ejmech.2009.12.027

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European Journal of Medicinal Chemistry

Volumul 45 / 2010 / ISSN 0223-5234 /ISSNe 1768-3254

Synthesis, structure and affinity of novel 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones for CNS central and peripheral benzodiazepine receptors

DOI:https://doi.org/10.1016/j.ejmech.2009.12.027

Pag. 1346-1351

Andronati Sergei¹, Semenishyna Ekaterina¹, Pavlovsky Victor¹, Simonov Yurii A.², Makan Svetlana¹, Boiko Iryna¹, Burenkova Natalya¹, Gdaniec Maria³, Cardinael Pascal⁴, Bouillon Jean-Philippe⁴, Mazepa Aleksandr¹

¹ A.V. Bogatsky Physico-Chemical Institute of the NAS of Ukraine,
² Institute of Applied Physics, Academy of Sciences of Moldova,
³ Adam Mickiewicz University in Poznan,
⁴ Rouen University

Disponibil în IBN: 4 iulie 2023

Rezumat

A series of novel 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones (7-15) was synthesized and their in vitro affinity for both the central benzodiazepine receptor (CBR) and the peripheral benzodiazepine receptor (PBR) of rat brain was studied. Racemic mixture of 7-bromo-3-(2-methoxy)ethoxy-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one (13) was separated into enantiomers 14, 15 by chiral HPLC. Absolute configuration of R-enantiomer 15 was determined by the method of X-ray diffraction analysis. The affinity of S-enantiomer 14 for CBR (I{cyrillic, ukrainian}C₅₀ = 245 nM) is 20-fold higher than the affinity of R-enantiomer 15 (I{cyrillic, ukrainian}C₅₀ = 4930 nM). A high selectivity for CBR versus PBR (I{cyrillic, ukrainian}C₅₀ (PBR) > 10000 nM) was shown by all reported compounds. Compound 12 was revealed as a potent (IC₅₀ = 9 nM) and selective CBR ligand among the synthesized 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-ones.

Cuvinte-cheie
3-alkoxy-1, 2-dihydro-3H-1, 4-bezodiazepin-2-ones, affinity, Central benzodiazepine receptor, enantiomer, Peripheral benzodiazepine receptor, X-ray analysis

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