Synthesis and selectivity of 1-methoxycarbonylmethyl-3-arylamino-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodi- azepin-2-ones binding for CNS benzodiazepine receptors

• Дата: 2009
• Автори: Burenkova, N.A., Pavlovsky, V.I., Oleinich, I.A., Boyko, I.A., Makan, S.Yu., Artemenko, A.G., Kuz’min, V.E.
• Формат: Стаття
• Мова: English
• Опубліковано: Інститут молекулярної біології і генетики НАН України 2009
• Онлайн доступ: http://dspace.nbuv.gov.ua/handle/123456789/7369
• Назва журналу: Digital Library of Periodicals of National Academy of Sciences of Ukraine
• Цитувати: Synthesis and selectivity of 1-methoxycarbonylmethyl-3-arylamino-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodi- azepin-2-ones binding for CNS benzodiazepine receptors / N.A. Burenkova, V.I. Pavlovsky, I.A. Oleinich, I.A. Boyko, S.Yu. Makan, A.G. Artemenko, V.E. Kuz’min // Ukrainica Bioorganica Acta. — 2009. — Т. 7, № 1. — С. 8-15. — Бібліогр.: 44 назв. — англ.

Earlier, the methoxycarbonylmethyl fragment at the 1-position and the nitrophenylamine fragment at the 3-position of the 1,4-benzodiazepine ring, on the base of the QSAR analysis of series of 1,4-benzodiazepin-2-one derivatives [1], have been shown to gave compounds with increased affinity for peripheral benzodiazepine receptors (PBR). The 3-arylamine derivatives of 1-methoxycarbonylmethyl-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one were proposed for the directed synthesis as a promising high selective ligands of PBR. The target compounds were synthesized through the condensation of 1-methoxycarbonylmethyl-3-chloro-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one with substituted anilines. Affinities of synthesized compounds for the CNS benzodiazepine receptors of peripheral (PBR) and central (CBR) types were determined by the radioligand method in vitro. Selective PBR ligand with a high affinity — 1-methoxycarbonylmethyl-3-(2'-nitro)phenylamino-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one, 7 (MX-1785, Ki(PBR)=19.1 nM, Ki(CBR)>10000 nM) was found among the studied compounds.