ALLA CHEM LLC;АЛЛА ХЕМ ЛЛС;ИВАЩЕНКО, Андрей Александрович;IVASHCHENKO, Andrey Alexandrovich;IVASHCHENKO;IVACHTCHENKO, Alexandre Vasilievich;ИВАЩЕНКО, Александр Васильевич; Andrey Alexandrovich
发明人:
MITKIN, Oleg Dmitrievich,МИТЬКИН, Олег Дмитриевич
申请号：
RURU2014/000742
公开号：
WO2015/053662A1
申请日:
2014.10.06
申请国别(地区):
RU
年份:
2015
代理人:
摘要：
The present invention relates to novel substituted esters of amido-phosphoric acid - (2R, 3R, 5R)-3-hydroxy-(5-pyrimidin-1-yl) tetrahydrofuran-2-ylmethyl aryl phosphoramidate of general formula 1, or a stereoisomer thereof, or pharmaceutically acceptable salts, where, in formula (I): R1 represents hydrogen, (CH3)2[(CH3)3C]Si, C2-C6 acyl, not necessarily substituted by an NR5R6 group, in which R5 and R6 represent, independently, hydrogen or a C1-C4 alkyl； 1-pyrrol-2-ylcarbonyl, piperidin-3-ylcarbonyl or piperidin-4-ylcarbonyl； R2 and R3 represent F； alternatively, R2 represents F or OH, and R3 represents CH3； R4 represents hydrogen or methyl； Ar represents phenyl, pyridyl or naphthyl, where phenyl, pyridyl or naphthyl are not-necessarily substituted by at least one of the following: C1-3 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-3 alkoxy, F, Cl, Br, I, nitro, cyano,-N(C1-3 alkyl)2； Pm represents 2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl, or 4-amino-2-oxo-2H-pyrimidin-1-yl, in which the amino group is not-necessarily substituted by the radical C(O)R8, where R8 represents (1) C1-C4 alkyl, not-necessarily substituted by an NR6R7 group, where R6 and R7 represent, independently, hydrogen or C1-C4 alkyl； C1-3 alkoxy, not-necessarily substituted by phenyl； (2) 1-pyrrol-2-ylcarbonyl, piperidin-3-ylcarbonyl, piperidin-4-ylcarbonyl； X represents O or N-R9, where R9 represents C1-C4 alkyl, not-necessarily substituted by OH or OCH3； n=1, 2 or 3. The novel compound can be used as a hepatitis C virus NS5B polymerase inhibitor, and for treating disease caused by the hepatitis C virus.La présente invention concerne de nouveaux éthers substitués d'acide amidophosphorique (2R,3R,5R)-3-hydroxy-(5-pyrimidin-1-yl) tétrahydrofuran-2-ylméthyle aryle phosphoramidate correspondant à la formule générale 1 ou son stéréoisomère ou un sel pharmaceutiquement acceptable de la formule (I) dans laquelle : R1 représente hydrogène, (CH3)2[(CH3)3С]Si, C2-C6acyle, éventuellement substitué par NR5R6, groupe d
