Macrocylic Inhibitors of Hepatitis C Virus
    7.
    发明申请
    Macrocylic Inhibitors of Hepatitis C Virus 有权
    丙型肝炎病毒的大胆抑制剂

    公开(公告)号:US20090105302A1

    公开(公告)日:2009-04-23

    申请号:US11995827

    申请日:2006-07-28

    摘要: Inhibitors of HCV replication of formula (I) and the N-oxides, salts, or stereoisomers thereof, wherein each dashed line (represented by - - - - -) represents an optional double bond; X is N, CH and where X bears a double bond it is C; R1 is —OR6, —NH—SO2R7; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, or C3-7cycloalkyl; n is 3, 4, 5, or 6; R4 and R5 independently from one another are hydrogen, halo, hydroxy, nitro, cyano, carboxyl, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkylcarbonyl, C1-6alkoxy-carbonyl, amino, azido, mercapto, C1-6alkylthio, polyhaloC1-6alkyl, aryl or Het; W is aryl or Het; R6 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; R7 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; aryl is phenyl or naphthyl, each optionally substituted with 1-3 substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1-4 heteroatoms each independently selected from N, O or S, and optionally substituted with 1-3 substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.

    摘要翻译: 式(I)的HCV复制抑制剂及其N-氧化物,盐或立体异构体,其中每个虚线(由 - - - - 表示)表示任选的双键; X为N,CH,X为双键,C为C; R1是-OR6,-NH-SO2R7; R2是氢,并且其中X是C或CH,R2也可以是C1-6烷基; R 3是氢,C 1-6烷基,C 1-6烷氧基C 1-6烷基或C 3-7环烷基; n为3,4,5或6; R 4和R 5彼此独立地是氢,卤素,羟基,硝基,氰基,羧基,C 1-6烷基,C 1-6烷氧基,C 1-6烷氧基C 1-6烷基,C 1-6烷基羰基,C 1-6烷氧基羰基,氨基,叠氮基,巯基, C 1-6烷硫基,多卤代C 1-6烷基,芳基或Het; W是芳基或Het; R6是氢; 芳基; Het; 任选被C 1-6烷基取代的C 3-7环烷基; 或任选被C 3-7环烷基,芳基或与Het取代的C 1-6烷基; R7是芳基; Het; 任选被C 1-6烷基取代的C 3-7环烷基; 或任选被C 3-7环烷基,芳基或与Het取代的C 1-6烷基; 芳基是苯基或萘基,各自任选被1-3个取代基取代; Het是含有1-4个杂原子的5或6元饱和的,部分不饱和的或完全不饱和的杂环,各自独立地选自N,O或S,并且任选被1-3个取代基取代; 含有化合物(I)的药物组合物和制备化合物(I)的方法。 还提供了式(I)的HCV抑制剂与利托那韦的生物可利用组合。

    MACROCYLIC INHIBITORS OF HEPATITIS C VIRUS
    8.
    发明申请
    MACROCYLIC INHIBITORS OF HEPATITIS C VIRUS 有权
    HEPATITIS C病毒的大肠抑制剂

    公开(公告)号:US20090247512A1

    公开(公告)日:2009-10-01

    申请号:US11995869

    申请日:2008-01-16

    摘要: Inhibitors of HCV replication of formula (I) and the N-oxides, salts, or stereoisomers thereof, wherein each dashed line represents an optional double bond; X is N, CH and where X bears a double bond it is C; R1 is —OR6, —NH—SO2R7; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, or C3-7cycloalkyl; n is 3, 4, 5, or 6; R4 and R5 taken together with the nitrogen atom to which they are attached form a bicyclic ring system selected from wherein said ring system may optionally be substituted with 1-3 substituents; R6 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; R7 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; aryl is phenyl or naphthyl, each of which may be optionally substituted with 1-3 substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms each independently selected from N, O or S, and being optionally substituted with 1-3 substituents pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.

    摘要翻译: 式(I)的HCV复制抑制剂及其N-氧化物,盐或立体异构体,其中每个虚线表示任选的双键; X为N,CH,X为双键,C为C; R1是-OR6,-NH-SO2R7; R2是氢,并且其中X是C或CH,R2也可以是C1-6烷基; R 3是氢,C 1-6烷基,C 1-6烷氧基C 1-6烷基或C 3-7环烷基; n为3,4,5或6; R4和R5与它们所连接的氮原子一起形成双环体系,其选自其中所述环系可以任选被1-3个取代基取代; R6是氢; 芳基; Het; 任选被C 1-6烷基取代的C 3-7环烷基; 或任选被C 3-7环烷基,芳基或与Het取代的C 1-6烷基; R7是芳基; Het; 任选被C 1-6烷基取代的C 3-7环烷基; 或任选被C 3-7环烷基,芳基或与Het取代的C 1-6烷基; 芳基是苯基或萘基,每个可以任选被1-3个取代基取代; Het是含有1至4个独立地选自N,O或S的杂原子的5或6元饱和的,部分不饱和的或完全不饱和的杂环,并且任选被1-3个取代基取代,含有化合物(I)的药物组合物和 制备化合物(I)。 还提供了式(I)的HCV抑制剂与利托那韦的生物可利用组合。