基本信息:
- 专利标题: MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS
- 专利标题(中):丙型肝炎病毒大肠杆菌抑制剂
- 申请号:PCT/EP2006/064817 申请日:2006-07-28
- 公开(公告)号:WO2007014923A1 公开(公告)日:2007-02-08
- 发明人: DE KOCK, Herman Augustinus , SIMMEN, Kenneth Alan , JÖNSSON, Carl Erik Daniel , AYESA ALVAREZ, Susana , CLASSON, Björn Olof , NILSSON, Karl Magnus , ROSENQUIST, Åsa Annica Kristina , SAMUELSSON, Bengt Bertil , WALLBERG, Hans Kristian
- 申请人: TIBOTEC PHARMACEUTICALS LTD. , MEDIVIR AB , DE KOCK, Herman Augustinus , SIMMEN, Kenneth Alan , JÖNSSON, Carl Erik Daniel , AYESA ALVAREZ, Susana , CLASSON, Björn Olof , NILSSON, Karl Magnus , ROSENQUIST, Åsa Annica Kristina , SAMUELSSON, Bengt Bertil , WALLBERG, Hans Kristian
- 申请人地址: Eastgate Village, Eastgate, Little Island, Co Cork IE
- 专利权人: TIBOTEC PHARMACEUTICALS LTD.,MEDIVIR AB,DE KOCK, Herman Augustinus,SIMMEN, Kenneth Alan,JÖNSSON, Carl Erik Daniel,AYESA ALVAREZ, Susana,CLASSON, Björn Olof,NILSSON, Karl Magnus,ROSENQUIST, Åsa Annica Kristina,SAMUELSSON, Bengt Bertil,WALLBERG, Hans Kristian
- 当前专利权人: TIBOTEC PHARMACEUTICALS LTD.,MEDIVIR AB,DE KOCK, Herman Augustinus,SIMMEN, Kenneth Alan,JÖNSSON, Carl Erik Daniel,AYESA ALVAREZ, Susana,CLASSON, Björn Olof,NILSSON, Karl Magnus,ROSENQUIST, Åsa Annica Kristina,SAMUELSSON, Bengt Bertil,WALLBERG, Hans Kristian
- 当前专利权人地址: Eastgate Village, Eastgate, Little Island, Co Cork IE
- 代理机构: DAELEMANS, Frank
- 优先权: EP05107071.2 20050729
- 主分类号: C07D401/12
- IPC分类号: C07D401/12 ; C07D403/12 ; C07D413/12 ; A61K31/538 ; A61P31/14
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; R 1 is -OR 6 , -NH-SO 2 R 7 ; R 2 is hydrogen, and where X is C or CH, R 2 may also be C 1-6 alkyl; R 3 is hydrogen, C 1-6 alkyl, C 1-6 alkoxyC 1-6 alkyl, or C 3-7 cycloalkyl; n is 3, 4, 5, or 6; R 4 and R 5 taken together with the nitrogen atom to which they are attached form a bicyclic ring system selected from formula (II) wherein said ring system may optionally be substituted with 1-3 substituents; R 6 is hydrogen; aryl; Het; C 3-7 cycloalkyl optionally substituted with C 1-6 alkyl; or C 1-6 alkyl optionally substituted with C 3-7 cycloalkyl, aryl or with Het; R 7 is aryl; Het; C 3-7 cycloalkyl optionally substituted with C 1-6 alkyl; or C 1-6 alkyl optionally substituted with C 3-7 cycloalkyl, 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(中):
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; R 1是-OR 6,-NH-SO 2 R 7, R 2是氢,并且其中X是C或CH,R 2也可以是C 1-6烷基; R 3是氢,C 1-6烷基,C 1-6烷氧基C 1-6烷基,或 ç 3-7 SUB>环烷基; n为3,4,5或6; R 4和R 5与它们所连接的氮原子一起形成选自式(II)的双环体系,其中所述环系可任选地被 1-3个取代基; R 6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; R 7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。
IPC结构图谱:
C | 化学;冶金 |
--C07 | 有机化学 |
----C07D | 杂环化合物 |
------C07D401/00 | 杂环化合物,含有两个或更多个杂环,以氮原子作为仅有的杂环原子,至少有1个环是仅含有1个氮原子的六元环 |
--------C07D401/02 | .含有两个杂环 |
----------C07D401/12 | ..被含有杂原子的链作为键链连接的 |