[发明专利]构象受限的完全合成的大环化合物

摘要

类型(I)的构象受限的、空间限定的12-30元大环环系包括三个不同的构造单元：芳族模板a，构象调节物b和间隔体部分c，如说明书和权利要求所详细描述。类型(I)大环通过平行合成或组合化学容易地制备。它们设计用来与特定的生物学靶标相互作用。尤其是，它们显示对下述的激动或拮抗活性：胃动素受体(MR受体)，亚型5-HT_2B的5-羟色胺受体(5-HT_2B受体)，和前列腺素F2α受体(FP受体)。从而，它们有效地用于治疗胃肠道运动减弱障碍比如糖尿病性胃轻瘫和便秘型肠易激综合征；与CNS有关的疾病比如偏头痛，精神分裂症，精神病或抑郁；高眼压症比如与青光眼有关的高眼压症和早产。

主权项

1.包括构造单元A、B和C的通式I化合物其中构造单元A中的圆圈部分a，构造单元B中的圆圈部分b和构造单元C中的圆圈部分c1-C3衍生自基础骨架，其适当地且独立地如下文所定义地被取代，a和b的基础骨架相应于下文表1和表2中描述的环系；表2：构造单元B的环系b1-b11取决于骨架b的取代模式，骨架b3和b4的备择结合模式是可行的，这种经由环外氮原子的结合由下述两种结构代表：桥亚单位c1-c3的圆圈部分代表任选经取代的基团，c1-c3的定义描述于下表3中，各自从连接体C的N-末端至C-末端阅读，所述连接体C在最简单的情况下包括一个亚单位c1，也即c1-1至c1-6，而对于由二或三个亚单位组成的实施方式，亚单位c1-c3和连接部分U、V和W的全部可能组合都是可能的；表3：连接体基团C的c1-c3亚单位的范围直接连接至构造单元A、B和C的取代基，也即R¹-R¹⁷，定义如下：R¹：H；F；Cl；Br；I；CF₃；OCF₃；OCHF₂；NO₂；CN；烷基；烯基；炔基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-(CR¹⁸R¹⁹)_qOR²⁰；-(CR¹⁸R¹⁹)_qSR²⁰；-(CR¹⁸R¹⁹)_qNR⁴R¹¹；-(CR¹⁸R¹⁹)_qOCONR⁴R¹¹；-(CR¹⁸R¹⁹)_qOCOOR²¹；-(CR¹⁸R¹⁹)_qNR⁴COOR²¹；-(CR¹⁸R¹⁹)_qNR⁴COR²²；-(CR¹⁸R¹⁹)_qNR⁴CONR⁴R¹¹；-(CR¹⁸R¹⁹)_qNR⁴SO₂R²³；-(CR¹⁸R¹⁹)_qNR⁴SO₂NR⁴R¹¹；-(CR¹⁸R¹⁹)_qCOOR²¹；-(CR¹⁸R¹⁹)_qCONR⁴R¹¹；-(CR¹⁸R¹⁹)_qSO₂NR⁴R¹¹；-(CR¹⁸R¹⁹)_qPO(OR²¹)₂；-(CR¹⁸R¹⁹)_qOPO(OR²¹)₂；-(CR¹⁸R¹⁹)_qCOR²²；-(CR¹⁸R¹⁹)_qSO₂R²³；-(CR¹⁸R¹⁹)_qOSO₃R²¹；-(CR¹⁸R¹⁹)_qR²⁴；-(CR¹⁸R¹⁹)_qR²⁵；或-(CR¹⁸R¹⁹)_qR²⁶；R²：H；CF₃；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-(CR¹⁸R¹⁹)_qOR²⁰；-(CR¹⁸R¹⁹)_qSR²⁰；-(CR¹⁸R¹⁹)_qNR⁴R¹¹；-(CR¹⁸R¹⁹)_qOCONR⁴R¹¹；-(CR¹⁸R¹⁹)_qOCOOR²¹；-(CR¹⁸R¹⁹)_qNR⁴COOR²¹；-(CR¹⁸R¹⁹)_qNR⁴COR²²；-(CR¹⁸R¹⁹)_qNR⁴CONR⁴R¹¹；-(CR¹⁸R¹⁹)_qNR⁴SO₂R²³；-(CR¹⁸R¹⁹)_qNR⁴SO₂NR⁴R¹¹；-(CR¹⁸R¹⁹)_qCOOR²¹；-(CR¹⁸R¹⁹)_qCONR⁴R¹¹；-(CR¹⁸R¹⁹)_qSO₂NR⁴R¹¹；-(CR¹⁸R¹⁹)_qPO(OR²¹)₂；-(CR¹⁸R¹⁹)_qCOR²²；-(CR¹⁸R¹⁹)_qSO₂R²³；-(CR¹⁸R¹⁹)_qR²⁴；-(CR¹⁸R¹⁹)_qR²⁵；或-(CR¹⁸R¹⁹)_qR²⁶；R³：H；CF₃；烷基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；R⁴：H；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；或适宜的N-保护基团；R⁵，R⁷和R⁹独立地定义为：H；F；CF₃；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-(CR¹⁸R¹⁹)_sOR²⁰；-(CR¹⁸R¹⁹)_sSR²⁰；-(CR¹⁸R¹⁹)_sNR⁴R¹¹；-(CR¹⁸R¹⁹)_sOCONR⁴R¹¹；-(CR¹⁸R¹⁹)_sOCOOR²¹；-(CR¹⁸R¹⁹)_sNR⁴COOR²¹；-(CR¹⁸R¹⁹)_sNR⁴COR²²；-(CR¹⁸R¹⁹)_sNR⁴CONR⁴R¹¹；-(CR¹⁸R¹⁹)_sNR⁴SO₂R²³；-(CR¹⁸R¹⁹)_sNR⁴SO₂NR⁴R¹¹；-(CR¹⁸R¹⁹)_qCOOR²¹；-(CR¹⁸R¹⁹)_qCONR⁴R¹¹；-(CR¹⁸R¹⁹)_qSO₂NR⁴R¹¹；-(CR¹⁸R¹⁹)_qPO(OR²¹)₂；-(CR¹⁸R¹⁹)_qCOR²²；-(CR¹⁸R¹⁹)_qSO₂R²³；-(CR¹⁸R¹⁹)_qR²⁴；-(CR¹⁸R¹⁹)_qR²⁵；或-(CR¹⁸R¹⁹)_qR²⁶；R⁶，R⁸和R¹⁰独立地定义为：H；F；CF₃；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；或杂芳基烷基；R¹¹：H；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；适宜的保护基团；-(CR¹⁸R¹⁹)_rOR²⁰；-(CR¹⁸R¹⁹)_rSR²⁰；-(CR¹⁸R¹⁹)_rNR⁴R²⁷；-(CR¹⁸R¹⁹)_rOCONR⁴R²⁷；-(CR¹⁸R¹⁹)_rOCOOR²¹；-(CR¹⁸R¹⁹)_rNR⁴COOR²¹；-(CR¹⁸R¹⁹)_rNR⁴CONR⁴R²⁷；-(CR¹⁸R¹⁹)_rNR⁴SO₂R²³；-(CR¹⁸R¹⁹)_rNR⁴SO₂NR⁴R²⁷；-(CR¹⁸R¹⁹)_qCOOR²¹；-(CR¹⁸R¹⁹)_qCONR⁴R²⁷；-(CR¹⁸R¹⁹)_qCOR²²；-(CR¹⁸R¹⁹)_qSO₂R²³；-(CR¹⁸R¹⁹)_qSO₂NR⁴R²⁷；-(CR¹⁸R¹⁹)_qR²⁴；-(CR¹⁸R¹⁹)_sR²⁵；或-(CR¹⁸R¹⁹)_qR²⁶；R¹²和R¹³独立地定义为H；或烷基；R¹⁴和R¹⁶独立地定义为：H；F；CF₃；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-(CR¹⁸R¹⁹)_sOR²⁰；-(CR¹⁸R¹⁹)_sNR⁴R¹¹；-(CR¹⁸R¹⁹)_sNR⁴COOR²¹；-(CR¹⁸R¹⁹)_sNR⁴COR²²；-(CR¹⁸R¹⁹)_sNR⁴CONR⁴R¹¹；-(CR¹⁸R¹⁹)_sNR⁴SO₂R²³；-(CR¹⁸R¹⁹)_sNR⁴SO₂NR⁴R¹¹；-(CR¹⁸R¹⁹)_qCOOR²¹；-(CR¹⁸R¹⁹)_qCONR⁴R¹¹；-(CR¹⁸R¹⁹)_qSO₂NR⁴R¹¹；或-(CR¹⁸R¹⁹)_qCOR²²；R¹⁵和R¹⁷独立地定义为：H；F；CF₃；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；或杂芳基烷基；引入残基R¹-R¹⁷的子定义的取代基定义如下：R¹⁸：H；F；CF₃；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-(CR²⁹R³⁰)_sOR³¹；-(CR²⁹R³⁰)_sSR³¹；-(CR²⁹R³⁰)_sNR²⁸R³¹；-(CR²⁹R³⁰)_sOCONR²⁸R³¹；-(CR²⁹R³⁰)_sOCOOR²¹；-(CR²⁹R³⁰)_sNR²⁸COOR²¹；-(CR²⁹R³⁰)_sNR²⁸COR³¹；-(CR²⁹R³⁰)_sNR²⁸CONR²⁸R³¹；-(CR²⁹R³⁰)_sNR²⁸SO₂R²³；-(CR²⁹R³⁰)_sNR²⁸SO₂NR²⁸R³¹；-(CR²⁹R³⁰)_qCOOR²¹；-(CR²⁹R³⁰)_qCONR²⁸R³¹；-(CR²⁹R³⁰)_qSO₂NR²⁸R³¹；-(CR²⁹R³⁰)_qPO(OR²¹)₂；-(CR²⁹R³⁰)_qCOR³¹；-(CR²⁹R³⁰)_qSO₂R²³；-(CR²⁹R³⁰)_qR²⁴；-(CR²⁹R³⁰)_qR²⁵；或-(CR²⁹R³⁰)_qR²⁶；R¹⁹：H；CF₃；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；R²⁰：H；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-(CR²⁹R³⁰)_rOR³¹；-(CR²⁹R³⁰)_rSR³¹；-(CR²⁹R³⁰)_rNR²⁸R³¹；-(CR²⁹R³⁰)_rOCONR²⁸R³¹；-(CR²⁹R³⁰)_rNR²⁸COOR²¹；-(CR²⁹R³⁰)_rNR²⁸COR³¹；-(CR²⁹R³⁰)_rNR²⁸CONR²⁸R³¹；-(CR²⁹R³⁰)_rNR²⁸SO₂R²³；-(CR²⁹R³⁰)_rNR²⁸SO₂NR²⁸R³¹；-(CR²⁹R³⁰)_qCOOR²¹；-(CR²⁹R³⁰)_qCONR²⁸R³¹；-(CR²⁹R³⁰)_qSO₂NR²⁸R³¹；-(CR²⁹R³⁰)_qCOR³¹；-(CR²⁹R³⁰)_qSO₂R²³；-(CR²⁹R³⁰)_qR²⁴；-(CR²⁹R³⁰)_qR²⁵；或-(CR²⁹R³⁰)_qR²⁶；R²¹：烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；或适宜的O-保护基团；R²²：烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-(CR²⁹R³⁰)_sOR³¹；-(CR²⁹R³⁰)_sSR³¹；-(CR²⁹R³⁰)_sNR²⁸R³¹；-(CR²⁹R³⁰)_sOCONR²⁸R³¹；-(CR²⁹R³⁰)_sNR²⁸COOR²¹；-(CR²⁹R³⁰)_sNR²⁸COR³¹；-(CR²⁹R³⁰)_sNR²⁸CONR²⁸R³¹；-(CR²⁹R³⁰)_sNR²⁸SO₂R²³；-(CR²⁹R³⁰)_sNR²⁸SO₂NR²⁸R³¹；-(CR²⁹R³⁰)_sCOOR²¹；-(CR²⁹R³⁰)_sCONR²⁸R³¹；-(CR²⁹R³⁰)_sSO₂NR²⁸R³¹；-(CR²⁹R³⁰)_tCOR³¹；-(CR²⁹R³⁰)_sSO₂R²³；-(CR²⁹R³⁰)_tR²⁴；-(CR²⁹R³⁰)_tR²⁵；或-(CR²⁹R³⁰)_tR²⁶；R²³：H；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；或-(CR³²R³³)_tR²⁴；R²⁴：芳基，优选类型C₆H₂R³⁴R³⁵R³¹的任选经取代的苯基；或杂芳基，优选示于下表4的式H1-H34基团之一；表4：式H1-H34基团R²⁵：示于下表5的式H35-H41基团之一；表5：式H35-H41残基R²⁶：示于下表6的式H42-H50基团之一；表6：式H43-H50基团R²⁷：H；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；适宜的保护基团；或-(CR²⁹R³⁰)_qR²⁴；R²⁸：H；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；适宜的N-保护基团；-(CR³²R³³)_sOR²¹；-(CR³²R³³)_sNR⁴³R⁴²；-(CR³²R³³)_sNR⁴²CONR⁴³R⁴²；-(CR³²R³³)_sNR⁴²COR²¹；-(CR³²R³³)_sNR⁴²SO₂NR²¹；-(CR³²R³³)_qCOOR²¹；-(CR³²R³³)_qCOR²³；-(CR³²R³³)_qSO₂R²¹；R²⁹：H；F；CF₃；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-(CR³²R³³)_sOR³¹；-(CR³²R³³)_sSR³¹；-(CR³²R³³)_sNR²⁸R³¹；-(CR³²R³³)_sOCONR²⁸R³¹；-(CR³²R³³)_sOCOOR²¹；-(CR³²R³³)_sNR²⁸COOR²¹；-(CR³²R³³)_sNR²⁸COR³¹；-(CR³²R³³)_sNR²⁸CONR²⁸R³¹；-(CR³²R³³)_sNR²⁸SO₂R²³；-(CR³²R³³)_sNR²⁸SO₂NR²⁸R³¹；-(CR³²R³³)_qCOOR²¹；-(CR³²R³³)_qCONR²⁸R³¹；-(CR³²R³³)_qSO₂NR²⁸R³¹；-(CR³²R³³)_qPO(OR²¹)₂；-(CR³²R³³)_qCOR³¹；-(CR³²R³³)_qSO₂R²³；-(CR³²R³³)_qR³¹；R³⁰：H；F；CF₃；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；R³¹：H；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；或示于下表7的式H51-H55的基团之一；表7：式H51-H55基团R³²和R³³独立地定义为H；F；CF₃；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；R³⁴和R³⁵独立地定义为H；F；Cl；CF₃；OCF₃；OCHF₂；NO₂；CN；烷基；烯基；炔基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-(CR²⁹R³⁰)_qOR³¹；-(CR²⁹R³⁰)_qSR³¹；-(CR²⁹R³⁰)_qNR²⁸R³¹；-(CR²⁹R³⁰)_qOCONR²⁸R³¹；-(CR²⁹R³⁰)_qNR²⁸COOR²¹；-(CR²⁹R³⁰)_qNR²⁸COR³¹；-(CR²⁹R³⁰)_qNR²⁸CONR²⁸R³¹；-(CR²⁹R³⁰)_qNR²⁸SO₂R²³；-(CR²⁹R³⁰)_qNR²⁸SO₂NR²⁸R³¹；-(CR²⁹R³⁰)_qCOOR²¹；-(CR²⁹R³⁰)_qCONR²⁸R³¹；-(CR²⁹R³⁰)_qSO₂NR²⁸R³¹；-(CR²⁹R³⁰)_qCOR³¹；-(CR²⁹R³⁰)_qSO₂R²³；或-(CR²⁹R³⁰)_qR³¹；R³⁶：H；烷基；烯基；炔基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；或-NR²⁸R³¹；R³⁷：H；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；适宜的N-保护基团；-(CR²⁹R³⁰)_rOR³¹；-(CR²⁹R³⁰)_rSR³¹；-(CR²⁹R³⁰)_rNR²⁸R³¹；-(CR²⁹R₃₀)_rOCONR²⁸R³¹；-(CR²⁹R³⁰)_rNR²⁸COOR²¹；-(CR²⁹R³⁰)_rNR²⁸COR³¹；-(CR²⁹R³⁰)_rNR²⁸CONR²⁸R³¹；-(CR²⁹R³⁰)_rNR²⁸SO₂R²³；-(CR²⁹R³⁰)_rNR²⁸SO₂NR²⁸R³¹；-(CR²⁹R³⁰)_qCOOR²¹；-(CR²⁹R³⁰)_qCONR²⁸R³¹；-(CR²⁹R³⁰)_rSO₂NR²⁸R³¹；-(CR²⁹R³⁰)_qCOR³¹；-(CR²⁹R³⁰)_qSO₂R²³；或-(CR²⁹R³⁰)_qR³¹；R³⁸：H；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-(CR²⁹R³⁰)_qOR³¹；-(CR²⁹R³⁰)_qSR³¹；-(CR²⁹R³⁰)_qNR²⁸R³¹；-(CR²⁹R³⁰)_qNR²⁸COOR²¹；-(CR²⁹R³⁰)_qNR²⁸COR³¹；-(CR²⁹R³⁰)_qNR²⁸CONR²⁸R³¹；-(CR²⁹R³⁰)_qCOOR²¹；-(CR²⁹R³⁰)_qCONR²⁸R³¹；-(CR²⁹R³⁰)_qCOR³¹；或-(CR²⁹R³⁰)_qR³¹；R³⁹：H；F；CF₃；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-(CR³²R³³)_uOR²¹；-(CR³²R³³)_uNR²⁸R⁴³；-(CR³²R³³)_tCOOR²¹；或-(CR³²R³³)_tCONR²⁸R⁴³；R⁴⁰：H；F；CF₃；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-(CR³²R³³)_uOR²¹；-(CR³²R³³)_uNR²⁸R⁴³；-(CR³²R³³)_tCOOR²¹；或-(CR³²R³³)_tCONR²⁸R⁴³；R⁴¹：H；CF₃；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-OR²¹；-NR²⁸R⁴³；-NR²⁸COR²³；-NR²⁸COOR²¹；-NR²⁸SO₂R²³；-NR²⁸CONR²⁸R⁴³；-COOR²¹；-CONR²⁸R⁴³；-C(＝NR⁴³)NR²⁸N⁴³；-NR²⁸C(＝NR⁴³)NR²⁸N⁴³；或示于下表8的式H56-H110的基团之一；表8：式H56-H110基团R⁴²：H；烷基；烯基；环烷基；环杂烷基；芳基；杂芳基；-(CR²³R³³)_sOR²¹；-(CR²³R³³)_sNR²⁸R⁴³；-(CR²³R³³)_qCOOR²¹；或-(CR²³R³³)_qCONR²¹R⁴³；R⁴³：H；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；或适宜的N-保护基团；R⁴⁴，R⁴⁵和R⁴⁶独立地定义为H；F；CF₃；OCF₃；OCHF₂；NO₂；CN；烷基；烯基；炔基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-OR²³；-NR²⁸R⁴³；-NR²⁸COR²³；-NR²⁸SO₂R²³；-NR²⁸CONR²⁸R⁴³；-COR²³；-SO₂R²³；R⁴⁷：H；CF₃；烷基；烯基；炔基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-COOR²¹；或-CONR²⁸R⁴³；R⁴⁸：H；F；CF₃；烷基；烯基；环烷基；环杂烷基；芳基；杂芳基；-(CR²³R³³)_tOR²¹；-(CR²³R³³)_tNR²⁸R⁴³；-(CR²³R³³)_tCOOR²¹；-(CR²³R³³)_tCONR²¹R⁴³；R⁴⁹和R⁵⁰独立地定义为H；F；CF₃；烷基；烯基；环烷基；杂环烷基；芳基；杂芳基；芳基烷基；杂芳基烷基；-(CR³²R³³)_qOR²¹；-(CR³²R³³)_qNR²⁸R⁴³；-(CR³²R³³)_qCOOR²¹；或-(CR³²R³³)_qCONR²⁸R⁴³；所述取代基的下述对一起能够限定环状结构组成部分：(R⁴和R¹¹)；(R⁴和R²⁷)；(R⁵和R⁶)；(R⁵和R⁷)；(R⁵和R⁹)；(R⁵和R¹⁴)；(R⁵和R¹⁶)；(R⁷和R⁸)；(R⁷和R⁹)；(R⁷和R¹⁶)；(R⁹和R¹⁰)；(R¹⁴和R¹⁵)；(R¹⁶和R¹⁷)；(R¹⁸和R¹⁹)；(R²⁷和R²⁸)；(R²⁸和R³¹)；(R²⁸和R⁴³)；(R²⁹和R³⁰)；(R³²和R³³)；(R³⁴和R³⁵)；(R³⁷和R³⁸)；(R³⁹和R⁴⁰)；(R³⁹和R⁴¹)；(R³⁹和R⁴⁹)；(R⁴²和R⁴³)；(R⁴⁴和R⁴⁵)；或(R⁴⁴和R⁴⁶)能够形成任选经取代的环烷基或杂环烷基部分；此外，结构组成部分-NR⁴R¹¹；-NR²⁷R²⁸；-NR²⁸R³¹或-NR²⁸R⁴³能够形成示于下表9的式H111-H118的基团之一；表9：通过连接二取代氨基-NR⁴R¹¹；-NR²⁷R²⁸；-NR²⁸R³¹或-NR²⁸R⁴³的残余部分而限定的杂环基团；前述结构中的可变杂原子和连接基团如下：Z：O；S；S(＝O)；S(＝O)₂；或NR²⁸；Y：O；S；或NR³⁷；X：O；S；S(＝O)；或S(＝O)₂；Q：O；S；或NR²⁸；U、V和W：如上表3中所定义；T：CR⁴⁶或N；在T在相同环结构中出现数次的情况下，各T独立于其它地进行定义；并且指数定义如下：q＝0-4；r＝2-4；s＝1-4；t＝0-2；和u＝1-2；其全部可能的立体异构体和药学上可接受的盐。