6,6-Dimethyl-1-(homopiperidin-1-ylcarbonyl)-5-hydroxymethylene-3-methylthio-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one | 252056-09-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 6,6-Dimethyl-1-(homopiperidin-1-ylcarbonyl)-5-hydroxymethylene-3-methylthio-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one
• 英文别名: 1-(azepane-1-carbonyl)-5-(hydroxymethylidene)-6,6-dimethyl-3-methylsulfanyl-7H-2-benzothiophen-4-one
• CAS: 252056-09-0
• 化学式: C₁₉H₂₅NO₃S₂
• 分子量: 379.544
• InChiKey: WXWJXQWHEWPGBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6,6-dimethyl-1-(homopiperidin-1-ylcarbonyl)-3-methylthio-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one 以57%的产率得到6,6-Dimethyl-1-(homopiperidin-1-ylcarbonyl)-5-hydroxymethylene-3-methylthio-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one
  参考文献：
  名称：

  Substituted thienobenzisoxazole derivatives for enhancing cognition

  摘要：

  本发明提供了式(I)的化合物及其药学上可接受的盐：##STR1##其中A为C.sub.1-6烷基，C.sub.2-6烯基，C.sub.2-6炔基，C.sub.3-6环烷基，芳基C.sub.1-6烷基，芳基，S(O).sub.p R.sup.1，OR.sup.1或NR.sup.1 R.sup.12；B为可选择取代的5-或6-成员杂芳环或C(O)NR.sup.10 R.sup.11；R.sup.1为氢，可选择取代的C.sub.1-6烷基，C.sub.2-6烯基，C.sub.2-6炔基，C.sub.3-6环烷基或C.sub.3-6环烯基，可选择取代的芳基，芳基C.sub.1-6烷基，芳基C.sub.2-6烯基或芳基C.sub.2-6炔基或可选择取代的5-或6-成员杂芳环；R.sup.2和R.sup.3为氢或C.sub.1-6烷基；R.sup.4为氢，C.sub.1-8烷基，C.sub.2-8烯基，C.sub.2-8炔基，芳基或CH.sub.2(CO).sub.m NR.sup.8 R.sup.9；R.sup.5为NR.sup.6 R.sup.7，C.sub.1-6烷基或C.sub.1-6烷氧基；R.sup.6独立定义为R.sup.4；R.sup.7为芳基，可选择取代的卤素，硝基或氰基；R.sup.8为氢，C.sub.1-6烷基，C.sub.3-6环烷基，C.sub.3-6环烯基，C.sub.2-6烯基，C.sub.2-6炔基；芳基C.sub.1-6烷基，芳基C.sub.2-6烯基或芳基C.sub.2-6炔基，可选择取代的卤素，硝基或氰基的芳基环；噻吩或吡啶；R.sup.9为C.sub.1-6烷基；C.sub.2-烯基；C.sub.2-6炔基；或苯基，可选择取代为一个，两个或三个独立选择的卤素，CF.sub.3，OCH.sub.3，硝基和氰基；R.sup.10和R.sup.11分别为氢，C.sub.1-6烷基，C.sub.2-6烯基，C.sub.2-6炔基或C.sub.3-8环烷基或R.sup.10和R.sup.11，与它们连接的氮原子一起形成饱和的4到8成员环，可选择包含一个氧原子或另一个氮原子作为环成员，另一个氮原子未取代或取代为C.sub.1-4烷基，C.sub.2-4烯基或C.sub.2-4炔基；R.sup.12为氢或C.sub.1-6烷基；m为零或1；p为零，1或2；q为0，1或2；r为0，1或2；这些化合物的制备，它们在增强认知能力中的应用，特别是在疾病状态下，尤其是阿尔茨海默病中的治疗方法。

  公开号：

  US06143773A1

文献信息

• Substituted thienobenzisoxazole derivatives for enhancing cognition
  申请人：Merck Sharp & Dohme Limited

  公开号：US06143773A1

  公开（公告）日：2000-11-07

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof: ##STR1## wherein A is C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-6 cycloalkyl, arylC.sub.1-6 alkyl, aryl, S(O).sub.p R.sup.1, OR.sup.1 or NR.sup.1 R.sup.12 ; B is optionally substituted 5- or 6-membered heteroaromatic ring or C(O)NR.sup.10 R.sup.11 ; R.sup.1 is hydrogen, optionally substituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-6 cycloalkyl or C.sub.3-6 cycloalkenyl, optionally substituted aryl, arylC.sub.1-6 alkyl, arylC.sub.2-6 alkenyl or arylC.sub.2-6 alkynyl or an optionally substituted 5- or 6-membered heteroaromatic ring; R.sup.2 and R.sup.3 are hydrogen or C.sub.1-6 alkyl; R.sup.4 is hydrogen, C.sub.1-8 alkyl, C.sub.2-8 alkenyl, C.sub.2-8 alkynyl, aryl or CH.sub.2 (CO).sub.m NR.sup.8 R.sup.9 ; R.sup.5 is NR.sup.6 R.sup.7, C.sub.1-6 alkyl or C.sub.1-6 alkoxy; R.sup.6 is independently as defined for R.sup.4 ; R.sup.7 is aryl optionally substituted by halogen, nitro or cyano; R.sup.8 is hydrogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkenyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl; arylC.sub.1-6 alkyl, arylC.sub.2-6 alkenyl or arylC.sub.2-6 alkynyl optionally substituted on the aryl ring by halogen, nitro or cyano; thiophene or pyridine; R.sup.9 is C.sub.1-6 alkyl; C.sub.2- alkenyl; C.sub.2-6 alkynyl; or phenyl optionally substituted by one, two or three substituents independently chosen from halogen, CF.sub.3, OCH.sub.3, nitro and cyano; R.sup.10 and R.sup.11 are individually hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl or C.sub.3-8 cycloalkyl or R.sup.10 and R.sup.11, together with the nitrogen atom to which they are attached, form a saturated 4 to 8 membered ring optionally containing an oxygen atom or a further nitrogen atom as a ring member, the further nitrogen atom being unsubstituted or substituted by C.sub.1-4 alkyl, C.sub.2-4 alkenyl or C.sub.2-4 alkynyl; R.sup.12 is hydrogen or C.sub.1-6 alkyl; m is zero or 1; p is zero, 1 or 2; q is 0, 1 or 2; and r is 0, 1 or 2; the preparation of these compounds, their use in enhancing cognition in disease states, particularly Alzheimer's disease, and methods of treatment using them.

  本发明提供了式(I)的化合物及其药学上可接受的盐：##STR1##其中A为C.sub.1-6烷基，C.sub.2-6烯基，C.sub.2-6炔基，C.sub.3-6环烷基，芳基C.sub.1-6烷基，芳基，S(O).sub.p R.sup.1，OR.sup.1或NR.sup.1 R.sup.12；B为可选择取代的5-或6-成员杂芳环或C(O)NR.sup.10 R.sup.11；R.sup.1为氢，可选择取代的C.sub.1-6烷基，C.sub.2-6烯基，C.sub.2-6炔基，C.sub.3-6环烷基或C.sub.3-6环烯基，可选择取代的芳基，芳基C.sub.1-6烷基，芳基C.sub.2-6烯基或芳基C.sub.2-6炔基或可选择取代的5-或6-成员杂芳环；R.sup.2和R.sup.3为氢或C.sub.1-6烷基；R.sup.4为氢，C.sub.1-8烷基，C.sub.2-8烯基，C.sub.2-8炔基，芳基或CH.sub.2(CO).sub.m NR.sup.8 R.sup.9；R.sup.5为NR.sup.6 R.sup.7，C.sub.1-6烷基或C.sub.1-6烷氧基；R.sup.6独立定义为R.sup.4；R.sup.7为芳基，可选择取代的卤素，硝基或氰基；R.sup.8为氢，C.sub.1-6烷基，C.sub.3-6环烷基，C.sub.3-6环烯基，C.sub.2-6烯基，C.sub.2-6炔基；芳基C.sub.1-6烷基，芳基C.sub.2-6烯基或芳基C.sub.2-6炔基，可选择取代的卤素，硝基或氰基的芳基环；噻吩或吡啶；R.sup.9为C.sub.1-6烷基；C.sub.2-烯基；C.sub.2-6炔基；或苯基，可选择取代为一个，两个或三个独立选择的卤素，CF.sub.3，OCH.sub.3，硝基和氰基；R.sup.10和R.sup.11分别为氢，C.sub.1-6烷基，C.sub.2-6烯基，C.sub.2-6炔基或C.sub.3-8环烷基或R.sup.10和R.sup.11，与它们连接的氮原子一起形成饱和的4到8成员环，可选择包含一个氧原子或另一个氮原子作为环成员，另一个氮原子未取代或取代为C.sub.1-4烷基，C.sub.2-4烯基或C.sub.2-4炔基；R.sup.12为氢或C.sub.1-6烷基；m为零或1；p为零，1或2；q为0，1或2；r为0，1或2；这些化合物的制备，它们在增强认知能力中的应用，特别是在疾病状态下，尤其是阿尔茨海默病中的治疗方法。