6,6-Dimethyl-3-methanesulphonyl-1-(pyrrolidin-1-ylcarbonyl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one | 252048-73-0

• 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-3-methanesulphonyl-1-(pyrrolidin-1-ylcarbonyl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one
• 英文别名: 6,6-dimethyl-3-methylsulfonyl-1-(pyrrolidine-1-carbonyl)-5,7-dihydro-2-benzothiophen-4-one
• CAS: 252048-73-0
• 化学式: C₁₆H₂₁NO₄S₂
• 分子量: 355.479
• InChiKey: SMALZSPQKVRPOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  108
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6,6-Dimethyl-3-methanesulphonyl-1-(pyrrolidin-1-ylcarbonyl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one 、 异丙硫醇 在 sodium hydroxide 作用下， 以44%的产率得到6,6-dimethyl-3-isopropylthio-1-(pyrrolidin-1-ylcarbonyl)-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
• 作为产物：
  描述：

  m-chloroperoxybenzoic acid 、 6,6-dimethyl-3-methylthio-1-(pyrrolidin-1-ylcarbonyl)-4,5,6,7-tetrahydrobenzo [c]thiophen-4-one 以 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 为溶剂， 生成 6,6-Dimethyl-3-methanesulphonyl-1-(pyrrolidin-1-ylcarbonyl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one
  参考文献：
  名称：

  Substituted thienlycyclohexanone derivatives for enhancing cognition

  摘要：

  本发明提供了式(I)的化合物或其药用可接受的盐：##STR1##其中A是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)，R.sup.1，OR.sup.1或NR.sup.1 R.sup.6；R.sup.1是氢；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，其中每种都可以被氨基，C.sub.1-6烷基氨基，二(C.sub.1-6烷基)氨基，C.sub.1-6烷氧基，C.sub.1-6烷基氨基甲酰，一个，两个或三个羟基，一个，两个或三个卤原子或含有氮原子的四、五或六元饱和杂环环，该环上的氮原子和/或进一步的氮原子，该环上的氮原子上可以被C.sub.1-4烷基取代；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，可选地在芳基环上被卤素，硝基，氰基，C.sub.1-6烷基羰基氨基，羟基或C.sub.1-6烷氧基取代；或者一个含有1、2、3或4个O、N和S杂原子的五元芳环，前提是不超过一个杂原子不是N，或者一个含有1、2、3或4个氮原子的六元芳环，每个环可选地被卤素，C.sub.1-6烷氧基，C.sub.1-6烷硫基，芳基，C.sub.1-6烷基，C.sub.2-6烯基或C.sub.2-6炔基取代；R.sup.2和R.sup.3分别是氢或C.sub.1-6烷基，或者与它们连接的碳原子一起形成C.sub.3-8环烷基；R.sup.4和R.sup.5分别是氢，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，或者R.sup.12和R.sup.13与它们连接的氮原子一起形成饱和的4至8成员环，该环可选地包含一个氧原子或另一个氮原子作为环成员，进一步的氮原子未取代或被C.sub.1-4烷基，C.sub.2-4烯基或C.sub.2-4炔基取代；R.sup.6是氢或C.sub.1-6烷基；p为零、1或2；q为0、1或2；这些化合物的制备，它们在增强认知功能的疾病状态中的应用，特别是阿尔茨海默病，并使用它们的治疗方法。

  公开号：

  US06156787A1

文献信息

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

  公开号：US06156787A1

  公开（公告）日：2000-12-05

  The present invention provides compounds of formula (I) or pharmaceutically acceptable salts thereof: ##STR1## where 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),R.sup.1, OR.sup.1 or NR.sup.1 R.sup.6 ; R.sup.1 is hydrogen; 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 each of which is optionally substituted by amino, C.sub.1-6 alkylamino, di(C.sub.1-6 alkyl)amino, C.sub.1-6 alkoxy, C.sub.1-6 alkylaminocarbonyl, one, two or three hydroxy groups, one, two or three halogen atoms or a four, five or six-membered saturated heterocyclic ring containing a nitrogen atom and optionally either an oxygen atom or a further nitrogen atom which ring is optionally substituted by C.sub.1-4 alkyl on the further nitrogen atom; aryl, 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, cyano, C.sub.1-6 alkylcarbonylamino, hydroxy or C.sub.1-6 alkoxy; or a five-membered aromatic ring containing 1, 2, 3 or 4 heteroatoms chosen from O, N and S provided that not more than one heteroatom is other than N, or a six-membered aromatic ring containing 1, 2, 3 or 4 nitrogen atoms, each of which rings is optionally substituted by halogen, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, aryl, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl; R.sup.2 and R.sup.3 are independently hydrogen or C.sub.1-6 alkyl or together with the carbon atom to which they are attached form a C.sub.3-8 cycloalkyl group; R.sup.4 and R.sup.5 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.12 and R.sup.13, 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.6 is hydrogen or C.sub.1-6 alkyl; p is zero, 1 or 2; and q 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)的化合物或其药用可接受的盐：##STR1##其中A是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)，R.sup.1，OR.sup.1或NR.sup.1 R.sup.6；R.sup.1是氢；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，其中每种都可以被氨基，C.sub.1-6烷基氨基，二(C.sub.1-6烷基)氨基，C.sub.1-6烷氧基，C.sub.1-6烷基氨基甲酰，一个，两个或三个羟基，一个，两个或三个卤原子或含有氮原子的四、五或六元饱和杂环环，该环上的氮原子和/或进一步的氮原子，该环上的氮原子上可以被C.sub.1-4烷基取代；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，可选地在芳基环上被卤素，硝基，氰基，C.sub.1-6烷基羰基氨基，羟基或C.sub.1-6烷氧基取代；或者一个含有1、2、3或4个O、N和S杂原子的五元芳环，前提是不超过一个杂原子不是N，或者一个含有1、2、3或4个氮原子的六元芳环，每个环可选地被卤素，C.sub.1-6烷氧基，C.sub.1-6烷硫基，芳基，C.sub.1-6烷基，C.sub.2-6烯基或C.sub.2-6炔基取代；R.sup.2和R.sup.3分别是氢或C.sub.1-6烷基，或者与它们连接的碳原子一起形成C.sub.3-8环烷基；R.sup.4和R.sup.5分别是氢，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，或者R.sup.12和R.sup.13与它们连接的氮原子一起形成饱和的4至8成员环，该环可选地包含一个氧原子或另一个氮原子作为环成员，进一步的氮原子未取代或被C.sub.1-4烷基，C.sub.2-4烯基或C.sub.2-4炔基取代；R.sup.6是氢或C.sub.1-6烷基；p为零、1或2；q为0、1或2；这些化合物的制备，它们在增强认知功能的疾病状态中的应用，特别是阿尔茨海默病，并使用它们的治疗方法。
• US6143773A
  申请人：——

  公开号：US6143773A

  公开（公告）日：2000-11-07
• US6156787A
  申请人：——

  公开号：US6156787A

  公开（公告）日：2000-12-05
• 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。