6,6-dimethyl-3-methylthio-1-(pyrid-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one | 252056-21-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 6,6-dimethyl-3-methylthio-1-(pyrid-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one
• 英文别名: 6,6-Dimethyl-3-methylsulfanyl-1-pyridin-3-yl-6,7-dihydro-5H-benzo[c]thiophen-4-one；6,6-dimethyl-3-methylsulfanyl-1-pyridin-3-yl-5,7-dihydro-2-benzothiophen-4-one
• CAS: 252056-21-6
• 化学式: C₁₆H₁₇NOS₂
• 分子量: 303.449
• InChiKey: IYEJMUDDGFBLEF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  83.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6,6-dimethyl-3-methylthio-1-(pyrid-3-yl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one 以34%的产率得到6,6-dimethyl-5-hydroxymethylene-3-methylthio-1-(pyrid-3-yl)-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：

  3-(1,1,1-三丁基甲锡烷)嘧啶 以29%的产率得到6,6-dimethyl-3-methylthio-1-(pyrid-3-yl)-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

• Identification of a Novel, Selective GABA_A α5 Receptor Inverse Agonist Which Enhances Cognition
  作者：Mark S. Chambers、John R. Atack、Howard B. Broughton、Neil Collinson、Susan Cook、Gerard R. Dawson、Sarah C. Hobbs、George Marshall、Karen A. Maubach、Goplan V. Pillai、Austin J. Reeve、Angus M. MacLeod

  DOI：10.1021/jm020582q

  日期：2003.5.1

  In pursuit of a GABA(A) alpha5-subtype-selective inverse agonist to enhance cognition, a series of 6,7-dihydro-2-benzothiophen-4(5H)-ones has been identified as a novel class of GABAA receptor ligands. These thiophenes have higher binding affinity for the GABA(A) alpha(5) receptor subtype compared to the GABA(A) alpha(1), alpha(2), and alpha(3) subtypes, and several analogues exhibit high GABA(A) (alpha(5) receptor inverse agonism. 6,6-Dimethyl-3-(2-hydroxyethyl)thio-1-(thiazol-2-yl)-6,7-dihydro2-benzothiophen-4(5H)-one (43) has been identified as a full inverse agonist at the GABA(A) alpha5 receptor and is functionally selective over the other major GABA(A) receptor subtypes. 43 readily penetrates into the CNS to give selective occupancy of GABA(A) alpha5 receptors. In addition, 43 enhances cognitive performance in rats in the delayed 'matching-to-place' Morris water maze test-a hippocampal-dependent memory task-without the convulsant or proconvulsant activity associated with nonselective, GABA(A) receptor inverse agonists.
• 6,7-Dihydro-2-benzothiophen-4(5<i>H</i>)-ones:  A Novel Class of GABA-A α5 Receptor Inverse Agonists
  作者：Mark S. Chambers、John R. Atack、Frances A. Bromidge、Howard B. Broughton、Susan Cook、Gerard R. Dawson、Sarah C. Hobbs、Karen A. Maubach、Austin J. Reeve、Guy R. Seabrook、Keith Wafford、Angus M. MacLeod

  DOI：10.1021/jm010471b

  日期：2002.3.1

  Nonselective inverse agonists at the benzodiazepine binding site on the GABA-A chloride ion channel enhance cognitive performance in animals but cannot be used in the treatment of cognitive disorders because of anxiogenic and convulsant side effects. We have identified a novel series of GABA-A alpha5 receptor ligands during our search for alpha5 receptor inverse agonists as potential cognition enhancers. In particular, 6,6-dimethyl-3-(2-hydroxyethyl)thio-1-(thiazol-2-yl)-6,7-dihydro- 2-benzothiophen-4(5H-)-one (26) has been identified as a functionally selective GABA-A alpha5 inverse agonist.
• US6143773A
  申请人：——

  公开号：US6143773A

  公开（公告）日：2000-11-07
• 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。