6,6-二甲基-3-(甲硫基)-4-氧代-4,5,6,7-四氢-2-苯并噻吩-1-羧酸 | 172516-41-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 中文名称: 6,6-二甲基-3-(甲硫基)-4-氧代-4,5,6,7-四氢-2-苯并噻吩-1-羧酸
• 英文名称: 6,6-dimethyl-3-methylthio-4-oxo-4,5,6,7-tetrahydro-2-benzothiophene-1-carboxylic acid
• 英文别名: 6,6-dimethyl-3-methylsulfanyl-4-oxo-4,5,6,7-tetrahydro-benzo[c]thiophene-1-carboxylic acid；6,6-dimethyl-3-methylthio-4-oxo-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxylic acid；6,6-dimethyl-3-methylthio-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one-1-carboxylic acid；6,6-Dimethyl-3-(methylthio)-4-oxo-4,5,6,7-tetrahydrobenzo[c]thiophene-1-carboxylic acid；6,6-dimethyl-3-methylsulfanyl-4-oxo-5,7-dihydro-2-benzothiophene-1-carboxylic acid
• CAS: 172516-41-5
• 化学式: C₁₂H₁₄O₃S₂
• 分子量: 270.373
• InChiKey: XOXHNCQEJNHCDW-UHFFFAOYSA-N

物化性质

• 沸点：
  443.3±45.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  6,6-二甲基-3-(甲硫基)-4-氧代-4,5,6,7-四氢-2-苯并噻吩-1-羧酸 生成 1-{1-[4-(3-Aminomethyl-phenyl)-piperidin-1-yl]-methanoyl}-6, 6-dimethyl-3-methylsulfanyl-6,7-dihydro-5H-benzo[c]thiophen-4-one trifluoroacetate
  参考文献：
  名称：

  Chemical compounds

  摘要：

  本文提供了具有胰蛋白酶抑制活性的新颖和有用化合物，包括含有这些化合物的药物组合物，以及治疗患有可以通过给予胰蛋白酶抑制剂（例如哮喘和炎症性疾病等）而得到改善的疾病、疾病或紊乱的方法。

  公开号：

  US20030187020A1

文献信息

• Thienycyclohexanone derivatives as ligands of the GABAA &agr;5 receptor subtype
  申请人：Merck Sharp & Dohme Limited

  公开号：US06262103B1

  公开（公告）日：2001-07-17

  A pharamceutical composition comprises a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein A is C1-6alkyl, C2-6alkenyl, C2-6-alkynyl, C3-6-cycloalkyl, arylC1-6alkyl, aryl, S(O)pR1.

  一种药物组合物包括式(I)的化合物或其药用可接受的盐，其中A为C1-6烷基，C2-6烯基，C2-6炔基，C3-6环烷基，芳基C1-6烷基，芳基，S(O)pR1。
• [EN] ARYLMETHYLAMINE DERIVATIVES FOR USE AS TRYPTASE INHIBITORS<br/>[FR] DERIVES D'ARYLMETHYLAMINE UTILISES COMME INHIBITEURS DE LA TRYPTASE
  申请人：AVENTIS PHARM PROD INC

  公开号：WO2001090101A1

  公开（公告）日：2001-11-29

  Provided herein are compounds of formula (I) wherein R1-4, n and Ar are as defined in claim 1, and their pharmaceutical compositions. These compounds are tryptase inhibitors and may be used in the treatment of e.g. asthma and inflammatory diseases.

  本发明提供了式(I)的化合物，其中R1-4、n和Ar如权利要求1所定义，以及它们的药物组成物。这些化合物是胰蛋白酶抑制剂，可用于治疗哮喘和炎症性疾病等疾病。
• 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.

  本发明提供了公式（I）的化合物及其药学上可接受的盐：##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）.sub.pR.sup.1，OR.sup.1或NR.sup.1R.sup.12；B是可选取代的5或6元杂环芳香环或C（O）NR.sup.10R.sup.11；R.sup.1是氢，可选取代的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炔基或可选取代的5或6元杂环芳香环；R.sup.2和R.sup.3是氢或C.sub.1-6烷基；R.sup.4是氢，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.mNR.sup.8R.sup.9；R.sup.5是NR.sup.6R.sup.7，C.sub.1-6烷基或C.sub.1-6烷氧基；R.sup.6是独立定义为R.sup.4；R.sup.7是芳基，可选取代卤素，硝基或氰基；R.sup.8是氢，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，可选取代卤素，硝基或氰基；噻吩或吡啶；R.sup.9是C.sub.1-6烷基；C.sub.2-烯基；C.sub.2-6炔基；或苯基，可选取代一个，两个或三个独立选择的取代基，所述取代基选自卤素，CF.sub.3，OCH.sub.3，硝基和氰基；R.sup.10和R.sup.11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，所述环可以是选自氧原子或进一步的氮原子的环成员，所述进一步的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是氢或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，它们在疾病状态下增强认知能力的用途，特别是阿尔茨海默病，并使用它们的治疗方法。
• 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.

  本发明提供了公式（I）的化合物或其药学上可接受的盐：##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.1R.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，其中每个基都可以被氨基，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烷基氨基甲酰基，一个，两个或三个羟基，一个，两个或三个卤原子或一个四，五或六元饱和杂环环，其中包含一个氮原子，并且可以选择在进一步的氮原子上用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，可选择在芳基环上用卤素，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; 或者是一个含有1,2,3或4个来自O，N和S的杂原子的五元芳香环，前提是不超过一个杂原子不是N，或者是一个含有1,2,3或4个氮原子的六元芳香环，其中每个环可选择用卤素，C.sub.1-6烷氧基，C.sub.1-6烷基硫代基，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独立地是氢或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到8成员环，可选择包含一个氧原子或作为环成员的进一步氮原子，进一步氮原子未取代或被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，它们在疾病状态中增强认知的用途，特别是阿尔茨海默病，并且使用它们的治疗方法。
• 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.