1-[3-(4,4-difluoropiperidin-1-yl)-[1,2,4]thiadiazol-5-yl]-4-[2-(4-methoxyphenyl)ethyl]piperazine | 1423042-07-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-[3-(4,4-difluoropiperidin-1-yl)-[1,2,4]thiadiazol-5-yl]-4-[2-(4-methoxyphenyl)ethyl]piperazine
• 英文别名: 1-[3-(4,4-Difluoro-piperidin-1-yl)-[1,2,4]thiadiazol-5-yl]-4-[2-(4-methoxy-phenyl)-ethyl]-piperazine；3-(4,4-difluoropiperidin-1-yl)-5-[4-[2-(4-methoxyphenyl)ethyl]piperazin-1-yl]-1,2,4-thiadiazole
• CAS: 1423042-07-2
• 化学式: C₂₀H₂₇F₂N₅OS
• 分子量: 423.53
• InChiKey: JNMBEQVBTVHKSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  73
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1-(4-methoxyphenethyl)piperazine dihydrochloride 在 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 、 乙醇 为溶剂， 反应 2.5h， 生成 1-[3-(4,4-difluoropiperidin-1-yl)-[1,2,4]thiadiazol-5-yl]-4-[2-(4-methoxyphenyl)ethyl]piperazine
  参考文献：
  名称：

  [EN] PIPERAZINE THIAZOLE DERIVATIVES USEFUL IN THE TREATMENT OF TAUOPATHIES SUCH AS ALZHEIMER'S DISEASE
  [FR] DÉRIVÉS DE PIPÉRAZINE THIAZOLE UTILES DANS LE TRAITEMENT DES TAUOPATHIES TELLES QUE LA MALADIE D'ALZHEIMER

  摘要：

  本发明涉及一种具有以下结构的化合物（IA），其中G1是较低的烷基；较低的烷基上被一个或多个卤素取代；环烷基；四氢吡喃-4-基；苯乙基；一个或多个卤素取代的苯乙基；苯氧甲基；一个或多个卤素取代的苯氧甲基；苄氧乙基；一个或多个卤素取代的苄氧乙基；或者是-NR2R3；R2是氢或较低的烷基；R3是较低的烷基；四氢吡喃-4-基；-CH2-环烷基；或者是环烷基，可选地被一个或多个卤素取代的较低烷基取代；或者R2和R3与它们连接的N原子一起形成一个由4或5个碳原子组成的杂环烷基基团，该基团可选地被一个或多个卤素选自取代；或者一个或多个卤素取代的较低烷基；X是-CH2-或-(CH2)2-；Ar是苯基或吡啶基；R4是卤素；较低的烷基；一个或多个卤素取代的较低烷基；或者较低的烷氧基；n是1或2；或者是其药用活性盐，立体异构体形式，包括化合物（IA）的单个对映异构体或对映体，以及其消旋或非消旋混合物。本发明还涉及使用化合物（IA）治疗由细胞毒性TAU蛋白错误折叠和/或聚集特征的某些神经退行性疾病。

  公开号：

  WO2013024168A1

文献信息

• PIPERAZINE THIAZOLE DERIVATIVES USEFUL IN THE TREATMENT OF TAUOPATHIES SUCH AS ALZHEIMER'S DISEASE
  申请人：Griffioen Gerard

  公开号：US20140206699A1

  公开（公告）日：2014-07-24

  The present invention relates to a compound of formula (IA), wherein G 1 is lower alkyl; lower alkyl substituted by one or more halogens; cycloalkyl; tetrahydropyran-4-yl; phenethyl; phenethyl substituted by one or more halogens; phenoxymethyl; phenoxymethyl substituted by one or more halogens; benzyloxyethyl; benzyloxy-ethyl substituted by one or more halogens; or is —NR 2 R 3 ; R 2 is hydrogen or lower alkyl; R 3 is lower alkyl; tetrahydropyran-4-yl; —CH 2 -cycloalkyl; or cycloalkyl optionally substituted by lower alkyl substituted by one or more halogens; or R 2 and R 3 form together with the N-atom to which they are attached a heterocycloalkyl group with 4 or 5 carbon atoms, which is optionally substituted by one or more substituents selected from halogen; or lower alkyl substituted by one or more halogens; X is —CH 2 — or —(CH 2 ) 2 —; Ar is phenyl or pyridinyl; R 4 is halogen; lower alkyl; lower alkyl substituted by one or more halogens; or lower alkoxy; n is 1 or 2; or to a pharmaceutically active salt thereof, to a stereoisomeric form, including an individual diastereoisomer or enantiomer of the compound of formula (IA) as well as to a racemic or non-racemic mixture thereof. The present invention also relates to the use of a compound of formula (IA) for treating certain neurodegenerative disorders characterized by cytotoxic TAU misfolding and/or aggregation.

  本发明涉及式（IA）的化合物，其中G1是低碳基；被一个或多个卤素取代的低碳基；环烷基；四氢吡喃-4-基；苯乙基；被一个或多个卤素取代的苯乙基；苯氧甲基；被一个或多个卤素取代的苯氧甲基；苄氧乙基；被一个或多个卤素取代的苄氧乙基；或为-NR2R3；R2为氢或低碳基；R3为低碳基；四氢吡喃-4-基；-CH2-环烷基；或环烷基，该环烷基可被一个或多个被一个或多个卤素取代的低碳基取代；或R2和R3与它们附着的N原子一起形成一个有4或5个碳原子的杂环烷基，该杂环烷基可被一个或多个取代基选自卤素；或被一个或多个卤素取代的低碳基取代；X为-CH2-或-(CH2)2-；Ar为苯基或吡啶基；R4为卤素；低碳基；被一个或多个卤素取代的低碳基；或低碳氧基；n为1或2；或其药物活性盐，立体异构体形式，包括化合物（IA）的单个对映异构体或对映体以及它们的外消旋或非外消旋混合物。本发明还涉及使用式（IA）的化合物治疗某些神经退行性疾病，其特征为细胞毒性TAU错折和/或聚集。
• Piperazine thiazole derivatives useful in the treatment of tauopathies such as alzheimer's disease
  申请人：Griffioen Gerard

  公开号：US09187440B2

  公开（公告）日：2015-11-17

  The present invention relates to a compound of formula (IA), wherein G1 is lower alkyl; lower alkyl substituted by one or more halogens; cycloalkyl; tetrahydropyran-4-yl; phenethyl; phenethyl substituted by one or more halogens; phenoxymethyl; phenoxymethyl substituted by one or more halogens; benzyloxyethyl; benzyloxy-ethyl substituted by one or more halogens; or is —NR2R3; R2 is hydrogen or lower alkyl; R3 is lower alkyl; tetrahydropyran-4-yl; —CH2-cycloalkyl; or cycloalkyl optionally substituted by lower alkyl substituted by one or more halogens; or R2 and R3 form together with the N-atom to which they are attached a heterocycloalkyl group with 4 or 5 carbon atoms, which is optionally substituted by one or more substituents selected from halogen; or lower alkyl substituted by one or more halogens; X is —CH2—or —(CH2)2—; Ar is phenyl or pyridinyl; R4 is halogen; lower alkyl; lower alkyl substituted by one or more halogens; or lower alkoxy; n is 1 or 2; or to a pharmaceutically active salt thereof, to a stereoisomeric form, including an individual diastereoisomer or enantiomer of the compound of formula (IA) as well as to a racemic or non-racemic mixture thereof. The present invention also relates to the use of a compound of formula (IA) for treating certain neurodegenerative disorders characterized by cytotoxic TAU misfolding and/or aggregation.

  本发明涉及IA式化合物，其中G1是低碳基；被一个或多个卤素取代的低碳基；环烷基；四氢吡喃-4-基；苯乙基；被一个或多个卤素取代的苯乙基；苯氧甲基；被一个或多个卤素取代的苯氧甲基；苄氧乙基；被一个或多个卤素取代的苄氧乙基；或为—NR2R3；R2为氢或低碳基；R3为低碳基；四氢吡喃-4-基；—CH2-环烷基；或被一个或多个卤素取代的低碳基取代的环烷基；或R2和R3与它们所附着的N原子一起形成一个具有4或5个碳原子的杂环烷基，该烷基可以被一个或多个卤素；或被一个或多个卤素取代的低碳基取代；X为—CH2—或—（CH2）2—；Ar为苯基或吡啶基；R4为卤素；低碳基；被一个或多个卤素取代的低碳基；或低碳氧基；n为1或2；或其药物活性盐，立体异构体形式，包括化合物IA的单个对映异构体或对映体以及其外消旋或非外消旋混合物。本发明还涉及使用化合物IA治疗由细胞毒性TAU错折和/或聚集所特征的某些神经退行性疾病。
• US9187440B2
  申请人：——

  公开号：US9187440B2

  公开（公告）日：2015-11-17
• US9808456B2
  申请人：——

  公开号：US9808456B2

  公开（公告）日：2017-11-07
• [EN] PIPERAZINE THIAZOLE DERIVATIVES USEFUL IN THE TREATMENT OF TAUOPATHIES SUCH AS ALZHEIMER'S DISEASE<br/>[FR] DÉRIVÉS DE PIPÉRAZINE THIAZOLE UTILES DANS LE TRAITEMENT DES TAUOPATHIES TELLES QUE LA MALADIE D'ALZHEIMER
  申请人：REMYND NV

  公开号：WO2013024168A1

  公开（公告）日：2013-02-21

  The present invention relates to a compound of formula (IA), wherein G1 is lower alkyl; lower alkyl substituted by one or more halogens; cycloalkyl; tetrahydropyran-4-yl; phenethyl; phenethyl substituted by one or more halogens; phenoxymethyl; phenoxymethyl substituted by one or more halogens; benzyloxyethyl; benzyloxy-ethyl substituted by one or more halogens; or is -NR2R3; R2 is hydrogen or lower alkyl; R3 is lower alkyl; tetrahydropyran-4-yl; -CH2-cycloalkyl; or cycloalkyl optionally substituted by lower alkyl substituted by one or more halogens; or R2 and R3 form together with the N-atom to which they are attached a heterocycloalkyl group with 4 or 5 carbon atoms, which is optionally substituted by one or more substituents selected from halogen; or lower alkyl substituted by one or more halogens; X is -CH2- or -(CH2)2-; Ar is phenyl or pyridinyl; R4 is halogen; lower alkyl; lower alkyl substituted by one or more halogens; or lower alkoxy; n is 1 or 2; or to a pharmaceutically active salt thereof, to a stereoisomeric form, including an individual diastereoisomer or enantiomer of the compound of formula (IA) as well as to a racemic or non-racemic mixture thereof. The present invention also relates to the use of a compound of formula (IA) for treating certain neurodegenerative disorders characterized by cytotoxic TAU misfolding and/or aggregation.

  本发明涉及一种具有以下结构的化合物（IA），其中G1是较低的烷基；较低的烷基上被一个或多个卤素取代；环烷基；四氢吡喃-4-基；苯乙基；一个或多个卤素取代的苯乙基；苯氧甲基；一个或多个卤素取代的苯氧甲基；苄氧乙基；一个或多个卤素取代的苄氧乙基；或者是-NR2R3；R2是氢或较低的烷基；R3是较低的烷基；四氢吡喃-4-基；-CH2-环烷基；或者是环烷基，可选地被一个或多个卤素取代的较低烷基取代；或者R2和R3与它们连接的N原子一起形成一个由4或5个碳原子组成的杂环烷基基团，该基团可选地被一个或多个卤素选自取代；或者一个或多个卤素取代的较低烷基；X是-CH2-或-(CH2)2-；Ar是苯基或吡啶基；R4是卤素；较低的烷基；一个或多个卤素取代的较低烷基；或者较低的烷氧基；n是1或2；或者是其药用活性盐，立体异构体形式，包括化合物（IA）的单个对映异构体或对映体，以及其消旋或非消旋混合物。本发明还涉及使用化合物（IA）治疗由细胞毒性TAU蛋白错误折叠和/或聚集特征的某些神经退行性疾病。