1-(1,2,4-噻二唑-5-基)哌嗪 | 67869-93-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 1-(1,2,4-噻二唑-5-基)哌嗪
• 英文名称: 1-(1,2,4-Thiadiazol-5-yl)piperazin
• 英文别名: 1-[1,2,4]thiadiazol-5-yl-piperazine；1-(1,2,4-Thiadiazol-5-YL)piperazine；5-piperazin-1-yl-1,2,4-thiadiazole
• CAS: 67869-93-6
• 化学式: C₆H₁₀N₄S
• 分子量: 170.238
• InChiKey: BLGDMQAEKJZPMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  69.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S,5S)-1-(tert-butoxycarbonyl)-5-(1-pyrrolidinylcarbonyl)-3-pyrrolidinecarboxylic acid 、 1-(1,2,4-噻二唑-5-基)哌嗪 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 17.0h， 生成 tert-butyl (2S,4S)-2-(1-pyrrolidinylcarbonyl)-4-{[4-(1,2,4-thiadiazol-5-yl)-1-piperazinyl]carbonyl}-1-pyrrolidinecarboxylate
  参考文献：
  名称：

  Design and synthesis of DPP-IV inhibitors lacking the electrophilic nitrile group

  摘要：

  A series of (4 beta-substituted)-L-prolylpyrrolidine analogs lacking the electrophilic nitrile function were synthesized and their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and duration of ex vivo activity were evaluated. Structural optimization of a N-(3-phenyl-1,2,4-thiadiazol-5-yl) piperazine analog 8, which was found by high-speed analog synthesis, was carried out to improve the potency and duration of action. A representative compound 26 was evaluated to assess its effect on the plasma glucose level after the oGTT (oral glucose tolerance test) in normal rats. Structure-activity relationships (SAR) are also presented. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.031
• 作为产物：
  描述：

  tert-butyl 4-(1,2,4-thiadiazol-5-yl)-1-piperazinecarboxylate 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 1-(1,2,4-噻二唑-5-基)哌嗪
  参考文献：
  名称：

  Design and synthesis of DPP-IV inhibitors lacking the electrophilic nitrile group

  摘要：

  A series of (4 beta-substituted)-L-prolylpyrrolidine analogs lacking the electrophilic nitrile function were synthesized and their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and duration of ex vivo activity were evaluated. Structural optimization of a N-(3-phenyl-1,2,4-thiadiazol-5-yl) piperazine analog 8, which was found by high-speed analog synthesis, was carried out to improve the potency and duration of action. A representative compound 26 was evaluated to assess its effect on the plasma glucose level after the oGTT (oral glucose tolerance test) in normal rats. Structure-activity relationships (SAR) are also presented. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.031

文献信息

• 1, 2, 4-Thiadiazol-5-Ylpiperazine derivatives useful in the treatment of neurodegenerative diseases
  申请人：Griffioen Gerard

  公开号：US20140128404A1

  公开（公告）日：2014-05-08

  The present invention relates to a compound of formula (IA) The present invention also relates to the use of the compound of formula IA for treating certain neurodegenerative disorders characterized by cytotoxic TAU misfolding and/or aggregation.

  本发明涉及一种化合物的公式（IA）。本发明还涉及利用公式IA化合物治疗由细胞毒性TAU错误折叠和/或聚集特征的某些神经退行性疾病。
• [DE] SUBSTITUIERTE 1-PROPIOLYL-PIPERAZINE MIT AFFINITÄT FÜR DEN MGLUR5 REZEPTOR ZUR BEHANDLUNG VON SCHMERZZUSTÄNDEN<br/>[EN] SUBSTITUTED 1-PROPIOLYLPIPERAZINES HAVING AN AFFINITY FOR THE MGLUR5 RECEPTOR IN ORDER TO TREAT PAINFUL CONDITIONS<br/>[FR] 1-PROPIOLYLPIPERAZINES SUBSTITUEES PRESENTANT UNE AFFINITE POUR LE RECEPTEUR MGLUR5, UTILISEES POUR LE TRAITEMENT DE DOULEURS
  申请人：GRUENENTHAL GMBH

  公开号：WO2006002981A1

  公开（公告）日：2006-01-12

  Die vorliegende Erfindung betrifft substituierte 1-Propiolyl-piperazine gemäss Formel (I), Verfahren zu ihrer Herstellung, Arzneimittel enthaltend diese Verbindungen sowie deren Verwendung zur Herstellung von Arzneimitteln. (I), worin X für N oder C-R2 steht und n einem Wert zwischen 0-8 entspricht.

  这项发明涉及按照式(I)的取代的1-丙炔基哌嗪，其制备方法，包含这些化合物的药物以及它们用于制备药物的用途。(I)，其中X代表N或C-R2，n为0-8之间的值。
• [EN] 1, 2, 4 -THIADIAZOL- 5 -YLPIPERAZINE DERIVATIVES USEFUL IN THE TREATMENT NEURODEGENERATIVE DISEASES<br/>[FR] DÉRIVÉS DE 1,2,4-THIADIAZOL-5-YLPIPÉRAZINE UTILES DANS LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：REMYND NV

  公开号：WO2013004642A1

  公开（公告）日：2013-01-10

  The present invention relates to a compound of formula (IA) The present invention also relates to the use of the compound of formula IA for treating certain neurodegenerative disorders characterized by cytotoxic TAU misfolding and/or aggregation.

  本发明涉及一种化合物，其化学式为（IA）。本发明还涉及利用化合物IA治疗某些以细胞毒性TAU错误折叠和/或聚集为特征的神经退行性疾病。
• Substituted 1-propiolylpiperazine compounds, their preparation and use
  申请人：Kuhnert Sven

  公开号：US20070112011A1

  公开（公告）日：2007-05-17

  Substituted 1-propiolylpiperazine compounds corresponding to formula I in which X denotes N or C—R 2 , and n is an integer from 0 to 8, a method for producing such substituted 1-propiolylpiperazine compounds, pharmaceutical compositions containing such substituted 1-propiolylpiperazine compounds, and the use of such substituted 1-propiolylpiperazine compounds for modulating mGluR5 receptor activity or for treating or inhibiting pain and various other conditions, especially conditions at least partly mediated by the mGluR5 receptor.

  将符合公式I的1-丙炔基哌嗪化合物替代为X代表N或C—R，n为0至8的整数，一种生产这种替代的1-丙炔基哌嗪化合物的方法，含有这种替代的1-丙炔基哌嗪化合物的药物组合物，以及利用这种替代的1-丙炔基哌嗪化合物调节mGluR5受体活性或用于治疗或抑制疼痛和其他各种病症，特别是至少部分由mGluR5受体介导的病症。
• [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。