4-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-5-methylthiazol-2-amine | 1235313-79-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-5-methylthiazol-2-amine
• 英文别名: 4-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-5-methyl-1,3-thiazol-2-amine
• CAS: 1235313-79-7
• 化学式: C₁₅H₁₆N₄OS
• 分子量: 300.384
• InChiKey: RPQXQQKSNPVMJZ-UHFFFAOYSA-N

物化性质

• 沸点：
  531.2±50.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-5-methylthiazol-2-amine 在 三氟乙酸 作用下， 反应 4.0h， 以88%的产率得到
  参考文献：
  名称：

  Radiosynthesis and evaluation of 5-methyl- N -(4-[ 11 C]methylpyrimidin-2-yl)-4-(1 H -pyrazol-4-yl)thiazol-2-amine ([ 11 C]ADX88178) as a novel radioligand for imaging of metabotropic glutamate receptor subtype 4 (mGluR4)

  摘要：

  ADX88178 (1) has been recently developed as a potent positive allosteric modulator for metabotropic glutamate receptor 4 (mGluR4). The aim of this study was to develop [C-11]1 as a novel positron emission tomography ligand and to evaluate its binding ability for mGluR4. Using stannyl precursor 3, [C-11]1 was efficiently synthesized by introducing an [C-11]methyl group into a pyrimidine ring via C-C-11 coupling and deprotection reactions, in 16 +/- 6% radiochemical yield (n = 10). At the end of synthesis, 0.54-1.10 GBq of [C-11]1 was acquired with > 98% radiochemical purity and 90-120 GBq/mu mol of specific activity. In vitro autoradiography and ex vivo biodistribution study in rat brains showed specific binding of [C-11]1 in the cerebellum, striatum, thalamus, cerebral cortex, and medulla oblongata, which showed dose-dependent decreases by administration with multi-dose of unlabeled 1. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.12.008
• 作为产物：
  描述：

  2-bromo-1-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)propan-1-one 、 硫脲 以 丙酮 为溶剂， 反应 3.0h， 以96%的产率得到4-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-5-methylthiazol-2-amine
  参考文献：
  名称：

  [EN] NOVEL THIAZOLES DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
  [FR] NOUVEAUX DÉRIVÉS DE THIAZOLE ET LEUR EMPLOI EN TANT QUE MODULATEURS ALLOSTÉRIQUES POSITIFS DES RÉCEPTEURS MÉTABOTROPIQUES DU GLUTAMATE

  摘要：

  本发明涉及式（I）的新化合物，其中M、P、A和（B）n如式（I）中所定义；该发明化合物是代谢型谷氨酸受体-亚型4（"mGluR4"）的调节剂，对于治疗或预防中枢神经系统疾病以及其他受mGluR4受体调节的疾病具有用处。该发明还涉及制药组合物以及利用这类化合物制造药物的用途，以及利用这类化合物预防和治疗涉及mGluR4的疾病的用途。

  公开号：

  WO2010079239A1

文献信息

• NOVEL THIAZOLES DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
  申请人：Bolea Christelle

  公开号：US20110257179A1

  公开（公告）日：2011-10-20

  The present invention relates to novel compounds of Formula (I), wherein M, P, A and (B) n are defined as in Formula (I); invention compounds are modulators of metabotropic glutamate receptors—subtype 4 (“mGluR4”) which are useful for the treatment or prevention of central nervous system disorders as well as other disorders modulated by mGluR4 receptors. The invention is also directed to pharmaceutical compositions and the use of such compounds in the manufacture of medicaments, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR4 is involved.

  本发明涉及公式（I）的新化合物，其中M，P，A和（B）n如公式（I）中所定义；发明化合物是代谢型谷氨酸受体-亚型4（“mGluR4”）的调节剂，对于治疗或预防中枢神经系统疾病以及其他由mGluR4受体调节的疾病有用。本发明还涉及制药组合物以及使用这种化合物制造药物的用途，以及使用这种化合物预防和治疗涉及mGluR4的疾病的用途。
• Thiazoles derivatives and their use as positive allosteric modulators of metabotropic glutamate receptors
  申请人：Boléa Christelle

  公开号：US09073907B2

  公开（公告）日：2015-07-07

  The present invention relates to novel compounds of Formula (I), wherein M, P, A and (B)n are defined as in Formula (I); invention compounds are modulators of metabotropic glutamate receptors—subtype 4 (“mGluR4”) which are useful for the treatment or prevention of central nervous system disorders as well as other disorders modulated by mGluR4 receptors. The invention is also directed to pharmaceutical compositions and the use of such compounds in the manufacture of medicaments, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR4 is involved.

  本发明涉及公式（I）的新化合物，其中M、P、A和（B）n如公式（I）中所定义；发明化合物是代谢型谷氨酸受体亚型4（“mGluR4”）的调节剂，可用于治疗或预防中枢神经系统疾病以及其他受mGluR4受体调节的疾病。本发明还涉及制药组合物以及使用这种化合物制造药物的用途，以及使用这种化合物预防和治疗涉及mGluR4的疾病的用途。
• US9073907B2
  申请人：——

  公开号：US9073907B2

  公开（公告）日：2015-07-07
• [EN] NOVEL THIAZOLES DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS<br/>[FR] NOUVEAUX DÉRIVÉS DE THIAZOLE ET LEUR EMPLOI EN TANT QUE MODULATEURS ALLOSTÉRIQUES POSITIFS DES RÉCEPTEURS MÉTABOTROPIQUES DU GLUTAMATE
  申请人：ADDEX PHARMACEUTICALS SA

  公开号：WO2010079239A1

  公开（公告）日：2010-07-15

  The present invention relates to novel compounds of Formula (I), wherein M, P, A and (B)n are defined as in Formula (I); invention compounds are modulators of metabotropic glutamate receptors - subtype 4 ("mGluR4") which are useful for the treatment or prevention of central nervous system disorders as well as other disorders modulated by mGluR4 receptors. The invention is also directed to pharmaceutical compositions and the use of such compounds in the manufacture of medicaments, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR4 is involved.

  本发明涉及式（I）的新化合物，其中M、P、A和（B）n如式（I）中所定义；该发明化合物是代谢型谷氨酸受体-亚型4（"mGluR4"）的调节剂，对于治疗或预防中枢神经系统疾病以及其他受mGluR4受体调节的疾病具有用处。该发明还涉及制药组合物以及利用这类化合物制造药物的用途，以及利用这类化合物预防和治疗涉及mGluR4的疾病的用途。
• Radiosynthesis and evaluation of 5-methyl- N -(4-[ 11 C]methylpyrimidin-2-yl)-4-(1 H -pyrazol-4-yl)thiazol-2-amine ([ 11 C]ADX88178) as a novel radioligand for imaging of metabotropic glutamate receptor subtype 4 (mGluR4)
  作者：Masayuki Fujinaga、Tomoteru Yamasaki、Nobuki Nengaki、Masanao Ogawa、Katsushi Kumata、Yoko Shimoda、Joji Yui、Lin Xie、Yiding Zhang、Kazunori Kawamura、Ming-Rong Zhang

  DOI：10.1016/j.bmcl.2015.12.008

  日期：2016.1

  ADX88178 (1) has been recently developed as a potent positive allosteric modulator for metabotropic glutamate receptor 4 (mGluR4). The aim of this study was to develop [C-11]1 as a novel positron emission tomography ligand and to evaluate its binding ability for mGluR4. Using stannyl precursor 3, [C-11]1 was efficiently synthesized by introducing an [C-11]methyl group into a pyrimidine ring via C-C-11 coupling and deprotection reactions, in 16 +/- 6% radiochemical yield (n = 10). At the end of synthesis, 0.54-1.10 GBq of [C-11]1 was acquired with > 98% radiochemical purity and 90-120 GBq/mu mol of specific activity. In vitro autoradiography and ex vivo biodistribution study in rat brains showed specific binding of [C-11]1 in the cerebellum, striatum, thalamus, cerebral cortex, and medulla oblongata, which showed dose-dependent decreases by administration with multi-dose of unlabeled 1. (C) 2015 Elsevier Ltd. All rights reserved.