5-amino-4-carboxymethylthiothieno<2,3-d>pyrimidine-6-carboxylic acid, 4,6-dimethyl ester | 94556-55-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 5-amino-4-carboxymethylthiothieno<2,3-d>pyrimidine-6-carboxylic acid, 4,6-dimethyl ester
• 英文别名: methyl 5-amino-4-(methoxycarbonylmethylthio)thieno<2,3-d>pyrimidine-6-carboxylate；methyl 5-amino-4-(methoxycarbonylmethylthio)thieno[2,3-d]pyrimidine-6-carboxylate；Methyl 5-amino-4-(2-methoxy-2-oxoethyl)sulfanylthieno[2,3-d]pyrimidine-6-carboxylate
• CAS: 94556-55-5
• 化学式: C₁₁H₁₁N₃O₄S₂
• 分子量: 313.358
• InChiKey: QDHPOANQWQIRIH-UHFFFAOYSA-N

物化性质

• 沸点：
  497.3±45.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  158
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-amino-4-carboxymethylthiothieno<2,3-d>pyrimidine-6-carboxylic acid, 4,6-dimethyl ester 在 溶剂黄146 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 29.0h， 生成 C₁₅H₁₂N₆OS
  参考文献：
  名称：

  Synthesis and SAR development of novel mGluR1 antagonists for the treatment of chronic pain

  摘要：

  High throughput screening identified the pyridothienopyrimidinone 1 as a ligand for the metabotropic glutamate receptor 1 (mGluR1 = 10 nM). Compound 1 has an excellent in vivo profile; however, it displays unfavorable pharmacokinetic issues and metabolic stability. Therefore, using 1 as a template, novel analogues (10i) were prepared. These analogues displayed improved oral exposure and activity in the Spinal Nerve Ligation (SNL) pain model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.048
• 作为产物：
  描述：

  4,6-bis(methoxycarbonylmethylthio)pyrimidine-5-carbonitrile 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以78%的产率得到5-amino-4-carboxymethylthiothieno<2,3-d>pyrimidine-6-carboxylic acid, 4,6-dimethyl ester
  参考文献：
  名称：

  Fused tricyclic mGIuR1 antagonists as therapeutic agents

  摘要：

  在其许多实施例中，本发明提供了公式I的三环化合物（其中J1-J3、X、Z和R1、R3和R4如本文所定义）作为代谢型谷氨酸受体（mGluR）拮抗剂，特别作为选择性代谢型谷氨酸受体1拮抗剂，含有该化合物的药物组合物，以及使用该化合物和组合物治疗与代谢型谷氨酸受体（例如mGluR1）相关的疾病的方法，例如疼痛、偏头痛、焦虑、尿失禁和阿尔茨海默病等神经退行性疾病。

  公开号：

  US20070072864A1

文献信息

• Fused tricyclic mGIuR1 antagonists as therapeutic agents
  申请人：Bennett E. Chad

  公开号：US20070072864A1

  公开（公告）日：2007-03-29

  In its many embodiments, the present invention provides tricyclic compounds of formula I (wherein J 1 -J 3 , X, Z, and R 1 , R 3 , and R 4 are as defined herein) useful as metabotropic glutamate receptor (mGluR) antagonists, particularly as selective metabotropic glutamate receptor 1 antagonists, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds and compositions to treat diseases associated with metabotropic glutamate receptor (e.g., mGluR1) such as, for example, pain, migraine, anxiety, urinary incontinence and neurodegenerative diseases such Alzheimer's disease.

  在其许多实施例中，本发明提供了公式I的三环化合物（其中J1-J3、X、Z和R1、R3和R4如本文所定义）作为代谢型谷氨酸受体（mGluR）拮抗剂，特别作为选择性代谢型谷氨酸受体1拮抗剂，含有该化合物的药物组合物，以及使用该化合物和组合物治疗与代谢型谷氨酸受体（例如mGluR1）相关的疾病的方法，例如疼痛、偏头痛、焦虑、尿失禁和阿尔茨海默病等神经退行性疾病。
• Heterocyclic studies. Part 43. Thieno[2,3-d:4,5-d′]dipyrimidines
  作者：Jim Clark、George Hitiris

  DOI：10.1039/p19840002005

  日期：——

  5-Aminothieno[2,3-d]pyrimidine-6-carboxamides or -6-carboxylic esters have been converted into thieno[2,3-d:4,5-d′]dipyrimidines with the reagents formamide, triethyl orthoformate, urea, methyl isothiocyanate, phenyl isocyanate, and guanidine.

  5-氨基噻吩并[2,3- d ]嘧啶-6-羧酰胺或-6-羧酸酯已与甲酰胺，原甲酸三乙酯，尿素一起转化为噻吩并[2,3- d：4,5- d ']双嘧啶，异硫氰酸甲酯，异氰酸苯酯和胍。
• [EN] TRICYCLIC COMPOUNDS AND THEIR USE AS MGLUR1 ANTAGONISTS<br/>[FR] COMPOSES TRICYCLIQUES ET LEUR UTILISATION COMME ANTAGONISTES DU MGLUR1
  申请人：SCHERING CORP

  公开号：WO2006002051A1

  公开（公告）日：2006-01-05

  In its many embodiments, the present invention provides tricyclic compounds of Formula (I) (wherein J1-J4, X, and R1-R5 are as defined herein) useful as metabotropic glutamate receptor (mGluR) antagonists, particularly as selective metabotropic glutamate receptor 1 antagonists, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds and compositions to treat diseases associated with metabotropic glutamate receptor (e.g., mGluR1) such as, for example, pain, migraine, anxiety, urinary incontinence and neurodegenerative diseases such Alzheimer's disease.

  在其多种实施方式中，本发明提供了式(I)的三环化合物（其中J1-J4，X和R1-R5如本文所定义），作为代谢型谷氨酸受体（mGluR）拮抗剂，特别是选择性代谢型谷氨酸受体1拮抗剂，含有该化合物的制药组合物，以及使用该化合物和组合物治疗与代谢型谷氨酸受体（例如mGluR1）相关的疾病的治疗方法，如疼痛，偏头痛，焦虑，尿失禁和神经退行性疾病，例如阿尔茨海默病。
• mGluR1 Antagonists as therapeutic agents
  申请人：Matasi J. Julius

  公开号：US20060167029A1

  公开（公告）日：2006-07-27

  In its many embodiments, the present invention provides tricyclic compounds of formula I (wherein J 1 -J 4 , X, and R 1 -R 5 are as defined herein) useful as metabotropic glutamate receptor (mGluR) antagonists, particularly as selective metabotropic glutamate receptor 1 antagonists, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds and compositions to treat diseases associated with metabotropic glutamate receptor (e.g., mGluR1) such as, for example, pain, migraine, anxiety, urinary incontinence and neurodegenerative diseases such Alzheimer's disease.

  在许多实施方案中，本发明提供了式 I 的三环化合物（其中 J 1 -J 4 、X 和 R 1 -R 5 如本文所定义）作为代谢型谷氨酸受体（mGluR）拮抗剂，特别是作为选择性代谢型谷氨酸受体 1 拮抗剂，含有这些化合物的药物组合物，以及使用这些化合物和组合物治疗与代谢型谷氨酸受体（如 mGluR1）相关疾病（如疼痛、偏头痛、焦虑、尿失禁和神经退行性疾病，如阿尔茨海默病）的方法。
• CLARK, J.;HITIRIS, G., J. CHEM. SOC. PERKIN TRANS., 1984, N 9, 2005-2018
  作者：CLARK, J.、HITIRIS, G.

  DOI：——

  日期：——