methyl 3-(3-(2,2,2-trichloroacetyl)ureido)thiophene-2-carboxylate | 860354-57-0

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: methyl 3-(3-(2,2,2-trichloroacetyl)ureido)thiophene-2-carboxylate
• 英文别名: Methyl 3-({[(trichloroacetyl)amino]carbonyl}amino)thiophene-2-carboxylate；methyl 3-[(2,2,2-trichloroacetyl)carbamoylamino]thiophene-2-carboxylate
• CAS: 860354-57-0
• 化学式: C₉H₇Cl₃N₂O₄S
• 分子量: 345.591
• InChiKey: HXSHPJSWYWWCAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3-(3-(2,2,2-trichloroacetyl)ureido)thiophene-2-carboxylate 在 甲醇 、 potassium tert-butylate 、 氨 、 溴 、 sodium carbonate 、 溶剂黄146 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 46.5h， 生成 6-bromo-2-chloro-N-(2-(pyrrolidin-1-yl)ethyl)thieno[3,2-d]pyrimidin-4-amine
  参考文献：
  名称：

  2,4-Diaminothienopyrimidines as Orally Active Antimalarial Agents

  摘要：

  A novel series of 2,4-diaminothienopyrimidines with potential as antimalarials was identified from whole-cell high-throughput screening of a SoftFocus ion channel library. Synthesis and structure activity relationship studies identified compounds with potent antiplasmodial activity and low in vitro cytotoxicity. Several of these analogues exhibited in vivo activity in the Plasmodium berghei mouse model when administered orally. However, inhibition of the hERG potassium channel was identified as a liability for this series.

  DOI：

  10.1021/jm401760c
• 作为产物：
  描述：

  三氯乙酰异氰酸酯 以97的产率得到methyl 3-(3-(2,2,2-trichloroacetyl)ureido)thiophene-2-carboxylate
  参考文献：
  名称：

  Thiophene derivatives as chk 1 inhibitors

  摘要：

  本发明涉及具有结构式（I）的新化合物，以及它们的制药组合物和使用方法。这些新化合物提供了治疗或预防癌症的方法。

  公开号：

  US20070010556A1

文献信息

• Synthesis and pharmacological characterization of the selective GluK1 radioligand (S)-2-amino-3-(6-[³H]-2,4-dioxo-3,4-dihydrothieno[3,2-d]pyrimidin-1(2H)-yl)propanoic acid ([³H]-NF608)
  作者：Anna Alcaide、Laura Marconi、Ales Marek、Isabell Haym、Birgitte Nielsen、Stine Møllerud、Mikael Jensen、Paola Conti、Darryl S. Pickering、Lennart Bunch

  DOI：10.1039/c6md00339g

  日期：——

  thus not attractive. Herein, we report the synthesis of [3H]-NF608 and subsequent pharmacological evaluation at homomeric recombinant rat GluK1 receptors. Binding affinities of a series of standard GluK1 ligands were shown to be in line with previously reported affinities obtained by use of already reported radioligands.

  藻酸受体属于离子型谷氨酸受体，包括五个亚基，称为GluK1-5。放射性配体是用于结合测定的重要工具，旨在进行配体-受体结构-活性关系研究。先前的工作导致了GluK1放射性配体[ 3 H] -SYM2081，[ 3 H] -UBP310和[ 3 H] -ATPA的合成，但是所有策略都需要大量工作，因此没有吸引力。在此，我们报道了[ 3 H] -NF608的合成以及随后在同源重组大鼠GluK1受体上的药理评价。一系列标准GluK1配体的结合亲和力显示与先前报道的通过使用已报道的放射性配体获得的亲和力一致。
• Thiophene and thiazole derivatives as CHK1 inhibitors
  申请人：AstraZeneca AB

  公开号：EP2305671A1

  公开（公告）日：2011-04-06

  This invention relates to novel compounds having the structural formula (I) and to their pharmaceutical compositions and to their methods of use. These novel compounds provide a treatment or prophylaxis of cancer.

  本发明涉及具有结构式 (I) 的新型化合物 及其药物组合物和使用方法。这些新型化合物可治疗或预防癌症。
• [EN] THIOPHENE DERIVATIVES AS CHK 1 INIHIBITORS<br/>[FR] HETEROCYCLES SUBSTITUES ET LEURS UTILISATIONS
  申请人：ASTRAZENECA AB

  公开号：WO2005066163A3

  公开（公告）日：2005-09-01
• Discovery of Checkpoint Kinase Inhibitor (<i>S</i>)-5-(3-Fluorophenyl)-<i>N</i>-(piperidin-3-yl)-3-ureidothiophene-2-carboxamide (AZD7762) by Structure-Based Design and Optimization of Thiophenecarboxamide Ureas
  作者：Vibha Oza、Susan Ashwell、Lynsie Almeida、Patrick Brassil、Jason Breed、Chun Deng、Thomas Gero、Michael Grondine、Candice Horn、Stephanos Ioannidis、Dongfang Liu、Paul Lyne、Nicholas Newcombe、Martin Pass、Jon Read、Shannon Ready、Siân Rowsell、Mei Su、Dorin Toader、Melissa Vasbinder、Dingwei Yu、Yan Yu、Yafeng Xue、Sonya Zabludoff、James Janetka

  DOI：10.1021/jm300025r

  日期：2012.6.14

  Checkpoint kinases CHK1 and CHK2 are activated in response to DNA damage that results in cell cycle arrest, allowing sufficient time for DNA repair. Agents that lead to abrogation of such checkpoints have potential to increase the efficacy of such compounds as chemo- and radiotherapies. Thiophenecarboxamide ureas (TCUs) were identified as inhibitors of CHK1 by high throughput screening. A structure-based approach is described using crystal structures of JNK1 and CHK1 in complex with 1 and 2 and of the CHK1-3b complex. The ribose binding pocket of CHK1 was targeted to generate inhibitors with excellent cellular potency and selectivity over CDK1 and IKK beta, key features lacking from the initial compounds, Optimization of 3b resulted in the identification of a regioisomeric 3-TCU lead 12a. Optimization of 12a led to the discovery of the clinical candidate 4 (AZD7762), which strongly potentiates the efficacy of a variety of DNA-damaging agents in preclinical models.
• THIOPHENE DERIVATIVES AS CHK 1 INHIBITORS
  申请人：AstraZeneca AB

  公开号：EP1732920A2

  公开（公告）日：2006-12-20