5-(4-chlorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one | 331761-45-6

• 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-(4-chlorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one
• 英文别名: 5-(4-chioro-phenyl)-3H-thieno[2,3-d]pyrimidin-4-one；5-(4-chlorophenyl)-3H-thieno[2,3-d]pyrimidin-4-one
• CAS: 331761-45-6
• 化学式: C₁₂H₇ClN₂OS
• mdl: MFCD01038374
• 分子量: 262.719
• InChiKey: VSUODCNBLBXSNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.7
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险标志：
  GHS06
• 危险性描述：
  H301
• 危险性防范说明：
  P301 + P310
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  5-(4-chlorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one 在 potassium carbonate 作用下， 以 丙酮 、 正丁醇 为溶剂， 反应 60.0h， 生成 N'-[(3,4-dihydroxyphenyl)methylene]-[4-oxo-5-(4-chlorophenyl)-thieno[2,3-d]pyrimidin-3(4H)-yl]acetohydrazone
  参考文献：
  名称：

  Synthesis and anti-tumor activities of N′-benzylidene-2-(4-oxothieno[2,3-d]pyrimidin-3(4H)-yl)acetohydrazone derivatives

  摘要：

  A compound with a cyclic thienopyrimidine moiety and an aceto-hydrazone moiety in its chemical structure was discovered in a cell-based screening to have noticeable cytotoxicity on several tumor cell lines. A total of 38 derivatives of this compound were synthesized at five steps with high yields. These compounds were tested in standard MTT assays, and several compounds exhibited improved cytotoxic activities. The most potent compounds have IC50 values of 10-20 mu M on A549, HeLa, and MBA-MD-231 tumor cells. Flow cytometry analysis of several active compounds and subsequent examination of caspase activation indicate that they induce caspase-dependent apoptosis in tumor cells. In addition, these compounds do not have obvious effect on a normal cell line HEK-293T, demonstrating the desired selectivity against tumor cells. Results from a fluorescence polarization-based in vitro binding assay indicate that this class of compounds does not significantly interrupt the interactions between Mcl-1 and Bid. Their cytotoxicity is achieved presumably through other mechanisms. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.061
• 作为产物：
  描述：

  2-[1-(4-氯苯基)亚乙基]丙二腈 在 碳酸氢钠 、 sulfur 作用下， 以 四氢呋喃 为溶剂， 生成 5-(4-chlorophenyl)thieno[2,3-d]pyrimidin-4(3H)-one
  参考文献：
  名称：

  Synthesis and evaluation of 4-anilinoquinazoline bioisosteres as potential anti-breast cancer agents

  摘要：

  Based on one of the four major categories of scaffold hopping theory namely hetrocycle replacements, a series of 5-arylthieno[2,3-d]pyrimidines had been prepared and evaluated as anti-breast cancer agents. Optimization by combination of different pharmacophores with the thienopyrimidine scaffold led to discovery of biologically active compounds. (c) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.08.056

文献信息

• Design and synthesis of novel protein kinase CK2 inhibitors on the base of 4-aminothieno[2,3-d]pyrimidines
  作者：Olga V. Ostrynska、Anatoliy O. Balanda、Volodymyr G. Bdzhola、Andriy G. Golub、Igor M. Kotey、Olexander P. Kukharenko、Andrii A. Gryshchenko、Nadiia V. Briukhovetska、Sergiy M. Yarmoluk

  DOI：10.1016/j.ejmech.2016.03.004

  日期：2016.6

  research work has resulted in a number of new ATP-competitive CK2 inhibitors that have been identified among 4-aminothieno[2,3-d]pyrimidine derivatives. The most active compounds obtained in the course of the research are 3-(5-p-tolyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5e (NHTP23, IC50 = 0.01 μM), 3-(5-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5g (NHTP25, IC50 = 0.065 μM) and 3

  我们先前研究工作的扩展已导致在4-氨基噻吩并[2,3-d]嘧啶衍生物中鉴定出许多新的与ATP竞争的CK2抑制剂。在研究过程中获得的活性最高的化合物是3-（5-对甲苯基-噻吩并[2,3-d]嘧啶-4-基氨基）苯甲酸5e（NHTP23，IC 50  = 0.01μM）， 3-（5-苯基-噻吩并[2,3-d]嘧啶-4-基氨基）-苯甲酸，5g（NHTP25，IC 50  = 0.065μM）和3-（6-甲基-5-苯基-噻吩并[2 ，3-d]嘧啶-4-基氨基）-苯甲酸，5n（NHTP33，IC 50 = 0.008μM）。研究了测试的4-氨基噻吩并[2,3-d]嘧啶衍生物的结构-活性关系，并提出了它们与CK2 ATP受体位点的结合方式。讨论了分子内氢键对化合物结构的负面影响。
• Design, Synthesis, and Biological Evaluation of 6-Substituted Thieno[3,2-<i>d</i>]pyrimidine Analogues as Dual Epidermal Growth Factor Receptor Kinase and Microtubule Inhibitors
  作者：Romeo Romagnoli、Filippo Prencipe、Paola Oliva、Stefania Baraldi、Pier Giovanni Baraldi、Santiago Schiaffino Ortega、Mariem Chayah、Maria Kimatrai Salvador、Luisa Carlota Lopez-Cara、Andrea Brancale、Salvatore Ferla、Ernest Hamel、Roberto Ronca、Roberta Bortolozzi、Elena Mariotto、Elena Mattiuzzo、Giampietro Viola

  DOI：10.1021/acs.jmedchem.8b01391

  日期：2019.2.14

  The clinical evidence for the success of tyrosine kinase inhibitors in combination with microtubule-targeting agents prompted us to design and develop single agents that possess both epidermal growth factor receptor (EGFR) kinase and tubulin polymerization inhibitory properties. A series of 6-aryl/heteroaryl-4-(3',4',5'-trimethoxyanilino)thieno[3,2- d]pyrimidine derivatives were discovered as novel

  酪氨酸激酶抑制剂与微管靶向剂成功结合的临床证据促使我们设计和开发具有表皮生长因子受体（EGFR）激酶和微管蛋白聚合抑制特性的单一药物。发现了一系列6-芳基/杂芳基-4-（3'，4'，5'-三甲氧基苯胺基）噻吩并[3,2-d]嘧啶衍生物，它们是新型的双微管蛋白聚合和EGFR激酶抑制剂。4-（3'，4'，5'-三甲氧基苯胺基）-6-（对甲苯基）噻吩并[3,2-d]嘧啶衍生物6g是该系列中最有效的化合物，具有抗增殖作用，其中一半最大抑制浓度（IC50）值在一位或两位数纳摩尔范围内。化合物6g与秋水仙碱位点的微管蛋白结合并抑制微管蛋白组装，IC50值为0.71μM，6g抑制EGFR活性，IC50值为30 nM。我们的数据表明，6g优异的体外和体内特性可能源于其对微管蛋白聚合和EGFR激酶的双重抑制作用。
• Novel 4-Oxothienopyrimidinyl Propanoic Acid Derivatives as AMPActivated Protein Kinase (AMPK) Activators
  作者：Pradip Sasmal、Mahaboobi Jaleel、P. Rao、M. Munikumar、Megha Bhattacharya、Nutakki Kumar、Poondla. Neelima、Khaji Rawoof、P. Rao、Chandrasekhar Abbineni、M. Roshaiah、S. Sridhar、Thammera Kumar、Menon Vinu、Vijay Potluri、Parimal Misra、Rashmi Talwar、Saibal Das

  DOI：10.2174/1570180811666140122003044

  日期：2014.5.31

  Adenosine 5’-monophosphate (AMP) activated protein kinase (AMPK) is a highly conserved sensor of cellular energy. AMPK has been recognized as a key regulator of mammalian metabolic function and has emerged as an attractive target for the treatment of metabolic disorders, including obesity and type 2 diabetes. The synthesis and biological evaluation of novel 3-(4-oxothieno[2,3-d]pyrimidin-3(4H)-yl)propanoic acid derivatives as AMPK activators are described. The in vivo proof of principle for plasma glucose lowering effect is exemplified with a lead compound from this series.

  腺苷5'-单磷酸(AMP)激活的蛋白激酶(AMPK)是一种高度保守的细胞能量感应器。AMPK已被确认为调节哺乳动物代谢功能的关键因子,并已成为治疗包括肥胖和2型糖尿病在内的代谢紊乱的理想靶点。本文描述了新型3-(4-氧代噻吩并[2,3-d]嘧啶-3(4H)-基)丙酸衍生物作为AMPK激活剂的合成和生物学评价。体内实验证明了本系列中的先导化合物具有降低血浆葡萄糖水平的原理验证作用。
• [EN] THIENOPYRIMIDINE DERIVATIVES AS POTASSIUM CHANNEL INHIBITORS<br/>[FR] UTILISATION DE DERIVES DE LA THIENOPYRIMIDINE COMME INHIBITEURS DES CANAUX POTASSIQUES
  申请人：XENTION DISCOVERY LTD

  公开号：WO2004111057A1

  公开（公告）日：2004-12-23

  The present invention provides thienopyrimidine compounds which are potasium channels inhibitors. Pharmaceutical compositions comprising the compounds and their use in the treatment of arrhythmia are also provided.

  本发明提供了硫代嘧啶类化合物，它们是钾通道抑制剂。还提供了包含这些化合物的药物组合物，以及它们在治疗心律失常中的用途。
• [EN] THIENOPYRIMIDINONE NMDA RECEPTOR MODULATORS AND USES THEREOF<br/>[FR] MODULATEURS DES RÉCEPTEURS NMDA À BASE DE THIÉNOPYRIMIDINONE ET LEURS UTILISATIONS
  申请人：LUC THERAPEUTICS

  公开号：WO2017100599A1

  公开（公告）日：2017-06-15

  Disclosed herein, in part, are heteroaromatic compounds and methods of use in treating neuropsychiatric disorders, e.g., schizophrenia and major depressive disorder. Pharmaceutical compositions and methods of making heteroaromatic compounds are provided. The compounds are contemplated to modulate the NMDA receptor.

  本文披露了部分杂环芳烃化合物以及在治疗神经精神障碍，如精神分裂症和重度抑郁症中的用途方法。提供了制备杂环芳烃化合物的药物组合物和方法。这些化合物被认为可以调节NMDA受体。