4-氯-5-(4-氯苯基)噻吩并[2,3-d]嘧啶 | 331761-46-7

• 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
• 中文名称: 4-氯-5-(4-氯苯基)噻吩并[2,3-d]嘧啶
• 中文别名: 4-氯-5-(4-氯苯基)噻吩并[2,3-D]吡啶
• 英文名称: 4-chloro-5-(4-chlorophenyl)thieno[2,3-d]pyrimidine
• CAS: 331761-46-7
• 化学式: C₁₂H₆Cl₂N₂S
• mdl: MFCD01038375
• 分子量: 281.165
• InChiKey: QDMQHIKVIOWCGY-UHFFFAOYSA-N

物化性质

• 熔点：
  139.5-141℃
• 沸点：
  443.1±45.0 °C(Predicted)
• 密度：
  1.490±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 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：
  54
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  4-氯-5-(4-氯苯基)噻吩并[2,3-d]嘧啶 在 hydrazine hydrate 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 (Z/E)(4-{[5-(4-chlorophenyl)thieno[2,3-d]pyrimidin-4-yl]hydrazonomethyl}phenyl)dimethylamine
  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
• 作为产物：
  描述：

  2-[1-(4-氯苯基)亚乙基]丙二腈 在 氯化亚砜 、 碳酸氢钠 、 sulfur 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 为溶剂， 生成 4-氯-5-(4-氯苯基)噻吩并[2,3-d]嘧啶
  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

• [EN] INHIBITORS OF KRAS G12C<br/>[FR] INHIBITEURS DE K-RAS G12C
  申请人：ARAXES PHARMA LLC

  公开号：WO2015054572A1

  公开（公告）日：2015-04-16

  Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R1, R2a, R3a, R3b, R4a, R4b, G1, G2, L1, L2, m1, m2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

  提供了作为G12C突变KRAS蛋白抑制剂活性的化合物。这些化合物具有以下结构（I）：或其药用可接受的盐、互变异构体、前药或立体异构体，其中R1、R2a、R3a、R3b、R4a、R4b、G1、G2、L1、L2、m1、m2、A、B、W、X、Y、Z和E如本文所定义。还提供了与制备和使用这些化合物相关的方法，包括含有这些化合物的药物组合物以及调节G12C突变KRAS蛋白活性以治疗癌症等疾病的方法。
• Design, Synthesis and Biological Evaluation of Some 5-Arylthieno[2,3-&lt;i&gt;d&lt;/i&gt;]pyrimidines as Potential Anti-cancer Agents
  作者：Afaf Kamal El-Ansary、Aliaa Mohammed Kamal、Mokhtar Abd-Hafiz Al-Ghorafi

  DOI：10.1248/cpb.c16-00291

  日期：——

  Structure-based design, synthesis and biological evaluation of new small molecules anti-cancer agents were described. On continuation of applying scaffold hopping theory, a series of 5-arylthieno[2,3-d]pyrimidines based on the structural features of lapatinib was designed, synthesized and characterized using IR, 1H-NMR, 13C-NMR, mass and microanalyses. Biological evaluation of the cytotoxic activity against MCF-7 cell line and the inhibition of the enzymatic activity of epidermal growth factor tyrosine kinase were carried out in vitro for the target compounds. Substituting the 4-anilino-5-arylthieno[2,3-d]pyrimidines with different pharmacophoric groups at ortho, meta and/or para positions led to discovery of two potent lead compounds 3b and f with excellent cytotoxic activity and enzymatic inhibition activity.

  基于结构的药物设计、合成和生物评价的新型小分子抗癌剂被详细描述。在延续应用骨架跃迁理论的基础上，根据拉帕替尼的结构特征，设计、合成了基于5-芳基噻吩并[2,3-d]嘧啶的一系列化合物，并通过IR、1H-NMR、13C-NMR、质谱和微量分析进行了表征。针对目标化合物，进行体外细胞毒活性对MCF-7细胞系的生物评价和表皮生长因子酪氨酸激酶的酶活性抑制试验。将4-苯胺基-5-芳基噻吩并[2,3-d]嘧啶中的不同药效团在邻位、间位和/或对位进行取代，发现了两种具有优异细胞毒活性和酶抑制活性的强效先导化合物3b和f。
• 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。
• [EN] COMBINATION THERAPIES FOR TREATMENT OF CANCER<br/>[FR] THÉRAPIES COMBINATOIRES POUR LE TRAITEMENT DU CANCER
  申请人：ARAXES PHARMA LLC

  公开号：WO2016044772A1

  公开（公告）日：2016-03-24

  Combination therapies for treatment of cancers associated with mutations in the KRAS gene are provided. Compositions comprising therapeutic agents for treatment of cancers associated with mutations in the KRAS gene are also provided.

  提供用于治疗与KRAS基因突变相关的癌症的联合疗法。还提供了包含治疗剂的组合物，用于治疗与KRAS基因突变相关的癌症。