4-chloro-6-nitrothieno[2,3-d]pyrimidine | 56844-13-4

• 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: 4-chloro-6-nitrothieno[2,3-d]pyrimidine
• CAS: 56844-13-4
• 化学式: C₆H₂ClN₃O₂S
• 分子量: 215.62
• InChiKey: XULYQYBOEGZFKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  99.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-chloro-6-nitrothieno[2,3-d]pyrimidine 在 氯化亚砜 、 铁粉 、 氯化铵 作用下， 以 乙醇 、 二氯甲烷 、 异丙醇 为溶剂， 反应 3.0h， 生成 (E)-N-(4-((3-chloro-4-fluorophenyl)amino)thieno[2,3-d]pyrimidin-6-yl)-4-(diethylamino)but-2-enamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel 6-alkenylamides substituted of 4-anilinothieno[2,3-d]pyrimidines as irreversible epidermal growth factor receptor inhibitors

  摘要：

  A novel series of 6-alkenylamides of 4-anilinothieno[2,3-d]pyrimidine derivatives was designed, synthesized and evaluated as irreversible inhibitors of the epidermal growth factor receptor (EGFR). Most of the compounds exhibited good potency against EGFR wild type (EGFR wt) and EGFR T790M/L858R. Among these, the half-maximal inhibitory concentration (IC50) values of 17 compounds against EGFR wt were less than 0.020 mu M, and those of 12 compounds were less than 0.010 mu M. The IC50 values of 10 compounds against EGFR T790M/L858R were less than 0.005 mu M. Compounds 8l, 9n, 9o, 9q and 9v almost completely blocked the phosphorylation of EGFR in the A431 cell line at 1 mu M. Compounds 8l, 9n, 9o, 9q and 9v blocked the autophosphorylation of EGFR in NCI-H1975 cells at high concentration (1 mu M), and compound 8l was confirmed to be an irreversible inhibitor through the dilution method. (c) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.01.035
• 作为产物：
  描述：

  methyl 2-formylaminothiophene-3-carboxylate 在 硝酸 、 甲酸铵 、 formamide 、 三氯氧磷 作用下， 以 硫酸 为溶剂， 反应 8.0h， 生成 4-chloro-6-nitrothieno[2,3-d]pyrimidine
  参考文献：
  名称：

  表皮生长因子受体的不可逆抑制剂：具有 α,β-不饱和酰胺侧链的噻吩并嘧啶核

  摘要：

  表皮生长因子受体 (EGFR) 酪氨酸激酶的过度表达已在多种癌症中发现，例如乳腺癌、卵巢癌、结肠癌和非小细胞肺癌，这与患者的不良预后有关。为了寻找有效的 EGFR 酪氨酸激酶家族（主要是 HER2）的不可逆抑制剂，以噻吩并 [3,2-d] 吡啶和噻吩并 [2,3-d] 吡啶为中心部分的两个系列 HER2 酪氨酸激酶抑制剂和开发了具有碱性α,β-不饱和酰胺侧链的化合物。位于 6 位的 α,β-不饱和酰胺侧链（迈克尔受体）与位于 EGFR 酶的 ATP 结合口袋中的 Cys773 形成共价键，是产生不可逆抑制的主要因素。在我们的研究中，使用噻吩并嘧啶代替喹唑啉作为中心结构，并在4位引入不同的取代基以研究构效关系。噻吩并[2,3-d]嘧啶衍生物16a-d对SK-BR-3细胞显示出有效的HER2酶抑制和抗增殖活性。特别是，(E)-N-(4-((3-chloro-4-(pyridin-2-ylmet

  DOI：

  10.1002/ardp.201400098

文献信息

• Design, synthesis and biological evaluation of 4-anilinothieno[2,3-d]pyrimidine-based hydroxamic acid derivatives as novel histone deacetylase inhibitors
  作者：Wei Yang、Lixuan Li、Xun Ji、Xiaowei Wu、Mingbo Su、Li Sheng、Yi Zang、Jia Li、Hong Liu

  DOI：10.1016/j.bmc.2014.08.030

  日期：2014.11

  3-d]pyrimidine-based hydroxamic acid derivatives as novel HDACs inhibitors were designed, synthesized and evaluated. Most of these compounds displayed good to excellent inhibitory activities against HDAC1, 3, 6. The IC50 values of compound 10r against HDAC1, HDAC3, HDAC6 was 1.14 ± 0.03 nM, 3.56 ± 0.08 nM, 11.43 ± 0.12 nM. Compound 10r noticeably up-regulated the level of histone H3 acetylation compared

  设计，合成和评估了一系列基于4-苯胺基噻吩并[2,3- d ]嘧啶的异羟肟酸衍生物。这些化合物中的大多数对HDAC1、3、6表现出良好或优异的抑制活性。化合物10r对HDAC1，HDAC3，HDAC6的IC 50值为1.14±0.03 nM，3.56±0.08 nM，11.43±0.12 nM。与SAHA相比，化合物10r明显上调了组蛋白H3乙酰化水平。大多数化合物对人癌细胞系（包括RMPI8226和HCT-116）显示出强大的抗增殖活性。化合物10r和10t的IC 50值对RPMI8226的抗性分别为2.39±0.20μM，1.41±0.44μM，并且HCT-116对化合物10h，10m，10r，10w敏感，IC 50值<1.9μM。
• Thieno-pyrimidine compounds having fungicidal activity
  申请人：Brewster Kirkland William

  公开号：US20060089370A1

  公开（公告）日：2006-04-27

  The present invention relates to thieno[2,3-d]-pyrimidine compounds having fungicidal activity.

  本发明涉及具有杀真菌活性的噻吩[2,3-d]-嘧啶化合物。
• 6-Cinnamoyl-4-arylaminothienopyrimidines as highly potent cytotoxic agents: Design, synthesis and structure-activity relationship studies
  作者：Mahsa Toolabi、Setareh Moghimi、Tayebeh Oghabi Bakhshaiesh、Somayeh Salarinejad、Ayoub Aghcheli、Zaman Hasanvand、Elahe Nazeri、Ali Khalaj、Rezvan Esmaeili、Alireza Foroumadi

  DOI：10.1016/j.ejmech.2019.111786

  日期：2020.1

  described the synthesis and cytotoxic activities of two new series of thieno[2,3-d]pyrimidine and thieno[3,2-d] pyrimidine derivatives. Most of the synthesized compounds had significant antiproliferative activities against PC3, MDA-MB-231, A549, and HeLa cell lines in comparison to the reference drug, erlotinib. Compounds N-(4-((3,5-dichlorophenyl)amino)thieno[2,3-d]pyrimidin-6-yl)cinnamamide 8e and (E)-N-(4-((3

  在本文中，我们描述了两个新系列的噻吩并[2,3-d]嘧啶和噻吩并[3,2-d]嘧啶衍生物的合成和细胞毒活性。与参考药物厄洛替尼相比，大多数合成的化合物对PC3，MDA-MB-231，A549和HeLa细胞系均具有显着的抗增殖活性。化合物N-（4-（（3,5-二氯苯基）氨基）噻吩并[2,3-d]嘧啶-6-基）肉桂酰胺8e和（E）-N-（4-（（3,4-二氯苯基）选择针对HeLa细胞系的IC50分别为4 nM和33 nM的氨基）噻吩并[2,3-d]嘧啶-6-基）-3-（4-甲氧基苯基）丙烯酰胺8g进行进一步研究。测定了细胞凋亡诱导的活性和细胞周期停滞，并且结果提供了证据，这些化合物通过细胞凋亡诱导细胞死亡并阻止了亚G1期细胞的生长。此外，蛋白质印迹分析显示出抑制EGFR信号通路（p-EGFR / p-ERK1 / 2）的有希望的结果。对接研究赞赏基于氢和共价结合相互作用的化合物8e的相当大的效
• Thienopyrimidines
  申请人：Imperial Chemical Industries Limited

  公开号：US04146716A1

  公开（公告）日：1979-03-27

  Thienopyrimidines of the formula: ##STR1## wherein R.sup.1 is straight or branched chain alkyl containing from 3 to 11 carbon atoms and optionally substituted with cyano or methoxy, cycloalkyl, benzyl optionally substituted on the .alpha. carbon atom with a lower alkyl group or in the ring with one or more alkoxy groups or halogen atoms, dimethylamino, phenylethyl optionally substituted at the .alpha.- or .beta.-carbon atoms with a lower alkyl group, tetrahydrofurfuryl; R.sup.3 is hydrogen or NH.sub.2 ; or R.sup.1 and R.sup.3 together form a carbon chain bridging group optionally saturated and containing one or more nitrogen atoms; R.sup.2 is hydrogen, methyl, ethyl, or chlorine; R.sup.5 is hydrogen or methyl; and R.sup.6 is hydrogen, methyl or acetylamino; or an optical isomer thereof; or a tautomer thereof; or a salt thereof. These and other thienopyrimidines are disclosed as useful for plant growth regulation and for combating fungal, viral and bacterial diseases of plants and insect pests.

  式为：##STR1##其中R.sup.1是直链或支链烷基，含有3到11个碳原子，并可选择地取代为氰基或甲氧基，环烷基，苄基，可选择地在α-碳原子上取代为较低的烷基或在环中含有一个或多个烷氧基或卤素原子，二甲氨基，苯乙基，可选择地在α-或β-碳原子上取代为较低的烷基，四氢呋喃基；R.sup.3是氢或NH.sub.2；或R.sup.1和R.sup.3一起形成一个碳链桥接基，可选择饱和并含有一个或多个氮原子；R.sup.2是氢，甲基，乙基或氯；R.sup.5是氢或甲基；R.sup.6是氢，甲基或乙酰氨基；或其光学异构体；或其互变异构体；或其盐。这些及其他噻吡嘧啶被披露为用于植物生长调节和对抗植物真菌、病毒和细菌病害以及昆虫害虫的有用化合物。
• Process for controlling eradicating or preventing infestations of
  申请人：ICI Australia Limited

  公开号：US04196207A1

  公开（公告）日：1980-04-01

  A process for the prevention of infestation by Ixodid ticks, or for the control or eradication of infestations of Ixodid ticks, which process comprises applying to the media to be protected or to the infested media an effective amount of a composition comprising as active ingredient a thienopyrimidine derivative of general formula I: ##STR1## xwherein R.sup.1 is chosen from alkyl optionally substituted with hydroxy, methoxy, cycloalkyl, aryl, heteroaryl, and heterocycloalkyl groups; alkenyl; alkynyl; cycloalkyl; R.sup.3 is chosen from hydrogen, alkyl and acyl; or R.sup.1 and R.sup.3 together form a saturated or unsaturated alkylene or heteroalkylene bridging group; R.sup.2 is chosen from hydrogen, hydroxy, mercapto, halo, cyano, optionally substituted-amino, optionally substituted hydrazino, alkyl, alkenyl, alkynyl, alkoxy, alkylthio, cycloalkyl, aralkyl, aryl and trifluoromethyl; R.sup.5 and R.sup.6 are independently chosen from hydrogen, optionally substituted alkyl, halogen and aryl; or R.sup.5 and R.sup.6 together form a saturated alkyl bridging group; or an optical isomer thereof; or a tautomer thereof; or a salt thereof; and a carrier therefor.

  一种预防蜱虫侵袭、控制或根除蜱虫侵袭的方法，该方法包括向需要保护或已被侵袭的介质中施加有效量的含有噻唑嘧啶衍生物的组合物，该噻唑嘧啶衍生物的一般式为I：##STR1## 其中，R1选自烷基，该烷基可以选择性地被羟基、甲氧基、环烷基、芳基、杂芳基和杂环烷基取代；烯基；炔基；环烷基；R3选自氢、烷基和酰基；或者R1和R3一起形成饱和或不饱和的烷基或杂烷基桥连基；R2选自氢、羟基、巯基、卤素、氰基、可以选择性地取代的氨基、可以选择性地取代的肼基、烷基、烯基、炔基、烷氧基、烷硫基、环烷基、芳基、芳基烷基和三氟甲基；R5和R6独立地选自氢、可以选择性取代的烷基、卤素和芳基；或者R5和R6一起形成饱和的烷基桥连基；或其光学异构体；或其互变异构体；或其盐；以及载体。