4-三氟甲基-2-羟基嘧啶-5-羧酸 | 251996-86-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 中文名称: 4-三氟甲基-2-羟基嘧啶-5-羧酸
• 中文别名: 4-氯噻吩并[2,3-C]吡啶-2-羧酸；4-氯噻吩并[2,3-c]吡啶-2-羧酸
• 英文名称: 4-chlorothieno[2,3-c]pyridine-2-carboxylic acid
• CAS: 251996-86-8
• 化学式: C₈H₄ClNO₂S
• 分子量: 213.644
• InChiKey: LLXSBUMTRUIFAL-UHFFFAOYSA-N

物化性质

• 密度：
  1.634

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  4-三氟甲基-2-羟基嘧啶-5-羧酸 以 二苯醚 为溶剂， 反应 20.0h， 以88%的产率得到4-chlorothieno[3,2-d]pyridine
  参考文献：
  名称：

  A facile and general synthesis of 2,4‐Di‐ and 2,4,7‐trisubstituted thieno[2,3‐c]pyridines

  摘要：

  Abstractmagnified imageTreatment of 3,5‐dibromo‐ or 3,5‐dichloro‐pyridine‐4‐carboxaldehyde 2 with one equivalent of methyl thioglycolate, followed by exposure to base, provided 4‐bromo‐ or 4‐chloro‐thieno[2,3‐c]pyridine‐2‐carboxylate 4 in good yields. Oxidation of the thieno[2,3‐c]pyridine scaffold such as 7 with mCPBA, followed by treatment with POBr3, introduced a bromine exclusively at the 7‐position of the heterocycle. The 4‐ or 7‐bromide of the thienopyridines readily underwent Suzuki, Stille coupling, and Buchwald amination reactions, to afford 4‐ or 7‐substituted analogs 6 or 11. The 2‐carboxylate of 4b or 12 was smoothly removed through saponification and decarboxylation to furnish 15 or 16. Deprotonation of the thienopyridine at C‐2 position, followed by trapping with trimethyltin chloride, afforded a 2‐stannyl analog, which was readily converted to other C‐2 derivatives via Stille reaction.

  DOI：

  10.1002/jhet.5570450106
• 作为产物：
  描述：

  4-氯噻吩并[2,3-c]吡啶-2-羧酸甲酯 在 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以92%的产率得到4-三氟甲基-2-羟基嘧啶-5-羧酸
  参考文献：
  名称：

  A facile and general synthesis of 2,4‐Di‐ and 2,4,7‐trisubstituted thieno[2,3‐c]pyridines

  摘要：

  Abstractmagnified imageTreatment of 3,5‐dibromo‐ or 3,5‐dichloro‐pyridine‐4‐carboxaldehyde 2 with one equivalent of methyl thioglycolate, followed by exposure to base, provided 4‐bromo‐ or 4‐chloro‐thieno[2,3‐c]pyridine‐2‐carboxylate 4 in good yields. Oxidation of the thieno[2,3‐c]pyridine scaffold such as 7 with mCPBA, followed by treatment with POBr3, introduced a bromine exclusively at the 7‐position of the heterocycle. The 4‐ or 7‐bromide of the thienopyridines readily underwent Suzuki, Stille coupling, and Buchwald amination reactions, to afford 4‐ or 7‐substituted analogs 6 or 11. The 2‐carboxylate of 4b or 12 was smoothly removed through saponification and decarboxylation to furnish 15 or 16. Deprotonation of the thienopyridine at C‐2 position, followed by trapping with trimethyltin chloride, afforded a 2‐stannyl analog, which was readily converted to other C‐2 derivatives via Stille reaction.

  DOI：

  10.1002/jhet.5570450106

文献信息

• Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors
  作者：Chao Che、Song Li、Bo Yang、Shengchang Xin、Zhixiong Yu、Taofeng Shao、Chuanye Tao、Shuo Lin、Zhen Yang

  DOI：10.3762/bjoc.8.94

  日期：——

  Sant-75 is a newly identified potent inhibitor of the hedgehog pathway. We designed a diversity-oriented synthesis program, and synthesized a series of Sant-75 analogues, which lays the foundation for further investigation of the structure–activity relationship of this important class of hedgehog-pathway inhibitors.

  Sant-75是一种新发现的对刺猬途径具有强大抑制作用的抑制剂。我们设计了一个多样性定向合成计划，并合成了一系列Sant-75类似物，为进一步研究这一重要类别的刺猬途径抑制剂的结构-活性关系奠定了基础。
• Synthesis of thieno[2,3-c]pyridine derived GRK2 inhibitors
  作者：Timea Balo、Attila Sapi、Arpad Kiss、Eric Raimbaud、Jérome Paysant、Marie-Elodie Cattin、Sylvie Berger、Andras Kotschy、Nicolas Faucher

  DOI：10.1007/s00706-021-02889-2

  日期：——

  motifs are frequently used as ATP-mimetic kinase inhibitors. Althought the thieno[2,3-c]pyridine scaffold also meets these criteria its use was limited so far by the availability of synthetic building blocks. Inspired by two X-ray structures of kinase bound thieno[2,3-c]pyridines we prepared a diverse collection of simple thieno[2,3-c]pyridine derivatives that could serve as starting points for future drug

  具有氢键供体-受体铰链结合基序的双环杂芳基基序经常用作 ATP 模拟激酶抑制剂。尽管噻吩并[2,3- c ]吡啶支架也符合这些标准，但到目前为止，它的使用受到合成构件的可用性的限制。受激酶结合的噻吩并[2,3- c ]吡啶的两种 X 射线结构的启发，我们制备了一系列简单的噻吩并[2,3- c ]吡啶衍生物，可作为未来药物发现计划的起点。在我们寻找 GRK2 激酶抑制剂的过程中，我们还发现了一种带有 thieno[2,3- c]吡啶部分。在结构驱动的优化过程之后，制备并表征了一系列有效且高效配体的抑制剂，这可以构成未来药物发现计划的基础。 图形概要
• Cell adhesion-inhibiting antiinflammatory compounds
  申请人：——

  公开号：US20010020030A1

  公开（公告）日：2001-09-06

  Compounds having Formula I 1 are useful for treating inflammation. Also disclosed are pharmaceutical compositions comprising compounds of Formula I, and methods of inhibiting/treating inflammatory diseases in a mammal.

  具有I1式的化合物对于治疗炎症有用。本文还公开了包含I式化合物的制药组合物，以及在哺乳动物中抑制/治疗炎症性疾病的方法。
• Thiadiazole modulators of PKB
  申请人：Zeng Qingping

  公开号：US20090298836A1

  公开（公告）日：2009-12-03

  The invention relates to thiazole compounds of Formula I and Formula II and compositions thereof useful for treating diseases mediated by protein kinase B (PKB) where the variables have the definitions provided herein. The invention also relates to the therapeutic use of such thiazole compounds and compositions thereof in treating disease states associated with abnormal cell growth, cancer, inflammation, and metabolic disorders.

  本发明涉及一种化合物，其为公式I和公式II的噻唑化合物，以及其组合物，可用于治疗由蛋白激酶B（PKB）介导的疾病，其中变量具有本文中提供的定义。本发明还涉及在治疗异常细胞生长、癌症、炎症和代谢紊乱等疾病状态中使用这种噻唑化合物和其组合物的治疗用途。
• 7-AMINOFUROPYRIDINE DERIVATIVES
  申请人：Hornberger Keith R.

  公开号：US20120046267A1

  公开（公告）日：2012-02-23

  Compounds of Formula 1, as shown below and defined herein: pharmaceutically acceptable salts thereof, synthesis, intermediates, formulations, and methods of disease treatment therewith, including treatment of cancers, such as tumors driven at least in part by TAK1 or for which an appropriate TAK1 inhibitor is effective. This Abstract is not limiting of the invention.

  公式1的化合物，如下所示并在此定义：其药学上可接受的盐，合成方法，中间体，配方以及使用它们进行疾病治疗的方法，包括治疗癌症，例如由TAK1至少部分驱动的肿瘤或适当的TAK1抑制剂有效的肿瘤。本摘要不限于该发明。