4-(2-氨基-1,3-噻唑-4-基)苯甲酸乙酯 | 651042-69-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(2-氨基-1,3-噻唑-4-基)苯甲酸乙酯
• 英文名称: ethyl 4-(2-amino-1,3-thiazol-4-yl)benzoate
• 英文别名: ethyl 4-(2-aminothiazol-4-yl)benzoate
• CAS: 651042-69-2
• 化学式: C₁₂H₁₂N₂O₂S
• 分子量: 248.305
• InChiKey: ZRQYVQKHYUPKST-UHFFFAOYSA-N

物化性质

• 沸点：
  438.0±28.0 °C(Predicted)
• 密度：
  1.279±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  93.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(1,3-苯并二氧代l-5-基)环丙烷羧酸 、 4-(2-氨基-1,3-噻唑-4-基)苯甲酸乙酯 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl 4-(2-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)thiazol-4-yl)benzoate
  参考文献：
  名称：

  Synthesis and biological evaluation of novel thiazole- VX-809 hybrid derivatives as F508del correctors by QSAR-based filtering tools

  摘要：

  The most common CF mutation, F508del, impairs the processing and gating of CFTR protein. This deletion results in the improper folding of the protein and its degradation before it reaches the plasma membrane of epithelial cells. Present correctors, like VX809 only induce a partial rescue of the mutant protein. Our previous studies reported a class of compounds, called aminoarylthiazoles (AATs), featuring an interesting activity as correctors. Some of them show additive effect with VX809 indicating a different mechanism of action. In an attempt to construct more interesting molecules, it was thought to generate chemically hybrid compounds, blending a portion of VX809 merged to the thiazole scaffold. This approach was guided by the development of QSAR analyses, which were performed based on the F508del correctors so far disclosed in the literature. This strategy was aimed at exploring the key requirements turning in the corrector ability of the collected derivatives and allowed us to derive a predictive model guiding for the synthesis of novel hybrids as promising correctors. The new molecules were tested in functional and biochemical assays on bronchial CFBE41o-cells expressing F508del-CFTR showing a promising corrector activity. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.12.030
• 作为产物：
  描述：

  4-乙酰基苯甲酸 在 硫酸 、 溴 作用下， 以 甲醇 、 乙醇 、 氯仿 为溶剂， 反应 24.0h， 生成 4-(2-氨基-1,3-噻唑-4-基)苯甲酸乙酯
  参考文献：
  名称：

  鉴定具有2-氨基噻唑部分的吡酸衍生物结合了双重PPARα/γ激活和双重5-LO / mPGES-1抑制

  摘要：

  最初提出双重PPARα/γ激活的概念作为治疗代谢综合征的新方法。但是，最近的结果表明，PPARα以及PPARγ活化也可能对炎症性疾病和癌症的治疗有益。我们最近已确定氨基噻唑为特征的吡rin酸为双5-脂氧合酶（5-LO）和微粒体前列腺素E 2合酶1（mPGES-1）抑制剂。在这里，我们介绍了这些氨基噻唑特征的吡rin酸作为双重PPARα/γ激动剂的结构与活性之间的关系，并讨论了它们作为双重5-LO / mPGES-1抑制剂在炎性和癌症疾病中的潜力的优势。多种吡喃酸衍生物已被确定为双重PPARα/γ激动剂。然而，在这一系列氨基噻唑特色的吡rin酸中，我们能够鉴定出最有效的选择性PPARγ激动性吡rin酸衍生物（化合物13，（2-[（4-氯-6-{[4-（萘-2-基）-1，3-噻唑-2-基]氨基}嘧啶-2-基）硫烷基]辛酸））。因此，进行13在PPARγ上的对接以确定潜在的结合模式。

  DOI：

  10.1016/j.bmcl.2014.06.077

文献信息

• Preparation of 3,4-Substituted-5-Aminopyrazoles and 4-Substituted-2-Aminothiazoles
  作者：Stepan Havel、Prashant Khirsariya、Naresh Akavaram、Kamil Paruch、Benoit Carbain

  DOI：10.1021/acs.joc.8b02655

  日期：2018.12.21

  3,4-Substituted-5-aminopyrazoles and 4-substituted-2-aminothiazoles are frequently used intermediates in medicinal chemistry and drug discovery projects. We report an expedient flexible synthesis of 3,4-substituted-5-aminopyrazoles (35 examples), based on palladium-mediated α-arylation of β-ketonitriles with aryl bromides. A library of 4-substituted-2-aminothiazoles (21 examples) was assembled by a

  3,4-取代的5-氨基吡唑和4-取代的2-氨基噻唑是药物化学和药物开发项目中经常使用的中间体。我们报道了基于钯介导的β-酮腈与芳基溴化物的α-芳基化反应的3,4-取代的5-氨基吡唑类化合物的便捷合成（35个例子）。通过使用新制备的，适当保护的4-硼酸-2-氨基噻唑的频哪醇酯和MIDA酯与（杂）芳基卤化物的Suzuki偶联的序列，组装4-取代的2-氨基噻唑的文库（21个实例）。
• Synthesis and in vitro kinetic evaluation of N-thiazolylacetamido monoquaternary pyridinium oximes as reactivators of sarin, O-ethylsarin and VX inhibited human acetylcholinesterase (hAChE)
  作者：Aditya Kapil Valiveti、Uma M. Bhalerao、Jyotiranjan Acharya、Hitendra N. Karade、Badri Narayan Acharya、G. Raviraju、Anand K. Halve、Mahabir Parshad Kaushik

  DOI：10.1016/j.bmc.2015.05.027

  日期：2015.8

  the newly synthesized oximes were evaluated for their physicochemical parameters (pKa) and correlated with their respective reactivation efficacies to assess the capability of the oxime reactivator. Three of these novel compounds showed promising reactivation efficacies toward OP inhibited hAChE. Molecular docking studies were performed in order to correlate the reactivation efficacies with their interactions

  由于各种药理和毒理学原因，目前可用的用于治疗有机磷中毒的药物不够有效。在这方面，我们在此报告了一系列N-噻唑基乙酰胺单季吡啶鎓肟及其类似物（1a - 1b至6a - 6b）的合成，并带有不同取代的噻唑环，并评估了它们在体外对神经毒剂（沙林，O-乙基沙林和VX）抑制人红细胞乙酰胆碱酯酶（h AChE）。进行再活化动力学以确定解离常数（K D），反应速率常数（K D）。k r）和所有化合物的二阶速率常数（k r2），并将其功效与市售解毒剂进行比较。2-PAM和obidoxime。评价所有新合成的肟的理化参数（p K a），并将其与各自的再活化效率相关联，以评估肟再活化剂的能力。这些新颖的化合物中的三个显示出对OP抑制h AChE有希望的再激活作用。进行了分子对接研究，以使再活化效率与其在AChE活性位点的相互作用相关联。
• Gut microsomal triglyceride transport protein inhibitors
  申请人：Vu Chi B.

  公开号：US20080249130A1

  公开（公告）日：2008-10-09

  Compounds represented by formula (I): are inhibitors of gut microsomal triglyceride transfer protein. Such compounds are useful in treating diseases or conditions such as diabetes and obesity, along with patients are risk for developing such diseases or conditions.

  化学式（I）所代表的化合物是肠道微粒体甘油三酯转移蛋白的抑制剂。这些化合物在治疗糖尿病和肥胖等疾病或病况的患者以及患有这些疾病或病况的风险患者中非常有用。
• MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-kB ACTIVITY AND USE THEREOF
  申请人：Yang Bingwei Vera

  公开号：US20100063051A1

  公开（公告）日：2010-03-11

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity including inflammatory and immune diseases, obesity and diabetes having the structure of formula (I) an enantiomer, diastereomer, tautomer, solvate (e.g. a hydrate), or a pharmaceutically-acceptable salt, thereof, wherein: M is selected from alkyl, substituted alkyl, cycloalkyl, aryl, heterocyclo, and heteroaryl, provided that if M is alkyl then R 6 and R 7 taken together with the carbon atom to which they are both attached are selected from a group other than cycloalkyl; Q is selected from (i) hydrogen, C 1 -C 4 alkyl, and substituted C 1 -C 4 alkyl; or (ii) Q and R 6 are combined with the carbon atoms to which they are attached to form a 3- to 6-membered cycloalkyl; or (iii) Q and M a M are combined with the carbon atom(s) to which they are attached to form a 3- to 7-membered ring containing 1-2 heteroatoms which are independently selected from the group consisting of O, S, SO 2 , and N which ring may be optionally substituted with 0-2 R 5 groups or carbonyl; Z is selected from cycloalkyl, heterocyclo, aryl, or heteroaryl; and M a , Z a , R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , and R 22 are as defined herein. Also provided are pharmaceutical compositions and methods of treating metabolic and inflammatory- or immune-associated diseases or disorders using said compounds.

  提供了一些新型非类固醇化合物，其在治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病中非常有用，包括炎症和免疫性疾病、肥胖症和糖尿病，具有以下结构公式（I）的对映体、顺反异构体、互变异构体、溶剂化物（例如水合物）或其医药上可接受的盐，其中：M选自烷基、取代烷基、环烷基、芳基、杂环烷基和杂芳基，但如果M是烷基，则R6和R7与它们都连接的碳原子一起选自环烷基之外的一组；Q选自（i）氢、C1-C4烷基和取代的C1-C4烷基；或（ii）Q和R6与它们连接的碳原子结合形成3-到6-成员的环烷基；或（iii）Q和MaM与它们连接的碳原子结合形成1-2个杂原子（独立于O、S、SO2和N组成）的3-到7-成员的环，该环可以选择性地用0-2个R5基团或羰基取代；Z选自环烷基、杂环烷基、芳基或杂芳基；而Ma、Za、R1、R2、R3、R4、R6、R7和R22如本文所定义。还提供了制药组合物和使用所述化合物治疗代谢和炎症或免疫相关疾病或紊乱的方法。
• WO2008/100423
  申请人：——

  公开号：——

  公开（公告）日：——