N-(5-acetyl-4-methyl-1,3-thiazol-2-yl)-3-chloropropanamide | 903735-61-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(5-acetyl-4-methyl-1,3-thiazol-2-yl)-3-chloropropanamide
• 英文别名: N-(5-acetyl-4-methylthiazol-2-yl)-3-chloropropionamide；N-(4-methyl-5-acetylthiazol-2-yl)-3-chloropropionamide；4-methyl-5-acetyl-2-(3-chloropropionylamino)thiazole
• CAS: 903735-61-5
• 化学式: C₉H₁₁ClN₂O₂S
• 分子量: 246.718
• InChiKey: DBJXYURSABTZAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  87.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(5-acetyl-4-methyl-1,3-thiazol-2-yl)-3-chloropropanamide 在 甲醇 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 9.5h， 生成 [3-[(5-Acetyl-4-methyl-1,3-thiazol-2-yl)amino]-3-oxopropyl]phosphonic acid
  参考文献：
  名称：

  Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors

  摘要：

  DOXP-reductoisomerase (DXR) is a validated target for the development of antimalarial drugs to address the increase in resistant strains of Plasmodium falciparum. Series of aryl- and heteroarylcarbamoylphosphonic acids, their diethyl esters and disodium salts have been prepared as analogues of the potent DXR inhibitor fosmidomycin. The effects of the carboxamide N-substituents and the length of the methylene linker have been explored using in silico docking studies, saturation transfer difference NMR spectroscopy and enzyme inhibition assays using both EcDXR and PfDXR. These studies indicate an optimal linker length of two methylene units and have confirmed the importance of an additional binding pocket in the PfDXR active site. Insights into the constraints of the PfDXR binding site provide additional scope for the rational design of DXR inhibitors with increased ligand-receptor interactions. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.076
• 作为产物：
  描述：

  乙酰丙酮 在 N-溴代丁二酰亚胺(NBS) 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 19.5h， 生成 N-(5-acetyl-4-methyl-1,3-thiazol-2-yl)-3-chloropropanamide
  参考文献：
  名称：

  Design, synthesis and neuraminidase inhibitory activity of 4-methyl-5-(3-phenylacryloyl) thiazoles

  摘要：

  研究人员设计、合成了一系列基于查耳酮的 4-甲基-5-(3-苯基丙烯酰基)噻唑，并在体外评估了它们对流感神经氨酸酶（NA）的抑制活性。初步的结构-活性关系（SAR）分析表明，含酰胺的噻唑类化合物具有更强的效力。分析还表明，苯环 4 位上的单羟基比其他释放电子的基团或撤回电子的基团更有效。化合物 A2 和 A26 对 NA 更有效，IC50 值分别为 8.2 ± 0.5 μg/mL 和 6.2 ± 1.4 μg/mL。分子对接研究表明，噻唑骨架有利于NA的抑制活性。

  DOI：

  10.1007/s11030-023-10639-1

文献信息

• N-(5-酰基噻唑-2-基)哌嗪基酰胺及其医药用 途
  申请人：湖南大学

  公开号：CN107235927B

  公开（公告）日：2019-04-16

  本发明公开了结构式Ⅰ和Ⅱ所示的N‑(5‑酰基噻唑‑2‑基)哌嗪基酰胺及其药学上可接受的盐，其制备方法和药物组合物以及其在制备流感病毒神经氨酸酶抑制剂中的应用。
• N-(5-酰基噻唑-2-基)酰胺及其制备方法与应 用
  申请人：湖南大学

  公开号：CN107141267B

  公开（公告）日：2019-04-09

  本发明公开了结构式Ⅰ所示的N‑(5‑酰基噻唑‑2‑基)酰胺及其药学上可接受的盐，其制备方法和药物组合物以及其在制备流感病毒神经氨酸酶抑制剂中的应用。
• Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors
  作者：Taryn Bodill、Anne C. Conibear、Marius K.M. Mutorwa、Jessica L. Goble、Gregory L. Blatch、Kevin A. Lobb、Rosalyn Klein、Perry T. Kaye

  DOI：10.1016/j.bmc.2013.04.076

  日期：2013.7

  DOXP-reductoisomerase (DXR) is a validated target for the development of antimalarial drugs to address the increase in resistant strains of Plasmodium falciparum. Series of aryl- and heteroarylcarbamoylphosphonic acids, their diethyl esters and disodium salts have been prepared as analogues of the potent DXR inhibitor fosmidomycin. The effects of the carboxamide N-substituents and the length of the methylene linker have been explored using in silico docking studies, saturation transfer difference NMR spectroscopy and enzyme inhibition assays using both EcDXR and PfDXR. These studies indicate an optimal linker length of two methylene units and have confirmed the importance of an additional binding pocket in the PfDXR active site. Insights into the constraints of the PfDXR binding site provide additional scope for the rational design of DXR inhibitors with increased ligand-receptor interactions. (C) 2013 Elsevier Ltd. All rights reserved.
• Design, synthesis and neuraminidase inhibitory activity of 4-methyl-5-(3-phenylacryloyl) thiazoles
  作者：Yu-Yang Liu、Yang-Jie Yi、Jiao Ye、Ai-Xi Hu

  DOI：10.1007/s11030-023-10639-1

  日期：——

  A series of 4-methyl-5-(3-phenylacryloyl)thiazoles based on chalcones were designed, synthesized and evaluated for their influenza neuraminidase (NA) inhibitory activity in vitro. A preliminary structure–activity relationship (SAR) analysis showed that thiazoles bearing amide had greater potency. It also showed that mono-hydroxyl group at 4-position on phenyl ring was more effective than other electron-releasing groups or electron-withdraw groups. Compounds A2 and A26 were more potent against NA with IC50 values of 8.2 ± 0.5 μg/mL and 6.2 ± 1.4 μg/mL, respectively. Molecular docking study demonstrated that thiazoles skeleton was benefit for the NA inhibitory activity.

  研究人员设计、合成了一系列基于查耳酮的 4-甲基-5-(3-苯基丙烯酰基)噻唑，并在体外评估了它们对流感神经氨酸酶（NA）的抑制活性。初步的结构-活性关系（SAR）分析表明，含酰胺的噻唑类化合物具有更强的效力。分析还表明，苯环 4 位上的单羟基比其他释放电子的基团或撤回电子的基团更有效。化合物 A2 和 A26 对 NA 更有效，IC50 值分别为 8.2 ± 0.5 μg/mL 和 6.2 ± 1.4 μg/mL。分子对接研究表明，噻唑骨架有利于NA的抑制活性。