1-{4-methyl-2-[(E)-2-[(3,4,5-trimethoxyphenyl)methylidene]hydrazin-1-yl]-1,3-thiazol-5-yl}ethan-1-one | 1489265-18-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-{4-methyl-2-[(E)-2-[(3,4,5-trimethoxyphenyl)methylidene]hydrazin-1-yl]-1,3-thiazol-5-yl}ethan-1-one
• 英文别名: (E)-1-(2-(2-(3,4,5-trimethoxybenzylidene)hydrazineyl)-4-methylthiazol-5-yl)ethan-1-one；1-[4-methyl-2-[(2E)-2-[(3,4,5-trimethoxyphenyl)methylene]hydrazino]thiazol-5-yl]ethanone；1-[4-methyl-2-[(2E)-2-[(3,4,5-trimethoxyphenyl)methylidene]hydrazinyl]-1,3-thiazol-5-yl]ethanone
• CAS: 1489265-18-0
• 化学式: C₁₆H₁₉N₃O₄S
• 分子量: 349.411
• InChiKey: IULVWCSWFBMHJK-CAOOACKPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲醛 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 1-{4-methyl-2-[(E)-2-[(3,4,5-trimethoxyphenyl)methylidene]hydrazin-1-yl]-1,3-thiazol-5-yl}ethan-1-one
  参考文献：
  名称：

  2-(2-Hydrazinyl)thiazole derivatives: Design, synthesis and in vitro antimycobacterial studies

  摘要：

  In an attempt to discover new potent inhibitors for Mycobacterium tuberculosis (Mtb), a series of 2-(2hydrazinyl)thiazole derivatives with a wide range of substitutions at 2-, 4- and 5-positions were designed by considering Lipinski rule. The designed compounds were synthesized, characterized and evaluated for their inhibitory potential against Mtb, H(37)Rv, by in vitro assay. The compounds, ethyl-4methyl-2-[(E)-24]-(pyridin-2-yl)ethylidene]hydrazin-1-yl]-1,3-thiazole-5-carboxylate, 4d, and ethyl-2[(E)-2-[(2-hydroxyphenyl)methylidenelhydrazin-1-yl]-4-methyl-1,3-thiazole-5-carboxylate, 2i showed noticeable inhibitory activity against Mtb, H37Rv with minimum inhibitory concentration (MIC) of 12.5 pM and 25 1.1M respectively. An attempt has been made to understand the mechanism of action by binding interactions of these molecules with 0-ketoacyl-ACP synthase protein through docking studies. The inhibition constants for compounds 4d and 2i were found to be 1.46 pM and 0.177 pM respectively. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.08.054

文献信息

• Azomethine-clubbed thiazoles as human tissue non-specific alkaline phosphatase (h-TNAP) and intestinal alkaline phosphatase (h-IAP) Inhibitors: kinetics and molecular docking studies
  作者：Aamer Saeed、Memona Javaid、Syed Jawad Ali Shah、Pervaiz Ali Channar、Ghulam Shabir、Arfa Tehzeeb、Jamshed Iqbal

  DOI：10.1007/s11030-022-10385-w

  日期：2022.12

  thiazoles (3a–i) was synthesized and appraised for their inhibitory potential against human tissue non-specific alkaline phosphatase (h-TNAP) and human intestinal alkaline phosphatase (h-IAP). Compounds 3c and 3f were found to be most potent compounds toward h-TNAP with IC50 values of 0.15 ± 0.01 and 0.50 ± 0.01 µM, respectively, whereas 3a and 3f exhibited maximum potency for h-IAP with IC50 value of 2

  摘要 噻唑衍生物是已知的碱性磷酸酶抑制剂，但各种副作用降低了它们的疗效。相反，带有偶氮甲碱键的化合物显示出广泛的生物学应用。因此，将两个支架结合在一个结构单元中应该会产生两者的联合有益效果。合成了一系列新的偶氮甲碱偶联噻唑 ( 3a–i )，并评估了它们对人体组织非特异性碱性磷酸酶 ( h -TNAP) 和人体肠道碱性磷酸酶 ( h -IAP) 的抑制潜力。化合物3c和3f被发现是对h -TNAP 最有效的化合物，IC为 50值分别为 0.15 ± 0.01 和 0.50 ± 0.01 µM，而3a和3f对h -IAP表现出最大效力，IC 50值分别为 2.59 ± 0.04 和 2.56 ± 0.02 µM。还进行了分子对接研究以发现潜在抑制剂和酶活性位点之间的结合相互作用类型。进行酶抑制动力学研究以确定酶抑制的机制。目前的研究导致发现了一些有效的碱性磷酸酶抑制剂，这些抑制剂有望用于鉴定具有药物特性的化合物。