1-(3-(5-methyl-1H-imidazol-1-yl)propyl)-3-(8-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)thiourea | 1442459-14-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 1-(3-(5-methyl-1H-imidazol-1-yl)propyl)-3-(8-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)thiourea
• 英文别名: 1-[3-(5-methylimidazol-1-yl)propyl]-3-(8-oxo-6,7-dihydro-5H-naphthalen-2-yl)thiourea
• CAS: 1442459-14-4
• 化学式: C₁₈H₂₂N₄OS
• 分子量: 342.465
• InChiKey: BBLKWRXKZDIBAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  91
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-(5-methyl-1H-imidazol-1-yl)propyl)-3-(8-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)thiourea 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以47%的产率得到1-(8-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-3-(3-(5-methyl-1H-imidazol-1-yl)propyl)thiourea
  参考文献：
  名称：

  Structure–activity relationship of human glutaminyl cyclase inhibitors having an N-(5-methyl-1H-imidazol-1-yl)propyl thiourea template

  摘要：

  In an effort to design inhibitors of human glutaminyl cyclase (QC), we have synthesized a library of N-aryl N-(5-methyl-1H-imidazol-1-yl)propyl thioureas and investigated the contribution of the aryl region of these compounds to their structure-activity relationships as cyclase inhibitors. Our design was guided by the proposed binding mode of the preferred substrate for the cyclase. In this series, compound 52 was identified as the most potent QC inhibitor with an IC50 value of 58 nM, which was two-fold more potent than the previously reported lead 2. Compound 52 is a most promising candidate for future evaluation to monitor its ability to reduce the formation of pGlu-A beta and A beta plaques in cells and transgenic animals. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.005
• 作为产物：
  描述：

  3-(5-methyl-1H-imidazol-1-yl)propan-1-amine 在 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 2.0h， 生成 1-(3-(5-methyl-1H-imidazol-1-yl)propyl)-3-(8-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)thiourea
  参考文献：
  名称：

  Structure–activity relationship of human glutaminyl cyclase inhibitors having an N-(5-methyl-1H-imidazol-1-yl)propyl thiourea template

  摘要：

  In an effort to design inhibitors of human glutaminyl cyclase (QC), we have synthesized a library of N-aryl N-(5-methyl-1H-imidazol-1-yl)propyl thioureas and investigated the contribution of the aryl region of these compounds to their structure-activity relationships as cyclase inhibitors. Our design was guided by the proposed binding mode of the preferred substrate for the cyclase. In this series, compound 52 was identified as the most potent QC inhibitor with an IC50 value of 58 nM, which was two-fold more potent than the previously reported lead 2. Compound 52 is a most promising candidate for future evaluation to monitor its ability to reduce the formation of pGlu-A beta and A beta plaques in cells and transgenic animals. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.005

文献信息

• Structure–activity relationship of human glutaminyl cyclase inhibitors having an N-(5-methyl-1H-imidazol-1-yl)propyl thiourea template
  作者：Phuong-Thao Tran、Van-Hai Hoang、Shivaji A. Thorat、Sung Eun Kim、Jihyae Ann、Yu Jin Chang、Dong Woo Nam、Hyundong Song、Inhee Mook-Jung、Jiyoun Lee、Jeewoo Lee

  DOI：10.1016/j.bmc.2013.04.005

  日期：2013.7

  In an effort to design inhibitors of human glutaminyl cyclase (QC), we have synthesized a library of N-aryl N-(5-methyl-1H-imidazol-1-yl)propyl thioureas and investigated the contribution of the aryl region of these compounds to their structure-activity relationships as cyclase inhibitors. Our design was guided by the proposed binding mode of the preferred substrate for the cyclase. In this series, compound 52 was identified as the most potent QC inhibitor with an IC50 value of 58 nM, which was two-fold more potent than the previously reported lead 2. Compound 52 is a most promising candidate for future evaluation to monitor its ability to reduce the formation of pGlu-A beta and A beta plaques in cells and transgenic animals. (C) 2013 Elsevier Ltd. All rights reserved.