(5Z)-3-[2-hydroxy-3-[3-(4-methylpiperazin-1-yl)propylamino]propyl]-5-[(4-methoxyphenyl)methylidene]imidazolidine-2,4-dione;hydrochloride | 1416719-63-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (5Z)-3-[2-hydroxy-3-[3-(4-methylpiperazin-1-yl)propylamino]propyl]-5-[(4-methoxyphenyl)methylidene]imidazolidine-2,4-dione;hydrochloride
• CAS: 1416719-63-5
• 化学式: C₂₂H₃₃N₅O₄*ClH
• 分子量: 467.996
• InChiKey: MJVRDKYJYSVWDS-VSOKSMTPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  97.4
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-(3-氨丙基)-4-甲基哌嗪 、 (Z)-5-(4-methoxybenzylidene)-3-(oxiran-2-ylmethyl)imidazolidine-2,4-dione 在 盐酸 作用下， 以 neat (no solvent) 为溶剂， 反应 0.27h， 以22%的产率得到(5Z)-3-[2-hydroxy-3-[3-(4-methylpiperazin-1-yl)propylamino]propyl]-5-[(4-methoxyphenyl)methylidene]imidazolidine-2,4-dione;hydrochloride
  参考文献：
  名称：

  Search for new tools to combat Gram-negative resistant bacteria among amine derivatives of 5-arylidenehydantoin

  摘要：

  A series of amine-alkyl derivatives of 5-arylidenehydantoin 3-21 was evaluated for their ability to improve antibiotic effectiveness in two strains of Gram-negative Enterobacter aerogenes: the reference strain (ATCC-13048) and the chloramphenicol-resistant derivative over-producing the AcrAB-TolC efflux pump (CM-64). Three antibiotics, chloramphenicol, nalidixic acid and sparfloxacin were used as markers of efflux pump activity. New compounds (5-16) were obtained within 3-4 step synthesis using Knoevenagel condensation, Mitsunobu reaction and microwave aided N-alkylation. Molecular modeling based structure-activity relationship (SAR) studies were performed. The most active compounds: (Z)-5-(4-(diethylamino) benzylidene)-3-(2-hydroxy-3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)imidazolidine-2,4-dione (14) and (Z)-5-(2,4-dimethoxybenzylidene)-3-(2-hydroxy-3-(isopropylamino)propyl)imidazolidine-2,4-dione (15) induced fourfold decrease of minimal inhibition concentration (MIC) of all tested antibiotics in the strain CM-64 overexpressing the AcrAB-TolC pump. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.10.053

文献信息

• Search for new tools to combat Gram-negative resistant bacteria among amine derivatives of 5-arylidenehydantoin
  作者：Jadwiga Handzlik、Ewa Szymańska、Sandrine Alibert、Jacqueline Chevalier、Ewa Otrębska、Elżbieta Pękala、Jean-Marie Pagès、Katarzyna Kieć-Kononowicz

  DOI：10.1016/j.bmc.2012.10.053

  日期：2013.1

  A series of amine-alkyl derivatives of 5-arylidenehydantoin 3-21 was evaluated for their ability to improve antibiotic effectiveness in two strains of Gram-negative Enterobacter aerogenes: the reference strain (ATCC-13048) and the chloramphenicol-resistant derivative over-producing the AcrAB-TolC efflux pump (CM-64). Three antibiotics, chloramphenicol, nalidixic acid and sparfloxacin were used as markers of efflux pump activity. New compounds (5-16) were obtained within 3-4 step synthesis using Knoevenagel condensation, Mitsunobu reaction and microwave aided N-alkylation. Molecular modeling based structure-activity relationship (SAR) studies were performed. The most active compounds: (Z)-5-(4-(diethylamino) benzylidene)-3-(2-hydroxy-3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)imidazolidine-2,4-dione (14) and (Z)-5-(2,4-dimethoxybenzylidene)-3-(2-hydroxy-3-(isopropylamino)propyl)imidazolidine-2,4-dione (15) induced fourfold decrease of minimal inhibition concentration (MIC) of all tested antibiotics in the strain CM-64 overexpressing the AcrAB-TolC pump. (C) 2012 Elsevier Ltd. All rights reserved.