(E)-5-(5-fluoro-1H-indol-3-ylmethylene)-2-imino-1,3-dimethylimidazolidin-4-one | 1187662-31-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (E)-5-(5-fluoro-1H-indol-3-ylmethylene)-2-imino-1,3-dimethylimidazolidin-4-one
• 英文别名: 5-fluoroaplysinopsin；(5E)-5-[(5-fluoro-1H-indol-3-yl)methylidene]-2-imino-1,3-dimethylimidazolidin-4-one
• CAS: 1187662-31-2
• 化学式: C₁₄H₁₃FN₄O
• 分子量: 272.282
• InChiKey: TUJNDQSRVJGZLW-ZSUDRMHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.99
• 重原子数：
  20.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  63.19
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为产物：
  描述：

  5-氟吲哚 在 三氯氧磷 作用下， 反应 0.67h， 生成 (E)-5-(5-fluoro-1H-indol-3-ylmethylene)-2-imino-1,3-dimethylimidazolidin-4-one
  参考文献：
  名称：

  Synthesis and Characterization of Aplysinopsin Analogs

  摘要：

  通过将 5-溴-5-氟-和 6-溴吲哚-3-甲醛与肌酐或 2-亚氨基-1-甲基-3-乙基咪唑烷-4-酮或 2-亚氨基-1-甲基-3-乙基咪唑烷-4-酮反应，合成了三种芹菜素类似物、5-bromo-4′-de-N-methylaplysinopsin DMF solvate [from creatinine, space group P21/n, lattice parameters a ；= 13.117(3) Å, b = 8.6663(15) Å, c = 14.743(3) Å, β = 99.538(10)° at 173 K], 5-fluoroaplysinopsin DMF solvate [from 2-imino-1,3-dimethyl-imidazolidin-4-one, space group P21/c, lattice parameters a = 11.114(3) Å, b = 19.118(2) Å, c = 8.503(2) Å, β = 112.290(7)°]，以及 6-溴吲哚-3-甲醛（空间群 P21/n，晶格参数 a = 7。657(2) 埃，b = 7.933(2) 埃，c = 13.521(3) 埃，β = 99.046(13)°）。表征包括利用 IR、UV、HRMS 以及 1H 和 13C NMR 进行光谱鉴定。5-Bromo-4′-de-N-methylaplysinopsin 和 5-fluoroaplysinopsin 以 E 构型存在。对 5-溴-4′-去-N-甲基芹菜苷、5-氟芹菜苷和 6-溴吲哚-3-甲醛进行了单晶 X 射线结构分析。

  DOI：

  10.1007/s10870-008-9480-1

文献信息

• Synthesis and structure–affinity relationships of novel small molecule natural product derivatives capable of discriminating between serotonin 5-HT1A, 5-HT2A, 5-HT2C receptor subtypes
  作者：David F. Cummings、Diana C. Canseco、Pratikkumar Sheth、James E. Johnson、John A. Schetz

  DOI：10.1016/j.bmc.2010.05.017

  日期：2010.7

  Efforts to develop ligands that distinguish between clinically relevant 5-HT2A and 5-HT2C serotonin receptor subtypes have been challenging, because their sequences have high homology. Previous studies reported that a novel aplysinopsin belonging to a chemical class of natural products isolated from a marine sponge was selective for the 5-HT2C over the 5-HT2A receptor subtype. Our goal was to explore the 5-HT2A/2C receptor structure-affinity relationships of derivatives based on the aplysinopsin natural product pharmacophore. Twenty aplysinopsin derivatives were synthesized, purified and tested for their affinities for cloned human serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptor subtypes. Four compounds in this series had >30-fold selectivity for 5-HT2A or 5-HT2C receptors. The compound (E)-5-((5,6-dichloro-1H-indol-3-yl) methylene)-2-imino-1,3-dimethylimidazolidin-4-one (UNT-TWU-22, 16) had approximately 2100-fold selectivity for the serotonin 5-HT2C receptor subtype: an affinity for 5-HT2C equal to 46 nM and no detectable affinity for the 5-HT1A or 5-HT2A receptor subtypes. The two most important factors controlling 5-HT2A or 5-HT2C receptor subtype selectivity were the combined R1,R3-alkylation of the imidazolidinone ring and the type and number of halogens on the indole ring of the aplysinopsin pharmacophore. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis and Characterization of Aplysinopsin Analogs
  作者：James E. Johnson、Diana C. Canseco、Debra D. Dolliver、John A. Schetz、Frank R. Fronczek

  DOI：10.1007/s10870-008-9480-1

  日期：2009.5

  Three aplysinopsin analogs were synthesized by reacting 5-bromo-5-fluoro- and 6-bromoindole-3-carboxaldehyde with either creatinine or 2-imino-1,3-dimethyl-imidazolidin-4-one or 2-imino-1-methyl-3-ethylimidazolidin-4-one Single crystal structures on 5-bromo-4′-de-N-methylaplysinopsin DMF solvate [from creatinine, space group P21/n, lattice parameters a = 13.117(3) Å, b = 8.6663(15) Å, c = 14.743(3) Å, β = 99.538(10)° at 173 K], 5-fluoroaplysinopsin DMF solvate [from 2-imino-1,3-dimethyl-imidazolidin-4-one, space group P21/c, lattice parameters a = 11.114(3) Å, b = 19.118(2) Å, c = 8.503(2) Å, β = 112.290(7)°], and 6-bromoindole-3-carboxaldehyde (space group P21/n, lattice parameters a = 7.657(2) Å, b = 7.933(2) Å, c = 13.521(3) Å, β = 99.046(13)°) have been determined. Characterizations include spectrometric identifications employing IR, UV, HRMS, and 1H and 13C NMR. 5-Bromo-4′-de-N-methylaplysinopsin and 5-fluoroaplysinopsin exist in the E configuration. Single crystal X-ray structural analyses were carried out on 5-bromo-4′-de-N-methylaplysinopsin, 5-fluoroaplysinopsin, and 6-bromoindole-3-carboxaldehyde.

  通过将 5-溴-5-氟-和 6-溴吲哚-3-甲醛与肌酐或 2-亚氨基-1-甲基-3-乙基咪唑烷-4-酮或 2-亚氨基-1-甲基-3-乙基咪唑烷-4-酮反应，合成了三种芹菜素类似物、5-bromo-4′-de-N-methylaplysinopsin DMF solvate [from creatinine, space group P21/n, lattice parameters a ；= 13.117(3) Å, b = 8.6663(15) Å, c = 14.743(3) Å, β = 99.538(10)° at 173 K], 5-fluoroaplysinopsin DMF solvate [from 2-imino-1,3-dimethyl-imidazolidin-4-one, space group P21/c, lattice parameters a = 11.114(3) Å, b = 19.118(2) Å, c = 8.503(2) Å, β = 112.290(7)°]，以及 6-溴吲哚-3-甲醛（空间群 P21/n，晶格参数 a = 7。657(2) 埃，b = 7.933(2) 埃，c = 13.521(3) 埃，β = 99.046(13)°）。表征包括利用 IR、UV、HRMS 以及 1H 和 13C NMR 进行光谱鉴定。5-Bromo-4′-de-N-methylaplysinopsin 和 5-fluoroaplysinopsin 以 E 构型存在。对 5-溴-4′-去-N-甲基芹菜苷、5-氟芹菜苷和 6-溴吲哚-3-甲醛进行了单晶 X 射线结构分析。