3',3"-dichlorophenolphthalein | 74920-86-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 3',3"-dichlorophenolphthalein
• 英文别名: 3,3-bis-(3-chloro-4-hydroxy-phenyl)-phthalide；3,3-Bis-(3-chlor-4-hydroxy-phenyl)-phthalid；3,3-Bis-(3-chloro-4-hydroxy-phenyl)-3H-isobenzofuran-1-one；3,3-bis(3-chloro-4-hydroxyphenyl)-2-benzofuran-1-one
• CAS: 74920-86-8
• 化学式: C₂₀H₁₂Cl₂O₄
• 分子量: 387.219
• InChiKey: DCEZOJIOLWHWEV-UHFFFAOYSA-N

物化性质

• 沸点：
  577.2±50.0 °C(Predicted)
• 密度：
  1.526±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氯苯甲醚 在 二硫化碳 、 三氯化铝 、 氢溴酸 、 溶剂黄146 作用下， 生成 3',3"-dichlorophenolphthalein
  参考文献：
  名称：

  HALOGEN DERIVATIVES OF DIARYLPHTHALIDES. II¹

  摘要：

  DOI：

  10.1021/ja01343a028

文献信息

• Thiel; Diehl, Sitzungsberichte der Gesellschaft zur Befoerderung der Gesamten Naturwissenschaften zu Marburg, vol. 62, p. 536
  作者：Thiel、Diehl

  DOI：——

  日期：——
• Phthalein Derivatives as a New Tool for Selectivity in Thymidylate Synthase Inhibition
  作者：Paola M. Costi、Marcella Rinaldi、Donatella Tondi、Piergiorgio Pecorari、Daniela Barlocco、Stefano Ghelli、Robert M. Stroud、Daniel V. Santi、Thomas J. Stout、Chiara Musiu、Elena M. Marangiu、Alessandra Pani、Donatella Congiu、Giulia A. Loi、Paolo La Colla

  DOI：10.1021/jm9900016

  日期：1999.6.1

  A new set of phthalein derivatives stemming from the lead compound, phenolphthalein, were designed to specifically complement structural features of a bacterial form of thymidylate synthase (Lactobacillus casei, LcTS) versus the human TS (hTS) enzyme. The new compounds were screened for their activity and their specificity against TS enzymes from different species, namely, L. casei (LcTS), Pneumocystis carinii (PcTS), Cryptococcus neoformans (CnTS), and human thymidylate synthase (hTS). Apparent inhibition constants (Ki) for all the compounds against LcTS were determined, and inhibition factors (IF,ratio between the initial rates of the enzymatic reaction in the presence and absence of each inhibitor) against each of the four TS species were measured. A strong correlation was found between the two activity parameters, IF and Ki, and therefore the simpler IF was used as a screening factor in order to accelerate biological evaluation. Compounds 5b, 5c, 5ba, and 6bc showed substantial inhibition of LcTS while remaining largely inactive against hTS, illustrating for the first time remarkable species specificity among TSs. Due to sequence homology between the enzymes, several compounds also showed high activity and specificity for CnTS. In particular, 3-hydroxy-3-(3-chloro-4-hydroxyphenyl)-6-nitro-1H,3H-naphtho[1,8-c,d]pyran-1-one, (6bc) showed an IF < 0.04 for CnTS (K-i = 0.45 mu M) while remaining inactive in the hTS assay at the maximum solubility concentration of the compound (200 mu M). In cell culture assays most Of the compounds were found to be noncytotoxic to human cell lines but were cytotoxic against several species of Grampositive bacteria. These results are consistent with the enzymatic assays. Intriguingly, several compounds also had selective activity against Cr. neoformans in cell culture assay. In general, the most active and selective compounds against the Gram-positive bacteria were those designed and found in the enzyme assay to be specific for LcTS versus hTS. The original lead compound was least selective against most of the cell lines tested. To our knowledge these compounds are the first TS inhibitors selective for bacterial TS with respect to hTS.
• Conformational analysis of phthalein derivatives acting as thymidylate synthase inhibitors by means of 1H NMR and quantum chemical calculations
  作者：Stefano Ghelli、Giulio Rastelli、Daniela Barlocco、Marcella Rinaldi、Donatella Tondi、Piergiorgio Pecorari、Maria Paola Costi

  DOI：10.1016/0968-0896(96)00193-9

  日期：1996.10

  The conformations of a set of phthalein derivatives with bacterial thymidylate synthase (TS) inibitory activity were investigated by H-1 NMR spectra, performed at both room and low temperature, and by quantum chemical calculations. Since the crystal structure of the binary complex of phenolphthalein with the enzyme is known, we set out to study the conformation of various of its analogues in solution in order to observe the effects of the substituents on the phenolic rings, of the alpha-naphthol derivative and of the rigid analogue, fluorescein, and compare the results with the X-ray crystal structure studies. A relationship between the chemical shift of the proton on C4 (H4) of the phthalidic ring and the averaged angle formed by the phthalidic and the aromatic ring planes was found in which the most perpendicular conformations have the lowest H4 chemical shift values. At room temperature, the rotational freedom of all the studied compounds was similar, while at lower temperature the naphthol derivative assumed a partially blocked conformation. Finally, a qualitative relationship between the inhibitory properties of the compounds and their conformations is discussed. Copyright (C) 1996 Elsevier Science Ltd
• US5814373A
  申请人：——

  公开号：US5814373A

  公开（公告）日：1998-09-29
• US6051294A
  申请人：——

  公开号：US6051294A

  公开（公告）日：2000-04-18