3,3-双-(4-羟基-苯基)-3H-苯并〔脱〕异苯并吡喃-1酮 | 5627-39-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 3,3-双-(4-羟基-苯基)-3H-苯并〔脱〕异苯并吡喃-1酮
• 英文名称: 3,3-bis-(4-hydroxy-phenyl)-3H-benz[de]isochromen-1-one
• 英文别名: 3,3-Bis-(4-hydroxy-phenyl)-3H-benz[de]isochromen-1-on；Phenolnaphthalein；3,3-Bis(4-hydroxyphenyl)benzo[de]isochromen-1(3H)-one；4,4-bis(4-hydroxyphenyl)-3-oxatricyclo[7.3.1.05,13]trideca-1(12),5,7,9(13),10-pentaen-2-one
• CAS: 5627-39-4
• 化学式: C₂₄H₁₆O₄
• 分子量: 368.389
• InChiKey: JCXWFZRDEFLLDH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,3-双-(4-羟基-苯基)-3H-苯并〔脱〕异苯并吡喃-1酮 在 一氯化碘 作用下， 以 溶剂黄146 为溶剂， 以71%的产率得到1,8-Naphthalein derivative, 9
  参考文献：
  名称：

  邻卤萘作为酪乳杆菌胸苷酸合酶的特异性抑制剂。构象性质和生物活性。

  摘要：

  胸苷酸合酶（TS）（EC 2.1.1.45）是一种参与原核和真核细胞DNA合成的酶，是开发抗癌和抗感染剂的潜在靶标。最近，我们描述了一系列作为TS抑制剂的邻苯二甲酸和萘衍生物。这些化合物具有与叶酸无关的结构（非模拟抗叶酸抑制剂，NAAI），并且对细菌和人TS（hTS）具有选择性。特别地，卤素取代的分子是最令人感兴趣的。在本文中，各种取代的3,3-双（4-羟苯基）-1H，3H-萘[2,3-c]呋喃-1-酮（1-5）和3,3-双（ 4-羟苯基）-1H，3H-萘[1,8-c，合成了d] pyran-1-one（6-14），以研究卤素取代对TS酶的抑制和选择性的生物学作用。探索了萘系列的构象性质，以突出显示相对于非物种特异性分子而言，具有物种特异性生物学特征的分子之间的可能差异。为此目的，通过NMR，在各种溶剂中和在不同温度下以及通过计算分析来研究合成的化合物的构象性质。发现干酪乳杆菌TS（LcTS）的表观抑制常数（K（i））为0

  DOI：

  10.1016/s0968-0896(02)00541-2
• 作为产物：
  描述：

  8-(4-羟基苯甲酰基)萘-1-羧酸 在 三氯化铝 、 苯酚 作用下， 生成 3,3-双-(4-羟基-苯基)-3H-苯并〔脱〕异苯并吡喃-1酮
  参考文献：
  名称：

  The Action of Aluminum Chloride on the Diphenyl Ester of Isophthalic, Terephthalic and Naphthalic Acids

  摘要：

  DOI：

  10.1021/ja01277a001

文献信息

• Matei; Bogdan, Chemische Berichte, 1938, vol. 71, p. 2292,2295
  作者：Matei、Bogdan

  DOI：——

  日期：——
• Mason, Journal of the Chemical Society, 1924, vol. 125, p. 2117
  作者：Mason

  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.
• Kaufmann, Angewandte Chemie, 1927, vol. 40, p. 863
  作者：Kaufmann

  DOI：——

  日期：——
• Jaubert, Chemische Berichte, 1895, vol. 28, p. 992
  作者：Jaubert

  DOI：——

  日期：——