benzhydryl 4-(2-methoxy-3,5,6-trimethyl-4-hydroxybenzoyloxy)-2-methoxy-3,5,6-trimethylbenzoate | 148014-40-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 缩酚酸和缩酚酸环醚类
• 英文名称: benzhydryl 4-(2-methoxy-3,5,6-trimethyl-4-hydroxybenzoyloxy)-2-methoxy-3,5,6-trimethylbenzoate
• 英文别名: 4-{[4-(benzhydryloxycarbonyl)-3-methoxy-2,5,6-trimethylphenoxy]carbonyl}-3-methoxy-2,5,6-trimethylphenol；(4-Benzhydryloxycarbonyl-3-methoxy-2,5,6-trimethylphenyl) 4-hydroxy-2-methoxy-3,5,6-trimethylbenzoate
• CAS: 148014-40-8
• 化学式: C₃₅H₃₆O₇
• 分子量: 568.667
• InChiKey: WLLUZJYUQQMTDV-UHFFFAOYSA-N

物化性质

• 熔点：
  183-185 °C
• 沸点：
  748.5±60.0 °C(Predicted)
• 密度：
  1.186±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  91.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  benzhydryl 4-(2-methoxy-3,5,6-trimethyl-4-hydroxybenzoyloxy)-2-methoxy-3,5,6-trimethylbenzoate 在 palladium on activated charcoal 正丁基锂 、 氢气 、 溶剂黄146 、 苯甲醚 、 三氟乙酸 作用下， 以 甲醇 为溶剂， 反应 0.5h， 生成 Succinic acid bis-[4-(4-carboxy-3-methoxy-2,5,6-trimethyl-phenoxycarbonyl)-3-methoxy-2,5,6-trimethyl-phenyl] ester
  参考文献：
  名称：

  Synthesis and Phospholipase A₂ Inhibitory Activity of Thielocin B3 Derivatives

  摘要：

  We prepared several types of derivatives of thielocin B3, a very potent naturally occurring inhibitor for human nonpancreatic secretory PLA(2) (sPLA(2)-II), and conducted a structure-activity relationship study to identify potent sPLA(2)-II inhibitors with the aim of developing antiinflammatory drugs. The total number of aromatic rings is critical for sPLA(2)-II inhibition, and the best result was obtained in the case of six rings. The structure of the central part of the inhibitors was not specific, and potent inhibitors were found among the sulfide, sulfone, ether, methylene, and amino derivatives. Although a diester of the terminal carboxylic acid lost its inhibitory activity, having both of the carboxylic acids was not necessary for expression of activity, as illustrated by a glycine derivative with the benzyl ester group 36. Among the newly synthesized derivatives, 18, 20, 29, and 36 showed very potent human sPLA(2)-II inhibitory activity comparable to that of natural thielocin B3. Their IC50 values are in the range 0.069-0.14 mu M, and they are a class of compounds showing the most potent sPLA(2)-II inhibition to date.

  DOI：

  10.1021/jm960437a
• 作为产物：
  描述：

  (4-Benzhydryloxycarbonyl-3-methoxy-2,5,6-trimethylphenyl) 2-methoxy-3,5,6-trimethyl-4-phenylmethoxybenzoate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 生成 benzhydryl 4-(2-methoxy-3,5,6-trimethyl-4-hydroxybenzoyloxy)-2-methoxy-3,5,6-trimethylbenzoate
  参考文献：
  名称：

  Synthesis and Phospholipase A₂ Inhibitory Activity of Thielocin B3 Derivatives

  摘要：

  We prepared several types of derivatives of thielocin B3, a very potent naturally occurring inhibitor for human nonpancreatic secretory PLA(2) (sPLA(2)-II), and conducted a structure-activity relationship study to identify potent sPLA(2)-II inhibitors with the aim of developing antiinflammatory drugs. The total number of aromatic rings is critical for sPLA(2)-II inhibition, and the best result was obtained in the case of six rings. The structure of the central part of the inhibitors was not specific, and potent inhibitors were found among the sulfide, sulfone, ether, methylene, and amino derivatives. Although a diester of the terminal carboxylic acid lost its inhibitory activity, having both of the carboxylic acids was not necessary for expression of activity, as illustrated by a glycine derivative with the benzyl ester group 36. Among the newly synthesized derivatives, 18, 20, 29, and 36 showed very potent human sPLA(2)-II inhibitory activity comparable to that of natural thielocin B3. Their IC50 values are in the range 0.069-0.14 mu M, and they are a class of compounds showing the most potent sPLA(2)-II inhibition to date.

  DOI：

  10.1021/jm960437a

文献信息

• Novel carboxylate derivatives exhibiting phospholipase A2 inhibitory activity
  申请人：SHIONOGI & CO., LTD.

  公开号：EP0646569A1

  公开（公告）日：1995-04-05

  Novel carboxylate derivatives exhibiting phospholipase A₂ inhibitory activity are disclosed. Specifically, the following compounds of the formula and pharmaceutically acceptable salts thereof are disclosed: wherein A is hydroxy, amino, or lower alkylamino; R¹ to R¹² are independently hydrogen, methyl, methoxy, or hydroxy, provided that all of R¹ to R¹² are not hydrogen; G¹ is a single bond, or a group of -(CH₂)xO(CH₂)y- wherein x and y are independently 0-5; G² is a single bond, oxygen, sulfur, carbonyl, etc.; G³ is alkyl, aryl, or a group of the formula: wherein R¹³ and R¹⁴ are independently hydrogen, alkyl, aryl, etc.; or R¹³ and R¹⁴ may be taken together with the adjacent nitrogen atom to form a heterocyclic group or a group of the formula: wherein Z is a carbon atom or a nitrogen atom,    J, K ,and L are independently hydrogen or aryl, etc.; p and q are independently 0, 1, or 2; and n is an integer of 1 to 8.

  本发明公开了具有磷脂酶 A₂ 抑制活性的新型羧酸盐衍生物。具体而言，本发明公开了下列式化合物及其药学上可接受的盐类： 其中，A 是羟基、氨基或低级烷基氨基；R¹ 至 R¹² 独立地是氢、甲基、甲氧基或羟基，条件是所有 R¹ 至 R¹² 都不是氢；G¹ 是单键，或 -(CH₂)xO(CH₂)y- 的基团，其中 x 和 y 独立地是 0-5；G² 是单键、氧、硫、羰基等；G³ 是烷基、芳基或式中的基团： 其中 R¹³ 和 R¹⁴ 独立地为氢、烷基、芳基等；或 R¹³ 和 R¹⁴ 可与相邻的氮原子一起形成杂环基团或式中的基团： 其中 Z 是碳原子或氮原子、 J、K 和 L 独立地为氢或芳基等；p 和 q 独立地为 0、1 或 2；n 为 1 至 8 的整数。
• Synthesis and Phospholipase A₂ Inhibitory Activity of Thielocin B3 Derivatives
  作者：Isao Teshirogi、Shigeru Matsutani、Kazuhiro Shirahase、Yasuhiko Fujii、Tadashi Yoshida、Kazushige Tanaka、Mitsuaki Ohtani

  DOI：10.1021/jm960437a

  日期：1996.1.1

  We prepared several types of derivatives of thielocin B3, a very potent naturally occurring inhibitor for human nonpancreatic secretory PLA(2) (sPLA(2)-II), and conducted a structure-activity relationship study to identify potent sPLA(2)-II inhibitors with the aim of developing antiinflammatory drugs. The total number of aromatic rings is critical for sPLA(2)-II inhibition, and the best result was obtained in the case of six rings. The structure of the central part of the inhibitors was not specific, and potent inhibitors were found among the sulfide, sulfone, ether, methylene, and amino derivatives. Although a diester of the terminal carboxylic acid lost its inhibitory activity, having both of the carboxylic acids was not necessary for expression of activity, as illustrated by a glycine derivative with the benzyl ester group 36. Among the newly synthesized derivatives, 18, 20, 29, and 36 showed very potent human sPLA(2)-II inhibitory activity comparable to that of natural thielocin B3. Their IC50 values are in the range 0.069-0.14 mu M, and they are a class of compounds showing the most potent sPLA(2)-II inhibition to date.