methyl 7-(4-fluorophenyl)-7-<3-(1-hydroxyethyl)-60methoxy-2,4,5-trimethylphenyl>heptanoate | 121099-68-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 7-(4-fluorophenyl)-7-<3-(1-hydroxyethyl)-60methoxy-2,4,5-trimethylphenyl>heptanoate
• 英文别名: Methyl 7-(4-fluorophenyl)-7-[5-(1-hydroxyethyl)-2-methoxy-3,4,6-trimethylphenyl]heptanoate
• CAS: 121099-68-1
• 化学式: C₂₆H₃₅FO₄
• 分子量: 430.56
• InChiKey: ZCSOGKILGJJPNP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 7-(4-fluorophenyl)-7-<3-(1-hydroxyethyl)-60methoxy-2,4,5-trimethylphenyl>heptanoate 在 manganese(IV) oxide 、 三溴化硼 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 6.5h， 生成 7-(3-acetyl-6-hydroxy-2,4,5-trimethylphenyl)-7-(4-fluorophenyl)heptanoic acid
  参考文献：
  名称：

  Synthesis and thromboxane A2/prostaglandin H2 receptor antagonistic activity of phenol derivatives

  摘要：

  Consideration of possible structural similarities between thromboxane A2 and the hydroquinone form of (R)-(+)-7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoic acid (R-(+)-AA-2414) led to the development of a new series of thromboxane A2/prostaglandin H-2 (TXA2/PGH2) receptor antagonists, namely 7-(4-fluorophenyl)-7-(2-hydroxyphenyl)heptanoic acids (I). These compounds were found to be potent TXA2/PGH2 receptor antagonists. Compounds having either a carbonyl or a hydroxymethyl group at the para-position of the phenolic hydroxy group exhibited most potent activities in this series. Compounds 14, 15, 18, and 26 inhibited the specific binding of [H-3]U-46619 to guinea pig platelet membranes (IC50 = 4.4, 80, 32, and 13 nM, respectively), and also inhibited U-46619-induced human platelet aggregation (IC50 = 310, 69, 79, and 78 nM, respectively). Comparison of the UV spectra of the compounds with a carbonyl group at the para-position of phenolic hydroxy group revealed that the activity tended to increase in accordance with a decrease in the torsional angle between the carbonyl group and the phenol ring. These results suggested that the spacial location of the carbonyl and hydroxymethyl oxygen are important for significant increase in activity and that the carbonyl and hydroxymethyl oxygen at the para-position of the phenolic hydroxy group might interact with one of the TXA2/PGH2 receptor sites.

  DOI：

  10.1021/jm00090a009
• 作为产物：
  描述：

  甲基溴化镁 、 methyl 7-(4-fluorophenyl)-7-(3-formyl-6-methoxy-2,4,5-trimethylphenyl)keptanoate 以 四氢呋喃 为溶剂， 以71%的产率得到methyl 7-(4-fluorophenyl)-7-<3-(1-hydroxyethyl)-60methoxy-2,4,5-trimethylphenyl>heptanoate
  参考文献：
  名称：

  Synthesis and thromboxane A2/prostaglandin H2 receptor antagonistic activity of phenol derivatives

  摘要：

  Consideration of possible structural similarities between thromboxane A2 and the hydroquinone form of (R)-(+)-7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoic acid (R-(+)-AA-2414) led to the development of a new series of thromboxane A2/prostaglandin H-2 (TXA2/PGH2) receptor antagonists, namely 7-(4-fluorophenyl)-7-(2-hydroxyphenyl)heptanoic acids (I). These compounds were found to be potent TXA2/PGH2 receptor antagonists. Compounds having either a carbonyl or a hydroxymethyl group at the para-position of the phenolic hydroxy group exhibited most potent activities in this series. Compounds 14, 15, 18, and 26 inhibited the specific binding of [H-3]U-46619 to guinea pig platelet membranes (IC50 = 4.4, 80, 32, and 13 nM, respectively), and also inhibited U-46619-induced human platelet aggregation (IC50 = 310, 69, 79, and 78 nM, respectively). Comparison of the UV spectra of the compounds with a carbonyl group at the para-position of phenolic hydroxy group revealed that the activity tended to increase in accordance with a decrease in the torsional angle between the carbonyl group and the phenol ring. These results suggested that the spacial location of the carbonyl and hydroxymethyl oxygen are important for significant increase in activity and that the carbonyl and hydroxymethyl oxygen at the para-position of the phenolic hydroxy group might interact with one of the TXA2/PGH2 receptor sites.

  DOI：

  10.1021/jm00090a009

文献信息

• Optically active phenol derivatives and preparation thereof
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：EP0582382A2

  公开（公告）日：1994-02-09

  An optically active tri-substituted methane compound having, as substituents, an aromatic ring group and a phenyl group having hydroxyl group at ortho or para position can be obtained by allowing a phenol compound unsubstituted at the ortho- or/and para-position to react with an optically active secondary carbinol compound having an aromatic ring group at the alpha-position in the presence of tri-substituted phosphine and diazodicarboxylate or diazodicarboxamide. These and other optically active tri-substituted methane compounds are useful as active ingredients for medicines or as intermediate compounds for preparing medicines.

  在三取代膦和重氮二羧酸盐或重氮二甲酰胺的存在下，使在正位或/和对位上未被取代的苯酚化合物与在α位上具有芳香环基的光学活性仲甲醇化合物反应，可得到光学活性三取代甲烷化合物，其取代基为芳香环基和在正位或对位上具有羟基的苯基。这些和其他具有光学活性的三取代甲烷化合物可用作药物的活性成分或制备药物的中间化合物。
• Phenol derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0295037B1

  公开（公告）日：1993-08-18
• US5162571A
  申请人：——

  公开号：US5162571A

  公开（公告）日：1992-11-10
• Synthesis and thromboxane A2/prostaglandin H2 receptor antagonistic activity of phenol derivatives
  作者：Shoji Fukumoto、Mitsuru Shiraishi、Zenichi Terashita、Yasuko Ashida、Yoshiyuki Inada

  DOI：10.1021/jm00090a009

  日期：1992.6

  Consideration of possible structural similarities between thromboxane A2 and the hydroquinone form of (R)-(+)-7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoic acid (R-(+)-AA-2414) led to the development of a new series of thromboxane A2/prostaglandin H-2 (TXA2/PGH2) receptor antagonists, namely 7-(4-fluorophenyl)-7-(2-hydroxyphenyl)heptanoic acids (I). These compounds were found to be potent TXA2/PGH2 receptor antagonists. Compounds having either a carbonyl or a hydroxymethyl group at the para-position of the phenolic hydroxy group exhibited most potent activities in this series. Compounds 14, 15, 18, and 26 inhibited the specific binding of [H-3]U-46619 to guinea pig platelet membranes (IC50 = 4.4, 80, 32, and 13 nM, respectively), and also inhibited U-46619-induced human platelet aggregation (IC50 = 310, 69, 79, and 78 nM, respectively). Comparison of the UV spectra of the compounds with a carbonyl group at the para-position of phenolic hydroxy group revealed that the activity tended to increase in accordance with a decrease in the torsional angle between the carbonyl group and the phenol ring. These results suggested that the spacial location of the carbonyl and hydroxymethyl oxygen are important for significant increase in activity and that the carbonyl and hydroxymethyl oxygen at the para-position of the phenolic hydroxy group might interact with one of the TXA2/PGH2 receptor sites.