4-(benzyloxy)-3-methoxy-α-(3-phenylpropyl)benzyl alcohol | 134611-99-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(benzyloxy)-3-methoxy-α-(3-phenylpropyl)benzyl alcohol
• 英文别名: 4-(Benzyloxy)-3-methoxy-alpha-(3-phenylpropyl)benzyl alcohol；1-(3-methoxy-4-phenylmethoxyphenyl)-4-phenylbutan-1-ol
• CAS: 134611-99-7
• 化学式: C₂₄H₂₆O₃
• 分子量: 362.469
• InChiKey: MSMULARSDQLDOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(benzyloxy)-3-methoxy-α-(3-phenylpropyl)benzyl alcohol 在 manganese dioxide 二氯甲烷 、 diethyl ether ethyl acetate 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以There is obtained 4'-(benzyloxy)-3'-methoxy-4-phenylbutyrophenone in the form of colorless crystals of m.p. 81°-82°的产率得到4'-(benzyloxy)-3'-methoxy-4-phenylbutyrophenone
  参考文献：
  名称：

  Catechol derivatives

  摘要：

  本发明揭示了公式##STR1##中Ra、Rb和Rc具有所述意义的邻二酚衍生物，以及在生理条件下可水解的酯和醚衍生物和其药学上可接受的盐，具有有价值的药理学特性。特别地，它们抑制儿茶酚-O-甲基转移酶（COMT）这种可溶性、依赖于镁离子的酶，该酶催化S-腺苷甲硫氨酸的甲基基团转移到邻二酚底物上，从而形成相应的甲基醚。适合被COMT甲基化并因此被去活化的底物，例如外周神经元的儿茶酚胺和外源性给药的具有邻二酚结构的治疗活性物质。公式Ia不仅包括本发明的化合物，还包括已知的化合物：本发明的化合物可以按照已知的方法制备。

  公开号：

  US05633371A1
• 作为产物：
  描述：

  4-苄氧基-3-甲氧基苯甲醛 、 (3-phenylpropyl)magnesium chloride 以 四氢呋喃 、 乙醚 为溶剂， 反应 1.0h， 生成 4-(benzyloxy)-3-methoxy-α-(3-phenylpropyl)benzyl alcohol
  参考文献：
  名称：

  Synthesis of 1-(3,4-Dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and Derivatives as Potent and Long-Acting Peripheral Inhibitors of Catechol-O-methyltransferase

  摘要：

  A homologous series of novel nitro-catechol structures (7a-7e) were synthesized and tested as inhibitors of the enzyme catechol-O-methyltransferase (COMT). Increasing chain length was found to have significant impact on both brain penetration and duration of COMT inhibition in the rat. Of this series, compound 7b (1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone) was found to exhibit the most potent and selective inhibition of peripheral COMT, with an inhibition profile more similar to entacapone 2 than tolcapone 1 (an equipotent peripheral and central inhibitor) but with much improved duration of action (7b, 70% inhibition and 2, 25% inhibition at 9 h after administration). The effects of structural modifications to 7b on COMT inhibitory profile were investigated, and it is concluded that the carbonyl group and preferably unsubstituted aromatic ring are essential features to maintain prolonged peripheral COMT inhibition. The introduction of the alpha-methylene group, the major structural difference between 7b and 1, would appear responsible for the observed enhancement in selectivity of peripheral COMT inhibition of 7b, which has more limited access to the brain than 1.

  DOI：

  10.1021/jm0109964

文献信息

• Catechol derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US05236952A1

  公开（公告）日：1993-08-17

  Catechol derivatives of the formula ##STR1## wherein Ra, Rb and Rc have the significance given herein, the ester and ether derivatives thereof which are hydrolyzable under physiological conditions and the pharmaceutically acceptable salts thereof are described and possess valuable pharmacological properties. In particular, they inhibit the enzyme catechol-O-methyltransferase (COMT), a soluble, magnesium-dependent enzyme which catalyses the transference of the methyl group of S-adensoylmethionine to a catechol substrate, whereby the corresponding methyl ethers are formed. Suitable substrates which can be O-methylated by COMT and which can thus be deactivated are, for example, extraneuornal catecholamines and exogeneously-administered therapeutically active substances having a catechol structure. Formula Ia above embraces not only compounds which form part of the invention, but also known compounds; the compounds which form part of the invention can be prepared according to known methods.

  公式##STR1##中的儿茶酚衍生物，其中Ra、Rb和Rc具有本文中给出的含义，以及在生理条件下可水解的酯和醚衍生物及其药学上可接受的盐已被描述，并具有有价值的药理特性。特别是，它们抑制儿茶酚-O-甲基转移酶(COMT)这种可溶性、依赖镁的酶，该酶催化S-腺苷甲硫氨酸的甲基基团转移到儿茶酚底物上，从而形成相应的甲基醚。可被COMT进行O-甲基化并因此被失活的适当底物包括，例如，外源性儿茶酚胺和具有儿茶酚结构的外源性给药的治疗活性物质。上述公式Ia不仅包括发明的一部分化合物，还包括已知的化合物；构成发明一部分的化合物可以按照已知方法制备。
• 3,5-Disubstituierte Pyrocatecholderivate
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0237929B1

  公开（公告）日：1993-06-02
• US5236952A
  申请人：——

  公开号：US5236952A

  公开（公告）日：1993-08-17
• US5389653A
  申请人：——

  公开号：US5389653A

  公开（公告）日：1995-02-14
• US5476875A
  申请人：——

  公开号：US5476875A

  公开（公告）日：1995-12-19