<3-methoxy-4-(phenylmethoxy)phenyl>phenylmethane | 96306-54-6

• 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: <3-methoxy-4-(phenylmethoxy)phenyl>phenylmethane
• 英文别名: 4-benzyloxy-3-methoxybenzophenone；Methanone, [3-methoxy-4-(phenylmethoxy)phenyl]phenyl-；(3-methoxy-4-phenylmethoxyphenyl)-phenylmethanone
• CAS: 96306-54-6
• 化学式: C₂₁H₁₈O₃
• 分子量: 318.372
• InChiKey: MJZQTPHOIYJBIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  <3-methoxy-4-(phenylmethoxy)phenyl>phenylmethane 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以81%的产率得到<3-methoxy-4-(phenylmethoxy)phenyl>phenylmethanone hydrazone
  参考文献：
  名称：

  Metabolites of cibenzoline: synthesis of hydroxylated 1,1-diphenyl-2-imidazolylcyclopropanes and 5,5-diphenyl-2H-pyrrolo[1,2-a]imidazolines

  摘要：

  DOI：

  10.1021/jo00213a004
• 作为产物：
  描述：

  4-苄氧基-3-甲氧基苯甲醛 在 环己酮 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 乙醚 、 甲苯 为溶剂， 反应 1.5h， 生成 <3-methoxy-4-(phenylmethoxy)phenyl>phenylmethane
  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

• Agents for the Treatment of Overactive Detrusor. IX. Synthesis and Pharmacological Properties of Metabolites of N-tert-Butyl-4,4-diphenyl-2-cyclopentenylamine(FK584) in Human Urine.
  作者：Kiyoshi TANIGUCHI、Yasuhiro MIYAO、Katsuhiro YAMANO、Takao YAMAMOTO、Takao TERAI、Takahiro KUSUNOKI、Kazunori TSUBAKI、Youichi SHIOKAWA

  DOI：10.1248/cpb.44.1188

  日期：——

  We synthesized the racemates of five presumed metabolites (1b-f) of (S)-(-)-N-tert-butyl-4, 4-diphenyl-2-cyclopentenylamine hydrochloride (FK584, S(-)-1a), a novel agent for the treatment of overactive detrusor syndrome, in order to confirm the structures of the metabolites and also to evaluate thier inhibitory activity against detrusor contraction. (±)-N-tert-Butyl-4-(4-hydroxyphenyl)- and 4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-cyclopenetenyl-amines (1b-e) were synthesized via 5-(4-methoxyphenyl)- and 5-(4-benzyloxy-3-methoxyphenyl)-5-phenyl-2-cyclopenten-1-one (9g, h), respectively. Compounds 1b-f prepared in this study were identical with the metabolites in human urine in gas chromatography-mass specrometry and analytical HPLC. The inhibitory activity of compounds 1b-f against detrusor contraction in vitro induced by electrical field stimulation in guinea-pigs was less potent than that of FK584.

  我们合成了 (S)-(-)-N-叔丁基-4, 4-二苯基-2-环戊烯胺盐酸盐 (FK584, S(-)-1a) 的五种推测代谢物 (1b-f) 的外消旋体，用于治疗逼尿肌过度活跃综合征的新型药物，以确认代谢物的结构并评估其对逼尿肌收缩的抑制活性。 (±)-N-叔丁基-4-(4-羟基苯基)-和4-(4-羟基-3-甲氧基苯基)-4-苯基-2-环戊烯基胺(1b-e)通过5-合成(4-甲氧基苯基)-和5-(4-苄氧基-3-甲氧基苯基)-5-苯基-2-环戊烯-1-酮(9g，h)。本研究中制备的化合物 1b-f 在气相色谱-质谱和分析型 HPLC 中与人尿中的代谢物相同。化合物1b-f对豚鼠体外由电场刺激诱导的逼尿肌收缩的抑制活性不如FK584有效。
• TILLEY, J. W.;CLADER, J. W.;WIRKUS, M.;BLOUNT, J. F., J. ORG. CHEM., 1985, 50, N 13, 2220-2224
  作者：TILLEY, J. W.、CLADER, J. W.、WIRKUS, M.、BLOUNT, J. F.

  DOI：——

  日期：——
• Synthesis of 1-(3,4-Dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and Derivatives as Potent and Long-Acting Peripheral Inhibitors of Catechol-<i>O</i>-methyltransferase
  作者：David A. Learmonth、Maria A. Vieira-Coelho、Jan Benes、Paula C. Alves、Nuno Borges、Ana P. Freitas、Patrício Soares-da-Silva

  DOI：10.1021/jm0109964

  日期：2002.1.1

  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.
• Metabolites of cibenzoline: synthesis of hydroxylated 1,1-diphenyl-2-imidazolylcyclopropanes and 5,5-diphenyl-2H-pyrrolo[1,2-a]imidazolines
  作者：Jefferson W. Tilley、John W. Clader、Maria Wirkus、John F. Blount

  DOI：10.1021/jo00213a004

  日期：1985.6