1-(4-(2-(2-fluoroethoxy)ethoxy)-3-methoxybenzyl)-6,7-dimethoxyisoquinoline | 1335093-54-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1-(4-(2-(2-fluoroethoxy)ethoxy)-3-methoxybenzyl)-6,7-dimethoxyisoquinoline
• 英文别名: 1-[[4-[2-(2-Fluoroethoxy)ethoxy]-3-methoxyphenyl]methyl]-6,7-dimethoxyisoquinoline
• CAS: 1335093-54-3
• 化学式: C₂₃H₂₆FNO₅
• 分子量: 415.462
• InChiKey: MBMPWSYMFRBNMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  59
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(4-(2-(2-fluoroethoxy)ethoxy)-3-methoxybenzyl)-6,7-dimethoxyisoquinoline 、 草酸 以 甲醇 、 乙酸乙酯 为溶剂， 反应 1.0h， 生成 1-(4-(2-(2-fluoroethoxy)ethoxy)-3-methoxybenzyl)-6,7-dimethoxyisoquinoline oxalate
  参考文献：
  名称：

  Synthesis and in vitro evaluation of new analogues as inhibitors for phosphodiesterase 10A

  摘要：

  A series of analogues were synthesized by optimizing the structure of papaverine. The in vitro PDE10A binding affinity (IC50) values for these new analogues were measured; for compounds that have IC50 value less than 60 nM for PDE10A, the binding affinities (IC50 value) for PDE3A and PDE3B were tested. Of these analogues, compounds 6a, 6b, 6n, 8b, 8c and 11 displayed relatively higher PDE10A potency with IC50 value in the range of 28-60 nM. The most potent compound 1-(4-(2-(2-fluoroethoxy)ethoxy)-3-methoxybenzyl)-6,7-dimethoxyisoquinoline (8c) has the IC50 value of 28 +/- 1.2 nM for PDE10A, 2200 +/- 437 nM for PDE3A and 2520 +/- 210 nM for PDE3B. Compared to papaverine, compound 8c displayed similar PDE10A potency but improved selectivity to PDE10A versus PDE3A and PDE3B. To identify high potent PDE10A inhibitor, further optimization of the structures of these analogues is necessary. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.072
• 作为产物：
  描述：

  α-(aminomethyl)-3,4-dimethoxybenzyl alcohol hydrochloride 在 盐酸 、 sodium carbonate 、 potassium carbonate 、 三氯氧磷 作用下， 以 乙醚 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 4.58h， 生成 1-(4-(2-(2-fluoroethoxy)ethoxy)-3-methoxybenzyl)-6,7-dimethoxyisoquinoline
  参考文献：
  名称：

  Synthesis and in vitro evaluation of new analogues as inhibitors for phosphodiesterase 10A

  摘要：

  A series of analogues were synthesized by optimizing the structure of papaverine. The in vitro PDE10A binding affinity (IC50) values for these new analogues were measured; for compounds that have IC50 value less than 60 nM for PDE10A, the binding affinities (IC50 value) for PDE3A and PDE3B were tested. Of these analogues, compounds 6a, 6b, 6n, 8b, 8c and 11 displayed relatively higher PDE10A potency with IC50 value in the range of 28-60 nM. The most potent compound 1-(4-(2-(2-fluoroethoxy)ethoxy)-3-methoxybenzyl)-6,7-dimethoxyisoquinoline (8c) has the IC50 value of 28 +/- 1.2 nM for PDE10A, 2200 +/- 437 nM for PDE3A and 2520 +/- 210 nM for PDE3B. Compared to papaverine, compound 8c displayed similar PDE10A potency but improved selectivity to PDE10A versus PDE3A and PDE3B. To identify high potent PDE10A inhibitor, further optimization of the structures of these analogues is necessary. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.072

文献信息

• Methods, Compositions and Kits for the Evaluation and Preservation of Sperm
  申请人：Richard François

  公开号：US20120225417A1

  公开（公告）日：2012-09-06

  The invention concerns methods and kits for evaluating the semen quality. The invention also concerns compounds and compositions for preserving a sperm sample, especially during cryopreservation. The invention is based on a correlation between sperm phosphodiesterase (PDE) activity and sperm fertility and on the use of selective phosphodiesterase inhibitors, more particularly PDE10 inhibitors.
• Synthesis and in vitro evaluation of new analogues as inhibitors for phosphodiesterase 10A
  作者：Zhanbin Zhang、Xiaoxia Lu、Jinbin Xu、Justin Rothfuss、Robert H. Mach、Zhude Tu

  DOI：10.1016/j.ejmech.2011.05.072

  日期：2011.9

  A series of analogues were synthesized by optimizing the structure of papaverine. The in vitro PDE10A binding affinity (IC50) values for these new analogues were measured; for compounds that have IC50 value less than 60 nM for PDE10A, the binding affinities (IC50 value) for PDE3A and PDE3B were tested. Of these analogues, compounds 6a, 6b, 6n, 8b, 8c and 11 displayed relatively higher PDE10A potency with IC50 value in the range of 28-60 nM. The most potent compound 1-(4-(2-(2-fluoroethoxy)ethoxy)-3-methoxybenzyl)-6,7-dimethoxyisoquinoline (8c) has the IC50 value of 28 +/- 1.2 nM for PDE10A, 2200 +/- 437 nM for PDE3A and 2520 +/- 210 nM for PDE3B. Compared to papaverine, compound 8c displayed similar PDE10A potency but improved selectivity to PDE10A versus PDE3A and PDE3B. To identify high potent PDE10A inhibitor, further optimization of the structures of these analogues is necessary. (C) 2011 Elsevier Masson SAS. All rights reserved.