4-benzyl-7-(3,4-dichlorophenyl)-7-[(4-methoxyphenoxy)methyl]-1,4-oxazepan-3-one | 1372186-67-8

• 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: 4-benzyl-7-(3,4-dichlorophenyl)-7-[(4-methoxyphenoxy)methyl]-1,4-oxazepan-3-one
• 英文别名: (7RS)-4-benzyl-7-(3,4-dichlorophenyl)-7-[(4-methoxyphenoxy)methyl]-1,4-oxazepan-3-one
• CAS: 1372186-67-8
• 化学式: C₂₆H₂₅Cl₂NO₄
• 分子量: 486.395
• InChiKey: ZGDOXPXLYBYQBD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-benzyl-7-(3,4-dichlorophenyl)-7-[(4-methoxyphenoxy)methyl]-1,4-oxazepan-3-one 在 aluminum (III) chloride 、 lithium aluminium tetrahydride 、 ammonium cerium (IV) nitrate 、 1-氯乙基氯甲酸酯 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 水 、 异丙醇 、 乙腈 为溶剂， 反应 5.75h， 生成 tert-butyl (7S)-7-(3,4-dichlorophenyl)-7-(hydroxymethyl)-1,4-oxazepane-4-carboxylate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of a novel series of peripheral-selective noradrenaline reuptake inhibitor

  摘要：

  Centrally acting noradrenaline reuptake inhibitor (NRI) is reportedly effective for patients with stress urinary incontinence (SUI) by increasing urethral closure in the clinical Phase IIa study with esreboxetine. Noradrenaline transporters are expressed in both central and peripheral nervous systems and the contribution of each site to efficacy has not been clarified. This report describes the development of a series of peripheral-selective 7-phenyl-1,4-oxazepane NRIs to investigate the contribution of the peripheral site to increasing urethral resistance in rats. (6S,7R)-1,4-Oxazepane derivative 7 exhibited noradrenaline transporter inhibition with high selectivity against inhibitions of serotonin and dopamine transporters. A replacement of hydroxyl with acetamide group contributed to enhancement of peripheral selectivity by increasing molecular polarity. Compound 12, N-{[(6S,7R)-7-(3,4-dichlorophenyl)-1,4-oxazepan-6-yl]methyl}acetamide 0.5 fumarate, which showed effectively no brain penetration in rats, increased urethral resistance in a dose-dependent manner and exhibited a maximal effect on par with esreboxetine. These results demonstrate that the urethral resistance-increasing effects of NRI in rats are mainly caused by the inhibition of noradrenaline transporters in the peripheral sites. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.017
• 作为产物：
  描述：

  3,4-二氯溴苯 在 aluminum (III) chloride 、 lithium aluminium tetrahydride 、 正丁基锂 、 碘 、 magnesium sulfate 、 magnesium 、 三乙胺 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 正己烷 为溶剂， 反应 28.26h， 生成 4-benzyl-7-(3,4-dichlorophenyl)-7-[(4-methoxyphenoxy)methyl]-1,4-oxazepan-3-one
  参考文献：
  名称：

  HETEROCYCLIC COMPOUNDS

  摘要：

  提供的是一种具有单胺再摄取抑制活性的化合物，其化学式表示为（I），其中环A是一个可选择取代的6元芳香环，环B是环A上的取代基可选择地与环A一起形成一个可选择取代的9或10元芳香融合环，其他符号如规范中定义的那样，或其盐。

  公开号：

  US20120088748A1

文献信息

• HETEROCYCLIC COMPOUNDS
  申请人：Ishichi Yuji

  公开号：US20120088748A1

  公开（公告）日：2012-04-12

  Provided is a compound having a monoamine reuptake inhibitory activity, which is represented by the formula (I) wherein ring A is an optionally substituted 6-membered aromatic ring, ring B is the substituents on ring A are optionally bonded to form, together with ring A, an optionally substituted 9- or 10-membered aromatic fused ring, and other symbols are as defined in the specification, or a salt thereof.

  提供的是一种具有单胺再摄取抑制活性的化合物，其化学式表示为（I），其中环A是一个可选择取代的6元芳香环，环B是环A上的取代基可选择地与环A一起形成一个可选择取代的9或10元芳香融合环，其他符号如规范中定义的那样，或其盐。
• 1,4-OXAZEPANE DERIVATIVES
  申请人：Ishichi Yuji

  公开号：US20130267494A1

  公开（公告）日：2013-10-10

  Provided is a compound having a monoamine reuptake inhibitory activity, which is represented by the formula (I) wherein ring A is an optionally substituted 6-membered aromatic ring, ring B is the substituents on ring A are optionally bonded to form, together with ring A, an optionally substituted 9- or 10-membered aromatic fused ring, and other symbols are as defined in the specification, or a salt thereof.

  提供了一种具有单胺再摄取抑制活性的化合物，其由式（I）表示，其中环A是可选取代的6元芳环，环B是环A上的取代基可选择与环A一起形成可选取代的9或10元芳香融合环，其他符号如规范中定义的那样，或其盐。
• Heterocyclic compounds
  申请人：Ishichi Yuji

  公开号：US08722662B2

  公开（公告）日：2014-05-13

  Provided is a compound having a monoamine reuptake inhibitory activity, which is represented by the formula (I) wherein ring A is an optionally substituted 6-membered aromatic ring, ring B is the substituents on ring A are optionally bonded to form, together with ring A, an optionally substituted 9- or 10-membered aromatic fused ring, and other symbols are as defined in the specification, or a salt thereof.

  提供了一种具有单胺再摄取抑制活性的化合物，其化学式表示为(I)，其中环A是可选取代的6元芳环，环B是环A上的取代基可选择与环A一起形成可选取代的9或10元芳环并融合，其他符号如规范中定义，或其盐。
• US8722662B2
  申请人：——

  公开号：US8722662B2

  公开（公告）日：2014-05-13
• [EN] 1,4-OXAZEPANE DERIVATIVES<br/>[FR] DÉRIVÉS DE 1,4-OXAZÉPANE
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2012046882A1

  公开（公告）日：2012-04-12

  Provided is a compound having a monoamine reuptake inhibitory activity, which is represented by the formula (I) wherein ring A is an optionally substituted 6-membered aromatic ring, ring B is the substituents on ring A are optionally bonded to form, together with ring A, an optionally substituted 9- or 10-membered aromatic fused ring, and other symbols are as defined in the specification, or a salt thereof.