(S)-3-[(R)-(2,6-dichloro-3,5-difluorophenoxy)phenyl-methyl]pyrrolidine-1-carboxylic acid t-butyl ester | 1204677-44-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (S)-3-[(R)-(2,6-dichloro-3,5-difluorophenoxy)phenyl-methyl]pyrrolidine-1-carboxylic acid t-butyl ester
• 英文别名: tert-butyl (3S)-3-[(R)-(2,6-dichloro-3,5-difluorophenoxy)-phenylmethyl]pyrrolidine-1-carboxylate
• CAS: 1204677-44-0
• 化学式: C₂₂H₂₃Cl₂F₂NO₃
• 分子量: 458.332
• InChiKey: DDTBLQWWGQYGMM-LIRRHRJNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-3-[(R)-(2,6-dichloro-3,5-difluorophenoxy)phenyl-methyl]pyrrolidine-1-carboxylic acid t-butyl ester 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 18.0h， 生成 (S)-3-[(R)-(2,6-dichloro-3,5-difluorophenoxy)phenylmethyl]pyrrolidine
  参考文献：
  名称：

  A novel class of 3-(phenoxy-phenyl-methyl)-pyrrolidines as potent and balanced norepinephrine and serotonin reuptake inhibitors: Synthesis and structure–activity relationships

  摘要：

  A series of 3-(phenoxy-phenyl-methyl)-pyrrolidine analogues were discovered to be potent and balanced norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors. Several of these compounds were identified to have suitable in vitro pharmacokinetic properties for an orally dosed and CNS-targeted drug. Compound 39b, in particular, was identified as a potent NET and SERT reuptake inhibitor (NSRI) with minimal off-target activity and demonstrated robust efficacy in the spinal nerve ligation model of pain behavior. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.061
• 作为产物：
  描述：

  (S)-1-Boc-3-羟甲基吡咯烷 在 sodium hypochlorite 、 2,2,6,6-四甲基哌啶氧化物 、 偶氮二甲酸二异丙酯 、 碳酸氢钠 、 三苯基膦 、 potassium bromide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 0.42h， 生成 (S)-3-[(R)-(2,6-dichloro-3,5-difluorophenoxy)phenyl-methyl]pyrrolidine-1-carboxylic acid t-butyl ester
  参考文献：
  名称：

  A novel class of 3-(phenoxy-phenyl-methyl)-pyrrolidines as potent and balanced norepinephrine and serotonin reuptake inhibitors: Synthesis and structure–activity relationships

  摘要：

  A series of 3-(phenoxy-phenyl-methyl)-pyrrolidine analogues were discovered to be potent and balanced norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors. Several of these compounds were identified to have suitable in vitro pharmacokinetic properties for an orally dosed and CNS-targeted drug. Compound 39b, in particular, was identified as a potent NET and SERT reuptake inhibitor (NSRI) with minimal off-target activity and demonstrated robust efficacy in the spinal nerve ligation model of pain behavior. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.061

文献信息

• 3-(PHENOXYPHENYLMETHYL)PYRROLIDINE COMPOUNDS
  申请人：Stangeland Eric

  公开号：US20100022616A1

  公开（公告）日：2010-01-28

  In one aspect, the invention relates to compounds of formula I: where a and R 1-6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds of formula I are serotonin and norepinephrine reuptake inhibitors. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

  在一个方面，该发明涉及到以下式I的化合物：其中a和R1-6如规范中所定义，或其药用可接受盐。式I的化合物是血清素和去甲肾上腺素再摄取抑制剂。在另一个方面，该发明涉及到包含这些化合物的药物组合物；使用这些化合物的方法；以及制备这些化合物的工艺和中间体。
• US7888386B2
  申请人：——

  公开号：US7888386B2

  公开（公告）日：2011-02-15
• US8242164B2
  申请人：——

  公开号：US8242164B2

  公开（公告）日：2012-08-14
• US8933249B2
  申请人：——

  公开号：US8933249B2

  公开（公告）日：2015-01-13
• A novel class of 3-(phenoxy-phenyl-methyl)-pyrrolidines as potent and balanced norepinephrine and serotonin reuptake inhibitors: Synthesis and structure–activity relationships
  作者：Lori Jean Van Orden、Priscilla M. Van Dyke、D. Roland Saito、Timothy J. Church、Ray Chang、Jacqueline A.M. Smith、William J. Martin、Sarah Jaw-Tsai、Eric L. Stangeland

  DOI：10.1016/j.bmcl.2012.12.061

  日期：2013.3

  A series of 3-(phenoxy-phenyl-methyl)-pyrrolidine analogues were discovered to be potent and balanced norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors. Several of these compounds were identified to have suitable in vitro pharmacokinetic properties for an orally dosed and CNS-targeted drug. Compound 39b, in particular, was identified as a potent NET and SERT reuptake inhibitor (NSRI) with minimal off-target activity and demonstrated robust efficacy in the spinal nerve ligation model of pain behavior. (c) 2012 Elsevier Ltd. All rights reserved.