{1-[6,6-bis-(4-fluoro-phenyl)-hexanoyl]-pyrrolidin-3-ylmethyl}-carbamic acid tert-butyl ester | 802983-59-1

• 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: {1-[6,6-bis-(4-fluoro-phenyl)-hexanoyl]-pyrrolidin-3-ylmethyl}-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[[1-[6,6-bis(4-fluorophenyl)hexanoyl]pyrrolidin-3-yl]methyl]carbamate
• CAS: 802983-59-1
• 化学式: C₂₈H₃₆F₂N₂O₃
• 分子量: 486.602
• InChiKey: UBYHUOUGRPPZIZ-UHFFFAOYSA-N

物化性质

• 沸点：
  627.9±55.0 °C(Predicted)
• 密度：
  1.142±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  35
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  {1-[6,6-bis-(4-fluoro-phenyl)-hexanoyl]-pyrrolidin-3-ylmethyl}-carbamic acid tert-butyl ester 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-{1-[6,6-bis-(4-fluoro-phenyl)-hexanoyl]-pyrrolidin-3-ylmethyl}-3,5-di-tert-butyl-4-methoxy-benzamide
  参考文献：
  名称：

  Structure–activity relationships of trimethoxybenzyl piperazine N-type calcium channel inhibitors

  摘要：

  We previously reported the small organic N-type calcium channel blocker NP078585 that while efficacious in animal models for pain, exhibited modest L-type calcium channel selectivity and substantial off-target inhibition against the hERG potassium channel. Structure-activity studies to optimize NP078585 preclinical properties resulted in compound 16, which maintained high potency for N-type calcium channel blockade, and possessed excellent selectivity over the hERG (similar to 120-fold) and L-type (similar to 3600-fold) channels. Compound 16 shows significant anti-hyperalgesic activity in the spinal nerve ligation model of neuropathic pain and is also efficacious in the rat formalin model of inflammatory pain. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.054
• 作为产物：
  描述：

  (1-苄基吡咯烷-3-基甲基)氨基甲酸叔丁酯 在 4-二甲氨基吡啶 、 5%-palladium/activated carbon 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 {1-[6,6-bis-(4-fluoro-phenyl)-hexanoyl]-pyrrolidin-3-ylmethyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Structure–activity relationships of trimethoxybenzyl piperazine N-type calcium channel inhibitors

  摘要：

  We previously reported the small organic N-type calcium channel blocker NP078585 that while efficacious in animal models for pain, exhibited modest L-type calcium channel selectivity and substantial off-target inhibition against the hERG potassium channel. Structure-activity studies to optimize NP078585 preclinical properties resulted in compound 16, which maintained high potency for N-type calcium channel blockade, and possessed excellent selectivity over the hERG (similar to 120-fold) and L-type (similar to 3600-fold) channels. Compound 16 shows significant anti-hyperalgesic activity in the spinal nerve ligation model of neuropathic pain and is also efficacious in the rat formalin model of inflammatory pain. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.054

文献信息

• [EN] 3-AMINOMETHYL-PYRROLIDINES AS N-TYPE CALCIUM CHANNEL BLOCKERS<br/>[FR] 3-AMINOMETHYLE-PYRROLIDINES COMME INHIBITEURS DE CANAUX CALCIQUES DE TYPE N
  申请人：NEUROMED TECH INC

  公开号：WO2004105750A1

  公开（公告）日：2004-12-09

  The invention relates to compounds that are derivatives of 3-aminomethyl-pyrrolidine of the formulas: wherein: Y is (X2)1A or (X1)mCR4A2; W is CR4 or N; R1-R4 are noninterfering substituents; n is 0-7; 1 and m are independently 0 or 1; X1-X2 are linkers; each A is independently a 5-7 membered optionally substitued aromatic or aliphatic ring optionally containing one or more heteroatoms selected from O, N and S. They generally contain at least one benzhydril moiety and are useful in treating conditions which benefit from blocking calcium ion channels.

  该发明涉及一种衍生自3-氨甲基吡咯烷的化合物，其化学式如下：其中：Y为(X2)1A或(X1)mCR4A2；W为CR4或N；R1-R4为非干扰基；n为0-7；1和m独立取0或1；X1-X2为连接基；每个A独立为一个5-7成员环，可选择地含有一个或多个来自O、N和S的杂原子的芳香或脂肪环。它们通常至少含有一个苯甲酰基团，并可用于治疗受益于阻断钙离子通道的疾病。
• N-type calcium channel blockers
  申请人：Pajouhesh Hassan

  公开号：US20050014748A1

  公开（公告）日：2005-01-20

  Compounds that are derivatives of 3-aminomethyl-pyrrolidine generally containing at least one benzhydril moiety are useful in treating conditions which benefit from blocking calcium ion channels.

  通常包含至少一个苯基甲基基团的3-氨基甲基吡咯烷衍生物化合物，对于治疗需要阻断钙离子通道的疾病具有益处。
• US7244758B2
  申请人：——

  公开号：US7244758B2

  公开（公告）日：2007-07-17
• Structure–activity relationships of trimethoxybenzyl piperazine N-type calcium channel inhibitors
  作者：Hassan Pajouhesh、Zhong-Ping Feng、Lingyun Zhang、Hossein Pajouhesh、Xinpo Jiang、Adam Hendricson、Haiheng Dong、Elizabeth Tringham、Yanbing Ding、Todd W. Vanderah、Frank Porreca、Francesco Belardetti、Gerald W. Zamponi、Lester A. Mitscher、Terrance P. Snutch

  DOI：10.1016/j.bmcl.2012.04.054

  日期：2012.6

  We previously reported the small organic N-type calcium channel blocker NP078585 that while efficacious in animal models for pain, exhibited modest L-type calcium channel selectivity and substantial off-target inhibition against the hERG potassium channel. Structure-activity studies to optimize NP078585 preclinical properties resulted in compound 16, which maintained high potency for N-type calcium channel blockade, and possessed excellent selectivity over the hERG (similar to 120-fold) and L-type (similar to 3600-fold) channels. Compound 16 shows significant anti-hyperalgesic activity in the spinal nerve ligation model of neuropathic pain and is also efficacious in the rat formalin model of inflammatory pain. (C) 2012 Elsevier Ltd. All rights reserved.