[(S)-3-(4-fluorobenzyl)-piperidin-1-yl]-[(3R,4S)-4-((R)-1-phenyl-ethylamino)-tetrahydrothiophen-3-yl]-methanone | 388114-49-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: [(S)-3-(4-fluorobenzyl)-piperidin-1-yl]-[(3R,4S)-4-((R)-1-phenyl-ethylamino)-tetrahydrothiophen-3-yl]-methanone
• 英文别名: [(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]-[(3R,4S)-4-[[(1R)-1-phenylethyl]amino]thiolan-3-yl]methanone
• CAS: 388114-49-6
• 化学式: C₂₅H₃₁FN₂OS
• 分子量: 426.598
• InChiKey: AYSIHKVWHNEKKW-BHLLPTRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(S)-3-(4-fluorobenzyl)-piperidin-1-yl]-[(3R,4S)-4-((R)-1-phenyl-ethylamino)-tetrahydrothiophen-3-yl]-methanone 在 palladium dihydroxide Oxone 、 硼烷 、 氢气 、 丙酮 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 为溶剂， 20.0 ℃ 、413.7 kPa 条件下， 生成 (3S,4S)-4-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-1,1-dioxo-tetrahydro-thiophen-3-ylamine
  参考文献：
  名称：

  CC chemokine receptor-3 (CCR3) antagonists: Improving the selectivity of DPC168 by reducing central ring lipophilicity

  摘要：

  DPC168, a benzylpiperidine-substituted aryl urea CCR3 antagonist evaluated in clinical trials, was a relatively potent inhibitor of the 2136 isoform of cytochrome P-450 (CYP2D6). Replacement of the cyclohexyl central ring with saturated heterocycles provided potent CCR3 antagonists with improved selectivity against CYP2D6. The favorable preclinical profile of DPC168 was maintained in an acetylpiperidine derivative, BMS-570520. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.065
• 作为产物：
  描述：

  4-乙氧羰基硫杂环戊-3-酮 在 三乙基硅烷 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 对甲苯磺酸 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 苯 为溶剂， 生成 [(S)-3-(4-fluorobenzyl)-piperidin-1-yl]-[(3R,4S)-4-((R)-1-phenyl-ethylamino)-tetrahydrothiophen-3-yl]-methanone
  参考文献：
  名称：

  CC chemokine receptor-3 (CCR3) antagonists: Improving the selectivity of DPC168 by reducing central ring lipophilicity

  摘要：

  DPC168, a benzylpiperidine-substituted aryl urea CCR3 antagonist evaluated in clinical trials, was a relatively potent inhibitor of the 2136 isoform of cytochrome P-450 (CYP2D6). Replacement of the cyclohexyl central ring with saturated heterocycles provided potent CCR3 antagonists with improved selectivity against CYP2D6. The favorable preclinical profile of DPC168 was maintained in an acetylpiperidine derivative, BMS-570520. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.065

文献信息

• N-ureidoheterocycloalkyl-piperidines as modulators of chemokine receptor activity
  申请人：——

  公开号：US20030032654A1

  公开（公告）日：2003-02-13

  The present application describes modulators of CCR3 of formula (I): 1 or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.

  本申请描述了CCR3的调节剂，其化学公式为(I)： 1 或其药用可接受的盐形式，用于预防哮喘和其他过敏性疾患。
• US6627629B2
  申请人：——

  公开号：US6627629B2

  公开（公告）日：2003-09-30
• US6949546B2
  申请人：——

  公开号：US6949546B2

  公开（公告）日：2005-09-27
• CC chemokine receptor-3 (CCR3) antagonists: Improving the selectivity of DPC168 by reducing central ring lipophilicity
  作者：James R. Pruitt、Douglas G. Batt、Dean A. Wacker、Lori L. Bostrom、Shon K. Booker、Erin McLaughlin、Gregory C. Houghton、Jeffrey G. Varnes、David D. Christ、Maryanne Covington、Anuk M. Das、Paul Davies、Danielle Graden、Ilona Kariv、Yevgeniya Orlovsky、Nicole C. Stowell、Krishna G. Vaddi、Eric A. Wadman、Patricia K. Welch、Swamy Yeleswaram、Kimberly A. Solomon、Robert C. Newton、Carl P. Decicco、Percy H. Carter、Soo S. Ko

  DOI：10.1016/j.bmcl.2007.03.065

  日期：2007.6

  DPC168, a benzylpiperidine-substituted aryl urea CCR3 antagonist evaluated in clinical trials, was a relatively potent inhibitor of the 2136 isoform of cytochrome P-450 (CYP2D6). Replacement of the cyclohexyl central ring with saturated heterocycles provided potent CCR3 antagonists with improved selectivity against CYP2D6. The favorable preclinical profile of DPC168 was maintained in an acetylpiperidine derivative, BMS-570520. (C) 2007 Elsevier Ltd. All rights reserved.