4-(3-苯基丙基)哌啶-4-醇 | 177172-37-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 4-(3-苯基丙基)哌啶-4-醇
• 英文名称: 4-hydroxy-4-(3-phenylpropyl)-piperidine
• 英文别名: 4-hydroxy-4-(3-phenylprop-1-yl)piperidine；4-hydroxy-4-(3-phenylpropyl)piperidine；4-(3-Phenylpropyl)piperidin-4-ol
• CAS: 177172-37-1
• 化学式: C₁₄H₂₁NO
• 分子量: 219.327
• InChiKey: MRKWQCUGCSVVFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(3-苯基丙基)哌啶-4-醇 在 palladium on activated charcoal 氢气 、 三乙酰氧基硼氢化钠 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 (S)-2-cyclohexyl-2-((3S,4S)-3-((4-hydroxy-4-(3-phenylpropyl)piperidin-1-yl)methyl)-4-phenylpyrrolidin-1-yl)acetic acid
  参考文献：
  名称：

  1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 4: Synthesis of N-1 acidic functionality affording analogues with enhanced antiviral activity against HIV

  摘要：

  A series of alpha-(pyrrolidin-1-yl)acetic acids is presented as selective and potent antivirals against HIV. Several of the pyrrolidine zwitterions demonstrated reasonable in vitro properties, enhanced antiviral activities and improved pharmacokinetic profiles over pyrrolidine 1. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00606-6
• 作为产物：
  描述：

  1-苄基-4-羟基-4-(3-苯基丙基)哌啶 在 氢氧化钯 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 4-(3-苯基丙基)哌啶-4-醇
  参考文献：
  名称：

  3-thienyl and 3-furanyl pyrrolidine modulators of chemokine receptor activity

  摘要：

  本发明涉及公式I的吡咯烷化合物（其中R1，R2，R3，R4c，R4d和R4f在此定义），其作为趋化因子受体活性调节剂具有用途。特别地，这些化合物是趋化因子受体CCR-3和/或CCR-5的调节剂。

  公开号：

  US06303593B1

文献信息

• Pyrrolidine modulators of chemokine receptor activity
  申请人：Merck & Co., Inc.

  公开号：US06265434B1

  公开（公告）日：2001-07-24

  The present invention is directed to pyrrolidine compounds of the formula 1: (wherein R1, R2, R3, R4, R5, R6 and n are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.

  本发明涉及式1的吡咯烷化合物：（其中R1、R2、R3、R4、R5、R6和n在此处定义），这些化合物可用作趋化因子受体活性的调节剂。具体来说，这些化合物可用作趋化因子受体CCR-5和/或CCR-3的调节剂。
• 3-thienyl and 3-furanyl pyrrolidine modulators of chemokine receptor activity
  申请人：Merck & Co., Inc.

  公开号：US06303593B1

  公开（公告）日：2001-10-16

  The present invention is directed to pyrrolidine compounds of the formula I: (wherein R1, R2, R3, R4c, R4d, and R4f are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-3 and/or CCR-5.

  本发明涉及式I的吡咯烷化合物（其中R1、R2、R3、R4c、R4d和R4f在此处定义），这些化合物可用作趋化因子受体活性的调节剂。具体而言，这些化合物可用作趋化因子受体CCR-3和/或CCR-5的调节剂。
• (1S,2S)-1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol: A Potent New Neuroprotectant Which Blocks N-Methyl-D-Aspartate Responses
  作者：B. L. Chenard、J. Bordner、T. W. Butler、L. K. Chambers、M. A. Collins、D. L. De Costa、M. F. Ducat、M. L. Dumont、C. B. Fox

  DOI：10.1021/jm00016a017

  日期：1995.8

  (1S,2S)-1-(4-Hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (20, CP-101,606) has been identified as a potent and selective N-methyl-D-aspartate NMDA) antagonist through a structure activity relation (SAR) program based on ifenprodil, a known antihypertensive agent with NMDA antagonist activity. Sites on the threo-ifenprodil skeleton explored in this report include the pendent methyl group (H, methyl, and ethyl nearly equipotent; propyl much weaker), the spacer group connecting the C-4 phenyl group to the piperidine ring (an alternating potency pattern with 0 and 2 carbon atoms yielding the greatest potency), and simple phenyl substitution (little effect). While potent NMDA antagonists were obtained with a two atom spacer, this arrangement also increased al adrenergic affinity. Introduction of a hydroxyl group into the C-4 position on the piperidine ring resulted in substantial reduction in alpha(1) adrenergic affinity. The combination of these observations was instrumental in the discovery of 20. This compound potently protects cultured hippocampal neurons from glutamate toxicity (IC50 = 10 nM) while possessing little of the undesired al adrenergic affinity (IC50 similar to 20 mu M) of ifenprodil. Furthermore, 20 appears to lack the psychomotor stimulant effects of nonselective competitive and channel-blocking NMDA antagonists. Thus, 20 shows great promise as a neuroprotective agent and may lack the side effects of compounds currently in clinical trials.

  (1S,2S)-1-(4-羟基苯基)-2-(4-羟基-4-苯基哌啶基)-1-丙醇(20, CP-101,606)通过基于已知抗高血压药物依非拉嗪的结构活性关系(SAR)研究被鉴定为一种高效且选择性的N-甲基-D-天冬氨酸(NMDA)拮抗剂，依非拉嗪具有NMDA拮抗活性。本报告中探索的 thro 如果én prodil框架上的位点包括悬挂的甲基基团（氢、甲基和乙基几乎等效；丙基弱得多）、连接C-4苯基和哌啶环的间隔基团（0和2个碳原子的交替模式产生最高活性），以及简单的苯基取代（影响较小）。虽然通过两原子间隔获得了强效的NMDA拮抗剂，但这种结构也增加了α肾上腺素亲和力。在哌啶环的C-4位置引入羟基导致α_(1)肾上腺素亲和力显著降低。将这些观察结果结合起来，促成了化合物20的发现。该化合物对培养的海马神经元具有强大的谷氨酸毒性保护作用（IC50 = 10 nM），同时几乎不含依非拉嗪所具有的不良α肾上腺素亲和力（IC50约为20 μM）。此外，20似乎缺乏非选择性竞争性和通道阻断型NMDA拮抗剂的精神运动兴奋作用。因此，20作为神经保护剂显示出了巨大的潜力，并且可能不具备目前在临床试验中化合物的副作用。
• [EN] CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEURS DE CGRP
  申请人：MERCK SHARP & DOHME

  公开号：WO2010107605A1

  公开（公告）日：2010-09-23

  Compounds of Formula (I) (wherein variables A1, A2, A3, ring-B, m, n, J, E1, E2, E3, R5, RPG and Y are as described herein), which are useful as antagonists of CGRP receptors, and useful in the treatment or prevention of diseases in which CGRP receptors are involved, such as headache, and in particular migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising the compounds of formula (I) and the use of these compounds and compositions in the prevention or treatment of diseases in which CGRP receptors are involved.

  公式（I）的化合物（其中变量A1、A2、A3、环B、m、n、J、E1、E2、E3、R5、RPG和Y如本文所述），这些化合物可用作CGRP受体的拮抗剂，并可用于治疗或预防涉及CGRP受体的疾病，如头痛，特别是偏头痛和群集性头痛。该发明还涉及包含公式（I）化合物的制药组合物以及在涉及CGRP受体的疾病的预防或治疗中使用这些化合物和组合物的用途。
• [EN] PYRROLIDINE MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY<br/>[FR] MODULATEURS DE PYRROLIDINE DE L'ACTIVITE DU RECEPTEUR DES CHIMIOKINES
  申请人：MERCK & CO INC

  公开号：WO2000059503A1

  公开（公告）日：2000-10-12

  The present invention is directed to pyrrolidine compounds of formula (I) (wherein R?1, R2, R3, R4, R5, R6¿ and n are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.

  本发明涉及式(I)的吡咯烷化合物（其中R1，R2，R3，R4，R5，R6和n的定义如下），它们可用作趋化因子受体活性调节剂。特别地，这些化合物可用作趋化因子受体CCR-5和/或CCR-3的调节剂。