(3R,4S)-3-(([tert-butyl(dimethyl)silyl]oxy)methyl)-4-phenylpyrrolidine | 300853-88-7

• 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: (3R,4S)-3-(([tert-butyl(dimethyl)silyl]oxy)methyl)-4-phenylpyrrolidine
• 英文别名: (3R,4S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-phenylpyrrolidine；tert-butyl-dimethyl-[[(3R,4S)-4-phenylpyrrolidin-3-yl]methoxy]silane
• CAS: 300853-88-7
• 化学式: C₁₇H₂₉NOSi
• 分子量: 291.509
• InChiKey: WPUCYMNXZNJBOO-HZPDHXFCSA-N

物化性质

• 沸点：
  348.0±25.0 °C(Predicted)
• 密度：
  0.936±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.01
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3R,4S)-3-(([tert-butyl(dimethyl)silyl]oxy)methyl)-4-phenylpyrrolidine 在 palladium on activated charcoal 草酰氯 、 TEA 、 四丁基氟化铵 、 氢气 、 三乙酰氧基硼氢化钠 、 二甲基亚砜 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 2-cyclohexyl-2-{3-[4-hydroxy-4-(3-phenylpropyl)hexahydro-1-pyridinylmethyl]-4-phenyltetrahydro-1H-1-pyrrolyl}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：

  (4S)-4-benzyl-3-[(2E)-3-phenylprop-2-enoyl]-1,3-oxazolidin-2-one 在 palladium dihydroxide lithium aluminium tetrahydride 、 碳酸氢铵 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 (3R,4S)-3-(([tert-butyl(dimethyl)silyl]oxy)methyl)-4-phenylpyrrolidine
  参考文献：
  名称：

  1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 1: discovery of the pyrrolidine scaffold and determination of its stereochemical requirements

  摘要：

  A series of 1,3,4-trisubstituted pyrrolidines was discovered to have the ability to displace [I-125]-MIP-1 alpha from the CCR5 receptor expressed on Chinese hamster ovary (CHO) cell membranes. CCR5 activity was found to be dependent on the regiochemistry and the absolute stereochemistry of the pyrrolidine. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00232-3
• 作为试剂：
  描述：

  2-(羟甲基)四氢呋喃-2-羧酸 、 以 (3R,4S)-3-(([tert-butyl(dimethyl)silyl]oxy)methyl)-4-phenylpyrrolidine 为溶剂， 生成 2-formyl-tetrahydro-2-furoic acid
  参考文献：
  名称：

  Pyrrolidine modulators of CCR5 chemokine receptor activity

  摘要：

  描述了式子I：1中的吡咯烷化合物（其中1、R2、R3、R4、R5、R6a、R6b、R7和R8在此定义）。这些化合物是CCR5趋化因子受体活性的调节剂。这些化合物可用于预防或治疗HIV感染和治疗艾滋病，作为化合物或药物可接受的盐，或作为制药组合物的成分，可选择与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。还描述了治疗艾滋病的方法和预防或治疗HIV感染的方法。

  公开号：

  US20020094989A1

文献信息

• Pyrrolidine modulators of ccr5 chemokine receptor activity
  申请人：——

  公开号：US20040087552A1

  公开（公告）日：2004-05-06

  Pyrrolidine compounds of Formula (I), (wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6a , R 6b , R 7 and R 8 are defined herein) are described. The compounds are modulators of CCR5 chemokine receptor activity. The compounds are useful, for example, in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described. 1

  本发明涉及式(I)的吡咯烷化合物（其中R1、R2、R3、R4、R5、R6a、R6b、R7和R8在此定义），这些化合物是CCR5趋化因子受体活性的调节剂。这些化合物可以作为化合物或药学上可接受的盐，或作为药物组合物中的成分使用，可选地与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用，例如用于预防或治疗HIV感染和治疗艾滋病。本发明还涉及治疗艾滋病的方法以及预防或治疗HIV感染的方法。
• Pyrrolidine modulators of chemokine receptor activity
  申请人：Merck & Co., Inc.

  公开号：US06399619B1

  公开（公告）日：2002-06-04

  The present invention is directed to pyrrolidine compounds of the formula I: (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.

  本发明涉及公式I的吡咯烷化合物：（其中R1，R2，R3，R4，R5，R6和n在此定义），该化合物可用作趋化因子受体活性的调节剂。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。
• Pyrrolidine derivative or salt thereof
  申请人：Hachiya Shunichiro

  公开号：US20090062366A1

  公开（公告）日：2009-03-05

  [Problem] To provide a compound which may be used in treating diseases in which a calcium sensing receptor (CaSR) is concerned, particularly hyperparathyroidism. [Means for Resolution] It was found that novel pyrrolidine derivatives which are characterized by the possession of aminomethyl group substituted with arylalkyl group or the like, or salts thereof, have excellent CaSR agonistic regulatory activity and also have excellent selectivity with CYP2D6 inhibitory activity having a possibility of causing drug interaction. Based on the above, these novel pyrrolidine derivatives are useful as therapeutic agents for treating diseases in which CaSR is concerned (hyperparathyroidism, renal osteodystrophy, hypercalcemia and the like).

  [问题] 提供一种可用于治疗钙敏感受体（CaSR）相关疾病，特别是甲状旁腺功能亢进症的化合物。 [解决方法] 发现了一种新型吡咯烷衍生物，其特征在于具有氨甲基基团，该基团被芳基烷基或类似物取代，或其盐，具有出色的CaSR激动调节活性，并且具有出色的选择性与CYP2D6抑制活性，可能导致药物相互作用。基于以上发现，这些新型吡咯烷衍生物可用作治疗CaSR相关疾病（甲状旁腺功能亢进症，肾性骨营养不良，高钙血症等）的治疗剂。
• WO2006/123725
  申请人：——

  公开号：——

  公开（公告）日：——
• CCR5 antagonists: bicyclic isoxazolidines as conformationally constrained N-1-substituted pyrrolidines
  作者：Christopher L Lynch、Amy L Gentry、Jeffrey J Hale、Sander G Mills、Malcolm MacCoss、Lorraine Malkowitz、Martin S Springer、Sandra L Gould、Julie A DeMartino、Salvatore J Siciliano、Margaret A Cascieri、George Doss、Anthony Carella、Gwen Carver、Karen Holmes、William A Schleif、Renee Danzeisen、Daria Hazuda、Joseph Kessler、Janet Lineberger、Michael Miller、Emilio A Emini

  DOI：10.1016/s0960-894x(01)00835-6

  日期：2002.2

  A series of CCR5 antagonists containing bicyclic isoxazolidines was generated through a nitrone mediated cycloaddition with olefins bearing the preferred pharmacophores previously described. Potent antagonists (3 and 16) were generated with enhanced affinity for the CCR5 receptor while maintaining antiviral activity against HIV. (C) 2002 Elsevier Science Ltd. All rights reserved.