tert-butyl [(1R,2R)-1-(5-bromo-1H-benzimidazol-2-yl)-2-methoxypropyl]carbamate | 1449475-32-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: tert-butyl [(1R,2R)-1-(5-bromo-1H-benzimidazol-2-yl)-2-methoxypropyl]carbamate
• 英文别名: tert-butyl ((1R,2R)-1-(5-bromo-1H-benzo[d]imidazol-2-yl)-2-methoxypropyl)carbamate；tert-butyl N-[(1R,2R)-1-(6-bromo-1H-benzimidazol-2-yl)-2-methoxypropyl]carbamate
• CAS: 1449475-32-4
• 化学式: C₁₆H₂₂BrN₃O₃
• 分子量: 384.273
• InChiKey: QBWWJPHYNREXQF-RNCFNFMXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  76.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl [(1R,2R)-1-(5-bromo-1H-benzimidazol-2-yl)-2-methoxypropyl]carbamate 在 dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) 、 sodium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 21.0h， 生成 4-{2-[(1R,2R)-1-amino-2-methoxypropyl]-1H-benzimidazol-5-yl}-3-fluorobenzonitrile formate
  参考文献：
  名称：

  The discovery and optimization of benzimidazoles as selective NaV1.8 blockers for the treatment of pain

  摘要：

  The voltage gated sodium channel Na(V)1.8 has been postulated to play a key role in the transmission of pain signals. Core hopping from our previously reported phenylimidazole leads has allowed the identification of a novel series of benzimidazole Na(V)1.8 blockers. Subsequent optimization allowed the identification of compound 9, PF-06305591, as a potent, highly selective blocker with an excellent preclinical in vitro ADME and safety profile.

  DOI：

  10.1016/j.bmc.2018.12.002
• 作为产物：
  描述：

  BOC-苏氨酸甲酯 在 N-甲基吗啉 、 溶剂黄146 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 109.0h， 生成 tert-butyl [(1R,2R)-1-(5-bromo-1H-benzimidazol-2-yl)-2-methoxypropyl]carbamate
  参考文献：
  名称：

  The discovery and optimization of benzimidazoles as selective NaV1.8 blockers for the treatment of pain

  摘要：

  The voltage gated sodium channel Na(V)1.8 has been postulated to play a key role in the transmission of pain signals. Core hopping from our previously reported phenylimidazole leads has allowed the identification of a novel series of benzimidazole Na(V)1.8 blockers. Subsequent optimization allowed the identification of compound 9, PF-06305591, as a potent, highly selective blocker with an excellent preclinical in vitro ADME and safety profile.

  DOI：

  10.1016/j.bmc.2018.12.002

文献信息

• [EN] BENZIIMIDAZOLE AND IMIDAZOPYRIDINE DERIVATIVES AS SODIUM CHANNEL MODULATORS<br/>[FR] DÉRIVÉS D'IMIDAZOPYRIDINE ET DE BENZIIMIDAZOLE EN TANT QUE MODULATEURS DU CANAL SODIUM
  申请人：PFIZER

  公开号：WO2013114250A1

  公开（公告）日：2013-08-08

  The invention relates to benzimidazole and imidazopyridine derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to new Nav1.8 modulators of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7. X and Y are as defined in the description. Nav1.8 modulators are potentially useful in the treatment of a wide range of disorders, particularly pain.

  这项发明涉及苯并咪唑和咪唑吡啶衍生物，它们在药物中的应用，含有它们的组合物，它们的制备方法以及用于这些方法的中间体。更具体地，该发明涉及公式(I)的新Nav1.8调节剂或其药用盐，其中R1、R2、R3、R4、R5、R6、R7、X和Y如描述中所定义。Nav1.8调节剂在治疗各种疾病，特别是疼痛方面，具有潜在的用途。
• Chemical Compounds
  申请人：Pfizer Limited

  公开号：US20130274243A1

  公开（公告）日：2013-10-17

  The invention relates to benzimidazole and imidazopyridine derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to new Na v 1.8 modulators of formula (I) or pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , X and Y are as defined in the description. Na v 1.8 modulators are potentially useful in the treatment of a wide range of disorders, particularly pain.

  本发明涉及苯并咪唑和咪唑吡啶衍生物，它们在医学上的使用、含有它们的组合物、制备它们的过程以及用于这种过程的中间体。更具体地，本发明涉及公式（I）或其药学上可接受的盐的新型Nav1.8调节剂，其中R1、R2、R3、R4、R5、R6、R7、X和Y如描述中所定义。Nav1.8调节剂在治疗广泛的疾病，尤其是疼痛方面具有潜在的用途。
• Chemical compounds
  申请人：Pfizer Limited

  公开号：US08927587B2

  公开（公告）日：2015-01-06

  The invention relates to benzimidazole and imidazopyridine derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to new Nav1.8 modulators of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7. X and Y are as defined in the description. Nav1.8 modulators are potentially useful in the treatment of a wide range of disorders, particularly pain.

  本发明涉及苯并咪唑和咪唑吡啶衍生物，其在医学上的应用，含有它们的组合物，其制备过程以及用于这种过程中的中间体。更具体地，本发明涉及公式（I）的新型Nav1.8调节剂或其药学上可接受的盐，其中R1，R2，R3，R4，R5，R6，R7，X和Y如描述中所定义。Nav1.8调节剂在治疗广泛的疾病，特别是疼痛方面具有潜在的用途。
• The discovery and optimization of benzimidazoles as selective NaV1.8 blockers for the treatment of pain
  作者：Alan D. Brown、Sharan K. Bagal、Paul Blackwell、David C. Blakemore、Bruce Brown、Peter J. Bungay、Martin Corless、James Crawforth、David Fengas、David R. Fenwick、Victoria Gray、Mark Kemp、Wolfgang Klute、Laia Malet Sanz、Duncan Miller、Yoshihisa Murata、C. Elizabeth Payne、Sarah Skerratt、Edward B. Stevens、Joseph S. Warmus

  DOI：10.1016/j.bmc.2018.12.002

  日期：2019.1

  The voltage gated sodium channel Na(V)1.8 has been postulated to play a key role in the transmission of pain signals. Core hopping from our previously reported phenylimidazole leads has allowed the identification of a novel series of benzimidazole Na(V)1.8 blockers. Subsequent optimization allowed the identification of compound 9, PF-06305591, as a potent, highly selective blocker with an excellent preclinical in vitro ADME and safety profile.