(2S,3R)-1-tert-butoxycarbonyl-3-hydroxy-3-(2-methylene-3-phenoxypropyl)-2-phenylpiperidine | 200956-05-4

• 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: (2S,3R)-1-tert-butoxycarbonyl-3-hydroxy-3-(2-methylene-3-phenoxypropyl)-2-phenylpiperidine
• 英文别名: tert-butyl (2S,3R)-3-hydroxy-3-[2-(phenoxymethyl)prop-2-enyl]-2-phenylpiperidine-1-carboxylate
• CAS: 200956-05-4
• 化学式: C₂₆H₃₃NO₄
• 分子量: 423.552
• InChiKey: MMROWAJCRZYURN-JYFHCDHNSA-N

物化性质

• 沸点：
  547.958±50.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.120±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3R)-1-tert-butoxycarbonyl-3-hydroxy-3-(2-methylene-3-phenoxypropyl)-2-phenylpiperidine 在 正丁基锂 、 臭氧 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 16.0h， 生成 (5R,6S)-3-Oxo-6-phenyl-1-oxa-7-aza-spiro[4.5]decane-7-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Spirocyclic NK1 antagonists II: [4.5]-spiroethers

  摘要：

  A series of novel spiroether-based neurokinin-1 (NK1) antagonists is described. The effect of modifications to the spiroether ring and aromatic substituents are discussed, leading to the identification of compounds with high affinity and excellent CNS penetration. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00509-7
• 作为产物：
  描述：

  cis-(3S)-hydroxy-(2S)-phenylpiperidine 在 光气 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (2S,3R)-1-tert-butoxycarbonyl-3-hydroxy-3-(2-methylene-3-phenoxypropyl)-2-phenylpiperidine
  参考文献：
  名称：

  Spirocyclic NK1 antagonists II: [4.5]-spiroethers

  摘要：

  A series of novel spiroether-based neurokinin-1 (NK1) antagonists is described. The effect of modifications to the spiroether ring and aromatic substituents are discussed, leading to the identification of compounds with high affinity and excellent CNS penetration. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00509-7

文献信息

• Spiro-piperidine derivatives and their use as tachykinin antagonists
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US06060469A1

  公开（公告）日：2000-05-09

  The present invention relates to compounds of formula (I), ##STR1## wherein R.sup.1 represents halogen, hydroxy, C.sub.1-6 alkyl group optionally substituted by one or three fluorine atoms, C.sub.1-6 alkoxy group optionally substituted by one to three fluorine atoms, or C.sub.1-6 alkylthio optionally substituted by one to three fluorine atoms; R.sup.2 represents hydrogen, halogen, C.sub.1-6 alkyl or C.sub.1-6 alkoxy; or when R.sup.2 is adjacent to R.sup.1, they may be joined together such that there is formed a 5- or 6-membered saturated or unsaturated ring containing one or two oxygen atoms; R.sup.3 represents an optionally substituted 5- or 6-membered aromatic heterocyclic group containing 1, 2, 3 or 4 heteroatoms, selected from nitrogen, oxygen and sulphur; m is 0-3 and n is 0-3, with the proviso that the sum total of m+n is 2 or 3; p is zero or 1; q is 1 or 2; and when m is 1 and n is 1 or 2, the broken line represents an optional double bond; R.sup.4, R.sup.5, R.sup.6, R.sup.9 and R.sup.10 are a variety of substituents defined in the specification; or a pharmaceutically acceptable salt thereof. The compounds are of particular use in the treatment or prevention of pain, inflammation, emesis and postherpetic neuralgia.

  本发明涉及式(I)的化合物，其中R.sup.1代表卤素，羟基，C.sub.1-6烷基（可选择性地被1或3个氟原子取代），C.sub.1-6烷氧基（可选择性地被1至3个氟原子取代），或C.sub.1-6烷硫基（可选择性地被1至3个氟原子取代）; R.sup.2代表氢，卤素，C.sub.1-6烷基或C.sub.1-6烷氧基; 或当R.sup.2邻接R.sup.1时，它们可以结合在一起形成一个含有一个或两个氧原子的5-或6-成员饱和或不饱和环; R.sup.3代表一个可选择性取代的5-或6-成员芳香杂环基，该杂环基含有1、2、3或4个杂原子，选择自氮、氧和硫; m为0-3，n为0-3，但满足m + n的总和为2或3; p为零或1; q为1或2; 当m为1且n为1或2时，断裂线表示可选择性的双键; R.sup.4、R.sup.5、R.sup.6、R.sup.9和R.sup.10是规范中定义的各种取代基; 或其药学上可接受的盐。该化合物特别适用于治疗或预防疼痛、炎症、呕吐和带状疱疹后神经痛。
• Use of NK-1 receptor antagonists for treating cognitive disorders
  申请人：Merck Sharp & Dohme Limited

  公开号：US06271230B1

  公开（公告）日：2001-08-07

  The present invention provides methods for the treatment or prevention of cognitive disorders which comprises oral administration of an orally active, long acting, CNS-penetrant NK-1 receptor antagonist and pharmaceutical compositions comprising such a NK-1 receptor antagonist.

  本发明提供了治疗或预防认知障碍的方法，其中包括口服具有口服活性、长效、能穿透中枢神经系统的NK-1受体拮抗剂，并且还提供了包含这种NK-1受体拮抗剂的制药组合物。
• Use of NK-1 receptor antagonists for treating stress disorders
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US06087348A1

  公开（公告）日：2000-07-11

  The present invention provides the use of an orally active, long acting, CNS-penetrant NK-1 receptor antagonist for the manufacture of a medicament adapted for oral administration for the treatment or prevention of stress disorders without concomitant therapy with other anti-stress agents, methods of treatment using such a NK-1 receptor antagonist and pharmaceutical compositions comprising it.

  本发明提供了使用一种口服、长效、能够穿透中枢神经系统的NK-1受体拮抗剂用于制备适合口服的药物，用于治疗或预防压力障碍，无需同时使用其他抗压药物的方法，以及使用这种NK-1受体拮抗剂的治疗方法和包含它的制药组合物。
• Spiro-azacyclic derivatives, their preparation and their use as
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US06046195A1

  公开（公告）日：2000-04-04

  The present invention relates to certain spiro-azacyclic derivatives which are tachykinin antagonists and are useful, for example, in the treatment or prevention of pain, inflammation, migraine, emesis and postherpetic neuralgia.

  本发明涉及某些螺环氮杂环衍生物，其是速激肽拮抗剂，并且可用于治疗或预防疼痛、炎症、偏头痛、恶心和带状疱疹后神经痛等症状。
• Spiro-piperidine derivatives and their use as therapeutic agents
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US06071927A1

  公开（公告）日：2000-06-06

  The present invention relates to certain spiro-piperdine derivatives which are tachykinnin antagonists and are useful, for example, in the treatment or prevention of pain, inflammation, migraine, emesis and postherpetic neuralgia.

  本发明涉及某些螺环哌啶衍生物，它们是快速肽激动剂拮抗剂，例如，它们在治疗或预防疼痛、炎症、偏头痛、恶心和带状疱疹后神经痛方面是有用的。