2-(1-o-chlorophenethyl-4-hydroxy-4-piperidyl)-N-butylpropionamide | 55313-61-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(1-o-chlorophenethyl-4-hydroxy-4-piperidyl)-N-butylpropionamide
• 英文别名: N-butyl-2-[1-[2-(2-chlorophenyl)ethyl]-4-hydroxypiperidin-4-yl]propanamide
• CAS: 55313-61-6
• 化学式: C₂₀H₃₁ClN₂O₂
• 分子量: 366.931
• InChiKey: KIMMWCCCBWYGKQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  52.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氯苯乙胺 在 盐酸 、 丙醇 、 sodium 、 溶剂黄146 、 lithium diisopropyl amide 作用下， 以 水 、 异丙醇 为溶剂， 反应 16.83h， 生成 2-(1-o-chlorophenethyl-4-hydroxy-4-piperidyl)-N-butylpropionamide
  参考文献：
  名称：

  4,4-二取代哌啶的合成和药理研究：一类具有强镇痛作用的新型化合物。

  摘要：

  已经合成了一系列的4，4-二取代的哌啶并评估了其止痛活性。这些类似物中的几种在小鼠扭动和甩尾试验中显示出与吗啡相当的镇痛效果。许多化合物对大鼠脑膜中的[3H]纳洛酮结合位点显示出高亲和力。在最有效的衍生物中是化合物15和48。尽管是鸦片样的，但尝试用各种取代基修饰该活性未能产生拮抗作用。这些类似物中的一些在豚鼠5-羟色胺毒性试验中和在小鼠中由DL-5-羟色氨酸诱导的头抽搐模型中也显示出明显的持久性5-羟色胺拮抗作用。

  DOI：

  10.1021/jm00355a010

文献信息

• (4-Hydroxy-4-piperidyl)-alkanoic acid amides
  申请人：Sandoz Ltd.

  公开号：US04178377A1

  公开（公告）日：1979-12-11

  The present invention concerns novel compounds of formula I, ##STR1## wherein R.sub.1 is phenethyl, phenethyl monosubstituted in the phenyl ring by fluorine, chlorine, bromine, lower alkyl or lower alkoxy, butyrophenone or butyrophenone monosubstituted in the phenyl ring by fluorine, chlorine, bromine, lower alkyl or lower alkoxy, R.sub.2 is an OR.sub.5 group, wherein R.sub.5 is lower alkyl, lower alkenyl, phenyl or phenyl monosubstituted by fluorine, chlorine, bromine, lower alkyl or lower alkoxy, or an ##STR2## group, wherein independently each of R.sub.6 and R.sub.7 is hydrogen, lower alkyl or cycloalkylalkyl, cycloalkyl, phenyl, phenyl monosubstituted by fluorine, chlorine, bromine, lower alkyl or lower alkoxy, lower phenylalkyl or lower phenylalkyl monosubstituted in the phenyl ring by fluorine, chlorine, bromine, lower alkyl or lower alkoxy, or wherein R.sub.6 and R.sub.7 together with the nitrogen atom to which they are bound, form a saturated heterocycle of 5 to 6 ring members, which may optionally contain as second hetero atom oxygen, sulphur or nitrogen substituted by lower alkyl, R.sub.3 is lower alkyl or cycloalkylalkyl, cycloalky, phenyl or phenyl monosubstituted by fluorine, chlorine, bromine, lower alkyl or lower alkoxy, or when R.sub.1 is phenethyl or phenethyl monosubstituted in the phenyl ring by fluorine, chlorine, bromine, lower alkyl or lower alkoxy, alternatively lower alkenyl, and R.sub.4 is hydrogen or lower alkyl, or R.sub.3 and R.sub.4 together with the carbon atom to which they are bound form a cycloalkyl ring of 4 to 6 carbon atoms, and analgesic pharmaceutical composition containing the compounds.

  本发明涉及公式I的新化合物，其中R.sub.1是苯乙基，苯乙基在苯环上被氟、氯、溴、低烷基或低烷氧基单取代，丁酰苯或丁酰苯在苯环上被氟、氯、溴、低烷基或低烷氧基单取代，R.sub.2是OR.sub.5基团，其中R.sub.5是低烷基、低烯基、苯或苯被氟、氯、溴、低烷基或低烷氧基单取代，或者是##STR2##基团，其中R.sub.6和R.sub.7中的每一个独立地是氢、低烷基或环烷基烷基、环烷基、苯、苯被氟、氯、溴、低烷基或低烷氧基单取代、低苯基烷基或低苯基烷基在苯环上被氟、氯、溴、低烷基或低烷氧基单取代，或者R.sub.6和R.sub.7与它们所结合的氮原子一起形成一个由5到6个环成的饱和杂环，该杂环可以选择性地包含作为第二杂原子的氧、硫或氮，被低烷基取代，R.sub.3是低烷基或环烷基烷基、环烷基、苯、苯被氟、氯、溴、低烷基或低烷氧基单取代，或者当R.sub.1是苯乙基或苯乙基在苯环上被氟、氯、溴、低烷基或低烷氧基单取代时，可以选择性地是低烯基，R.sub.4是氢或低烷基，或者R.sub.3和R.sub.4与它们所结合的碳原子一起形成4到6个碳原子的环烷基环，并且包含这些化合物的镇痛药物组成物。
• Organic compounds
  申请人：Sandoz Ltd.

  公开号：US04248877A1

  公开（公告）日：1981-02-03

  The present invention concerns novel compounds of formula I, ##STR1## wherein R.sub.1 is phenethyl, phenethyl monosubstituted in the phenyl ring by fluorine, chlorine, bromine, lower alkyl or lower alkoxy, butyrophenone or butyrophenone monosubstituted in the phenyl ring by fluorine, chlorine, bromine, lower alkyl or lower alkoxy, R.sub.2 is an OR.sub.5 group, wherein R.sub.5 is lower alkyl, lower alkenyl, phenyl or phenyl monosubstituted by fluorine, chlorine, bromine, lower alkyl or lower alkoxy, or an ##STR2## 10 group, wherein independently each of R.sub.6 and R.sub.7 is hydrogen, lower alkyl or cycloalkylalkyl, cycloalkyl, phenyl, phenyl monosubstituted by fluorine, chlorine, bromine, lower alkyl or lower alkoxy, lower phenylalkyl or lower phenylalkyl monosubstituted in the phenyl ring by fluorine, chlorine, bromine, lower alkyl or lower alkoxy, or wherein R.sub.6 and R.sub.7 together with the nitrogen atom to which they are bound, form a saturated heterocycle of 5 to 6 ring members, which may optionally contain as second hetero atom oxygen, sulphur or nitrogen substituted by lower alkyl, R.sub.3 is lower alkyl or cycloalkylalkyl, cycloalkyl, phenyl or phenyl monosubstituted by fluorine, chlorine, bromine, lower alkyl or lower alkoxy, or when R.sub.1 is phenethyl or phenethyl monosubstituted in the phenyl ring by fluorine, chlorine, bromine, lower alkyl or lower alkoxy, alternatively lower alkenyl, and R.sub.4 is hydrogen or lower alkyl, or R.sub.3 and R.sub.4 together with the carbon atom to which they are bound form a cycloalkyl ring of 4 to 6 carbon atoms, and analgesic pharmaceutical compositions containing the compounds.

  本发明涉及公式I的新化合物，其中R1是苯乙烯，苯乙烯在苯环中单取代为氟、氯、溴、低烷基或低烷氧基，丁酰苯或丁酰苯在苯环中单取代为氟、氯、溴、低烷基或低烷氧基，R2是OR5基团，其中R5是低烷基、低烯基、苯或苯单取代为氟、氯、溴、低烷基或低烷氧基，或者是##STR2## 10基团，其中独立的每个R6和R7是氢、低烷基或环烷基烷基、环烷基、苯、苯单取代为氟、氯、溴、低烷基或低烷氧基、低苯基烷基或低苯基烷基在苯环中单取代为氟、氯、溴、低烷基或低烷氧基，或者R6和R7与它们结合的氮原子一起形成5到6个环成员的饱和杂环，该环可能包含作为第二杂原子的氧、硫或氮，被低烷基取代，R3是低烷基或环烷基烷基、环烷基、苯、苯单取代为氟、氯、溴、低烷基或低烷氧基，或者当R1是苯乙烯或苯乙烯在苯环中单取代为氟、氯、溴、低烷基或低烷氧基时，可以是低烯基，R4是氢或低烷基，或者R3和R4与它们结合的碳原子一起形成4到6个碳原子的环烷基环，并且包含这些化合物的镇痛药物组成物。
• US4178377A
  申请人：——

  公开号：US4178377A

  公开（公告）日：1979-12-11
• US4248877A
  申请人：——

  公开号：US4248877A

  公开（公告）日：1981-02-03
• Synthesis and pharmacological studies of 4,4-disubstituted piperidines: a new class of compounds with potent analgesic properties
  作者：Bruno S. Huegi、Anton M. Ebnoether、Erwin Rissi、Fulvio Gadient、Daniel Hauser、Dietmar Roemer、Heinz H. Buescher、Trevor J. Petcher

  DOI：10.1021/jm00355a010

  日期：1983.1

  activity. Several of these analogues show analgesic potency comparable to morphine in the mouse writhing and tail-flick tests. A number of compounds exhibit high affinity for [3H]naloxone binding sites in rat brain membranes. Among the most potent derivatives are compounds 15 and 48. Although opiate-like, attempts to modify this activity with various substituents have failed to produce antagonistic properties

  已经合成了一系列的4，4-二取代的哌啶并评估了其止痛活性。这些类似物中的几种在小鼠扭动和甩尾试验中显示出与吗啡相当的镇痛效果。许多化合物对大鼠脑膜中的[3H]纳洛酮结合位点显示出高亲和力。在最有效的衍生物中是化合物15和48。尽管是鸦片样的，但尝试用各种取代基修饰该活性未能产生拮抗作用。这些类似物中的一些在豚鼠5-羟色胺毒性试验中和在小鼠中由DL-5-羟色氨酸诱导的头抽搐模型中也显示出明显的持久性5-羟色胺拮抗作用。