4-(3-Bromophenylsulphonyl)-1-[2-(2,4-difluorophenyl)ethyl]piperidine | 285995-09-7

• 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: 4-(3-Bromophenylsulphonyl)-1-[2-(2,4-difluorophenyl)ethyl]piperidine
• 英文别名: 4-(3-Bromophenyl)sulfonyl-1-[2-(2,4-difluorophenyl)ethyl]piperidine
• CAS: 285995-09-7
• 化学式: C₁₉H₂₀BrF₂NO₂S
• 分子量: 444.34
• InChiKey: WAKDAEYYFAGDKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  45.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(3-Bromophenylsulphonyl)-1-[2-(2,4-difluorophenyl)ethyl]piperidine 在 1,1'-双(二苯基膦)二茂铁 、 三甲基铝 、 palladium diacetate 、 氯化铵 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 36.0h， 生成 3-[[1-(2-(2,4-Difluorophenyl)ethyl)-4-piperidinyl]sulfonyl]benzamide
  参考文献：
  名称：

  4-(Phenylsulfonyl)piperidines:  Novel, Selective, and Bioavailable 5-HT_2A Receptor Antagonists

  摘要：

  On the basis of a spirocyclic ether screening lead, a series of acyclic sulfones have been identifed as high-affinity, selective 5-HT2A receptor antagonists. Bioavailability lacking in the parent, 1-(2-(2,4-difluorophenyl)ethyl)-4-(phenylsulfonyl)piperidine (12), was introduced by using stability toward rat liver microsomes as a predictor of bioavailability. By this means, the 4-cyano- and 4-carboxamidophenylsulfonyl derivatives 26 and 31 were identified as orally bioavailable, brain-penetrant analogues suitable for evaluation in animal models. Bioavailability was also attainable by N substitution leading to the N-phenacyl derivative 35. IKr activity detected through counterscreening was reduced to insignificant levels in vivo with the latter compound.

  DOI：

  10.1021/jm011030v
• 作为产物：
  描述：

  4-(3-溴苯磺酰基)哌啶-1-羧酸叔丁酯 在 盐酸 、 potassium carbonate 、 sodium iodide 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 21.0h， 生成 4-(3-Bromophenylsulphonyl)-1-[2-(2,4-difluorophenyl)ethyl]piperidine
  参考文献：
  名称：

  4-(Phenylsulfonyl)piperidines:  Novel, Selective, and Bioavailable 5-HT_2A Receptor Antagonists

  摘要：

  On the basis of a spirocyclic ether screening lead, a series of acyclic sulfones have been identifed as high-affinity, selective 5-HT2A receptor antagonists. Bioavailability lacking in the parent, 1-(2-(2,4-difluorophenyl)ethyl)-4-(phenylsulfonyl)piperidine (12), was introduced by using stability toward rat liver microsomes as a predictor of bioavailability. By this means, the 4-cyano- and 4-carboxamidophenylsulfonyl derivatives 26 and 31 were identified as orally bioavailable, brain-penetrant analogues suitable for evaluation in animal models. Bioavailability was also attainable by N substitution leading to the N-phenacyl derivative 35. IKr activity detected through counterscreening was reduced to insignificant levels in vivo with the latter compound.

  DOI：

  10.1021/jm011030v

文献信息

• [EN] PHENYLSULPHONYL DERIVATIVES AS 5-HT RECEPTOR LIGANDS<br/>[FR] DERIVES DE PHENYLSULPHONYLE EN TANT QUE LIGANDS DU RECEPTEUR 5-HT
  申请人：MERCK SHARP & DOHME

  公开号：WO2000043362A1

  公开（公告）日：2000-07-27

  A class of phenylsulphonyl derivatives wherein the sulphonyl moiety is also attached to an N-arylalkyl-substituted azetidine, pyrrolidine or piperidine ring are selective antagonists of the human 5-HT2A receptor and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of adverse conditions of the central nervous system, including schizophrenia and depression.

  一类苯磺酰基衍生物，其中磺酰基部分也附着在N-芳基烷基取代的氮杂环丙烷，吡咯烷或哌啶环上，是人类5-HT2A受体的选择性拮抗剂，因此可用作药物，特别是用于治疗和/或预防中枢神经系统的不良病症，包括精神分裂症和抑郁症。
• Phenylsulphonyl derivatives as 5-HT receptor ligands
  申请人：Merck & Co., Inc.

  公开号：US20030203889A1

  公开（公告）日：2003-10-30

  A class of phenylsulphonyl derivatives wherein the sulphonyl moiety is also attached to an N-arylalkyl-substituted azetidine, pyrrolidine or piperidine ring are selective antagonists of the human 5-HT 2A receptor and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of adverse conditions of the central nervous system, including schizophrenia and depression.

  一类苯磺酰衍生物，其中磺酰基还与N-芳基烷基取代的氮杂环（如氮杂环戊烷、吡咯烷或哌啶）环结合，是人类5-HT2A受体的选择性拮抗剂，因此在药物制剂中具有广泛的应用，尤其是在治疗和/或预防中枢神经系统的不良症状，包括精神分裂症和抑郁症方面。
• PHENYLSULPHONYL DERIVATIVES AS 5-HT RECEPTOR LIGANDS
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP1147084B1

  公开（公告）日：2004-05-19
• US6559166B1
  申请人：——

  公开号：US6559166B1

  公开（公告）日：2003-05-06
• US6777430B2
  申请人：——

  公开号：US6777430B2

  公开（公告）日：2004-08-17