1-(2,4-difluorophenethyl)-4-((4-fluorophenyl)sulfonyl)piperidine | 400729-09-1

• 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: 1-(2,4-difluorophenethyl)-4-((4-fluorophenyl)sulfonyl)piperidine
• 英文别名: 1-[2-(2,4-difluorophenyl)ethyl]-4-(4-fluorophenylsulfonyl) piperidine；1-(2,4-Difluorophenethyl)-4-(4-fluorophenylsulfonyl)piperidine；1-[2-(2,4-difluorophenyl)ethyl]-4-(4-fluorophenyl)sulfonylpiperidine
• CAS: 400729-09-1
• 化学式: C₁₉H₂₀F₃NO₂S
• 分子量: 383.435
• InChiKey: RFHWREWMZPGWCN-UHFFFAOYSA-N

物化性质

• 沸点：
  495.2±45.0 °C(Predicted)
• 密度：
  1.296±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 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：
  6

反应信息

• 作为反应物：
  描述：

  1-(2,4-difluorophenethyl)-4-((4-fluorophenyl)sulfonyl)piperidine 在 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 生成 4-({1-[2-(2,4-difluorophenyl)ethyl]-4-fluoropiperidin-4-yl}sulfonyl)benzonitrile
  参考文献：
  名称：

  4-Fluorosulfonylpiperidines: Selective 5-HT2A ligands for the treatment of insomnia

  摘要：

  Incorporation of fluorine at the 4-position of an existing series of sulfonyl piperidine 5-HT2A antagonists gave compounds with increased selectivity over the IKr potassium channel. This work led to the identification of 3b, a compound that gave no increase in QT(c) in the anesthetized dog up to plasma levels as high as 148 mu M. Furthermore, 3b has been shown to increase slow-wave sleep bout duration and to decrease the number of awakenings in rats, indicating the potential utility of 5-HT2A antagonists in the treatment of insomnia. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.104
• 作为产物：
  描述：

  1-氟-4-[(4-氟苯基)二硫烷基]苯 在 盐酸 、 aluminum oxide 、 Oxone 、 三丁基膦 、 potassium carbonate 、 sodium iodide 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 水 、 乙腈 为溶剂， 反应 87.0h， 生成 1-(2,4-difluorophenethyl)-4-((4-fluorophenyl)sulfonyl)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] 4-ARYLSULPHONYLPIPERIDINE DERIVATIVES FOR ANTAGONISM OF THE 5-HT2A RECEPTOR<br/>[FR] DERIVES DE 4-ARYLSULPHONYLPIPERIDINE POUR L'ANTAGONISME DU RECEPTEUR DE 5-HT2A
  申请人：MERCK SHARP & DOHME

  公开号：WO2004101518A1

  公开（公告）日：2004-11-25

  Compounds of formula (I): are selective antagonists of the 5-HT2A receptor, and hence are useful in treatment of adverse conditions at the central nervous system, such as sleep disorders and schizophrenia.

  式(I)的化合物是5-HT2A受体的选择性拮抗剂，因此在治疗中枢神经系统的不良症状，如睡眠障碍和精神分裂症方面具有用处。
• Piperidine and piperazine derivatives which function as 5-ht2a receptor antagonists
  申请人：——

  公开号：US20030130287A1

  公开（公告）日：2003-07-10

  Compounds of the formula I 1 in which R 1 , R 2 , X, Y and alk are as defined in claim 1, are potent 5-HT 2A antagonists and are suitable for the treatment of psychoses, schizophrenia, depression, neurological disorders, memory disorders, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, eating disorders, such as bulimia, anorexia nervosa, premenstrual syndrome and/or for positively influencing obsessive-compulsive disorder (OCD).

  公式I1的化合物，其中R1，R2，X，Y和alk的定义如权利要求书1所述，是有效的5-HT2A拮抗剂，适用于治疗精神病、精神分裂症、抑郁症、神经系统疾病、记忆障碍、帕金森病、肌萎缩性侧索硬化症、阿尔茨海默病、亨廷顿病、进食障碍（如贪食症、厌食症、经前期综合征）和/或对强迫症有积极影响。
• 4-Arylsulphonylpiperidine derivatives for antagonism of the 5-ht2a receptor
  申请人：Gilligan Myra

  公开号：US20060211735A1

  公开（公告）日：2006-09-21

  Compounds of formula (I): are selective antagonists of the 5-HT 2A receptor, and hence are useful in treatment of adverse conditions at the central nervous system, such as sleep disorders and schizophrenia.

  公式为(I)的化合物是5-HT2A受体的选择性拮抗剂，因此可用于治疗中枢神经系统的不良症状，如睡眠障碍和精神分裂症。
• PIPERIDIN- UND PIPERAZINDERIVATE ALS 5-HT2A REZEPTOR ANTAGONISTEN
  申请人：MERCK PATENT GmbH

  公开号：EP1246803A1

  公开（公告）日：2002-10-09
• 4-ARYLSULPHONYLPIPERIDINE DERIVATIVES FOR ANTAGONISM OF THE 5-HT2A RECEPTOR
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP1641756A1

  公开（公告）日：2006-04-05