N-去甲基匹莫范色林 | 639863-77-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: N-去甲基匹莫范色林
• 英文名称: 1-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-(piperidin-4-yl)urea
• 英文别名: AC-279；N-Desmethyl Pimavanserin；1-[(4-fluorophenyl)methyl]-3-[[4-(2-methylpropoxy)phenyl]methyl]-1-piperidin-4-ylurea
• CAS: 639863-77-7
• 化学式: C₂₄H₃₂FN₃O₂
• 分子量: 413.535
• InChiKey: CJAUQHPXNICIJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  53.6
• 氢给体数：
  2
• 氢受体数：
  4

制备方法与用途

生物活性

N-Desmethyl Pimavanserin 是 Pimavanserin 的活性代谢物。Pimavanserin 是选择性的 5-HT2A 受体反向激动剂，其 pIC50 和 pKd 分别为 8.73 和 9.3。

体外研究

Pimavanserin 及其代谢物 N-Desmethyl Pimavanserin (AC-279) 的平均血浆半衰期分别为 57 小时和 200 小时。

反应信息

• 作为反应物：
  描述：

  N-去甲基匹莫范色林 、 [11C]methyl triflate 以 丙酮 为溶剂， 反应 0.03h， 生成 [¹¹C]-pimavanserin
  参考文献：
  名称：

  11C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand

  摘要：

  Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the C-11-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [C-11] Pimavanserin was obtained by N-methylation of an appropriate precursor using [C-11] MeOTf in acetone at 60 degrees C giving radiochemical yields in the range of 1-1.7 GBq (n = 4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT(2A)Rs. However, this binding could not be blocked by either ketanserin or pimavanserin itself, indicating high nonspecific binding. The lack of displacement by the 5-HT2R antagonist and binding in the thalamus suggests that [C-11] pimavanserin is not selective for the 5-HT2AR in pigs. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.01.017
• 作为产物：
  描述：

  4-羟基苯乙酸甲酯 在 1,8-双二甲氨基萘 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 DMF (N,N-dimethyl-formamide) 、 二氯甲烷 为溶剂， 反应 101.25h， 生成 N-去甲基匹莫范色林
  参考文献：
  名称：

  [EN] N-SUBSTITUTED PIPERIDINE DERIVATIVES AS SEROTONIN RECEPTOR AGENTS
  [FR] DERIVES DE PIPERIDINE SUBSTITUES EN N EN TANT QU'AGENTS RECEPTEURS DE LA SEROTONINE

  摘要：

  公开号：

  WO2004000808A3

文献信息

• N-SUBSTITUTED PIPERIDINE DERIVATIVES AS SEROTONIN RECEPTOR AGENTS
  申请人：Uldam Henriette Kold

  公开号：US20090082342A1

  公开（公告）日：2009-03-26

  Disclosed herein are isolated forms of the compounds of Formula (I), (II), (III), (IV) and (V), or a pharmaceutically acceptable salt, prodrug, hydrate, solvate, polymorph, or ester thereof. Also disclosed are methods of inhibiting an activity of a serotonin receptor, methods inhibiting an activation of a serotonin receptor, and methods of alleviating or treating various disease conditions and side effects.

  本文披露了公式(I)、(II)、(III)、(IV)和(V)化合物的分离形式，或其药物可接受的盐、前药、水合物、溶剂化物、多晶形或酯。本文还披露了抑制5-羟色胺受体活性的方法、抑制5-羟色胺受体激活的方法，以及缓解或治疗各种疾病状况和副作用的方法。
• N-substituted piperidine derivatives as serotonin receptor agents
  申请人：Andersson Carl-Magnus

  公开号：US20060094758A1

  公开（公告）日：2006-05-04

  Disclosed herein are compounds of Formula I, or a pharmaceutically acceptable salt, amide, ester, or prodrug thereof. Also disclosed are methods of inhibiting an activity of a monoamine receptor comprising contacting the monoamine receptor or a system containing the monoamine receptor with an effective amount of one or more of the compounds of Formula I. Disclosed are also methods of inhibiting an activation of a monoamine receptor comprising contacting the monoamine receptor or a system containing the monoamine receptor with an effective amount of one or more of the compounds of Formula I. Furthermore, methods of treating psychotic disease using a compound of Formula I are disclosed.

  本文披露了公式I的化合物，或其药学上可接受的盐、酰胺、酯或前药。还披露了抑制单胺受体活性的方法，包括将单胺受体或含有单胺受体的系统与公式I的一种或多种化合物的有效量接触。还披露了抑制单胺受体激活的方法，包括将单胺受体或含有单胺受体的系统与公式I的一种或多种化合物的有效量接触。此外，本文还披露了使用公式I的化合物治疗精神疾病的方法。
• USE OF 4-AMINO-PIPERIDINES FOR TREATING SLEEP DISORDERS
  申请人：van Kammen Daniel

  公开号：US20080051429A1

  公开（公告）日：2008-02-28

  Inverse agonists and antagonists of serotonin receptors are disclosed for use in treating sleep disorders such as insomnia, and specifically sleep maintenance insomnia. The compound increase slow wave sleep, decrease the number of awakenings after sleep onset, and decrease the time awake after sleep onset.

  揭示了逆向激动剂和拮抗剂的血清素受体，用于治疗睡眠障碍，如失眠，特别是睡眠维持失眠。该化合物增加慢波睡眠，减少入睡后醒来的次数，减少入睡后清醒的时间。
• CO-ADMINISTRATION OF PIMAVANSERIN WITH OTHER AGENTS
  申请人：Hacksell Uli

  公开号：US20090082388A1

  公开（公告）日：2009-03-26

  As disclosed herein, co-administration of pimavanserin with an agent that ameliorates one or more cholinergic abnormalities can have a synergistic effect on the efficacy of the agent. Disclosed herein are compositions which include pimavanserin in combination with an agent that ameliorates one or more cholinergic abnormalities. Also disclosed herein are methods for ameliorating or treating a disease condition characterized by one or more cholinergic abnormalities that can include administering pimavanserin in combination with an agent that ameliorates one or more cholinergic abnormalities.

  如本文所述，联合使用pimavanserin和改善一个或多个胆碱能异常的药物可以增强该药物的疗效。本文还披露了包括pimavanserin和改善一个或多个胆碱能异常的药物在内的组合物。本文还披露了一种改善或治疗由一个或多个胆碱能异常特征的疾病状况的方法，该方法可以包括使用pimavanserin和改善一个或多个胆碱能异常的药物。
• [EN] PHOSPHAMIDE DERIVATIVE, METHOD FOR MANUFACTURING THE SAME, AND USES THEREOF<br/>[FR] DÉRIVÉ DE PHOSPHAMIDE, SON PROCÉDÉ DE FABRICATION ET SES UTILISATIONS<br/>[ZH] 一种磷酰胺衍生物及制备方法和用途
  申请人：SICHUAN HAISCO PHARMACEUTICAL CO LTD

  公开号：WO2017133517A1

  公开（公告）日：2017-08-10

  公开了一种磷酰胺衍生物及制备方法和用途。特别公开了一种通式(I)所示化合物及其药学上可接受的盐或立体异构体 (I)，其中，G、L、Q、s如说明书中所定义。