NP078585 | 346408-98-8

• 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: NP078585
• 英文别名: NPO78585；6,6-bis-(4-fluorophenyl)-1-[4-(3,4,5-trimethoxyphenylmethyl)piperazin-1-yl]hexane；1-[6,6-Bis(4-fluorophenyl)hexyl]-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine
• CAS: 346408-98-8
• 化学式: C₃₂H₄₀F₂N₂O₃
• 分子量: 538.678
• InChiKey: FSLMXULFVDTVHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  39
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  34.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6,6-Bis(4-fluorophenyl)-1-[4-(3,4,5-trimethoxybenzoyl)piperazin-1-yl]hexan-1-one 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 NP078585
  参考文献：
  名称：

  Scaffold-based design and synthesis of potent N-type calcium channel blockers

  摘要：

  The therapeutic agents flunarizine and lomerizine exhibit inhibitory activities against a variety of ion channels and neurotransmitter receptors. We have optimized their scaffolds to obtain more selective N-type calcium channel blockers. During this optimization, we discovered NP118809 and NP078585, two potent N-type calcium channel blockers which have good selectivity over L-type calcium channels. Upon intraperitoneal administration both compounds exhibit analgesic activity in a rodent model of inflammatory pain. NP118809 further exhibits a number of favorable preclinical characteristics as they relate to overall pharmacokinetics and minimal off-target activity including the hERG potassium channel. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.09.008

文献信息

• COMBINATION THERAPY COMPRISING AN N-TYPE CALCIUM CHANNEL BLOCKER FOR THE ALLEVIATION OF PAIN
  申请人：Neuromed Pharmaceuticals, Ltd.

  公开号：EP1871372A1

  公开（公告）日：2008-01-02
• Combination Therapy for Relief of Pain
  申请人：Snutch Terrance P.

  公开号：US20080300262A1

  公开（公告）日：2008-12-04

  The present invention relates to analgesic compositions comprising a non-peptidyl N-type calcium channel blocker, and at least one other analgesic compound, and to methods of using N-type calcium channel blockers in combination with at least one other pain-relieving compound that alleviates pain through a mechanism other than N-type calcium channel blockage, or with a non-pharmacological therapeutic protocol.
• HUMAN N-TYPE CALCIUM CHANNEL BLOCKERS
  申请人：Zelle Robert

  公开号：US20090012095A1

  公开（公告）日：2009-01-08

  This invention features a method for modulating human N-type calcium channel α 1B+SFVG subunit activity. The method includes administering to a subject in need thereof an effective amount of a compound of formula (I), (II), or (III):
• [EN] COMBINATION THERAPY COMPRISING AN N-TYPE CALCIUM CHANNEL BLOCKER FOR THE ALLEVIATION OF PAIN<br/>[FR] THÉRAPIE DE COMBINAISON QUI COMPREND UN AGENT BLOQUANT LES CANAUX CALCIQUES DE TYPE N POUR LE SOULAGEMENT DE LA DOULEUR
  申请人：NEUROMED PHARMACEUTICALS LTD

  公开号：WO2006105670A1

  公开（公告）日：2006-10-12

  [EN] The present invention relates to analgesic compositions comprising a non-peptidyl N-type calcium channel blocker, and at least one other analgesic compound, and to methods of using N-type calcium channel blockers in combination with at least one other pain-relieving compound that alleviates pain through a mechanism other than N-type calcium channel blockage, or with a non-pharmacological therapeutic protocol.
  [FR] La présente invention concerne des compositions analgésiques qui comprennent un agent bloquant les canaux calciques de type N non peptidyle, et au moins un autre composé analgésique, et des méthodes pour utiliser des agents bloquant des canaux calciques de type N en combinaison avec au moins un autre composé calmant la douleur par un mécanisme autre que l'obstruction des canaux calciques de type N, ou par un protocole thérapeutique non pharmacologique.
• Scaffold-based design and synthesis of potent N-type calcium channel blockers
  作者：Gerald W. Zamponi、Zhong-Ping Feng、Lingyun Zhang、Hossein Pajouhesh、Yanbing Ding、Francesco Belardetti、Hassan Pajouhesh、David Dolphin、Lester A. Mitscher、Terrance P. Snutch

  DOI：10.1016/j.bmcl.2009.09.008

  日期：2009.11

  The therapeutic agents flunarizine and lomerizine exhibit inhibitory activities against a variety of ion channels and neurotransmitter receptors. We have optimized their scaffolds to obtain more selective N-type calcium channel blockers. During this optimization, we discovered NP118809 and NP078585, two potent N-type calcium channel blockers which have good selectivity over L-type calcium channels. Upon intraperitoneal administration both compounds exhibit analgesic activity in a rodent model of inflammatory pain. NP118809 further exhibits a number of favorable preclinical characteristics as they relate to overall pharmacokinetics and minimal off-target activity including the hERG potassium channel. (C) 2009 Elsevier Ltd. All rights reserved.