(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-4-(4-pentanon-1-yl)piperazine | 489437-61-8

• 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: (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-4-(4-pentanon-1-yl)piperazine
• 英文别名: 5-[(3R)-4-[3,5-bis(trifluoromethyl)benzoyl]-3-(1H-indol-3-ylmethyl)piperazin-1-yl]pentan-2-one
• CAS: 489437-61-8
• 化学式: C₂₇H₂₇F₆N₃O₂
• 分子量: 539.521
• InChiKey: AYLDHTWOPFYOLA-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  56.4
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-4-(4-pentanon-1-yl)piperazine 、 4-(2-(aminooxy)ethyl)morpholin-4-ium chloride 在 sodium acetate 作用下， 以 乙醇 为溶剂， 生成 [3,5-bis(trifluoromethyl)phenyl]-[(2R)-2-(1H-indol-3-ylmethyl)-4-[4-(2-morpholin-4-ylethoxyimino)pentyl]piperazin-1-yl]methanone
  参考文献：
  名称：

  哌嗪基肟醚作为NK-1受体拮抗剂。

  摘要：

  描述了新型的中枢活性NK-1受体拮抗剂的合成与构效关系。新化合物基于哌嗪2并含有肟醚官能团。几种新化合物对NK-1受体具有高亲和力，并且在沙鼠脚踏试验中显示出良好的拮抗活性。

  DOI：

  10.1016/j.bmcl.2005.10.077
• 作为产物：
  描述：

  5-氯-2-戊酮 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 生成 (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-4-(4-pentanon-1-yl)piperazine
  参考文献：
  名称：

  哌嗪基肟醚作为NK-1受体拮抗剂。

  摘要：

  描述了新型的中枢活性NK-1受体拮抗剂的合成与构效关系。新化合物基于哌嗪2并含有肟醚官能团。几种新化合物对NK-1受体具有高亲和力，并且在沙鼠脚踏试验中显示出良好的拮抗活性。

  DOI：

  10.1016/j.bmcl.2005.10.077

文献信息

• Piperazine oxime dervatives having nk-1 receptor antagonistic activity
  申请人：——

  公开号：US20040176389A1

  公开（公告）日：2004-09-09

  The present invention relates to a group of novel piperazine oxime derivatives having interesting NK-1 antagonistic activity. The invention relates to compounds of the general formula (1) wherein: X represents phenyl or pyridyl substituted with 1 or 2 substituents from the group CH 3 , CF 3 , OCH 3 , halogen, cyano and 5-CF 3 -tetrazol-1-yl; Y represents 2- or 3-indolyl, phenyl, 7-aza-indol-3-yl or 3-indazolyl, 2-naphthyl, 3-benzo[b]thiophenyl, 2-benzofuranyl, which groups may be substituted with one or more halogen or alkyl (1-3C); n has the value 0-3; m has the value 0-2; R 1 represents NH 2 , NH-alkyl (1-3C), dialkyl (1-3C)N, morpholino or morpholino substituted with one or two methyl and/or methoxymethyl groups, thiomorpholino, 1,1-dioxothiomorpholino, 2-, 3- or 4-pyridyl or 4-CH 3 -piperazinyl; R 2 is hydrogen, alkyl (1-4C) or phenyl, or R 2 together with (CH 2 ) m wherein m is 1, and the intermediate carbon nitrogen and oxygen atoms forms an isoxazolyl or a 4,5-dihydroisoxazolyl group; R 3 and R 4 independently represent hydrogen or methyl, or R 3 and R 4 together are oxygen. The invention also relates to a method for the preparation of the novel compounds, and to pharmaceutical compositions comprising compounds with formula (1) as an active ingredient and the use of these compounds for the treatment of disorders in which neurokinin-1 receptors are involved. 1

  本发明涉及一组新型哌嗪肟衍生物，具有有趣的NK-1拮抗活性。该发明涉及一般式（1）的化合物，其中：X代表苯基或吡啶基，被1或2个取代基取代，所述取代基来自CH3、CF3、OCH3、卤素、氰基和5-CF3-四唑-1-基；Y代表2-或3-吲哚基、苯基、7-氮杂吲哚-3-基或3-吲唑基、2-萘基、3-苯并[b]噻吩基、2-苯并呋喃基，这些基团可以被一个或多个卤素或烷基（1-3C）取代；n的值为0-3；m的值为0-2；R1代表NH2、NH-烷基（1-3C）、二烷基（1-3C）N、吗啉基或被一个或两个甲基和/或甲氧基甲基取代的吗啉基、硫代吗啉基、1,1-二氧硫代吗啉基、2-、3-或4-吡啶基或4-CH3-哌嗪基；R2是氢、烷基（1-4C）或苯基，或R2与(CH2)m（其中m为1）一起，中间的碳氮和氧原子形成异噁唑基或4,5-二氢异噁唑基；R3和R4独立地代表氢或甲基，或R3和R4一起代表氧。该发明还涉及一种制备新化合物的方法，以及包含式（1）化合物作为活性成分的药物组合物和这些化合物用于治疗涉及神经激肽-1受体的疾病的用途。
• Piperazine oxime dervatives having NK-1 receptor antagonistic activity
  申请人：Solvay Pharmaceuticals B.V.

  公开号：US07094779B2

  公开（公告）日：2006-08-22

  The present invention relates to a group of novel piperazine oxime derivatives having interesting NK-1 antagonistic activity. The invention relates to compounds of the general formula (1) wherein: X represents phenyl or pyridyl substituted with 1 or 2 substituents from the group CH3, CF3, OCH3, halogen, cyano and 5-CF3-tetrazol-1-yl; Y represents 2- or 3-indolyl, phenyl, 7-aza-indol-3-yl or 3-indazolyl, 2-naphthyl, 3-benzo[b]thiophenyl, 2-benzofuranyl, which groups may be substituted with one or more halogen or alkyl (1–3C); n has the value 0–3; m has the value 0–2; R1 represents NH2, NH-alkyl (1–3C), dialkyl (1–3C)N, morpholino or morpholino substituted with one or two methyl and/or methoxymethyl groups, thiomorpholino, 1,1-dioxothiomorpholino, 2-, 3- or 4-pyridyl or 4-CH3-piperazinyl; R2 is hydrogen, alkyl (1–4C) or phenyl, or R2 together with (CH2)m wherein m is 1, and the intermediate carbon, nitrogen and oxygen atoms forms an isoxazolyl or a 4,5-dihydroisoxazolyl group; R3 and R4 independently represent hydrogen or methyl, or R3 and R4 together are oxygen. The invention also relates to a method for the preparation of the novel compounds, and to pharmaceutical compositions comprising compounds with formula (1) as an active ingredient and the use of these compounds for the treatment of disorders in which neurokinin-1 receptors are involved

  本发明涉及一组新型哌嗪肟衍生物，具有有趣的NK-1拮抗活性。该发明涉及通式（1）的化合物，其中：X代表苯基或取代有1或2个基团的吡啶基，所述基团来自CH3，CF3，OCH3，卤素，氰基和5-CF3-四唑-1-基; Y代表2-或3-吲哚基，苯基，7-氮杂吲哚-3-基或3-吲唑基，2-萘基，3-苯并[b]噻吩基，2-苯并呋喃基，这些基团可以被一个或多个卤素或烷基（1-3C）取代; n的值为0-3; m的值为0-2; R1代表NH2，NH-烷基（1-3C），二烷基（1-3C）N，吗啉基或取代有一个或两个甲基和/或甲氧甲基基团的吗啉基，硫代吗啉基，1,1-二氧硫代吗啉基，2-，3-或4-吡啶基或4-CH3-哌嗪基; R2是氢，烷基（1-4C）或苯基，或R2与（CH2）m（其中m为1）一起，中间的碳，氮和氧原子形成异噁唑基或4,5-二氢异噁唑基; R3和R4独立地代表氢或甲基，或R3和R4一起代表氧。该发明还涉及一种制备新化合物的方法，以及包含通式（1）化合物作为活性成分的制药组合物和使用这些化合物治疗涉及神经激肽1受体的疾病的用途。
• Piperazinyl oxime ethers as NK-1 receptor antagonists
  作者：Adri van den Hoogenband、Jan H. van Maarseveen、Andrew C. McCreary、Arie T. Mulder、Guus J.M. van Scharrenburg、Herman H. van Stuivenberg、Theo J.J. Zethof、Barbara Zijta、Wouter I. Iwema Bakker

  DOI：10.1016/j.bmcl.2005.10.077

  日期：2006.2

  The synthesis and structure-activity relations for a new class of centrally active NK-1 receptor antagonists are described. The new compounds are based on piperazine 2 and contain an oxime ether functionality. Several new compounds have high affinity for the NK-1 receptor and show good antagonistic activity in the gerbil foot-tapping assay.

  描述了新型的中枢活性NK-1受体拮抗剂的合成与构效关系。新化合物基于哌嗪2并含有肟醚官能团。几种新化合物对NK-1受体具有高亲和力，并且在沙鼠脚踏试验中显示出良好的拮抗活性。