5,5-Dimethyl-1-[(2-methylpropan-2-yl)oxycarbonyl]-3-[4-(trifluoromethyl)phenoxy]piperidine-3-carboxylic acid | 1000894-85-8

• 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: 5,5-Dimethyl-1-[(2-methylpropan-2-yl)oxycarbonyl]-3-[4-(trifluoromethyl)phenoxy]piperidine-3-carboxylic acid
• CAS: 1000894-85-8
• 化学式: C₂₀H₂₆F₃NO₅
• 分子量: 417.425
• InChiKey: KDRGLLYTBPKPHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5,5-Dimethyl-1-[(2-methylpropan-2-yl)oxycarbonyl]-3-[4-(trifluoromethyl)phenoxy]piperidine-3-carboxylic acid 在 盐酸 、 水 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 为溶剂， 生成
  参考文献：
  名称：

  Core modification of substituted piperidines as Novel inhibitors of HDM2–p53 protein–protein interaction

  摘要：

  The discovery of 3,3-disubstituted piperidine 1 as novel p53-HDM2 inhibitors prompted us to implement subsequent SAR follow up directed towards piperidine core modifications. Conformational restrictions and further functionalization of the piperidine core were investigated as a strategy to gain additional interactions with HDM2. Substitutions at positions 4, 5 and 6 of the piperidine ring were explored. Although some substitutions were tolerated, no significant improvement in potency was observed compared to 1. Incorporation of an allyl side chain at position 2 provided a drastic improvement in binding potency. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.055
• 作为产物：
  描述：

  氯仿 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 1.33h， 生成 5,5-Dimethyl-1-[(2-methylpropan-2-yl)oxycarbonyl]-3-[4-(trifluoromethyl)phenoxy]piperidine-3-carboxylic acid
  参考文献：
  名称：

  Substituted Piperidines that Increase P53 Activity and the Uses Thereof

  摘要：

  在其多种实施形式中，本发明披露了作为HDM2蛋白抑制剂的新型化合物，制备这种化合物的方法，包括一种或多种这种化合物的药物组合物，以及利用这种化合物或药物组合物进行与HDM2蛋白或P53相关的一种或多种疾病的治疗、预防、抑制方法。

  公开号：

  US20080004287A1

文献信息

• US7884107B2
  申请人：——

  公开号：US7884107B2

  公开（公告）日：2011-02-08
• [EN] SUBSTITUTED PIPERIDINES THAT INCREASE P53 ACTIVITY AND THE USES THEREOF<br/>[FR] PIPÉRIDINES SUBSTITUÉES QUI AUGMENTENT L'ACTIVITÉ P53 ET LEURS UTILISATIONS
  申请人：SCHERING CORP

  公开号：WO2008005268A1

  公开（公告）日：2008-01-10

  [EN] In its many embodiments, the present invention discloses novel compounds, as inhibitors of HDM2 protein, methods for preparing such compounds, pharmaceutical compositions including one or more such compounds, methods of treatment, prevention, inhibition, of one or more diseases associated with the HDM2 protein or P53 using such compounds or pharmaceutical compositions.
  [FR] Dans ses nombreux modes de réalisation, La présente invention concerne des composés innovants inhibiteurs de protéines HDM2, des procédés de préparation de tels composés, des compositions pharmaceutiques incluant un ou plusieurs composés de ce genre et des procédés de traitement, de prévention, d'inhibition d'une ou plusieurs maladies associées à la protéine HDM2 ou à la P53 à l'aide de tels composés ou compositions pharmaceutiques.
• Substituted Piperidines that Increase P53 Activity and the Uses Thereof
  申请人：Ma Yao

  公开号：US20080004287A1

  公开（公告）日：2008-01-03

  In its many embodiments, the present invention discloses novel compounds, as inhibitors of HDM2 protein, methods for preparing such compounds, pharmaceutical compositions including one or more such compounds, methods of treatment, prevention, inhibition, of one or more diseases associated with the HDM2 protein or P53 using such compounds or pharmaceutical compositions.

  在其多种实施形式中，本发明披露了作为HDM2蛋白抑制剂的新型化合物，制备这种化合物的方法，包括一种或多种这种化合物的药物组合物，以及利用这种化合物或药物组合物进行与HDM2蛋白或P53相关的一种或多种疾病的治疗、预防、抑制方法。
• Core modification of substituted piperidines as Novel inhibitors of HDM2–p53 protein–protein interaction
  作者：Weidong Pan、Brian R. Lahue、Yao Ma、Latha G. Nair、Gerald W. Shipps、Yaolin Wang、Ronald Doll、Stéphane L. Bogen

  DOI：10.1016/j.bmcl.2014.02.055

  日期：2014.4

  The discovery of 3,3-disubstituted piperidine 1 as novel p53-HDM2 inhibitors prompted us to implement subsequent SAR follow up directed towards piperidine core modifications. Conformational restrictions and further functionalization of the piperidine core were investigated as a strategy to gain additional interactions with HDM2. Substitutions at positions 4, 5 and 6 of the piperidine ring were explored. Although some substitutions were tolerated, no significant improvement in potency was observed compared to 1. Incorporation of an allyl side chain at position 2 provided a drastic improvement in binding potency. (C) 2014 Elsevier Ltd. All rights reserved.