tert-butyl 3,3-dimethyl-5-oxopiperidine-1-carboxylate | 1000894-83-6

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 3,3-dimethyl-5-oxopiperidine-1-carboxylate
• 英文别名: 1-Boc-5,5-dimethyl-3-piperidone
• CAS: 1000894-83-6
• 化学式: C₁₂H₂₁NO₃
• 分子量: 227.304
• InChiKey: XIVWTYQQVHHCFB-UHFFFAOYSA-N

物化性质

• 沸点：
  303.4±35.0 °C(Predicted)
• 密度：
  1.035±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 3,3-dimethyl-5-oxopiperidine-1-carboxylate 在 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， 生成 tert-butyl 3-(4-(2-(2-methoxyethoxy)phenyl)piperazine-1-carbonyl)-5,5-dimethyl-3-(4-(trifluoromethyl)phenoxy)piperidine-1-carboxylate
  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：

  (3R,7aS)-6,6-dimethyl-3-phenyl-1,3,7,7a-tetrahydropyrrolo[1,2-c][1,3]oxazol-5-one 在 lithium aluminium tetrahydride 、 10 wt% Pd(OH)2 on carbon 、 氢气 、 戴斯-马丁氧化剂 、 三乙胺 、 三氟乙酸酐 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 96.0h， 生成 tert-butyl 3,3-dimethyl-5-oxopiperidine-1-carboxylate
  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

文献信息

• 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。
• [EN] PLASMA KALLIKREIN INHIBITORS<br/>[FR] INHIBITEURS DE KALLICRÉINE PLASMATIQUE
  申请人：MERCK SHARP & DOHME

  公开号：WO2022109161A1

  公开（公告）日：2022-05-27

  The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age related macular edema, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.

  本发明提供了式(I)的化合物及包含一种或多种所述化合物的制药组合物，以及使用所述化合物治疗或预防可能受益于抑制血浆卡利肌酶的一种或多种疾病状态的方法，包括遗传性血管性水肿、葡萄膜炎、后部葡萄膜炎、湿性年龄相关性黄斑水肿、糖尿病性黄斑水肿、糖尿病视网膜病变和视网膜静脉阻塞。这些化合物是血浆卡利肌酶的选择性抑制剂。
• 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.
• [EN] PLASMA KALLIKREIN INHIBITORS<br/>[FR] INHIBITEURS DE LA KALLIKRÉINE PLASMATIQUE
  申请人：[en]MERCK SHARP & DOHME LLC

  公开号：WO2022225828A1

  公开（公告）日：2022-10-27

  The present invention provides a compound of Formula I and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing one or more disease states that could benefit from inhibition of plasma kallikrein, including hereditary angioedema, uveitis, posterior uveitis, wet age-related macular degeneration, diabetic macular edema, diabetic retinopathy and retinal vein occlusion. The compounds are selective inhibitors of plasma kallikrein.