N-tert-butoxymalonamic acid ethyl ester | 608520-17-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-tert-butoxymalonamic acid ethyl ester
• 英文别名: ethyl N-tert-butoxymalonamate；Ethyl 3-(tert-butoxyamino)-3-oxopropanoate；ethyl 3-[(2-methylpropan-2-yl)oxyamino]-3-oxopropanoate
• CAS: 608520-17-8
• 化学式: C₉H₁₇NO₄
• 分子量: 203.238
• InChiKey: MAJPYRUMXCHEAU-UHFFFAOYSA-N

物化性质

• 密度：
  1.053±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-tert-butoxymalonamic acid ethyl ester 在 哌啶 、 氢氧化钾 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 27.0h， 生成 N-tert-butoxy-2-(3-phenoxybenzyl)malonamic acid
  参考文献：
  名称：

  针对金属蛋白酶家族的新型异羟肟酸文库：设计，平行合成和筛选。

  摘要：

  我们在此报告基于丙二酸-异羟肟酸模板的217种化合物的设计和平行合成。这些化合物是通过两步溶液阶段法获得的。所使用的各种不同的构建基组使该策略适合于寻找各种金属蛋白酶的抑制剂，并适合于研究新的金属蛋白酶的生物学作用。作为概念证明，我们在中性氨基肽酶（APN； EC 3.4.11.2）（M1家族的原型酶）上筛选了该文库。鉴定了几种亚微摩尔抑制剂。

  DOI：

  10.1016/j.bmc.2006.10.010
• 作为产物：
  描述：

  丙二酸单乙酯 、 O-叔丁基羟胺盐酸盐 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 N-tert-butoxymalonamic acid ethyl ester
  参考文献：
  名称：

  Design, synthesis and antimalarial activity of novel, quinoline-Based, zinc metallo-aminopeptidase inhibitors

  摘要：

  PfA-M1, a neutral zinc aminopeptidase of Plasmodium falciparum, is a new potential target for the discovery of anti-malarials. The design and synthesis of a library of 45 quinoline-based inhibitors of PfA-M1 is reported. The best inhibitor displays an IC50 of 854 nM. The antimalarial activity on a CQ-resistant strain and the specificity towards mammalian aminopeptidase N are also discussed. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00550-x

文献信息

• Pyrido[2,3-d]pyrimidines and their use as kinase inhibitors
  申请人：GPC Biotech Inc.

  公开号：EP1914234A1

  公开（公告）日：2008-04-23

  The present invention provides derivatives of pyrido [2,3-d]pyrimidin-7-one of formula (I). These compounds are kinase inhibitors, including compounds that show anti-proliferative activity, including against tumor cells, and are useful in the treatment of diseases including cancer.

  本发明提供了公式(I)的吡啶并[2,3-d]嘧啶-7-酮衍生物。这些化合物是激酶抑制剂，包括显示抗增殖活性的化合物，包括对肿瘤细胞，对治疗癌症等疾病有用。
• Structure–Activity Relationships and Blood Distribution of Antiplasmodial Aminopeptidase-1 Inhibitors
  作者：Rebecca Deprez-Poulain、Marion Flipo、Catherine Piveteau、Florence Leroux、Sandrine Dassonneville、Isabelle Florent、Louis Maes、Paul Cos、Benoit Deprez

  DOI：10.1021/jm301506h

  日期：2012.12.27

  Malaria is a severe infectious disease that causes between 655 000 and 1.2 million deaths annually. To overcome the resistance to current drugs, new biological targets are needed for drug development. Aminopeptidase M1 (PfAM1), a zinc metalloprotease, has been proposed as a new drug target to fight malaria. Herein, we disclosed the structure-activity relationships of a selective family of hydroxamate PfAM1 inhibitors based on the malonic template. In particular, we performed a "fluoro-scanning" around hit 1 that enlightened the key positions of the halogen for activity. The docking of the best inhibitor 2 is consistent with in vitro results. The stability of 2 was evaluated in microsomes, in plasma, and toward glutathione. The in vivo distribution study performed with the nanomolar hydroxamate inhibitor 2 (BDM14471) revealed that it reaches its site of action. However, it fails to kill the parasite at concentrations relevant to the enzymatic inhibitory potency, suggesting that killing the parasite remains a challenge for potent and druglike catalytic-site binding PfAM1 inhibitors. In all, this study provides important insights for the design of inhibitors of PfAM1 and the validity of this target.
• WO2008/150260
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, synthesis and antimalarial activity of novel, quinoline-Based, zinc metallo-aminopeptidase inhibitors
  作者：Marian Flipo、Isabelle Florent、Philippe Grellier、Christian Sergheraert、Rebecca Deprez-Poulain

  DOI：10.1016/s0960-894x(03)00550-x

  日期：2003.8

  PfA-M1, a neutral zinc aminopeptidase of Plasmodium falciparum, is a new potential target for the discovery of anti-malarials. The design and synthesis of a library of 45 quinoline-based inhibitors of PfA-M1 is reported. The best inhibitor displays an IC50 of 854 nM. The antimalarial activity on a CQ-resistant strain and the specificity towards mammalian aminopeptidase N are also discussed. (C) 2003 Elsevier Ltd. All rights reserved.
• A library of novel hydroxamic acids targeting the metallo-protease family: Design, parallel synthesis and screening
  作者：Marion Flipo、Terence Beghyn、Julie Charton、Virginie A. Leroux、Benoit P. Deprez、Rebecca F. Deprez-Poulain

  DOI：10.1016/j.bmc.2006.10.010

  日期：2007.1.1

  We report here the design and parallel synthesis of 217 compounds based on a malonic-hydroxamic acid template. These compounds are obtained via a two-step solution-phase procedure. The set of diverse building-blocks used makes this strategy suitable for the search of inhibitors of various metallo-proteases and for the investigation of the biological role of new metallo-proteases. As a proof of concept

  我们在此报告基于丙二酸-异羟肟酸模板的217种化合物的设计和平行合成。这些化合物是通过两步溶液阶段法获得的。所使用的各种不同的构建基组使该策略适合于寻找各种金属蛋白酶的抑制剂，并适合于研究新的金属蛋白酶的生物学作用。作为概念证明，我们在中性氨基肽酶（APN； EC 3.4.11.2）（M1家族的原型酶）上筛选了该文库。鉴定了几种亚微摩尔抑制剂。