(2E)-3-(3-{[(tert-butoxy)carbonyl]amino}phenyl)prop-2-enoic acid | 1041867-60-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (2E)-3-(3-{[(tert-butoxy)carbonyl]amino}phenyl)prop-2-enoic acid
• 英文别名: (E)-3-[3-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]prop-2-enoic acid
• CAS: 1041867-60-0
• 化学式: C₁₄H₁₇NO₄
• 分子量: 263.293
• InChiKey: ZAWVCJCZCIEHTI-BQYQJAHWSA-N

物化性质

• 沸点：
  377.1±25.0 °C(Predicted)
• 密度：
  1.230±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Merrifield resin 、 (2E)-3-(3-{[(tert-butoxy)carbonyl]amino}phenyl)prop-2-enoic acid 在 cesium carbonate 、 四丁基碘化铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 (R)-8-amino-1,2,3,4-tetrahydronaphthalen-2-ol
  参考文献：
  名称：

  [EN] NON-STEROIDAL FXR AGONISTS
  [FR] AGONISTES FXR NON STEROIDIQUES

  摘要：

  公开号：

  WO2004046162A3
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 (2E)-3-(3-氨基苯基)丙烯酸 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 (2E)-3-(3-{[(tert-butoxy)carbonyl]amino}phenyl)prop-2-enoic acid
  参考文献：
  名称：

  组织转谷氨酰胺酶的肉桂酰基抑制剂†

  摘要：

  转谷氨酰胺酶（TGase）催化某些蛋白质的分子间交联，而组织TGase（TG2）参与多种生物过程。不受调节的高TGase活性与几种生理疾病有关，但几乎没有可逆的TG2抑制剂报道。在这里，我们报告了一系列新型反式的合成-肉桂酰胺衍生物，被发现是豚鼠肝脏转谷氨酰胺酶的有效抑制剂。评估的最有效的抑制剂可分为两类：取代的肉桂酰基苯并三唑基酰胺和3-（取代的肉桂酰基）吡啶，通常被称为氮杂环庚烷。对这两个亚类的动力学评估表明，它们在IC 50值低至18μM时显示可逆的抑制作用，并且与酰基供体TGase底物竞争。对这些抑制剂系列中的结构活性关系的分析允许鉴定潜在的重要结合相互作用。对一些最有效抑制剂的进一步测试表明它们对TG2的选择性以及其进一步开发的潜力。

  DOI：

  10.1021/jo8004843

文献信息

• Discovery and optimization of non-steroidal FXR agonists from natural product-like librariesElectronic supplementary information (ESI) available: schemes describing the synthesis of compounds in Fig. 2, 4, 5, 6 and 7. All final compounds were characterized by 1H NMR spectroscopy and HRMS are available on request. See http://www.rsc.org/suppdata/ob/b3/b300525a/
  作者：K. C. Nicolaou、Ronald M. Evans、A. J. Roecker、Robert Hughes、Michael Downes、Jeffery A. Pfefferkorn

  DOI：10.1039/b300525a

  日期：2003.3.13

  The efficient regulation of cholesterol biosynthesis, metabolism, acquisition, and transport is an essential component of lipid homeostasis. The farnesoid X receptor (FXR) is a transcriptional sensor for bile acids, the primary product of cholesterol metabolism. Accordingly, the development of potent, selective, small molecule agonists, partial agonists, and antagonists of FXR would be an important step in further deconvoluting FXR physiology. Herein, we describe the development of four novel classes of potent FXR activators originating from natural product-like libraries. Initial screening of a 10 000-membered, diversity-orientated library of benzopyran containing small molecules for FXR activation utilizing a cell-based reporter assay led to the identification of several lead compounds possessing low micromolar activity (EC50's = 5–10 µM). These compounds were systematically optimized employing parallel solution-phase synthesis and solid-phase synthesis to provide four classes of compounds that potently activate FXR. Two series of compounds, bearing stilbene or biaryl moieties, contain members that are the most potent FXR agonists reported to date in cell-based assays. These compounds may find future utility as chemical tools in studies aimed at further defining the physiological role of FXR and discovering potential therapeutic agents for the treatment of diseases linked to cholesterol and bile acid metabolism and homeostasis.

  胆固醇生物合成的有效调控、代谢、获取和转运是脂质稳态的重要组成部分。法尼醇X受体（FXR）是胆汁酸的转录感应器，胆汁酸是胆固醇代谢的主要产物。因此，开发高效、选择性的小分子FXR激动剂、部分激动剂和拮抗剂将是进一步解析FXR生理功能的重要步骤。本文描述了四种源自天然产物样库的新型高效FXR激活剂的开发。最初利用基于细胞的报告基因检测法对一个含有10,000个成员、以多样性为导向的含苯并吡喃小分子库进行FXR激活筛选，发现了几个具有低微摩尔活性的先导化合物（EC50值为5-10 µM）。通过平行溶液相合成和固相合成系统地优化这些化合物，得到了四种能够高效激活FXR的化合物。其中两个系列的化合物，含有芪或双芳基部分，在基于细胞的检测中，它们是迄今为止报道的最强效的FXR激动剂。这些化合物可能在旨在进一步定义FXR生理作用和发现与胆固醇及胆汁酸代谢和稳态相关疾病潜在治疗药物的研究中作为化学工具发挥未来实用性。
• STRUCTURE OF THE FARNESOID X RECEPTOR LIGAND BINDING DOMAIN AND METHODS OF USE THEREFOR
  申请人：Downes Michael R.

  公开号：US20110018866A1

  公开（公告）日：2011-01-27

  The present invention provides compositions comprising the ligand binding domain (LBD) of a farnesoid X receptor (FXR) in crystalline form. In alternative embodiments, the LBD of FXR is complexed with a ligand therefor. There are provided high resolution structures of FXR complexed with a novel high affinity agonist fexaramine. The discovered structure of a FXR LBD provides the first three-dimensional view of the structural basis for FXR ligand binding. The present invention further provides a computer for producing a time-dimensional representation of FXR or a complex thereof, and a computer for determining at least a portion of the structure coordinates of FXR or a complex thereof. The present invention further provides methods of using this structural information to predict molecules capable of binding to FXR; to identify compounds with agonist, antagonist or partial agonist activity for FXR; and to determine whether a test compound is capable of binding to the LBD of FXR. The present invention further provides compositions comprising compounds identified by such invention methods.
• US7647217B2
  申请人：——

  公开号：US7647217B2

  公开（公告）日：2010-01-12
• US7671085B2
  申请人：——

  公开号：US7671085B2

  公开（公告）日：2010-03-02
• US8212006B2
  申请人：——

  公开号：US8212006B2

  公开（公告）日：2012-07-03