pyrrolidine-1-carboxylic acid (4-amino-phenyl)amide | 851651-90-6

• 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: pyrrolidine-1-carboxylic acid (4-amino-phenyl)amide
• 英文别名: N-(4-aminophenyl)-1-pyrrolidinecarboxamide；N-(4-aminophenyl)pyrrolidine-1-carboxamide
• CAS: 851651-90-6
• 化学式: C₁₁H₁₅N₃O
• 分子量: 205.26
• InChiKey: VRWJGKUUKHPXAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  58.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  pyrrolidine-1-carboxylic acid (4-amino-phenyl)amide 、 丙烯酰氯 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 pyrrolidine-1-carboxylic acid (4-acryloylaminophenyl)-amide
  参考文献：
  名称：

  Discovery and Structure–Activity Relationship of Potent and Selective Covalent Inhibitors of Transglutaminase 2 for Huntington’s Disease

  摘要：

  Tissue transglutaminase 2 (TG2) is a multifunctional protein primarily known for its calcium-dependent enzymatic protein cross-linking activity via isopeptide bond formation between glutamine and lysine residues. TG2 overexpression and activity have been found to be associated with Huntington's disease (HD); specifically, TG2 is up-regulated in the brains of HD patients and in animal models of the disease. Interestingly, genetic deletion of TG2 in two different HD mouse models, R6/1 and R6/2, results in improved phenotypes including a reduction in neuronal death and prolonged survival. Starting with phenylacrylamide screening hit 7d, we describe the SAR of this series leading to potent and selective TG2 inhibitors. The suitability of the compounds as in vitro tools to elucidate the biology of TG2 was demonstrated through mode of inhibition studies, characterization of druglike properties, and inhibition profiles in a cell lysate assay.

  DOI：

  10.1021/jm201310y
• 作为产物：
  描述：

  N-(4-nitrophenyl)pyrrolidine-1-carboxamide 在 镍 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 pyrrolidine-1-carboxylic acid (4-amino-phenyl)amide
  参考文献：
  名称：

  [DE] THIOZOLIDINONE, DEREN HERSTELLUNG UND VERWENDUNG ALS ARZNEIMITTEL
  [EN] THIOZOLIDINONES, PRODUCTION AND USE THEREOF AS MEDICAMENTS
  [FR] THIAZOLIDINONES, LEUR PRODUCTION ET LEUR UTILISATION COMME MEDICAMENTS

  摘要：

  通用公式（I）中的噻唑烷酮，其中Q、A、B、X、R1和R2具有描述中指定的含义，以及通用公式（IA）中的Q、A、B、X、R1和R2a具有描述中指定的含义，它们的制备和用途作为Polo-Like激酶（PLK）的抑制剂，用于治疗各种疾病，以及用于制备噻唑烷酮的中间体已经描述。

  公开号：

  WO2005042505A1

文献信息

• An efficient and practical synthesis of 2,4-substituted pyrido[4,3-d]pyrimidin-5(6H)-ones
  作者：Xinrong Tian、Dominic P. Suarez、William Hoi Hong Li、Allison K. McSherry、Robert M. Sanchez、Michael L. Moore、Jeffrey M. Axten

  DOI：10.1016/j.tetlet.2019.151312

  日期：2019.12

  We describe an efficient synthesis of 2,4-substituted pyrido[4,3-d]pyrimidin-5(6H)-ones, which involves the acid-promoted cyclization of cyano enamine 15 to afford 2,4-bis-thiomethyl pyrido[4,3-d]pyrimidin-5(6H)-one 17 as a key intermediate. Selective displacement of the 4-methylthio group by a wide range of anilines followed by oxidation of the 2-methylthio group and subsquent substitution by amines

  我们描述了2,4-取代的吡啶并[4,3- d ]嘧啶-5（6 H）-ones的有效合成，其中涉及酸促成氰基烯胺15的环化反应，从而提供2,4-双-硫代甲基吡啶基并[4,3- d ]嘧啶-5（6 ħ） -酮17，为关键中间体。通过广泛的苯胺选择性置换4-甲硫基，然后氧化2-甲硫基并随后被胺取代，使得能够合成各种2,4-二取代的吡啶并[4,3- d ]嘧啶- 5（6 H）-个。
• [DE] THIOZOLIDINONE, DEREN HERSTELLUNG UND VERWENDUNG ALS ARZNEIMITTEL<br/>[EN] THIOZOLIDINONES, PRODUCTION AND USE THEREOF AS MEDICAMENTS<br/>[FR] THIAZOLIDINONES, LEUR PRODUCTION ET LEUR UTILISATION COMME MEDICAMENTS
  申请人：SCHERING AG

  公开号：WO2005042505A1

  公开（公告）日：2005-05-12

  Es werden Thiazolidinone der allgemeinen Formel ( I ), in der Q, A, B, X, R1 und R2 die in der Beschreibung angegebenen Bedeutungen haben, sowie der allgemeinen Formel (IA) in der Q, A, B, X, R1 und R2a die in der Beschreibung angegebenen Bedeutungen haben, deren Herstellung und Verwendung als Inhibitoren der Polo Like Kinase (PLK) zur Behandlung verschiedener Erkrankungen sowie Zwischenprodukte zur Herstellung der Thiazolidinone beschrieben.

  通用公式（I）中的噻唑烷酮，其中Q、A、B、X、R1和R2具有描述中指定的含义，以及通用公式（IA）中的Q、A、B、X、R1和R2a具有描述中指定的含义，它们的制备和用途作为Polo-Like激酶（PLK）的抑制剂，用于治疗各种疾病，以及用于制备噻唑烷酮的中间体已经描述。
• Thiazolidinones, their production and use as pharmaceutical agents
  申请人：Siemeister Gerhard

  公开号：US20070037862A1

  公开（公告）日：2007-02-15

  Thiazolidinones of general formula I in which Q, A, B, X, R 1 and R 2 have the meanings that are indicated in the description, as well as those of general formula IA in which Q, A, B, X, R 1 and R 2a have the meanings that are indicated in the description, their production and use as inhibitors of the polo-like kinase (PLK) for treating various diseases as well as intermediate products for the production of thiazolidinones are described.

  通用公式I中的噻唑烷酮，其中Q、A、B、X、R1和R2具有描述中指示的含义，以及通用公式IA中的噻唑烷酮，其中Q、A、B、X、R1和R2ahave具有描述中指示的含义，描述了它们作为极化样激酶（PLK）抑制剂用于治疗各种疾病以及用于噻唑烷酮的生产和使用的中间体产品。
• CHEMICAL COMPOUNDS
  申请人：Atkinson Francis Louis

  公开号：US20110136838A1

  公开（公告）日：2011-06-09

  The invention is directed to pyrido[4,3-d]pyrimidin-5(6H)-one derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R 1 , R 2 , R 3 , and R 4 are defined below. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及吡啶并[4,3-d]嘧啶-5(6H)-酮衍生物。具体而言，本发明涉及以下式I的化合物：其中R1、R2、R3和R4如下所定义。本发明的化合物是PDK1的抑制剂，可用于治疗由恒定活化的ACG激酶所表征的疾病，例如癌症，更具体地说是乳腺癌、结肠癌和肺癌。因此，本发明还涉及包含本发明化合物的制药组合物。本发明还进一步涉及使用本发明化合物或包含本发明化合物的制药组合物来抑制PDK1活性和治疗与其相关的疾病的方法。
• Chemical compounds
  申请人：Atkinson Francis Louis

  公开号：US08383635B2

  公开（公告）日：2013-02-26

  The invention is directed to pyrido[4,3-d]pyrimidin-5(6H)-one derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R1, R2, R3, and R4 are defined below. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及吡啶并[4,3-d]嘧啶-5(6H)-酮衍生物。具体而言，本发明涉及以下式子I的化合物：其中R1、R2、R3和R4的定义如下。本发明的化合物是PDK1的抑制剂，可用于治疗由恒定激活的ACG激酶引起的疾病，如癌症，更具体地是乳腺癌、结肠癌和肺癌。因此，本发明进一步涉及包含本发明化合物的制药组合物。本发明还涉及使用本发明化合物或包含本发明化合物的制药组合物来抑制PDK1活性和治疗与之相关的疾病的方法。