dimethyl <3-(dimethylamino)-2-(ethoxycarbonyl)-2-propenylidene>malonate | 33707-21-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: dimethyl <3-(dimethylamino)-2-(ethoxycarbonyl)-2-propenylidene>malonate
• 英文别名: 2-O-ethyl 1-O,1-O-dimethyl (3E)-4-(dimethylamino)buta-1,3-diene-1,1,2-tricarboxylate
• CAS: 33707-21-0
• 化学式: C₁₃H₁₉NO₆
• 分子量: 285.297
• InChiKey: RCZFOQVLWIOZIK-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  dimethyl <3-(dimethylamino)-2-(ethoxycarbonyl)-2-propenylidene>malonate 在 lithium hydroxide 、 ammonium cerium(IV) nitrate 、 TEA 、 叠氮磷酸二苯酯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 lithium iodide 作用下， 以 1,4-二氧六环 、 吡啶 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 50.6h， 生成 2-(3-benzyloxycarbonylamino-4-carboxy-2-oxo-1,2-dihydro-1-pyridyl)-N-(2-tert-butyldimethylsilyloxy-3,3,3-trifluoro-1-isopropylpropyl)acetamide
  参考文献：
  名称：

  Nonpeptidic Inhibitors of Human Neutrophil Elastase. 7. Design, Synthesis, and in Vitro Activity of a Series of Pyridopyrimidine Trifluoromethyl Ketones

  摘要：

  Using molecular modeling and the information derived from X-ray crystal structures of human neutrophil elastase (HNE) and porcine pancreatic elastase (PPE) complexed to peptidic ligands, we have developed a new series of nonpeptidic inhibitors of HNE, the pyridopyrimidine trifluoromethyl ketones (TFMKs). These bicyclic inhibitors were designed to extend the concept of the related pyridone trifluoromethyl ketones by incorporating a rigidly positioned carbonyl group to participate in a hydrogen bonding interaction with the backbone NH groups of Gly-218 and Gly-219 of the enzyme. In addition, the pyrimidine ring serves as a scaffold to vector substituents toward the S-5-S-4 subsites of the enzyme's extended binding pocket. Furthermore, the heteroatoms of the pyrimidine ring generally increase the aqueous solubility of the pyridopyrimidines relative to pyridone TFMKs. Pyridopyrimidine TFMKs containing a 6-phenyl substituent afforded potent inhibitors of elastase, and several inhibitors from this class of compounds possessed aqueous solubilities of > 0.1 mg/mL and K-i values of less than or equal to 10 nM.

  DOI：

  10.1021/jm950684z
• 作为产物：
  描述：

  dimethyl <2-(ethoxycarbonyl)ethylidene>malonate 、 N,N-二甲基甲酰胺二乙基缩醛 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以80%的产率得到dimethyl <3-(dimethylamino)-2-(ethoxycarbonyl)-2-propenylidene>malonate
  参考文献：
  名称：

  Nonpeptidic Inhibitors of Human Neutrophil Elastase. 7. Design, Synthesis, and in Vitro Activity of a Series of Pyridopyrimidine Trifluoromethyl Ketones

  摘要：

  Using molecular modeling and the information derived from X-ray crystal structures of human neutrophil elastase (HNE) and porcine pancreatic elastase (PPE) complexed to peptidic ligands, we have developed a new series of nonpeptidic inhibitors of HNE, the pyridopyrimidine trifluoromethyl ketones (TFMKs). These bicyclic inhibitors were designed to extend the concept of the related pyridone trifluoromethyl ketones by incorporating a rigidly positioned carbonyl group to participate in a hydrogen bonding interaction with the backbone NH groups of Gly-218 and Gly-219 of the enzyme. In addition, the pyrimidine ring serves as a scaffold to vector substituents toward the S-5-S-4 subsites of the enzyme's extended binding pocket. Furthermore, the heteroatoms of the pyrimidine ring generally increase the aqueous solubility of the pyridopyrimidines relative to pyridone TFMKs. Pyridopyrimidine TFMKs containing a 6-phenyl substituent afforded potent inhibitors of elastase, and several inhibitors from this class of compounds possessed aqueous solubilities of > 0.1 mg/mL and K-i values of less than or equal to 10 nM.

  DOI：

  10.1021/jm950684z

文献信息

• [EN] NAPHTHYRIDINE DERIVATIVES AS INHIBITORS OF HYPOXIA INDUCIBLE FACTOR (HIF) HYDROXYLASE<br/>[FR] DÉRIVÉS DE NAPHTHYRIDINE EN TANT QU'INHIBITEURS D'UN FACTEUR INDUCTIBLE PAR L'HYPOXIE
  申请人：FIBROGEN INC

  公开号：WO2012106472A1

  公开（公告）日：2012-08-09

  The present disclosure relates to novel compounds, methods, and compositions capable of inhibiting HIF hydroxylase enzyme activity, thereby increasing the stability and/or activity of hypoxia inducible factor (HIF).

  本公开涉及能够抑制HIF羟化酶活性的新化合物、方法和组合物，从而增加缺氧诱导因子（HIF）的稳定性和/或活性。
• NAPHTHYRIDINE DERIVATIVES AS INHIBITORS OF HYPOXIA INDUCIBLE FACTOR (HIF) HYDROXYLASE
  申请人：Ng Danny

  公开号：US20140088101A1

  公开（公告）日：2014-03-27

  The present disclosure relates to novel compounds, methods, and compositions capable of inhibiting HIF hydroxylase enzyme activity, thereby increasing the stability and/or activity of hypoxia inducible factor (HIF).

  本公开涉及新型化合物、方法和组合物，能够抑制HIF羟化酶酶活性，从而增加缺氧诱导因子（HIF）的稳定性和/或活性。
• New synthesis of substituted 2(1H)-pyridones. Synthesis of a potential camptothecin intermediate
  作者：Richard F. Borch、Charles V. Grudzinskas、Douglas A. Peterson、Lynda D. Weber

  DOI：10.1021/jo00973a015

  日期：1972.4
• NAPHTHYRIDINE DERIVATIVES AS INHIBITORS OF HYPOXIA INDUCIBLE FACTOR
  申请人：Fibrogen, Inc.

  公开号：EP2670750B1

  公开（公告）日：2016-09-14
• US8921389B2
  申请人：——

  公开号：US8921389B2

  公开（公告）日：2014-12-30