2-氰基-N-(1-乙氧基亚乙基)甘氨酸乙酯 | 191982-67-9

• 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
• 中文名称: 2-氰基-N-(1-乙氧基亚乙基)甘氨酸乙酯
• 英文名称: 2-cyano-N-(1-ethoxyethylidene)glycine ethyl ester
• CAS: 191982-67-9
• 化学式: C₉H₁₄N₂O₃
• 分子量: 198.222
• InChiKey: JUUFNEVADWLNCD-XFFZJAGNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14.0
• 可旋转键数：
  4.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  71.68
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-氰基-N-(1-乙氧基亚乙基)甘氨酸乙酯 在 三乙胺 作用下， 以 乙醇 、 苯 为溶剂， 反应 20.0h， 生成 Ethyl 1-benzyl-2-methyl-5-(methylcarbamoylamino)imidazole-4-carboxylate
  参考文献：
  名称：

  Potent Tetracyclic Guanine Inhibitors of PDE1 and PDE5 Cyclic Guanosine Monophosphate Phosphodiesterases with Oral Antihypertensive Activity

  摘要：

  Tetracyclic guanines have been shown to be potent and selective inhibitors of the cGMP-hydrolyzing enzymes PDE1 and PDE5. In general, these compounds are inactive or only weakly active as inhibitors of PDE3, which is a major isozyme involved in cAMP hydrolysis. Structure-activity relationships are developed at N-1, C-2, N-3, and N-5 on the core nucleus. Compound 31, with an IC50 of 70 pM, is the most potent inhibitor of PDE1, while 50, with an IC50 of 4 nM, is the most potent inhibitor of PDE5. Compounds 20, 22, 30, and 50 are potent dual inhibitors with IC50 values below 30 nM for both PDE1 and PDE5. Compounds 12, 20, and 28 reduced blood pressure by more than 45 mmHg when administered orally at 10 mg/kg to the spontaneously hypertensive rat (SHR).

  DOI：

  10.1021/jm9608467
• 作为产物：
  描述：

  2-肟氰乙酸乙酯 在 sodium dithionite 、 碳酸氢钠 作用下， 反应 22.0h， 生成 2-氰基-N-(1-乙氧基亚乙基)甘氨酸乙酯
  参考文献：
  名称：

  Potent Tetracyclic Guanine Inhibitors of PDE1 and PDE5 Cyclic Guanosine Monophosphate Phosphodiesterases with Oral Antihypertensive Activity

  摘要：

  Tetracyclic guanines have been shown to be potent and selective inhibitors of the cGMP-hydrolyzing enzymes PDE1 and PDE5. In general, these compounds are inactive or only weakly active as inhibitors of PDE3, which is a major isozyme involved in cAMP hydrolysis. Structure-activity relationships are developed at N-1, C-2, N-3, and N-5 on the core nucleus. Compound 31, with an IC50 of 70 pM, is the most potent inhibitor of PDE1, while 50, with an IC50 of 4 nM, is the most potent inhibitor of PDE5. Compounds 20, 22, 30, and 50 are potent dual inhibitors with IC50 values below 30 nM for both PDE1 and PDE5. Compounds 12, 20, and 28 reduced blood pressure by more than 45 mmHg when administered orally at 10 mg/kg to the spontaneously hypertensive rat (SHR).

  DOI：

  10.1021/jm9608467

文献信息

• Novel Heterocyclic Compound Classes for Signaling Modulation
  申请人：SignalRx Pharmaceuticals, Inc.

  公开号：US20150315207A1

  公开（公告）日：2015-11-05

  The invention relates to compounds of Formulas I-VII (or pharmaceutically acceptable salts thereof) as defined herein, pharmaceutical compositions thereof, and their use in manufactures and methods for modulating cellular signaling pathways and biological processes associated therewith including inhibition of kinase activity such as PI-3 kinase or inhibition of bromodomain proteins or both at the same time as well as to therapeutic methods for treating a disease associated with aberrant PI3K and/or bromodomain proteins.

  本发明涉及公式I-VII化合物（或其药学上可接受的盐），药物组合物以及它们在制造和调节细胞信号通路和与之相关的生物过程方面的用途，包括抑制激酶活性，如PI-3激酶或抑制溴域蛋白或同时抑制两者，以及治疗与异常PI3K和/或溴域蛋白相关的疾病的治疗方法。
• Heterocyclic compound classes for signaling modulation
  申请人：SignalRx Pharmaceuticals, Inc.

  公开号：US10174032B2

  公开（公告）日：2019-01-08

  The invention relates to compounds of Formulas I-VII (or pharmaceutically acceptable salts thereof) as defined herein, pharmaceutical compositions thereof, and their use in manufactures and methods for modulating cellular signaling pathways and biological processes associated therewith including inhibition of kinase activity such as PI-3 kinase or inhibition of bromodomain proteins or both at the same time as well as to therapeutic methods for treating a disease associated with aberrant PI3K and/or bromodomain proteins.

  本发明涉及本文定义的式 I-VII 的化合物（或其药学上可接受的盐）、其药物组合物及其在制造和方法中的用途，用于调节细胞信号通路和与之相关的生物过程，包括抑制激酶活性（如 PI-3 激酶）或抑制溴链蛋白或同时抑制二者，以及用于治疗与异常 PI3K 和/或溴链蛋白相关疾病的治疗方法。