methyl (2-imino-3-methyl-2,3-dihydrothiazol-4-yl)acetate hydroiodide | 1586872-68-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl (2-imino-3-methyl-2,3-dihydrothiazol-4-yl)acetate hydroiodide
• 英文别名: Methyl 2-(2-imino-3-methyl-1,3-thiazol-4-yl)acetate;hydroiodide；methyl 2-(2-imino-3-methyl-1,3-thiazol-4-yl)acetate;hydroiodide
• CAS: 1586872-68-5
• 化学式: C₇H₁₀N₂O₂S*HI
• 分子量: 314.147
• InChiKey: CYCDPMHSRDIQOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  78.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (2-imino-3-methyl-2,3-dihydrothiazol-4-yl)acetate hydroiodide 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 19.0h， 以88%的产率得到(2-imino-3-methyl-2,3-dihydrothiazol-4-yl)acetic acid hydrochloride
  参考文献：
  名称：

  Structure–Activity Relationship Studies toward the Discovery of Selective Apelin Receptor Agonists

  摘要：

  Apelin is the endogenous ligand for the previously orphaned G protein-coupled receptor APJ. Apelin and its receptor are widely distributed in the brain, heart, and vasculature, and are emerging as an important regulator of body fluid homeostasis and cardiovascular functions. To further progress in the pharmacology and the physiological role of the apelin receptor, the development of small, bioavailable agonists and antagonists of the apelin receptor, is crucial. In this context, E339-3D6 (1) was described as the first nonpeptidic apelin receptor agonist. We show here that 1 is actually a mixture of polymethylated species, and we describe an alternative and versatile solid-phase approach that allows access to highly pure 27, the major component of 1. This approach was also applied to prepare a series of derivatives in order to identify the crucial structural determinants required for the ligand to maintain its affinity for the apelin receptor as well as its capacity to promote apelin receptor signaling and internalization. The study of the structure activity relationships led to the identification of ligands 19, 21, and 38, which display an increased affinity compared to that of 27. The latter and 19 behave as full agonists with regard to cAMP production and apelin receptor internalization, whereas 21 is a biased agonist toward cAMP production. Interestingly, the three ligands display a much higher stability in mouse plasma (T-1/2 > 10 h) than the endogenous apelin-17 peptide 2 (T-1/2 < 4 min).

  DOI：

  10.1021/jm401789v
• 作为产物：
  描述：

  2-氨基-4-噻唑乙酸甲酯 、 碘甲烷 以 四氢呋喃 为溶剂， 反应 72.0h， 以93%的产率得到methyl (2-imino-3-methyl-2,3-dihydrothiazol-4-yl)acetate hydroiodide
  参考文献：
  名称：

  Structure–Activity Relationship Studies toward the Discovery of Selective Apelin Receptor Agonists

  摘要：

  Apelin is the endogenous ligand for the previously orphaned G protein-coupled receptor APJ. Apelin and its receptor are widely distributed in the brain, heart, and vasculature, and are emerging as an important regulator of body fluid homeostasis and cardiovascular functions. To further progress in the pharmacology and the physiological role of the apelin receptor, the development of small, bioavailable agonists and antagonists of the apelin receptor, is crucial. In this context, E339-3D6 (1) was described as the first nonpeptidic apelin receptor agonist. We show here that 1 is actually a mixture of polymethylated species, and we describe an alternative and versatile solid-phase approach that allows access to highly pure 27, the major component of 1. This approach was also applied to prepare a series of derivatives in order to identify the crucial structural determinants required for the ligand to maintain its affinity for the apelin receptor as well as its capacity to promote apelin receptor signaling and internalization. The study of the structure activity relationships led to the identification of ligands 19, 21, and 38, which display an increased affinity compared to that of 27. The latter and 19 behave as full agonists with regard to cAMP production and apelin receptor internalization, whereas 21 is a biased agonist toward cAMP production. Interestingly, the three ligands display a much higher stability in mouse plasma (T-1/2 > 10 h) than the endogenous apelin-17 peptide 2 (T-1/2 < 4 min).

  DOI：

  10.1021/jm401789v