3-phenylpropyl-5-aminoisoxazole

• 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: 3-phenylpropyl-5-aminoisoxazole
• 英文别名: 3-(3-phenylpropyl)isoxazol-5-amine；3-(3-Phenylpropyl)-1,2-oxazol-5-amine
• 化学式: C₁₂H₁₄N₂O
• 分子量: 202.256
• InChiKey: RENBDRDSZNKVPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  52
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-phenylpropyl-5-aminoisoxazole 在 Hoveyda-Grubbs catalyst second generation 作用下， 以 乙醇 为溶剂， 反应 36.0h， 以89%的产率得到
  参考文献：
  名称：

  一种合成2H-氮杂环丙烯酰胺的方法

  摘要：

  本发明涉及一种合成2H‑氮杂环丙烯酰胺的方法，将5‑氨基异恶唑原料加入到反应溶剂中，再加入荷维达‑格拉布催化剂，在绿光光照进行催化反应，将得到的反应液除去反应溶剂后再进行纯化，即得。本发明的合成方法所需要的条件十分温和、绿色，并且收率高，适用的底物范围广泛，如2H‑氮杂烯酰胺的三元环的2位可以是各种取代苯基、杂环、烯烃、烷烃，3位可以是甲基、烯丙基、苯基、1‑苯基烯丙基，酰胺可以芳烃取代胺、烷烃取代、酰基取代。

  公开号：

  CN107628979B
• 作为产物：
  描述：

  3-oxo-6-phenylhexanenitrile 在 盐酸羟胺 、 sodium hydroxide 作用下， 以 水 为溶剂， 以70%的产率得到3-phenylpropyl-5-aminoisoxazole
  参考文献：
  名称：

  Identification of diphenylalkylisoxazol-5-amine scaffold as novel activator of cardiac myosin

  摘要：

  To identify novel potent cardiac myosin activator, a series of diphenylalkylisoxazol-5-amine compounds 4-7 have been synthesized and evaluated for cardiac myosin ATPase activation. Among the 37 compounds, 4a (CMA at 10 µM = 81.6%), 4w (CMA at 10 µM = 71.2%) and 6b (CMA at 10 µM = 67.4%) showed potent cardiac myosin activation at a single concentration of 10 µM. These results suggested that the introduction of the amino-isoxazole ring as a bioisostere for urea group is acceptable for the cardiac myosin activation. Additional structure-activity relationship (SAR) studies were conducted. Para substitution (-Cl, -OCH₃, -SO₂N(CH₃)₂) to the phenyl rings or replacement of a phenyl ring with a heterocycle (pyridine, piperidine and tetrahydropyran) appeared to attenuate cardiac myosin activation at 10 µM. Additional hydrogen bonding acceptor next to the amino group of the isoxazoles did not enhance the activity. The potent isoxazole compounds showed selectivity for cardiac myosin activation over skeletal and smooth muscle myosin, and therefore these potent and selective isoxazole compounds could be considered as a new series of cardiac myosin ATPase activators for the treatment of systolic heart failure.

  DOI：

  10.1016/j.bmc.2020.115742

文献信息

• Identification of diphenylalkylisoxazol-5-amine scaffold as novel activator of cardiac myosin
  作者：Pulla Reddy Boggu、Eeda Venkateswararao、Manoj Manickam、Niti Sharma、Jong Seong Kang、Sang-Hun Jung

  DOI：10.1016/j.bmc.2020.115742

  日期：2020.11

  To identify novel potent cardiac myosin activator, a series of diphenylalkylisoxazol-5-amine compounds 4-7 have been synthesized and evaluated for cardiac myosin ATPase activation. Among the 37 compounds, 4a (CMA at 10 µM = 81.6%), 4w (CMA at 10 µM = 71.2%) and 6b (CMA at 10 µM = 67.4%) showed potent cardiac myosin activation at a single concentration of 10 µM. These results suggested that the introduction of the amino-isoxazole ring as a bioisostere for urea group is acceptable for the cardiac myosin activation. Additional structure-activity relationship (SAR) studies were conducted. Para substitution (-Cl, -OCH₃, -SO₂N(CH₃)₂) to the phenyl rings or replacement of a phenyl ring with a heterocycle (pyridine, piperidine and tetrahydropyran) appeared to attenuate cardiac myosin activation at 10 µM. Additional hydrogen bonding acceptor next to the amino group of the isoxazoles did not enhance the activity. The potent isoxazole compounds showed selectivity for cardiac myosin activation over skeletal and smooth muscle myosin, and therefore these potent and selective isoxazole compounds could be considered as a new series of cardiac myosin ATPase activators for the treatment of systolic heart failure.
• 一种合成2H-氮杂环丙烯酰胺的方法
  申请人：南京工业大学

  公开号：CN107628979B

  公开（公告）日：2020-04-14

  本发明涉及一种合成2H‑氮杂环丙烯酰胺的方法，将5‑氨基异恶唑原料加入到反应溶剂中，再加入荷维达‑格拉布催化剂，在绿光光照进行催化反应，将得到的反应液除去反应溶剂后再进行纯化，即得。本发明的合成方法所需要的条件十分温和、绿色，并且收率高，适用的底物范围广泛，如2H‑氮杂烯酰胺的三元环的2位可以是各种取代苯基、杂环、烯烃、烷烃，3位可以是甲基、烯丙基、苯基、1‑苯基烯丙基，酰胺可以芳烃取代胺、烷烃取代、酰基取代。