2-phenyl-N-(3-phenylisoxazol-5-yl)acetamide | 1105629-28-4

• 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: 2-phenyl-N-(3-phenylisoxazol-5-yl)acetamide
• 英文别名: 2-phenyl-N-(3-phenyl-1,2-oxazol-5-yl)acetamide
• CAS: 1105629-28-4
• 化学式: C₁₇H₁₄N₂O₂
• 分子量: 278.31
• InChiKey: YRZMOYBTQABTHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  苯甲酸甲酯 在 4-二甲氨基吡啶 、 盐酸羟胺 、 sodium hydride 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 16.0h， 生成 2-phenyl-N-(3-phenylisoxazol-5-yl)acetamide
  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

• Novel therapeutic compounds
  申请人：Breinlinger Eric C.

  公开号：US20090069288A1

  公开（公告）日：2009-03-12

  Disclosed herein are novel compounds of Formula (I), wherein the variables are defined as herein. The compounds of Formula (I) are useful as kinase inhibitors and as such would be useful in treating certain conditions and diseases, especially inflammatory conditions and diseases as well as proliferative disorders such as cancer.

  本文公开了公式（I）的新化合物，其中变量如本文所定义。公式（I）的化合物可用作激酶抑制剂，因此可用于治疗某些疾病和病症，特别是炎症性疾病和疾病以及增生性疾病，如癌症。
• [EN] NOVEL THERAPEUTIC COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS THÉRAPEUTIQUES
  申请人：ABBOTT LAB

  公开号：WO2009011850A2

  公开（公告）日：2009-01-22

  Disclosed herein are novel compounds of Formula (I), wherein the variables are defined as herein. The compounds of Formula (I) are useful as kinase inhibitors and as such would be useful in treating certain conditions and diseases, especially inflammatory conditions and diseases as well as proliferative disorders such as cancer.
• 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.