methyl 2-(3-(4-methoxyphenyl)-4,5-dihydroisoxazol-5-yl)acetate | 211388-28-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: methyl 2-(3-(4-methoxyphenyl)-4,5-dihydroisoxazol-5-yl)acetate
• 英文别名: (+/-)-methyl 3-(4-methoxyphenyl)-2-isoxazoline-5-acetate；methyl 3-(p-methoxyphenyl)-5-isoxazolinylacetate；Methyl 2-[3-(4-methoxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate
• CAS: 211388-28-2
• 化学式: C₁₃H₁₅NO₄
• 分子量: 249.266
• InChiKey: GAVWDQIPZVIKEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  57.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-(3-(4-methoxyphenyl)-4,5-dihydroisoxazol-5-yl)acetate 在 sodium 作用下， 以 正己醇 为溶剂， 反应 0.5h， 以82%的产率得到(+/-)-5-[2-(4-methoxyphenyl)-2-oxoethyl]-3-isoxazolidinone
  参考文献：
  名称：

  A Novel Base Promoted Reaction of Methyl 2-Isoxazoline-5-acetates to 5-(2-oxoethyl)-3-isoxazolidinones

  摘要：

  The 5-(2-aryl-2-oxoethyl)-3-isoxazolidinones 3a-e were prepared from the methyl 3-aryl-2-isoxazoline-5-acetates 2a-e and sodium hexanolate in boiling hexanol in yields from 46 to 86%. The reaction conditions were optimized and a mechanism for this reaction is proposed and discussed.

  DOI：

  10.1080/00397919808004297
• 作为产物：
  描述：

  对甲氧基苯甲醛肟 在 N-氯代丁二酰亚胺 、 三甲基氯硅烷 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 methyl 2-(3-(4-methoxyphenyl)-4,5-dihydroisoxazol-5-yl)acetate
  参考文献：
  名称：

  Synthesis and bio-evaluation of human macrophage migration inhibitory factor inhibitor to develop anti-inflammatory agent

  摘要：

  Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is involved in the development of an array of inflammatory disorders including rheumatoid arthritis, inflammatory bowel disease, psoriasis, multiple sclerosis and sepsis. The synthesis of MIF-inhibitor is a rationale approach to develop novel anti-inflammatory agent to treat multitude of inflammatory diseases. In this work, we have synthesized and evaluated MIF-inhibitory activity of a series of small molecules containing isoxazoline skeleton. Mode of binding of this inhibitor to human MIF (huMIF) was determined by docking studies. The synthesized molecules inhibit tautomerase activity of huMIF. The anti-inflammatory activity of the most active inhibitor, 4-((3-(4-hydroxy-3-methoxyphenyl)-4, 5-dihydroisoxazol-5-yl) methoxy) benzaldehyde (4b) was evaluated against huMIF-induced inflammation in a cellular model (RAW 264.7 cell). Compound 4b significantly inhibits huMIF-mediated NF-kappa B translocation to the nucleus, up-regulation of inducible nitric oxide synthase and nitric oxide production in RAW 264.7 cell which are the markers for inflammation. The compound 4b is not cytotoxic as evident from cell viability assay. Hence, the compound 4b has potential to be a novel anti-inflammatory agent. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.056

文献信息

• Δ²-Isoxazolines from β,γ-unsaturated oximes
  作者：Michael D. Mosher、Laura G. Emmerich、Katherine S. Frost、Benjamin Anderson

  DOI：10.1002/jhet.5570430303

  日期：2006.5

  3,5-Disubstituted Δ2-isoxazolines can be prepared using the palladium-mediated nucleometalation / methoxycarbonylation of β,γ-unsaturated oximes. This novel route to this class of compounds is tolerant of a wide variety of functionality in the starting material, and provides a rapid route to highly functionalized isoxazolines.

  3,5-二取代的Δ 2 -isoxazolines可使用β，γ不饱和肟的钯介导nucleometalation /甲氧基羰基来制备。这种通往这类化合物的新颖途径可耐受起始材料中的多种官能团，并提供了快速途径来制备高度官能化的异恶唑啉。
• Isoxazoline compounds having MIF antagonist activity
  申请人：——

  公开号：US20030008908A1

  公开（公告）日：2003-01-09

  Methods of use and pharmaceutical compositions for a genus of low molecular weight compounds comprising optionally substituted isoxazoline ring systems that act as inhibitors of MIF (macrophage migration inhibitory factor) are disclosed. Specifically, the compounds are useful for treating a variety of diseases involving inflammatory activity or pro-inflammatory cytokine responses, such as autoimmune diseases (including rheumatiod arthritis, insulin-dependent diabetes, multiple sclerosis, graft versus host disease, lupus syndromes), asthma, arthritis, ARDS, psoriasis, interleukin-2 toxicity, proliferative vascular disease, and various forms of sepsis and septic shock, and other conditions characterized by underlying MIF responses including, for instance, tumor growth and neovascularization (angiogenesis).

  本发明公开了一种低分子量化合物的使用方法和药物组合物，该化合物包含可选取代的异噁唑啉环系统，可作为 MIF（巨噬细胞迁移抑制因子）的抑制剂。具体来说，这些化合物可用于治疗多种涉及炎症活动或促炎细胞因子反应的疾病，如自身免疫性疾病（包括风湿性关节炎、胰岛素依赖型糖尿病、多发性硬化症、移植物抗宿主病、狼疮综合征）、慢性肾脏病、糖尿病、高血压、高血脂、高血糖等、狼疮综合征）、哮喘、关节炎、ARDS、银屑病、白细胞介素-2毒性、增生性血管疾病、各种形式的败血症和脓毒性休克，以及其他以潜在的 MIF 反应为特征的疾病，包括肿瘤生长和血管新生（血管生成）等。
• ISOXAZOLINE COMPOUNDS HAVING MIF ANTAGONIST ACTIVITY
  申请人：Cytokine Pharmasciences, Inc.

  公开号：EP1411930B1

  公开（公告）日：2013-01-16
• Isoxazoline Compounds Having MIF Antagonist Activity
  申请人：Al-Abed Yousef

  公开号：US20100016391A1

  公开（公告）日：2010-01-21

  Methods of use and pharmaceutical compositions for a genus of low molecular weight compounds comprising optionally substituted isoxazoline ring systems that act as inhibitors of MIF (macrophage migration inhibitory factor) are disclosed. Specifically, the compounds are useful for treating a variety of diseases involving inflammatory activity or pro-inflammatory cytokine responses, such as autoimmune diseases (including rheumatoid arthritis, insulin-dependent diabetes, multiple sclerosis, graft versus host disease, lupus syndromes), asthma, arthritis, ARDS, psoriasis, interleukin-2 toxicity, proliferative vascular disease, and various forms of sepsis and septic shock, and other conditions characterized by underlying MIF responses including, for instance, tumor growth and neovascularization (angiogenesis).
• US7491740B2
  申请人：——

  公开号：US7491740B2

  公开（公告）日：2009-02-17