2-(3-(4-methoxyphenyl)-4,5-dihydroisoxazol-5-yl)acetic acid | 193267-59-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(3-(4-methoxyphenyl)-4,5-dihydroisoxazol-5-yl)acetic acid
• 英文别名: 2-[3-(4-methoxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetic acid
• CAS: 193267-59-3
• 化学式: C₁₂H₁₃NO₄
• 分子量: 235.24
• InChiKey: CFZUPCFKZGJDQX-UHFFFAOYSA-N

物化性质

• 沸点：
  415.2±51.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  68.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(3-(4-methoxyphenyl)-4,5-dihydroisoxazol-5-yl)acetic acid 在 三甲基氯硅烷 、 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 8.5h， 生成 [3-(4-Hydroxy-phenyl)-4,5-dihydro-isoxazol-5-yl]-acetic acid ethyl ester
  参考文献：
  名称：

  WO2007/112036

  摘要：

  公开号：
• 作为产物：
  描述：

  乙烯基乙酸 在 N-氯代丁二酰亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 以100%的产率得到2-(3-(4-methoxyphenyl)-4,5-dihydroisoxazol-5-yl)acetic acid
  参考文献：
  名称：

  WO2007/112036

  摘要：

  公开号：

文献信息

• 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。
• Compounds, compositions, processes of making, and methods of use related to inhibiting macrophage migration inhibitory factor
  申请人：Sielecki-Dzurdz Thais

  公开号：US20050250826A1

  公开（公告）日：2005-11-10

  The present invention provides a compound having Formula I or II: wherein B, R, X, Ar, and Y are defined herein, pharmaceutically acceptable salts thereof and pharmaceutically acceptable prodrugs thereof. The present invention also provides methods of making and using the compound.

  本发明提供了具有式 I 或式 II 的化合物： 其中 B、R、X、Ar 和 Y 在此定义的化合物、其药学上可接受的盐及其药学上可接受的原药。本发明还提供了制造和使用该化合物的方法。
• Synthesis and bio-evaluation of human macrophage migration inhibitory factor inhibitor to develop anti-inflammatory agent
  作者：Athar Alam、Chinmay Pal、Manish Goyal、Milan Kumar Kundu、Rahul Kumar、Mohd Shameel Iqbal、Sumanta Dey、Samik Bindu、Souvik Sarkar、Uttam Pal、Nakul C. Maiti、Susanta Adhikari、Uday Bandyopadhyay

  DOI：10.1016/j.bmc.2011.10.056

  日期：2011.12

  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.
• Critical modifications of the ISO-1 scaffold improve its potent inhibition of macrophage migration inhibitory factor (MIF) tautomerase activity
  作者：Kai Fan Cheng、Yousef Al-Abed

  DOI：10.1016/j.bmcl.2006.04.038

  日期：2006.7

  Based on the scaffold of (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), an inhibitor of the proinflammatory cytokine MIF, two critical modifications and chiral resolution have significantly improved the potency of the inhibition. Compound (R)-17 is 20-fold more potent than ISO-1 and inhibits MIF tautomerase activity with an IC50 of 550 nM. (c) 2006 Elsevier Ltd. All rights reserved.
• A Convenient Synthesis of 3- and 3,4-Substituted 4,5-Dihydroisoxazole-5-Acetic Acids
  作者：Eichinger, Karl、Wokurek, Michael、Zauner, Bernd、Rostami, Mohammad Reza

  DOI：10.1080/00397919708004145

  日期：1997.8

  The 4,5-dihydroisoxazole-5-acetic acids 4a-j were prepared from the ketoximes 1a-j, 2,2-dimethyl-5-methoxymethylene-1,3-dioxan-4,6-dione (2) and butyllithium in yields from 35 to 79%.