(S)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (S)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester
• 英文别名: (S)-methyl 2-(3-(4-hydroxyphenyl)-4,5-dihydroisoxazol-5-yl)acetate；methyl 2-[(5S)-3-(4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate
• 化学式: C₁₂H₁₃NO₄
• 分子量: 235.24
• InChiKey: AIXMJTYHQHQJLU-JTQLQIEISA-N

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 、 三溴化硼 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 (S)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester
  参考文献：
  名称：

  Critical modifications of the ISO-1 scaffold improve its potent inhibition of macrophage migration inhibitory factor (MIF) tautomerase activity

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2006.04.038

文献信息

• ISOINDOLIN-1-ONES AS MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) INHIBITORS
  申请人：Controlled Chemicals, Inc.

  公开号：US20150175540A1

  公开（公告）日：2015-06-25

  Compounds having an isoindolin-1-one backbone of Formula (I) are disclosed which have utility in treating and/or preventing microbial infections, tumor growth, metastasis and other macrophage migration inhibitory factor (MIF)-modulated pathological conditions. Pharmaceutical compositions and methods and use of compounds of Formula (I) are also disclosed.

  公开了具有式(I)的异吲哚啉-1-酮骨架的化合物，其在治疗和/或预防微生物感染、肿瘤生长、转移以及其他巨噬细胞迁移抑制因子（MIF）调节的病理条件方面具有用途。还公开了式(I)化合物的药物组合物、方法和用途。
• MODIFIED MACROPHAGE MIGRATION INHIBITORY FACTOR INHIBITORS
  申请人：Al-Abed Yousef

  公开号：US20130190369A1

  公开（公告）日：2013-07-25

  Provided are various compounds of Formula I (I). Also provided are various compounds of Formula II (II). Also provided are pharmaceutical compositions comprising the above compounds. Additionally, methods of inhibiting macrophage migration inhibitory factor (MIF) activity in a mammal are provided, as are methods of treating or preventing inflammation in a mammal. Further provided are methods of treating a mammal having sepsis, septicemia, and/or endotoxic shock. Also provided are methods of treating a mammal having an autoimmune disease, and methods of treating a mammal having a tumor.

  提供了多种化合物的公式I（I）。还提供了多种化合物的公式II（II）。还提供了包含上述化合物的制药组合物。此外，提供了抑制哺乳动物中巨噬细胞迁移抑制因子（MIF）活性的方法，以及治疗或预防哺乳动物炎症的方法。此外，还提供了治疗感染性休克、败血症和/或内毒素休克的哺乳动物的方法。还提供了治疗自身免疫疾病的哺乳动物的方法，以及治疗患有肿瘤的哺乳动物的方法。
• Pharmaceutical Compounds Targeted by MIF Affinity-Tethered Moieties
  申请人：RJS Biologics LLC

  公开号：US20150352217A1

  公开（公告）日：2015-12-10

  There is disclosed a compound, a pharmaceutical composition and a method of treatment using a pharmaceutical composition comprising a tethering moiety that is capable of binding to a macrophage migration inhibitory factor (MIF) polypeptide, optionally linked to a linker moiety and further covalently bound to a drug moiety or imaging agent. More specifically, there is disclosed a genus of affinity-tethering moieties covalently bound to a drug moiety or imaging agent either directly or optionally via a linker moiety to covalently link the tethering moiety to a drug moiety. Without being bound by theory, the disclosed pharmaceutical compounds are targeted to cancer cells or immune cells via an affinity-tethering moiety that hitch-hikes to or into its target cell while bound to endogenous MIF.

  本发明涉及一种化合物、一种药物组合物和使用药物组合物的治疗方法，其中药物组合物包括一种可结合到巨噬细胞迁移抑制因子（MIF）多肽的系留基，可选地与连接基团连接，并进一步共价结合到药物基团或成像剂上。更具体地，本发明涉及一类亲和系留基，它们与药物基团或成像剂直接或可选地通过连接基团共价结合，以共价连接系留基和药物基团。本发明所披露的药物化合物通过亲和系留基定向靶向癌细胞或免疫细胞，系留基通过与内源性MIF结合，搭便车到达或进入其靶细胞。
• Controlled-release otic structure modulating and innate immune system modulating compositions and methods for the treatment of otic disorders
  申请人：Lichter Jay

  公开号：US10092580B2

  公开（公告）日：2018-10-09

  Disclosed herein are compositions and methods for the treatment of otic disorders with otic structure modulating compositions administered locally to an individual afflicted with an otic disorder, through direct application of these compositions and compositions onto or via perfusion into the targeted auris structure(s).

  本文公开了用于治疗耳部疾病的组合物和方法，通过将这些组合物和成分直接施用到或通过灌注到目标虹膜结构，对患有耳部疾病的人局部施用调节耳部结构的组合物。
• Methods for treating and diagnosing blinding eye diseases
  申请人：Translatum Medicus Inc.

  公开号：US10265418B2

  公开（公告）日：2019-04-23

  This invention relates to, in part, methods and compositions that are useful for the diagnosis, treatment, or prevention of a blinding eye disease, including in the discovery of drugs that are efficacious against these diseases. Diseases include, for example, age related macular degeneration and reticular pseudodrusen disease, and the methods described herein include, for example, the method named delayed near infrared analysis (DNIRA).

  本发明部分涉及有助于诊断、治疗或预防致盲性眼病的方法和组合物，包括发现对这些疾病有效的药物。疾病包括，例如，与年龄相关的黄斑变性和网状假性变性疾病，本文所述的方法包括，例如，名为延迟近红外分析（DNIRA）的方法。