methyl 2-(acetylthio)-2-(4-methoxyphenyl)acetate

• 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-(acetylthio)-2-(4-methoxyphenyl)acetate
• 英文别名: methyl (acetylthio)(p-methoxyphenyl)acetate；Methyl 2-acetylsulfanyl-2-(4-methoxyphenyl)acetate
• 化学式: C₁₂H₁₄O₄S
• 分子量: 254.307
• InChiKey: ULUULGBTCHKGGU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  77.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2-(acetylthio)-2-(4-methoxyphenyl)acetate 在 甲醇 、 potassium hydroxide 作用下， 反应 5.5h， 以99%的产率得到2-mercapto-2-(4-methoxyphenyl)acetic acid
  参考文献：
  名称：

  Development and evaluation of ST-1829 based on 5-benzylidene-2-phenylthiazolones as promising agent for anti-leukotriene therapy

  摘要：

  Different inflammatory diseases and allergic reactions are mediated by leukotrienes, which arise from the oxygenation of arachidonic acid catalyzed by 5-lipoxygenase (5-LO). One promising approach for an effective anti-leukotriene therapy is the inhibition of this key enzyme. This study presents the synthesis and development of a potent and direct 5-LO inhibitor based on the well characterized 5-benzylidene-2-phenylthiazolone C06, whose further pharmacological investigation was precluded due to its low solubility. Through optimization of C06, evaluation of structure activity relationships including profound assessment of the thiazolone core and consideration of the solubility, the 5-benzyl-2-phenyl-4-hydroxythiazoles represented by 46 (ST-1829, 5-(4-chlorobenzyl)-2-p-tolylthiazol-4-ol) were developed. Compound 46 showed an improved 5-LO inhibitory activity in cell-based (IC50 values 0.14 mu M) and cell-free assays (IC50 values 0.03 mu M) as well as a prominent enhanced solubility. Furthermore, it kept its promising inhibitory potency in the presence of blood serum, excluding excessive binding to serum proteins. These facts combined with the non-cytotoxic profile mark a major step towards an effective anti-inflammatory therapy. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.10.054
• 作为产物：
  描述：

  4-甲氧基苯乙酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 sodium hydride 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 6.0h， 生成 methyl 2-(acetylthio)-2-(4-methoxyphenyl)acetate
  参考文献：
  名称：

  Development and evaluation of ST-1829 based on 5-benzylidene-2-phenylthiazolones as promising agent for anti-leukotriene therapy

  摘要：

  Different inflammatory diseases and allergic reactions are mediated by leukotrienes, which arise from the oxygenation of arachidonic acid catalyzed by 5-lipoxygenase (5-LO). One promising approach for an effective anti-leukotriene therapy is the inhibition of this key enzyme. This study presents the synthesis and development of a potent and direct 5-LO inhibitor based on the well characterized 5-benzylidene-2-phenylthiazolone C06, whose further pharmacological investigation was precluded due to its low solubility. Through optimization of C06, evaluation of structure activity relationships including profound assessment of the thiazolone core and consideration of the solubility, the 5-benzyl-2-phenyl-4-hydroxythiazoles represented by 46 (ST-1829, 5-(4-chlorobenzyl)-2-p-tolylthiazol-4-ol) were developed. Compound 46 showed an improved 5-LO inhibitory activity in cell-based (IC50 values 0.14 mu M) and cell-free assays (IC50 values 0.03 mu M) as well as a prominent enhanced solubility. Furthermore, it kept its promising inhibitory potency in the presence of blood serum, excluding excessive binding to serum proteins. These facts combined with the non-cytotoxic profile mark a major step towards an effective anti-inflammatory therapy. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.10.054

文献信息

• Urea-Induced Acid Amplification: A New Approach for Metal-Free Insertion Chemistry
  作者：Erica D. Couch、Tyler J. Auvil、Anita E. Mattson

  DOI：10.1002/chem.201403283

  日期：2014.7.1

  α‐aryldiazoacetates in high yield. This methodology was found to be generally applicable to a broad substrate scope and presents a conceptually new approach for organocatalytic diazo insertion reactions. Mechanistic investigations suggest that the reaction pathway involves a urea‐induced protonation of the α‐aryldiazoester.

  事实证明，增强二氟硼酸脲的催化活性对于提高酸度α-芳基重氮乙酸酯的无金属OH和SH插入反应而言是必不可少的。发现该方法通常适用于广泛的底物范围，并且提出了用于有机催化重氮插入反应的概念上新的方法。机理研究表明，该反应途径涉及尿素诱导的α-芳基重氮酯的质子化。
• Study of the Rh2(OAc)4- or BF3·OEt2-Mediated Reaction of Thioacetic S-Acid with α-Diazocarbonyl Compounds
  作者：Wengang Yao、Mingyi Liao、Xiaomei Zhang、Hao Xu、Jianbo Wang

  DOI：10.1002/ejoc.200210592

  日期：2003.5

  The Rh2(OAc)4-catalyzed reaction of methyl aryldiazoacetates with thioacetic S-acid gives exclusively the S−H insertion products in high yields, while the corresponding reaction mediated by BF3·OEt2 gives O-esters. The mechanism of the reaction is discussed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003

  Rh2(OAc)4 催化重氮基乙酸甲酯与硫代乙酸 S-酸的反应以高产率仅产生 S-H 插入产物，而由 BF3·OEt2 介导的相应反应产生 O-酯。讨论了反应机理。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003
• PROCESS FOR PRODUCING THIOPHENE COMPOUND AND INTERMEDIATE THEREOF
  申请人：Yanagihara Kazufumi

  公开号：US20110124884A1

  公开（公告）日：2011-05-26

  To provide a novel process for producing a 2-aryl-3-hydroxy-4-substituted carbonyl thiophene compound or an intermediate thereof useful as an intermediate for production of medicines and agricultural chemicals. A 2-aryl acetate compound represented by the formula (1): wherein R 1 is an aryl group or the like, R 4 is a C 1-3 alkyl group or the like, and X is a leaving group, is reacted with a thioacetic acid compound to form a thioacetyl compound (3), the thioacetyl compound (3) is reacted with a vinyl ketone compound to form a γ-ketosulfide compound (5), which is cyclized under basic conditions to form a dihydrothiophene compound (6), and the dihydrothiophene compound (6) is oxidized by using an oxidizing agent to produce a 2-aryl-3-hydroxy-4-substituted carbonyl thiophene compound (7).

  提供一种新型方法，用于生产用作药物和农药中间体的2-芳基-3-羟基-4-取代羰基噻吩化合物或其中间体。将式（1）代表的2-芳基乙酸酯化合物：其中R1是芳基或类似物，R4是C1-3烷基或类似物，X是离去基团，与硫代乙酸化合物反应形成硫代乙酰化合物（3），硫代乙酰化合物（3）与乙烯基酮化合物反应形成γ-酮磺醚化合物（5），在碱性条件下环化形成二氢噻吩化合物（6），使用氧化剂氧化二氢噻吩化合物（6）以产生2-芳基-3-羟基-4-取代羰基噻吩化合物（7）。
• PROCESS FOR PRODUCTION OF THIOPHENE COMPOUND AND INTERMEDIATE THEREOF
  申请人：Nissan Chemical Industries, Ltd.

  公开号：EP2246343B1

  公开（公告）日：2016-05-18
• US8399685B2
  申请人：——

  公开号：US8399685B2

  公开（公告）日：2013-03-19