2-(4-methylsulfanylbenzyl)malonic acid diethyl ester | 124663-44-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-(4-methylsulfanylbenzyl)malonic acid diethyl ester
• 英文别名: diethyl 2-(4-(methylthio)benzyl)malonate；Diethyl 2-[(4-methylsulfanylphenyl)methyl]propanedioate
• CAS: 124663-44-1
• 化学式: C₁₅H₂₀O₄S
• 分子量: 296.387
• InChiKey: QGLDQIPGKPWSFL-UHFFFAOYSA-N

物化性质

• 沸点：
  389.9±32.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 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：

  2-(4-methylsulfanylbenzyl)malonic acid diethyl ester 在 sodium hydroxide 、 sodium hydride 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 11.0h， 生成 2-[2-(Dimethylamino)ethyl]-2-[(4-methylsulfanylphenyl)methyl]propanedioic acid
  参考文献：
  名称：

  Structure−Activity Relationships of Dimethindene Derivatives as New M₂-Selective Muscarinic Receptor Antagonists

  摘要：

  A series of 2,3-disubstituted indenes, which are analogues of the widely used histamine H, receptor antagonist dimethindene, have been synthesized and studied as muscarinic and histamine receptor antagonists. The affinities of these compounds for the five human muscarinic receptor subtypes (M-1-M-5) and for human histamine H, receptors were determined in radioligand binding studies using membranes from transfected Chinese hamster ovary (CHO) cells and [H-3]N-methylscopolamine ([H-3]NMS). The results demonstrate that the diisopropyl analogue 19 has a similar high affinity as (S)-dimethindene at M-2 receptors ((S)-dimethindene: pK(i) = 7.52; (-)-19: pK(i) = 7.37) with an improved selectivity pattern ((S)-dimethindene: M-2/M-1 = 6-fold, M-2/M-3 = 5-fold, M-2/M-4 = 10-fold, M-2/M-5 = 25-fold; (-)-19: M-2/M-1 = 36-fold, M-2/M-3 = 96-fold, M-2/M-4 = 42-fold, M-2/M-5 = 275-fold). In addition, compound (-)-19 showed 35-fold lower affinity at histamine H-1 receptors (pK(i) = 5.61) than (S)-dimethindene (pK(i) = 7.16). Another interesting compound is the fluoroethyl derivative 20 (pK(i)/M-2 = 7.49), which also exhibits a higher M-2 selectivity (M-2/M-1 = 19-fold; M-2/M-3 = 22-fold; M-2/M-4 = 13-fold; M-2/ M-5 = 62-fold) than (S)-dimethindene. Unfortunately, compound 20 also shows a high affinity for histamine H-1 receptors (pK(i) = 8.14). The compound with the highest affinity for M-2 receptors (pK(i) = 7.91), the dimethylaminomethylene analogue 31, displayed only a small preference for M-2 receptors. In conclusion, compound (-)-19 might be useful to test the hypothesis that blockade of muscarinic M-2 receptors in the brain is a viable mechanism by which to produce improved cognition. This second-generation dimethindene analogue might also be the starting point for the development Of M-2-selective muscarinic antagonists useful for quantifying M-2 receptors in the central nervous system with positron emission tomography imaging.

  DOI：

  10.1021/jm020895l
• 作为产物：
  描述：

  茴香硫醚 在 三氯化铝 、 乙醇 、 sodium 作用下， 以 乙二醇二甲醚 为溶剂， 反应 7.0h， 生成 2-(4-methylsulfanylbenzyl)malonic acid diethyl ester
  参考文献：
  名称：

  Structure−Activity Relationships of Dimethindene Derivatives as New M₂-Selective Muscarinic Receptor Antagonists

  摘要：

  A series of 2,3-disubstituted indenes, which are analogues of the widely used histamine H, receptor antagonist dimethindene, have been synthesized and studied as muscarinic and histamine receptor antagonists. The affinities of these compounds for the five human muscarinic receptor subtypes (M-1-M-5) and for human histamine H, receptors were determined in radioligand binding studies using membranes from transfected Chinese hamster ovary (CHO) cells and [H-3]N-methylscopolamine ([H-3]NMS). The results demonstrate that the diisopropyl analogue 19 has a similar high affinity as (S)-dimethindene at M-2 receptors ((S)-dimethindene: pK(i) = 7.52; (-)-19: pK(i) = 7.37) with an improved selectivity pattern ((S)-dimethindene: M-2/M-1 = 6-fold, M-2/M-3 = 5-fold, M-2/M-4 = 10-fold, M-2/M-5 = 25-fold; (-)-19: M-2/M-1 = 36-fold, M-2/M-3 = 96-fold, M-2/M-4 = 42-fold, M-2/M-5 = 275-fold). In addition, compound (-)-19 showed 35-fold lower affinity at histamine H-1 receptors (pK(i) = 5.61) than (S)-dimethindene (pK(i) = 7.16). Another interesting compound is the fluoroethyl derivative 20 (pK(i)/M-2 = 7.49), which also exhibits a higher M-2 selectivity (M-2/M-1 = 19-fold; M-2/M-3 = 22-fold; M-2/M-4 = 13-fold; M-2/ M-5 = 62-fold) than (S)-dimethindene. Unfortunately, compound 20 also shows a high affinity for histamine H-1 receptors (pK(i) = 8.14). The compound with the highest affinity for M-2 receptors (pK(i) = 7.91), the dimethylaminomethylene analogue 31, displayed only a small preference for M-2 receptors. In conclusion, compound (-)-19 might be useful to test the hypothesis that blockade of muscarinic M-2 receptors in the brain is a viable mechanism by which to produce improved cognition. This second-generation dimethindene analogue might also be the starting point for the development Of M-2-selective muscarinic antagonists useful for quantifying M-2 receptors in the central nervous system with positron emission tomography imaging.

  DOI：

  10.1021/jm020895l

文献信息

• Highly Efficient Molybdenum(II)-Catalyzed Intramolecular Allylic Alkylation of Arenes
  作者：Marco Bandini、Astrid Eichholzer、Peter Kotrusz、Achille Umani-Ronchi

  DOI：10.1002/adsc.200700607

  日期：2008.3.7

  The Friedel–Crafts-type intramolecular allylic alkylation of simple arenes is performed in the presence of a catalytic amount of [Mo(II) (CO)4Br2]2 (2.5 mol%). The moisture-tolerant protocol provided a mild and direct access to a large library of functionalized 4-vinyl-1,2,3,4-tetrahydronaphthalenes in high yields.

  简单芳烃的Friedel-Crafts型分子内烯丙基烷基化反应是在催化量的[Mo（II）（CO）4 Br 2 ] 2（2.5 mol％）的存在下进行的。耐湿协议可以温和而直接地以高产率直接访问功能化的4-乙烯基-1,2,3,4-四氢萘的大型文库。
• [EN] HETEROCYCLIC INHIBITORS OF ENPP1<br/>[FR] INHIBITEURS HÉTÉROCYCLIQUES D'ENPP1
  申请人：VOLASTRA THERAPEUTICS INC

  公开号：WO2021257614A1

  公开（公告）日：2021-12-23

  The present disclosure relates generally to inhibitors of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), compositions thereof, and methods of using said compounds and compositions thereof. More specifically, the present disclosure relates to triazolopyrimidine and imidazolopyrimidine inhibitors of ENPP1 and methods of their use for treating disease mediated by ENPP1.

  本公开涉及抑制细胞外核苷酸焦磷酸酶/磷酸二酯酶1（ENPP1）的抑制剂，其组成物和使用该化合物和其组成物的方法。更具体地，本公开涉及三唑嘧啶和咪唑嘧啶抑制剂的ENPP1及其使用方法，用于治疗由ENPP1介导的疾病。
• Ligand-Free Silver(I)-Catalyzed Intramolecular Friedel-Crafts Alkylation of Arenes with Allylic Alcohols
  作者：Marco Bandini、Astrid Eichholzer、Peter Kotrusz、Michele Tragni、Stefano Troisi、Achille Umani-Ronchi

  DOI：10.1002/adsc.200800628

  日期：2009.2

  Abstractmagnified imageThe silver‐catalyzed direct activation of allylic alcohols as electrophilic partners for intramolecular Friedel–Crafts alkylation of arenes is described. Use of silver triflate (AgOTf; 10 mol%) enabled functionalized 1‐vinyl‐1,2,3,4‐tetrahydronaphthalenes and a 4‐vinyl‐1,2,3,4‐tetrahydroisoquinoline to be isolated in good yields with high levels of regiochemistry, under a ligand‐free regime.