dimethylthiocarbamic acid O-(4-acetyl-2-methoxy-phenyl) ester | 69114-69-8

• 英文名称: dimethylthiocarbamic acid O-(4-acetyl-2-methoxy-phenyl) ester
• 英文别名: 4-dimethylthiocarbamoyloxy-3-methoxyacetophenone；O-(4-acetyl-2-methoxyphenyl) N,N-dimethylcarbamothioate
• CAS: 69114-69-8
• 化学式: C₁₂H₁₅NO₃S
• 分子量: 253.322
• InChiKey: WZKSGMFRHHJIKZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  70.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  dimethylthiocarbamic acid O-(4-acetyl-2-methoxy-phenyl) ester 在 氢氧化钾 作用下， 以 乙二醇 为溶剂， 反应 2.0h， 生成 1-(4-thio-3-methoxyphenyl)ethanone
  参考文献：
  名称：

  Carboxy-Substituted Cinnamides:  A Novel Series of Potent, Orally Active LTB₄ Receptor Antagonists

  摘要：

  A series of carboxy-substituted cinnamides were investigated as antagonists of the human cell surface leukotriene B-4 (LTB4) receptor. Binding was determined through measurement of [H-3]-LTB4 displacement from human neutrophils. Receptor antagonism was confirmed through a functional assay, which measures inhibition of Ca2+ release in human neutrophils. Potent antagonists were discovered through optimization of a random screening hit, a p-(alpha-methylbenzyloxy)cinnamide, having low-micromolar activity. Substantial improvement of in vitro potency was realized by the attachment of a carboxylic acid moiety to the cinnamide phenyl ring through a flexible tether, leading to identification of compounds with low-nanomolar potency. Modification of the benzyloxy substituent, either through ortho-substitution on the benzyloxy phenyl group or through replacement of the ether oxygen with a methylene or sulfur atom, produced achiral antagonists of equal or greater potency. The most potent compounds in vitro were assayed for oral activity using the arachidonic acid-induced mouse ear edema model of inflammation. Several compounds in this series were found to significantly inhibit edema formation and myeloperoxidase activity in this model up to 17 h after oral administration. Representatives of this series have been shown to be potent and long-acting orally active inhibitors of the LTB4 receptor.

  DOI：

  10.1021/jm980540v
• 作为产物：
  描述：

  二甲氨基硫代甲酰氯 、 香草乙酮 在 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 生成 dimethylthiocarbamic acid O-(4-acetyl-2-methoxy-phenyl) ester
  参考文献：
  名称：

  EP1690538

  摘要：

  公开号：

文献信息

• Aryl-substituted acrylamides with Leukotriene B4 (LTB-4) receptor antagonist activity
  申请人：Novartis AG

  公开号：US06291530B1

  公开（公告）日：2001-09-18

  Disclosed are compounds of formula (I) wherein W is CH or N; R is (mono- or di cabocyclic or heterocyclic aryl)-lower alkyl; R1 is hydrogen or lower alkyl; R2 and R3 are hydrogen, lower alkyl, lower alkoxy-lower alkyl or aryl-lower alkyl; or R2 and R3 joined together represent lower alkylene optionally interrupted by O, NH, N-lower alkyl or S so as to form a ring with the amide nitrogen; X is O, S, SO, S2 or a direct bond; X1 is O, S, SO, SO2 or a direct bond; Y is a direct bond, lower alkylene or lower alkylidene; and Z is carboxyl, 5-tetrazolyl,, hydroxymethyl or carboxyl derivatized in the form of a pharmaceutically acceptable ester, and pharmaceutically acceptable salts thereof; which arm useful as LTB-4 antagonists.

  本发明涉及一种式子（I）的化合物，其中W为CH或N；R为（单环或双环芳基或杂环芳基）-较低烷基；R1为氢或较低烷基；R2和R3为氢、较低烷基、较低烷氧基-较低烷基或芳基-较低烷基；或者R2和R3结合在一起，用较低烷基烷基可选地中断的O、NH、N-较低烷基或S表示，以形成与酰胺氮原子形成环的环；X为O、S、SO、S2或直接键；X1为O、S、SO、SO2或直接键；Y为直接键、较低烷基或较低烷基亚甲基；Z为羧基、5-四唑基、羟甲基或以药学上可接受的酯形式衍生的羧基，并且其药学上可接受的盐；它们有用作LTB-4拮抗剂。
• Structural Factors Affecting Cytotoxic Activity of (<i>E</i>)-1-(Benzo[<i>d </i>][1,3]oxathiol-6-yl)-3-phenylprop-2-en-1-one Derivatives
  作者：Marek T. Konieczny、Anita Bułakowska、Justyna Polak、Danuta Pirska、Wojciech Konieczny、Patrycja Gryń、Andrzej Skladanowski、Michał Sabisz、Krzysztof Lemke、Anna Pieczykolan、Marlena Gałązka、Katarzyna Wiciejowska、Joanna Wietrzyk

  DOI：10.1111/cbdd.12296

  日期：2014.7

  Derivatives of (E)‐1‐(5‐alkoxybenzo[d][1,3]oxathiol‐6‐yl)‐3‐phenylprop‐2‐en‐1‐one demonstrated exceptionally high in vitro cytotoxic activity, with IC50 values of the most active derivatives in the nanomolar range. To identify structural fragments necessary for the activity, several analogs deprived of selected fragments were prepared, and their cytotoxic activity was tested. It was found that the activity depends on combined effects of (i) the heterocyclic ring, (ii) the alkoxy group at position 5 of the benzoxathiole ring, and (iii) the substituents in the phenyl ring B. Replacement of the sulfur atom by oxygen does not influence the activity. None of the listed structural fragments alone assured high cytotoxic activity.
• ARYL-SUBSTITUTED ACRYLAMIDES WITH LEUKOTRIENE B4 (LTB-4) RECEPTOR ANTAGONIST ACTIVITY
  申请人：Novartis AG

  公开号：EP0942903A1

  公开（公告）日：1999-09-22
• US4178442A
  申请人：——

  公开号：US4178442A

  公开（公告）日：1979-12-11
• US6291530B1
  申请人：——

  公开号：US6291530B1

  公开（公告）日：2001-09-18