ethyl 2-((4-chloro-6-((2,3-dimethylphenyl)amino)pyrimidin-2-yl)sulfanyl)acetate | 54061-62-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: ethyl 2-((4-chloro-6-((2,3-dimethylphenyl)amino)pyrimidin-2-yl)sulfanyl)acetate
• 英文别名: [4-chloro-6-(2,3-dimethyl-anilino)-pyrimidin-2-ylsulfanyl]-acetic acid ethyl ester；[4-chloro-6-(2,3-dimethylphenylamino)pyrimidin-2-ylsulfanyl]acetic Acid Ethyl Ester；[4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid ethyl ester；ethyl 2-[4-chloro-6-(2,3-dimethylanilino)pyrimidin-2-yl]sulfanylacetate
• CAS: 54061-62-0
• 化学式: C₁₆H₁₈ClN₃O₂S
• 分子量: 351.857
• InChiKey: VLHVDZUDKXZHOH-UHFFFAOYSA-N

物化性质

• 熔点：
  88-90 °C(Solv: ethanol (64-17-5))
• 沸点：
  480.9±45.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  89.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 2-((4-chloro-6-((2,3-dimethylphenyl)amino)pyrimidin-2-yl)sulfanyl)acetate 在 乙醇 、 potassium hydroxide 作用下， 生成 匹立尼酸
  参考文献：
  名称：

  Rational design of a pirinixic acid derivative that acts as subtype-selective PPARγ modulator

  摘要：

  Peroxisome proliferator-activated receptor gamma (PPAR gamma) is involved in glucose and lipid homeostasis. PPAR gamma agonists are in clinical use for the treatment of type 2 diabetes. Lately, a new class of selective PPAR gamma modulators (SPPAR gamma Ms) was developed, which are believed to show less side effects than full PPAR gamma agonists. We have previously shown that alpha-substitution of pirinixic acid, a moderate agonist of PPAR alpha and PPAR gamma, leads to low micromolar active balanced dual agonists of PPAR alpha and PPAR alpha. Herein we present modifications of pirinixic acid leading to subtype-selective PPAR gamma agonists and furthermore the development of a selective PPAR gamma modulator guided by molecular docking studies. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.03.008
• 作为产物：
  描述：

  3-(二甲基氨基)-2-(2-噻吩羰基)-丙烯腈 在 三乙胺 、 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 9.0h， 生成 ethyl 2-((4-chloro-6-((2,3-dimethylphenyl)amino)pyrimidin-2-yl)sulfanyl)acetate
  参考文献：
  名称：

  调优Wy14,643对选择性类视黄醇X受体调制的核受体选择性。

  摘要：

  脂肪酸感应核受体家族类视黄醇X受体（RXRs）和过氧化物酶体增殖物激活受体（PPARs）在神经退行性变中具有治疗潜力。在这种情况下，Wy14,643的有价值的多效性活性超过了其已知的PPAR激动特性。在这里，我们将化合物表征为RXR激动剂，解释了多效性效应，并报告了其系统的结构-活性关系分析，并发现了驱动PPAR和RXR的特定分子决定因素。我们设计了该药物的紧密类似物，包括对RXR和PPAR的选择性和双重激动作用，可以作为研究各种病理学中核受体的作用和相互作用的优良药理学工具。系统优化的高效RXR激动剂揭示了体内活性和脑中活性浓度。与传统的类维生素A相比，由于缺乏RXR /肝X受体介导的副作用和出色的特性，它建立了新型的创新RXR调节剂，以克服针对RXR靶向药物发现的关键挑战。

  DOI：

  10.1021/acs.jmedchem.8b01848

文献信息

• 2-PYRIMIDINYLTHIO)ALKANOIC ACIDS, ESTERS, AMIDES AND HYDRAZIDES
  申请人：——

  公开号：US03940394A1

  公开（公告）日：1976-02-24

  (2-Pyrimidinylthio)alkanoic acid, esters, amides and hydrazides as well as various 4- and 6-substituted derivatives thereof as depicted by the structural formula: ##SPC1## In which R and R.sup.2 are independently --H or lower alkyl; R.sup.1 is --H, -halo or lower alkoxy; Z is --OH, OM, lower alkoxy or --(NH).sub.1 --NH.sub.2, wherein p is 0 to 1 and M is an alkali metal, alkaline earth metal or ammonium cation; Y is an aryl, amino or substituted amino radical; and m is an integer from 0 to 2, exhibit anti-lipemic activity in warm-blooded animals.

  (2-嘧啶基硫)烷酸，酯，酰胺和肼以及各种4-和6-取代衍生物，如下所示的结构式：##SPC1## 其中R和R.sup.2独立为--H或较低的烷基；R.sup.1为--H，-卤素或较低的烷氧基；Z为--OH，OM，较低的烷氧基或--(NH).sub.1 --NH.sub.2，其中p为0至1，M为碱金属，碱土金属或铵阳离子；Y为芳基，氨基或取代氨基基团；m为0至2的整数，在温血动物中表现出抗脂质活性。
• α-Alkyl Substituted Pirinixic Acid Derivatives as Potent Dual Agonists of the Peroxisome Proliferator Activated Receptor Alpha and Gamma
  作者：Oliver Rau、Yvonne Syha、Heiko Zettl、Michael Kock、Andreas Bock、Manfred Schubert-Zsilavecz

  DOI：10.1002/ardp.200700209

  日期：2008.3

  Peroxisome proliferator‐activated receptors (PPAR) are nuclear receptors, playing a pivotal role in energy homeostasis. Activators of the PPARα subtype are in widespread use for the treatment of hyperlipidemia, while activators of the PPARγ subtype are in clinical use for the treatment of type‐2 diabetes. Since both of these diseases are frequently associated, the combined treatment with one drug simultaneously

  过氧化物酶体增殖物激活受体 (PPAR) 是核受体，在能量稳态中起关键作用。PPARα 亚型激活剂广泛用于治疗高脂血症，而 PPARγ 亚型激活剂在临床上用于治疗 2 型糖尿病。由于这两种疾病经常相互关联，因此用一种同时激活 PPARα 和 PPARγ 的药物进行联合治疗似乎是值得的。从吡立昔酸开始，它是一种中等活性的双 PPARα/γ 激动剂，我们通过用脂肪链取代 α- 位来提高对人 PPARα 和 PPARγ 的效力。分别在四个碳和六个碳的链长处达到最大效果，导致 PPARα 的活性诱导因子分别为 36 和 PPARγ 的因子为 18。
• Compounds, compositions and methods for modulating beta-amyloid production
  申请人：Active Pass Pharmaceuticals, Inc.

  公开号：US20030191144A1

  公开（公告）日：2003-10-09

  Methods and compositions useful in the treatment of amyloidosis and conditions and diseases associated therewith, such as Alzheimer's disease, are provided. The methods involve administering to a subject in need thereof a pharmaceutical composition including one or more agents that modulate PPAR&agr; and/or PPAR&dgr; activity, resulting in an inhibition of &bgr;-amyloid production and/or release from cells of the subject, particularly brain cells.

  提供了在治疗淀粉样变性及相关疾病和病况（如阿尔茨海默病）中有用的方法和组合物。这些方法涉及向需要治疗的对象施用包括一个或多个调节PPAR&agr;和/或PPAR&dgr;活性的药物组合物，导致抑制β-淀粉样蛋白从对象的细胞（尤其是脑细胞）中的产生和/或释放。
• Novel pyrimidine and 1,3,5-triazine hypolipemic agents
  作者：Gaetano D'Atri、Piero Gomarasca、Giuseppe Resnati、Giovanni Tronconi、Carlo Scolastico、Cesare R. Sirtori

  DOI：10.1021/jm00378a016

  日期：1984.12

  New compounds were synthesized by changing the substituents of a trisubstituted pyrimidine, i.e., [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio] acetic acid, a potent hypolipidemic agent, impaired, however, by a marked hepatomegaly-inducing effect. The structural variations led to the subsidence (14b, i.e., 4-chloro-2-(dimethylamino)-6-[(2,3-dimethylphenyl)amino]pyrimidine) or to the reduction (18b, [[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]amino] acetic acid) of said untoward effect but still maintained the hypolipidemic effect that, although markedly decreased, still proves significant for serum cholesterol and triglycerides (18b) or for serum triglycerides only (14b).
• DATRI, G.;GOMARASCA, P.;RESNATI, G.;TRONCONI, G.;SCOLASTICO, C.;SIRTORI, +, J. MED. CHEM., 1984, 27, N 12, 1621-1629
  作者：DATRI, G.、GOMARASCA, P.、RESNATI, G.、TRONCONI, G.、SCOLASTICO, C.、SIRTORI, +

  DOI：——

  日期：——