2-((4-chloro-6-((2,3-dimethylphenyl)(methyl)amino)pyrimidin-2-yl)sulfanyl)acetic acid | 86627-39-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-((4-chloro-6-((2,3-dimethylphenyl)(methyl)amino)pyrimidin-2-yl)sulfanyl)acetic acid
• 英文别名: 2-[4-chloro-6-(N,2,3-trimethylanilino)pyrimidin-2-yl]sulfanylacetic acid
• CAS: 86627-39-6
• 化学式: C₁₅H₁₆ClN₃O₂S
• 分子量: 337.83
• InChiKey: QPKAYXPTNWRYPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  91.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  {4-Chloro-6-[(2,3-dimethyl-phenyl)-methyl-amino]-pyrimidin-2-ylsulfanyl}-acetic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 0.08h， 以75.8%的产率得到2-((4-chloro-6-((2,3-dimethylphenyl)(methyl)amino)pyrimidin-2-yl)sulfanyl)acetic acid
  参考文献：
  名称：

  Novel pyrimidine and 1,3,5-triazine hypolipemic agents

  摘要：

  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).

  DOI：

  10.1021/jm00378a016

文献信息

• Tuning Nuclear Receptor Selectivity of Wy14,643 towards Selective Retinoid X Receptor Modulation
  作者：Julius Pollinger、Leonie Gellrich、Simone Schierle、Whitney Kilu、Jurema Schmidt、Lena Kalinowsky、Julia Ohrndorf、Astrid Kaiser、Jan Heering、Ewgenij Proschak、Daniel Merk

  DOI：10.1021/acs.jmedchem.8b01848

  日期：2019.2.28

  The fatty acid sensing nuclear receptor families retinoid X receptors (RXRs) and peroxisome proliferator-activated receptors (PPARs) hold therapeutic potential in neurodegeneration. Valuable pleiotropic activities of Wy14,643 in models of such conditions exceed its known PPAR agonistic profile. Here, we characterize the compound as an RXR agonist explaining the pleiotropic effects and report its systematic

  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。
• 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。
• 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：——
• 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).