4-氯-6-(甲氧基甲基)-2-苯基嘧啶 | 325685-59-4

• 物质功能分类: 医药中间体 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4-氯-6-(甲氧基甲基)-2-苯基嘧啶
• 中文别名: 4-氯-6-甲氧甲基-2-苯基嘧啶
• 英文名称: 4-chloro-6-methoxymethyl-2-phenylpyrimidine
• 英文别名: 4-chloro-6-methoxymethyl-2-phenyl-pyrimidine；4-Chloro-6-(methoxymethyl)-2-phenylpyrimidine
• CAS: 325685-59-4
• 化学式: C₁₂H₁₁ClN₂O
• 分子量: 234.685
• InChiKey: GSSSCZAOXFZADM-UHFFFAOYSA-N

物化性质

• 熔点：
  54-56°
• 沸点：
  258.5±22.0 °C(Predicted)
• 密度：
  1.220±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  4-氯-6-(甲氧基甲基)-2-苯基嘧啶 在 potassium permanganate 、 草酰氯 、 三溴化硼 、 三乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 4-{(S)-4-tert-butoxycarbonyl-2-[(6-chloro-2-phenyl-pyrimidine-4-carbonyl)-amino]-butyryl}-piperazine-1-carboxylic acid butyl ester
  参考文献：
  名称：

  Optimization of 2-phenyl-pyrimidine-4-carboxamides towards potent, orally bioavailable and selective P2Y12 antagonists for inhibition of platelet aggregation

  摘要：

  2-Phenyl-pyrimidine-4-carboxamide analogs were identified as P2Y12 antagonists. Optimization of the carbon-linked or nitrogen-linked substituent at the 6-position of the pyrimidine ring provided compounds with excellent ex vivo potency in the platelet aggregation assay in human plasma. Compound 23u met the objectives for activity, selectivity and ADMET properties.

  DOI：

  10.1016/j.bmcl.2014.06.070
• 作为产物：
  描述：

  6-(甲氧基甲基)-2-苯基-4-羟基嘧啶 生成 4-氯-6-(甲氧基甲基)-2-苯基嘧啶
  参考文献：
  名称：

  Phosphonic acid derivates and their use as P2Y12 receptor antagonists

  摘要：

  本发明涉及含有磷酸基团的2-苯基嘧啶衍生物及其作为P2Y12受体拮抗剂在治疗和/或预防外周血管、内脏、肝脏和肾脏血管、心血管和脑血管疾病或与血小板聚集有关的疾病或情况，包括人类和其他哺乳动物中的血栓形成的用途。 (I)。

  公开号：

  US08518912B2

文献信息

• Driven Evolution of a Constitutional Dynamic Library of Molecular Helices Toward the Selective Generation of [2 × 2] Gridlike Arrays under the Pressure of Metal Ion Coordination
  作者：Nicolas Giuseppone、Jean-Louis Schmitt、Jean-Marie Lehn

  DOI：10.1021/ja0666452

  日期：2006.12.1

  regioselectivity, occurring only at the extremities of the helical strands, allow one to perform directional terminal polymerization/depolymerization processes when starting with dissymmetric strands. A particular library is subsequently brought to express quantitatively [2 x 2] gridlike metallosupramolecular arrays in the presence of ZnII ions by component recombination generating the correct ligand from the dynamic

  结构动力学、自组装和螺旋折叠控制在高效的 Sc(OTf)3/微波催化的螺旋寡腙链的转化中结合在一起，通过组件的组装、解离和交换产生高度多样化的互变成分动态库. ScIII 促进的交换的转亚胺型机制及其区域选择性仅发生在螺旋链的末端，允许从不对称链开始时进行定向末端聚合/解聚过程。随后，在 ZnII 离子存在的情况下，通过从相互转换链的动态组中生成正确配体的组分重组，一个特定的库被用于定量表达 [2 x 2] 网格状金属超分子阵列。
• 2-PHENYL-6-AMINOCARBONYL-PYRIMIDINE DERIVATIVES AND THEIR USE AS P2Y12 RECEPTOR
  申请人：Caroff Eva

  公开号：US20090291962A1

  公开（公告）日：2009-11-26

  The invention relates to 2-phenyl-6-aminbcarbonyl-pyrimidinc derivatives and their use as P2Y 12 receptor antagonists in the treatment and/or prevention and/or treatment of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. Formula (1).

  这项发明涉及2-苯基-6-氨基羰基嘧啶衍生物及其作为P2Y12受体拮抗剂在治疗和/或预防和/或治疗外周血管、内脏-、肝脏和肾脏血管、心血管和脑血管疾病或与血小板聚集有关的疾病或病况的用途，包括人类和其他哺乳动物中的血栓形成。公式（1）。
• Pyrimidine Derivatives and Their Use as P2Y12 Receptor Antagonists
  申请人：Caroff Eva

  公开号：US20080194576A1

  公开（公告）日：2008-08-14

  The invention relates to 4-aminocarbonyl-pyrimidine derivatives and their use as P2Y 12 receptor antagonists in the treatment and/or prevention and/or treatment of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.

  该发明涉及4-氨基甲酰基嘧啶衍生物及其作为P2Y12受体拮抗剂在治疗和/或预防外周血管、内脏-、肝脏-和肾脏血管、心血管和脑血管疾病或与血小板聚集有关的疾病或状况的用途，包括在人类和其他哺乳动物中的血栓形成。
• Enforced Helicity: Efficient Access to Self-Organized Helical Molecular Strands by the Imine Route
  作者：Kevin M. Gardinier、Richard G. Khoury、Jean-Marie Lehn

  DOI：10.1002/1521-3765(20001117)6:22<4124::aid-chem4124>3.0.co;2-m

  日期：2000.11.17

  These molecular strands are shown to adopt helical conformations of 1.5 and 2.5 turns, respectively. The helical shape of 1 has been confirmed and structurally characterized by X-ray crystallography. The results indicate that the pyrimidine-hydrazone unit is a satisfatory helicity codon, so that the facile hydrazone formation provides an efficient procedure for generating helical structures. This

  两个低聚杂环醛 8 和 16 与双肼 17 缩合得到双腙1 和 2。显示这些分子链分别采用 1.5 和 2.5 圈的螺旋构象。1 的螺旋形状已被 X 射线晶体学证实并在结构上表征。结果表明嘧啶-腙单元是一个令人满意的螺旋密码子，因此容易的腙形成为产生螺旋结构提供了有效的方法。这极大地拓宽了基于设计的杂环序列来增强分子链螺旋性的方法的范围，并为各种衍生结构开辟了有趣的途径。
• 4-((<i>R</i>)-2-{[6-((<i>S</i>)-3-Methoxypyrrolidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino}-3-phosphonopropionyl)piperazine-1-carboxylic Acid Butyl Ester (ACT-246475) and Its Prodrug (ACT-281959), a Novel P2Y₁₂ Receptor Antagonist with a Wider Therapeutic Window in the Rat Than Clopidogrel
  作者：Eva Caroff、Francis Hubler、Emmanuel Meyer、Dorte Renneberg、Carmela Gnerre、Alexander Treiber、Markus Rey、Patrick Hess、Beat Steiner、Kurt Hilpert、Markus A. Riederer

  DOI：10.1021/acs.jmedchem.5b00933

  日期：2015.12.10

  Recent post hoc analyses of several clinical trials with P2Y(12) antagonists showed the need for new molecules being fully efficacious as antiplatelet agents and having a reduced propensity to cause major bleeding. We have previously reported the discovery of the 2-phenylpyrimidine-4-carboxamide analogs as P2Y(12) antagonists with nanomolar potency in the disease-relevant platelet aggregation assay in human plasma. Herein we present the optimization steps that led to the discovery of clinical candidate ACT-246475 (30d). The key step was the replacement of the carboxylic acid functionality by a phosphonic acid group which delivered the most potent molecules of the program. In addition, low in vivo clearance in rat and dog was achieved for the first time. Since the bioavailability of 30d was low in rat and dog, we developed the bis((isopropoxycarbonyl)oxy)methyl ester prodrug (ACT-281959, 45). Compound 30d showed efficacy in the rat ferric chloride thrombosis model when administered intravenously as parent or orally as its prodrug 45. Moreover, 30d displays a wider therapeutic window as compared to clopidogrel in the rat surgical blood loss model.