2-(benzylthio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile | 138608-95-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-(benzylthio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile
• 英文别名: 2-benzylsulfanyl-4-(4-methoxyphenyl)-6-oxo-1H-pyrimidine-5-carbonitrile
• CAS: 138608-95-4
• 化学式: C₁₉H₁₅N₃O₂S
• 分子量: 349.413
• InChiKey: ATEZFHHLPZOZKY-UHFFFAOYSA-N

物化性质

• 熔点：
  248-250 °C
• 沸点：
  518.2±60.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  99.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  哌啶-4-甲酰胺 、 2-(benzylthio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以41%的产率得到1-[2-Benzylsulfanyl-5-cyano-6-(4-methoxyphenyl)pyrimidin-4-yl]piperidine-4-carboxamide
  参考文献：
  名称：

  Synthesis of a 2,4,6-trisubstituted 5-cyano-pyrimidine library and evaluation of its immunosuppressive activity in a Mixed Lymphocyte Reaction assay

  摘要：

  A series of novel pyrimidine analogues were synthesized and evaluated for immunosuppressive activity in the Mixed Lymphocyte Reaction assay, which is well-known as the in vitro model for in vivo rejection after organ transplantation. Systematic variation of the substituents at positions 2, 4 and 6 of the pyrimidine scaffold led to the discovery of 2-benzylthio-5-cyano-6-(4-methoxyphenyl)-4-morpholinopyrimidine with an IC50 value of 1.6 mu M in the MLR assay. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.032
• 作为产物：
  描述：

  4-甲氧基苯甲醛 在 哌啶 、 potassium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 生成 2-(benzylthio)-4-(4-methoxyphenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile
  参考文献：
  名称：

  Synthesis of a 2,4,6-trisubstituted 5-cyano-pyrimidine library and evaluation of its immunosuppressive activity in a Mixed Lymphocyte Reaction assay

  摘要：

  A series of novel pyrimidine analogues were synthesized and evaluated for immunosuppressive activity in the Mixed Lymphocyte Reaction assay, which is well-known as the in vitro model for in vivo rejection after organ transplantation. Systematic variation of the substituents at positions 2, 4 and 6 of the pyrimidine scaffold led to the discovery of 2-benzylthio-5-cyano-6-(4-methoxyphenyl)-4-morpholinopyrimidine with an IC50 value of 1.6 mu M in the MLR assay. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.032

文献信息

• An efficient and facile synthesis of inhibitors for hepatitis C viral and anti-SARS agents: 4-aryl-5-cyano-1,6-dihydro-2-thiouracils
  作者：Liangce Rong、Shan Yin、Sheng Xia、Shimin Tao、Yanhui Shi、Shujiang Tu

  DOI：10.1007/s11164-011-0434-4

  日期：2012.3

  One-pot, multicomponent reaction for the synthesis of 4-aryl-5-cyano-1,6-dihydro-2-thiouracils via three-component from aromatic aldehydes, ethyl 2-cyanoacetate and S-benzylisothiourea hydrochloride (methyl carbamimidothioate sulfate) under methanol is described. These compounds have many drug activities, such as anti-hepatitis C viral, anti-Severe acute respiratory syndrome and anti-HIV-1 integrese activity. The advantages of this procedure include the short reaction time, mild reaction conditions and excellent yields.

  描述了一种一锅法多组分反应，通过芳香醛、乙基2-氰基乙酸酯和盐酸硫代脲苄基（甲基氨基硫酸酯）在甲醇中合成4-芳基-5-氰基-1,6-二氢-2-硫脲嘧啶的三组分反应。这些化合物具有多种药物活性，如抗丙型肝炎病毒、抗严重急性呼吸综合症和抗HIV-1整合酶活性。这种方法的优点包括反应时间短、反应条件温和和产率优秀。
• Synthesis and Anti-HIV-1 Integrase Activitiy of Cyano Pyrimidinones
  作者：R. Ramajayam、Nilesh B. Mahera、Nouri Neamati、Mange Ram Yadav、Rajani Giridhar

  DOI：10.1002/ardp.200900066

  日期：2009.12

  6‐dihydropyrimidine‐5‐carbonitrile were synthesized and tested against recombinant HIV‐1 integrase in an enzyme assay. 2‐(Phenethylthio)‐4‐(4‐chlorophenyl)‐6‐oxo‐1,6‐dihydropyrimidine‐5‐carbonitrile 4m and 2‐(phenethylthio)‐4‐(3‐chlorophenyl)‐6‐oxo‐1,6‐dihydropyrimidine‐5‐carbonitrile 4o showed significant inhibition against integrase in the assay (strand transfer: IC50 values of 16 and 17 μM, respectively).

  合成了一系列 2-苯乙基/苄硫基-6-氧代-4-苯基-1,6-二氢嘧啶-5-甲腈，并在酶测定中针对重组 HIV-1 整合酶进行了测试。2-(苯乙硫基)-4-(4-氯苯基)-6-氧代-1,6-二氢嘧啶-5-甲腈4m和2-(苯乙硫基)-4-(3-氯苯基)-6-氧代-1,6 -dihydropyrimidine-5-carbonitrile 4o 在测定中显示出对整合酶的显着抑制（链转移：IC50 值分别为 16 和 17 μM）。
• Synthesis, docking studies, and evaluation of pyrimidines as inhibitors of SARS-CoV 3CL protease
  作者：R. Ramajayam、Kian-Pin Tan、Hun-Ge Liu、Po-Huang Liang

  DOI：10.1016/j.bmcl.2010.04.118

  日期：2010.6

  A series of 2-(benzylthio)-6-oxo-4-phenyl-1,6-dihydropyrimidine as SARS-CoV 3CL protease inhibitors were developed and their potency was evaluated by in vitro protease inhibitory assays. Two candidates had encouraging results for the development of new anti-SARS compounds. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis of a 2,4,6-trisubstituted 5-cyano-pyrimidine library and evaluation of its immunosuppressive activity in a Mixed Lymphocyte Reaction assay
  作者：Alessandro Stella、Kristien Van Belle、Steven De Jonghe、Thierry Louat、Jean Herman、Jef Rozenski、Mark Waer、Piet Herdewijn

  DOI：10.1016/j.bmc.2012.12.032

  日期：2013.3

  A series of novel pyrimidine analogues were synthesized and evaluated for immunosuppressive activity in the Mixed Lymphocyte Reaction assay, which is well-known as the in vitro model for in vivo rejection after organ transplantation. Systematic variation of the substituents at positions 2, 4 and 6 of the pyrimidine scaffold led to the discovery of 2-benzylthio-5-cyano-6-(4-methoxyphenyl)-4-morpholinopyrimidine with an IC50 value of 1.6 mu M in the MLR assay. (C) 2013 Elsevier Ltd. All rights reserved.