2,4-diamino-5-methyl-furo[2,3-d]pyrimidine | 67194-84-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃[2,3-d]嘧啶
• 英文名称: 2,4-diamino-5-methyl-furo[2,3-d]pyrimidine
• 英文别名: 5-methylfuro[2,3-d]pyrimidine-2,4-diamine
• CAS: 67194-84-7
• 化学式: C₇H₈N₄O
• 分子量: 164.167
• InChiKey: IPOUWOKMRNPBCG-UHFFFAOYSA-N

物化性质

• 熔点：
  264-266 °C
• 沸点：
  445.9±55.0 °C(Predicted)
• 密度：
  1.444±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  91
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,4-diamino-5-methyl-furo[2,3-d]pyrimidine 、 1-奈硫酚 在 碘 作用下， 以 乙醇 、 水 为溶剂， 以52.5%的产率得到2,4-diamino-5-methyl-6-(1-naphthylthio)furo[2,3-d]pyrimidine
  参考文献：
  名称：

  2,4-二氨基-5-甲基-6-取代芳硫基-呋喃[2,3-d]嘧啶作为新型经典和非经典抗叶酸剂作为潜在的双胸苷酸合酶和二氢叶酸还原酶抑制剂

  摘要：

  一种新型经典抗叶酸剂N -{4-[(2,4-diamino-5-methyl-furo[2,3 - d ]pyrimidin-6-yl)thio]-benzoyl} -l -glutamic acid 5和 11 非经典抗叶酸剂6 - 16被设计、合成并评估为二氢叶酸还原酶 (DHFR) 和胸苷酸合酶 (TS) 的抑制剂。非经典化合物6-16是由20通过使用碘氧化加成取代的苯硫酚合成的。中间体酸21 的肽偶联，然后皂化得到经典的类似物5。化合物5据我们所知，第一个例子是 2,4-二氨基呋喃 [2,3- d ]嘧啶经典抗叶酸，它对人类 DHFR 和人类 TS 都具有抑制活性。与哺乳动物 DHFR 相比，经典类似物5是卡氏肺囊虫DHFR 和鸟分枝杆菌DHFR的纳摩尔抑制剂和显着选择性抑制剂，分别为 263 倍和 2107 倍。非经典类似物6-16对病原体 DHFR 或 TS 具有中等效力。该研究表明呋喃[2

  DOI：

  10.1016/j.bmc.2009.11.029
• 作为产物：
  描述：

  一氯丙酮 、 2,4-二氨基-6-羟基嘧啶 以 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 以26%的产率得到2,4-diamino-5-methyl-furo[2,3-d]pyrimidine
  参考文献：
  名称：

  2,4-二氨基-5-甲基-6-取代芳硫基-呋喃[2,3-d]嘧啶作为新型经典和非经典抗叶酸剂作为潜在的双胸苷酸合酶和二氢叶酸还原酶抑制剂

  摘要：

  一种新型经典抗叶酸剂N -{4-[(2,4-diamino-5-methyl-furo[2,3 - d ]pyrimidin-6-yl)thio]-benzoyl} -l -glutamic acid 5和 11 非经典抗叶酸剂6 - 16被设计、合成并评估为二氢叶酸还原酶 (DHFR) 和胸苷酸合酶 (TS) 的抑制剂。非经典化合物6-16是由20通过使用碘氧化加成取代的苯硫酚合成的。中间体酸21 的肽偶联，然后皂化得到经典的类似物5。化合物5据我们所知，第一个例子是 2,4-二氨基呋喃 [2,3- d ]嘧啶经典抗叶酸，它对人类 DHFR 和人类 TS 都具有抑制活性。与哺乳动物 DHFR 相比，经典类似物5是卡氏肺囊虫DHFR 和鸟分枝杆菌DHFR的纳摩尔抑制剂和显着选择性抑制剂，分别为 263 倍和 2107 倍。非经典类似物6-16对病原体 DHFR 或 TS 具有中等效力。该研究表明呋喃[2

  DOI：

  10.1016/j.bmc.2009.11.029
• 作为试剂：
  描述：

  哌嗪 、 3-氨基-8-甲基-2,4,9-噻唑双环[4.3.0]壬烷-3,7,10-三烯-5-酮 在 2,4-diamino-5-methyl-furo[2,3-d]pyrimidine 、 (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 N,N-二甲基甲酰胺 为溶剂， 生成 6-methyl-4-piperazin-1-yl-7H-pyrrolo[2,3-d]pyrimidin-2-amine
  参考文献：
  名称：

  Synthesis and evaluation of novel ligands for the histamine H4 receptor based on a pyrrolo[2,3-d]pyrimidine scaffold

  摘要：

  Starting from a known H4R ligand based on a pyrimidine skeleton, a series of novel analogues based on a pyrrolo[2,3-d]pyrimidine scaffold have been prepared. Whereas the original pyrimidine congener shows good affinity at hH(4)R (K-i = 0.5 mu M), its lacks selectivity with a K-i value for the hH(3)R of 1 mu M. Within the newly synthesized pyrrolo[2,3-d]pyrimidines, several congeners show K-i values of less than 1 mu M at the hH(4)R and show a much improved selectivity profile. Therefore, these series represent an interesting starting point for the discovery of novel hH(4)R ligands. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.139

文献信息

• Analogues of 4-[(7-Bromo-2-methyl-4-oxo-3<i>H</i>-quinazolin-6-yl)methylprop-2-ynylamino]-<i>N</i>-(3-pyridylmethyl)benzamide (CB-30865) as Potent Inhibitors of Nicotinamide Phosphoribosyltransferase (Nampt)
  作者：Jeffrey W. Lockman、Brett R. Murphy、Daniel F. Zigar、Weston R. Judd、Paul M. Slattum、Zhong-Hua Gao、Kirill Ostanin、Jeremy Green、Rena McKinnon、Ryan T. Terry-Lorenzo、Tracey C. Fleischer、J. Jay Boniface、Mark Shenderovich、J. Adam Willardsen

  DOI：10.1021/jm101145b

  日期：2010.12.23

  We have shown previously that the target of the potent cytatoxic agent 4-[(7-bromo-2-methyl-4-oxo-3H-quinazolin-6-yl)methyl-prop-2-ynylamino]-N-(3-pyridylmethyl)benzamide (CB38065, 1) is nicotinamide phosphoribosyltransferase (Nampt). With its cellular target known we sought to optimize the biochemical and cellular Nampt activity of 1 as well as its cytotoxicity. It was found that a 3-pyridyl-methylamide substituent in the A region was critical to cellular Nampt activity and cytotoxicity, although other aromatic substitution did yield compounds with submicromolar enzymatic inhibition. Small unsaturated groups worked best in the D-region of the molecule, with 3,3-dimethylallyl providing optimal potency. The E region required a quinazolin-4-one or 1,2,3-benzotriazin-4-one group for activity, and many substituents were tolerated at C(2) of the quinazolin-4-one. The best compounds showed subnanomolar inhibition of Nampt and low nanomolar cytotoxicity in cellular assays.
• Studies directed toward a total synthesis of nucleoside Q. Annulation of 2,6-diaminopyrimidin-4-one with .alpha.-halo carbonyls to form pyrrolo[2,3-d]pyrimidines and furo[2,3-d]pyrimidines
  作者：John A. Secrist、Paul S. Liu

  DOI：10.1021/jo00414a029

  日期：1978.9
• 2,4-Diamino-5-methyl-6-substituted arylthio-furo[2,3-d]pyrimidines as novel classical and nonclassical antifolates as potential dual thymidylate synthase and dihydrofolate reductase inhibitors
  作者：Aleem Gangjee、Hiteshkumar D. Jain、Jaclyn Phan、Xin Guo、Sherry F. Queener、Roy L. Kisliuk

  DOI：10.1016/j.bmc.2009.11.029

  日期：2010.1

  A novel classical antifolate N-4-[(2,4-diamino-5-methyl-furo[2,3-d]pyrimidin-6-yl)thio]-benzoyl}-l-glutamic acid 5 and 11 nonclassical antifolates 6–16 were designed, synthesized, and evaluated as inhibitors of dihydrofolate reductase (DHFR) and thymidylate synthase (TS). The nonclassical compounds 6–16 were synthesized from 20 via oxidative addition of substituted thiophenols using iodine. Peptide

  一种新型经典抗叶酸剂N -4-[(2,4-diamino-5-methyl-furo[2,3 - d ]pyrimidin-6-yl)thio]-benzoyl} -l -glutamic acid 5和 11 非经典抗叶酸剂6 - 16被设计、合成并评估为二氢叶酸还原酶 (DHFR) 和胸苷酸合酶 (TS) 的抑制剂。非经典化合物6-16是由20通过使用碘氧化加成取代的苯硫酚合成的。中间体酸21 的肽偶联，然后皂化得到经典的类似物5。化合物5据我们所知，第一个例子是 2,4-二氨基呋喃 [2,3- d ]嘧啶经典抗叶酸，它对人类 DHFR 和人类 TS 都具有抑制活性。与哺乳动物 DHFR 相比，经典类似物5是卡氏肺囊虫DHFR 和鸟分枝杆菌DHFR的纳摩尔抑制剂和显着选择性抑制剂，分别为 263 倍和 2107 倍。非经典类似物6-16对病原体 DHFR 或 TS 具有中等效力。该研究表明呋喃[2
• Synthesis and evaluation of novel ligands for the histamine H4 receptor based on a pyrrolo[2,3-d]pyrimidine scaffold
  作者：Ling-Jie Gao、J. Stephan Schwed、Lilia Weizel、Steven De Jonghe、Holger Stark、Piet Herdewijn

  DOI：10.1016/j.bmcl.2012.10.139

  日期：2013.1

  Starting from a known H4R ligand based on a pyrimidine skeleton, a series of novel analogues based on a pyrrolo[2,3-d]pyrimidine scaffold have been prepared. Whereas the original pyrimidine congener shows good affinity at hH(4)R (K-i = 0.5 mu M), its lacks selectivity with a K-i value for the hH(3)R of 1 mu M. Within the newly synthesized pyrrolo[2,3-d]pyrimidines, several congeners show K-i values of less than 1 mu M at the hH(4)R and show a much improved selectivity profile. Therefore, these series represent an interesting starting point for the discovery of novel hH(4)R ligands. (C) 2012 Elsevier Ltd. All rights reserved.