6-(4-Amino-phenyl)-N*4*-indan-2-yl-pyrimidine-2,4-diamine | 247587-08-2

• 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: 6-(4-Amino-phenyl)-N*4*-indan-2-yl-pyrimidine-2,4-diamine
• 英文别名: 6-(4-aminophenyl)-4-N-(2,3-dihydro-1H-inden-2-yl)pyrimidine-2,4-diamine
• CAS: 247587-08-2
• 化学式: C₁₉H₁₉N₅
• 分子量: 317.393
• InChiKey: PFXGNCHRDYIPQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  89.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2H-色烯-2-醇 、 6-(4-Amino-phenyl)-N*4*-indan-2-yl-pyrimidine-2,4-diamine 在 sodium cyanoborohydride 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 0.83h， 以59%的产率得到2-(3-{4-[2-Amino-6-(indan-2-ylamino)-pyrimidin-4-yl]-phenylamino}-propyl)-phenol
  参考文献：
  名称：

  Novel Inhibitors of Erm Methyltransferases from NMR and Parallel Synthesis

  摘要：

  The Erm family of methyltransferases confers resistance to the macrolide-lincosamide-streptogramin type B (MLS) antibiotics through the methylation of 23S ribosomal RNA. Upon the methylation of RNA, the MLS antibiotics lose their ability to bind to the ribosome and exhibit their antibiotic activity. Using an NMR-based screen, we identified a series of triazine-containing compounds that bind weakly to ErmAM. These initial lead compounds were optimized by the parallel synthesis of a large number of analogues, resulting in compounds which inhibit the Erm-mediated methylation of rRNA in the low micromolar range. NMR and X-ray structures of enzyme/inhibitor complexes reveal that the inhibitors bind to the S-adenosylmethionine binding site on the Erm protein. These compounds represent novel methyltransferase inhibitors that serve as new leads for the reversal of Erm-mediated MLS antibiotic resistance.

  DOI：

  10.1021/jm990293a
• 作为产物：
  描述：

  2-氨基茚满盐酸盐 在 Pd-BaSO₄ 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 正丁醇 为溶剂， 反应 17.5h， 生成 6-(4-Amino-phenyl)-N*4*-indan-2-yl-pyrimidine-2,4-diamine
  参考文献：
  名称：

  Novel Inhibitors of Erm Methyltransferases from NMR and Parallel Synthesis

  摘要：

  The Erm family of methyltransferases confers resistance to the macrolide-lincosamide-streptogramin type B (MLS) antibiotics through the methylation of 23S ribosomal RNA. Upon the methylation of RNA, the MLS antibiotics lose their ability to bind to the ribosome and exhibit their antibiotic activity. Using an NMR-based screen, we identified a series of triazine-containing compounds that bind weakly to ErmAM. These initial lead compounds were optimized by the parallel synthesis of a large number of analogues, resulting in compounds which inhibit the Erm-mediated methylation of rRNA in the low micromolar range. NMR and X-ray structures of enzyme/inhibitor complexes reveal that the inhibitors bind to the S-adenosylmethionine binding site on the Erm protein. These compounds represent novel methyltransferase inhibitors that serve as new leads for the reversal of Erm-mediated MLS antibiotic resistance.

  DOI：

  10.1021/jm990293a

文献信息

• Novel Inhibitors of Erm Methyltransferases from NMR and Parallel Synthesis
  作者：Philip J. Hajduk、Jürgen Dinges、Jeffrey M. Schkeryantz、David Janowick、Michele Kaminski、Michael Tufano、David J. Augeri、Andrew Petros、Vicki Nienaber、Ping Zhong、Rachel Hammond、Michael Coen、Bruce Beutel、Leonard Katz、Stephen W. Fesik

  DOI：10.1021/jm990293a

  日期：1999.9.1

  The Erm family of methyltransferases confers resistance to the macrolide-lincosamide-streptogramin type B (MLS) antibiotics through the methylation of 23S ribosomal RNA. Upon the methylation of RNA, the MLS antibiotics lose their ability to bind to the ribosome and exhibit their antibiotic activity. Using an NMR-based screen, we identified a series of triazine-containing compounds that bind weakly to ErmAM. These initial lead compounds were optimized by the parallel synthesis of a large number of analogues, resulting in compounds which inhibit the Erm-mediated methylation of rRNA in the low micromolar range. NMR and X-ray structures of enzyme/inhibitor complexes reveal that the inhibitors bind to the S-adenosylmethionine binding site on the Erm protein. These compounds represent novel methyltransferase inhibitors that serve as new leads for the reversal of Erm-mediated MLS antibiotic resistance.