(2S,4S)-4-(((2S,3S,4R,5R)-5-(6-(2-(biphenyl-4-yl)ethyl-amino)-2-chloro-9H-purin-9-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl)methylthio)pyrrolidine-2-carboxylic acid | 901775-99-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: (2S,4S)-4-(((2S,3S,4R,5R)-5-(6-(2-(biphenyl-4-yl)ethyl-amino)-2-chloro-9H-purin-9-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl)methylthio)pyrrolidine-2-carboxylic acid
• 英文别名: (2S,4S)-4-(((2S,3S,4R,5R)-5-(6-(2-(biphenyl-4-yl)ethylamino)-2-chloro-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methylthio)pyrrolidine-2-carboxylic acid；(2S,4S)-4-[[(2S,3S,4R,5R)-5-[2-chloro-6-[2-(4-phenylphenyl)ethylamino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methylsulfanyl]pyrrolidine-2-carboxylic acid
• CAS: 901775-99-3
• 化学式: C₂₉H₃₁ClN₆O₅S
• 分子量: 611.121
• InChiKey: JUNARBZTVSAGMF-ODXIBGGOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  180
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  在 水 、 三氟乙酸 作用下， 生成 (2S,4S)-4-(((2S,3S,4R,5R)-5-(6-(2-(biphenyl-4-yl)ethyl-amino)-2-chloro-9H-purin-9-yl)-3,4-dihydroxy-tetrahydrofuran-2-yl)methylthio)pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Constrained (l-)-S-adenosyl-l-homocysteine (SAH) analogues as DNA methyltransferase inhibitors

  摘要：

  Potent SAH analogues with constrained homocysteine units have been designed and synthesized as inhibitors of human DNMT enzymes. The five membered (2S,4S)-4-mercaptopyrrolidine-2-carboxylic acid, in 1a, was a good replacement for homocysteine, while the corresponding six-member counterpart was less active. Further optimization of 1a, changed the selectivity pro. le of these inhibitors. A Chloro substituent at the 2-position of 1a, compound 1d, retained potency against DNMT1, while N-6 alkylation, compound 7a, conserved DNMT3b2 activity. The concomitant substitutions of 1a at both 2- and N-6 positions reduced activity against both enzymes. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.132

文献信息

• Inhibitors of DNA Methyltransferase
  申请人：Wahhab Amal

  公开号：US20080132525A1

  公开（公告）日：2008-06-05

  The invention relates to the inhibition of DNA methyltransferase isoforms DNMT1 and DNMT3b2. The invention provides compounds and methods for inhibiting DNMT1 and DNMT3b2.

  这项发明涉及抑制DNA甲基转移酶亚型DNMT1和DNMT3b2。该发明提供了用于抑制DNMT1和DNMT3b2的化合物和方法。