N-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methylcarbamothioyl]benzamide | 954117-25-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 2 '，5'-二脱氧核苷
• 英文名称: N-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methylcarbamothioyl]benzamide
• 英文别名: N-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methylcarbamothioyl]benzamide
• CAS: 954117-25-0
• 化学式: C₁₈H₂₀N₄O₅S
• 分子量: 404.447
• InChiKey: KSTKXUGRPAWENC-MJBXVCDLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  152
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5'-amino-5'-deoxy-α-thymidine 、 苯甲酰基异硫氰酸酯 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以51%的产率得到N-[[(2R,3S,5S)-3-hydroxy-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methylcarbamothioyl]benzamide
  参考文献：
  名称：

  Rational Design of 5‘-Thiourea-Substituted α-Thymidine Analogues as Thymidine Monophosphate Kinase Inhibitors Capable of Inhibiting Mycobacterial Growth

  摘要：

  Recently, thymidine monophosphate kinase (TMPK) emerged as an attractive target for developing inhibitors of Mycobacterium tuberculosis growth. The elucidation of the X-ray structure of TMPK of M. tuberculosis (TMPKmt), as well as the structure of an earlier serendipitously discovered dimeric thymidine inhibitor, laid the foundation for the design of potent and selective TMPKmt inhibitors reported here. Several hits identified within a series of 3'-C-branched thiourea-substituted P-thymidine derivatives inspired us to construct a set of 5'-thiourea-substituted a-thymidine derivatives characterized by a similar relative orientation of the thymine and arylthiourea moieties. (x-Thymidine derivative 15, featuring a (3-trifluoromethyl-4-chlorophenyl)thiourea moiety, has a K-i of 0.6 mu M and a selectivity index of 600 versus human TMPK. Moreover, it represents the first TMPK inhibitor showing good inhibitory activity on growing M. bovis (MIC99 = 20 mu g/mL) and M. tuberculosis (MIC50 = 6.25 mu g/mL) strains.

  DOI：

  10.1021/jm0706158

文献信息

• Rational Design of 5‘-Thiourea-Substituted α-Thymidine Analogues as Thymidine Monophosphate Kinase Inhibitors Capable of Inhibiting Mycobacterial Growth
  作者：Ineke Van Daele、Hélène Munier-Lehmann、Matheus Froeyen、Jan Balzarini、Serge Van Calenbergh

  DOI：10.1021/jm0706158

  日期：2007.11.1

  Recently, thymidine monophosphate kinase (TMPK) emerged as an attractive target for developing inhibitors of Mycobacterium tuberculosis growth. The elucidation of the X-ray structure of TMPK of M. tuberculosis (TMPKmt), as well as the structure of an earlier serendipitously discovered dimeric thymidine inhibitor, laid the foundation for the design of potent and selective TMPKmt inhibitors reported here. Several hits identified within a series of 3'-C-branched thiourea-substituted P-thymidine derivatives inspired us to construct a set of 5'-thiourea-substituted a-thymidine derivatives characterized by a similar relative orientation of the thymine and arylthiourea moieties. (x-Thymidine derivative 15, featuring a (3-trifluoromethyl-4-chlorophenyl)thiourea moiety, has a K-i of 0.6 mu M and a selectivity index of 600 versus human TMPK. Moreover, it represents the first TMPK inhibitor showing good inhibitory activity on growing M. bovis (MIC99 = 20 mu g/mL) and M. tuberculosis (MIC50 = 6.25 mu g/mL) strains.