[5-(2-methylphenyl)-2-[(2S)-6-nitro-4-oxo-2,3-dihydro-1H-quinazolin-2-yl]phenyl] (2R)-3,3-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate | 1044499-58-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [5-(2-methylphenyl)-2-[(2S)-6-nitro-4-oxo-2,3-dihydro-1H-quinazolin-2-yl]phenyl] (2R)-3,3-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate
• CAS: 1044499-58-2
• 化学式: C₃₂H₃₆N₄O₇
• 分子量: 588.66
• InChiKey: KNHRPLCZPSGUTM-SVBPBHIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  43
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  152
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [5-(2-methylphenyl)-2-[(2S)-6-nitro-4-oxo-2,3-dihydro-1H-quinazolin-2-yl]phenyl] (2R)-3,3-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate 在 一水合肼 作用下， 以 四氢呋喃 为溶剂， 以80%的产率得到
  参考文献：
  名称：

  Asymmetric Synthesis of 2,3-Dihydro-2-arylquinazolin-4-ones: Methodology and Application to a Potent Fluorescent Tubulin Inhibitor with Anticancer Activity

  摘要：

  For several decades the 2,3-dihydroquinazolinone (DHQZ) heterocycle has been known to possess a variety of important biological and medicinal properties. Despite the many interesting facets of these molecules, synthetic access to nonracemic DHQZ analogues has remained elusive. Herein, we disclose a synthetic route that allows access to either enantiomer of a variety of DHQZ derivatives. We illustrate the utility of this chemistry with the asymmetric preparation and biological evaluation of a new chiral fluorescent tubulin binding agent with extremely potent antiproliferative properties against human cancer cells. A computational rationale for the increased potency of the (S)-enantiomer over the (R)-enantiomer is given, based on the crystal structure of alpha,beta-tubulin complexed with colchicine. Taking advantage of the inherent fluorescence of these molecules, confocal images of GMC-5-193 (compound 7) in the cytoplasm of human melanoma cells (MDA-MB-435) cells are presented.

  DOI：

  10.1021/jm800271c
• 作为产物：
  描述：

  N-Boc-D-tert-leucine[5-(2'-tolyl)-2-formyl]phenyl ester 、 2-氨基-5-硝基苯酰胺 在 三氟乙酸 作用下， 以 乙腈 为溶剂， 以37%的产率得到[5-(2-methylphenyl)-2-[(2S)-6-nitro-4-oxo-2,3-dihydro-1H-quinazolin-2-yl]phenyl] (2R)-3,3-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate
  参考文献：
  名称：

  Asymmetric Synthesis of 2,3-Dihydro-2-arylquinazolin-4-ones: Methodology and Application to a Potent Fluorescent Tubulin Inhibitor with Anticancer Activity

  摘要：

  For several decades the 2,3-dihydroquinazolinone (DHQZ) heterocycle has been known to possess a variety of important biological and medicinal properties. Despite the many interesting facets of these molecules, synthetic access to nonracemic DHQZ analogues has remained elusive. Herein, we disclose a synthetic route that allows access to either enantiomer of a variety of DHQZ derivatives. We illustrate the utility of this chemistry with the asymmetric preparation and biological evaluation of a new chiral fluorescent tubulin binding agent with extremely potent antiproliferative properties against human cancer cells. A computational rationale for the increased potency of the (S)-enantiomer over the (R)-enantiomer is given, based on the crystal structure of alpha,beta-tubulin complexed with colchicine. Taking advantage of the inherent fluorescence of these molecules, confocal images of GMC-5-193 (compound 7) in the cytoplasm of human melanoma cells (MDA-MB-435) cells are presented.

  DOI：

  10.1021/jm800271c