tert-butyl 2-((4-hydroxyphenyl)carbamothioyl)hydrazine-1-carboxylate | 1318765-53-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: tert-butyl 2-((4-hydroxyphenyl)carbamothioyl)hydrazine-1-carboxylate
• CAS: 1318765-53-5
• 化学式: C₁₂H₁₇N₃O₃S
• 分子量: 283.351
• InChiKey: GTIMFPKBWDOWNX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.12
• 重原子数：
  19.0
• 可旋转键数：
  1.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  82.62
• 氢给体数：
  4.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-((4-hydroxyphenyl)carbamothioyl)hydrazine-1-carboxylate 在 盐酸 、 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 生成 (Z)-N-(4-hydroxyphenyl)-2-(2-oxoindolin-3-ylidene)hydrazinecarbothioamide
  参考文献：
  名称：

  Synthesis and Structure–Activity Evaluation of Isatin-β-thiosemicarbazones with Improved Selective Activity toward Multidrug-Resistant Cells Expressing P-Glycoprotein

  摘要：

  Cancer multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters presents a significant unresolved clinical challenge. One strategy to resolve MDR is to develop compounds that selectively kill cells overexpressing the efflux transporter P-glycoprotein (MDR1, P-gp, ABCB1). We have previously reported structure-activity studies based around the lead compound NSC73306 (1, 1-isatin-4-(4'-methoxyphenyl)-3-thiosemicarbazone, 4.3-fold selective). Here we sought to extend this work on MDR1-selective analogues by establishing whether 1 showed "robust" activity against a range of cell lines expressing P-gp. We further aimed to synthesize and test analogues with varied substitution at the N4-position, and substitution around the N4-phenyl ring of isatin-beta-thiosemicarbazones (IBTs), to identify compounds with increased MDR1-selectivity. Compound 1 demonstrated MDR1-selectivity against all P-gp-expressing cell lines examined. This selectivity was reversed by inhibitors of P-gp ATPase activity. Structural variation at the 4'-phenyl position of 1 yielded compounds of greater MDR1-selectivity. Two of these analogues, 1-isatin-4-(4'-nitrophenyl)-3-thiosemicarbazone (22, 8.3-fold selective) and 1-isatin-4-(4'-tert-butyl phenyl)-3-thiosemicarbazone (32, 14.8-fold selective), were selected for further testing and were found to retain the activity profile of 1. These compounds are the most active IBTs identified to date.

  DOI：

  10.1021/jm2006047