Ethyl 6,8-dichloroimidazo[2,1-b][1,3]benzothiazole-2-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: Ethyl 6,8-dichloroimidazo[2,1-b][1,3]benzothiazole-2-carboxylate
• 化学式: C₁₂H₈Cl₂N₂O₂S
• 分子量: 315.18
• InChiKey: SYYAOKDHJQDQSK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  71.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-4,6-二氯苯并噻唑 、 3-溴丙酮酸乙酯 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 Ethyl 6,8-dichloroimidazo[2,1-b][1,3]benzothiazole-2-carboxylate
  参考文献：
  名称：

  Synthesis, in vitro and in vivo cytotoxicity, and prediction of the intestinal absorption of substituted 2-ethoxycarbonyl-imidazo[2,1-b]benzothiazoles

  摘要：

  The imidazobenzothiazole compounds 3-17 together with the imidazobenzoxazole 18, and the imidazobenzoimidazole 19 were prepared and their cytotoxic activity evaluated at the National Cancer Institute (NCI) for testing against a panel of approximately 60 tumor cell lines. Compounds 5, 7, 8, and 16 exhibited interesting in vitro cytotoxic activity. The most active imidazobenzothiazole derivative 8 was further evaluated as a cytotoxic agent in the hollow fiber assay and showed a score greater than the minimum values for xenograft testing together with a net cell kill. Comparison with the results displayed in the in vivo assay by standard antitumor drugs in clinical use revealed a significant in vivo activity of the benzothiazole compound. COMPARE analyses for compounds 4-19 against the NCI's standard agent database show poor or no correlation, and it might suggest for these compounds a mechanism of action unrelated to that of any known drug. Furthermore. the benzothiazole 8 did not show significant antitumor activity in a panel of two xenotransplanted tumors (i.e. colon and non-small cell lung tumors). By computing the polar surface area of compounds 3-19 with the MAREA computer program it was established that the most active compounds 5, 7, 8, and 16 should experience good intestinal permeability. (C) 2001 Elsevier Science B.V. All rights reserved.

  DOI：

  10.1016/s0928-0987(01)00173-7

文献信息

• Synthesis and benzodiazepine receptor binding of some imidazoand pyrimido[2,1-b]benzothiazoles
  作者：G Trapani、M Franco、A Latrofa、A Carotti、G Gerichi、M Serra、G Biggio、G Liso

  DOI：10.1016/0223-5234(96)89553-5

  日期：1996.1

  A series of substituted imidazo[2,1-b]benzothiazoles 2a-u was synthesized and the compounds evaluated for their affinity at the central benzodiazepine receptors. Substitution at the 7-position generally resulted in a decreased ligand affinity whereas a significant increase was observed for 5-substituted compounds. The intrinsic efficacy of selected high-affinity ligands 2j,k,q, as well as some previously reported pyrimido[2,1-b]benzothiazoles 1, was measured in vitro through the determination of the GABA ratio and [S-35]TBPS displacement. Consistent with a partial inverse agonist profile, the benzothiazole derivatives 2j,k,q increased [S-35]TBPS binding. For compounds 1c and 1d, a discrepancy between GABA ratio and [S-35]TBPS binding data was observed. Only the latter assay was in full agreement with the pharmacological data, which indicated an inverse agonist and a partial agonist profile for 2k,q and 1c,d respectively. The affinity and intrinsic activity data of compounds 1c,d and 2j,k,q are discussed in the light of the recently proposed pharmacophore model by Skolnick/Cook; in particular, the agonistic activity of 1c,d is interpreted on the basis of a possible interaction of substitutents in position 6 with the receptors lipophilic area L3 of Skolnick/Cook, whereas the observed inverse agonist profile of 2j,k,q is explained taking into account their structural analogy with the well known proconvulsant beta-CCE.