3-[(4-Chlorophenoxy)methyl]-7-(4-methylphenyl)-5,6-dihydroimidazo[2,1-c][1,2,4]triazole | 1018855-84-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-[(4-Chlorophenoxy)methyl]-7-(4-methylphenyl)-5,6-dihydroimidazo[2,1-c][1,2,4]triazole
• CAS: 1018855-84-9
• 化学式: C₁₈H₁₇ClN₄O
• 分子量: 340.812
• InChiKey: FRLONHJRHOUZIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  43.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  对氯苯氧乙酸 、 1-(4-methylphenyl)-2-hydrazonoimidazolidine 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以59.3%的产率得到3-[(4-Chlorophenoxy)methyl]-7-(4-methylphenyl)-5,6-dihydroimidazo[2,1-c][1,2,4]triazole
  参考文献：
  名称：

  Synthesis, determination of the lipophilicity, anticancer and antimicrobial properties of some fused 1,2,4-triazole derivatives

  摘要：

  3-Unsubstituted and 3-substituted-7-aryl-5H-6,7-dihydroimidazo[2,1-c][1,2,4]triazoles (1-14) were designed and obtained from biologically active 1-aryl-2-hydrazonoimidazolidines by cyclocondensation reaction with triethyl orthoformates (1-4), phenoxyacetic acid derivatives (5-13) and carbon disulfide (14), respectively. Their chemical structures were confirmed by IR, H-1 NMR, 13 C NMR, MS spectra and elemental analysis. In the high performance liquid chromatographic series of experiments, fourteen synthesized compounds (1-14) were chromatographed on octadecyl silica adsorbent and their lipophilicity parameter (log k(w)) was determined using various aqueous systems: mixture of water and organic modifiers (methanol - MeOH, acetorritrile - MeCN or dioxane - DX). Compounds 7 and 12 were evaluated for their cytotoxic activity against three cancer cell lines: human Caucasian colon adenocarcinoma cell line - LS180 (ECACC 87021202), human uterus carcinoma cell line - SiHa (ECACC 85060701) and human breast carcinoma cell line - T47D (ECACC 85102201). Compound 12 was found to be the most effective in vitro against human colon adenocarcinoma cell line (LS 180). Moreover, the distinctly marked lower cytotoxicity of compounds 7 and 12 against the normal cell line - human skin fibroblasts (HSF) and almost several-fold higher against the examined cancer cell lines was ascertained. The cytotoxic effect of imidazotriazole 7 was noticed on DNA structure of breast cancer cell line (T47D) by using the comet assay. Compound 7 in concentration of 29.3 mu M was found to possess efficiency for DNA strand breakage. In particular, this led to cutting of the DNA strands and formation of small fragments of DNA - two higher and one lighter in comparison with control DNA. Moreover, significant viability decreases in the human leukaemic RPMI 8226 cells treated with different concentrations of imidazotriazoles 8-12 were observed, suggesting their antiproliferative properties. Besides, three tested compounds (9, 13, 14) revealed significant antimicrobial activities with MIC values in the range of 30.9-44.0 mu M. Compound 13 showed superior antibacterial activity to ampicillin and chloramphenicol in vitro, whereas 14 displayed superior antifungal activity to miconazole. (c) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2007.03.033

文献信息

• Synthesis, determination of the lipophilicity, anticancer and antimicrobial properties of some fused 1,2,4-triazole derivatives
  作者：Krzysztof Sztanke、Tomasz Tuzimski、Jolanta Rzymowska、Kazimierz Pasternak、Martyna Kandefer-Szerszeń

  DOI：10.1016/j.ejmech.2007.03.033

  日期：2008.2

  3-Unsubstituted and 3-substituted-7-aryl-5H-6,7-dihydroimidazo[2,1-c][1,2,4]triazoles (1-14) were designed and obtained from biologically active 1-aryl-2-hydrazonoimidazolidines by cyclocondensation reaction with triethyl orthoformates (1-4), phenoxyacetic acid derivatives (5-13) and carbon disulfide (14), respectively. Their chemical structures were confirmed by IR, H-1 NMR, 13 C NMR, MS spectra and elemental analysis. In the high performance liquid chromatographic series of experiments, fourteen synthesized compounds (1-14) were chromatographed on octadecyl silica adsorbent and their lipophilicity parameter (log k(w)) was determined using various aqueous systems: mixture of water and organic modifiers (methanol - MeOH, acetorritrile - MeCN or dioxane - DX). Compounds 7 and 12 were evaluated for their cytotoxic activity against three cancer cell lines: human Caucasian colon adenocarcinoma cell line - LS180 (ECACC 87021202), human uterus carcinoma cell line - SiHa (ECACC 85060701) and human breast carcinoma cell line - T47D (ECACC 85102201). Compound 12 was found to be the most effective in vitro against human colon adenocarcinoma cell line (LS 180). Moreover, the distinctly marked lower cytotoxicity of compounds 7 and 12 against the normal cell line - human skin fibroblasts (HSF) and almost several-fold higher against the examined cancer cell lines was ascertained. The cytotoxic effect of imidazotriazole 7 was noticed on DNA structure of breast cancer cell line (T47D) by using the comet assay. Compound 7 in concentration of 29.3 mu M was found to possess efficiency for DNA strand breakage. In particular, this led to cutting of the DNA strands and formation of small fragments of DNA - two higher and one lighter in comparison with control DNA. Moreover, significant viability decreases in the human leukaemic RPMI 8226 cells treated with different concentrations of imidazotriazoles 8-12 were observed, suggesting their antiproliferative properties. Besides, three tested compounds (9, 13, 14) revealed significant antimicrobial activities with MIC values in the range of 30.9-44.0 mu M. Compound 13 showed superior antibacterial activity to ampicillin and chloramphenicol in vitro, whereas 14 displayed superior antifungal activity to miconazole. (c) 2007 Elsevier Masson SAS. All rights reserved.