1-(3-N,N-dimethylaminopropyloxy)-4-iodopyrazole | 572909-05-8

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 英文名称: 1-(3-N,N-dimethylaminopropyloxy)-4-iodopyrazole
• 英文别名: 3-(4-iodopyrazol-1-yl)oxy-N,N-dimethylpropan-1-amine
• CAS: 572909-05-8
• 化学式: C₈H₁₄IN₃O
• 分子量: 295.123
• InChiKey: VQOKZIWBMVQAJW-UHFFFAOYSA-N

物化性质

• 沸点：
  320.5±48.0 °C(Predicted)
• 密度：
  1.62±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  30.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-N,N-dimethylaminopropyloxy)-4-iodopyrazole 在 四(三苯基膦)钯 potassium phosphate 、 正丁基锂 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 正己烷 为溶剂， 反应 53.0h， 生成 1-(3-N,N-dimethylaminopropyloxy)-5-ethyl-4-phenylpyrazolo[4,3-a]naphthalene
  参考文献：
  名称：

  N-Alkoxypyrazoles as biomimetics for the alkoxyphenyl group in tamoxifen

  摘要：

  The preparation of a series of novel analogues of the selective antiestrogen tamoxifen is reported. 1Z-alkoxyphenyl group in tamoxifen has been replaced by a N-alkoxypyrazole, while functionalised phenyl groups or heteroaromatics were introduced at the 2Z-position using sequential Suzuki cross coupling of 1,2-(bis)borylpinacol 1-phenylbutene with 4- or 5-iodo-1-N,N-dimethylaminoethyl or propyl-pyrazoles. Approximately 50 tamoxifen analogues were obtained and tested in an estrogen receptor (ERalpha) affinity assay. Several compounds exhibited binding affinities 2-5-fold lower than tamoxifen. Dose-response experiments with six selected compounds were carried out using two different human breast cancer cell lines, MCF-7 and the tamoxifen resistant cell line MCF-/TAM(R)-1. Both cell lines exhibited growth inhibition upon treatment with the tamoxifen analogues. Co-treatment of the cells, with estradiol and the individual compounds, were also performed. The results indicated that the observed growth inhibitory effect was mediated by the ERalpha. Analogues of the potent antiestrogen 4-hydroxytamoxifen (4-OHT) were synthesised where the 1E-4-hydroxyphenyl was replaced by a 1-hydroxypyrazol-4-yl group. However, modest growth inhibition of MCF-7 cells was observed upon treatment with these analogues. In contrast, 1Z-, 2Z-ringclosed tamoxifen analogue (59) was shown to possess antiproliferative effects on MCF-7 and MCF-/TAM(R)-1 cells in lower doses than tamoxifen. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00566-7
• 作为产物：
  描述：

  N,N-二甲氨基氯丙烷盐酸盐 、 1-羟基-4-碘吡唑 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以90%的产率得到1-(3-N,N-dimethylaminopropyloxy)-4-iodopyrazole
  参考文献：
  名称：

  N-Alkoxypyrazoles as biomimetics for the alkoxyphenyl group in tamoxifen

  摘要：

  The preparation of a series of novel analogues of the selective antiestrogen tamoxifen is reported. 1Z-alkoxyphenyl group in tamoxifen has been replaced by a N-alkoxypyrazole, while functionalised phenyl groups or heteroaromatics were introduced at the 2Z-position using sequential Suzuki cross coupling of 1,2-(bis)borylpinacol 1-phenylbutene with 4- or 5-iodo-1-N,N-dimethylaminoethyl or propyl-pyrazoles. Approximately 50 tamoxifen analogues were obtained and tested in an estrogen receptor (ERalpha) affinity assay. Several compounds exhibited binding affinities 2-5-fold lower than tamoxifen. Dose-response experiments with six selected compounds were carried out using two different human breast cancer cell lines, MCF-7 and the tamoxifen resistant cell line MCF-/TAM(R)-1. Both cell lines exhibited growth inhibition upon treatment with the tamoxifen analogues. Co-treatment of the cells, with estradiol and the individual compounds, were also performed. The results indicated that the observed growth inhibitory effect was mediated by the ERalpha. Analogues of the potent antiestrogen 4-hydroxytamoxifen (4-OHT) were synthesised where the 1E-4-hydroxyphenyl was replaced by a 1-hydroxypyrazol-4-yl group. However, modest growth inhibition of MCF-7 cells was observed upon treatment with these analogues. In contrast, 1Z-, 2Z-ringclosed tamoxifen analogue (59) was shown to possess antiproliferative effects on MCF-7 and MCF-/TAM(R)-1 cells in lower doses than tamoxifen. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00566-7