氰基乙酰肼在杂环合成中的应用：具有抗肿瘤活性的吡唑衍生物的新合成方法。
Uses of cyanoacetylhydrazine in heterocyclic synthesis: novel synthesis of pyrazole derivatives with anti-tumor activities.
机构信息
Departrment of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.
出版信息
Molecules. 2012 Jul 12;17(7):8449-63. doi: 10.3390/molecules17078449.
Abstract
The reaction of cyanoacetylhydrazine with chloroacetyl chloride gave N'-(2-chloroacetyl)-2-cyanoacetohydrazide. The latter underwent cyclization to afford 1-(5 amino-3-hydroxy-1H-pyrazol-1-yl)-2-chloroethanone, which underwent nucleophilic substitution to give 3-(5-amino-3-hydroxy-1H-pyrazol-1-yl)-3-oxopropanenitrile. The latter two compounds were used as key synthons to synthesize new thiophene, pyran, thiazole and some fused heterocyclic derivatives. The antitumor activity of the newly synthesized compounds was evaluated against three human tumor cells lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) and some of these compounds were found to exhibit much higher inhibitory effects towards the three tumor cell lines than the Gram positive control doxorubicin.
摘要
氰基乙酰胺与氯乙酰氯反应得到N'-(2-氯乙酰基)-2-氰基乙酰胺。后者环化得到 1-(5 氨基-3-羟基-1H-吡唑-1-基)-2-氯乙酮，后者进行亲核取代得到 3-(5-氨基-3-羟基-1H-吡唑-1-基)-3-氧代丙腈。后两种化合物 被用作合成新的噻吩、吡喃、噻唑和一些稠合杂环衍生物的关键合成子。新合成的化合物的抗肿瘤活性针对三种人类肿瘤细胞系，即乳腺癌（MCF-7）、非小细胞肺癌（NCI-H460）和中枢神经系统癌症（SF-268）进行了评估，其中一些化合物对三种肿瘤细胞系的抑制作用明显高于革兰氏阳性对照阿霉素。
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