Uses of cyanoacetylhydrazine in heterocyclic synthesis: novel synthesis of pyrazole derivatives with anti-tumor activities.
The reaction of cyanoacetylhydrazine with chloroacetyl chloride gave <em>N'</em>-(2-chloroacetyl)-2-cyanoacetohydrazide. The latter underwent cyclization to afford 1-(5 amino-3-hydroxy-1<em>H</em>-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<strong> </strong>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.
Departrment of Chemistry, Faculty of Science, Cairo University, Giza, Egypt. raafat_mohareb@yahoo.com
Rafat M
RM
Mohareb
Nahed N E
NN
El-Sayed
Mahmoud A
MA
Abdelaziz
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D006834:Hydrazines / Q000737:chemistry*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D006834:Hydrazines; D011720:Pyrazoles; C031280:pyrazole