Potential antitumor agents. 12. 2-Formyl-4-aminophenylpyridine thiosemicarbazones.
The antitumor agent 2-formyl-4-(m-amino)phenylpyridine thiosemicarbazone (4-APPT) has been synthesized by a new route to give significantly better overall yields than previously reported. 4-Phenyl-2-picoline was formed by methylation o4-phenylpyridine with CH3Li which upon nitration produced a mixture of o-, m-, and p-nitro-substituted derivatives. These isomers were separated by the solubility differences of their hydrochloride or nitrate salts in 10, 27, and 40% yields, respectively. Identification and confirmation of the structure of these isomers were carried out by mmr. Each isomer was individually subjected to a series of reactions to oxidize the 2-CH3 group to the corresponding carboxaldehyde and to reduce the NO2 function to an amino group. These agents were tested for antineoplastic activity in mice bearing Sarcoma 180 ascites cells; while the o- and p-amino-substituted derivatives were inactive, the m-amino-substituted agent (4-APPT) approved to be an extremely potent antineoplastic agent.
D000814:Aniline Compounds / Q000138:chemical synthesis / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D005260:Female; D051379:Mice; D011725:Pyridines / Q000138:chemical synthesis* / Q000627:therapeutic use; D012510:Sarcoma 180 / Q000188:drug therapy; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000627:therapeutic use
D000814:Aniline Compounds; D000970:Antineoplastic Agents; D011725:Pyridines; D013882:Thiosemicarbazones