• K C Agrawal, B A Booth, S M DeNuzzo, and A C Sartorelli.
• J. Med. Chem. 1975 Apr 1; 18 (4): 368-71.

AbstractThe 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.

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