Potential CNS antitumor agents - Phenothiazines. II: Fluphenazine analogs

Article abstract of DOI:10.1002/jps.2600670209

Fluphenazine was found to possess moderate, reproducible activity against the intraperitoneal L-1210 and P-388 leukemia murine tumor models. Seven ether derivatives of fluphenazine and eight compounds in which the terminal side-chain hydroxyl group was replaced by an amine function were prepared and evaluated in the intraperitoneal L-1210, P-388, and B16 melanoma systems as well as the intracerebral L-1210 and ependymoblastoma brain tumor models. While no substantial intracerebral activity was observed, seven derivatives possessed reproducible activity in the intraperitoneal L-1210 or P-388 system. Several gave T/C [(treated survival/control survival) x 100%] values of 150%. No B16 melanoma activity was observed. These compounds were also tested for their cytototoxic properties in culture against L-1210, P-388, and KB cells. The amine isosteres, while possessing little in vivo activity, were the most cytotoxic of the compounds prepared, with several having ED₅₀ values <1 μg/ml.