Synthesis and antitumor activity of halogen-substituted 4-(3,3-dimethyl-1-triazeno)quinolines

Halogenated 4-(3,3-dimethyl-1-triazeno)quinolines were synthesized as potential antitumor agents on the basis of the biochemical pharmacological properties of existing triazenes, their structural-activity relationships, and the high melanin binding of chloroquine and iodoquine in vivo and in vitro. They were synthesized by diazotization of appropriate halogen-substituted 4-aminoquinolines in fluoboric acid at -5 degrees C followed by coupling with dimethylamine. Among these new compounds, 8-chloro-4-(3,3-dimethyl-1-triazeno)quinoline produces significant antitumor activity against both P-388 and L1210 murine leukemias. Although only marginally active or inactive against P-388, the other chloro, bromo, or iodo analogues show activity against L1210 comparable to that of dacarbazine (DIC). However, none of these compounds is active against B-16 melanoma. Compared with DIC these new agents demonstrate a higher in vitro affinity for melanin; however, this affinity is apparently not correlated with their antitumor activity.