Di- and tri-methoxystyryl derivatives of heterocyclic nitrogen compounds.

A series of mono-, di-, and trimethoxystyryl derivatives of heterocyclic nitrogen compounds were prepared to test the N-O-O triangulation hypothesis of Zee-Cheng and Cheng. Of 29 free bases submitted for KB cell culture test, only 2-(3,4-methylenedioxystyryl)benzoxazole and 4-(2,5-dimethoxystyryl)cinnoline were active (ED50 of 4 microgram/ml or less). Methiodide salts were more potent: 8 of 14 were active. 2-(2,4,6-Trimethoxystyryl)quinoline methiodide and 4-(2,4,5-trimethoxystyryl)quinoline methiodide had ED50 of 0.4 and 0.9 microgram/ml, respectively. The methiodides of 2-(2,3,4-, 4-(2,4,5-, 4-(2,4,6-, and 2,4-bis-(2,4,6-trimethoxystyryl)quinoline and 1-(2,4,6-trimethoxystyryl) isoquinoline and the propiodide of 4-(2,4,6-trimethoxystyryl)quinoline were active against P388 leukemia. Several of the active compounds do not conform to the dimensions of the Zee-Cheng and Cheng triangle.