Studies of the relationship between chemical structure and porphyria-inducing activity—IV: Investigations in a cell culture system

Abstract

A series of compounds has been synthesized and tested for porphyria-inducing activity in chick embryo liver cells. The results obtained support the idea that the critical feature for activity in a series of aliphatic and aromatic compounds studied is an ester or amide group which is sterically hindered from hydrolysis. Important features required for porphyria-inducing activity in the griseofulvin molecule were revealed by testing a series of griseofulvin analogues. The (+)— and (−)— isomers of glutethimide were shown to have equal porphyria-inducing activity. The activity of a series of analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine was investigated in which the 4-methyl substituent was replaced with other substituents. In the analogue containing a 4-isopropyl group activity was retained, whereas in analogues containing a benzyl, cyclohexyl or cyclohex-3-enyl substituent only very weak activity was retained.