Porphyria-inducing activity of a series of pyridine and dihydropyridine compounds. Investigation in a cell culture system.

Abstract

A series of analogs of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC)was prepared and tested for porphyria-inducing activity in chick embryo liver cells. One of the analogs tested, viz.3,5-di-tert-butoxycarbonyl-1,4-dihydro-2,6-dimethylpyridine, was found to be highly active despite the absence of a 4-alkyl substituent. It was concluded that tert-butoxycarbonyl groups are resistant to enzymic hydrolysis and that compounds containing such groups are resistant to inactivation by chick embryo liver cells. Several analogs of DDC were found with considerably higher activity. These should be useful in inducing high levels of beta-aminolevulinic acid synthetase prior to undertaking the isolation of the enzyme.