Benzo[b]thiophene derivatives. XXIII. Derivatives of 5,6-dihydroxy-3-benzo[b] thienylacetic acid

A series of 5,6-disubstituted benzob]thiophenes have been synthesized for biological evaluation. These include analogs of tryptamine, melatonin and harmaline types, having hydroxy, methoxy, methoxymethyloxy, or isopropylidenedioxy groups at both the 5- and 6- positions. In order to synthesize these, the appropriate mercaptoguaiacols were prepared, and condensed with chloroacetoacetic esters to the 4-arylthioacetoacetic esters. Cyclization of these ketones was best accomplished when the free phenolic groups were masked by methoxymethyl groups. The benzob] thienylacetic esters were then converted to corresponding amides, reduced to tryptamine analogs, acetylated to melatonin analogs, and cyclized to harmaline analogs. N-Acetyltryptamine and 1-methylmelatonin were also synthesized for comparison. Preliminary bioassay results on the melatonin analogs, which showed activity, are reported.