Phenethylamines biological effects

In the 1970s, Fuller examined the effects of jS,/f-difluoro substitution on the biological properties of a series of arylethylamines. Among the compounds prepared were p,p-difluoroamphetamine (19), )S,)S-difluoro phenethylamine (20), and A/-cyclopropyl-4-chloro-jS,jS-difluorophenylethylamine (21). A drop in amine pKg of about 2.5 pH units resulted from the fluorine substitution. Included in biological studies were effects on activities toward MAO. In vitro )S,)S-difluoroamphetamine was a less active inhibitor of MAO than amphetamine and )S,)S-difluorophenylethylamine was a poorer substrate for deamination than phenylethylamine. A/-Cyclopropyl-4-chlorophenylethylamine is an irreversible inhibitor of MAO. There was little difference in vivo in MAO inhibition in various tissues of the rat [72]. 

A variety of thiochromans possess biological activity. For example, 7-sulfamoylthiochroman 1,1-dioxides are effective diuretics 130-134 thiochroman-6-acetic acids possess antiinflammatory, antipyretic, and analgesic activity 135-136 phenethylamines from the Mannich reaction on thiochroman-4-ones are a-sympatliolytic137 and antidepressant 138 4-substituted aminothiochromans are active as antihypertensives, as antidepressants, and as agents against angina pains 139-142 3,3-dibromo-6-halothiochroman-4-one S-oxides exhibit antitumor characteristics 143 substituted 4-phenylthiochroman-4-ols have been prepared... 

These possible steric effects have been evaluated by an approach involving partition coefficients. In this way, an estimate of comparative lipophilicity can be made since this property is felt to influence the ease of membrane transport and thus eventual availability to the site of action. A number of psychotomimetic phenylisopropylamines have been studied in an octanol-water partition system, and the correlation of the resulting values, with central activity has provided a relationship that suggests an optimum lipophilicity for maximum biological activity (Barfknecht et al. 1975). These partition values have been correlated to serotonin receptor stimulation capability (Nichols and Dyer 1977) and have recently been extended to a number of phenethylamine compounds (Nichols et al. 1977). 

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