2-(Arylthio)ethanamines and α-(arylthio) propionamides with antidepressant activity

Abstract

Reaction of regiospecifically aziridine with thiophenols affords 2-arylthioethanamines; with 2-methylaziridine, ring opening occurs to provide l-arylthio-2-prbpanamines. The structure of one member of this group, l-(4-chlorophenylthio)-2-propanamine, (7) has been proved by other unambiguous syntheses. 7 and isomer 12 arise from the alkylation of 4-chlorothiophenc 1 with 2-chloropropylamine as well as from the displacement of the tosyl group in l-(4-chlorophenylthio)-2-tosyloxypropanc (13). Alkylation of 4-chlorothiophenol with α-chloropropionamide affords 11 which leads to 12 on LAH reduction Ethsnamines and propanamines are converted into guanidines, amides ureas and thioureas. Many arylthioethanarn ines,e.g. 7,22,28,38 and 39 (as HCL salts) and α-arylthiopropionamides, e.g. 11,86,91,93 and 96 exhibit good activity in the DO PA potentiation and reserpine antagonism tests. Among these, 7 HC1 [l-(4-chlorophenylthio)-2-propanamine hydrochloride, C 2998-Go] is the most potent and does not inhibit rat brain MAO activity. In clinical trials, C 2998-Go compares favourably with imipramine.