Tricyclics with analgesic and antidepressant activity. 2. [[(Alkylamino)ethyl]thio]dibenzo[b,f]thiepins and 10,11-dihydro derivatives

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Abstract
A series of [[(alkylamino)ethyl]thio]dibenz-[b,f]-thiepins (III) [10-[[.beta.-(dimethylamino)ethyl]thio]dibenzo-[b,f]-thiepin hydrochloride; 10,11-dihydro-10-[[.beta.-(methylamino)ethyl]thio]dibenzo-[b,f]-thiepin hydrochloride; 10-[[.beta.-[N-methyl-N-(phenoxycarbonyl)amino]ethyl]-thio]dibenzo-[b,f]-thiepin; 10-[[.beta.-(methylamino)ethyl]thio]dibenzo-[b,f]-thiepin maleate; 2-hydroxy-11-[[.beta.-(methylamino)ethyl]dibenzo-[b,f]-thiepin; and 2-fluoro-11-[[.beta.-(methylamino)ethyl]thio]dibenzo-[b,f]-thiepin] and their 10,11-dihydro derivatives (IV) [10-[[.beta.-bromoethyl]thio]-10,11-dihydrodibenzo-[b,f]-thiepin; 2-fluoro-11-[[.beta.-bromoethyl]thio]-10,11-dihydrodibenzo-[b,f]-thiepin; 2-chloro-11-[(.beta.-bromoethyl)thio]-10,11-dihydrobenzo-[b,f]-thiepin; and 10,11-dihydro-10-[[.beta.-(methylamino)ethyl]thio]dibenzo-[b,f]thiepin hydrochloride] was synthesized and subjected to broad analgesic/CNS screening. Preliminary results indicated a combination of analgesic/antidepressant profiles, similar to that observed for the [[(alkylamino)ethyl]thio]dibenz[b,f]oxepins (I) and their corresponding dihydro derivatives (II). The most active congener from the present series, shows an antinociceptive potency in the pentazocine range as assessed by phenyl-p-quinone-induced writhing (PQW) and tail flick in mice. It is more than twice as active as imipramine in preventing tetrabenazine-induced ptosis (TBZ), a test widely recognized to be of predictive value for clinically efficacious antidepressants.

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