8 Chloro (S) and (R) 10 [(S) and (R) 3' methylethylaminopyrrolidino] 10,11 dihydrodibenzo [b,f] thiepins. Synthesis and pharmacological studies

Article abstract of DOI:10.1021/jm00223a009

The synthesis of 8 chloro (S) and (R) 10 [(S) and (B) 3' methylethylaminopyrrolidino] 10,11 dihydrodibenzo[b,f]thiepins is presented. The absolute configuration at position 3' of the aminopyrrolidino side chain is known from synthesis and corresponds to the asymmetric carbon atom in (S) or (R) aspartic acid. The absolute configuration at C-10 of the dihydrodibenzo[b,f]thiepin ring system was deduced from ORD-CD analysis coupled with degradation of partially resolved (+) 8 chloro 10 amino 10,11 dihydrodibenzo[b,f]thiepin to (+) (S) 1,2 diphenylethylamine. The 4 isomers were studied in mice for their ability to block conditioned avoidance responding, antagonize oxotremorine, and act as analgetics and anticonvulsants. These compounds were found to be nonselective antagonists of histamine, acetylcholine, and BaCl₂ in vitro. The compounds exerted effects similar to those of chlorpromazine. Stereoselective differences in activity between diastereoisomers, rather than between enantiomorphs, were generally observed.