Neuroleptic agents of the benzocycloheptapyridoisoquinoline series. 1. Syntheses and stereochemical and structural requirements for activity of butaclamol and related compounds.

The syntheses and the structural and stereochemical requirements for antagonism of (+)-amphetamine-induced sterotypy are described for a series of benzocycloheptapyridoisoquinoline derivatives. One of these compounds, (plus or minus)-(4a,13b-trans)[3(OH),13b(H)-trans[-3-tert-butyl-2,3,4,4a,8,9,13b,14-octahydro-1H-benzo[6,7]cyclohepta[1,2,3-de]pyrido[2,1-a]isoquinolin-3ol hydrochloride (butaclamol hydrochloride, USAN), is currently being studied in man. The relationship between structure and antiamphetamine activity in this class of compounds is discussed.