Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans

Article abstract of DOI:10.1021/jm00361a002

A series of 1-piperazino-3-phenylindans was synthesized and tested for neuroleptic and thymoleptic activity. Neuroleptic activity was found only in trans racemates and was associated with one of the enantiomers only. The potent and long-acting neuroleptic compound trans-4-[3-(4-fluorophenyl)-6-(trifluoromethyl)indan-1-yl]-1-piperazineeth anol (Lu 18-012, tefludazine) was developed by systematic variation of structural components. Thymoleptic activity was optimized, especially with respect to dopamine-uptake inhibition. No geometrical stereoselectivity was found with regard to dopamine-uptake inhibition, but a high enantioselectivity could be demonstrated for both cis and trans racemates. The most potent compounds were 1-piperazino-3-(3,4-dichlorophenyl)indans with IC₅₀ values of about 2 nM for inhibition of dopamine uptake.