Abstract
cis- and trans-2,3,3a,4,5,9b-hexahydro-1H-benz [e]indoles were
synthesized as conformationally rigid analogues of
3-phenylpyrrolidine and evaluated for dopamine (DA) D2S and D3
receptor binding affinity. The tricyclic benz[e]indole nucleus was
constructed by a previously reported reductive
amination-cyclization procedure. Several unexpectedside products
were isolated and characterized using the general method. The
trans-diastereoisomers exhibited greater affinities for the DA D3
receptor than the corresponding cis-isomers. In both the cis- and
trans- series the greatest affinity for DA D3 receptors was shown
by compounds substituted with N-n-propyl or N-allyl groups. The
cis-(+-)-N-allyl derivative 21e demonstrated a D2S/D3 selectivity
of 290. Resolution of cis-(+-)-5 and trans-(+-)- 21c into
individual enantiomers showed that in both series the more active
isomer had 3aR absolute configuration. These novel ligands may be
useful tools for gaining additional information about the DA D3
receptor. Copyright Elsevier, Paris.dopamine / D2S receptor / D3
receptor / cis- and
trans-2,3,3a,4,5,9b-hexahydro-1H-benz[e]indoles / receptor binding
affinity.
Original language | English |
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Journal | European Journal of Medicinal Chemistry |
Volume | 34 |
Pages (from-to) | 487-503 |
ISSN | 0223-5234 |
Publication status | Published - 1999 |