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Dopamine Receptor Ligands. Part VII [1]: Novel 3‐Substituted 5‐Phenyl‐1, 2, 3, 4, 5, 6‐hexahydro‐azepino‐[4, 5‐ b ]indoles as Ligands for the Dopamine Receptors
Author(s) -
Decker Michael,
Lehmann Jochen
Publication year - 2003
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200300777
Subject(s) - chemistry , dopamine receptor , dopamine , stereochemistry , receptor , dopamine receptor d2 , d 1 , combinatorial chemistry , biochemistry , neuroscience , biology
A number of 5‐phenyl‐1, 2, 3, 4, 5, 6‐hexahydro‐azepino‐[4, 5‐ b ]indoles 3 were synthesized with different substituents at the azepine‐N position (methyl‐, allyl‐, 2‐phenyl‐ethyl‐, cyclopropylmethyl‐ and unsubstituted). Furthermore, the indole‐N‐methylated compound was generated and by using norephedrines and norpseudoephedrines as a chiral pool, 4‐methyl‐5‐phenyl‐1, 2, 3, 4, 5, 6‐hexahydro‐azepino‐[4, 5‐ b ]indoles were prepared which contained racemisation at the reacting C‐atom. These compounds, as well as the ring‐open amino‐alcohols, were screened for their affinity to the hD 1 ‐, hD 5 ‐, hD 2L ‐, and hD 4 ‐receptors (ç please check sentence). They had micromolar affinities for the receptors and showed the highest affinity to the D 1 ‐subtype family. The cyclic compounds possessed the highest affinity, with the cyclopropylmethyl‐( 3c ) and methyl‐substituents ( 3e ) being the most active of the tested compounds. Based on an intracellular cAMP‐assay, the unsubstituted compound (at the azepine‐N position) turned out to be an agonist for the D 1 ‐and D 5 ‐subtype family, whereas the substituted compounds showed (partial) agonistic, or even inverse agonistic activity.