title: Residues at the indole-NH of LE300 modulate affinities and selectivities for dopamine receptors.
abstract: To further investigate SAR in the class of azecine-type dopamine receptor antagonists, we synthesized a series of derivatives, substituted at the indole-NH of the lead compound LE300 by different alkyl chains in addition to phenylpropyl, allyl, propargyl, and acetyl residues. The affinities of the target compounds for all human dopamine receptors (D(1) -D(5) ) were investigated by radioligand binding assay and their functionality by a calcium assay. Both the affinities and selectivities for the dopamine receptors were found to be affected by the nature of the substituent. The N14-methylated derivative displayed the highest affinities for all D-receptors. In general, the affinities decreased with increasing chain length of the N-alkyl. Different substituents, partly led to altered affinity, and selectivity profile when compared with our lead LE300.
authors.affiliation: Institut für Pharmazie, Lehrstuhl für Pharmazeutische/Medizinische Chemie, Friedrich Schiller Universität Jena, Germany.
authors.forename: Dina
authors.initials: D
authors.lastname: Robaa
authors.forename: Robert
authors.initials: R
authors.lastname: Kretschmer
authors.forename: Oliver
authors.initials: O
authors.lastname: Siol
authors.forename: Shams Eldin
authors.initials: SE
authors.lastname: Abulazm
authors.forename: Elsayeda
authors.initials: E
authors.lastname: Elkhawass
authors.forename: Jochen
authors.initials: J
authors.lastname: Lehmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Enzensperger
mesh_terms: D018492:Dopamine Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: C409874:7-methyl-6,7,8,9,14,15-hexahydro-5H-benz(d)indolo(2,3-g)azecine; D018492:Dopamine Antagonists; D007211:Indoles; D011954:Receptors, Dopamine