title: Chiral indolo[3,2-f][3]benzazecine-type dopamine receptor antagonists: synthesis and activity of racemic and enantiopure derivatives.
abstract: Racemic and enantiopure 8-substituted derivatives of the lead dopamine receptor antagonist LE 300 (1) were prepared, and their affinities for the dopamine receptors (D(1)-D(5)) were tested. The separate enantiomers showed significantly different affinities; the (8S)-methyl and (8R)-hyroxymethyl derivatives where the substituents point below the reference plane of the indolo[3,2-f][3]benzazecine scaffold were markedly more active than their enantiomeric counterparts. The racemic 8-carboxy derivative was shown to be selective for the D(5)-receptor, even against D(1).
authors: Institut für Pharmazie, Abteilung Medizinische Chemie, Martin Luther Universität Halle-Wittenberg, Germany.
authors: Dina
authors: D
authors: Robaa
authors: Christoph
authors: C
authors: Enzensperger
authors: Shams
authors: S
authors: Eldin Abulazm
authors: Mohamed M
authors: MM
authors: Hefnawy
authors: Hussein I
authors: HI
authors: El-Subbagh
authors: Tanveer A
authors: TA
authors: Wani
authors: Jochen
authors: J
authors: Lehmann
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D057809:HEK293 Cells; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D018492:Dopamine Antagonists; D006576:Heterocyclic Compounds, 4 or More Rings; D007211:Indoles