Chiral indolo[3,2-f][3]benzazecine-type dopamine receptor antagonists: synthesis and activity of racemic and enantiopure derivatives.

Dina Robaa, Christoph Enzensperger, Shams Eldin Abulazm, Mohamed M Hefnawy, Hussein I El-Subbagh, Tanveer A Wani, Jochen Lehmann

Institut für Pharmazie, Abteilung Medizinische Chemie, Martin Luther Universität Halle-Wittenberg, Germany.

Journal of medicinal chemistry 2011 Oct 27

filter terms:

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).

Citation

Dina Robaa, Christoph Enzensperger, Shams Eldin Abulazm, Mohamed M Hefnawy, Hussein I El-Subbagh, Tanveer A Wani, Jochen Lehmann. Chiral indolo[3,2-f][3]benzazecine-type dopamine receptor antagonists: synthesis and activity of racemic and enantiopure derivatives. Journal of medicinal chemistry. 2011 Oct 27;54(20):7422-6