(4-Benzylpiperidine-1-yl)-(6-hydroxy-1H-indole-2-yl)-methanone (6a) derived from (E)-1-(4-benzylpiperidin-1-yl)-3-(4-hydroxy-phenyl)-propenone (5) was identified as a potent NR2B subunit-selective antagonist of the NMDA receptor. To establish the structure-activity relationship (SAR) and to attempt the improvement of the ADME properties of the lead, a series of compounds were prepared and tested. Several derivatives showed low nanomolar activity both in the binding and in the functional assay. In a formalin-induced hyperalgesia model in mice, 6a and (4-benzylpiperidine-1-yl)-[5(6)-hydroxy-1H-benzimidazol-2-yl]-methanone (60a) were as active as besonprodil (2) after oral administration. A CoMSIA model was developed based on binding data of a series of indole- and benzimidazole-2-carboxamides.

No abstract

No abstract

Bei Bestrahlung der Titelverbindungen, wie z.B. (I) und (VII), in z.B. Ethanol entstehen sechs Arten von heterocyclischen Produkten: Benzotriazepine, wie z.B. (II), Chinazoline, wie z.B. (III) oder (VIII), Dichinazolinylethane, wie z.B. (IX), N‐Chinazolinylmethylcarbamate, wie z.B. (X), 4‐Alkoxychinazoline, wie z.B. (IV) und 3‐Acylam.inochinazolinone, wie z.B. (VI) (letztere können beim Einsatz von (Ia) identifiziert werden).