Kombination von On-Chip-Synthese einer fokussierten kombinatorischen Bibliothek mit computergestützter Vorhersage der biologischen Aktivität enthüllt Imidazopyridine als GPCR-Liganden†

Am Beispiel der Ugi-Dreikomponentenreaktion stellen wir ein schnelles und effizientes Verfahren fur die Kopplung von On-Chip-Mikroflusssynthesen mit einer neuen Methode zur Vorhersage biologischer Targets vor, um neue Liganden-Protein-Beziehungen zu entdecken. Wir konnten auf diese Weise eine GPCR-modulierende, kombinatorisch zugangliche Verbindungsklasse identifizieren. Diese effizienten Liganden binden mit antagonistischen Eigenschaften an die humanen Adenosin-A1/2B- und adrenergen α1A/B-Rezeptoren. Die Integration von Mikrofluidiksystemen fur die chemische Synthese mit computergestutzten Targetvorhersagen ist ein vielversprechendes Verfahren zur raschen Erstellung fokussierter Substanzbibliotheken mit hohen Trefferraten.

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