Privilegierte Strukturen neu betrachtet

Privilegierte Strukturen inspirieren den Entwurf von Substanzbibliotheken fur die medizinische Chemie. Wir haben 1.4 Millionen bioaktive Substanzen hinsichtlich der Dominanz bestimmter chemischer Grundgeruste (“frameworks”) untersucht. Dabei diente die Shannon-Entropie als ein quantitatives Mas fur deren Promiskuitat bezuglich der verschiedenen Targetfamilien. Diese Analyse offenbarte eine inverse Beziehung zwischen der Zahl an Wasserstoffbruckenakzeptoren und der beobachteten Promiskuitat des Grundgerusts. Des Weiteren scheinen sich strukturell einfache Geruste besonders fur Substanzbibliotheken mit unterschiedlichem Promiskuitatsgrad zu eignen, wohingegen sp3-reiche heterozyklische Grundgeruste den Entwurf von Target-fokussierten Bibliotheken ermoglichen. Die Resultate unserer Studie erlauben ein kritisches Hinterfragen von oft nur vermuteten besonderen Eigenschaften so genannter privilegierter Strukturen und weisen einen Weg zu deren systematischer Nutzung in der medizinischen Chemie.

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