Entwicklung chemischer Sonden zur Untersuchung von TGFβ-Rezeptoren und Ausweitung des chemischen Raums von Indolen

In this thesis, a 1,4-DHP-based tool box was developed with the aim to design and synthesize chemical probes for photoaffinity-labeling proteomics to enable target identification (target-ID). In addition to high potency and selectivity, a decisive attribute of a good chemical probe is the availability of an inactive, structurally closely related negative control probe. Based on these and other parameters, extensive physicochemical characterization resulted in the nomination of high-quality probes, thus providing excellent molecular tools for target-ID studies of these TβRII degraders.

The second part of this thesis was dedicated to expanding the chemical space of indoles. The focus was on the underrepresented class of 3,4-disubstituted indoles, which provided access to novel indole-based heterocycles by means of a selected multicomponent reaction. The scope and limitation of this reaction was systematically explored and furnished a unique indole-focused compound library.

 

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