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Higher Carbon Analogues of 1,4‐Dihydropyridines as Potent TGFβ/Smad Inhibitors
Author(s) -
Barth Eva R.,
Längle Daniel,
Wesseler Fabian,
Golz Christopher,
Krupp Anna,
Schade Dennis,
Strohmann Carsten
Publication year - 2020
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.201901223
Subject(s) - chemistry , tetrahedron , molecule , potency , stereochemistry , biological activity , small molecule , combinatorial chemistry , crystallography , biochemistry , organic chemistry , in vitro
The C to Si and Ge exchange in bioactive compounds has often led to positive changes in the molecular properties, whereby Ge analogues are underrepresented. This is only possible at tetrahedral positions, and it is necessary for the analogue building blocks to withstand the synthetic conditions. Here, we present the synthesis of Si and Ge analogues of a TGFβ inhibiting 1,4‐dihydropyridine, which has a tetrahedral carbon in an important position for its activity. The molecular properties are compared by the discussion of the single X‐ray crystal structures and the electrostatic potential on the molecule surface which could play a role in the target interaction. Biological activities show that the C to Si and Ge exchange goes with full preservation of the potency, thus representing good starting points to modify physicochemical features and pharmacokinetics of these TGFβ inhibitors.