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Updated: Jul 10, 2026

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: optimising brain penetration
Jens-Uwe Peters1, Thomas Lübbers, Alexander Alanine
1Discovery Chemistry, Pharma Division, F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland. jens-uwe.peters@roche.com
Abstract:
The optimisation of molecular properties within a series of 2-amino dihydroquinazoline 5-HT5A/5-HT7 receptor ligands resulted in a significantly improved brain-to-plasma ratio, enhancing the pharmacological utility of these compounds. By modulating the lipophilicity and pKa, a 20-fold increase in brain-to-plasma ratio could be achieved, leading to micromolar brain concentrations after oral administration. The enantiomers of one representative of this series of improved compounds were separated, and the configuration of the eutomer was determined by X-ray crystallography.
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