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Updated: Jul 10, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Discovery of the first nonpeptidic, small-molecule, highly selective somatostatin receptor subtype 5 antagonists: a
Rainer E Martin1, Luke G Green, Wolfgang Guba
1Discovery Chemistry, Lead Generation, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
Abstract:
We disclose the first selective, nonpeptidic, small-molecule somatostatin receptor subtype 5 (SST5R) antagonists that were identified by a chemogenomics approach based on the analysis of the homology of amino acids defining the putative consensus drug binding site of SST5R. With this strategy, opioid, histamine, dopamine, and serotonine receptors were identified as the closest neighbors of SST5R. The H1 antagonist astemizole was chosen as a seed structure and subsequently transformed into a SST5 receptor antagonist with nanomolar binding affinity devoid of the original target activity.
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