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Benzoxazole piperidines as selective and potent somatostatin receptor subtype 5 antagonists |
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| Authors: | Rainer E. Martin Peter Mohr Hans Peter Maerki Wolfgang Guba Christoph Kuratli Olivier Gavelle Alfred Binggeli Stefanie Bendels Rubén Alvarez-Sánchez André Alker Liudmila Polonchuk Andreas D. Christ |
| Affiliation: | 1. F. Hoffmann-La Roche Ltd, Pharmaceuticals Division, Medicinal Chemistry, CH-4070 Basel, Switzerland;2. F. Hoffmann-La Roche Ltd, Pharmaceuticals Division, Nonclinical Drug Safety, CH-4070 Basel, Switzerland;3. F. Hoffmann-La Roche Ltd, Pharmaceuticals Division, Molecular Structure Research, CH-4070 Basel, Switzerland;4. F. Hoffmann-La Roche Ltd, Pharmaceuticals Division, Discovery Metabolic and Vascular Diseases, CH-4070 Basel, Switzerland |
| Abstract: | SAR studies of a recently described SST5R selective benzoxazole piperidine lead series are described with particular focus on the substitution pattern on the benzyl and benzoxazole side-chains. Introduction of a second meta substituent at the benzyl unit significantly lowers residual hH1 activity and insertion of substituents onto the benzoxazole periphery entirely removes remaining h5-HT2B activity. Compounds with single digit nM activity, functional antagonism and favorable physicochemical properties endowed with a good pharmacokinetic profile in rats are described which should become valuable tools for exploring the pharmacological role of the SST5 receptor in vivo. |
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