Refinement of histamine H3 ligands pharmacophore model leads to a new class of potent and selective naphthalene inverse agonists |
| |
Authors: | Roche Olivier Nettekoven Matthias Vifian Walter Sarmiento Rosa Maria Rodriguez |
| |
Affiliation: | aF. Hoffmann-La Roche Ltd., Pharmaceutical Research Basel, Discovery Chemistry, CH-4070 Basel, Switzerland |
| |
Abstract: | The refinement of our original five point pharmacophore model for the H3 receptor with the addition of a new acceptor feature is presented. The importance of this new acceptor feature for the binding and the selectivity against H1, H2 and H4 has been validated using a newly synthesized naphthalene series. With the SAR deduced from several hundred naphthalene derivatives in various sub-classes the specific role of each pharmacophoric feature, by varying the geometry, size and charge of the molecules, was elucidated. This led to the discovery of a highly potent and selective new compounds series. |
| |
Keywords: | Histamine H3 receptor SAR Pharmacophore model Naphthalene GPCR |
本文献已被 ScienceDirect PubMed 等数据库收录! |