Selective naphthalene H 3 receptor inverse agonists with reduced potential to induce phospholipidosis and their quinoline analogs

…, S Taylor, JM Plancher, H Richter, O Roche

Index: Rodriguez Sarmiento, Rosa Maria; Nettekoven, Matthias H.; Taylor, Sven; Plancher, Jean-Marc; Richter, Hans; Roche, Olivier Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 15 p. 4495 - 4500

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Citation Number: 22

Abstract

We reported earlier the refinement of our initial five-point pharmacophore model for the Histamine 3 receptor (H3R), with a new acceptor feature important for binding and selectivity against the other histamine receptor subtypes 1, 2 and 4. This approach was validated with a new series of H3R inverse agonists: the naphthalene series. In this Letter, we describe our efforts to overcome the phospholipidosis flag identified with our initial lead compound (1a) ...