Phenyl‐oxazoles, a New Family of Inverse Agonists at the H3 Histamine Receptor

Biogenic amines, such as histamine, are very important in human physiology. In particular, histamine is implicated in allergy (H1 receptor), [1] gastric secretion (H2R), [2] sleep/wake cycles or cognition (H3R) [3] and inflammatory/immunological processes (H4R). [4] The cloning and characterisation of H3R [5] have allowed many pharmaceutical companies to run highthroughput screening (HTS) campaigns and successfully come up with drug candidates. Pfizer, Sanofi-Aventis and Cephalon all currently have a compound in phase I clinical trials (PF3654746, SAR-110894, and CEP-26401 for Alzheimer’s disease). Moreover GlaxoSmithKline, Johnson & Johnson, Bioprojet, Transtech and Schering-Plough each have a compound in phase II (GSK-239512, BF2.649 and JNJ-31001074 as cognition enhancers, 9] SCH-497079 and HPP-404 against obesity, and BF2.649 for schizophrenia). A phase II study on another compound, GSK-189254, for the treatment of narcolepsy has recently been terminated. Several other candidates are in preclinical development or have reached some point in development for which results are expected in the near future.

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