637000-19-2Relevant academic research and scientific papers
Structure-Based Design and Optimization of FPPQ, a Dual-Acting 5-HT3and 5-HT6Receptor Antagonist with Antipsychotic and Procognitive Properties
Zajdel, Pawe?,Grychowska, Katarzyna,Mogilski, Szczepan,Kurczab, Rafa?,Sata?a, Grzegorz,Bugno, Ryszard,Kos, Tomasz,Go?e?biowska, Joanna,Malikowska-Racia, Natalia,Nikiforuk, Agnieszka,Chaumont-Dubel, Séverine,Bantreil, Xavier,Paw?owski, Maciej,Martinez, Jean,Subra, Gilles,Lamaty, Frédéric,Marin, Philippe,Bojarski, Andrzej J.,Popik, Piotr
, p. 13279 - 13298 (2021/09/20)
In line with recent clinical trials demonstrating that ondansetron, a 5-HT3receptor (5-HT3R) antagonist, ameliorates cognitive deficits of schizophrenia and the known procognitive effects of 5-HT6receptor (5-HT6R) antagonists, we applied the hybridization strategy to design dual-acting 5-HT3/5-HT6R antagonists. We identified the first-in-class compoundFPPQ, which behaves as a 5-HT3R antagonist and a neutral antagonist 5-HT6R of the Gs pathway.FPPQshows selectivity over 87 targets and decent brain penetration. Likewise,FPPQinhibits phencyclidine (PCP)-induced hyperactivity and displays procognitive properties in the novel object recognition task. In contrast toFPPQ, neither 5-HT6R inverse agonist SB399885 nor neutral 5-HT6R antagonist CPPQ reversed (PCP)-induced hyperactivity. Thus, combination of 5-HT3R antagonism and 5-HT6R antagonism, exemplified byFPPQ, contributes to alleviating the positive-like symptoms. Present findings reveal critical structural features useful in a rational polypharmacological approach to target 5-HT3/5-HT6receptors and encourage further studies on dual-acting 5-HT3/5-HT6R antagonists for the treatment of psychiatric disorders.
NEW COMPOUNDS USEFUL FOR THE TREATMENT OF OBESITY, TYPE II DIABETES AND CNS DISORDERS
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, (2008/06/13)
The present invention relates to compounds of the general formula (I), wherein P is sulfone or sulfonamide; and A, B, W, X, Y and R3 are as defined in the description;to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the prophylaxis and treatment of medical conditions relating to obesity, type II diabetes, and/or CNS disorders, to achieve reduction of body weight and of body weight gain.
