1-[(4-hydroxypiperidine-4-yl) methyl] pyridine-2(1H)-one derivatives, preparation method and use thereof

Abstract

The present invention relates to N-[(4-hydroxypiperidine-4- Base) methyl] pyridin-2 (1H)-one derivatives, their stereoisomers, their pharmaceutically acceptable salts and their solvates, and their preparation methods, and their use in the prevention or treatment of 5-HT system dysfunction Related central nervous system diseases such as depression, anxiety, cognitive deficits, mania, schizophrenia, pain, etc., or used as a tool drug to study 5-HT function and its 5-HT dysfunction related diseases, and pharmaceutical compositions containing these compounds. Each substituent in formula I is as described in the specification.

Description

technical field [0001] The present invention relates to having 5-hydroxytryptamine 1A (5-HT) as shown in general formula I 1A ) receptor ligands and serotonin reuptake inhibitors (SSRI) dual active N-[(4-hydroxypiperidin-4-yl)methyl]pyridin-2(1H)-one derivatives, their stereoiso Constructs, their pharmaceutically acceptable salts and their solvates, and their preparation methods, and their use in the prevention or treatment of central nervous system diseases such as depression, anxiety, cognitive deficits, and mania associated with 5-HT system dysfunction schizophrenia, pain, etc., or as a tool drug for studying 5-HT function and diseases related to 5-HT dysfunction, and pharmaceutical compositions containing these compounds. Background technique [0002] 5-hydroxytryptamine (5-HT), also known as serotonin, is not only an important monoamine neurotransmitter, but also a vasoactive substance. 5-HT is widely distributed in the central nervous system (CNS) , participate in th...

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Problems solved by technology

[0008] Vilazodone (Vilazodone, EMD68843), an early discovered arylpiperazine compound, exhibits the effects of SSRIs and 5-HT 1A R partial agonism, showing good antidepressant effect, is currently in Phase III clinical research, but its clinical treatment effect is still not ideal (ME Page, et al.JPharmacol Exp Ther, 2002, 302: 1220; MJMilan.Neurotherapeutics , 2009, 6: 53); and SB-649915 has its effect on 5-HT 1A / 1B R has an antagonistic effect and can also inhibit the reuptake of 5-HT, and in vitro experiments have confirmed that it can exert an anti-anxiety effect relatively quickly (MJ Milan. Neurotherapeutics, 2009, 6: 53)

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