Synthesis and Biological Evaluation of Isoxazoline and Isoxazole Derivatives as 5-HT2A and 5-HT2C Receptor Ligands

Title
Synthesis and Biological Evaluation of Isoxazoline and Isoxazole Derivatives as 5-HT2A and 5-HT2C Receptor Ligands
Authors
윤해석이은주이지은박우규백두종조용서고훈영추현아배애님
Keywords
Isoxazoline; Isoxazole; Antidepressant; Serotonin; Serotonin receptor
Issue Date
2009-08
Publisher
Bulletin of the Korean Chemical Society
Citation
VOL 30, NO 8, 1873-1876
Abstract
Antidepressants have been available since 1950s. The first generation drugs are monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). The second generation antidepressants are selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs), which are more selectively bound to the targets such as serotonin transporter and/or norepinephrine transporter resulting in reduced side effects. However, all antidepressants in clinical use show limited efficacy, slow onset of action, and variable degree of side effects such as changes in sexual performance. To fulfill these unmet needs of the antidepressants, there have been efforts to find new mechanisms that can be exploited for developing faster-acting and more efficient antidepressants. Several potential mechanisms have been reported, which include antagonism of the serotonin autoreceptors (5-HT1A), postsynaptic serotonin receptors (5-HT2A and 5-HT2C), neurokinin receptors, and corticotrophin- releasing factor (CRF). It is worth to note that the effect of citalopram, one of the SSRIs, can be augmented by pre-treatment with either 5-HT2A antagonist or 5-HT2C antagonist.6b Therefore, 5-HT2A and 5-HT2C receptors represent reasonable targets for the improved treatment of depression. In this study, in order to discover 5-HT2A and 5-HT2C receptor antagonists, we synthesized a series of isoxazoline and ioxazole derivatives and evaluated their binding affinities to 5-HT2A and 5-HT2C receptors.
URI
http://pubs.kist.re.kr/handle/201004/35760
ISSN
0253-2964
Appears in Collections:
KIST Publication > Article
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