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Identification of Novel 1-O-Substituted Aporphine Analogues as Potent 5-HT2C Receptor Agonists.

Abstract：

:The 5-HT2C receptor has emerged as a promising target in the treatment of a variety of central nervous system disorders. We have first identified aporphines as a new class of 5-HT2C receptor agonists. Structure-activity relationship results indicate that the aporphine core may be required for 5-HT2C receptor activity, and substitutions at its C1 position are important for 5-HT2C receptor activity. Our efforts to optimize our hit 15781 lead to the identification of the highly potent and selective 5-HT2C agonist 18b (MQ02-439) with an EC50 value of 104 nM and weak antagonism at the 5-HT2A and 5-HT2B receptors. The findings may serve as good starting points for the development of more potent and selective 5-HT2C agonists as valuable pharmacological tools or potential drug candidates.

journal_name

ACS Chem Neurosci

journal_title

ACS chemical neuroscience

authors

Mao Q,Zhang B,Li W,Tian S,Shui W,Ye N

doi

10.1021/acschemneuro.9b00563

subject

Has Abstract

pub_date

2020-02-19 00:00:00

pages

549-559

issue

4

issn

1948-7193

journal_volume

11

pub_type

杂志文章

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