%0 Journal Article
%T Identification of Novel 1-O-Substituted Aporphine Analogues as Potent 5-HT2C Receptor Agonists.
%A Mao Q
%A Zhang B
%A Li W
%A Tian S
%A Shui W
%A Ye N
%J ACS Chem Neurosci
%V 11
%N 4
%D 02 2020 19
%M 31968160
%F 5.78
%R 10.1021/acschemneuro.9b00563
%X 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.