Aporphinoid antagonists of 5-HT2A receptors: further evaluation of ring A substituents and the size of ring C.

ABSTRACT: A series of ring A-modified analogs of nantenine as well as structural variants in ring C were synthesized and evaluated for antagonist activity at 5-HT2A and α1A receptors. Halogenation improves 5-HT2A antagonist potency in molecules containing a C1 methoxyl/C2 methoxyl or C1 methoxyl/C2 hydroxyl moiety. Bromination or iodination (but not chlorination) with the latter moiety also significantly increased α1A antagonist potency. Homologation or contraction of ring C adversely affected antagonist activity at both receptors, implying that a six-membered ring C motif is beneficial for high antagonist potency at both receptors. Molecular docking studies suggest that the improved antagonist activity (by virtue of improved affinity) of C3-halogenated aporphines in this study is attributable to fa

SUBMITTER: Ponnala S 

PROVIDER: S-EPMC4197079 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature