Bollinger S, Hübner H, Heinemann FW, Meyer K, Gmeiner P (2010)
Publication Type: Journal article, Original article
Publication year: 2010
Original Authors: Bollinger S., Hübner H., Heinemann F.W., Meyer K., Gmeiner P.
Publisher: American Chemical Society
Book Volume: 53
Pages Range: 7167-7179
Journal Issue: 19
DOI: 10.1021/jm100835q
To further improve the maximal serotonergic efficacy and better understand the configurational requirements for 5-HT binding and activation, we generated and biologically investigated structural variants of the lead structure befiradol. For a bioisosteric replacement of the 3-chloro-4-fluoro moiety, a focused library of 63 compounds by solution phase parallel synthesis was developed. Target binding of our compound collection was investigated, and their affinities for 5-HT, α, and α-adrenergic as well as D-D dopamine receptors were compared. For particularly interesting test compounds, intrinsic activities at 5-HT were examined in vitro employing a GTPγS assay. The investigation guided us to highly selective 5HT superagonists. The benzothiophene-3-carboxamide 8bt revealed almost exclusive 5HT recognition with a K value of 2.7 nM and a maximal efficacy of 124%. To get insights into the bioactive conformation of our compound collection, we synthesized conformationally constrained bicyclic scaffolds when SAR data indicated a chair-type geometry and an equatorially dispositioned aminomethyl substituent for the 4,4-disubstituted piperidine moiety. © 2010 American Chemical Society.
APA:
Bollinger, S., Hübner, H., Heinemann, F.W., Meyer, K., & Gmeiner, P. (2010). Novel pyridylmethylamines as highly selective 5-HT1A superagonists. Journal of Medicinal Chemistry, 53(19), 7167-7179. https://doi.org/10.1021/jm100835q
MLA:
Bollinger, Stefan, et al. "Novel pyridylmethylamines as highly selective 5-HT1A superagonists." Journal of Medicinal Chemistry 53.19 (2010): 7167-7179.
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