Synthesis and evaluation of nuciferine and roemerine enantiomers as 5-HT2 and α1 receptor antagonists. Issue 3 (26th February 2018)

• Record Type: Journal Article
• Authors: Heng, Hui Li; Chee, Chin Fei; Chin, Sek Peng; Ouyang, Yifan; Wang, Hao; Buckle, Michael J. C.; Herr, Deron R.; Paterson, Ian C.; Doughty, Stephen W.; Abd. Rahman, Noorsaadah; Chung, Lip Yong
• Is Part Of: MedChemComm. Volume 9:Issue 3(2018)
• Page Start: 576
• Page End: 582
• Publication Date: 2018-02-26
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c7md00629b
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : ( R )-roemerine was found to be a potent 5-HT2A/C receptor antagonist with good selectivity compared to 5-HT2B and α1 receptor subtypes. Abstract : In this study, the ( S )-enantiomers of the aporphine alkaloids, nuciferine and roemerine, were prepared via a synthetic route involving catalytic asymmetric hydrogenation and both stereoisomers were evaluated in vitro for functional activity at human 5-HT2 and adrenergic α1 receptor subtypes using a transforming growth factor-α shedding assay. Both enantiomers of each of the compounds were found to act as antagonists at 5-HT2 and α1 receptors. ( R )-roemerine was the most potent compound at 5-HT2A and 5-HT2C receptors (p K b = 7.8–7.9) with good selectivity compared to ( S )-roemerine at these two receptors and compared to its activity at 5-HT2B, α1A, α1B and α1D receptors.