title: Practical access to four stereoisomers of naftidrofuryl and their binding affinity towards 5-hydroxytryptamine 2A receptor.
abstract: Naftidrofuryl oxalate (Praxilene®, 1) has been used for the treatment of intermittent claudication for more than 30 years. It selectively blocks vascular and platelet 5-hydroxytryptamine 2 (5-HT(2)) receptors. This drug is marketed as a mixture of four stereoisomers, and so far there is no individual biological evaluation on the single isomers. The purpose of this study is to provide an improved method for the preparation of all four stereoisomers of naftidrofuryl, and more importantly, to distinguish them in terms of their binding affinity to 5-hydroxytryptamine 2A (5-HT(2A)) receptor. The bioassay results revealed that the C-2S configuration of naftidrofuryl was crucial for the binding affinity with 5-HT(2A) receptor, and the C-2' configuration was less important for binding. In conclusion, our study may pave the way to develop single naftidrofuryl isomers with C-2S configuration as inhibitors of 5-HT(2A) receptor that have clinical significance as vasodilators and CNS agents.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Hao
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Yiwu
authors.initials: Y
authors.lastname: Yao
authors.forename: Murad
authors.initials: M
authors.lastname: Hossain
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nagatomo
authors.forename: Hequan
authors.initials: H
authors.lastname: Yao
authors.forename: Lingyi
authors.initials: L
authors.lastname: Kong
authors.forename: Hongbin
authors.initials: H
authors.lastname: Sun
mesh_terms: D001681:Biological Assay; D009257:Nafronyl / Q000737:chemistry* / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D009257:Nafronyl