title: Traceless solid-phase synthesis of nitrogen-containing heterocycles and their biological evaluations as inhibitors of neuronal sodium channels.
abstract: The preparation of pyrimidine-2-thione, pyrimidine-2-one, pyrimidine, and benzo[b][1,4]diazepine derivatives using traceless solid-phase sulfone linker strategy is described. Key steps involved are (i) sulfinate S-alkylation, (ii) sulfone anion alkylation with an epoxide, (iii) gamma-hydroxyl sulfone --> gamma-ketosulfone oxidation, and (iv) traceless product release by a one-pot elimination-cyclization process. Elimination-cyclization was carried out under basic conditions with thiourea, methyl thiourea, methyl urea, guanidine hydrochloride, benzamidine hydrochloride and ortho-phenylene diamine. Twenty-three compounds were prepared, and 14 of them were evaluated by the Batrachotoxin (BTX) radioligand binding assay for their binding affinity to neuronal sodium channels. Compound 7c was found to be a potential neuronal sodium channels blocker.
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543, Singapore.
authors.forename: Kah-Hoe
authors.initials: KH
authors.lastname: Kong
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiang
authors.initials: X
authors.lastname: Ma
authors.forename: Wai Keung
authors.initials: WK
authors.lastname: Chui
authors.forename: Yulin
authors.initials: Y
authors.lastname: Lam
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009584:Nitrogen / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis; D051381:Rats; D026941:Sodium Channel Blockers / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
chemical_list: D006571:Heterocyclic Compounds; D011743:Pyrimidines; D026941:Sodium Channel Blockers; D001569:Benzodiazepines; D009584:Nitrogen