title: Synthesis and in vitro evaluation of 2,4-diamino-1,3,5-triazine derivatives as neuronal voltage-gated sodium channel blockers.
abstract: Neuronal sodium channels blockers interfere with ion flux and have been used for managing neuropathic pain, epilepsy, and cerebral ischemic disorders. In the current study, four groups of 2,4-diamino-1,3,5-triazine derivatives were synthesized and investigated for their neuronal sodium channels binding activity. 5-Aryl-1,3,5-triazaspiro[5.5]undeca-1,3-diene-2,4-diamines (4a-4j) were found to have the best neuronal sodium binding activity among the four groups of triazines evaluated. Derivatives 4a-4j blocked the sodium channels with IC50 values ranged from 4.0 to 14.7 microM. The result from this study showed that analogues of 2,4-diamino-1,3,5-triazines could be used as leads for the discovery of neuronal sodium channels blockers for managing central nervous system related disorders.
authors.affiliation: Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore. chemx@nus.edu.sg
authors.forename: Xiang
authors.initials: X
authors.lastname: Ma
authors.forename: Thong-Yuen
authors.initials: TY
authors.lastname: Poon
authors.forename: Peter Tsun Hon
authors.initials: PT
authors.lastname: Wong
authors.forename: Wai-Keung
authors.initials: WK
authors.lastname: Chui
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D002493:Central Nervous System Diseases / Q000188:drug therapy; D026941:Sodium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015222:Sodium Channels / Q000737:chemistry* / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D014227:Triazines; D013762:Tetrahydrofolate Dehydrogenase