Synthesis and in vitro evaluation of 2,4-diamino-1,3,5-triazine derivatives as neuronal voltage-gated sodium channel blockers

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 μM. 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.

Graphical abstractA series of 2,4-diamino-1,3,5-triazine derivatives was synthesized and examined as neuronal voltage-gated sodium channel blockers. Compound 4c has shown significant in vitro neuronal sodium channel binding activity with no antifolate effect.Figure optionsDownload full-size imageDownload as PowerPoint slide