Pyrazine compounds

Abstract

This patent describes the synthesis of a series of pyrazine compounds that are claimed as sodium (Na⁺) channel blockers which are particularly good anticonvulsants. Pharmacological data are not provided to support this mechanism of action. The compounds are reported to produce anticonvulsant activity with ED₅₀ values in the range 1 - 20 mg/kg ip. in a single model of electrically evoked tonic seizures in rats. Additional biological results regarding the particularly preferred example 2,6-diamino-3-(2,3,5-tri- chlorophenyl)pyrazine (GW273293X) have been disclosed elsewhere by the Glaxo Wellcome inventors. These confirm the Na⁺ channel blocking properties of GW273293X and extend the compound’s anticonvulsant profile across a diverse range of seizure models. As for many of their mechanistic predecessors, which include Glaxo Wellcome’s own compound lamotrigine, the pyrazines may be useful for treating epilepsy and potentially other conditions such as bipolar disorder.

• analgesics
• anticonvulsants
• bipolar disorder
• epilepsy
• sodium channel blockers