Patent EA-002102-B1 (EA)
Title: Aminoarylpyrazine derivatives and use thereof
Inventor: COX BRIAN
IPC: C07D241/26
Filed: 1998-02-26
Abstract: 1. A compound of formula (I)   wherein R<1> is selected from the group consisting of phenyl substituted by one or more halogen atoms, naphthyl and naphthyl substituted by one or more halogen atoms; R<2> is selected from the group consisting of -NH2 and --NHC(.dbd.O)R<a> ; R<3> is selected from the group consisting of -NR<b> R<c>, --NHC(.dbd.O) R<a> and hydrogen; R<4> is selected from the group consisting of hydrogen, -C1-4 alkyl, --CN, --CH2OH, --CH2R<d>, --CH2S(O)xR<d> and - C1-4 alkyl substituted by one or more halogen atoms; wherein R<a> represents C1-4 alkyl or C3-7 cycloalkyl, and R<b> and R<c>, which may be the same or different, are selected from hydrogen and C1-4 alkyl, or together with the nitrogen atom to which they are attached, form a 6-membered saturated heterocycle which heterocycle can be further substituted with one or more C1-4 alkyl; R<d> is selected from C1-4 alkyl or C1-4 alkyl substituted by one or more halogen atoms; x is an integer zero, one or two; and pharmaceutically acceptable derivatives thereof; with the proviso that R<1> does not represent    when R<2> is -NH2, and both R<3> and R<4> are hydrogen. 2. A compound according to claim 1 wherein R<1> is phenyl substituted by one or more halogen atoms. 3. A compound according to claim 2 wherein R<1> is 2,3,5-trichlorophenyl. 4. A compound according to claims 1 to 3wherein R<2> and R<3> are -NH2. 5. A compound according to claims 1 to 4 wherein R<4> is hydrogen or -CH2OH. 6. A compound according to claim 5 wherein R<4> is hydrogen. 7. The compound which is 2,6-diamino-3-(2,3,5-trichlorophenyl)pyrazine and pharmaceutically acceptable derivatives thereof. 8. A compound according to any of claims 1 to 7 for use in therapy. 9. A pharmaceutical composition comprising a compound according to claims 1 to 7, together with a pharmaceutically acceptable carrier. 10. The use of a compound according to any of claims 1 to 7 in the manufacture of a medicament for use in the treatment of epilepsy, bipolar disorder or manic depression, pain, neurogenerative diseases, neuroprotection, neurodegeneration, or prevention or reducing dependence on, or preventing or reducing tolerance or reverse tolerance to, a dependence-inducing agent. 11. A method of treating a patient suffering from, or susceptible to, epilepsy, bipolar disorder or manic depression, pain, functional bowel disorders, neurogenerative diseases, neuroprotection, neurodegeneration, or dependent on, or having tolerance or reverse tolerance to, a dependence-inducing agent administering an effective amount of a compound according to any of claims 1 to 7. 12. A process for preparing a compound of formula (I) as defined in claim 1 which comprises: a compound of formula (II)   submitting compound of formula (II) where Hal (B) represents a halogen atom, to suitable reaction conditions; compounds of formula (I) may be converted into corresponding compounds of formula (I) by employing suitable reaction techniques. 13. A process for preparing a compound of formula (I) as defined in claim 1 which comprises: a compound of formula (VII)   reacting a compound of formula (VII) where Hal represents a halogen atom, with a compound of formula (IV) R<1>B(OH)2; compounds of formula (I) may be converted into corresponding compounds of formula (I) by employing suitable reaction techniques. 14. A process for preparing a compound of formula (I) as defined in claim 1 which comprises: where R<2> represents NH2, by cylisation and oxidation of a compound of formula (XI)    or a salt thereof according to conventional procedures;  compounds of formula (I) may be converted into corresponding compounds of formula (I) by employing suitable reaction techniques.