Patent EA-001711-B1 (EA)
Title: Pyridazino [4,5-b]-quinoline 5-oxide derivatives or pharmaceutically acceptable salts thereof, use therein as gliycineb antagonists, pharmaceutical composition, method for producing pyridazino [4,5-b]-quinoline 5-oxide derivatives or quinoline salts thereof
Inventor: DANYSZ WOJCIECH
IPC: C07D471/04
Filed: 1997-07-25
Abstract: 1. Pyridazino[4,5-b]quinoline-5-oxide derivatives having the following formula:   wherein R1 and R2 are selected from the group consisting of hydrogen, halogen, and methoxy or wherein R1 and R2 together form methylenedioxy, or a pharmaceutically-acceptable salt thereof. 2. A compound of Claim 1 wherein the salt is selected from a choline and a 4-tetramethyl ammonium salt thereof. 3. A compound of Claim 1 which is selected from the group consisting of 4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, 8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, 8-bromo-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, 8-fluoro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, 7,8-dichloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, 7-bromo-8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, and 7-chloro-8-bromo-4-hydroxy-1-oxo-1,2-dihydropyridazino-[4,5-b]quinoline-5-oxide, and a pharmaceutically-acceptable salt of any of the foregoing. 4. A compound of Claim 2 selected from the group consisting of 4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, 8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, 8-bromo-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, 8-fluoro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, 7,8-dichloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, 7-bromo-8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, and 7-chloro-8-bromo-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt. 5. A pharmaceutical composition containing as active ingredient an effective relative to glycineB antagonistic amount of a compound of Claim 1 together with a pharmaceutically-acceptable carrier or diluent. 6. A pharmaceutical composition according to Claim 5 containing as active ingredient a compound of Claim 1 in the form of a choline salt. 7. A pharmaceutical composition according to Claim 5 containing a compound selected from the group consisting of 4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, 8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, 8-bromo-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, 8-fluoro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, 7,8-dichloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, 7-bromo-8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, and 7-chloro-8-bromo-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, or a pharmaceutically-acceptable salt of any of the foregoing. 8. A pharmaceutical composition according to Claim 6 containing as choline salt an effective amount of a compound selected from the group consisting of 4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt; 8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, 8-bromo-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, 8-fluoro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, 7,8-dichloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, 7-bromo-8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, and 7-chloro-8-bromo-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt. 9. The use of compound according Claim 1 for producing medical product for combatting neurological disorders, associated with excytotoxicity and glutamatergic neurotransmission dysfunction in a living animal with proviso that said product comprises a compound according Claim 1 in effective with respect to glycineB antagonistic amount. 10. The use according Claim 9 wherein a compound of Claim 1 in the form of a choline salt is used. 11. The use according Claim 9 wherein a compound selected from the group consisting of 4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, 8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, 8-bromo-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, 8-fluoro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, 7,8-dichloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, 7-bromo-8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, and 7-chloro-8-bromo-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide, or a pharmaceutically-acceptable salt of any of the foregoing is used. 12. The use according Claim 10 wherein a compound selected from the group consisting of 4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, 8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, 8-bromo-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, 8-fluoro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, 7,8-dichloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, 7-bromo-8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt, and 7-chloro-8-bromo-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt. 13. The method for producing pyridazino[4,5-b]quinoline-5-oxide derivatives and pharmaceutically-acceptable salts according Claim 1 comprising the stage of converting dimethyl quinoline-2,3-dicarboxylate-1-oxide into hydrazin salt by means of reaction with hydrazin-hydrate and hydrolysis of obtained hydrazin salt with further obtaining, if necessary, corresponding pharmaceutically-acceptable salt. 14. The method according Claim 13, wherein obtained 4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide is converted into choline salt thereof by means of reaction with choline hydrate.