Claims
- 1. A compound of the formula (I) ##STR48## wherein: Z is aryl, substituted aryl, phenyl-lower-alkyl, hetero-aryl selected from the group consisting of pyrazolyl, imidazolyl, isoxazolyl, tetrazolyl, furyl, thienyl, oxazolyl, thiazolyl, piperidyl, morpholinyl, imidazolinyl, piperazinyl, and thiamorpholinyl, substituted heteroaryl, heterocycloalkyl, heterocyclocalkyl-lower-alkyl, hetero-aryl-lower-alkyl wherein one or more hydrogens of aryl and heteroaryl is optionally replaced by A and B;
- Y is phenyl, phenyl-lower-alkyl, wherein one or more hydrogens of phenyl is optionally replaced by A and B;
- X is --CONH.sub.2, CONHOH, CON(R).sub.2, or CONR--CHR--CO--A or CONR--(CHR).sub.n --A;
- A and B are independently H, OH, OR, lower alkyl, N(R).sub.2, CON(R).sub.2, SR, NHSO.sub.2 R, hydroxy-lower-alkyl, NHCOR, NRSO.sub.2 CF.sub.3, OSO.sub.2 CF.sub.3, or CN;
- R is phenyl-lower-alkyl, hydroxy-lower-alkyl, CO-lower-alkyl, or CO--(CH.sub.2).sub.n -aryl; and
- is 1, 2, or 3,
- a pharmaceutically acceptable salt thereof.
- 2. A compound having the formula (II) ##STR49## wherein: Z is aryl, phenyl-lower-alkyl, hetero-aryl selected from the group consisting of, pyrazolyl, imidazolyl, isoxazolyl, tetrazolyl, furyl, thienyl, oxazolyl, thiazolyl, piperidyl, morpholinyl, imidazolinyl, piperazinyl, and thiamorpholinyl, heterocycloalkyl, heterocycloalkyl-lower-alkyl, hetero-aryl-lower-alkyl wherein one or more hydrogens of aryl and heteroaryl is optionally replaced by A and B;
- A and B arc independently H, OH, OR, lower alkyl, N(R).sub.2, CON(R).sub.2, SR, NHSO.sub.2 R, hydroxy-lower-alkyl, NHCOR, NRSO.sub.2 CF.sub.3, OSO.sub.2 CF.sub.3, or CN;
- R is H, phenyl-lower-alkyl, hydroxy-lower-alkyl, CO-lower-alkyl, or CO--(CH.sub.2).sub.n -aryl; and
- n is 1, 2, or 3,
- or a pharmaceutically acceptable salt thereof.
- 3. The compound of claim 1 selected from the group consisting of 1,4-Dihydro-1 -(2-chloro-4- hydroxyphenyl)-4-oxo-7-(3-furyl)-3-quinolinecarboxamide, 1,4-Dihydro-1-(2-chloro-4-hydroxyphenyl)-4-oxo-7-(4-pyridazinyl)-3-quinolinecarboxamide, 1,4-Dihydro-1-(2-chloro-4-hydroxyphenyl)-4-oxo-7-(3-pyrazolyl)-3-quinolinecarboxamide, 1,4-Dihydro-1-(2-chloro-4-hydroxyphenyl)-4-oxo-7-(3-chloro-4-pyridazinyl)-3-quinolinecarboxamide, and 1,4-Dihydro-1-(2-chloro-4-hydroxyphenyl)-4-oxo-7-phenyl-3-quinolinecarboxamide.
- 4. The compound of claim 1 selected from the group consisting of: 1,4-Dihydro-1-(-4-hydroxy-2-pyridyl)-4-oxo-7-(2-pyridyl)-3-quinoline-carboxamide.
- 5. The compound of claim 1 which is 1,4-Dihydro-1-(4-trifluoromethylsulfonyloxyphenyl)-4-oxo-7-(4-pyridyl)-3-quinolinecarboxamide.
- 6. The compound of claim 1 selected from the group consisting of: 1,4-Dihydro-1-(4-hydroxyphenyl)-4-oxo-7-bromo-3-quinolinecarboxamide, 1,4-Dihydro-1-(4-hydroxyphenyl)-4-oxo-3-quinolinecarboxamide, 1,4-Dihydro-1-(4-hydroxyphenyl)-4-oxo-7-phenyl-3-quinolinecarboxamide and 1,4-Dihydro-1-(2-chloro-4-hydroxyphenyl)-4-oxo-7-(3,5-dimethyl-4-isoxazolyl)-3-quinolinecarboxamide.
- 7. A pharmaceutical composition for the treatment or inhibition of ischemia-induced neurodegenerative diseases in a mammal comprising an effective amount of a compound of the formula (I) ##STR50## wherein: Z is aryl, substituted aryl, phenyl-lower-alkyl, hetero-aryl selected from the group consisting of pyrazolyl, imidazolyl, isoxazolyl, tetrazolyl, furyl, thienyl, oxazolyl, thiazolyl, piperidyl, morpholinyl, imidazolinyl, piperazinyl, and thiamorpholinyl, substituted heteroaryl, heterocycloalkyl, heterocyclocalkyl-lower-alkyl, hetero-aryl-lower-alkyl wherein one or more hydrogens of aryl and heteroaryl is optionally replaced by A and B;
- Y is phenyl, phenyl-lower-alkyl, wherein one or more hydrogens of phenyl is optionally replaced by A and B;
- X is --CONH.sub.2, CONHOH, CON(R).sub.2, or CONR--CHR--CO--A or CONR--(CHR).sub.n --A;
- A and B are independently H, OH, OR, lower alkyl, N(R).sub.2, CON(R).sub.2, SR, NHSO.sub.2 R, hydroxy-lower-alkyl, NHCOR, NRSO.sub.2 CF.sub.3, OSO.sub.2 CF.sub.3, or CN;
- R is phenyl-lower-alkyl, hydroxy-lower-alkyl, CO-lower-alkyl, or CO--(CH.sub.2).sub.n -aryl; and
- n is 1, 2, or 3,
- or a pharmaceutically acceptable salt thereof.
- 8. The pharmaceutical composition for the treatment or inhibition of ischemia-induced neurodegenerative diseases in a mammal comprising an effective amount of a compound of the formula (II) ##STR51## wherein: Z is aryl, phenyl-lower-alkyl, hetero-aryl selected from the group consisting of pyrazolyl, imidazolyl, isoxazolyl, tetrazolyl, furyl, thienyl, oxazolyl, thiazolyl, piperidyl, morpholinyl, imidazolinyl, piperazinyl, and thiamorpholinyl, heterocycloalkyl, heterocycloalkyl-lower-alkyl, hetero-aryl-lower-alkyl wherein one or more hydrogens of aryl and heteroaryl is optionally replaced by A and B;
- A and B are independently H, OH, OR, lower alkyl, N(R).sub.2, CON(R).sub.2, SR, NHSO.sub.2 R, hydroxy-lower-alkyl, NHCOR, NRSO.sub.2 CF.sub.3, OSO.sub.2 CF.sub.3, or CN;
- R is H, phenyl-lower-alkyl, hydroxy-lower-alkyl, CO-lower-alkyl, or CO--(CH.sub.2).sub.n -aryl; and
- n is 1,2, or 3,
- or a pharmaceutically acceptable salt thereof.
- 9. A pharmaceutical composition for the treatment or inhibition of ischemia-induced neurodegenerative disease wherein said compound is selected from the group consisting of: 1,4-Dihydro-l-(2-chloro-4-hydroxyphenyl)-4-oxo-7-(4-pyridazinyl)-3-quinolinecarboxamide, 1,4-Dihydro-1-(2-chloro-4-hydroxyphenyl)-4-oxo-7-(3-pyrazolyl)-3-quinolinecarboxamide, 1,4-Dihydro-1-(2-chloro-4-hydroxyphenyl)-4-oxo-7-(3-pyrazolyl)-3-quinolinecarboxamide, 1,4-Dihydro-1 -(2-chloro-4-hydroxyphenyl)-4-oxo-7-(3-chloro-4-pyridazinyl)-3-quinolinecarboxamide, and 1,4-Dihydro-1-(2-chloro-4-hydroxyphenyl)-4-oxo-7-phenyl-3-quinolinecarboxamide.
- 10. A pharmaceutical composition for the treatment or inhibition of ischemia-induced neurodegenerative disease wherein said compound is 1,4-Dihydro-1-(4-trifluoromethylsulfonyloxyphenyl)-4-oxo-7-(4-pyridyl)-3-quinolinecarboxamide.
- 11. The pharmaceutical composition of claim 7 wherein said compound is selected from the group consisting of: 1,4-Dihydro-1-(4-hydroxyphenyl)-4-oxo-3quinolinecarboxamide, 1,4-Dihydro-l-(4-hydroxyphenyl)-4-oxo-7-phenyl-3quinolinecarboxamide and 1,4-Dihydro-1-(2-chloro-4-hydroxyphenyl)-4-oxo-7-(3,5-dimethyl-4-isoxazolyl)-3-quinolinecarboxamide.
- 12. A method of treating or inhibiting ischemia-induced neurodegenerative disease in a mammal comprising the administration to said mammal an effective amount of a composition according to claim 7.
- 13. A method of treating or inhibiting ischemia-induced neurodegenerative disease in a mammal comprising the administration to said mammal an effective amount of a composition according to claim 8.
- 14. A method of treating or inhibiting ischemia-induced neurodegenerative disease in a mammal comprising the administration to said mammal an effective amount of a composition according to claim 9.
- 15. A method of treating or inhibiting ischemia-induced neurodegenerative disease in a mammal comprising the administration to said mammal an effective amount of a composition according to claim 10.
- 16. A method of treating or inhibiting ischemia-induced neurodegenerative disease in a mammal comprising the administration to said mammal an effective amount of a composition according to claim 11.
Parent Case Info
This application is a division of application Ser. No. 08/054,122, filed on Apr. 26, 1993.
Non-Patent Literature Citations (1)
Entry |
Wentland, Mark P., "3-Quinolinecarboxamides", J Med Chem, vol. 36, pp. 1580-1596, 1993. |
Divisions (1)
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Number |
Date |
Country |
Parent |
54122 |
Apr 1993 |
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