Derivatives of 7 alkynyl-1,8 naphthyridones, preparation method thereof and use of same in therapeutics
View Patent ↗The disclosure relates to method of treating a disease in which VEGFR-3 is involved, comprising administering a therapeutically effective amount of a compound of the formula wherein R 1 , R 2 , R 3 , and R 4 are as defined in the disclosure, to compositions containing them, to processes for preparing them, and to their use in therapeutics.
1. A method treating a disease selected from the group consisting of restenosis, nephrosclerosis, and liver cirrhosis, comprising administering to a patient in need thereof an effective dose of a compound of formula (I):
wherein:
R 1 and R 2 represent, independently of one another:
a hydrogen atom, or
a C 1 -C 7 alkyl group optionally substituted by one or more alkoxy groups;
R 3 represents a C 1 -C 7 alkyl group;
R 4 represents a hydrogen atom or a C 1 -C 4 alkyl group;
Y represents a C 1 -C 4 alkoxy group or an —NRR′ or —O(CH 2 ) n —C(O)—NRR′ group where R and R′ are as defined below and n is an integer equal to 1 or 2;
R″ represents a C 1 -C 4 alkyl group; and
R and R′ represent, independently of one another, a hydrogen atom, a —CO—(C 1 -C 4 alkyl) group or a —COOR″ group, where R″ is as defined above;
or an acid addition salt thereof, or an enantiomer or diastereoisomer thereof, or a mixture thereof.
2. The method according to claim 1 wherein the disease is restinosis.
3. The method according to claim 1 or 2 , wherein Y represents a C 1 -C 4 -alkoxy group;
or an acid addition salt thereof, or an enantiomer or diastereoisomer thereof, or a mixture thereof.
4. The method according to claim 1 or 2 , wherein Y represents an —NRR′ group,
or an acid addition salt thereof, or an enantiomer or diastereoisomer thereof, or a mixture thereof.
5. The method according to claim 1 or 2 , wherein Y represents an —O(CH 2 ) n —C(O)—NRR′ group n is an integer equal to 1 or 2;
or an acid addition salt thereof, or an enantiomer or diastereoisomer thereof, or a mixture thereof.
6. The method according to claim 1 or 2 , where the compound is selected from the group consisting of:
(±)-2-amino-7-(3,4-dimethoxy-3-methylbut-1-yn-1-yl)-1-ethyl-N-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide;
2-amino-7-[3-(2-amino-2-oxoethoxy)-3-methylbut-1-yn-1-yl]-1-ethyl-N-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide; and
2-amino-1-ethyl-7-(3-methoxyprop-1-yn-1-yl)-N-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide;
or an acid addition salt thereof.
7. The method according to claim 1 or 2 wherein R 1 and R 2 are hydrogen, R 3 is ethyl, R 4 is methyl and Y is
or an acid addition salt thereof.
8. The method according to claim 1 or 2 where R 1 , R 2 and R 4 is methyl, R 3 is ethyl and Y is NH 2 or an acid addition salt thereof.