Substituted oxazolidinones and their use
View Patent ↗The invention relates to novel substituted oxazolidinones, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and their use for preparing medicaments for the treatment and/or prophylaxis of diseases, in particular of thromboembolic disorders.
1. A compound of the formula
in which
R 1 represents chlorine, trifluoromethoxy, methyl, ethyl, n-propyl, methoxy, methoxymethyl or ethoxymethyl,
R 2 represents hydrogen or methyl, and
R 3 represents a group of the formula
where
* is the point of attachment to the oxopyridine ring,
n represents the number 1, 2, 3 or 4,
m represents the number 1 or 2,
R 4 represents, methyl, ethyl, cyclopropyl, cyclobutyl, 2-hydroxyeth-1-yl, 3-hydroxyprop-1-yl, 2-methoxyeth-1-yl, 3-methoxyprop-1-yl, 4-hydroxycyclohex-1-yl, tetrahydrofuran-2-ylmethyl or 1,4-dioxan-2-ylmethyl,
R 5 represents hydrogen, methyl or ethyl, or
R 4 and R 5 together with the nitrogen atom to which they are attached form a pyrrolidin-1-yl ring, a 2-methoxymethylpyrrolidin-1-yl ring, a morpholin-4-yl ring, a 1,1-dioxothiomorpholin-4-yl ring, a 1,4-oxazepan-4-yl ring, a 4-methylpiperazin-1-yl or a 4-hydroxypiperidin-1-yl ring,
R 6 represents hydrogen, methyl, ethyl, cyclopropyl, cyclobutyl, 2-hydroxyeth-1-yl, 3-hydroxyprop-1-yl, 2-methoxyeth-1-yl, 3-methoxyprop-1-yl, 4-hydroxycyclohex-1-yl, tetrahydrofuran-2-ylmethyl or 1,4-dioxan-2-ylmethyl,
R 7 represents hydrogen, methyl or ethyl,
R 6 and R 7 together with the nitrogen atom to which they are attached form a pyrrolidin-1-yl ring, a 2-methoxymethylpyrrolidin-1-yl ring, a morpholin-4-yl ring, a 1,1-dioxothiomorpholin-4-yl ring, a 1,4-oxazepan-4-yl ring, a 4-methylpiperazin-1-yl or a 4-hydroxypiperidin-1-yl ring,
or one of its salt.
2. A compound according to claim 1 , wherein
R 1 represents chlorine, trifluoromethoxy, methyl, ethyl, n-propyl, methoxy or methoxymethyl,
R 2 represents hydrogen or methyl, and
R 3 represents a group of the formula
where
* is the point of attachment to the oxopyridine ring,
n is the number 1, 2 or 3,
m represents the number 1 or 2,
R 4 represents, methyl, ethyl, cyclopropyl, cyclobutyl, 2-hydroxyeth-1-yl, 3-hydroxyprop-1-yl, 2-methoxyeth-1-yl, 3 -methoxyprop-1-yl, 4-hydroxycyclohex-1-yl, tetrahydrofuran-2-ylmethyl or 1,4-dioxan-2-ylmethyl,
R 5 represents hydrogen, methyl or ethyl, or
R 4 and R 5 together with the nitrogen atom to which they are attached form a pyrrolidin-1-yl ring, a 2-methoxymethylpyrrolidin-1-yl ring, a morpholin-4-yl ring, a 1,1-dioxothiomorpholin-4-yl ring, a 1,4-oxazepan-4-yl ring, a 4-methylpiperazin-1-yl or a 4-hydroxypiperidin-1-yl ring,
R 6 represents hydrogen, methyl, ethyl, cyclopropyl, cyclobutyl, 2-hydroxyeth-1-yl, 3-hydroxyprop-1-yl, 2-methoxyeth-1-yl, 3-methoxyprop-1-yl, 4-hydroxycyclohex-1-yl, tetrahydrofuran-2-ylmethyl or 1,4-dioxan-2-ylmethyl,
R 7 represents hydrogen, methyl or ethyl, R 6 and R 7 together with the nitrogen atom to which they are attached form a pyrrolidin-1-yl ring, a 2-methoxymethylpyrrolidin-1-yl ring, a morpholin-4-yl ring, a 1,1-dioxothiomorpholin-4-yl ring, a 1,4-oxazepan-4-yl ring, a 4-methylpiperazin-1-yl or a 4-hydroxypiperidin-1-yl ring,
or one of its salts.
3. A compound according to claim 1 , wherein
R 1 represents methyl, ethyl, n-propyl, methoxy or methoxymethyl,
R 2 represents hydrogen or methyl, and
R 3 represents a group of the formula
where
* is the point of attachment to the oxopyridine ring,
n is the number 1, 2 or 3,
m represents the number 1 or 2,
R 4 represents, methyl, ethyl, cyclopropyl, cyclobutyl, 2-hydroxyeth-1-yl, 3-hydroxyprop-1-yl, 2-methoxyeth-1-yl, 3-methoxyprop-1-yl, 4-hydroxycyclohex-1-yl, tetrahydrofuran-2-ylmethyl or 1,4-dioxan-2-ylmethyl,
R 5 represents hydrogen, methyl or ethyl,
R 6 represents hydrogen, methyl, ethyl, cyclopropyl, cyclobutyl, 2-hydroxyeth-1-yl, 3-hydroxyprop-1-yl, 2-methoxyeth-1-yl, 3-methoxyprop-1-yl, 4-hydroxycyclohex-1-yl, tetrahydrofuran-2-ylmethyl or 1,4-dioxan-2-ylmethyl,
R 7 represents hydrogen, methyl or ethyl,
or one of its salts.
4. A compound according to claim 1 , wherein
R 1 represents methyl or methoxy,
R 2 represents hydrogen, or
R 1 represents methyl,
R 2 represents methyl, and
R 3 represents a group of the formula
where
* is the point of attachment to the oxopyridine ring,
n represents the number 2,
m represents the number 1,
R 4 represents 2-hydroxyeth-1-yl or 4-hydroxycyclohex-1-yl,
R 5 represents hydrogen,
R 6 represents 2-hydroxyeth-1-yl or 4-hydroxycyclohex-1-yl,
R 7 represents hydrogen,
or one of its salts.
5. A compound according to claim 1 , wherein
R 1 represents methoxymethyl,
R 2 represents hydrogen, or
R 1 represents methyl,
R 2 represents methyl, and
R 3 represents a group of the formula
where
* is the point of attachment to the oxopyridine ring,
n represents the number 2,
R 4 represents 2-hydroxyeth-1-yl or 4-hydroxycyclohex-1-yl,
R 5 represents hydrogen,
or one of its salts.
6. A compound according to claim 1 , wherein
R 1 represents methyl,
R 2 represents hydrogen, or
R 1 represents methyl,
R 2 represents methyl, and
R 3 represents a group of the formula
where
* is the point of attachment to the oxopyridine ring,
m represents the number 1,
R 6 represents 2-hydroxyeth-1-yl or 4-hydroxycyclohex-1-yl,
R 7 represents hydrogen,
or one of its salts.
7. A process for preparing a compound of the formula (I) or one or its salts according to claim 1 , comprising:
[A] reacting a compound of the formula
in which n, R 1 and R 2 have the meaning given in claim 1 , and
X represents hydroxyl or bromine,
with a compound of the formula
in which R 4 and R 5 have the meaning given in claim 1 ,
to give a compound of the formula
in which n, R 1 , R 2 , R 4 and R 5 have the meaning given in claim 1 , or
[B] reacting a compound of the formula
in which m, R 1 and R 2 have the meaning given in claim 1 , and
Y represents hydroxyl or chlorine,
with a compound of the formula
in which R 6 and R 7 have the meaning given in claim 1 ,
to give a compound of the formula
in which m, R 1 , R 2 , R 6 and R 7 have the meaning given in claim 1 .
8. A pharmaceutical composition comprising a compound according to claim 1 and an inert nontoxic pharmaceutically acceptable auxiliary.
9. A pharmaceutical composition comprising a compound according to claim 1 in combination with a further active compound.
10. A method for the treatment and/or prophylaxis of thromboembolic disorders comprising administering to a human or animal in need thereof an anticoagulatory effective amount of at least one compound according to claim 1 .
11. A method for preventing blood coagulation in vitro, wherein an anticoagulatory effective amount of a compound according to claim 1 is added.