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 method of treatment and/or prophylaxis of disseminated intravascular coagulation, comprising administering to a human or animal in need thereof an anticoagulatory effective amount of at least one compound of formula (I):
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 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 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,
or
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.
2. The method of 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 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 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,
or
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. The method of 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 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 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. The method of 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. The method of 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. The method of 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. The method of claim 1 , wherein the disseminated intravascular coagulation occurs during sepsis.
8. A method of treatment and/or prophylaxis of a thromboembolic disorder selected from the group consisting of myocardial infarction with ST segment elevation (STEMI), myocardial infarction without ST segment elevation (non-STEMI), stable angina pectoris, unstable angina pectoris, reocclusions and restenoses after coronary intervention, a peripheral arterial occlusion disease, a pulmonary embolism, deep venous thrombosis, kidney venous thrombosis, a transitory ischaemic attack, a thrombotic stroke, and a thromboembolic stroke, comprising administering to a human or animal in need thereof an anticoagulatory effective amount of at least one compound of formula (I) as defined in claim 1 .
9. The method of claim 8 , wherein the coronary intervention is angioplasty or aortocoronary bypass.