Substituted oxazolidinones and their use in the field of blood coagulation
View Patent ↗This invention relates to compounds of formula (I) wherein R 1 represents optionally substituted phenyl, R 2 represents optionally substituted and the remaining “R” groups are as defined in the specification and claims, as well as a method for making such materials, pharmaceutical compositions containing such materials, and methods of using such materials in medical treatment.
1. A compound of the formula (I)
in which
R 1 represents phenyl, where the ring may be mono- to trisubstituted, independently of one another, by halogen, (C 1 –C 6 )-alkyl, amino, mono- or di-(C 1 –C 6 )-alkylamino, hydroxyl, (C 1 –C 6 )-alkoxy, (C 1 –C 6 )-alkoxycarbonyl, (C 1 –C 6 )-alkanoyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, nitro, oxo, carboxyl or cyano,
R 2 represents a radical —N(R 10 )C(O)R 11 ,
where R 10 and R 11 together with the N—C(O) group to which they are attached form a
which may furthermore be mono- to trisubstituted, independently of one another, by halogen, (C 1 –C 6 )-alkyl, amino, mono- or di-(C 1 –C 6 )-alkylamino, hydroxyl, (C 1 –C 6 )-alkoxy, trifluoromethyl or cyano,
R 3 , R 4 , R 5 and R 6 , independently of one another, represent hydrogen, halogen, (C 1 –C 6 )-alkyl, amino, mono- or di-(C 1 –C 6 )-alkylamino, mono- or di-(C 1 –C 6 )-alkylaminocarbonyl, hydroxyl, C 1 –C 6 )-alkoxy, C 1 –C 6 )-alkanoyl, C 1 –C 6 )-alkanoylamino, trifluoromethyl, carbamoyl, nitro or cyano, and
R 7 represents hydrogen or (C 1 –C 6 )-alkyl,
or a pharmaceutically acceptable salt, hydrate, hydrate of a salt, or solvate thereof.
2. The compound of the formula (I) as claimed in claim 1 , in which
R 1 represents phenyl, where the ring may be mono- to trisubstituted, independently of one another, by halogen, (C 1 –C 6 )-alkyl, amino, mono- or di-(C 1 –C 6 )-alkylamino, hydroxyl, (C 1 –C 6 )-alkoxy, (C 1 –C 6 )-alkoxycarbonyl, (C 1 –C 6 )-alkanoyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, nitro, oxo, carboxyl or cyano,
R 2 represents a radical —N(R 10 )C(O)R 11
where
R 10 and R 11 together with the N—C(O) group to which they are attached form a
which may furthermore be mono- to trisubstituted, independently of one another, by halogen, (C 1 –C 6 )-alkyl, amino, mono- or di-(C 1 –C 6 )-alkylamino, hydroxyl, (C 1 –C 6 )-alkoxy, trifluoromethyl or cyano,
R 3 , R 4 , R 5 and R 6 , independently of one another, represent hydrogen, halogen, (C 1 –C 6 )-alkyl, amino, mono- or di-(C 1 –C 6 )-alkylamino, mono- or di-(C 1 –C 6 )-alkylaminocarbonyl, hydroxyl, C 1 –C 6 )-alkoxy, (C 1 –C 6 )-alkanoyl, (C 1 –C 6 )-alkanoylamino, trifluoromethyl, carbamoyl, nitro or cyano, and
R 7 represents hydrogen or (C 1 –C 6 )-alkyl,
or a pharmaceutically acceptable salt, hydrate, hydrate of a salt, or solvate thereof.
3. The compound of the formula (I) as claimed in claim 1 , in which
R 1 represents phenyl, where the ring may be mono- to trisubstituted, independently of one another, by halogen, (C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkoxy, cyano, trifluoromethyl, trifluoromethoxy or trifluoromethylthio,
R 2 represents a radical —N(R 10 )C(O)R 11
where
R 10 and R 11 together with the N—C(O) group to which they are attached form a
which may furthermore be mono- to trisubstituted, independently of one another, by halogen, (C 1 –C 6 )-alkyl, amino, mono- or di-C 1 –C 6 )-alkylamino, hydroxyl, (C 1 –C 6 )-alkoxy, trifluoromethyl or cyano,
R 3 and R 6 , independently of one another, represent hydrogen, halogen, (C 1 –C 6 )-alkyl, amino, mono- or di-(C 1 –C 6 )-alkylamino, hydroxyl, (C 1 –C 6 )-alkoxy, (C 1 –C 6 )-alkanoylamino, cyano, trifluoromethyl or nitro,
R 4 R 5 represent hydrogen, and
R 7 represents hydrogen or (C 1 –C 4 )-alkyl,
or a pharmaceutically acceptable salt, hydrate, hydrate of a salt, or solvate thereof.
4. The compound of the formula (I) as claimed in claim 1 , in which
R 1 represents phenyl, where the ring may be mono- to trisubstituted, independently of one another, by fluorine, chlorine, bromine, (C 1 –C 4 )-alkyl, trifluoromethyl, trifluoromethoxy or trifluoromethylthio,
R 2 represents a radical —N(R 10 )C(O)R 11
where
R 10 and R 11 together with the N—C(O) group to which they are attached represent
where the ring may be mono- or disubstituted by (C 1 –C 4 )-alkyl,
R 3 represents hydrogen, fluorine, chlorine, bromine, (C 1 –C 4 )-alkyl, amino, mono- or di-(C 1 –C 3 )-alkylamino, cyano or nitro,
R 4 , R 5 and R 6 represent hydrogen, and
R 7 represents hydrogen,
or a pharmaceutically acceptable salt, hydrate, hydrate of a salt, or solvate thereof.
5. A process for preparing compounds of the formula (I) as claimed in claim 1 , characterized in that a compound of the formula (II)
in which R 2 , R 3 , R 4 , R 5 , R 6 and R 7 are as defined above in claim 1 is reacted with a carboxylic acid of the formula (III)
in which R 1 is as defined above,
or else with the corresponding carbonyl halide or else with the corresponding symmetric or mixed carboxylic anhydride of the carboxylic acid of the formula (III) defined above.
6. A pharmaceutical composition comprising at least one compound of the formula (I) as claimed in claim 1 and at least one further auxiliary.
7. A method for the prevention and/or treatment of a thromboembolic disorder selected from the group consisting of myocardial infarction, angina pectoris (including unstable angina), reocclusions and restenoses after angioplasty or aortocoronay bypass, cerebro vascular accident, transitory ischemic attacks, peripheral occlusive diseases, pulmonary embolisms and deep vein thromboses, comprising administering to a subject an effective amount of a compound of claim 1 .
8. A method for the prevention and/or treatment of disseminated intravasal coagulation (DIC) comprising administering to a subject an effective amount of a compound of claim 1 .
9. A process for preventing the coagulation of blood in vitro, characterized in that compounds of the general formula (I) as claimed in claim 1 are added to said blood.
10. The process of claim 9 wherein said blood is banked blood or a biological sample containing factor Xa.