2-phenyl-4-cyclopropyl-pyrimidine derivatives
View Patent ↗The present invention relates to 2-phenyl-4-cyclopropyl-pyrimidine derivatives and their use as P2Y 12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.
1. A compound of formula I
wherein
R 1 represents phenyl optionally substituted once by halogen, methyl, methoxy, trifluoromethyl or trifluoromethoxy; and
R 2 represents hydrogen, hydroxymethyl or alkoxymethyl;
or a salt of such a compound.
2. A compound according to claim 1 , which is also a compound of formula I CE
wherein
R 1 represents phenyl optionally substituted once by halogen; and
R 2 represents hydrogen, hydroxymethyl alkoxymethyl;
or a salt of such a compound.
3. A compound according to claim 1 , wherein R 1 represents phenyl optionally substituted once by fluorine;
or a salt of such a compound.
4. A compound according to claim 1 , wherein R 2 represents hydrogen;
or a salt of such a compound.
5. A compound according to claim 1 , wherein R 2 represents hydroxymethyl or alkoxymethyl;
or a salt of such a compound.
6. A compound according to claim 5 , wherein R 2 represents hydroxymethyl;
or a salt of such a compound.
7. A compound according to claim 5 , wherein R 2 represents alkoxymethyl;
or a salt of such a compound.
8. A compound according to claim 1 , which is selected from the group consisting of:
4-{(S)-4-carboxy-2-[(6-cyclopropyl-2-phenyl-pyrimidine-4-carboyl)amino]-butyryl}-piperazine-1-carboxylic acid butyl ester;
4-((S)-4-carboxy-{[6-(trans-2-metoxymethyl-cyclopropyl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid butyl ester;
4-((S)-4-carboxy-2-{[6-((1S,2S)-2-methoxymethyl-cyclopropyl)-phenyl-pyrimidine-4-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid butyl ester;
4-((S)-4-carboxy-2-{[6-((1S,2S)-2-hydroxymethyl-cyclopropyl)-2-phenyl-pyrimidine-4-carbonyl]amino}-butyryl)-piperazine-1-carboxylic acid butyl ester;
4-((S)-4-carboxy-2-({[2-4-fluoro-phenyl)-6-((1S,2S)-methoxymethyl-cyclopropyl)-pyrimidine-4-carbonyl]amino}-butyryl)-piperazine-1-carboxylic acid butyl ester;
4-((S)-4-carboxy-2-{[6-(cis-2-methoxymethyl-cyclopropyl)-2-phenyl-pyrimidine-4-carbonyl]-amino}-butyryl)-piperazine-1-carboxylic acid butyl ester;
or a salt of such a compound.
9. A pharmaceutical composition containing at least one compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents or excipients.
10. A method for the treatment of thrombosis comprising administering to a subject a pharmaceutically active amount of a compound according to claim 1 , or of a pharmaceutically acceptable salt thereof.