Amidino derivatives and anticoagulants and thrombosis therapeutic agents containing them
Amidino derivatives represented by the following general formula (I): {where X is a group represented by R 1 SO 2 NR 2 — (wherein R 1 represents optionally substituted C 6-14 aryl, etc. and R 2 represents hydrogen atom, etc.), etc., Ar 1 represents 2,6-naphthylene, etc., R 3 represents hydrogen atom, etc. and Y represents carboxyphenyl, etc.} and their pharmacologically acceptable salts or solvates.
1. An amidino derivative represented by the following general formula (I):
where X represents C 1-6 alkyl, a halogen atom, —NH 2 or a group represented by the following formula:
where R 1 represents optionally substituted C 1-6 alkyl, optionally substituted C 1-6 alkoxy, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-14 aryl, optionally substituted C 7-20 aralkyl, an optionally substituted 5- to 14-membered aromatic heterocyclic group or a group represented by the following formula:
where R 4 represents hydrogen atom, C 1-6 alkyl or optionally substituted C 2-7 acyl),
R 2 represents hydrogen atom or C 1-6 alkyl, and
X 2 represents —CO—, —SO 2 —, —NH—CO— or a single bond,
R 3 represents hydrogen atom, hydroxyl, C 2-7 acyl or C 2-7 alkoxycarbonyl,
Y represents a group of the formula —Ar 2 —CO 2 R 5 (where Ar 2 represents optionally substituted C 6-14 aryl, an optionally substituted 5- to 14-membered aromatic heterocyclic group or a single bond and R 5 represents hydrogen atom or C 1-6 alkyl), and
Ar 1 represents 2,6-naphthylene, 1,4-phenylene, 1,3-phenylene, a group represented by the following formula:
or a group represented by the following formula:
(where the ethyl end is linked to oxygen and the phenyl end is linked to amidine carbon);
or a pharmacologically acceptable salt or solvate thereof.
2. An amidino derivative or a pharmacologically acceptable salt or solvate thereof according to claim 1 , wherein said amidino derivative is represented by the following general formula (II):
(where X, Y, Ar 1 and R 3 have the same definitions as X, Y, Ar 1 and R 3 in claim 1 ).
3. An amidino derivative or a pharmacologically acceptable salt or solvate thereof according to claim 1 , wherein said amidino derivative is represented by the following general formula (III):
(where X, Y and R 3 have the same definitions as X, Y and R 3 in claim 1 ).
4. An amidino derivative or a pharmacologically acceptable salt or solvate thereof according to claim 1 , wherein R 3 is hydrogen atom.
5. An amidino derivative or a pharmacologically acceptable salt or solvate thereof according to claim 1 , wherein X is C 1-6 alkyl or a group represented by the formula R 1 —SO 2 NH— (where R 1 has the same definition as R 1 in claim 1 ).
6. An amidino derivative or a pharmacologically acceptable salt or solvate thereof according to claim 1 , wherein X is a group represented by the formula R 1 —SO 2 NH— {where R 1 represents optionally substituted C 6-14 aryl or a group represented by the following formula:
(where R 4 represents optionally substituted C 2-7 acyl)}.
7. An amidino derivative or a pharmacologically acceptable salt or solvate thereof according to claim 1 , wherein Y is carboxyl or optionally substituted carboxyphenyl.
8. An amidino derivative or a pharmacologically acceptable salt or solvate thereof according to claim 1 , wherein Y is a group represented by the following formula:
9. A blood clotting factor VIIa inhibitor comprising an amidino derivative or a pharmacologically acceptable salt or solvate thereof according to claim 1 .
10. An anticoagulant containing, as an active ingredient, an amidino derivative or a pharmacologically acceptable salt or solvate thereof according to claim 1 .
11. A thrombosis therapeutic agent containing, as an active ingredient, an amidino derivative or a pharmacologically acceptable salt or solvate thereof according to claim 1 .
12. A method for inhibiting blood clotting factor VIIa, which involves administering an amidino derivative or a pharmacologically acceptable salt or solvate thereof according to claim 1 .
13. A method for treating or preventing coagulation, which involves administering an amidino derivative or a pharmacologically acceptable salt or solvate thereof according to claim 1 .
14. A method for treating or preventing thrombosis, which involves administering an amidino derivative or a pharmacologically acceptable salt or solvate thereof according to claim 1 .
15. A treatment method for clinical conditions involving thrombogenesis in which extrinsic blood clotting mechanisms are implicated, which involves administering an amidino derivative or a pharmacologically acceptable salt or solvate thereof according to claim 1 .
16. A prophylactic method for clinical conditions involving thrombogenesis in which extrinsic blood clotting mechanisms are implicated, which involves administering an amidino derivative or a pharmacologically acceptable salt or solvate thereof according to claim 1 .