Amide type carboxamide derivative
The present invention provides an amide-type carboxamide derivative of the formula [1]: wherein X is a group of the formula: —N═ or the formula: —CH═; R 1 is a halogen atom, a lower alkyl group, and the like; R 2 is a group of the formula: and the like; Y 1 and Y 2 are the same or different and each is a group selected from a halogen atom, a lower alkyl group, a lower alkoxy group, and the like; Ring A is phenyl group, and the like, or a pharmaceutically acceptable salt thereof, which is useful as an inhibitor of FXa.
1. An amide-type carboxamide derivative of the formula [1]:
wherein X is a group of the formula: —N═ or the formula: —CH═;
Y 1 and Y 2 are the same or different and each is a group selected from a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a lower alkyl group substituted by halogen atom, a lower alkoxycarbonyl group, a carboxyl group, a lower alkylcarbamoyl group and a phenyl group;
R 1 is a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group;
R 2 is a group of the formula: —CO—R 21 —R 22 ;
R 21 is a lower alkylene group or a cycloalkanediyl group; and
R 22 is a group of the formula:
wherein R 23 and R 24 are the same or different and each is a lower alkyl group or an amino-lower alkyl group optionally substituted by a lower alkyl group; or combine together at the ends to form an optionally substituted nitrogen-containing saturated heterocyclic group along with the adjacent group: —N—C(═O)—; R 25 and R 26 are the same or different and each is a lower alkyl group or an amino-lower alkyl group optionally substituted by a lower alkyl group; or combine together at the ends to form an optionally substituted nitrogen-containing saturated heterocyclic group along with the adjacent nitrogen atom; and
Ring A is an aromatic hydrocarbon, a monocyclic heteroaromatic ring or a condensed thiophene ring,
or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , wherein Ring A is benzene, naphthalene, pyridine, furan, thiophene, pyrazole, benzothiophene or thienopyridine.
3. The compound according to claim 2 , wherein R 2 is
R 22 is a group of the formula:
is a group of the formula:
4. The compound according to claim 2 , wherein R 1 is a halogen atom or a lower alkyl group;
R 2 is a group of the formula:
R 22 is a group of the formula:
is a group of the formula:
and
Y 1 and Y 2 are the same or different and each is a group selected from a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group and a carboxyl group.
5. The compound according to claim 4 , wherein
is a group of the formula:
6. A pharmaceutical composition, which comprises as an active ingredient a compound according to any one of claims 1 to 5 , or a pharmaceutically acceptable salt thereof.
7. A method for treatment of thrombosis, which comprises administering an effective amount of a compound according to any one of claims 1 to 5 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof.