Benzofuran derivative

1. A benzofuran derivative of the formula [1]:

wherein X is a group of the formula: —N—

Y is a cycloalkyl group optionally substituted by a group selected from

(i) an amino group optionally substituted by a group selected from the following:

(1) a lower alkyl group;

(2) a cycloalkyl group,

(3) a hydroxy-lower alkyl group,

(4) a lower alkyl group substituted by an amino group optionally substituted by a group selected from (a) a lower alkyl group, (b) a lower alkanoyl group, (c) a lower alkanoyl group substituted by an amino group substituted by a lower alkyl group, and (d) a lower alkoxycarbonyl group,

(5) a lower alkyl group substituted by a cyano group,

(6) a lower alkyl group substituted by a lower alkoxycarbonyl group,

(7) a lower alkyl group substituted by a carboxyl group,

(8) a lower alkyl group substituted by a carbamoyl group optionally substituted by a lower alkyl group,

(9) a lower alkyl group substituted by an aryl group,

(10) a lower alkoxycarbonyl group,

(11) a lower alkanoyl group substituted by a di-lower alkyl amino group,

(12) a lower alkanoyl group,

(13) a lower alkylsulfonyl group,

(14) a carbamoyl group substituted by a lower alkyl group,

(15) a carbonyl group substituted by an aryl group,

(16) a lower alkanoyl group substituted by a lower alkoxy group,

(17) a lower alkanoyl group substituted by a lower alkanoyloxy group,

(18) an aryl group substituted by a hydroxyl group, and

(19) a hydroxy-lower alkanoyl group,

(ii) a group of a formula:

optionally substituted by an oxo group, and

(iii) a lower alkyl group optionally substituted by

an amino group optionally substituted by a group selected from (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, and (c) a lower alkanoyl group; or

A is a single bond, a carbon chain optionally having a double bond within or at the end(s) of the chain, or an oxygen atom; R 1 is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a cyano group or an amino group optionally substituted by a lower alkyl group;

Ring B of the formula:

is a benzene ring optionally substituted by a group(s) selected independently from

(i) a halogen atom,

(ii) a lower alkyl group optionally substituted by a group selected from the following:

(1) a lower alkoxycarbonyl group,

(2) a carboxyl group,

(3) a carbamoyl group optionally substituted by a group selected from (a) a lower alkyl group, (b) a lower alkoxylower alkyl group, (c) a lower alkyl group substituted by a hydroxyl group, and (d) a lower alkoxy group,

(4) a carbonyl group substituted by a morpholinyl group,

(5) a hydroxyl group;

(iii) a hydroxy group,

(iv) a lower alkoxy group optionally substituted by a group selected from the following:

(1) a carboxyl group,

(2) a lower alkoxycarbonyl group,

(3) a lower alkoxy group,

(4) a hydroxyl group,

(5) an aminooxy group optionally substituted by a lower alkoxycarbonyl group,

(6) a lower alkoxy group substituted by a lower alkoxy group,

(7) an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, and (c) a lower alkanoyl group,

(8) a carbamoyl group optionally substituted by a group selected from (a) a lower alkyl group, (b) a lower alkoxy-lower alkyl group, (c) a lower alkyl group substituted by a hydroxyl group, and (d) a lower alkyl group substituted by a di-lower alkylamino group; and

(9) a group of the formula: —O—NH—C(═NH)NH 2 ;

(v) a carbonyl group substituted by a group selected from the following:

(1) a lower alkoxy group,

(2) a hydroxyl group,

(3) an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxy group, (c) a lower alkoxy-lower alkyl group, (d) a hydroxy-lower alkyl group, (e) a lower alkyl group substituted by an amino group optionally substituted by a lower alkyl group, (f) a lower alkyl group substituted by an aryl group, and

(4) a morpholinyl group,

(vi) an amino group optionally substituted by a group selected from the following:

(1) a lower alkyl group,

(2) a lower alkoxy-lower alkyl group,

(3) a hydroxy-lower alkyl group,

(4) a lower alkanoyl group,

(5) a lower alkoxy-lower alkanoyl group,

(6) a hydroxy-lower alkanoyl group,

(7) a lower alkanoyl group substituted by a lower alkanoyloxy group,

(8) a lower alkanoyl group substituted by an amino group optionally substituted by a group selected from (a) a lower alkyl group and (b) a lower alkanoyl group,

(9) a lower alkoxycarbonyl group,

(10) a lower alkoxycarbonyl group substituted by an aryl group,

(11) a carbamoyl group substituted by a lower alkyl group, and

(12) a lower alkylsulfonyl group,

(vii) a nitro group,

(viii) a cyano group, and

(x) a group of the formula:

R 3 is a hydrogen atom or a lower alkyl group, or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein B is an unsubstituted benzene ring; and

Y is a cycloalkyl group optionally substituted by the following:

A) an amino group optionally substituted by the following:

(1) a lower alkyl group,

2) a cycloalkyl group,

(3) a hydroxy-lower alkyl group,

(4) a lower alkyl group substituted by an amino group

optionally substituted by a group selected from (a) a lower alkyl group, (b) a lower alkanoyl group, (c) a lower alkanoyl group substituted by an amino group substituted by a lower alkyl group, and (d) a lower alkoxycarbonyl group,

(5) a lower alkyl group substituted by a cyano group,

(6) a lower alkyl group substituted by a lower alkoxycarbonyl group,

(7) a lower alkyl group substituted by a carboxyl group,

(8) a lower alkyl group substituted by a carbamoyl group optionally substituted by a lower alkyl group,

(9) a lower alkyl group substituted by an aryl group,

(10) a lower alkoxycarbonyl group,

(11) a lower alkanoyl group substituted by a di-lower alkyl amino group,

(12) a lower alkanoyl group,

(13) a lower alkylsulfonyl group,

(14) a carbamoyl group substituted by a lower alkyl group,

(15) a carbonyl group substituted by an aryl group,

(16) a lower alkanoyl group substituted by a lower alkoxy group,

(17) a lower alkanoyl group substituted by a lower alkanoyloxy group,

(18) an aryl group substituted by a hydroxy group, or

(19) hydroxy-lower alkanoyl group;

B) a group of a formula:

that is optionally substituted by an oxo group; or

C) a lower alkyl group optionally substituted by an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, and (c) a lower alkanoyl group.

3. The compound according to claim 1 , wherein Ring B is a benzene ring substituted by a lower alkyl group optionally substituted by a group selected from the following:

(1) a lower alkoxycarbonyl group,

(2) a carboxyl group,

(3) a carbamoyl group optionally substituted by a group selected from (a) a lower alkyl group, (b) a lower alkoxy-lower alkyl group, (c) a lower alkyl group substituted by a hydroxyl group, and (d) a lower alkoxy group, and

(4) a hydroxyl group; and Y is a cycloalkyl group optionally substituted by the following:

A) an amino group optionally substituted by the following:

(1) a lower alkyl group,

(2) a cycloalkyl group,

(3) a hydroxy-lower alkyl group,

(4) a lower alkyl group substituted by an amino group optionally substituted by a group selected from (a) a lower alkyl group, (b) a lower alkanoyl group, (c) a lower alkanoyl group substituted by an amino group substituted by a lower alkyl group, and (d) a lower alkoxycarbonyl group,

(5) a lower alkyl group substituted by a cyano group,

(6) a lower alkyl group substituted by a lower alkoxycarbonyl group,

(7) a lower alkyl group substituted by a carboxyl group,

(8) a lower alkyl group substituted by a carbamoyl group optionally substituted by a lower alkyl group,

(9) a lower alkyl group substituted by an aryl group,

(10) a lower alkoxycarbonyl group,

(11) a lower alkanoyl group substituted by a di-lower alkyl amino group,

(12) a lower alkanoyl group,

(13) a lower alkylsulfonyl group,

(14) a carbamoyl group substituted by a lower alkyl group,

(15) a carbonyl group substituted by an aryl group,

(16) a lower alkanoyl group substituted by a lower alkoxy group,

(17) a lower alkanoyl group substituted by a lower alkanoyloxy group,

(18) an aryl group substituted by a hydroxy group, or

(19) a hydroxy-lower alkanoyl group;

B) a group of a formula:

that is optionally substituted by an oxo group; or

C) a lower alkyl group optionally substituted by

an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, and (c) a lower alkanoyl group.

4. The compound according to claim 1 , wherein Ring B is a benzene ring substituted by a lower alkoxy group optionally substituted by a group selected from the following:

(1) a carboxyl group,

(2) a lower alkoxycarbonyl group,

(3) a lower alkoxy group,

hydroxyl group,

an aminooxy group optionally substituted by a lower alkoxycarbonyl group,

(6) a lower alkoxy group substituted by a lower alkoxy group,

(7)an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, and (c) a lower alkanoyl group,

(8) a carbamoyl group optionally substituted by a group selected from (a) a lower alkyl group, (b) a lower alkoxylower alkyl group, (c) a lower alkyl group substituted by a hydroxyl group, and (d) a lower alkyl group substituted by a di-lower alkylamino group; and

(9) a group of the formula: —O—NH—C(═NH)NH 2 ; and

Y is a cycloalkyl group optionally substituted by the following:

A) an amino group optionally substituted by the following:

(1) a lower alkyl group,

(2) a cycloalkyl group,

(3) a hydroxy-lower alkyl group,

(4) a lower alkyl group substituted by an amino group optionally substituted by a group selected from (a) a lower alkyl group, (b) a lower alkanoyl group, (c) a lower alkanoyl group substituted by an amino group substituted by a lower alkyl group, and (d) a lower alkoxycarbonyl group,

(5) a lower alkyl group substituted by a cyano group,

(6) a lower alkyl group substituted by a lower alkoxycarbonyl group,

(7) a lower alkyl group substituted by a carboxyl group,

(8) a lower alkyl group substituted by a carbamoyl group optionally substituted by a lower alkyl group,

(9) a lower alkyl group substituted by an aryl group,

(10) a lower alkoxycarbonyl group,

(11) a lower alkanoyl group substituted by a di-lower alkyl amino group,

(12) a lower alkanoyl group,

(13) a lower alkylsulfonyl group,

(14) a carbamoyl group substituted by a lower alkyl group,

(15) a carbonyl group substituted by an aryl group,

(16) a lower alkanoyl group substituted by a lower alkoxy group,

(17) a lower alkanoyl group substituted by a lower alkanoyloxy group,

(18) an aryl group substituted by a hydroxy group, or

(19) a hydroxy-lower alkanoyl group;

B) a group of a formula:

that is optionally substituted by an oxo group; or

C a lower alkyl group optionally substituted by

an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, or (c) a lower alkanoyl group.

5. The compound according to claim 1 , wherein Ring B is a benzene ring substituted by a carbonyl group substituted by a group selected from the following:

(1) a lower alkoxy group,

(2) a hydroxyl group,

(3) an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxy group, (c) a lower alkoxy-lower alkyl group, (d) a hydroxy-lower alkyl group, (e) a lower alkyl group substituted by an amino group optionally substituted by a lower alkyl group, or (f) a lower alkyl group substituted by an aryl group, and

(4) a morpholinyl group,

Y is a cycloalkyl group optionally substituted by the following:

A) an amino group optionally substituted by the following:

(1) a lower alkyl group,

(2) a cycloalkyl group,

(3) a hydroxy-lower alkyl group,

(4) a lower alkyl group substituted by an amino group optionally substituted by a group selected from (a) a lower alkyl group, (b) a lower alkanoyl group, (c) a lower alkanoyl group substituted by an amino group substituted by a lower alkyl group, and (d) a lower alkoxycarbonyl group,

(5) a lower alkyl group substituted by a cyano group,

(6) a lower alkyl group substituted by a lower alkoxycarbonyl group,

(7) a lower alkyl group substituted by a carboxyl group,

(8) a lower alkyl group substituted by a carbamoyl group optionally substituted by a lower alkyl group,

(9) a lower alkyl group substituted by an aryl group,

(10) a lower alkoxycarbonyl group,

(11) a lower alkanoyl group substituted by a di-lower alkyl amino group,

(12) a lower alkanoyl group,

(13) a lower alkylsulfonyl group,

(14) a carbamoyl group substituted by a lower alkyl group,

(15) a carbonyl group substituted by an aryl group,

(16) a lower alkanoyl group substituted by a lower alkoxy group,

(17) a lower alkanoyl group substituted by a lower alkanoyloxy group,

(18) an aryl group substituted by a hydroxy group, or

(19) a hydroxy-lower alkanoyl group;

B) a group of a formula:

that is optionally substituted by an oxo group; or

C) a lower alkyl group optionally substituted by

an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, or (c) a lower alkanoyl group.

6. The compound according to claim 1 , wherein the group of the formula:

is the group of the formula:

and the group of the formula:

is a group of the formula:

1 R 1 is a halogen atom or a lower alkyl group; R 2 is a group selected from the following:

A) a hydrogen atom,

B) a lower alkyl group optionally substituted by a group selected from the following:

(1) a lower alkoxycarbonyl group,

(2) a carboxyl group,

(3) a carbamoyl group optionally substituted by a group selected from (a) a lower alkyl group, (b) a lower alkoxy-lower alkyl group, (c) a lower alkyl group substituted by a hydroxyl group, and (d) a lower alkoxy group,

(4) a carbonyl group substituted by a morpholinyl group,

(5) a hydroxyl group;

C) a lower alkoxy group optionally substituted by a group selected from the following:

(1) a carboxyl group,

(2) a lower alkoxycarbonyl group,

(3) a lower alkoxy group,

(4) a hydroxyl group,

(5) an aminooxy group optionally substituted by a lower alkoxycarbonyl group,

(6) a lower alkoxy group substituted by a lower alkoxy group,

(7) an amino group optionally substituted by a group selected from (a) a lower alkyl group,(b) a lower alkoxycarbonyl group, and(c)a lower alkanoyl group,

(8) a carbamoyl group optionally substituted by a group selected from (a) a lower alkyl group, (b) a lower alkoxy-lower alkyl group, (c) a lower alkyl group substituted by a hydroxyl group, and (d) a lower alkyl group substituted by a di-lower alkylamino group, and

(9) a group of the formula: —O—NH—C(═NH)NH 2 ; or

D) a carbonyl group substituted by a group selected from the following:

(1) a lower alkoxy group,

(2) a hydroxyl group,

(3) an amino group optionally substituted by a group selected from (a)a lower alkyl group, (b) a lower alkoxy group, (c) a lower alkoxy-lower alkyl group, (d) a hydroxyl lower alkyl group, (e) a lower alkyl group substituted by an amino group optionally substituted by a lower alkyl group, (f) a lower alkyl group substituted by an aryl group, and (g) and

(4) a morpholinyl group,

A is a single bond; and R 3 is a hydrogen atom.

7. The compound according to claim 6 , wherein Y is a group selected from the following:

(1) a cycloalkyl group substituted by an amino group optionally substituted by a group selected from (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, and (c) a lower alkanoyl group,

(2) a cycloalkyl group substituted by a group of a formula:

that is optionally substituted by an oxo group,

(3) a cycloalkyl group substituted by an amino group substituted by a lower alkyl group substituted by an amino group optionally substituted by a group selected from (a) a lower alkanoyl group and (b) a lower alkoxycarbonyl group, and

(4) a cyoloalkyl group substituted by a lower alkyl group substituted by an amino group optionally substituted by a lower alkyl group; and

R 2 is a group selected from the following:

(1) a hydrogen atom,

(2) a lower alkoxy group,

(3) a lower alkoxy group substituted by a lower alkoxy group,

(4) a lower alkoxy group substituted by a hydroxyl group,

(5) a lower alkoxy group substituted by an amino group optionally substituted by a lower alkyl group,

(6) a lower alkoxycarbonyl group,

(7) a carboxyl group,

(8) an aminocarbonyl group optionally substituted by a group selected from (a) lower alkyl group, and (b) a hydroxy-lower alkyl group,

(9) a morpholinylcarbonyl group,

(10) a lower alkyl group,

(11) a lower alkyl group substituted by a lower alkoxycarbonyl group,

(12) a carboxy-lower alkyl group,

a lower alkyl group substituted by a carbamoyl group optionally substituted by a group selected from (a) a lower alkyl group and (b) a hydroxy-lower alkyl group, and

(13) a hydroxy-lower alkyl group.

8. The compound according to claim 6 , wherein Y is a cycloalkyl group substituted by a group of a formula

that is optionally substituted by an oxo group, or a cycloalkyl group substituted by an amino group optionally substituted by a. group selected from (a) a lower alkyl group and (b) a lower alkanoyl group; and R 2 is a group selected from the following;

(1) a hydrogen atom,

(2) a lower alkoxycarbonyl group,

(3) a morpholinylcarbonyl group,

(4) a lower alkyl group substituted by a lower alkyl group-substituted carbamoyl group,

(5) a carboxy-lower alkyl group, and

(6) a hydroxy-lower alkyl group.

9. The compound according to claim 6 , wherein Y is a cycloalkyl group substituted by an oxopyrrolidinyl group, or a cycloalkyl group substituted by an amino group optionally substituted by a group selected from (a) a lower alkyl group and (b) a lower alkanoyl group; and

R 2 is a group selected from the following:

(1) a hydrogen atom,

(2) a hydroxy-lower alkyl group,

(3) a carboxy-lower alkyl group,

(4) a lower alkoxy group substituted by a lower alkoxy group, and

(5) a carbonyl group substituted by a group selected from (a) an amino group optionally substituted by a lower alkyl group and (b) a morpholinyl group.

10. The compound according to claim 6 , wherein Y is a group selected from the following:

(1) a cycloalkyl group substituted by an amino group substituted by a lower alkyl group having 1 to 3 carbon atoms,

(2) a cycloalkyl group substituted by an amino group substituted by a lower alkanoyl group having 1 to 2 carbon atoms,

(3) a cycloalkyl group substituted by a pyrrolidin-l-yl group optionally substituted by an oxo group,

(4) a cycloalkyl group substituted by a lower alkyl group substituted by an amino group substituted by a lower alkyl group having 1 to 3 carbon atoms, and

(5) a cycloalkyl group substituted by a lower alkyl group substituted by an amino group substituted by a lower alkanoyl group having 1 to 2 carbon atoms.

11. A compound selected from

trans-5-dimethylaminocarbonyl-3-[4-(N-formyl-N-methylamino) cyclohexylcarbonylamino]-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide;

trans-3-[4-(N-acetyl-N-methylamino)cyclohexylcarbonylamino]-5-(2-hydroxyethyl-N-(5-chloropyridin2yl) benzofuran-2-carboxamide;

trans-5-(morpholine-4-ylcarbonyl )-3-[4-(2- oxo-pyrrolidin-1-yl)cyclohexylcarbonylamino-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide; and trans-3-(4-dimethylaminocyclohexylcarbonylamino)-N-(5-chloropyridin-2-yl) benzofuran-2-carboxamide

or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 1 , which is trans-5-dimethylaminocarbonyl3[4(N-formyl-N-methylamino)cyclohexylcarbonylamino]-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide; or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 1 , which is trans-3-[4-(N-acetyl-N- methylamino)cyclohexylcarbonylamino]-5-(2-hydroxyethyl-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide; or a pharmaceutically acceptable salt thereof.

14. The compound according to claim 1 , which is trans-5-(morpholine-4-ylcarbonyl)-3-[4-(2-oxo-pyrrolidin- 1-yl)cyclohexylcarbonylamino-N-(5-chloropyridin-2-yl)benzofuran-2-carboxamide; or a pharmaceutically acceptable salt thereof.

15. The compound according to claim 1 , which is trans-3-(4-dimethylaminocyclohexylcarbonylamino)-N-(5-chloropyridin-2-yl) benzofuran-2-carboxamide;

or a pharmaceutically acceptable salt thereof.

16. A pharmaceutical composition, which comprises as an active ingredient a compound according to any one of claims 1 , 2 , 3 , 4 , 5 , 6 , 11 and 12 - 15 or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

17. A method for treatment of thrombosis, which comprises administering an effective amount of a compound according to any one of claims 1 , 2 , 3 , 4 , 5 , 6 , 11 and 12 - 15 or a pharmaceutically acceptable salt thereof, to a patient in need thereof.