Benzofuran Derivatives

Abstract

The present invention provides a benzofuran derivative of the formula [1]: wherein x is a group of the formula: —N═ or —CH═; Y is an optionally substituted amino group, an optionally substituted cycloalkyl group or an optionally substituted saturated heterocyclic group; 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 or a halogen atom; Ring B is an optionally substituted benzene ring; and R 3 is a hydrogen atom, or a pharmaceutically acceptable salt thereof, which is useful as a medicament, especially as an activated blood coagulation factor X inhibitor.

1 . A benzofuran derivative of the formula [1]: 
     
       
         
         
             
             
         
       
     
     wherein x is a group of the formula: —N═ or the formula: —CH═;
 Y is an optionally substituted amino group, an optionally substituted cycloalkyl group or an optionally substituted saturated heterocyclic group; 
 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 an optionally substituted benzene ring; and
 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 Ring B is a benzene ring optionally substituted by a group(s) selected independently from a halogen atom, an optionally substituted lower alkyl group, a hydroxy group, an optionally substituted lower alkoxy group, an oxy group substituted by an optionally substituted saturated heterocyclic group, a substituted carbonyl group, an optionally substituted amino group, a nitro group, a cyano group, a 4,5-dihydroxazolyl group or a group of the formula: 
     
       
         
         
             
             
         
       
     
     and
 the “optionally substituted cycloalkyl group” for Y is a cycloalkyl group optionally substituted by a group selected from an optionally substituted amino group, an optionally substituted group of a formula 
 selected from the formulas: 
 
     
       
         
         
             
             
         
       
     
     and an optionally substituted lower alkyl group. 
   
   
       3 . The compound according to  claim 2 , wherein the “optionally substituted saturated heterocyclic group” for Y is a saturated heterocyclic group optionally substituted by a group selected from the followings:
 (1) a lower alkyl group,   (2) a lower alkyl group substituted by a pyridyl group,   (3) a piperidyl group substituted by a lower alkyl group,   (4) a piperidyl group,   (5) a piperidyl group substituted by a lower alkoxycarbonyl group,   (6) an unsaturated heterocyclic group selected from a pyridyl group, a pyrimidinyl group, a 4,5-dihydroxazolyl group and a thiazolyl group,   (7) a lower alkanoyl group,   (8) a lower alkanoyl group substituted by a di-lower alkylamino group,   (9) a carbonyl group substituted by a pyridyl group,   (10) a lower alkylsulfonyl group,   (11) a lower alkoxycarbonyl group,   (12) a lower alkyl group substituted by a di-lower alkylamino group, and   (13) an oxo group;   the “optionally substituted amino group” for Y is an amino group optionally substituted by a group selected from the followings:   (1) a piperidyl group substituted by a lower alkyl group,   (2) a lower alkyl group, and   (3) a lower alkoxycarbonyl group;   the “optionally substituted amino group” as a substituent on the cycloalkyl group for Y is an amino group optionally substituted by a group selected from the followings:   (1) a lower alkyl group,   (2) a cycloalkyl group,   (3) a hydroxy-lower alkyl group,   (4) a 1,3-dioxanyl group substituted by a lower alkyl group,   (5) 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,   (6) a lower alkyl group substituted by a cyano group,   (7) a lower alkyl group substituted by a lower alkoxycarbonyl group,   (8) a lower alkyl group substituted by a carboxyl group,   (9) a lower alkyl group substituted by a carbamoyl group optionally substituted by a lower alkyl group,   (10) a lower alkyl group substituted by an aryl group,   (11) a lower alkyl group substituted by a pyridyl group,   (12) a lower alkoxycarbonyl group,   (13) a lower alkanoyl group substituted by a di-lower alkyl amino group,   (14) a lower alkanoyl group,   (15) a pyrimidinyl group,   (16) a lower alkanoyl group substituted by a morpholinyl group,   (17) a lower alkylsulfonyl group,   (18) a carbamoyl group substituted by a lower alkyl group,   (19) a carbonyl group substituted by an aryl group,   (20) a lower alkanoyl group substituted by a lower alkoxy group,   (21) a lower alkanoyl group substituted by a lower alkanoyloxy group,   (22) an aryl group substituted by a hydroxyl group, and   (23) a hydroxy-lower alkanoyl group;   the “optionally substituted group of a formula selected from the formulas:   
     
       
         
         
             
             
         
       
     
     as a substituent on the cycloalkyl group for Y is a group selected from the groups of the formulas: 
     
       
         
         
             
             
         
       
     
     that is optionally substituted by an oxo group;
 the “optionally substituted lower alkyl group” as a substituent on the cycloalkyl group for Y is a lower alkyl group optionally substituted by a group selected from the followings: 
 (1) an oxopyrrolidinyl group, and 
 (2) an oxomorpholinyl group, and 
 (3) 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; 
 the “optionally substituted lower alkyl group” as a substituent for Ring B is a lower alkyl group optionally substituted by a group selected from the followings: 
 (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 piperidylcarbonyl group substituted by a hydroxy-lower alkyl group, 
 (6) a pyrrolidinylcarbonyl group substituted by a hydroxy-lower alkyl group, 
 (7) a carbonyl group substituted by a hydroxyl group-substituted piperidyl group, and 
 (8) a hydroxyl group; 
 the “optionally substituted lower alkoxy group” as a substituent for Ring B is a lower alkoxy group optionally substituted by a group selected from the followings: 
 (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) a carbonyl group substituted by a morpholinyl group, a piperidyl group or a pyrrolidinyl group, 
 (8) a carbonyl group substituted by a hydroxypiperidyl group, 
 (9) a piperidylcarbonyl group substituted by a hydroxy-lower alkyl group, 
 (10) a pyrrolidinylcarbonyl group substituted by a hydroxy-lower alkyl group, 
 (11) a carbonyl group substituted by a lower alkyl-piperazinyl group, 
 (12) an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, and (c) a lower alkanoyl group, 
 (13) 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 
 (14) a group of the formula: —O—NH—C(═NH)NH 2 ; 
 the “oxy group substituted by an optionally substituted saturated heterocyclic group” as a substituent for Ring B is an oxy group substituted by a heterocyclic group optionally substituted by an aryl group; 
 the “substituted carbonyl group” as a substituent for Ring B is a carbonyl group substituted by a group selected from the followings: 
 (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 (g) a lower alkyl group substituted by a pyridyl group, 
 (4) a morpholinyl group, a pyrrolidinyl group, a piperidyl group or a thiomorpholinyl group, 
 (5) a hydroxypiperidyl group, 
 (6) a piperidyl group substituted by a hydroxy-lower alkyl group, 
 (7) a pyrrolidinyl group substituted by a hydroxy-lower alkyl group, and 
 (8) a lower alkyl-piperazinyl group; 
 the “optionally substituted amino group” as a substituent for Ring B is an amino group optionally substituted by a group selected from the followings: 
 (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, 
 (12) a lower alkylsulfonyl group, and 
 (13) a lower alkylsulfonyl group substituted by a morpholinyl group. 
 
   
   
       4 . The compound according to  claim 3 , wherein B is an unsubstituted benzene ring; and
 Y is a saturated heterocyclic group optionally substituted by a group selected from the followings:   (1) a lower alkyl group,   (2) a lower alkyl group substituted by a pyridyl group   (3) a piperidyl group substituted by a lower alkyl group,   (4) a piperidyl group,   (5) a piperidyl group substituted by a lower alkoxycarbonyl group,   (6) an unsaturated heterocyclic group selected from a pyridyl group, a pyrimidinyl group, a 4,5-dihydroxazolyl group and a thiazolyl group,   (7) a lower alkanoyl group,   (8) a lower alkanoyl group substituted by a di-lower alkylamino group,   (9) a carbonyl group substituted by a pyridyl group,   (10) a lower alkylsulfonyl group,   (11) a lower alkoxycarbonyl group,   (12) a lower alkyl group substituted by a di-lower alkylamino group, and   (13) an oxo group.   
   
   
       5 . The compound according to  claim 3 , wherein B is an unsubstituted benzene ring; and
 Y is an amino group optionally substituted by a group selected from the followings:   (1) a piperidyl group substituted by a lower alkyl group,   (2) a lower alkyl group, and   (3) a lower alkoxycarbonyl group.   
   
   
       6 . The compound according to  claim 3 , wherein B is an unsubstituted benzene ring; and
 Y is a cycloalkyl group optionally substituted by the followings:   A) an amino group optionally substituted by the followings:   (1) a lower alkyl group,   (2) a cycloalkyl group,   (3) a hydroxy-lower alkyl group,   (4) a 1,3-dioxanyl group substituted by a lower alkyl group,   (5) 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,   (6) a lower alkyl group substituted by a cyano group,   (7) a lower alkyl group substituted by a lower alkoxycarbonyl group,   (8) a lower alkyl group substituted by a carboxyl group,   (9) a lower alkyl group substituted by a carbamoyl group optionally substituted by a lower alkyl group,   (10) a lower alkyl group substituted by an aryl group,   (11) a lower alkyl group substituted by a pyridyl group,   (12) a lower alkoxycarbonyl group,   (13) a lower alkanoyl group substituted by a di-lower alkyl amino group,   (14) a lower alkanoyl group,   (15) a pyrimidinyl group,   (16) a lower alkanoyl group substituted by a morpholinyl group,   (17) a lower alkylsulfonyl group,   (18) a carbamoyl group substituted by a lower alkyl group,   (19) a carbonyl group substituted by an aryl group,   (20) a lower alkanoyl group substituted by a lower alkoxy group,   (21) a lower alkanoyl group substituted by a lower alkanoyloxy group,   (22) an aryl group substituted by a hydroxy group, and   (23) a hydroxy-lower alkanoyl group;   B) a group of a formula selected from the formulas:   
     
       
         
         
             
             
         
       
     
     that is optionally substituted by an oxo group; or
 C) a lower alkyl group optionally substituted by a group selected from the followings: 
 (1) an oxopyrrolidinyl group, 
 (2) an oxomorpholinyl group, and 
 (3) an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, and (c) a lower alkanoyl group. 
 
   
   
       7 . The compound according to  claim 3 , wherein Ring B is a benzene ring substituted by a lower alkyl group optionally substituted by a group selected from the followings:
 (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 piperidylcarbonyl group substituted by a hydroxy-lower alkyl group,   (6) a pyrrolidinylcarbonyl group substituted by a hydroxy-lower alkyl group,   (7) a carbonyl group substituted by a hydroxyl group-substituted piperidyl group, and   (8) a hydroxyl group; and   Y is a saturated heterocyclic group optionally substituted by a group selected from the followings:   (1) a lower alkyl group,   (2) a lower alkyl group substituted by a pyridyl group   (3) a piperidyl group substituted by a lower alkyl group,   (4) a piperidyl group,   (5) a piperidyl group substituted by a lower alkoxycarbonyl group,   (6) an unsaturated heterocyclic group selected from a pyridyl group, a pyrimidinyl group, a 4,5-dihydroxaolyl group and a thiazolyl group,   (7) a lower alkanoyl group,   (8) a lower alkanoyl group substituted by a di-lower alkylamino group,   (9) a carbonyl group substituted by a pyridyl group,   (10) a lower alkylsulfonyl group,   (11) a lower alkoxycarbonyl group,   (12) a lower alkyl group substituted by a di-lower alkylamino group, and   (13) an oxo group.   
   
   
       8 . The compound according to  claim 3 , wherein Ring B is a benzene ring substituted by a lower alkyl group optionally substituted by a group selected from the followings:
 (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 piperidylcarbonyl group substituted by a hydroxy-lower alkyl group,   (6) a pyrrolidinylcarbonyl group substituted by a hydroxy-lower alkyl group,   (7) a carbonyl group substituted by a hydroxyl group-substituted piperidyl group, and   (8) a hydroxyl group; and   Y is an amino group optionally substituted by a group selected from the followings:   (1) a piperidyl group substituted by a lower alkyl group,   (2) a lower alkyl group, and   (3) a lower alkoxycarbonyl group.   
   
   
       9 . The compound according to  claim 3 , wherein Ring B is a benzene ring substituted by a lower alkyl group optionally substituted by a group selected from the followings:
 (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 piperidylcarbonyl group substituted by a hydroxy-lower alkyl group,   (6) a pyrrolidinylcarbonyl group substituted by a hydroxy-lower alkyl group,   (7) a carbonyl group substituted by a hydroxyl group-substituted piperidyl group, and   (8) a hydroxyl group; and   Y is a cycloalkyl group optionally substituted by the followings:   A) an amino group optionally substituted by the followings:   (1) a lower alkyl group,   (2) a cycloalkyl group,   (3) a hydroxy-lower alkyl group,   (4) a 1,3-dioxanyl group substituted by a lower alkyl group,   (5) 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,   (6) a lower alkyl group substituted by a cyano group,   (7) a lower alkyl group substituted by a lower alkoxycarbonyl group,   (8) a lower alkyl group substituted by a carboxyl group,   (9) a lower alkyl group substituted by a carbamoyl group optionally substituted by a lower alkyl group,   (10) a lower alkyl group substituted by an aryl group,   (11) a lower alkyl group substituted by a pyridyl group,   (12) a lower alkoxycarbonyl group,   (13) a lower alkanoyl group substituted by a di-lower alkyl amino group,   (14) a lower alkanoyl group,   (15) a pyrimidinyl group,   (16) a lower alkanoyl group substituted by a morpholinyl group,   (17) a lower alkylsulfonyl group,   (18) a carbamoyl group substituted by a lower alkyl group,   (19) a carbonyl group substituted by an aryl group,   (20) a lower alkanoyl group substituted by a lower alkoxy group,   (21) a lower alkanoyl group substituted by a lower alkanoyloxy group,   (22) an aryl group substituted by a hydroxy group, and   (23) a hydroxy-lower alkanoyl group;   B) a group of a formula selected from the formulas:   
     
       
         
         
             
             
         
       
     
     that is optionally substituted by an oxo group; or
 C) a lower alkyl group optionally substituted by a group selected from the followings: 
 (1) an oxopyrrolidinyl group, 
 (2) an oxomorpholinyl group, and 
 (3) an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, and (c) a lower alkanoyl group. 
 
   
   
       10 . The compound according to  claim 3 , wherein Ring B is a benzene ring substituted by a lower alkoxy group optionally substituted by a group selected from the followings:
 (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) a carbonyl group substituted by a morpholinyl group, a piperidyl group or a pyrrolidinyl group,   (8) a carbonyl group substituted by a hydroxypiperidyl group,   (9) a piperidylcarbonyl group substituted by a hydroxy-lower alkyl group,   (10) a pyrrolidinylcarbonyl group substituted by a hydroxy-lower alkyl group,   (11) a carbonyl group substituted by a lower alkyl-piperazinyl group,   (12) an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, and (c) a lower alkanoyl group,   (13) 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   (14) a group of the formula: —O—NH—C(═NH)NH 2 ; and   Y is a saturated heterocyclic group optionally substituted by a group selected from the followings:   (1) a lower alkyl group,   (2) a lower alkyl group substituted by a pyridyl group   (3) a piperidyl group substituted by a lower alkyl group,   (4) a piperidyl group,   (5) a piperidyl group substituted by a lower alkoxycarbonyl group,   (6) an unsaturated heterocyclic group selected from a pyridyl group, a pyrimidinyl group, a 4,5-dihydroxaolyl group and a thiazolyl group,   (7) a lower alkanoyl group,   (8) a lower alkanoyl group substituted by a di-lower alkylamino group,   (9) a carbonyl group substituted by a pyridyl group,   (10) a lower alkylsulfonyl group,   (11) a lower alkoxycarbonyl group,   (12) a lower alkyl group substituted by a di-lower alkylamino group, and   (13) an oxo group.   
   
   
       11 . The compound according to  claim 3 , wherein Ring B is a benzene ring substituted by a lower alkoxy group optionally substituted by a group selected from the followings:
 (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) a carbonyl group substituted by a morpholinyl group, a piperidyl group or a pyrrolidinyl group,   (8) a carbonyl group substituted by a hydroxypiperidyl group,   (9) a piperidylcarbonyl group substituted by a hydroxy-lower alkyl group,   (10) a pyrrolidinylcarbonyl group substituted by a hydroxy-lower alkyl group,   (11) a carbonyl group substituted by a lower alkyl-piperazinyl group,   (12) an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, and (c) a lower alkanoyl group,   (13) 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   (14) a group of the formula: —O—NH—C(═NH)NH 2 ; and   Y is an amino group optionally substituted by a group selected from the followings:   (1) a piperidyl group substituted by a lower alkyl group,   (2) a lower alkyl group, and   (3) a lower alkoxycarbonyl group.   
   
   
       12 . The compound according to  claim 3 , wherein Ring B is a benzene ring substituted by a lower alkoxy group optionally substituted by a group selected from the followings:
 (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) a carbonyl group substituted by a morpholinyl group, a piperidyl group or a pyrrolidinyl group,   (8) a carbonyl group substituted by a hydroxypiperidyl group,   (9) a piperidylcarbonyl group substituted by a hydroxy-lower alkyl group,   (10) a pyrrolidinylcarbonyl group substituted by a hydroxy-lower alkyl group,   (11) a carbonyl group substituted by a lower alkyl-piperazinyl group,   (12) an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, and (c) a lower alkanoyl group,   (13) 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   (14) a group of the formula: —O—NH—C(═NH)NH 2 ; and   Y is a cycloalkyl group optionally substituted by the followings:   A) an amino group optionally substituted by the followings:   (1) a lower alkyl group,   (2) a cycloalkyl group,   (3) a hydroxy-lower alkyl group,   (4) a 1,3-dioxanyl group substituted by a lower alkyl group,   (5) 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,   (6) a lower alkyl group substituted by a cyano group,   (7) a lower alkyl group substituted by a lower alkoxycarbonyl group,   (8) a lower alkyl group substituted by a carboxyl group,   (9) a lower alkyl group substituted by a carbamoyl group optionally substituted by a lower alkyl group,   (10) a lower alkyl group substituted by an aryl group,   (11) a lower alkyl group substituted by a pyridyl group,   (12) a lower alkoxycarbonyl group,   (13) a lower alkanoyl group substituted by a di-lower alkyl amino group,   (14) a lower alkanoyl group,   (15) a pyrimidinyl group,   (16) a lower alkanoyl group substituted by a morpholinyl group,   (17) a lower alkylsulfonyl group,   (18) a carbamoyl group substituted by a lower alkyl group,   (19) a carbonyl group substituted by an aryl group,   (20) a lower alkanoyl group substituted by a lower alkoxy group,   (21) a lower alkanoyl group substituted by a lower alkanoyloxy group,   (22) an aryl group substituted by a hydroxy group, and   (23) a hydroxy-lower alkanoyl group;   B) a group of a formula selected from the formulas:   
     
       
         
         
             
             
         
       
     
     that is optionally substituted by an oxo group; or
 C) a lower alkyl group optionally substituted by a group selected from the followings: 
 (1) an oxopyrrolidinyl group, 
 (2) an oxomorpholinyl group, and 
 (3) an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, and (c) a lower alkanoyl group. 
 
   
   
       13 . The compound according to  claim 3 , wherein Ring B is a benzene ring substituted by a carbonyl group substituted by a group selected from the followings:
 (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 (g) a lower alkyl group substituted by a pyridyl group,   (4) a morpholinyl group, a pyrrolidinyl group, a piperidyl group or a thiomorpholinyl group,   (5) a hydroxypiperidyl group,   (6) a piperidyl group substituted by a hydroxy-lower alkyl group,   (7) a pyrrolidinyl group substituted by a hydroxy-lower alkyl group, and   (8) a lower alkyl-piperazinyl group; and   Y is a saturated heterocyclic group optionally substituted by a group selected from the followings:   (1) a lower alkyl group,   (2) a lower alkyl group substituted by a pyridyl group   (3) a piperidyl group substituted by a lower alkyl group,   (4) a piperidyl group,   (5) a piperidyl group substituted by a lower alkoxycarbonyl group,   (6) an unsaturated heterocyclic group selected from a pyridyl group, a pyrimidinyl group, a 4,5-dihydroxaolyl group and a thiazolyl group,   (7) a lower alkanoyl group,   (8) a lower alkanoyl group substituted by a di-lower alkylamino group,   (9) a carbonyl group substituted by a pyridyl group,   (10) a lower alkylsulfonyl group,   (11) a lower alkoxycarbonyl group,   (12) a lower alkyl group substituted by a di-lower alkylamino group, and   (13) an oxo group.   
   
   
       14 . The compound according to  claim 3 , wherein Ring B is a benzene ring substituted by a carbonyl group substituted by a group selected from the followings:
 (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 (g) a lower alkyl group substituted by a pyridyl group,   (4) a morpholinyl group, a pyrrolidinyl group, a piperidyl group or a thiomorpholinyl group,   (5) a hydroxypiperidyl group,   (6) a piperidyl group substituted by a hydroxy-lower alkyl group,   (7) a pyrrolidinyl group substituted by a hydroxy-lower alkyl group, and   (8) a lower alkyl-piperazinyl group; and   Y is an amino group optionally substituted by a group selected from the followings:   (1) a piperidyl group substituted by a lower alkyl group,   (2) a lower alkyl group, and   (3) a lower alkoxycarbonyl group.   
   
   
       15 . The compound according to  claim 3 , wherein Ring B is a benzene ring substituted by a carbonyl group substituted by a group selected from the followings:
 (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 (g) a lower alkyl group substituted by a pyridyl group,   (4) a morpholinyl group, a pyrrolidinyl group, a piperidyl group or a thiomorpholinyl group,   (5) a hydroxypiperidyl group,   (6) a piperidyl group substituted by a hydroxy-lower alkyl group,   (7) a pyrrolidinyl group substituted by a hydroxy-lower alkyl group, and   (8) a lower alkyl-piperazinyl group; and   Y is a cycloalkyl group optionally substituted by the followings:   A) an amino group optionally substituted by the followings:   (1) a lower alkyl group,   (2) a cycloalkyl group,   (3) a hydroxy-lower alkyl group,   (4) a 1,3-dioxanyl group substituted by a lower alkyl group,   (5) 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,   (6) a lower alkyl group substituted by a cyano group,   (7) a lower alkyl group substituted by a lower alkoxycarbonyl group,   (8) a lower alkyl group substituted by a carboxyl group,   (9) a lower alkyl group substituted by a carbamoyl group optionally substituted by a lower alkyl group,   (10) a lower alkyl group substituted by an aryl group,   (11) a lower alkyl group substituted by a pyridyl group,   (12) a lower alkoxycarbonyl group,   (13) a lower alkanoyl group substituted by a di-lower alkyl amino group,   (14) a lower alkanoyl group,   (15) a pyrimidinyl group,   (16) a lower alkanoyl group substituted by a morpholinyl group,   (17) a lower alkylsulfonyl group,   (18) a carbamoyl group substituted by a lower alkyl group,   (19) a carbonyl group substituted by an aryl group,   (20) a lower alkanoyl group substituted by a lower alkoxy group,   (21) a lower alkanoyl group substituted by a lower alkanoyloxy group,   (22) an aryl group substituted by a hydroxy group, and   (23) a hydroxy-lower alkanoyl group;   B) a group of a formula selected from the formulas:   
     
       
         
         
             
             
         
       
     
     that is optionally substituted by an oxo group; or
 C) a lower alkyl group optionally substituted by a group selected from the followings: 
 (1) an oxopyrrolidinyl group, 
 (2) an oxomorpholinyl group, and 
 (3) an amino group optionally substituted by (a) a lower alkyl group, (b) a lower alkoxycarbonyl group, and (c) a lower alkanoyl group. 
 
   
   
       16 . The compound according to any one of  claims 1 ,  2 ,  3 ,  4 ,  7 ,  10  and  13 , wherein the saturated heterocyclic ring is a saturated 4- to 7-membered heterocyclic group containing 1 to 4 hetero atoms selected independently from the group consisting of nitrogen atom, oxygen atom and sulfur atom. 
   
   
       17 . The compound according to any one of  claims 1 ,  2 ,  3 ,  4 ,  7 ,  10  and  13 , wherein the saturated heterocyclic group is imidazolidinyl, piperazolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, homopiperidyl, pyrrolidinyl, oxazolidinyl or 1,3-dioxanyl. 
   
   
       18 . The compound according to  claim 3 , wherein the group of the formula: 
     
       
         
         
             
             
         
       
     
     is the group of the formula: 
     
       
         
         
             
             
         
       
     
     and the group of the formula: 
     
       
         
         
             
             
         
       
     
     is a group of the formula: 
     
       
         
         
             
             
         
       
       R 1  is a halogen atom or a lower alkyl group; 
       R 2  is a group selected from the followings: 
       A) a hydrogen atom, 
       B) a lower alkyl group optionally substituted by a group selected from the followings: 
       (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 piperidylcarbonyl group substituted by a hydroxy-lower alkyl group, 
       (6) a pyrrolidinylcarbonyl group substituted by a hydroxy-lower alkyl group, 
       (7) a carbonyl group substituted by a hydroxyl group-substituted piperidyl group, and 
       (8) a hydroxyl group; 
       C) a lower alkoxy group optionally substituted by a group selected from the followings: 
       (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) a carbonyl group substituted by a morpholinyl group, a piperidyl group or a pyrrolidinyl group, 
       (8) a carbonyl group substituted by a hydroxypiperidyl group, 
       (9) a piperidylcarbonyl group substituted by a hydroxy-lower alkyl group, 
       (10) a pyrrolidinylcarbonyl group substituted by a hydroxy-lower alkyl group, 
       (11) a carbonyl group substituted by a lower alkyl-piperazinyl group, 
       (12) 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, 
       (13) 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 
       (14) a group of the formula: —O—NH—C(═NH)NH 2 ; or 
       D) a carbonyl group substituted by a group selected from the followings: 
       (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 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 (g) a lower alkyl group substituted by a pyridyl group, 
       (4) a morpholinyl group, a pyrrolidinyl group, a piperidyl group or a thiomorpholinyl group, 
       (5) a hydroxypiperidyl group, 
       (6) a piperidyl group substituted by a hydroxy-lower alkyl group, 
       (7) a pyrrolidinyl group substituted by a hydroxy-lower alkyl group, and 
       (8) a lower alkyl-piperazinyl group; 
       A is a single bond; and 
       R 3  is a hydrogen atom. 
     
   
   
       19 . The compound according to  claim 18 , wherein Y is a group selected from the followings:
 (1) a piperidyl group substituted by a lower alkyl group,   (2) 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,   (3) a cycloalkyl group substituted by a group of a formula selected from the formulas:   
     
       
         
         
             
             
         
       
     
     that is optionally substituted by an oxo group,
 (4) 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 
 (5) a cycloalkyl 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 followings: 
 (1) a hydrogen atom, 
 (2) a cyano group, 
 (3) an amino group optionally substituted by a lower alkyl group, 
 (4) a hydroxyl group, 
 (5) a lower alkoxy group, 
 (6) a lower alkoxy group substituted by a lower alkoxy group, 
 (7) a lower alkoxy group substituted by a hydroxyl group, 
 (8) a lower alkoxy group substituted by an amino group optionally substituted by a lower alkyl group, 
 (9) a lower alkoxycarbonyl group, 
 (10) a carboxyl group, 
 (11) an aminocarbonyl group optionally substituted by a group selected from (a) lower alkyl group, and (b) a hydroxy-lower alkyl group, 
 (12) a morpholinylcarbonyl group, a pyrrolidinylcarbonyl group, a piperidylcarbonyl group or a thiomorpholinylcarbonyl group, 
 (13) a piperidylcarbonyl group substituted by a hydroxy-lower alkyl group or a pyrrolidinylcarbonyl group substituted by a hydroxy-lower alkyl group, 
 (14) a lower alkyl group, 
 (15) a lower alkyl group substituted by a lower alkoxycarbonyl group, 
 (16) a carboxy-lower alkyl group, 
 (17) a lower alkyl group substituted by a carbamoyl group optionally substituted by a group selected from (a) lower alkyl group and (b) a hydroxy-lower alkyl group, 
 (18) a lower alkyl group substituted by a morpholinylcarbonyl group, 
 (19) a lower alkyl group substituted by a piperidylcarbonyl group substituted by a hydroxy-lower alkyl group, or a lower alkyl group substituted by a pyrrolidinylcarbonyl group substituted by a hydroxy-lower alkyl group, or 
 (20) a hydroxy-lower alkyl group. 
 
   
   
       20 . The compound according to  claim 18 , wherein Y is a cycloalkyl group substituted by a group of a formula selected from the formulas: 
     
       
         
         
             
             
         
       
     
     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 followings: 
 (1) a hydrogen atom, 
 (2) an amino group-substituted carbonyl group optionally substituted by a group selected from (a) a lower alkyl group and (b) a lower alkoxy-lower alkyl group, 
 (3) a lower alkoxycarbonyl group, 
 (4) a morpholinylcarbonyl group, a pyrrolidinylcarbonyl group, a piperidylcarbonyl group or a thiomorpholinylcarbonyl group, 
 (5) a lower alkyl group substituted by a lower alkyl group-substituted carbamoyl group, 
 (6) a carboxy-lower alkyl group, 
 (7) a lower alkyl group substituted by a morpholinylcarbonyl group, and 
 (8) a hydroxy-lower alkyl group. 
 
   
   
       21 . The compound according to  claim 18 , wherein Y is a cycloalkyl group substituted by an oxopyrrolidinyl group, a cycloalkyl group substituted by an oxomorpholinyl 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 followings:   (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, or   (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.   
   
   
       22 . The compound according to  claim 18 , wherein Y is a group selected from the followings:
 (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-1-yl group optionally substituted by an oxo group,   (4) a cycloalkyl group substituted by a piperidin-1-yl group optionally substituted by an oxo group,   (5) a cycloalkyl group substituted by a morpholin-4-yl group optionally substituted by an oxo group,   (6) 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, or   (7) 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.   
   
   
       23 . 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-chloropyridin-2-yl)benzofuran-2-carboxamide; 
     trans-5-(morpholine-4-ylcarbonyl)-3-[4-(2-oxo-pyrroridin-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. 
     
       
         
         
             
             
         
       
     
     wherein the symbols are the same as defined above, or a salt thereof. 
   
   
       24 . A pharmaceutical composition, which comprises as an active ingredient a compound according to any one of  claims 1  to  24 , or a pharmaceutically acceptable salt thereof. 
   
   
       25 . A method for treatment of thrombosis, which comprises administering an effective amount of a compound according to any one of  claims 1  to  24 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof 
   
   
       26 . Use of a compound according to any one of  claims 1  to  24  above or a pharmaceutically acceptable salt thereof in treatment of patients suffering from thrombosis. 
   
   
       27 . A medicament for treatment of thrombosis substantially free of phospholipidosis, which comprises as an active ingredient a factor. Xa (FXa) inhibitor showing a distribution volume of 0.1-3.0 L/kg and an FXa inhibitory effect with the IC 50  value of 100 nM or below. 
   
   
       28 . A medicament for treatment of thrombosis substantially free of hepatotoxicity, which comprises as an active ingredient an FXa inhibitor showing a distribution volume of 0.1-3.0 L/kg or below and an FXa inhibitory effect with the IC 50  value of 100 nM or below. 
   
   
       29 . A medicament for oral administration for treatment of thrombosis substantially free of phospholipidosis, which comprises as an active ingredient a factor Xa (FXa) inhibitor showing a distribution volume of 0.1-3.0 L/kg and an FXa inhibitory effect with the IC 50  value of 100 nM or below. 
   
   
       30 . A medicament for oral administration for treatment of thrombosis substantially free of hepatotoxicity, which comprises as an active ingredient an FXa inhibitor showing a distribution volume of 0.1-3.0 L/kg or below and an FXa inhibitory effect with the IC 50  value of 100 nM or below. 
   
   
       31 . A medicament for treatment of thrombosis substantially free of phospholipidosis, which comprises as an active ingredient an FXa inhibitor having a partial structure of the formula: 
     
       
         
         
             
             
         
       
     
     and showing a distribution volume of 0.1-3.0 L/kg and an FXa inhibitory effect with the IC 50  value of 100 nM or below. 
   
   
       32 . A medicament for treatment of thrombosis substantially free of hepatotoxicity, which comprises as an active ingredient an FXa inhibitor having a partial structure of the formula: 
     
       
         
         
             
             
         
       
     
     and showing a distribution volume of 0.1-3.0 L/kg and an FXa inhibitory effect with the IC 50  value of 100 nM or below. 
   
   
       33 . A medicament for oral administration for treatment of thrombosis substantially free of phospholipidosis, which comprises as an active ingredient an FXa inhibitor having a partial structure of the formula: 
     
       
         
         
             
             
         
       
     
     and showing a distribution volume of 0.1-3.0 L/kg and an FXa inhibitory effect with the IC 50  value of 100 nM or below. 
   
   
       34 . A medicament for oral administration for treatment of thrombosis substantially free of hepatotoxicity, which comprises as an active ingredient an FXa inhibitor having a partial structure of the formula: 
     
       
         
         
             
             
         
       
     
     and showing a distribution volume of 0.1-3.0 L/kg and an FXa inhibitory effect with the IC 50  value of 100 nM or below.