Fused quinoline derivative and use thereof

Abstract

The present invention aims at provision of a quinoline derivative having a neurokinin 2 (NK2) receptor antagonistic action and relates to a compound represented by the formula (I) wherein R 1 is a hydrogen atom and the like; R 2 is a hydrogen atom, a hydrocarbon group optionally having substituent(s) and the like; R 3 is unsubstituted (i.e., absence), a hydrogen atom and the like; R 4 and R 5 are the same or different and each is a hydrogen atom, a hydrocarbon group optionally having substituent(s), and the like; R 6 is (cyclic group optionally having substituent(s))-carbonyl, and the like; R 7 , R 8 , R 9 and R 10 are the same or different and each is a hydrogen atom, halogen and the like; or R 7 and R 8 , R 8 and R 9 , and R 9 and R 10 may form a ring together with the adjacent carbon atoms; n is an integer of 1 to 5; represents unsubstituted (i.e., absence) or a single bond; and represents a single bond or a double bond, or a salt thereof, and the like.

1 . A compound represented by the formula (I) 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is (1) unsubstituted, (2) a hydrogen atom, (3) a hydrocarbon group optionally having substituent(s) or (4) acyl; 
 R 2  is (1) a hydrogen atom, (2) a hydrocarbon group optionally having substituent(s), (3) hydroxy optionally having a substituent, (4) amino optionally having substituent(s), (5) thiol optionally having a substituent, (6) a heterocyclic group optionally having substituent(s) or (7) acyl; 
 R 3  is (1) unsubstituted, (2) a hydrogen atom, (3) a hydrocarbon group optionally having substituent(s), (4) hydroxy optionally having a substituent, (5) amino optionally having substituent(s), (6) thiol optionally having a substituent or (7) acyl; 
 R 4  and R 5  are the same or different and each is (1) a hydrogen atom, (2) a hydrocarbon group optionally having substituent(s), (3) hydroxy optionally having a substituent, (4) amino optionally having substituent(s), (5) thiol optionally having a substituent or (6) acyl; 
 R 6  is (1) (cyclic group optionally having substituent(s))-carbonyl, (2) alkenylcarbonyl optionally having substituent(s), (3) alkylcarbonyl having substituent(s) selected from (i) cycloalkyl optionally having substituent(s), (ii) amino optionally having substituent(s) and (iii) a heterocyclic group optionally having substituent(s) or (4) a heterocyclic group optionally having substituent(s); 
 R 7 , R 8 , R 9  and R 10  are the same or different and each is (1) a hydrogen atom, (2) halogen, (3) cyano, (4) nitro, (5) a hydrocarbon group optionally having substituent(s), (6) hydroxy optionally having a substituent, (7) amino optionally having substituent(s), (8) thiol optionally having a substituent, (9) a heterocyclic group optionally having substituent(s) or (10) acyl; or 
 R 7  and R 8 , R 8  and R 9 , and R 9  and R 10  may form a ring together with the adjacent carbon atoms; 
 n is an integer of 1 to 5; 
    represents unsubstituted or a single bond; and; 
    represents a single bond or a double bond, or a salt thereof. 
 
     
     
         2 . The compound of  claim 1 , wherein R 6  is (1) (cyclic group optionally having substituent(s))-carbonyl, (2) alkenylcarbonyl optionally having substituent(s), (3) alkylcarbonyl having substituent(s) selected from (i) cycloalkyl optionally having substituent(s) and (ii) amino optionally having substituent(s) or (4) a heterocyclic group optionally having substituent(s). 
     
     
         3 . The compound of  claim 1 , wherein
 R 1  is   (1) unsubstituted,   (2) a hydrogen atom,   (3) C 1-6  alkyl,   (4) C 7-12  aralkyl or   (5) C 1-6  alkyl-carbonyl;   R 2  is   (1) a hydrogen atom,   (2) C 1-6  alkyl optionally having 1 to 3 substituents selected from (1′) hydroxy, (2′) C 1-6  alkoxy, (3′) C 7-12  aralkyloxy, (4′) mono- or di-C 1-6  alkylamino, (5′) N—C 1-6  alkoxy-carbonyl-N—C 1-6  alkylamino, (6′) amino, (7′) C 1-6  alkyl-carbonylamino optionally having 1 to 3 halogens, (8′) C 7-12  aralkyloxy-carbonylamino and (9′) C 1-6  alkoxy-carbonylamino optionally having 1 to 3 halogens,   (3) C 3-8  cycloalkyl,   (4) C 6-10  aryl optionally having 1 to 3 substituents selected from (1′) halogen, (2′) C 1-6  alkyl optionally having 1 to 3 halogens, (3′) cyano, (4′) C 1-6  alkoxy-carbonyl and (5′) C 1-6  alkyl-thio,   (5) C 1-6  alkoxy-carbonyl, or   (6) a 5- or 6-membered heterocyclic group optionally having substituent(s) selected from (1′) hydroxy, (2′) C 1-6  alkyl optionally having C 1-6  alkyl-carbonyloxy, (3′) C 7-19  aralkyl optionally having C 1-6  alkoxy, (4′) C 7-12  aralkyloxy, (5′) C 7-12  aralkyloxy-carbonyl, (6′) mono-C 1-6  alkyl-carbamoyl and (7′) C 1-6  alkoxy-carbonyl;   R 3  is   (1) unsubstituted,   (2) a hydrogen atom or   (3) C 1-6  alkyl;   R 4  is a hydrogen atom;   R 5  is a hydrogen atom;   R 6  is   (1) a group represented by the formula   
       
         
           
           
               
               
           
         
       
       wherein ring A is cyclopentane, cyclohexane or bicyclo[2.2.2]octane;
 R 11  is 
 (1′) amino, 
 (2′) C 7-12  aralkylamino, 
 (3′) C 1-6  alkyl-carbonylamino optionally having substituent(s) selected from (1″) halogen, (2″) hydroxy, (3″) C 1-6  alkoxy-carbonyl, (4″) mono- or di-C 1-6  alkylamino optionally substituted by hydroxy, (5″) morpholino, (6″) C 1-6  alkyl-carbonylamino, (7″) carbamoylamino, (8″) a 5- or 6-membered aromatic heterocyclic group, (9″) C 6-10  arylamino, (10″)(5- or 6-membered aromatic heterocyclic group)-carbonylamino and (11″) C 1-6  alkoxy, 
 (4′) C 2-6  alkenyl-carbonylamino optionally having substituent(s) selected from (1″) C 6-10  aryl optionally having substituent(s) selected from halogen, C 1-6  alkyl, C 1-6  alkoxy and halogeno-C 1-6  alkyl and (2″) a 5- or 6-membered aromatic heterocyclic group optionally having C 1-6  alkyl, 
 (5′) C 3-8  cycloalkyl-carbonylamino, 
 (6′) C 6-10  aryl-carbonylamino optionally having substituent(s) selected from (1″) halogen, (2″) cyano, (3″) C 1-6  alkyl optionally having amino or C 1-6  alkyl-carbonylamino, (4″) halogeno-C 1-6  alkyl, (5″) hydroxy-C 1-6  alkyl, (6″) C 1-6  alkoxy, (7″) carboxy, (8″) C 1-6  alkoxy-carbonyl, (9″) mono- or di-C 1-6  alkylamino optionally having hydroxy or C 1-6  alkoxy, (10″) carbamoyl, (11″) halogeno-C 1-6  alkoxy, (12″) C 1-6  alkyl-carbonylamino, (13″) aminosulfonyl, (14″) C 1-6  alkyl-sulfonyl and (15″) a 5- or 6-membered heterocyclic group, or a fused ring group of benzene ring and 5- or 6-membered heterocycle, which may have substituent(s) selected from C 1-6  alkyl and oxo, 
 (7′) C 7-12  aralkyl-carbonylamino, 
 (8′) C 1-6  alkoxy-carbonylamino, 
 (9′) (5- or 6-membered heterocyclic group, or fused ring group of benzene ring and 5- or 6-membered heterocycle)-carbonylamino, which may have substituent(s) selected from (1″) amino, (2″) C 1-6  alkyl, (3″) halogeno-C 1-6  alkyl, (4″) C 6-10  aryl, (5″) oxo and (6″) a 5- or 6-membered heterocyclic group optionally having C 1-6  alkyl, 
 (10′) C 6-10  aryl-sulfonylamino, 
 (11′) carbamoylcarbonylamino, 
 (12′) 3-C 1-6  alkyl-ureido optionally having substituent(s) selected from (1″) hydroxy, (2″) carboxy, (3″) C 1-6  alkoxy, (4″) C 1-6  alkoxy-carbonyl, (5″) C 1-6  alkoxy-carbonylamino, (6″) amino, (7″) halogen, (8″) carbamoyl, (9″) C 1-6  alkylsulfonyl, (10″) a heterocyclic group optionally substituted by oxo and (11″) C 1-6  alkyl-carbonylamino, 
 (13′) 3-C 3-8  cycloalkyl-ureido, 
 (14′) 3-C 6-10  aryl-ureido optionally having substituent(s) selected from (1″) halogen, (2″) cyano, (3″) halogeno-C 1-6  alkyl, (4″) C 1-6  alkyl, (5″) C 1-6  alkoxy, (6″) methylenedioxy, (7″) C 1-6  alkoxy-carbonyl, (8″) carbamoyl and (9″) a 5- or 6-membered aromatic heterocyclic group, 
 (15′) 3-C 1-6  alkyl-3-C 6-10  aryl-ureido, 
 (16′) 3-C 7-12  aralkyl-ureido optionally having substituent(s) selected from (1″) halogen and (2″) C 1-6  alkoxy, 
 (17′) 3-C 1-6  alkoxy-ureido, 
 (18′) 3-C 6-10  arylsulfonyl-ureido, 
 (19′) 3-(5- or 6-membered heterocyclic group, or fused ring group of benzene ring and 5- or 6-membered heterocycle)-ureido, which may have 5- or 6-membered heterocyclic group, 
 (20′) piperidylureido optionally having C 1-6  alkyl-carbonyl, or 
 (21′) phthalimidol, 
 (2) a group represented by the formula 
 
       
         
           
           
               
               
           
         
       
       wherein R 12  is (1′) a hydrogen atom, (2′) C 6-10  aryl-carbonyl optionally having halogeno-C 1-6  alkyl, (3′) C 7-12  aralkyl-oxycarbonyl or (4′) C 6-10  aryl-aminocarbonyl; m is 0 or 1; and p is 0 or 1,
 (3) a group represented by the formula 
 
       
         
           
           
               
               
           
         
       
       wherein R 13  is C 6-10  aryl-carbonyl,
 (4) a group represented by the formula 
 
       
         
           
           
               
               
           
         
       
       wherein ring B is a pyrrolidine ring or a piperidine ring, each optionally substituted by amino; R 14  is (1′) a hydrogen atom, (2′) C 7-12  aralkyl, (3′) C 1-6  alkyl-carbonyl, (4′) C 6-10  aryl-carbonyl, (5′) C 7-12  aralkyl-carbonyl, (6′) C 1-6  alkoxy-carbonyl or (7′) C 7-12  aralkyl-carbamoyl,
 (5) C 2-6  alkenyl-carbonyl optionally having substituent(s) selected from (1′) carboxy, (2′) C 1-6  alkoxy-carbonyl and (3′) C 6-10  aryl-aminocarbonyl, 
 (6) C 1-6  alkyl-carbonyl having substituent(s) selected from (1′) amino, (2′) C 6-10  aryl-carbonylamino, (3′) C 1-6  alkoxy-carbonylamino and (4′) a 5- or 6-membered heterocyclic group, or a fused ring group of benzene ring and 5- or 6-membered heterocycle, each optionally substituted by oxo, 
 (7) 1,2,3,4-tetrahydronaphthylcarbonyl, 
 (8) pyrrolidinyl having C 7-12  aralkyl, or 
 (9) a group represented by the formula 
 
       
         
           
           
               
               
           
         
       
       wherein R 15  is C 6-10  aryl-carbonyl; r is 0 or 1; and s is 0 or 1;
 R 7  is a hydrogen atom; 
 R 8  is (1) a hydrogen atom, (2) halogen, (3) cyano, (4) C 1-6  alkyl optionally having 1 to 3 halogens, (5) C 6-10  aryl-carbonyl, (6) C 1-6  alkoxy, (7) C 6-10  aryloxy or (8) sulfamoyl; R 9  is (1) a hydrogen atom, (2) halogen, (3) cyano, (4) C 1-6  alkyl or (5) C 1-6  alkoxy; R 10  is (1) a hydrogen atom, (2) halogen, (3) C 1-6  alkyl or (4) C 1-6  alkoxy; and n is 2 or 3. 
 
     
     
         4 . The compound of  claim 1 , wherein
 R 1  is   (1) unsubstituted,   (2) a hydrogen atom,   (3) C 1-6  alkyl or   (4) C 1-6  alkyl-carbonyl;   R 2  is   (1) a hydrogen atom,   (2) C 1-6  alkyl optionally having 1 to 3 substituents selected from (1′) hydroxy, (2′) C 1-6  alkoxy, (3′) C 7-12  aralkyloxy, (4′) mono-C 1-6  alkylamino and (5′) N—C 1-6  alkoxy-carbonyl-N—C 1-6  alkylamino,   (3) C 3-8  cycloalkyl,   (4) C 6-10  aryl optionally having 1 to 3 substituents selected from (1′) halogen, (2′) C 1-6  alkyl optionally having 1 to 3 halogens, (3′) cyano and (4′) C 1-6  alkoxy-carbonyl, or   (5) a 5- or 6-membered aromatic heterocyclic group optionally having substituent(s) selected from (1′) hydroxy, (2′) C 1-6  alkyl optionally having C 1-6  alkyl-carbonyloxy, (3′) C 7-12  aralkyl optionally having C 1-6  alkoxy and (4′) C 7-12  aralkyloxy;   R 3  is   (1) unsubstituted,   (2) a hydrogen atom or   (3) C 1-6  alkyl;   R 4  is a hydrogen atom;   R 5  is a hydrogen atom;   R 6  is   (1) a group represented by the formula   
       
         
           
           
               
               
           
         
       
       wherein ring A is cyclopentane, cyclohexane or bicyclo[2.2.2]octane; R 11  is (1′) amino, (2′) C 7-12  aralkylamino, (3′) C 1-6  alkyl-carbonylamino optionally having substituent(s) selected from (1″) halogen, (2″) hydroxy, (3″) C 1-6  alkoxy-carbonyl, (4″) di-C 1-6  alkylamino and (5″) morpholino, (4′) C 3-8  cycloalkyl-carbonylamino, (5′) C 6-10  aryl-carbonylamino optionally having substituent(s) selected from (1″) halogen, (2″) cyano, (3″) C 1-6  alkyl, (4″) halogeno-C 1-6  alkyl, (5″) hydroxy-C 1-6  alkyl, (6″) C 1-6  alkoxy, (7″) carboxy and (8″) C 1-6  alkoxy-carbonyl, (6′) C 7-12  aralkyl-carbonylamino, (7′) C 1-6  alkoxy-carbonylamino, (8′) (5- or 6-membered aromatic heterocyclic group)-carbonylamino, (9′) piperidinocarbonylamino, (10′) C 6-10  aryl-sulfonylamino, (11′) 3-C 1-6  alkyl-ureido optionally having substituent(s) selected from (1″) hydroxy, (2″) carboxy, (3″) C 1-6  alkoxy and (4″) C 1-6  alkoxy-carbonyl, (12′) 3-C 3-8  cycloalkyl-ureido, (13′) 3-C 6-10  aryl-ureido optionally having substituent(s) selected from (1″) halogen, (2″) cyano, (3″) halogeno-C 1-6  alkyl, (4″) C 1-6  alkyl, (5″C 1-6  alkoxy and (6″) methylenedioxy, (14′) 3-C 7-12  aralkyl-ureido optionally having substituent(s) selected from (1″) halogen and (2″) C 1-6  alkoxy,
 (15′) 3-(5- or 6-membered aromatic heterocyclic group)-ureido, (16′) piperidinoureido optionally having C 1-6  alkyl-carbonyl or (17′) phthalimido, 
 (2) a group represented by the formula 
 
       
         
           
           
               
               
           
         
       
       wherein R 12  is (1′) a hydrogen atom, (2′) C 6-10  aryl-carbonyl optionally having halogeno-C 1-6  alkyl or (3′)
 C 7-12  aralkyl-oxycarbonyl; m is 0 or 1; and p is 0 or 1, 
 (3) a group represented by the formula 
 
       
         
           
           
               
               
           
         
       
       wherein R 13  is C 6-10  aryl-carbonyl,
 (4) a group represented by the formula 
 
       
         
           
           
               
               
           
         
       
       wherein ring B is a pyrrolidine ring or a piperidine ring; R 14  is (1′) a hydrogen atom, (2′) C 7-12  aralkyl, (3′) C 1-6  alkyl-carbonyl, (4′) C 6-10  aryl-carbonyl, (5′) C 7-12  aralkyl-carbonyl or (6′) C 1-6  alkoxy-carbonyl,
 (5) C 2-6  alkenyl-carbonyl optionally having substituent(s) selected from (1′) carboxy, (2′) C 1-6  alkoxy-carbonyl and (3′) C 6-10  aryl-aminocarbonyl, 
 (6) C 1-6  alkyl-carbonyl having substituent(s) selected from (1′) amino, (2′) C 6-10  aryl-carbonylamino and (3′) C 1-6  alkoxy-carbonylamino, 
 (7) 1,2,3,4-tetrahydronaphthylcarbonyl or 
 (8) pyrrolidinyl having C 7-12  aralkyl; 
 R 7  is a hydrogen atom; 
 R 8  is (1) a hydrogen atom, (2) halogen, (3) cyano, (4) C 1-6  alkyl optionally having 1 to 3 halogens, (5) C 6-10  aryl-carbonyl, (6) C 1-6  alkoxy or (7) C 6-10  aryloxy; 
 R 9  is (1) a hydrogen atom, (2) halogen, (3) cyano, (4) C 1-6  alkyl or (5) C 1-6  alkoxy; 
 R 10  is (1) a hydrogen atom, (2) halogen, (3) C 1-6  alkyl or (4) C 1-6  alkoxy; and 
 n is 2 or 3. 
 
     
     
         5 . The compound of  claim 1 , wherein R 1  is a hydrogen atom. 
     
     
         6 . The compound of  claim 1 , wherein R 2  is (1) C 1-6  alkyl optionally having substituent(s) selected from (1′) C 1-6  alkoxy and (2′) mono-C 1-6  alkylamino, (2) C 3-8  cycloalkyl, (3) C 6-10  aryl optionally having halogen or (4) a 5- or 6-membered aromatic heterocyclic group optionally having C 1-6  alkyl. 
     
     
         7 . The compound of  claim 1 , wherein R 3  is (1) a hydrogen atom or (2) C 1-6  alkyl. 
     
     
         8 . The compound of  claim 1 , wherein R 6  is
 (1) a group represented by the formula   
       
         
           
           
               
               
           
         
       
       wherein ring A′ is cyclohexane or bicyclo[2.2.2]octane, R 11 ′ is (1′) C 1-6  alkyl-carbonyl optionally having substituent(s) selected from (1″) halogen, (2″) hydroxy, (3″) C 1-6  alkoxy-carbonyl and (4″) morpholino, (2′) C 6-10  aryl-carbonyl optionally having substituent(s) selected from (1″) halogen, (2″) cyano, (3″) C 1-6  alkyl, (4″) halogeno-C 1-6  alkyl, (5″) hydroxy-C 1-6  alkyl, (6″) C 1-6  alkoxy and (7″) C 1-6  alkoxy-carbonyl, (3′) C 7-12  aralkyl-carbonyl, (4′) (5- or 6-membered aromatic heterocyclic group)-carbonyl, (5′) C 1-6  alkyl-aminocarbonyl optionally having substituent(s) selected from (1″) hydroxy, (2″) C 1-6  alkoxy and (3″) C 1-6  alkoxy-carbonyl, (6′) C 3-8  cycloalkyl-aminocarbonyl, (7′) C 6-10  aryl-aminocarbonyl optionally having substituent(s) selected from (1″) halogen, (2″) cyano, (3″) halogeno-C 1-6  alkyl, (4″) C 1-6  alkyl, (5″) C 1-6  alkoxy and (6″) methylenedioxy, (8′) C 7-12  aralkyl-aminocarbonyl optionally having substituent(s) selected from (1″) halogen and (2″) C 1-6  alkoxy, (9′) (5- or 6-membered aromatic heterocyclic group)-aminocarbonyl or (10′) piperidinoaminocarbonyl optionally having C 1-6  alkyl-carbonyl, or
 (2) a group represented by the formula 
 
       
         
           
           
               
               
           
         
       
       wherein R 12 ′ is C 6-10  aryl-carbonyl. 
     
     
         9 . The compound of  claim 1 , wherein R 8  is a hydrogen atom or halogen. 
     
     
         10 . The compound of  claim 1 , wherein R 9  is a hydrogen atom or halogen. 
     
     
         11 . The compound of  claim 1 , wherein R 10  is a hydrogen atom or halogen. 
     
     
         12 . The compound of  claim 1 , wherein n is 2. 
     
     
         13 . N-((1R,2S)-2-{[(3aR,4R,9bR)-4-(1H-imidazol-2-yl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexyl)benzamide, N-phenyl-N′-((1R,2S)-2-{[(3aR,4R,9bR)-4-phenyl-2,3,4a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexyl)urea, 2-methyl-N-((1R,2S)-2-{[(3aR,4S,9bR)-4-propyl-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexyl)-1H-benzimidazole-5-carboxamide, N-((1R,2S)-2-{[(3aR,4R,9bR)-4-(methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexyl)-1H-1,2,3-benzotriazole-5-carboxamide, 4-(1H-imidazol-2-yl)-N-((1R,2S)-2-{[(3aR,4R,9bR)-4-(methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexyl)benzamide, N-((1R,2S)-2-{[(3aR,4R,9bR)-4-(methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexyl)-N′-[4-(1H-pyrazol-1-yl)phenyl]urea, 4-cyano-N-((1R,2S)-2-{[(3aR,4R,9bR)-4-(1H-imidazol-2-yl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexyl)benzamide, N-((1R,2S)-2-{[(3aR,4R,9bR)-4-(methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexyl)-4-(methylamino)benzamide, 4-(Dimethylamino)-N-((1R,2S)-2-{[(3aR,4R,9bR)-4-(methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexyl)benzamide, or salts thereof. 
     
     
         14 . A production method of a compound represented by the formula (Ic) 
       
         
           
           
               
               
           
         
       
       wherein R 6 ′ is (1) (cyclic group optionally having substituent(s))-carbonyl, (2) alkenylcarbonyl optionally having substituent(s) or (3) alkylcarbonyl having substituent(s) selected from (i) cycloalkyl optionally having substituent(s) and (ii) amino optionally having substituent(s), and other symbols are as defined in  claim 1 , or a salt thereof, which comprises
 [1] subjecting a compound represented by the formula (II) 
 
       
         
           
           
               
               
           
         
       
       wherein each symbol is as defined in  claim 1 , or a salt thereof,
 a compound represented by the formula (III) 
 R 2 —CHO (III) 
 
       wherein R 2  is as defined in  claim 1 , or a salt thereof, and
 a compound represented by the formula (IV) 
 
       
         
           
           
               
               
           
         
       
       wherein P is a protecting group, and other symbols are as defined in  claim 1 , or a salt thereof to a condensation reaction to give a compound represented by the formula (Ia) 
       
         
           
           
               
               
           
         
       
       wherein each symbol is as defined above, or a salt thereof, and then eliminating the protecting group P, or
 [2] subjecting a compound represented by the formula (II) 
 
       
         
           
           
               
               
           
         
       
       wherein each symbol is as defined above, or a salt thereof,
 a compound represented by the formula (III) 
 R 2 —CHO (III) 
 
       wherein R 2  is as defined above, or a salt thereof, and
 a compound represented by the formula (V) 
 
       
         
           
           
               
               
           
         
       
       wherein R 5  are the same or different and each is C 1-6  alkyl, P′ is a protecting group, and n is as defined in  claim 1 , or a salt thereof to a condensation reaction to give a compound represented by the formula (Ib) 
       
         
           
           
               
               
           
         
       
       wherein each symbol is as defined above, or a salt thereof, and then eliminating the protecting group P′, and
 reacting a compound represented by the formula (VI) 
 
       
         
           
           
               
               
           
         
       
       wherein each symbol is as defined above, or a salt thereof, which is obtained in the above [1] or [2], with a compound represented by the formula (VII)
 R 6 ′-OH (VII) 
 
       wherein R 6 ′ is as defined above, or a salt thereof. 
     
     
         15 . A NK2 receptor antagonist comprising a compound having a partial structure represented by the formula 
       
         
           
           
               
               
           
         
       
       wherein n is an integer of 1 to 5; and
    represents a single bond or a double bond, or a salt thereof. 
 
     
     
         16 . A prodrug of the compound of  claim 1 . 
     
     
         17 . A pharmaceutical agent comprising the compound of  claim 1 , or a prodrug thereof. 
     
     
         18 . The pharmaceutical agent of  claim 17 , which is a NK2 receptor antagonist. 
     
     
         19 . The pharmaceutical agent of  claim 17 , which is an agent for the prophylaxis or treatment of functional gastrointestinal diseases. 
     
     
         20 . The pharmaceutical agent of  claim 17 , which is an agent for the prophylaxis or treatment of irritable bowel syndrome or nonulcer dyspepsia. 
     
     
         21 . A method of antagonizing a NK2 receptor, which comprises administering an effective amount of the compound of  claim 1 , or a prodrug thereof to a mammal. 
     
     
         22 . A method of preventing or treating functional gastrointestinal diseases, which comprises administering an effective amount of the compound of  claim 1 , or a prodrug thereof to a mammal. 
     
     
         23 . Use of the compound of  claim 1 , or a prodrug thereof for the production of a NK2 receptor-antagonist. 
     
     
         24 . Use of the compound of  claim 1 , or a prodrug thereof for the production of an agent for the prophylaxis or treatment of functional gastrointestinal diseases. 
     
     
         25 . The pharmaceutical agent of  claim 17 , which is an agent for the prophylaxis or treatment of melancholia. 
     
     
         26 . A method of preventing or treating melancholia, which comprises administering an effective amount of the compound of  claim 1 , or a prodrug thereof to a mammal.