Nitrogen-containing heterocyclic compound and use of same

Abstract

The present invention relates to a compound represented by the formulawherein ring A is a nitrogen-containing heterocycle;ring B is an aromatic ring optionally having substituent(s);ring D is an aromatic ring optionally having substituent(s);L is a group represented by the formulaR2, R3, R4a ′ and R4b are each independently a hydrogen atom, an optionally halogenated C1-6 alkyl group or an optionally halogenated C3-6 cycloalkyl group, or R2 and R3 are optionally bonded via an alkylene chain or an alkenylene chain, or R4a and R4b are optionally bonded via an alkylene chain or an alkenylene chain;R1 is a hydrogen atom or a substituent;m and n are each independently an integer of 0 to 5;m+n is an integer of 2 to 5; andis a single bond or double bond, or a salt thereof; and the like. The compound has a superior tachykinin receptor antagonistic action, and is useful as an agent for the prophylaxis or treatment of various diseases such as lower urinary tract diseases, digestive tract diseases, central neurological disease and the like.

The invention claimed is: 
     
      
       1. A compound represented by the formula 
       
         
           
           
               
               
           
         
       
       wherein:
 ring A is a piperidine ring or a pyrrolidine ring and each straight line is a single bond and   is a single bond; 
 ring B is an aromatic ring optionally having substituent(s); 
 ring D is an aromatic ring optionally having substituent(s), wherein 6-quinolyl is excluded; 
 L is a group represented by the formula 
 
       
         
           
           
               
               
           
         
         R 2 , R 3 , R 4a  and R 4b  are each independently a hydrogen atom, an optionally halogenated C 1-6  alkyl group or an optionally halogenated C 3-6  cycloalkyl group, or R 2  and R 3  are optionally bonded via an alkylene chain or an alkenylene chain, or R 4a  and R 4b  are optionally bonded via an alkylene chain or an alkenylene chain; 
         R 1  is a hydrogen atom or a substituent; 
         m and n are each independently an integer of 0 to 3; and 
         m+n is an integer of 2 to 3; 
         provided that when Lisa group represented by the formula 
       
       
         
           
           
               
               
           
         
       
       wherein each of R 4a  and R 4b  is as defined above, then ring D is an aromatic ring having substituent(s);
 excluding: N-[4-(biphenyl-4-yl)piperidin-3-yl]-N′-(naphthalen-2-yl)urea; 
 
       or a salt thereof. 
      
     
     
      
       2. The compound or salt according to  claim 1 , wherein ring B is a phenyl group optionally having substituent(s) or a pyridyl group optionally having substituent(s). 
      
     
     
      
       3. The compound or salt according to  claim 1 , wherein ring B is phenyl group optionally having substituent(s) or a thienyl group optionally having substituent(s). 
      
     
     
      
       4. The compound or salt according to  claim 1 , wherein ring D is a phenyl group optionally having substituent(s). 
      
     
     
      
       5. The compound or salt according to  claim 1 , wherein R 1  is a hydrogen atom, a hydrocarbon group optionally having substituent(s), an acyl group, a heterocyclic group optionally having substituent(s), or a group represented by —NR 5 R 6  wherein R 5  and R 6  are each independently a hydrogen atom, a hydrocarbon group optionally having substituent(s) or an acyl group, or R 5  and R 6  optionally form, together with the adjacent nitrogen atom, a nitroso group (—N═O). 
      
     
     
      
       6. The compound or salt according to  claim 1 , wherein R 2  is a hydrogen atom or a C 1-6  alkyl group. 
      
     
     
      
       7. The compound or salt according to  claim 1 , wherein L is a group represented by the formula 
       
         
           
           
               
               
           
         
       
       wherein R 3′  is a hydrogen atom or a C 1-6  alkyl group. 
      
     
     
       8. The compound or salt according to  claim 1 , wherein ring D is a 3,5-bis(trifluoromethyl)phenyl group or a 3,5-dichlorophenyl group. 
     
     
       9. Methyl 4-{[(3S,4R)-3-[{[3,5-bis(trifluoromethyl)phenyl](methyl)carbamoyl}(methyl)amino]-4-(4-fluorophenyl)pyrrolidin-1-yl]carbonyl}piperidine-1-carboxylate, or a salt thereof. 
     
     
       10. 1-[(3S,4R)-4-(4-Chlorophenyl)-1-{[4-(methylsulfonyl)piperazin-1-yl]carbonyl}pyrrolidin-3-yl]-3-(3,5-dichlorophenyl)-1,3-dimethylurea, or a salt thereof. 
     
     
       11. 1-[3,5-Bis(trifluoromethyl)phenyl]-3-[(3S,4R)-4-(5-fluoropyridin-2-yl)-1-({trans-4-[5-(trifluoromethyl)-1H-tetrazol-1-yl]cyclohexyl}carbonyl)pyrrolidin-3-yl]-1,3-dimethylurea, or a salt thereof. 
     
     
      
       12. A pharmaceutical composition comprising the compound or salt according to  claim 1  and a pharmaceutically acceptable carrier. 
      
     
     
      
       13. A method of antagonizing an NK1 receptor in a mammal, comprising administering the pharmaceutical composition according to  claim 12  to the mammal. 
      
     
     
      
       14. The method according to  claim 13 , wherein the method further antagonizes an NK2 receptor and/or an NK3 receptor. 
      
     
     
      
       15. A method of antagonizing an NK2 receptor in a mammal, comprising administering the pharmaceutical composition according to  claim 12  to the mammal. 
      
     
     
      
       16. The method according to  claim 15 , wherein the method further antagonizes an NK1 receptor and/or an NK3 receptor. 
      
     
     
       17. A method for the treatment of vomiting, nausea, depression, anxiety neurosis, or anxiety, comprising administering an effective amount of the compound or salt according to  claim 1  to a mammal. 
     
     
       18. A compound represented by the formula 
       
         
           
           
               
               
           
         
       
       wherein:
 ring B is an aromatic heterocyclic group optionally having substituent(s); 
 ring D is an aromatic heterocyclic group optionally having substituent(s), wherein 6-quinolyl is excluded; 
 R 2  is a hydrogen atom, a halogenated C 1-6  alkyl group or an optionally halogenated C 3-6  cycloalkyl group; 
 R 1  is a heterocyclic group optionally having substituent(s); 
 
       or a salt thereof.  
     
     
       19. The compound or salt according to claim 18, wherein R 2  is a hydrogen atom.  
     
     
       20. The compound or salt according to claim 18, wherein ring B is selected from furyl, thienyl, pyridyl, pyrrolyl, imidazolyl, pyrazolyl, indolyl, thiazolyl, oxazolyl, thiadiazolyl, triazolyl, and tetrazolyl.  
     
     
       21. The compound or salt according to claim 20, wherein the ring B is selected from pyridyl, pyrrolyl, imidazolyl, pyrazolyl, and indolyl.  
     
     
       22. The compound or salt according to claim 20, wherein the Ring B is selected from thiazolyl, oxazolyl, thiadiazolyl, triazolyl, and tetrazolyl.  
     
     
       23. The compound or salt according to claim 18, wherein R 1  is a heterocyclic group having substituent(s).  
     
     
       24. The compound or salt according to claim 23, wherein the substituent is an alkyl group.  
     
     
       25. The compound or salt according to claim 23, wherein the substituent is a C 1-6  alkoxy group.  
     
     
       26. The compound or salt according to claim 18, wherein ring D is an aromatic heterocyclic group optionally substituted by 1 to 3 substituents.  
     
     
       27. The compound or salt according to claim 26, wherein ring D is an aromatic heterocyclic group that is a 5- or 6-membered aromatic heterocyclic group containing 1 to 3 hetero atoms of one or two kinds selected from a nitrogen atom, an oxygen atom and a sulfur atom.  
     
     
       28. The compound or salt according to claim 27, wherein ring D is an aromatic heterocyclic group selected from the group consisting of furyl, thienyl, pyridyl, pyrrolyl, imidazolyl, pyrazolyl, indolyl, thiazolyl, oxazolyl, thiadiazolyl, triazolyl and tetrazolyl.  
     
     
       29. The compound or salt according to claim 28, wherein ring D is imidazolyl or pyrazolyl optionally substituted by 1 to 3 substituents.  
     
     
       30. The compound or salt according to claim 29, wherein ring D is imidazolyl or pyrazolyl substituted by 1 to 3 substituents.  
     
     
       31. The compound or salt according to claim 26, wherein ring D is an aromatic heterocyclic group that is a bicyclic or tricyclic fused ring group containing 1 to 4 hetero atoms of one or two kinds selected from a nitrogen atom, an oxygen atom and a sulfur atom.  
     
     
       32. The compound or salt according to claim 31, wherein ring D is an aromatic heterocyclic group that is a condensation of a 5- to 6-membered aromatic heterocycle and one or two 5- or 6-membered heterocycles containing, besides carbon atoms, 1 to 4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom.  
     
     
       33. The compound or salt according to claim 32, wherein the 5- to 6-membered aromatic heterocycle is imidazolyl or pyrazolyl optionally substituted by 1 to 3 substituents.  
     
     
       34. The compound or salt according to claim 32, wherein the 5- to 6-membered aromatic heterocycle is imidazolyl or pyrazolyl substituted by 1 to 3 substituents.  
     
     
       35. A pharmaceutical composition comprising the compound or salt according to claim 18 and a pharmaceutically acceptable carrier.  
     
     
       36. A method of antagonizing an NK1 receptor in a mammal, comprising administering an effective amount of the pharmaceutical composition according to claim 35 to the mammal.  
     
     
       37. The method according to claim 36, wherein the method further antagonizes an NK2 receptor and/or an NK3 receptor.  
     
     
       38. A method of antagonizing an NK2 receptor, comprising administering an effective amount of the pharmaceutical composition according to claim 18 to a mammal in need thereof.  
     
     
       39. The method according to claim 38, wherein the method further antagonizes an NK1 receptor and/or an NK3 receptor.  
     
     
       40. A method for the treatment of vomiting, nausea, depression, anxiety neurosis, or anxiety, comprising administering an effective amount of the compound or salt according to claim 18 to a mammal in need thereof.