Azaindole derivative having pgd2 receptor antagonistic activity

Abstract

The present invention creates an azaindole derivative having DP receptor antagonistic activity and a pharmaceutical composition comprising the said compound as an active ingredient, and further providing a therapeutic agent for treating allergic diseases. A compound of the general formula (I) wherein the ring A is an aromatic carbocyclic ring etc.; the ring B is a 3- to 8-membered nitrogen-containing non-aromatic heterocyclic ring etc.; the formula of —X 1 ═X 2 —X 3 ═X 4 — is a formula of —C(R 1 )═C(R 2 )—C(R 3 )═N— etc.; R 1 , R 2 , R 3 , R 4 and R 5 are independently a hydrogen atom or a halogen atom etc.; R 6 is optionally substituted C1-C6 alkyloxy etc.; R 7 is independently a halogen atom etc.; R 8 is optionally substituted C1-C6 alky etc.; R 9 is carboxy etc.; M is sulfonyl etc.; Y is a single bond etc.; L 1 , L 2 and L 3 are a single bond or alkylene optionally containing one or two heteroatoms etc.; n is 0 etc.; q is 0 etc.; a pharmaceutically acceptable salt or hydrate thereof.

1 - 22 . (canceled) 
     
     
         23 . A compound of the general formula (I): 
       
         
           
           
               
               
           
         
         wherein the ring A is a heterocyclic ring; 
         the ring B is a 3- to 8-membered nitrogen-containing non-aromatic heterocyclic ring or a 3- to 8-membered nitrogen-containing aromatic heterocyclic ring; 
         the formula of —X 1 ═X 2 —X 3 ═X 4 — is a formula of —C(R 1 )═C(R 2 )—C(R 3 )═N—; 
         R 1 , R 2 , R 3 , R 4  and R 5  are independently a hydrogen atom, a halogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cyloalkyl, optionally substituted cyloalkenyl, hydroxy, optionally substituted alkyloxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted cycloalkyloxy, optionally substituted cycloalkenyloxy, mercapto, optionally substituted allylthio, optionally substituted alkenylthio, optionally substituted alkynylthio, optionally substituted alkylsulfinyl, optionally substituted alkylsulfonyl, optionally substituted alkylsulfonyloxy, optionally substituted cycloalkylthio, optionally substituted cycloalkylsulfinyl, optionally substituted cycloalkylsulfonyl, optionally substituted cycloalkylsulfonyloxy, optionally substituted cycloalkenylthio, optionally substituted cycloalkenylsulfinyl, optionally substituted cycloalkenylsulfonyl, optionally substituted cycloalkenylsulfonyloxy, optionally substituted amino, acyl, optionally substituted alkyloxycarbonyl, optionally substituted alkenyloxycarbonyl, optionally substituted alkynyloxycarbonyl, optionally substituted carbamoyl, optionally substituted sulfamoyl, cyano, nitro, optionally substituted aryl, optionally substituted aryloxy, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfony, optionally substituted arylsulfonyoxy, optionally substituted heteroaryl, optionally substituted heteroaryloxy, optionally substituted heteroarylthio, optionally substituted heteroarylsulfinyl, optionally substituted heteroarylsulfonyl, optionally substituted heteroarylsulfonyloxy, or an optionally substituted non-aromatic heterocyclic group; 
         R 6  is a hydrogen atom, optionally substituted C1-C6alkyloxy, optionally substituted C2-C6 alkenyloxy, optionally substituted C2-C6 alkynyloxy, optionally substituted C3-C6 cycloalkyloxy, optionally substituted C3-C6 cycloalkenyloxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted C1-C6 alkylthio, optionally substituted C2-C6 alkenylthio, optionally substituted C2-C6 alkynylthio, optionally substituted C3-C6 cycloalkylthio, optionally substituted C3-C6 cycloalkenylthio, optionally substituted arylthio, or optionally substituted heteroarylthio; 
         R 7  is independently a halogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, hydroxy, optionally substituted alkyloxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted cycloalkyloxy, optionally substituted cycloalkenyloxy, mercapto, optionally substituted alkylthio, optionally substituted alkenylthio, optionally substituted alkynylthio, optionally substituted alkylsulfinyl, optionally substituted alkylsulfonyl, optionally substituted alkylsulfonyloxy, optionally substituted cycloalkylthio, optionally substituted cycloalkylsulfinyl, optionally substituted cycloalkylsulfonyl, optionally substituted cycloalkylsulfonyloxy, optionally substituted cycloalkenylthio, optionally substituted cycloalkenylsulfinyl, optionally substituted cycloalkenylsulfonyl, optionally substituted cycloalkenylsulfonyloxy, optionally substituted amino, acyl, optionally substituted alkyloxycarbonyl, optionally substituted alkenyloxycarbonyl, optionally substituted alkynyloxycarbonyl, optionally substituted carbamoyl, optionally substituted sulfamoyl, cyano, nitro, optionally substituted aryl, optionally substituted aryloxy, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl, optionally substituted arylsulfonyloxy, optionally substituted heteroaryl, optionally substituted heteroaryloxy, optionally substituted heteroarylthio, optionally substituted heteroarylsulfinyl, optionally substituted heteroarylsulfonyl, optionally substituted heteroarylsulfonyloxy, or optionally substituted non-aromatic heterocyclic group; 
         R 8  is independently a halogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted alkyloxy, oxo, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted non-aromatic heterocyclic group; 
         R 9  is carboxy, optionally substituted alkyloxycarbonyl, optionally substituted carbamoyl or a carboxy equivalent; 
         M is carbonyl or sulfonyl; 
         Y is a single bond, optionally substituted alkylene optionally containing one or two heteroatom(s), an oxygen atom, a sulfur atom or —N(R 10 )—. 
         L 1 , L 2  and L 3  are independently a single bond, optionally substituted alkylene optionally containing one or two heteroatom(s), optionally substituted alkenylene optionally containing one or two heteroatom(s), optionally substituted alkynylene optionally containing one or two heteroatom(s) or —N(R 11 )—. 
         R 10  and R 11  are independently a hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cychialkyl, acyl, optionally substituted alkyloxy, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted non-aromatic heterocyclic group; 
         n is 0, 1 or 2; and 
         q is 0, 1, 2 or 3; 
         a pharmaceutically acceptable salt or hydrate thereof. 
       
     
     
         24 . A compound of the general formula (II): 
       
         
           
           
               
               
           
         
         wherein the ring C is a formula of 
       
       
         
           
           
               
               
           
         
         the formula of —X 1 ═X 2 —X 3 ═X 4 — is a formula of —C(R)═C(R 2 )—C(R 3 )═N—; 
         R 1 , R 2 , R 3 , R 4  and R 5  are independently a hydrogen atom, halogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, hydroxy, optionally substituted alkyloxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, optionally substituted cycloalkyloxy, optionally substituted cycloalkenyloxy, mercapto, optionally substituted alkylthio, optionally substituted alkenylthio, optionally substituted alkynylthio, optionally substituted alkylsulfinyl, optionally substituted alkyl sulfonyl, optionally substituted alkylsulfonyloxy, optionally substituted cycloalkylthio, optionally substituted cycloalkylsulfinyl, optionally substituted cycloalkylsulfonyl, optionally substituted cycloalkylsulfonyloxy, optionally substituted cycloalkenylthio, optionally substituted cycloalkenylsulfinyl, optionally substituted cycloalkenylsulfonyl, optionally substituted cycloalkenylsulfonyloxy, optionally substituted amino, acyl, optionally substituted alkyloxycarbonyl, optionally substituted alkenyloxycarbonyl, optionally substituted alkynyloxycarbonyl, optionally substituted carbamoyl, optionally substituted sulfamoyl, cyano, nitro, optionally substituted aryl, optionally substituted aryloxy, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl, optionally substituted arylsulfonyloxy, optionally substituted heteroaryl, optionally substituted heteroaryloxy, optionally substituted heteroarylthio, optionally substituted heteroarylsulfinyl, optionally substituted heteroarylsulfonyl, optionally substituted heteroarylsulfonyloxy, or optionally substituted non-aromatic heterocyclic group; 
         R 12  is optionally substituted C1-C6 alkyloxy, optionally substituted C2-C6 alkenyloxy, optionally substituted C2-C6 alkynyloxy, optionally substituted C1-C6 alkylthio, optionally substituted C2-C6 alkenylthio, optionally substituted C2-C6 alkynylthio, optionally substituted C3-C6 cycloalkyloxy, optionally substituted C3-C6 cycloalkylthio, optionally substituted aryloxy or optionally substituted arylthio; 
         R 13  is independently a halogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amino, acyl, optionally substituted alkyloxycarbonyl, optionally substituted carbamoyl, optionally substituted sulfamoyl, cyano, nitro, optionally substituted aryl, optionally substituted arylsulfonyloxy, optionally substituted heteroaryl or optionally substituted non-aromatic heterocyclic group; 
         R 14  is independently optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, oxo, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted non-aromatic heterocyclic group; 
         M is carbonyl or sulfoyl; 
         Y and L 4  are independently a single bond or optionally substituted alkylene optionally containing one or two heteroatom(s); 
         Z is N; 
         n is 0, 1 or 2; and 
         q is 0, 1, 2 or 3; 
         a pharmaceutically acceptable salt or hydrate thereof. 
       
     
     
         25 . A compound of the general formula (III): 
       
         
           
           
               
               
           
         
         wherein the ring D is a formula of 
       
       
         
           
           
               
               
           
         
         R 15 , R 16  and R 18  are independently a hydrogen atom, a halogen atom, optionally substituted alkyl, optionally substituted alkyloxy, optionally substituted alkylthio, optionally substituted alkylsulfinyl, optionally substituted alkylsulfonyl, optionally substituted amino, cyano, nitro, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted non-aromatic heterocyclic group; 
         R 17  is independently a hydrogen atom, a halogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cyloalkyl, optionally substituted cyloalkenyl, hydroxy, optionally substituted alkyloxy, optionally substituted alkenyloxy, optionally substituted alkynyloxy, mercapto, optionally substituted alkylthio, optionally substituted alkenylthio, optionally substituted alkynylthio, optionally substituted alkylsulfinyl, optionally substituted alkynylsulfonyl, optionally substituted alkynylsulfonyloxy, optionally substituted amino, acyl, optionally substituted alkyloxycarbonyl, optionally substituted alkenyloxycarbonyl, optionally substituted alkynyloxycarbonyl, optionally substituted carbamoyl, optionally substituted sulfamoyl, cyano, nitro, optionally substituted aryl, optionally substituted aryloxy, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl, optionally substituted arylsulfonyloxy, optionally substituted heteroaryl, optionally substituted heteroaryloxy, optionally substituted heteroarylthio, optionally substituted heteroarylsulfinyl, optionally substituted heteroarylsulfonyl, optionally substituted heteroarylsulfonyloxy, or an optionally substituted non-aromatic heterocyclic group; 
         R 19  is optionally substituted C1-C6 alkyloxy, optionally substituted C2-C6 alkenyloxy, optionally substituted C2-C6 alkynyloxy, optionally substituted C1-C6 alkylthio, optionally substituted C2-C6 alkenylthio, optionally substituted C2-C6 alkynylthio, optionally substituted C3-C6 cycloalkyloxy, optionally substituted C3-C6 cycloalkylthio, optionally substituted aryloxy or optionally substituted arylthio; 
         R 20  is independently a halogen atom, optionally substituted alkyl, optionally substituted cyloalkyl, optionally substituted amino, acyl, optionally substituted alkyloxycarbonyl, optionally substituted carbamoyl, optionally substituted sulfamoyl, cyano, nitro, optionally substituted aryl, optionally substituted arylsulfonyloxy, optionally substituted heteroaryl or an optionally substituted non-aromatic heterocyclic group; 
         R 21  is independently optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, oxo, optionally substituted aryl, optionally substituted heteroaryl, or an optionally substituted non-aromatic heterocyclic group;
 M is carbonyl or sulfonyl; 
 Z is N; 
 n is 0, 1 or 2 and 
 q is 0, 1, 2 or 3; 
 a pharmaceutically acceptable salt or hydrate thereof. 
 
       
     
     
         26 . A compound of  claim 25 , wherein R 17  is a hydrogen atom, a halogen atom, optionally substituted alkyl, optionally substituted alkyloxy, optionally substituted amino, optionally substituted carbamoyl, optionally substituted aryl, optionally substituted heteroaryl or an optionally substituted non-aromatic heterocyclic ring;
 a pharmaceutically acceptable salt or hydrate thereof.   
     
     
         27 . A compound of  claim 25 , wherein R 15 , R 16  and R 18  are hydrogen atoms, a pharmaceutically acceptable salt or hydrate thereof. 
     
     
         28 . A compound of  claim 25 , wherein R 19  is optionally substituted C1-C6 alkyl or optionally substituted C1-C6 alkylthio, a pharmaceutically acceptable salt or hydrate thereof. 
     
     
         29 . A compound of  claim 25 , wherein R 20  is a halogen atom, optionally substituted alkyl or optionally substituted alkyloxy, and q is 0 or 1, a pharmaceutically acceptable salt or hydrate thereof. 
     
     
         30 . A compound of  claim 25 , wherein M is sulfonyl, a pharmaceutically acceptable salt or hydrate thereof. 
     
     
         31 . A compound of any one of  claims 25 - 30 , wherein R 21  is alkyl or oxo, and n is 0, a pharmaceutically acceptable salt or hydrate thereof. 
     
     
         32 . A pharmaceutical composition comprising the compound of any one of  claims 23 - 30 , a pharmaceutically acceptable salt or hydrate thereof. 
     
     
         33 . A pharmaceutical composition comprising the compound of  claim 31 , a pharmaceutically acceptable salt or hydrate thereof.