Indole compounds and pharmaceutical use thereof

Abstract

Provided is an agent for the treatment or prophylaxis of inflammatory diseases, allergic diseases, autoimmune diseases, transplant rejection or the like. A compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof, or a solvate thereof: wherein each symbol is as described in the specification.

1 .- 26 . (canceled) 
     
     
         27 . A process for producing a compound of formula [I-c] 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof comprising
 deprotecting a compound of formula [19] 
 
       
       
         
           
           
               
               
           
         
         to remove R 12  to form the compound of formula [1-c], 
         wherein 
         R 1  is
 (1) a hydrogen atom, 
 (2) a hydroxy group, or 
 (3) a C 1-6  alkoxy group optionally substituted by C 6-10  aryl group(s); 
 
         R 2  and R 3  are the same or different and each is
 (1) a hydrogen atom, or 
 (2) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from
 (a) a hydroxy group, and 
 (b) a C 1-6  alkoxy group; 
 
 
         R 7  is
 (1) a hydrogen atom, or 
 (2) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from
 (a) a hydroxy group, 
 (b) a C 1-6  alkoxy group, and 
 (c) an amino group optionally mono- or di-substituted by C 1-6  alkyl group(s), 
 
 
         R 8  is
 (1) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from
 (a) a hydroxy group, 
 (b) a C 1-6  alkoxy group optionally substituted by C 6-10  aryl group(s), 
 (c) a C 3-6  cycloalkyl group optionally substituted by C 1-6  alkoxy group(s), 
 (d) a C 6-10  aryl group, 
 (e) a 5- or 6-membered unsaturated heterocyclic group optionally substituted by oxo group(s), 
 (f) a 5- to 8-membered saturated heterocyclic group optionally substituted by 1 to 3 substituents selected from
 (i) a hydroxy group, 
 (ii) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a C 1-6  alkoxy group, 
 (iii) a C 1-6  alkoxy group, and 
 (iv) an oxo group, 
 
 (g) a C 3-6  cycloalkyloxy group, 
 (h) a C 6-10  aryloxy group, 
 (i) a 5- or 6-membered unsaturated heterocyclyloxy group, 
 (j) a 5- or 6-membered saturated heterocyclyloxy group, and 
 (k) an amino group optionally mono- or di-substituted by substituents selected from
 (i) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group, a carboxy group and a carboxy-C 1-6  alkoxy group, 
 (ii) a C 1-6  alkyl-carbonyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a C 1-6  alkoxy group, 
 (iii) a C 1-6  alkoxy-carbonyl group optionally substituted by C 6-10  aryl group(s), and 
 (iv) a C 3-6  cycloalkyl-carbonyl group optionally substituted by C 1-6  alkoxy group(s), 
 
 
 (2) a C 1-6  alkoxy group optionally substituted by C 6-10  aryl group(s), 
 (3) a C 3-6  cycloalkyl group optionally substituted by 1 to 3 substituents selected from
 (a) a hydroxy group, and 
 (b) a C 1-6  alkoxy group, 
 
 (4) a C 6-10  aryl group optionally substituted by C 1-6  alkyl group(s) optionally substituted by 1 to 3 halogen atoms, 
 (5) an amino group optionally mono- or di-substituted by C 1-6  alkyl group(s) optionally substituted by C 6-10  aryl group(s), 
 (6) a 5- or 6-membered unsaturated heterocyclic group optionally substituted by C 1-6  alkyl group(s), 
 (7) a 5- or 6-membered saturated heterocyclic group optionally substituted by 1 to 3 substituents selected from
 (a) a C 1-6  alkyl group, 
 (b) a C 1-6  alkyl-carbonyl group, and 
 (c) an oxo group, 
 
 (8) a C 3-6  cycloalkyloxy group, or 
 (9) a C 6-10  aryl-carbonyl group, or 
 
         R 7  and R 8  form, together with the nitrogen atom and carbon atom they are bonded to, a 5- or 6-membered cyclic amine substituted by an oxo group and optionally further substituted by 1 to 3 substituents selected from
 (a) a hydroxy group, 
 (b) a C 1-6  alkyl group optionally substituted by hydroxy group(s), 
 (c) a C 1-6  alkoxy group, and 
 (d) a C 3-6  cycloalkyl group; and 
 
         R 12  is an amino-protecting group. 
       
     
     
         28 . The method of  claim 27 , wherein the compound of formula [19] is prepared by condensing a compound of formula [17] 
       
         
           
           
               
               
           
         
       
       with a compound of formula [18] 
       
         
           
           
               
               
           
         
       
       to form the compound of formula [19]. 
     
     
         29 . The method of  claim 28 , wherein the compound of formula [17] is prepared by reducing a compound of formula [16] 
       
         
           
           
               
               
           
         
       
       wherein R 13  is an alkyl or benzyl group, to form the compound of formula [17]. 
     
     
         30 . The method of  claim 29 , wherein the compound of formula [16] is prepared by subjecting a compound of formula [15] 
       
         
           
           
               
               
           
         
       
       to an alkylating agent in a solvent in the presence of a base to form the compound of formula [16]. 
     
     
         31 . The method of  claim 30 , wherein the compound of formula [15] is prepared by subjecting a compound of formula [14] 
       
         
           
           
               
               
           
         
       
       to a Curtius rearrangement in the presence of an alcohol of the formula R 13 OH to provide a compound of formula [15]. 
     
     
         32 . The method of  claim 31 , wherein the compound of formula [14] is prepared by deprotecting a compound of formula [13] 
       
         
           
           
               
               
           
         
       
       wherein R 11  is a carboxy-protecting group, to remove R 11  to form a compound of formula [14]. 
     
     
         33 . The method of  claim 32 , wherein the compound of formula [13] is prepared by introducing an amino-protecting group R 12  into a compound of formula [10] 
       
         
           
           
               
               
           
         
       
       to form a compound of formula [13].