Amide compound and medicinal use thereof

Abstract

A compound of formula [I-W]: wherein each symbol is as defined in the description, or a pharmaceutically acceptable salt thereof.

1 .- 23 . (canceled) 
     
     
         24 . A method of preventing a disease in a mammal selected from the group consisting of autoimmune disease, allergic disease, metabolic disease, dry eye, and fibrosis comprising administering to the mammal a therapeutically effective amount of a compound of formula [I-W]: 
       
         
           
           
               
               
           
         
         wherein 
       
       
         
           
           
               
               
           
         
         
           R a  is 
         
         (1) C 5-12  alkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, or 
         (2) 
       
       
         
           
           
               
               
           
         
       
       wherein
 Y a  is 
 (i) single bond, or 
 (ii) C 1-6  alkylene group, 
 cyclic moiety U is 
 (i) C 3-7  cycloalkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, 
 (ii) C 5-11  spirocyclic cycloalkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, or 
 (iii) C 6-10  aryl group which may be substituted with the same or different 1 to 5 substituents selected from Group A;
 R b  is a group selected from the following (1) to (3): 
 
 (1) C 1-3  alkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, 
 (2) C 2-3  alkenyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, 
 (3) C 3-7  cycloalkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A;
 R c  is 
 
 (1) hydrogen atom, or 
 (2) C 1-6  alkyl group;
 Y c  is a group selected from the following (1) to (7): 
 
 (1) single bond, 
 (2) C 1-6  alkylene group which may be substituted with the same or different 1 to 5 substituents selected from Group A, 
 (3) —NR C1 — wherein R C1  is hydrogen atom or C 1-6  alkyl group, 
 (4) —O—, 
 (5) C 3-10  cycloalkylene group which may be substituted with the same or different 1 to 5 substituents selected from Group A, 
 (6) C 6-10  arylene group which may be substituted with the same or different 1 to 5 substituents selected from Group A, 
 (7) monocyclic heteroaromatic group which may be substituted with the same or different 1 to 5 substituents selected from Group A wherein the monocyclic heteroaromatic ring consists of carbon atoms and the same or different 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, and is 3 to 7-membered;
 Y d1  is 
 
 (1) single bond, or 
 (2) C 1-6  alkylene group which may be substituted with the same or different 1 to 5 substituents selected from Group A; or alternatively
 both Y c  and Y d1  may be methine and be linked each other directly or via C 1-4  alkylene group to form C 3-7  cycloalkyl ring; 
 Y d2  is 
 
 (1) single bond, or 
 (2) C 1-6  alkylene group;
 R d1 , R d2 , R d3 , R d4 , and R d5  are the same or different group selected from the following (1) to (7): 
 
 (1) hydrogen atom 
 (2) halogen atom, 
 (3) C 1-6  alkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, 
 (4) —OR d10  wherein R d10  is hydrogen atom or C 1-6  alkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, 
 (5) —COOR d11  wherein R d11  is hydrogen atom or C 1-6  alkyl group, 
 (6) C 3-7  cycloalkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, 
 (7) cyano group, or alternatively
 R d1  and R d2 , or R d2  and R d3  can be taken together to form a C 6-10  aryl ring fused to the benzene ring to which they are all attached wherein the C 6-10  aryl ring may be substituted with the same or different 1 to 4 substituents selected from Group A; 
 R e  is 
 
 (1) hydrogen atom, or 
 (2) C 1-3  alkyl group, or alternatively
 R e  and R d1 , or R e  and R d5  can be taken together to form C 1-4  alkylene; 
 n c1  is an integer selected from 0 or 1 to 4, 
 n c2  is an integer selected from 0 or 1 to 3, 
 n d  is an integer selected from 0 or 1 to 3, 
 Group A is 
 
 (a) C 1-6  alkyl group, 
 (b) halogen atom, and 
 (c) —OR A1  wherein R A1  is hydrogen atom or C 1-6  alkyl group, 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         25 . The method according to  claim 24 , wherein the autoimmune disease is selected from the group consisting of rheumatoid arthritis, psoriasis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, ankylosing spondylitis, uveitis, polymyalgia rheumatica, and type I diabetes. 
     
     
         26 . The method according to  claim 24 , wherein the metabolic disease is diabetes. 
     
     
         27 . The method of  claim 24 , wherein the compound of formula [I-W] has the following structure: 
       
         
           
           
               
               
           
         
         wherein 
       
       
         
           
           
               
               
           
         
         
           R a  is 
         
         (1) C 5-12  alkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, or 
         (2) 
       
       
         
           
           
               
               
           
         
       
       wherein
 Y a  is 
 (i) single bond, or 
 (ii) C 1-6  alkylene group, 
 cyclic moiety U is 
 (i) C 3-7  cycloalkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, or 
 (ii) C 5-11  spirocyclic cycloalkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A;
 R b  is a group selected from the following (1) to (3): 
 
 (1) C 1-3  alkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, 
 (2) C 2-3  alkenyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, 
 (3) C 3-7  cycloalkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A;
 R c  is 
 
 (1) hydrogen atom, or 
 (2) C 1-6  alkyl group;
 Y c  is a group selected from the following (1) to (7): 
 
 (1) single bond, 
 (2) C 1-6  alkylene group which may be substituted with the same or different 1 to 5 substituents selected from Group A, 
 (3) —NR C1 — wherein R C1  is hydrogen atom or C 1-6  alkyl group, 
 (4) —O—, 
 (5) C 3-10  cycloalkylene group which may be substituted with the same or different 1 to 5 substituents selected from Group A, 
 (6) C 6-10  arylene group which may be substituted with the same or different 1 to 5 substituents selected from Group A, 
 (7) monocyclic heteroaromatic group which may be substituted with the same or different 1 to 5 substituents selected from Group A wherein the monocyclic heteroaromatic ring consists of carbon atoms and the same or different 1 to 4 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom, and is 3 to 7-membered;
 Y d1  is 
 
 (1) single bond, or 
 (2) C 1-6  alkylene group which may be substituted with the same or different 1 to 5 substituents selected from Group A;
 Y d2  is 
 
 (1) single bond, or 
 (2) C 1-6  alkylene group;
 R d1 , R d2 , R d3 , R d4 , and R d5  are the same or different group selected from the following (1) to (4): 
 
 (1) hydrogen atom 
 (2) halogen atom, 
 (3) C 1-6  alkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, 
 (4) —OR d10  wherein R d10  is hydrogen atom or C 1-6  alkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, or alternatively
 R d1  and R d2 , or R d2  and R d3  can be taken together to form a C 6-10  aryl ring fused to the benzene ring to which they are all attached wherein the C 6-10  aryl ring may be substituted with the same or different 1 to 4 substituents selected from Group A; 
 n c1  is an integer selected from 0 or 1 to 3, 
 n c2  is an integer selected from 0 or 1 to 3, 
 n d  is an integer selected from 0 or 1 to 3, 
 R e  is hydrogen atom, 
 Group A is 
 
 (a) C 1-6  alkyl group, 
 (b) halogen atom, and 
 (c) —OR A1  wherein R A1  is hydrogen atom or C 1-6  alkyl group, 
 
       or a pharmaceutically acceptable salt thereof.