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 . 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 
       
       
         
           
           
               
               
           
         
       
       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. 
     
     
         2 - 10 . (canceled) 
     
     
         11 . The compound according to  claim 1  which is selected from the group consisting of the following formulas or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         12 . The compound according to  claim 1  which is the following compound or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         13 - 23 . (canceled) 
     
     
         24 . The compound of formula [V] according to  claim 1 : 
       
         
           
           
               
               
           
         
         wherein each symbol is as defined in  claim 1 , 
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         25 . The compound of formula [V-A] according to  claim 1 : 
       
         
           
           
               
               
           
         
         wherein each symbol is as defined in  claim 1 , 
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         26 . The compound of formula [V-B] according to  claim 1 : 
       
         
           
           
               
               
           
         
         wherein each symbol is as defined in  claim 1 , 
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         27 . The compound according to any one of  claims 1  and  24 - 26 , wherein R b  is C 3-7  cycloalkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, or a pharmaceutically acceptable salt thereof. 
     
     
         28 . The compound according to any one of  claims 1  and  24 - 26 , wherein R b  is cyclopropyl group, or a pharmaceutically acceptable salt thereof. 
     
     
         29 . The compound according to any one of  claims 1  and  24 - 26 , wherein the cyclic moiety U is C 3-7  cycloalkyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, or a pharmaceutically acceptable salt thereof. 
     
     
         30 . The compound according to any one of  claims 1  and  24 - 26 , wherein the cyclic moiety U is cyclobutyl group which may be substituted with the same or different 1 to 5 substituents selected from Group A, or a pharmaceutically acceptable salt thereof. 
     
     
         31 . The compound according to  claim 1  which is a compound of one of the following formulas: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         32 . The compound according to  claim 1 , which is the compound of the following formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         33 . The compound according to  claim 1 , which is the compound of the following formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         34 . The compound according to  claim 1 , which is the compound of the following formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         35 . The compound according to  claim 1 , which is the compound of the following formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         36 . The compound according to  claim 1 , which is the compound of the following formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         37 . The compound according to  claim 1 , which is the compound of the following formula: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         38 . A pharmaceutical composition comprising the compound according to any one of  claims 1  and  32 - 37  or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         39 . A method of inhibiting RORγ in a mammal, comprising administering to said mammal a therapeutically effective amount of the compound according to any one of  claims 1  and  32 - 37  or a pharmaceutically acceptable salt thereof. 
     
     
         40 . A method of treating or 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 the compound according to any one of  claims 1  and  32 - 37  or a pharmaceutically acceptable salt thereof. 
     
     
         41 . The method according to  claim 40 , 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. 
     
     
         42 . A method of treating or preventing a disease in a mammal selected from the group consisting of autoimmune disease, allergic disease, dry eye, and fibrosis comprising administering to the mammal a therapeutically effective amount of the compound according to any one of  claims 1  and  32 - 37  or a pharmaceutically acceptable salt thereof. 
     
     
         43 . The method according to  claim 42 , 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. 
     
     
         44 . The method according to  claim 40  wherein the metabolic disease is diabetes.