Heterocyclic compound

Abstract

wherein each symbol is as defined in the specification.

1 . A compound represented by the following formula (I): 
       
         
           
           
               
               
           
         
         wherein
 Ring A is an optionally further substituted 6-membered aromatic ring, 
 R 1  is 
 
         (1) a group represented by the formula: -Q(R 1a )(R 1b )(R 1c ) wherein Q is a carbon atom, a silicon atom or a germanium atom, and R 1a , R 1b  and R 1c  are each independently a substituent, or R 1a  and R 1b  in combination optionally form, together with the adjacent Q, an optionally further substituted ring, and R 1c  is optionally bonded to one substituent for Ring A to form an optionally further substituted ring, 
         (2) a neo-pentyl group, or 
         (3) a trimethylsilylmethyl group,
 R 11  is —CR 12 R 12′ —R 12″ , —C(═O)—R 4  or —SO 2 —R 3 , 
 R 12 , R 12′  and R 12″  are each independently a hydrogen atom, a halogen atom, a cyano group, a nitro group, an optionally substituted C 1-6  alkyl group, an optionally substituted C 2-6  alkenyl group, an optionally substituted C 2-6  alkynyl group, an optionally substituted heterocyclic group or an optionally substituted thiocarbamoyl group, 
 R 4  is an optionally substituted C 1-6  alkyl group, an optionally substituted C 2-6  alkenyl group, an optionally substituted C 2-6  alkynyl group, an optionally substituted heterocyclic group, an acyl group, an optionally substituted amino group, an optionally substituted carbamoyl group, an optionally substituted thiocarbamoyl group, an optionally substituted sulfamoyl group, an optionally substituted hydroxy group, an optionally substituted sulfanyl(SH) group or an optionally substituted silyl group, 
 wherein the “C 1-6  alkyl group”, the “C 2-6  alkenyl group” and the “C 2-6  alkynyl group” of the “optionally substituted C 1-6  alkyl group”, the “optionally substituted C 2-6  alkenyl group” and the “optionally substituted C 2-6  alkynyl group” for R 4  are each optionally substituted by 1 to 5 substituents selected from (1) a halogen atom, (2) a nitro group, (3) a cyano group, (4) an oxo group, (5) a hydroxy group, (6) a C 1-6  alkoxy group optionally substituted by substituent(s) selected from a halogen atom and a carboxy group, (7) a C 6-14  aryloxy group, (8) a C 7-16  aralkyloxy group, (9) a 5- to 14-membered aromatic heterocyclyloxy group, (10) a 3- to 14-membered non-aromatic heterocyclyloxy group, (11) a C 1-6  alkyl-carbonyloxy group, (12) a C 6-14  aryl-carbonyloxy group, (13) a C 1-6  alkoxy-carbonyloxy group, (14) a mono- or di-C 1-6  alkyl-carbamoyloxy group, (15) a C 6-14  aryl-carbamoyloxy group, (16) a 5- to 14-membered aromatic heterocyclylcarbonyloxy group, (17) a 3- to 14-membered non-aromatic heterocyclylcarbonyloxy group, (18) an optionally halogenated C 1-6  alkylsulfonyloxy group, (19) a C 6-14  arylsulfonyloxy group optionally substituted by C 1-6  alkyl group(s), (20) an optionally halogenated C 1-6  alkylthio group, (21) a 5- to 14-membered aromatic heterocyclic group optionally substituted by substituent(s) selected from a hydroxy group, a C 1-6  alkyl group, a C 1-6  alkoxy group and a carboxy group, (22) a 3- to 14-membered non-aromatic heterocyclic group optionally substituted by substituent(s) selected from an oxo group and a C 1-6  alkyl group, (23) a formyl group, (24) a carboxy group, (25) an optionally halogenated C 1-6  alkyl-carbonyl group, (26) a C 6-14  aryl-carbonyl group, (27) a 5- to 14-membered aromatic heterocyclylcarbonyl group, (28) a 3- to 14-membered non-aromatic heterocyclylcarbonyl group, (29) a C 1-6  alkoxy-carbonyl group, (30) a C 6-14  aryloxy-carbonyl group, (31) a C 7-16  aralkyloxy-carbonyl group, (32) a carbamoyl group, (33) a thiocarbamoyl group, (34) a mono- or di-C 1-6  alkyl-carbamoyl group, (35) a C 6-14  aryl-carbamoyl group, (36) a 5- to 14-membered aromatic heterocyclylcarbamoyl group, (37) a 3- to 14-membered non-aromatic heterocyclylcarbamoyl group, (38) an optionally halogenated C 1-6  alkylsulfonyl group, (39) a C 6-14  arylsulfonyl group, (40) a 5- to 14-membered aromatic heterocyclylsulfonyl group, (41) an optionally halogenated C 1-6  alkylsulfinyl group, (42) a C 6-14  arylsulfinyl group, (43) a 5- to 14-membered aromatic heterocyclylsulfinyl group, (44) an amino group, (45) a mono- or di-C 1-6  alkylamino group (the C 1-6  alkyl is optionally substituted by carboxy group(s)), (46) a mono- or di-C 6-14  arylamino group, (47) a 5- to 14-membered aromatic heterocyclylamino group, (48) a C 7-16  aralkylamino group, (49) a formylamino group, (50) a C 1-6  alkyl-carbonylamino group, (51) a (C 1-6  alkyl) (C 1-6  alkyl-carbonyl)amino group, (52) a C 6-14  aryl-carbonylamino group, (53) a C 1-6  alkoxy-carbonylamino group, (54) a C 7-16  aralkyloxy-carbonylamino group, (55) a C 1-6  alkylsulfonylamino group, (56) a C 6-14  arylsulfonylamino group optionally substituted by C 1-6  alkyl group(s), (57) an optionally halogenated C 1-6  alkyl group, (58) a C 2-6  alkenyl group, and (59) a C 2-6  alkynyl group, 
 R 13  is a substituent, 
 Ring B is a benzene ring, a pyridine ring or a dihydropyridine ring, each of which is optionally further substituted, 
 the partial structure represented by the formula: 
 
       
       
         
           
           
               
               
           
         
         is CR 5a ═CR 6 , CR 5b ═N or C(═O)—NR 7 ,
 R 5a  and R 5b  are each independently an optionally substituted alkyl group, an optionally substituted alkoxy group, an optionally substituted alkylsulfonyl group, a cyano group, an optionally substituted cyclic amino group or an oxetan-3-yloxy group, and 
 R 6  and R 7  are each independently a hydrogen atom or a substituent, or 
 the substituent that Ring B optionally further has and R 5a  or R 5b  in combination optionally form Ring D, wherein Ring D is a 5- or 6-membered oxygen-containing heterocycle containing 1 to 2 oxygen atoms as heteroatoms in addition to carbon atoms, and is fused at the ring forming position, or 
 R 5a  and R 6  in combination optionally form Ring D′, wherein Ring D′ is a 5- or 6-membered oxygen-containing heterocycle containing 1 to 2 oxygen atoms as heteroatoms in addition to carbon atoms, and is fused at the ring forming position, 
 Y is an optionally substituted methylene group or an oxygen atom, and 
 W is an optionally substituted C 1-2  alkylene group, 
 
         or a salt thereof. 
       
     
     
         2 . The compound or salt of  claim 1 , wherein R 1  is a trimethylsilyl group, an ethyldimethylsilyl group or an optionally substituted tert-butyl group, or a group represented by the formula: —C(R 1a )(R 1b )(R 1c ) wherein R 1a  and R 1b  are each independently a substituent, or R 1a  and R 1b  in combination optionally form, together with the adjacent carbon atom, an optionally further substituted ring, and R 1c  is bonded to one substituent for Ring A to form an optionally further substituted ring. 
     
     
         3 . The compound or salt of  claim 1 , wherein Ring A is a benzene ring optionally further substituted by a halogen atom or a cyano group. 
     
     
         4 . The compound or salt of  claim 1 , wherein R 4  is (1) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from (a) a halogen atom, (b) a cyano group, (c) a hydroxy group, (d) a 5- to 6-membered monocyclic aromatic heterocyclic group, (e) a 4- to 6-membered monocyclic non-aromatic heterocyclic group, and (f) a carboxy group, or (2) an optionally substituted heterocyclic group. 
     
     
         5 . The compound or salt of  claim 1 , wherein Ring D′ is a dioxole ring. 
     
     
         6 . The compound or salt of  claim 1 , wherein Y and W are both methylene groups. 
     
     
         7 . The compound or salt of  claim 1 , wherein R 5a  is (1) an optionally substituted C 1-6  alkyl group, (2) an optionally substituted C 1-6  alkoxy group, or (3) an optionally substituted C 1-6  alkylsulfonyl group. 
     
     
         8 . The compound or salt of  claim 1 , wherein R 5b  is (1) an optionally substituted C 1-4  alkoxy group, or (2) an optionally substituted C 1-4  alkyl group. 
     
     
         9 . The compound or salt of  claim 1 , wherein R 6  is a hydrogen atom. 
     
     
         10 . The compound or salt of  claim 1 , wherein Ring B is a benzene ring or a pyridine ring, each of which is optionally further substituted. 
     
     
         11 . 5-((5R)-5-((7-Fluoro-1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)carbamoyl)-2-methoxy-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)-5-oxopentanoic acid or a salt thereof. 
     
     
         12 . (1-(((6R)-6-((3,5-Difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-8,9-dihydro[1,3]dioxolo[4,5-f]isoquinolin-7(6H)-yl)carbonyl)azetidin-3-yl)acetic acid or a salt thereof. 
     
     
         13 . (1-(((5R)-5-((3,5-Difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-2-methoxy-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)carbonyl)azetidin-3-yl)acetic acid or a salt thereof. 
     
     
         14 . A medicament comprising the compound or salt of  claim 1 . 
     
     
         15 . The medicament of  claim 14 , which is a RORγt inhibitor. 
     
     
         16 . The medicament of  claim 14 , which is an agent for the prophylaxis or treatment of psoriasis, inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD), rheumatoid arthritis, multiple sclerosis, uveitis, asthma, ankylopoietic spondylarthritis or systemic lupus erythematosus (SLE). 
     
     
         17 . A method of inhibiting RORγt, which comprises administering an effective amount of the compound or salt of  claim 1  to a mammal. 
     
     
         18 . A method for the prophylaxis or treatment of psoriasis, inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD), rheumatoid arthritis, multiple sclerosis, uveitis, asthma, ankylopoietic spondylarthritis or systemic lupus erythematosus (SLE), which comprises administering an effective amount of the compound or salt of  claim 1  to a mammal. 
     
     
         19 . Use of the compound or salt of  claim 1  for the production of an agent for the prophylaxis or treatment of psoriasis, inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD), rheumatoid arthritis, multiple sclerosis, uveitis, asthma, ankylopoietic spondylarthritis or systemic lupus erythematosus (SLE). 
     
     
         20 . The compound or salt of  claim 1  for use in the prophylaxis or treatment of psoriasis, inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD), rheumatoid arthritis, multiple sclerosis, uveitis, asthma, ankylopoietic spondylarthritis or systemic lupus erythematosus (SLE).