Heterocyclic compound

Abstract

The present invention provides a compound having a superior JAK inhibitory action, which is useful as an agent for the prophylaxis or treatment of autoimmune diseases (rheumatoid arthritis, psoriasis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis, systemic lupus erythematosus, etc.), cancer (leukemia, uterine leiomyosarcoma, prostate cancer, multiple myeloma, cachexia, myelofibrosis, etc.) and the like, or a salt thereof. The present invention relates to a compound represented by the formula wherein each symbol is as defined in the specification, or a salt thereof.

1 . A compound represented by the formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         Ring A moiety is a nitrogen-containing aromatic heterocycle
 wherein 
 Q is a carbon atom or a nitrogen atom, and 
 X 2  and X 3  are each independently a carbon atom or a nitrogen atom, and any one of them is a nitrogen atom; 
 
         R 1  is a hydrogen atom, a halogen atom, a cyano group, an acyl group, an optionally substituted C 1-6  alkyl group, an optionally substituted C 3-6  cycloalkyl group or an optionally substituted hydroxy group; 
         R 2  is a substituted C 1-2  alkyl group, an optionally substituted C 3-6  alkyl group, an acyl group, an optionally substituted hydroxy group, an optionally substituted amino group, an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; and 
         R 3  is a substituted C 1-2  alkyl group, an optionally substituted C 3-6  alkyl group, an acyl group, an optionally substituted hydroxy group, an optionally substituted amino group, an optionally substituted carbocyclic group or an optionally substituted heterocyclic group, 
         provided that 3-(3-fluorophenyl)-1-trityl-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one is excluded, 
         or a salt thereof. 
       
     
     
         2 . The compound or salt of  claim 1 , wherein
 R 1  is   (1) a hydrogen atom,   (2) a halogen atom,   (3) a cyano group,   (4) a carboxy group,   (5) a C 1-6  alkyl-carbonyl group,   (6) a C 1-6  alkoxy-carbonyl group,   (7) a carbamoyl group optionally mono- or di-substituted by C 1-6  alkyl group(s),   (8) a C 1-6  alkyl group optionally substituted by 1 to 3 hydroxy groups, or   (9) a C 3-6  cycloalkyl group;   R 2  is   (1) a C 1-2  alkyl group substituted by 1 to 3 substituents selected from
 (a) a C 6-14  aryl group optionally substituted by 1 to 3 C 1-6  alkoxy groups, and 
 (b) a 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted by 1 to 3 C 1-6  alkyl groups, 
   (2) a C 3-6  alkyl group optionally substituted by 1 to 3 substituents selected from
 (a) a hydroxy group, and 
 (b) a C 1-6  alkoxy group, 
   (3) a C 3-10  cycloalkyl group optionally substituted by 1 to 3 substituents selected from
 (a) a hydroxy group, 
 (b) a C 1-6  alkyl group, 
 (c) an oxo group, 
 (d) a C 1-6  alkylenedioxy group, 
 (e) a C 6-14  aryl group, 
 (f) a halogen atom, and 
 (g) an amino group, 
   (4) a C 6-14  aryl group optionally substituted by 1 to 3 substituents selected from
 (a) a halogen atom, 
 (b) a C 1-6  alkyl group optionally substituted by 1 to 3 halogen atoms, 
 (c) a cyano group, 
 (d) a carbamoyl group, 
 (e) an amino group, and 
 (f) a C 1-6  alkoxy group, 
   (5) a 3- to 8-membered monocyclic non-aromatic heterocyclic group, or   (6) a 5- to 7-membered monocyclic aromatic heterocyclic group; and   R 3  is   (1) a C 1-2  alkyl group substituted by 1 to 3 substituents selected from a C 6-14  aryl group optionally substituted by 1 to 3 sulfamoyl groups,   (2) a C 3-10  cycloalkyl group,   (3) a C 3-10  cycloalkenyl group,   (4) a C 6-14  aryl group optionally substituted by 1 to 3 substituents selected from
 (a) a halogen atom, 
 (b) a nitro group, 
 (c) a cyano group, 
 (d) a carbamoyl group optionally mono- or di-substituted by C 1-6  alkyl group(s) optionally substituted by 1 to 3 substituents selected from
 (i) a C 1-6  alkoxy group, 
 (ii) a hydroxy group, and 
 (iii) an amino group optionally mono- or di-substituted by C 1-6  alkyl group(s), 
 
 (e) a sulfamoyl group optionally mono- or di-substituted by C 1-6  alkyl group(s), 
 (f) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from
 (i) a halogen atom, 
 (ii) a cyano group, 
 (iii) a hydroxy group, 
 (iv) a carbamoyl group optionally mono- or di-substituted by substituent(s) selected from a C 1-6  alkyl group and a C 3-10  cycloalkyl group, 
 (v) an amino group optionally mono- or di-substituted by C 1-6  alkyl group(s), and 
 (vi) a 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from an oxo group and a halogen atom, 
 
 (g) a C 1-6  alkoxy group optionally substituted by 1 to 3 substituents selected from
 (i) a halogen atom, 
 (ii) a cyano group, 
 (iii) a hydroxy group, and 
 (iv) a carbamoyl group optionally mono- or di-substituted by substituent(s) selected from a C 1-6  alkyl group optionally substituted by 1 to 3 C 1-6  alkoxy groups, 
 
 (h) a C 1-6  alkoxy-carbonyl group, 
 (i) an amino group optionally mono- or di-substituted by substituent(s) selected from
 (i) a C 1-6  alkyl-carbonyl group, and 
 (ii) a C 1-6  alkyl group optionally substituted by 1 to 3 C 1-6  alkoxy groups, 
 
 (j) a 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from
 (i) an oxo group, 
 (ii) a C 1-6  alkyl group, 
 (iii) 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, 
 (iv) a carbamoyl group optionally mono- or di-substituted by C 1-6  alkyl group(s), 
 (v) a C 1-6  alkylsulfonyl group, and 
 (vi) a halogen atom, and 
 
 (k) a C 1-6  alkylenedioxy group, 
   (5) a 5- to 7-membered monocyclic aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from
 (a) a carboxy group, 
 (b) a cyano group, 
 (c) a C 1-6  alkoxy-carbonyl group, 
 (d) a carbamoyl group optionally mono- or di-substituted by substituent(s) selected from
 (i) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a cyano group, 
 (ii) a C 3-10  cycloalkyl group optionally substituted by 1 to 3 cyano groups, 
 (iii) a 5- to 7-membered monocyclic aromatic heterocyclic group optionally substituted by 1 to 3 C 1-6  alkyl groups, and 
 (iv) a 3- to 8-membered monocyclic non-aromatic heterocyclic group, 
 
 (e) a 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted by 1 to 3 oxo groups, 
 (f) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from
 (i) a cyano group, 
 (ii) a carbamoyl group, and 
 (iii) a 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted by 1 to 3 oxo groups, 
 
 (g) a C 3-10  cycloalkyl group, 
 (h) a 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group, and 
 (i) an amino group, 
   (6) a 8- to 12-membered fused aromatic heterocyclic group optionally substituted by 1 to 3 C 1-6  alkyl groups,   (7) a 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from
 (a) an oxo group, and 
 (b) a C 1-6  alkyl group, 
   (8) a 8- to 12-membered fused non-aromatic heterocyclic group optionally substituted by 1 to 3 oxo groups, or   (9) an amino group optionally mono- or di-substituted by substituent(s) selected from
 (a) a C 6-14  aryl group optionally substituted by 1 to 3 substituents selected from
 (i) a carbamoyl group, and 
 (ii) a sulfamoyl group, 
 
 (b) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from a C 6-14  aryl group optionally substituted by 1 to 3 C 1-6  alkoxy groups, and 
 (c) a C 6-14  aryl-carbonyl group. 
   
     
     
         3 . The compound or salt of  claim 1 , which is 4-(1-cyclopentyl-4-oxo-4,5-dihydro-1H-pyrrolo[3,2-c]pyridin-3-yl)thiophene-2-carboxamide. 
     
     
         4 . The compound or salt of  claim 1 , which is 2-(4-(1-(2,6-difluorophenyl)-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-3-yl)phenyl)acetamide. 
     
     
         5 . The compound or salt of  claim 1 , which is 3-((1-cyclopentyl-4-oxo-4,5-dihydro-1H-pyrazolo[4,3-c]pyridin-3-yl)amino)benzenesulfonamide. 
     
     
         6 . A medicament comprising the compound or salt of  claim 1 . 
     
     
         7 . The medicament of  claim 6 , which is a janus kinase inhibitor. 
     
     
         8 . The medicament of  claim 6 , which is an agent for the prophylaxis or treatment of autoimmune disease. 
     
     
         9 . The compound or salt of  claim 1  for use in the prophylaxis or treatment of autoimmune diseases. 
     
     
         10 . A method of inhibiting janus kinase in a mammal, which comprises administering an effective amount of the compound or salt of  claim 1  to the mammal. 
     
     
         11 . A method for the prophylaxis or treatment of autoimmune diseases, which comprises administering an effective amount of the compound or salt of  claim 1  to the mammal. 
     
     
         12 . Use of the compound or salt of  claim 1  for the production of an agent for the prophylaxis or treatment of autoimmune diseases.