Heterocyclic compound and use thereof

Abstract

The present invention provides a heterocycle derivative having a superior amyloid β production inhibitory activity and/or a superior γ-secretase modulation activity, and use thereof. A compound represented by the formula (I): wherein each symbol is as defined in the present specification, or a salt thereof.

1 . A compound represented by the formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         ring A is an optionally substituted oxazole ring, an optionally substituted triazole ring, an optionally substituted imidazole ring, an optionally substituted pyridine ring, or an optionally substituted pyrazole ring, 
         ring B is an optionally substituted benzene ring, an optionally substituted pyridine ring, or an optionally substituted pyrimidine ring, and 
         partial structure (1): 
       
       
         
           
           
               
               
           
         
         is 
       
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 2  are the same or different and each is a substituent, 
         L is a bond, —Y—, —O—, —YO—, —OY—, —S—, —SO—, —SO 2 —, —CONR a —, —NR a CO—, —NR a —, —YNR a —, —NR a Y—, —YCONR a —, —NR a COY—, —OCONR a —, —NR a COO— or —NR b CONR a — 
         wherein 
         Y is an optionally substituted C 1-6  alkylene group, 
         R a  is a hydrogen atom or an optionally substituted C 1-6  alkyl group, 
         R b  is a hydrogen atom or an optionally substituted C 1-6  alkyl group, 
         R 3  is a substituent, and 
         n is an integer of 0-6, 
         provided that 2-{(8R)-3-[3-Methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-8-(3,4,5-trifluorophenoxy)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-8-yl}propan-2-ol is excluded, 
         or a salt thereof. 
       
     
     
         2 . The compound according to  claim 1 , wherein R 1  is a hydroxy group, an optionally substituted C 1-6  alkyl group, an optionally substituted C 1-6  alkoxy group, an optionally substituted aminocarbonyl group, a carboxy group, a C 1-6  alkyl-carbonyl group or an optionally substituted C 1-6  alkoxy-carbonyl group,
 R 2  is a halogen atom, an optionally substituted hydrocarbon ring group or an optionally substituted heterocyclic group, or a salt thereof.   
     
     
         3 . The compound according to  claim 1 , wherein ring A is an optionally substituted oxazole ring, or a salt thereof. 
     
     
         4 . The compound according to  claim 1 , wherein ring A is an optionally substituted imidazole ring, or a salt thereof. 
     
     
         5 . The compound according to  claim 1 , wherein ring B is an optionally substituted benzene ring or an optionally substituted pyridine ring, or a salt thereof. 
     
     
         6 . The compound according to  claim 1 , wherein the partial structure (1): 
       
         
           
           
               
               
           
         
         is 
       
       
         
           
           
               
               
           
         
         wherein each symbol is the same as  claim 1 , or a salt thereof. 
       
     
     
         7 . The compound according to  claim 1 , wherein R 1  is a C 1-6  alkyl group substituted by a hydroxy group, or a salt thereof. 
     
     
         8 . The compound according to  claim 1 , wherein R 2  is an optionally substituted C 6-14  aryl group or an optionally substituted aromatic heterocyclic group, or a salt thereof. 
     
     
         9 . The compound according to  claim 1 , wherein L is —O—, or a salt thereof. 
     
     
         10 . The compound according to  claim 1 , which is 2-{8-(4-Chloro-3-fluorophenoxy)-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-8-yl}propan-2-ol or a salt thereof. 
     
     
         11 . (canceled) 
     
     
         12 . The compound according to  claim 1 , which is 2-{3-[3-Methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-8-[3-(trifluoromethyl)phenoxy]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-8-yl}propan-2-ol or a salt thereof. 
     
     
         13 . The compound according to  claim 1 , which is 2-{3-[3-Methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-8-[4-(trifluoromethyl)phenoxy]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-8-yl}propan-2-ol or a salt thereof. 
     
     
         14 . The compound according to  claim 1 , which is 2-{8-(3,5-Difluorophenoxy)-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-8-yl}propan-2-ol or a salt thereof. 
     
     
         15 . The compound according to  claim 1 , which is 2-{(8R)-3-[6-Methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]-8-(3,4,5-trifluorophenoxy)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-8-yl}propan-2-ol or a salt thereof. 
     
     
         16 . A medicament containing the compound according to  claim 1  or a salt thereof. 
     
     
         17 . The drug according to  claim 16 , which is for the prophylaxis or therapy of mild cognitive impairment or Alzheimer's disease. 
     
     
         18 . An amyloid β production inhibitor containing the compound according to  claim 1  or a salt thereof. 
     
     
         19 . A γ-secretase modulator containing the compound according to  claim 1  or a salt thereof. 
     
     
         20 - 23 . (canceled) 
     
     
         24 . The compound according to  claim 1  or a salt thereof for modulating γ-secretase. 
     
     
         25 . The compound according to  claim 1  or a salt thereof for the prophylaxis or treatment of mild cognitive impairment or Alzheimer's disease. 
     
     
         26 - 29 . (canceled)