Benzimidazole compound

Abstract

An object of the present invention is to provide a novel chemical compound useful as a therapeutic or prophylactic agent for acid-related diseases, having an excellent inhibitory effect against gastric acid secretion, an excellent effect of maintaining the inhibitory effect against gastric acid secretion, thereby maintaining intragastric pH high for a long time, and having more safety and appropriate physicochemical stability. Provided is a compound represented by where R 1 and R 3 may be the same or different and each represent a hydrogen atom or a C1-C6 alkyl group; R 2 represents (5,5-dimethyl-1,3-dioxan-2-yl)methoxy group, 5,7-dioxaspiro[2.5]oct-6-ylmethoxy group, 1,5,9-trioxaspiro[5.5]undec-3-ylmethoxy group, or (2,2-dimethyl-1,3-dioxan-5-yl)methoxy group; R 4 , R 5 , R 6 and R 7 represent a hydrogen atom, halogen atom, C1-C6 alkyl group, C1-C6 haloalkyl group, C1-C6 alkoxy group or C1-C6 haloalkoxy group; and W 1 represents a single bond, methylene or ethylene group, a salt thereof or a solvate of these.

1 . A compound represented by  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  and R 3  may be the same or different and each represent a hydrogen atom or a C1-C6 alkyl group;  
 R 2  is a group represented by  
                     
 wherein W 2  represents a hydrogen atom, C1-C6 alkyl group or halogen atom (with the proviso that, occurrence of W 2  on a benzene ring may be 1 to 3, and may be the same or different) n1 represents 1 to 5; n2 represents 1 to 4; and n3 represents 1 to 6,  
 said group optionally having 1 to 4 groups selected from the group A1 consisting of a halogen atom, C1-C6 alkyl group, C1-C6 alkoxy group, C1-C6 haloalkyl group, C1-C6 alkoxy C1-C6 alkyl group and hydroxyl group;  
 R 4 , R 5 , R 6  and R 7  may be the same or different and each represent a hydrogen atom, hydroxyl group, halogen atom, C1-C6 alkyl group, C1-C6 haloalkyl group, C1-C6 alkoxy group or C1-C6 haloalkoxy group, or a combination of R 5  and R 6  represents a methylenedioxy group or an ethylenedioxy group; and  
 W 1  represents a single bond, or straight or branched alkylene group having 1 to 8 carbon atoms,  
 or a salt thereof, or a solvate of these.  
 
   
   
       2 . The compound or a salt thereof, or a solvate of these according to  claim 1 , wherein R 1  is a hydrogen atom or a methyl group.  
   
   
       3 . The compound or a salt thereof, or a solvate of these according to  claim 1 , wherein R 1  is a methyl group.  
   
   
       4 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  3 , wherein R 2  is a group represented by  
     
       
         
         
             
             
         
       
       wherein W 2  represents a hydrogen atom, C1-C6 alkyl group or halogen atom (with the proviso that, occurrence of W 2  on a benzene ring may be 1 to 3, and may be the same or different); n1 represents 1 to 5; n2 represents 1 to 4; and n3 represents 1 to 6  
       said group optionally having 1 or 2 groups selected from the group A2 consisting of a fluoride atom, a methyl group, ethyl group, propyl group, methoxy group and monofluoromethyl group.  
     
   
   
       5 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  3 , wherein R 2  is a group represented by the formula (4):  
     
       
         
         
             
             
         
       
     
   
   
       6 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  3 , wherein R2 is a group represented by  
     
       
         
         
             
             
         
       
     
   
   
       7 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  6 , wherein R 3  is a hydrogen atom or a methyl group.  
   
   
       8 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  6 , wherein R 3  is a methyl group.  
   
   
       9 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  8 , wherein R 4  is a hydrogen atom, hydroxyl group, methyl group, ethyl group, methoxy group, ethoxy group or fluorine atom.  
   
   
       10 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  8 , wherein R 4  is a hydrogen atom, methyl group or fluorine atom.  
   
   
       11 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  8 , wherein R 4  is a hydrogen atom.  
   
   
       12 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  11 , wherein R 5  is a hydrogen atom, hydroxyl group, methyl group, ethyl group, methoxy group, ethoxy group or fluorine atom.  
   
   
       13 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  11 , wherein R 5  is a hydrogen atom, methyl group or fluorine atom.  
   
   
       14 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  11 , wherein R 5  is a hydrogen atom.  
   
   
       15 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  14 , wherein R 6  is a hydrogen atom, hydroxyl group, methyl group, ethyl group, methoxy group, ethoxy group or fluorine atom.  
   
   
       16 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  14 , wherein R 6  is a hydrogen atom, methyl group or fluorine atom.  
   
   
       17 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  14 , wherein R 6  is a hydrogen atom.  
   
   
       18 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  17 , wherein R 7  is a hydrogen atom, hydroxyl group, methyl group, ethyl group, methoxy group, ethoxy group or fluorine atom.  
   
   
       19 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  17 , wherein R 7  is a hydrogen atom, methyl group or fluorine atom.  
   
   
       20 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  17 , wherein R 7  is a hydrogen atom.  
   
   
       21 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  20 , wherein W 1  is a single bond, methylene group, or ethylene group.  
   
   
       22 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  20 , wherein W 1  is a methylene group.  
   
   
       23 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  4 , wherein all occurrences of W 2  are hydrogen atoms.  
   
   
       24 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  4 , wherein n1 is 1 to 3.  
   
   
       25 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  4 , wherein n1 is 1 or 2.  
   
   
       26 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  4 , wherein n2 is 1 or 2.  
   
   
       27 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  4 , wherein n3 is 1 to 4.  
   
   
       28 . The compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  4 , wherein n3 is 1 or 2.  
   
   
       29 . The compound or a salt thereof, or a solvate of these according to  claim 1 , wherein the compound is one selected from the following group consisting of 
 2-(((4-((5,5-dimethyl-1,3-dioxan-2-yl)methoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole,    2-(((4-(5,7-dioxaspiro[2.5]oct-6-ylmethoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole,    2-(((3-methyl-4-(1,5,9-trioxaspiro[5.5]undec-3-ylmethoxy)pyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole,    2-(((4-((2,2-dimethyl-1,3-dioxan-5-yl)methoxy)-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole,    2-(((3-methyl-4-(2-(8-methyl-1,4,7,9-tetraoxaspiro[4.5]dec-8-yl)ethoxy)pyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole,    2-(((4-(5,9-dioxaspiro[3.5]non-7-yloxy)pyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole,    2-(((4-(2-(8-ethyl-1,4,7,9-tetraoxaspiro[4.5]dec-8-yl)ethoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole,    2-(((4-(1,3-dioxolan-4-ylmethoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole,    2-(((4-((2,2-bis(fluoromethyl)-1,3-dioxan-5-yl)methoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole,    2-(((4-(5,9-dioxaspiro[3.5]non-7-yloxy)-3-methylpyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole,    2-(((4-((2-methoxy-1,3-dioxan-5-yl)methoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole,    2-(((3-methyl-4-((8-methyl-1,4,7,9-tetraoxaspiro[4.5]dec-8-yl)methoxy)pyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole,    2-(((4-(5,9-dioxaspiro[3.5]non-7-ylmethoxy)pyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole, and    2-(((4-((5,5-difluoro-1,3-dioxan-2-yl)methoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole.    
   
   
       30 . 2-(((4-((5,5-dimethyl-1,3-dioxan-2-yl)methoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole, or a salt thereof, or a solvate of these.  
   
   
       31 . 2-(((4-(5,7-dioxaspiro[2.5]oct-6-ylmethoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole or a salt thereof, or a solvate of these.  
   
   
       32 . 2-(((3-methyl-4-(1,5,9-trioxaspiro[5.5]undec-3-ylmethoxy)pyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole or a salt thereof, or a solvate of these.  
   
   
       33 . 2-(((4-((2,2-dimethyl-1,3-dioxan-5-yl)methoxy)-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzimidazole or a salt thereof, or a solvate of these.  
   
   
       34 . A medicament comprising the compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  33 .  
   
   
       35 . A gastric acid secretion inhibitor comprising the compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  33 .  
   
   
       36 . A therapeutic agent or prophylactic agent for acid-related diseases or symptoms, comprising the compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  33 .  
   
   
       37 . The therapeutic agent or prophylactic agent according to  claim 36 , wherein the acid-related diseases or symptoms are gastric ulcer, duodenal ulcer, anastomotic ulcer, gastroesophageal reflux disease, Zollinger-Ellison syndrome, symptomatic gastroesophageal reflux disease, endoscopically negative gastroesophageal reflux disease, non-erosive gastroesophageal reflux disease, gastroesophageal regurgitation, NUD (non-ulcer dyspepsia), abnormal sensation in the throat, Barrett's esophagus, NSAID-induced ulcer, gastritis, gastric bleeding, hemorrhagic gastritis, gastrointestinal bleeding, peptic ulcer, bleeding ulcer, stress ulcer, gastric hyperacidity, dyspepsia, gastroparesis, elderly person's ulcer, intractable ulcer, acute gastric mucosal lesion, heartburn, pyrosis of sleep apnea syndrome, bruxism, gastralgia, heavy stomach feeling, gagging, nausea, temporomandibular joint arthrosis, or erosive gastritis.  
   
   
       38 . The therapeutic agent or prophylactic agent according to  claim 36 , wherein the acid-related disease or symptom is gastric ulcer, duodenal ulcer, anastomotic ulcer, gastroesophageal reflux disease, Zollinger-Ellison syndrome, symptomatic gastroesophageal reflux disease, endoscopically negative gastroesophageal reflux disease, non-erosive gastroesophageal reflux disease, or acute gastric mucosal lesion.  
   
   
       39 . The therapeutic agent or prophylactic agent according to  claim 36 , wherein the acid-related diseases or symptoms are gastroesophageal reflux disease or symptomatic gastroesophageal reflux disease.  
   
   
       40 . The therapeutic agent or prophylactic agent according to  claim 36 , wherein the acid-related diseases are gastric ulcer or duodenal ulcer.  
   
   
       41 . An bactericidal agent or an auxiliary bactericidal agent against  Helicobacter pylori  in the stomach, comprising the compound or a salt thereof, or a solvate of these according to any one of  claims 1  to  33 .