Proton pump inhibitors

Abstract

A proton pump inhibitor containing a compound represented by the formula (I) wherein X and Y are the same or different and each is a bond or a spacer having 1 to 20 carbon atoms in the main chain, R 1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, R 2 , R 3 and R 4 are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted thienyl group, an optionally substituted benzo[b]thienyl group, an optionally substituted furyl group, an optionally substituted pyridyl group, an optionally substituted pyrazolyl group, an optionally substituted pyrimidinyl group, an acyl group, a halogen atom, a cyano group or a nitro group, R 5 and R 6 are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, which has a superior proton pump action and shows an antiulcer activity and the like after conversion to a proton pump inhibitor in the body, or a salt thereof. or a prodrug thereof is provided.

1 - 4 . (canceled) 
     
     
         5 . A compound represented by the formula (II-a) 
       
         
           
           
               
               
           
         
       
       wherein
 X 1  is —SO 2 —, —SO 2 —N(R 7 )— (wherein R 7  is a hydrogen atom or an optionally substituted hydrocarbon group), —N(R 8 )—SO 2 — (wherein R 8  is a hydrogen atom or an optionally substituted hydrocarbon group), —N(R 9 )— (wherein R 9  is a hydrogen atom or an optionally substituted hydrocarbon group) or —O—, 
 Y 1  is an optionally substituted alkylene group, R 10  is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, 
 R 11  is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted thienyl group, an optionally substituted benzo[b]thienyl group, an optionally substituted furyl group, an optionally substituted pyridyl group, an optionally substituted pyrazolyl group or an optionally substituted pyrimidinyl group, 
 R 12  and R 13  are each independently a hydrogen atom, an optionally substituted hydrocarbon group, an acyl group, a halogen atom, a cyano group or a nitro group (provided that R 12  and R 13  are not simultaneously hydrogen atoms), and R 14  and R 15  are each independently a hydrogen atom or an optionally substituted hydrocarbon group, 
 with the proviso that 3-[[2,3-dimethyl-1-(4-methylphenyl)sulfonyl]-1H-pyrrol-4-yl]-2-methyl-alanine methyl ester is excluded, or a salt thereof. 
 
     
     
         6 . A compound represented by the formula (II-b) 
       
         
           
           
               
               
           
         
       
       wherein
 X 2  is a —SO 2 —N(R 7 )— (wherein R 7  is a hydrogen atom or an optionally substituted hydrocarbon group), —N(R 8 )—SO 2 — (wherein R 8  is a hydrogen atom or an optionally substituted hydrocarbon group), —N(R 9 )— (wherein R 9  is a hydrogen atom or an optionally substituted hydrocarbon group) or —O—, 
 Y 2  is an optionally substituted alkylene group, 
 R 16  is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, 
 R 17  is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted thienyl group, an optionally substituted benzo[b]thienyl group, an optionally substituted furyl group, an optionally substituted pyridyl group, an optionally substituted pyrazolyl group or an optionally substituted pyrimidinyl group, 
 R 18  and R 19  are each a hydrogen atom, and 
 R 20  and R 21  are each independently a hydrogen atom or an optionally substituted hydrocarbon group, 
 provided that R 17  should not be a 1,3-dioxaindan-6-yl group, 
 
       or a salt thereof. 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . A prodrug of the compound of  claim 5  or  claim 6 . 
     
     
         10 . A pharmaceutical agent comprising the compound of  claim 5  or  claim 6 . 
     
     
         11 . The pharmaceutical agent of  claim 10 , which is an agent for the prophylaxis or treatment of peptic ulcer, Zollinger-Ellison syndrome, gastritis, reflux esophagitis, gastroesophageal reflux disease (Symptomatic Gastroesophageal Reflux Disease (symptomatic GERD)) free of esophagitis, NUD (Non Ulcer Dyspepsia), gastric cancer, stomach MALT lymphoma, ulcer caused by a non-steroidal anti-inflammatory agent or gastric hyperacidity and ulcer due to postoperative stress; or an inhibitor of upper gastrointestinal hemorrhage due to peptic ulcer, acute stress ulcer, hemorrhagic gastritis or invasive stress. 
     
     
         12 . A method for the prophylaxis or treatment of peptic ulcer, Zollinger-Ellison syndrome, gastritis, reflux esophagitis, gastroesophageal reflux disease (Symptomatic Gastroesophageal Reflux Disease (symptomatic GERD)) free of esophagitis, NUD (Non Ulcer Dyspepsia), gastric cancer, stomach MALT lymphoma, ulcer caused by a non-steroidal anti-inflammatory agent or gastric hyperacidity and ulcer due to postoperative stress; or a method of inhibiting upper gastrointestinal hemorrhage due to peptic ulcer, acute stress ulcer, hemorrhagic gastritis or invasive stress, which comprises administering an effective amount of the compound of  claim 5  or  claim 6  or a prodrug thereof to a mammal. 
     
     
         13 . (canceled) 
     
     
         14 . A method for acid secretion inhibition, which comprises administering an effective amount of a compound of formula (I) 
       
         
           
           
               
               
           
         
       
       wherein
 X and Y are the same or different and each is a bond or a spacer having 1 to 20 atoms in the main chain, 
 R 1  is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, 
 R 2 , R 3  and R 4  are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted thienyl group, an optionally substituted benzo[b]thienyl group, an optionally substituted furyl group, an optionally substituted pyridyl group, an optionally substituted pyrazolyl group, an optionally substituted pyrimidinyl group, an acyl group, a halogen atom, a cyano group or a nitro group, and 
 R 5  and R 6  are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, 
 
       or a salt thereof, or a prodrug thereof, to a mammal. 
     
     
         15 . The method of  claim 14 , wherein X is —SO 2 —, —SO 2 —N(R 7 )— (wherein R 7  is a hydrogen atom or an optionally substituted hydrocarbon group), —N(R 8 )—SO 2 — (wherein R 8  is a hydrogen atom or an optionally substituted hydrocarbon group), —N(R 9 )— (wherein R 9  is a hydrogen atom or an optionally substituted hydrocarbon group) or —O—. 
     
     
         16 . The method of  claim 14 , wherein X is —SO 2 —. 
     
     
         17 . A method for the prophylaxis or treatment of peptic ulcer, Zollinger-Ellison syndrome, gastritis, reflux esophagitis, gastroesophageal reflux disease (Symptomatic Gastroesophageal Reflux Disease (symptomatic GERD)) free of esophagitis, NUD (Non Ulcer Dyspepsia), gastric cancer, stomach MALT lymphoma, ulcer caused by a non-steroidal anti-inflammatory agent or gastric hyperacidity and ulcer due to postoperative stress; or a method of inhibiting upper gastrointestinal hemorrhage due to peptic ulcer, acute stress ulcer, hemorrhagic gastritis or invasive stress, which comprises administering an effective amount of a compound of formula (I) 
       
         
           
           
               
               
           
         
       
       wherein
 X and Y are the same or different and each is a bond or a spacer having 1 to 20 atoms in the main chain, 
 R 1  is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, 
 R 2 , R 3  and R 4  are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted thienyl group, an optionally substituted benzo[b]thienyl group, an optionally substituted furyl group, an optionally substituted pyridyl group, an optionally substituted pyrazolyl group, an optionally substituted pyrimidinyl group, an acyl group, a halogen atom, a cyano group or a nitro group, and 
 R 5  and R 6  are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, 
 
       or a salt thereof, or a prodrug thereof, to a mammal. 
     
     
         18 . A method for proton pump inhibition, which comprises administering an effective amount of a compound of formula (I) 
       
         
           
           
               
               
           
         
       
       wherein
 X and Y are the same or different and each is a bond or a spacer having 1 to 20 atoms in the main chain, 
 R 1  is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, 
 R 2 , R 3  and R 4  are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted thienyl group, an optionally substituted benzo[b]thienyl group, an optionally substituted furyl group, an optionally substituted pyridyl group, an optionally substituted pyrazolyl group, an optionally substituted pyrimidinyl group, an acyl group, a halogen atom, a cyano group or a nitro group, and 
 R 5  and R 6  are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, 
 
       or a salt thereof, or a prodrug thereof, to a mammal. 
     
     
         19 . The method of  claim 18 , wherein X is —SO 2 —, —SO 2 —N(R 7 )— (wherein R 7  is a hydrogen atom or an optionally substituted hydrocarbon group), —N(R 8 )—SO 2 — (wherein R 8  is a hydrogen atom or an optionally substituted hydrocarbon group), —N(R 9 )— (wherein R 9  is a hydrogen atom or an optionally substituted hydrocarbon group) or —O—. 
     
     
         20 . The method of  claim 18 , wherein X is —SO 2 —. 
     
     
         21 . A method for the prophylaxis or treatment of peptic ulcer, Zollinger-Ellison syndrome, gastritis, reflux esophagitis, gastroesophageal reflux disease (Symptomatic Gastroesophageal Reflux Disease (symptomatic GERD)) free of esophagitis, NUD (Non Ulcer Dyspepsia), gastric cancer, stomach MALT lymphoma, ulcer caused by a non-steroidal anti-inflammatory agent or gastric hyperacidity and ulcer due to postoperative stress; or a method of inhibiting upper gastrointestinal hemorrhage due to peptic ulcer, acute stress ulcer, hemorrhagic gastritis or invasive stress, which comprises administering an effective amount of a compound of formula (I) 
       
         
           
           
               
               
           
         
       
       wherein
 X and Y are the same or different and each is a bond or a spacer having 1 to 20 atoms in the main chain, 
 R 1  is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, 
 R 2 , R 3  and R 4  are the same or different and each is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted thienyl group, an optionally substituted benzo[b]thienyl group, an optionally substituted furyl group, an optionally substituted pyridyl group, an optionally substituted pyrazolyl group, an optionally substituted pyrimidinyl group, an acyl group, a halogen atom, a cyano group or a nitro group, and 
 R 5  and R 6  are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, 
 
       or a salt thereof, or a prodrug thereof, to a mammal.