US2009209592A1PendingUtilityA1

Inhibitors of the gastric h+, k+-atpase with enhanced therapeutic properties

Assignee: AUSPEX PHARMACEUTICALS INCPriority: Oct 6, 2005Filed: Mar 27, 2009Published: Aug 20, 2009
Est. expiryOct 6, 2025(expired)· nominal 20-yr term from priority
A61P 43/00A61P 31/04A61P 29/00A61P 17/06A61P 1/04A61P 1/00C07D 401/12
64
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Claims

Abstract

Chemical syntheses and medical uses of novel inhibitors of the gastric H + , K + -ATPase for the treatment and/or management of duodenal ulcers, heartburn, acid reflux, other conditions mediated by gastric acid secretion and/or psoriasis are described.

Claims

exact text as granted — not AI-modified
1 - 36 . (canceled) 
     
     
         36 . A compound of Formula 1 
       
         
           
           
               
               
           
         
         or a single enantiomer, a mixture of enantiomers, an individual diastereomer, a mixture of diastereomers, or a pharmaceutically acceptable salt thereof, wherein: 
         R 1 , R 4 , R 9  and R 10  are each independently hydrogen or deuterium; 
         R 2 , R 3 , R 6 , and R 8  are each independently selected from the group consisting of hydrogen, deuterium, C 1 -C 6  alkyl, and C 1 -C 6  alkyloxy; 
         R 5  is selected from the group consisting of —CH 2 —, —CHD- and —CD 2 -; and 
         R 7  is selected from the group consisting of hydrogen, deuterium, —NO 2 , C 1 -C 6  alkyl, and C 1 -C 6  alkyloxy; 
         if R 1 , R 3 , and R 4  are deuterium, R 2  is —OCH 3 , R 6  is —CH 3 , R 7  is —OCH 3 , R 8  is —CH 3 , then at least one of R 5  and R 9  has deuterium enrichment of at least about 1%; 
         if R 1 , R 3 , and R 4  are deuterium, R 2  is —OCH 3 , R 6  is —CH 3 , R 7  is —OCH 3 , and R 8  is —CH 3 , then at least one of R 5 , R 9 , and R 10  has deuterium enrichment of at least about 1%; 
         if R 1 , R 2 , R 3 , and R 4  are deuterium, R 6  is —CH 3 , and R 7  is —OCH 2 CF 3 , then at least one of R 8 , R 9 , and R 10  has deuterium enrichment of at least about 1%; 
         provided that if R 2  is hydrogen or C 1 -C 4  alkyloxy, R 6  is C 1 -C 4  alkyl or C 1 -C 4  alkyloxy, R 7  is C 1 -C 4  alkyl, C 1 -C 4  alkyloxy, or C 2 -C 8  alkyloxyalkyloxy, and R 8  is hydrogen or C 1 -C 4  alkyl, and at least one of the hydrogen atoms of R 2 , R 6 , R 7 , and R 8  is replaced with deuterium, then at least one of R 1 , R 3 , R 4 , R 5 , R 9 , and R 10  has deuterium enrichment of at least about 1%; and provided that if R 2  is —OCHF 2 , R 6  is —OCH 3 , and R 7  is —OCH 3 , and at least one of the hydrogen atoms of R 2 , R 6 , and R 7  is replaced with deuterium, then at least one of R 1 , R 3 , R 4 , R 5 , R 8 , R 9 , and R 10  has deuterium enrichment of at least about 1%; and 
         provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10  has deuterium enrichment of at least about 1%. 
         provided that said compound of Formula 1 contains at least one deuterium atom; and 
         provided that deuterium enrichment in said compound of Formula 1 is at least about 1%. 
       
     
     
         37 . The compound of  claim 36 , wherein said compound contains about 90% or more by weight of the (R)-enantiomer of said compound and about 10% or less by weight of (S)-enantiomer of said compound. 
     
     
         38 . The compound of  claim 36 , wherein said compound contains about 90% or more by weight of the (S)-enantiomer of said compound and about 10% or less by weight of (R)-enantiomer of said compound. 
     
     
         39 . The compound of  claim 36 , wherein said alkyl is selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, and tert-butyl. 
     
     
         40 . The compound of  claim 36 , wherein said alkyloxy is selected from the group consisting of methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, sec-butoxy, and tert-butoxy. 
     
     
         41 . A compound as recited in claim  1 , having a structural formula selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a single enantiomer, a mixture of enantiomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         42 . A compound having a structural formula selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a single enantiomer, a mixture of enantiomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         43 . A compound having the structural formula: 
       
         
           
           
               
               
           
         
         or a single enantiomer, a mixture of enantiomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         44 . The compound of  claim 43 , wherein said compound contains about 90% or more by weight of the (R)-enantiomer of said compound and about 10% or less by weight of (S)-enantiomer of said compound. 
     
     
         45 . The compound of  claim 43 , wherein said compound contains about 90% or more by weight of the (S)-enantiomer of said compound and about 10% or less by weight of (R)-enantiomer of said compound. 
     
     
         46 . A compound having the structural formula: 
       
         
           
           
               
               
           
         
         or a single enantiomer, a mixture of enantiomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         47 . The compound of  claim 46 , wherein said compound contains about 90% or more by weight of the (R)-enantiomer of said compound and about 10% or less by weight of (S)-enantiomer of said compound. 
     
     
         48 . The compound of  claim 46 , wherein said compound contains about 90% or more by weight of the (S)-enantiomer of said compound and about 10% or less by weight of (R)-enantiomer of said compound. 
     
     
         49 . A compound having the structural formula: 
       
         
           
           
               
               
           
         
         or a single enantiomer, a mixture of enantiomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         50 . The compound of  claim 49 , wherein said compound contains about 90% or more by weight of the (R)-enantiomer of said compound and about 10% or less by weight of (S)-enantiomer of said compound. 
     
     
         51 . The compound of  claim 49 , wherein said compound contains about 90% or more by weight of the (S)-enantiomer of said compound and about 10% or less by weight of (R)-enantiomer of said compound. 
     
     
         52 . A compound having the structural formula: 
       
         
           
           
               
               
           
         
         or a single enantiomer, a mixture of enantiomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         53 . The compound of  claim 52 , wherein said compound contains about 90% or more by weight of the (R)-enantiomer of said compound and about 10% or less by weight of (S)-enantiomer of said compound. 
     
     
         54 . The compound of  claim 52 , wherein said compound contains about 90% or more by weight of the (S)-enantiomer of said compound and about 10% or less by weight of (R)-enantiomer of said compound. 
     
     
         55 . A compound having the structural formula: 
       
         
           
           
               
               
           
         
         or a single enantiomer, a mixture of enantiomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         56 . The compound of  claim 55 , wherein said compound contains about 90% or more by weight of the (R)-enantiomer of said compound and about 10% or less by weight of (S)-enantiomer of said compound. 
     
     
         57 . The compound of  claim 55 , wherein said compound contains about 90% or more by weight of the (S)-enantiomer of said compound and about 10% or less by weight of (R)-enantiomer of said compound. 
     
     
         58 . A compound having the structural formula: 
       
         
           
           
               
               
           
         
         or a single enantiomer, a mixture of enantiomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         59 . The compound of  claim 58 , wherein said compound contains about 90% or more by weight of the (R)-enantiomer of said compound and about 10% or less by weight of (S)-enantiomer of said compound. 
     
     
         60 . The compound of  claim 58 , wherein said compound contains about 90% or more by weight of the (S)-enantiomer of said compound and about 10% or less by weight of (R)-enantiomer of said compound. 
     
     
         61 . A compound having the structural formula: 
       
         
           
           
               
               
           
         
         or a single enantiomer, a mixture of enantiomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         62 . The compound of  claim 61 , wherein said compound contains about 90% or more by weight of the (R)-enantiomer of said compound and about 10% or less by weight of (S)-enantiomer of said compound. 
     
     
         63 . The compound of  claim 61 , wherein said compound contains about 90% or more by weight of the (S)-enantiomer of said compound and about 10% or less by weight of (R)-enantiomer of said compound. 
     
     
         64 . A compound having the structural formula: 
       
         
           
           
               
               
           
         
         or a single enantiomer, a mixture of enantiomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         65 . The compound of  claim 64 , wherein said compound contains about 90% or more by weight of the (R)-enantiomer of said compound and about 10% or less by weight of (S)-enantiomer of said compound. 
     
     
         66 . The compound of  claim 64 , wherein said compound contains about 90% or more by weight of the (S)-enantiomer of said compound and about 10% or less by weight of (R)-enantiomer of said compound. 
     
     
         67 . A compound having the structural formula: 
       
         
           
           
               
               
           
         
         or a single enantiomer, a mixture of enantiomers, or a pharmaceutically acceptable salt thereof. 
       
     
     
         68 . The compound of  claim 67 , wherein said compound contains about 90% or more by weight of the (R)-enantiomer of said compound and about 10% or less by weight of (S)-enantiomer of said compound. 
     
     
         69 . The compound of  claim 67 , wherein said compound contains about 90% or more by weight of the (S)-enantiomer of said compound and about 10% or less by weight of (R)-enantiomer of said compound. 
     
     
         70 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to  claim 36 , together with a pharmaceutically acceptable carrier.

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