Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1

Abstract

The present invention relates to using a compound having the formula (I) wherein T is I) thienyl, which optionally is substituted with halogen, or II) phenyl optionally substituted with halogen and/or C 1-6 -alkyl; E is a bond, —CH 2 — or —CO—; L is a bond, —CH 2 —, —CHR 4 — or —NR 3 —; R 3 is H, C 1-6 -alkyl, C 1-6 -acyl or —COR 4 ; R 4 is morpholino or C 1-6 -amido; R 6 and R 7 are independently hydrogen or C 1-6 -alkyl; and R 8 and R 9 are independently hydrogen or C 1-6 -alkyl, as well as pharmaceutically acceptable salts, hydrates and solvates thereof, in the manufacture of a medicament for the treatment or prevention of diabetes, syndrome X, obesity, glaucoma, hyperlipidemia, hyperglycemia, hyperinsulinemia, osteoporosis, tuberculosis, dementia, depression, virus diseases and inflammatory disorders.

1 - 12 . (canceled)  
   
   
       13 . A method for the treatment or prevention of osteoporosis, cognitive impairment, depression, virus diseases and inflammatory disorders and to achieve immuno-modulation, said method comprising administering to a mammal, including man, in need of such treatment, an effective amount of a compound having the formula (I)  
     
       
         
         
             
             
         
       
     
     wherein 
 T is  
 I) thienyl, which optionally is substituted with at least one halogen or  
 II) phenyl substituted with  
 a) at least one of C 2-6  alkyl; or  
 b) at least one C 1-6  alkyl and at least one halogen; or  
 c) at least three halogens;  
 E is a bond, —CH 2 — or —CO—;  
 L is a bond, —CH 2 —, —CHR 4 — or —NR 3 —;  
 R 3  is H, C 1-6  alkyl, C 1-6  acyl or —COR 4 —;  
 R 4  is morpholinyl or C 1-6  amido;  
 R 6  and R 7  are independently hydrogen or C 1-6  alkyl and  
 R 8  and R 9  are independently hydrogen or C 1-6  alkyl, as well as pharmaceutically acceptable salts, hydrates and solvates thereof.  
 
   
   
       14 . A method according to  claim 13 , wherein the immuno-modulation is achieved by the treatment or prevention of tuberculosis, lepra and psorasis.  
   
   
       15 . A method according to  claim 13 , wherein 
 T is    I) thienyl, which optionally is substituted with at least one halogen selected from chloro and bromo, or    II) phenyl substituted with    a) at least one n-propyl; or    b) at least one methyl and at least one halogen selected from chloro and bromo; or    c) at least three halogens selected from fluoro, bromo and chloro;    E is a bond, —CH 2 — —CO—;    L is a bond, —CH 2 —, —CHR 4 — or —NR 3 —;    R 3  is methyl, acetyl or —COR 4 ;    R 4  is morpholinyl or propionamido;    R 6  and R 7  are both hydrogen; and    R 8  and R 9  are independently hydrogen or methyl.    
   
   
       16 . A method according to  claim 13 , wherein the compound is selected from the group of: 
 N-(5-Acetyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-yl)-3-chloro-2-methylbenzenesulfonamide;    2,4-dichloro-6-methyl-N-(5,6,6-trimethyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridine-2-yl)benzenesulfonamide;    2,4-dichloro-6-methyl-N-[5-(4-morpholinylcarbonyl)-4,5,6,7-tetrahydro [1,3]thiazolo[5,4-c]pyridin-2-yl]benzenesulfonamide;    2,4-Dichloro-6-methyl-N-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)benzenesulfonamide;    4-Bromo-N-(5,6-dihydro-4H-cyclopenta[d][1,3]thiazol-2-yl)-2,5-difluorobenzenesulfonamide;    2,3,4-Trichloro-N-(5,6-dihydro-4H-cyclopenta[d][1,3]thiazol-2-yl)benzenesulfonamide;    N-(2-{[(2,4-dichloro-6-methylphenyl)sulfonyl]amino}-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl)propanamide;    2,4-Dichloro-N-(5,5-dimethyl-7-oxo-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)-6-methylbenzenesulfonamide;    2,3,4-Trichloro-N-(5,5-dimethyl-7-oxo-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)benzenesulfonamide;    4,5-Dichloro-N-(5,5-dimethyl-7-oxo-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)-2-thiophenesulfonamide;    4-Bromo-5-chloro-N-(5,5-dimethyl-7-oxo-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)-2-thiophenesulfonamide;    3-Bromo-5-chloro-N-(5,5-dimethyl-7-oxo-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)-2-thiophenesulfonamide;    N-(5-Methyl-7-oxo-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)-4-propylbenzenesulfonamide;    4,5-Dichloro-N-(5-methyl-7-oxo-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)-2-thiophenesulfonamide;    2,4-Dichloro-6-methyl-N-(5-methyl-7-oxo-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)benzenesulfonamide; and    4-Bromo-2-methyl-N-(5-methyl-7-oxo-4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)benzenesulfonamide, and    pharmaceutically acceptable salts, hydrates and solvates thereof.