Pyridinic sulfonamide derivatives method of production and use thereof

Abstract

New pyridinic sulfonamide derivatives represented by a general formula (I), wherein R 1 represents a mono- or polyhalogenated C 1-12 -alkyl or a mono- or polyhalogenated C 3-8 -cycloalkyl group. The method of production of such derivatives and their use as active therapeutic substance in the treatment of diseases such as inflammation, arthrosis, cancer, angiogenesis and asthma are also reported.

1 . A pyridinic sulfonamide derivative acts as COX-2 selective inhibitor, said pyridinic sulfonamide derivative being represented by a formula (I):  
     
       
         
         
             
             
         
       
     
     wherein 
 A represents a Nitrogen or a —N═O group;  
 X represents Oxygen, Sulphur or an element selected from the group consisting of —NR 3 , —CR 3 R 4 , —SO, —SO 2 , and —CO; wherein R 3  and R 4  which can be identical or different, denotes each independently one element selected from the group consisting of hydrogen, a mono- or polyhalogenated C 1-2 -alkyl, a mono- or polyhalogenated C 3-8 -cycloalkyl, a C 1-12 -alkyl and a C 3-8 -cycloalkyl;  
 R 1  represents a mono- or polyhalogenated C 1-12 -alkyl or a mono or polyhalogenated C 3-8 -cycloalkyl group;  
 R 2  represents a C 3-8 -cycloalkyl group or a non-substituted aryl group or an aryl group wherein one or more of hydrogen atom(s) of the aryl group is/are substituted by one of the elements selected from the group consisting of halogen, C 1-12 -alkyl, C 3-8 -cycloalkyl, R 1 , hydroxy, C 1-6 -alkoxy, C 1-6 -alkoxy-C 1-6 -alkyl, nitro, amino, cyano, cyanomethyl; perhalomethyl, C 1-6 -monoalkyl- or dialkylamino, sulfamoyl, C 1-6 -alkylthio, C 1-6 -alkylsulfonyl, C 1-6 -alkylsulfinyl, formyl, C 1-6 -alkylcarbonylamino, R 5 -arylthio, R 5 -arylsulfinyl, R 5 -arylsulfonyl, C 1-6 -alkoxycarbonyl, C 1-6 -alkoxycarbonyl-C 1-6 -alkyl; carbamyl; carbamylmethyl; C 1-6 -monoalkyl- or dialkylaminocarbonyl, C 1-6 -monoalkyl- or dialkylaminothiocarbonyl, ureido, C 1-6 -monoalkyl- or dialkylaminocarbonylamino, thioureido, C 1-6 -monoalkyl- or dialkylaminothiocarbonylamino, C 1-6 -monoalkyl- or dialkylaminosulfonyl, carboxy, carboxy-C 1 - 6 -alkyl, acyl, R 5 -aryl, R 5 -arylalkyl, and R 5 -aryloxy, where R 5  denotes one or several elements selected from the group consisting of hydrogen, C 1-6 -alkyl, halogen, hydroxy and C 1-6 -alkoxy.  
 
   
   
       2 . A method of preparing an active substance in a drug, said method comprising the step of utilizing a pyridinic sulfonamide derivatives, or a pharmaceutically acceptable salt thereof with a pharmaceutically acid or base or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form, said pyridinic sulfonamide derivative being represented by a formula (I):  
     
       
         
         
             
             
         
       
     
     wherein 
 A represents a Nitrogen or a —N═O group;  
 X represents Oxygen, Sulphur or an element selected from the group consisting of —NR 3 , —CR 3 R 4 , —SO, —SO 2 , and —CO; wherein R 3  and R 4  which can be identical or different, denotes each independently one element selected from the group consisting of hydrogen, a mono- or polyhalogenated C 1-12 -alkyl, a mono- or polyhalogenated C 3-8 -cycloalkyl , a C 1-12 -alkyl and a C 3-8 -cycloalkyl;  
 R 1  represents a mono- or polyhalogenated C 1-12 -alkyl or a mono or polyhalogenated C 3-8 -cycloalkyl group;  
 R 2  represents a C 3-8 -cycloalkyl group or a non-substituted aryl group or an aryl group wherein one or more of hydrogen atom(s) of the aryl group is/are substituted by one of the elements selected from the group consisting of halogen, C 1-12 -alkyl, C 3-8 -cycloalkyl, R 1 , hydroxy, C 1-6 -alkoxy, C 1-6 -alkoxy-C 1-6 -alkyl, nitro, amino, cyano, cyanomethyl; perhalomethyl, C 1-6 -monoalkyl- or dialkylamino, sulfamoyl, C 1-6 -alkylthio, C 1-6 -alkylsulfonyl, C 1-6 -alkylsulfinyl, formyl, C 1-6 -alkylcarbonylamino, R 5 -arylthio, R 5 -arylsulfinyl, R 5 -arylsulfonyl, C 1-6 -alkoxycarbonyl, C 1-6 -alkoxycarbonyl-C 1-6 -alkyl; carbamyl; carbamylmethyl; C 1-6 -monoalkyl- or dialkylaminocarbonyl, C 1-6 -monoalkyl- or dialkylaminothiocarbonyl, ureido, C 1-6 -monoalkyl- or dialkylaminocarbonylamino, thioureido, C 1-6 -monoalkyl- or dialkylaminothiocarbonylamino, C 1-6 -monoalkyl- or dialkylaminosulfonyl, carboxy, carboxy-C 1-6 -alkyl, acyl, R 5 -aryl, R 5 -arylalkyl, and R 5 -aryloxy, where R 5  denotes one or several elements selected from the group consisting of hydrogen, C 1-6 -alkyl, halogen, hydroxy and C 1-6 -alkoxy.  
 
   
   
       3 . A method of preparing a medicament comprising the step of utilizing of a pyridinic sulfonamide derivative or a pharmaceutically acceptable salt thereof with a pharmaceutically acid or base or any optical isomer or mixture of optical isomers, including a racemic mixture, or any tautomeric form, said pyridinic sulfonamide derivative being represented by a formula (I):  
     
       
         
         
             
             
         
       
     
     wherein 
 A represents a Nitrogen or a —N═O group;  
 X represents Oxygen, Sulphur or an element selected from the group consisting of —NR 3 , —CR 3 R 4 , —SO, —SO 2 , and —CO; wherein R 3  and R 4  which can be identical or different, denotes each independently one element selected from the group consisting of hydrogen, a mono- or polyhalogenated C 1-12 -alkyl, a mono- or polyhalogenated C 3-8 -cycloalkyl , a C 1-12 -alkyl and a C 3-8 -cycloalkyl;  
 R 1  represents a mono- or polyhalogenated C 1-12 -alkyl or a mono or polyhalogenated C 3-8 -cycloalkyl group;  
 R 2  represents a C 3-8 -cycloalkyl group or a non-substituted aryl group or an aryl group wherein one or more of hydrogen atom(s) of the aryl group is/are substituted by one of the elements selected from the group consisting of halogen, C 1-12 -alkyl, C 3-8 -cycloalkyl, R 1 , hydroxy, C 1-6 -alkoxy, C 1-6 -alkoxy-C 1-6 -alkyl, nitro, amino, cyano, cyanomethyl; perhalomethyl, C 1-6 -monoalkyl- or dialkylamino, sulfamoyl, C 1-6 -alkylthio, C 1-6 -alkylsulfonyl, C 1-6 -alkylsulfinyl, formyl, C 1-6 -alkylcarbonylamino, R 5 -arylthio, R 5 -arylsulfinyl, R 5 -arylsulfonyl, C 1-6 -alkoxycarbonyl, C 1-6 -alkoxycarbonyl-C 1-6 -alkyl; carbamyl; carbamylmethyl; C 1-6 -monoalkyl- or dialkylaminocarbonyl, C 1-6 -monoalkyl- or dialkylaminothiocarbonyl, ureido, C 1-6 -monoalkyl- or dialkylaminocarbonylamino, thioureido, C 1-6 -monoalkyl- or dialkylaminothiocarbonylamino, C 1-6 -monoalkyl- or dialkylaminosulfonyl, carboxy, carboxy-C 1-6 -alkyl, acyl, R 5 -aryl, R 5 -arylalkyl, and R 5 -aryloxy, where R 5  denotes one or several elements selected from the group consisting of hydrogen, C 1-6 -alkyl, halogen, hydroxy and C 1-6 -alkoxy.  
 
   
   
       4 . A method of preparing a medicament comprising the step of utilizing a pyridinic sulfonamide derivative to prepare a medicament, said pyridinic sulfonamide derivative being represented by a formula (I):  
     
       
         
         
             
             
         
       
     
     wherein 
 A represents a Nitrogen or a —N═O group;  
 X represents Oxygen, Sulphur or an element selected from the group consisting of —NR 3 , —CR 3 R 4 , —SO, —SO 2 , and —CO; wherein R 3  and R 4  which can be identical or different, denotes each independently one element selected from the group consisting of hydrogen, a mono- or polyhalogenated C 1-12 -alkyl, a mono- or polyhalogenated C 3-8 -cycloalkyl , a C 1-12 -alkyl and a C 3-8 -cycloalkyl;  
 R 1  represents a mono- or polyhalogenated C 1-12 -alkyl or a mono or polyhalogenated C 3-8 -cycloalkyl group;  
 R 2  represents a C 3-8 -cycloalkyl group or a non-substituted aryl group or an aryl group wherein one or more of hydrogen atom(s) of the aryl group is/are substituted by one of the elements selected from the group consisting of halogen, C 1-12 -alkyl, C 3-8 -cycloalkyl, R 1 , hydroxy, C 1-6 -alkoxy, C 1-6 -alkoxy-C 1-6 -alkyl, nitro, amino, cyano, cyanomethyl; perhalomethyl, C 1-6 -monoalkyl- or dialkylamino, sulfamoyl, C 1-6 -alkylthio, C 1-6 -alkylsulfonyl, C 1-6 -alkylsulfinyl, formyl, C 1-6 -alkylcarbonylamino, R 5 -arylthio, R 5 -arylsulfinyl, R 5 -arylsulfonyl, C 1-6 -alkoxycarbonyl, C 1-6 -alkoxycarbonyl-C 1-6 -alkyl; carbamyl; carbamylmethyl; C 1-6 -monoalkyl- or dialkylaminocarbonyl, C 1-6 -monoalkyl- or dialkylaminothiocarbonyl, ureido, C 1-6 -monoalkyl- or dialkylaminocarbonylamino, thioureido, C 1-6 -monoalkyl- or dialkylaminothiocarbonylamino, C 1-6 -monoalkyl- or dialkylaminosulfonyl, carboxy, carboxy-C 1-6 -alkyl, acyl, R 5 -aryl, R 5 -arylalkyl, and R 5 -aryloxy, where R 5  denotes one or several elements selected from the group consisting of hydrogen, C 1-6 -alkyl, halogen, hydroxy and C 1-6 -alkoxy.