Treatment of metabolic disorders in equine animals

Abstract

The present invention relates to SGLT2 inhibitor or a pharmaceutically acceptable form thereof for use in the treatment and/or prevention of a metabolic disorder of an equine animal. In particular, the present invention relates the SGLT2 inhibitor or a pharmaceutically acceptable form thereof for use in the treatment and/or prevention of insulin resistance, hyperinsulinemia, impaired glucose tolerance, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, obesity, and/or regional adiposity in an equine animal.

What is claimed is: 
     
         1 . An SGLT2 inhibitor or a pharmaceutically acceptable form thereof for use in the treatment and/or prevention of a metabolic disorder of an equine animal. 
     
     
         2 . The SGLT2 inhibitor or a pharmaceutically acceptable form thereof for a use according to  claim 1 , wherein the metabolic disorder is one or more disorders selected from insulin resistance, hyperinsulinemia, impaired glucose tolerance, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, obesity, and/or regional adiposity, wherein preferably the metabolic disorder is insulin resistance, hyperinsulinemia, and/or a clinical condition associated with insulin resistance and/or hyperinsulinaemia. 
     
     
         3 . The SGLT2 inhibitor or pharmaceutically acceptable form thereof for a use according to  claim 2 , wherein said clinical condition is one or more conditions selected from impaired glucose tolerance, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, obesity, and/or regional adiposity. 
     
     
         4 . The SGLT2 inhibitor or pharmaceutically acceptable form thereof for a use according to  claim 3 , wherein the equine animal is suffering from one or more of impaired glucose tolerance, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, which also comprises adipose tissue, obesity, and/or regional adiposity. 
     
     
         5 . The SGLT2 inhibitor or pharmaceutically acceptable form thereof for a use according to  claim 4 , wherein said impaired glucose tolerance, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, obesity, and/or regional adiposity is associated with insulin resistance and/or hyperinsulinemia. 
     
     
         6 . The SGLT2 inhibitor or pharmaceutically acceptable form thereof for a use according to  claim 1 , wherein the metabolic disorder is hyperinsulinemia and/or insulin resistance, wherein said hyperinsulinemia or insulin resistance is optionally associated with one or more of impaired glucose tolerance, dyslipidemia, dysadipokinemia, subclinical inflammation, systemic inflammation, low grade systemic inflammation, which also comprises adipose tissue, obesity, and/or regional adiposity. 
     
     
         7 . The SGLT2 inhibitor or pharmaceutically acceptable form thereof for a use according to  claim 1 , wherein the equine animal is a horse or a pony. 
     
     
         8 . The SGLT2 inhibitor or pharmaceutically acceptable form thereof for a use according to  claim 1 , wherein the equine animal is obese and/or exhibits regional adiposity. 
     
     
         9 . The pharmaceutically acceptable form of an SGLT2 inhibitor for a use according to  claim 1 , wherein the pharmaceutically acceptable form is a crystalline complex between the SGLT2 inhibitor and one or more amino acids, preferably wherein the one or more amino acids is proline. 
     
     
         10 . The SGLT2 inhibitor or pharmaceutically acceptable form thereof for a use according to  claim 1 , for oral or parenteral administration, preferably for oral administration. 
     
     
         11 . The SGLT2 inhibitor or a pharmaceutically acceptable form thereof for a use according to  claim 1 , for the administration of 0.01 to 3.0 mg/kg body weight per day. 
     
     
         12 . The SGLT2 inhibitor or pharmaceutically acceptable form thereof for a use according to  claim 1 , wherein such SGLT2 inhibitor or pharmaceutically acceptable form is to be administered only once per day. 
     
     
         13 . The SGLT2 inhibitor or pharmaceutically acceptable form thereof for a use according to  claim 1 , wherein the SGLT2 inhibitor is a glucopyranosyl-substituted benzene derivative. 
     
     
         14 . A SGLT2 inhibitor or pharmaceutically acceptable form thereof for a use according to  claim 1 , wherein said SGLT2 inhibitor is selected from the group consisting of:
 (1) a glucopyranosyl-substituted benzene derivative of the formula (1)   
       
         
           
           
               
               
           
         
         
           wherein R 1  denotes cyano, Cl or methyl; 
           R 2  denotes H, methyl, methoxy or hydroxyl; and 
           R 3  denotes cyclopropyl, hydrogen, fluorine, chlorine, bromine, iodine, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, 3-methyl-but-1-yl, cyclobutyl, cyclopentyl, cyclohexyl, 1-hydroxy-cyclopropyl, 1-hydroxy-cyclobutyl, 1-hydroxy-cyclopentyl, 1-hydroxy-cyclohexyl, ethinyl, ethoxy, difluoromethyl, trifluoromethyl, pentafluoroethyl, 2-hydroxyl-ethyl, hydroxymethyl, 3-hydroxy-propyl, 2-hydroxy-2-methyl-prop-1-yl, 3-hydroxy-3-methyl-but-1-yl, 1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-methyl-ethyl, 2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl, 2-methoxy-ethyl, 2-ethoxy-ethyl, hydroxy, difluoromethyloxy, trifluoromethyloxy, 2-methyloxy-ethyloxy, methylsulfanyl, methylsulfinyl, methlysulfonyl, ethylsulfinyl, ethylsulfonyl, trimethylsilyl, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy or cyano, 
           or a derivative thereof wherein one or more hydroxyl groups of the β-D-glucopyranosyl group are acylated with groups selected from (C 1-18 -alkyl)carbonyl, (C 1-18 -alkyl)oxycarbonyl, phenylcarbonyl and phenyl-(C 1-3 -alkyl)-carbonyl; 
         
         (2) 1-cyano-2-(4-cyclopropyl-benzyl)-4-(β-D-glucopyranos-1-yl)-benzene, represented by formula (2): 
       
       
         
           
           
               
               
           
         
         (3) Dapagliflozin, represented by formula (3): 
       
       
         
           
           
               
               
           
         
         (4) Canagliflozin, represented by formula (4): 
       
       
         
           
           
               
               
           
         
         (5) Empagliflozin, represented by formula (5): 
       
       
         
           
           
               
               
           
         
         (6) Luseogliflozin, represented by formula (6): 
       
       
         
           
           
               
               
           
         
         (7) Tofogliflozin, represented by formula (7): 
       
       
         
           
           
               
               
           
         
         (8) Ipragliflozin, represented by formula (8): 
       
       
         
           
           
               
               
           
         
         (9) Ertugliflozin, represented by formula (9): 
       
       
         
           
           
               
               
           
         
         (10) Atigliflozin, represented by formula (10): 
       
       
         
           
           
               
               
           
         
         (11) Remogliflozin, represented by formula (11): 
       
       
         
           
           
               
               
           
         
         (12) a thiophene derivative of the formula (12) 
       
       
         
           
           
               
               
           
         
         
           wherein R denotes methoxy or trifluoromethoxy; 
         
         (13) 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene; represented by formula (13); 
       
       
         
           
           
               
               
           
         
         (14) a spiroketal derivative of the formula (14): 
       
       
         
           
           
               
               
           
         
         
           wherein R denotes methoxy, trifluoromethoxy, ethoxy, ethyl, isopropyl or tert. butyl; 
         
         (15) a pyrazole-O-glucoside derivative of the formula (15) 
       
       
         
           
           
               
               
           
         
         
           wherein 
           R 1  denotes C 1-3 -alkoxy, 
           L 1 , L 2  independently of each other denote H or F, 
           R 6  denotes H, (C 1-3 -alkyl)carbonyl, (C 1-6 -alkyl)oxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl or benzylcarbonyl; 
         
         (16) a compound of the formula (16): 
       
       
         
           
           
               
               
           
         
         (17) Sergliflozin, represented by formula (17): 
       
       
         
           
           
               
               
           
         
         (18) a compound represented by formula (18): 
       
       
         
           
           
               
               
           
         
         
           wherein R 3  is selected from cyclopropyl, ethyl, ethinyl, ethoxy, (R)-tetrahydrofuran-3-yloxy or (S)-tetrahydrofuran-3-yloxy). 
         
       
     
     
         15 . A pharmaceutical composition comprising the SGLT2 inhibitor of  claim 14  or a pharmaceutically acceptable form thereof.