Deuterated secnidazole for use in the treatment of bacterial vaginosis and methods and uses thereof

Abstract

The present invention is related to deuterated secnidazole, a prodrug thereof, a hydrate thereof, a solvate thereof, a polymorph thereof, or a pharmaceutically acceptable salt thereof and its use for the treatment of bacterial vaginosis or trichomoniasis in a subject in need thereof. The present invention is also related to pharmaceutical compositions and methods and uses of treating bacterial vaginosis, trichomoniasis, amoebiasis, giardiasis, or a combination thereof.

What is claimed is: 
     
         1 . A compound of formula I: 
       
         
           
           
               
               
           
         
         or a prodrug thereof, a hydrate thereof, a solvate thereof, a polymorph thereof, or a pharmaceutically acceptable salt thereof, 
         wherein X 1  to X 10  are independently selected from the group consisting of hydrogen and deuterium, and at least one of X 1  to X 10  is deuterium. 
       
     
     
         2 . The compound according to  claim 1 , wherein:
 (a) one or more of X 4 , X 5 , X 6 , X 7 , X 8 , and X 9  is deuterium;   (b) one or more of X 1 , X 2 , and X 3  is deuterium;   (c) X 10  is deuterium; or   (d) a combination thereof.   
     
     
         3 . The compound according to  claim 1 , wherein X 10  is deuterium and X 1  to X 9  are hydrogen. 
     
     
         4 . The compound according to  claim 1 , wherein X 10  is hydrogen and X 1  to X 9  are deuterium. 
     
     
         5 . The compound according to  claim 1 , wherein X 1  to X 10  are deuterium. 
     
     
         6 . The compound according to  claim 1 , wherein X 1 , X 2 , and X 3  are deuterium and X 4 , X 5 , X 6 , X 7 , X 8 , and X 9  are hydrogen. 
     
     
         7 . The compound according to  claim 1 , wherein X 1 , X 2 , and X 3  are hydrogen and X 4 , X 5 , X 6 , X 7 , X 8 , and X 9  are deuterium. 
     
     
         8 . The compound according to  claim 1 , wherein X 1 , X 2 , and X 3  are deuterium and X 10  is hydrogen. 
     
     
         9 . The compound according to  claim 1 , wherein X 5 , X 6 , X 7 , X 8 , and X 9  are deuterium and X 10  is hydrogen. 
     
     
         10 . A pharmaceutical composition comprising (a) the compound of formula I, a prodrug thereof, a hydrate thereof, a solvate thereof, a polymorph thereof, a pharmaceutically acceptable salt thereof of  claim 1 , or a combination thereof, and (b) at least one pharmaceutically acceptable carrier. 
     
     
         11 . The pharmaceutical composition according to  claim 10 , wherein the amount of the compound of formula I, the prodrug thereof, the hydrate thereof, the solvate thereof, the polymorph thereof, or the pharmaceutically acceptable salt thereof in the pharmaceutical composition is from about 0.1 mg to about 2000 mg. 
     
     
         12 . The pharmaceutical composition according to  claim 10 , wherein the pharmaceutical composition is in the form of a tablet, granules, microgranules, vaginal suppository, soft gelatin capsule, taste-masked tablet, taste-masked granules, taste-masked microgranules, or a combination thereof. 
     
     
         13 . The pharmaceutical composition according to  claim 10 , wherein the pharmaceutical composition is in the form of a plurality of granules, a plurality of microgranules, a plurality of taste-masked granules, a plurality of taste-masked microgranules, or a combination thereof. 
     
     
         14 . The pharmaceutical composition according to  claim 10 , further comprising at least one pharmaceutically acceptable excipient. 
     
     
         15 . The pharmaceutical composition according to  claim 14 , wherein the pharmaceutically acceptable excipient is selected from a group consisting of an inert core, a dispersion agent, a binding agent, a coating agent, a modified release coating agent, an anti-tacking agent, and a combination thereof. 
     
     
         16 . The pharmaceutical composition according to  claim 10 , wherein the elimination half-life of the compound of formula I, the prodrug thereof, the hydrate thereof, the solvate thereof, the polymorph thereof, or the pharmaceutically acceptable salt thereof is from about 29 hours to about 58 hours. 
     
     
         17 . The pharmaceutical composition according to  claim 16 , wherein the elimination half-life of the compound of formula I, the prodrug thereof, the hydrate thereof, the solvate thereof, the polymorph thereof, or the pharmaceutically acceptable salt thereof is from about 34 hours to about 58 hours. 
     
     
         18 . A method for treating bacterial vaginosis, trichomoniasis, amoebiasis, giardiasis, or a combination thereof in a subject in need thereof comprising:
 selecting the subject in need of treatment for bacterial vaginosis, trichomoniasis, amoebiasis, giardiasis, or a combination thereof; and   administering to the subject a therapeutically effective amount of a compound of formula I, wherein the compound of formula I is:   
       
         
           
           
               
               
           
         
         or a prodrug thereof, a hydrate thereof, a solvate thereof, a polymorph thereof, or a pharmaceutically acceptable salt thereof, 
         wherein X 1  to X 10  are independently selected from the group consisting of hydrogen and deuterium, and at least one of X 1  to X 10  is deuterium. 
       
     
     
         19 . The method according to  claim 18 , wherein:
 (a) one or more of X 4 , X 5 , X 6 , X 7 , X 8 , and X 9  is deuterium;   (b) one or more of X 1 , X 2 , and X 3  is deuterium;   (c) X 10  is deuterium; or   (d) a combination thereof.   
     
     
         20 . The method according to  claim 18 , wherein X 10  is deuterium and X 1  to X 9  are hydrogen. 
     
     
         21 . The method according to  claim 18 , wherein X 10  is hydrogen and X 1  to X 9  are deuterium. 
     
     
         22 . The method according to  claim 18 , wherein X 1  to X 10  are deuterium. 
     
     
         23 . The method according to  claim 18 , wherein X 1 , X 2 , and X 3  are deuterium and X 4 , X 5 , X 6 , X 7 , X 8 , and X 9  are hydrogen. 
     
     
         24 . The method according to  claim 18 , wherein X 1 , X 2 , and X 3  are hydrogen and X 4 , X 5 , X 6 , X 7 , X 8 , and X 9  are deuterium. 
     
     
         25 . The method according to  claim 18 , wherein X 1 , X 2 , and X 3  are deuterium and X 10  is hydrogen. 
     
     
         26 . The method according to  claim 18 , wherein X 5 , X 6 , X 7 , X 8 , and X 9  are deuterium and X 10  is hydrogen. 
     
     
         27 . The method according to  claim 18 , wherein the subject is human female or a pregnant human female. 
     
     
         28 . The method according to  claim 18 , wherein the therapeutically effective amount of compound of formula I is from about 0.1 mg to about 2000 mg. 
     
     
         29 . The method according to  claim 18 , wherein the therapeutically effective amount of the compound of formula I is administered as a single dose. 
     
     
         30 . The method according to  claim 18 , wherein the therapeutically effective amount of the compound of formula I is administered orally. 
     
     
         31 . The method according to  claim 18 , wherein the therapeutically effective amount of the compound of formula I is co-administered with an additional compound selected from ethinyl estradiol (EE2), norethindrone (NET), and a combination thereof. 
     
     
         32 . The method according to  claim 31 , wherein the additional compound is administered on the same day or a different day as the therapeutically effective amount of the compound of formula I. 
     
     
         33 . The method according to  claim 31 , wherein the compound of formula I does not affect the contraceptive efficacy of the additional compound. 
     
     
         34 . The method according to  claim 18 , wherein the composition of formula I is in the form of a tablet, granules, microgranules, vaginal suppository, soft gelatin capsule, taste-masked tablet, taste-masked granules, taste-masked microgranules, or a combination thereof. 
     
     
         35 . The method according to  claim 18 , wherein the compound of formula I is in the form of a plurality of granules, a plurality of microgranules, a plurality of taste-masked granules, a plurality of taste-masked microgranules, or a combination thereof. 
     
     
         36 . The method according to  claim 18 , wherein the compound of formula I is administered to the subject as a pharmaceutical composition. 
     
     
         37 . The method according to  claim 36 , wherein the pharmaceutical composition further comprises at least one pharmaceutically acceptable excipient, at least one pharmaceutically acceptable carrier, or a combination thereof. 
     
     
         38 . The method according to  claim 37 , wherein the pharmaceutically acceptable excipient is selected from a group consisting of an inert core, a dispersion agent, a binding agent, a coating agent, a modified release coating agent, an anti-tacking agent, and a combination thereof. 
     
     
         39 . The method according to  claim 18 , wherein the elimination half-life of the compound of formula I, the prodrug thereof, the hydrate thereof, the solvate thereof, the polymorph thereof, or the pharmaceutically acceptable salt thereof is from about 29 hours to about 58 hours. 
     
     
         40 . The method according to  claim 18 , wherein the elimination half-life of the compound of formula I, the prodrug thereof, the hydrate thereof, the solvate thereof, the polymorph thereof, or the pharmaceutically acceptable salt thereof is from about 34 hours to about 58 hours.