Provided are novel prodrug salts of selective aquaporin inhibitors, their use as pharmaceuticals, and pharmaceutical compositions comprising them, and novel processes for their synthesis and novel intermediates for use in their synthesis. Also provided is use of a compound for the prophylaxis, treatment, and control of aquaporin-mediated conditions. Aquaporin inhibitors, e.g., inhibitors of AQP4 and/or AQP2, may be of utility in the treatment or control of diseases of water imbalance, for example edema (particularly edema of the brain and spinal cord), hyponatremia, and excess fluid retention, as well as diseases such as epilepsy, retinal ischemia and other diseases of the eye, myocardial ischemia, myocardial ischemia/reperfusion injury, myocardial infarction, myocardial hypoxia, congestive heart failure, sepsis, and neuromyelitis optica, as well as migraines.
1. A compound of Formula III
wherein:
R 30 , R 31 , R 32 , R 33 , and R 34 are independently H, halogen, C 1-4 -alkyl, C 1-4 -haloalkyl, or cyano; and
R 35 and R 36 are independently —(CH 2 CH 2 ) n —Si(R 37 ) 3 , wherein each R 37 is independently C 1-6 -alkyl and n is 0 or 1.
2. The compound of claim 1 , wherein R 30 , R 32 , and R 34 are independently halogen or C 1-4 -haloalkyl and R 31 and R 33 are H.
3. The compound of claim 1 , wherein R 30 , R 32 , and R 34 are independently F, Cl, Br, or —CF 3 and R 31 and R 33 are H.
4. The compound of claim 1 , wherein R 30 is halogen, R 31 and R 33 are H, and R 32 and R 34 are independently C 1-4 -haloalkyl.
5. The compound of claim 1 , wherein R 30 is Cl and R 32 and R 34 are —CF 3 .
6. The compound of claim 1 , wherein each R 37 is independently C 1-4 -alkyl.
7. The compound of claim 1 , wherein R 35 and R 36 are the same.
8. The compound of claim 1 , wherein R 35 and R 36 are —CH 2 —CH 2 —Si(CH 3 ) 3 .
9. The compound of claim 1 , wherein the compound is