Carbonate prodrugs and methods of using the same
View Patent ↗The present invention provides carbonate prodrugs which comprise a carbonic phosphoric anhydride prodrug moiety attached to the hydroxyl or carboxyl group of a parent drug moiety. The prodrugs may provide improved physicochemical properties over the parent drug. Also provided are methods of treating a disease or condition that is responsive to the parent drug using the carbonate prodrugs, as well as kits and unit dosages.
1. A process for preparing a compound of the formula
or a pharmaceutically acceptable salt thereof,
comprising the steps of:
a) reacting a compound of the formula
with trifluoroacetic acid to provide the compound of the formula
and
b) optionally converting the compound of the formula
to a pharmaceutically acceptable salt.
2. The process of claim 1 , wherein step a) uses acetic acid as a solvent.
3. The process of claim 1 , wherein step a) is performed at room temperature.
4. The process of claim 1 , wherein the compound of the formula
is formed from step a) within 30 minutes.
5. The process of claim 1 , wherein the compound of the formula
of step a) is prepared by reacting the compound of the formula
with di-tert-butyl hydrogen phosphate and triethylamine.
6. The process of claim 5 , wherein chloroform is used as a solvent in the preparation of the compound of formula
7. The process of claim 5 , wherein the compound di-tert-butyl hydrogen phosphate is prepared by reacting di-tert-butyl phosphite, potassium bicarbonate, and potassium permanganate.
8. The process of claim 7 , wherein water is used as a solvent in the preparation of di-tert-butyl hydrogen phosphate.
9. The process of claim 5 , wherein the compound of the formula
is prepared by reacting 4-acetominophenol, phosgene, and N,N-diethylaniline.
10. The process of claim 9 , wherein ethyl acetate is used as a solvent in the preparation of the compound of formula