Nucleoside phosphoramidate prodrugs
Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.
1. A compound of formula I-6:
wherein:
(a) R 1 is H, —CH 3 , phenyl, p-bromo-phenyl, p-chloro-phenyl or p-fluoro-phenyl;
(b) R 2 is H;
(c) R 3a is H and R 3b is H, —CH 3 , —CH(CH 3 ) 2 , —CH 2 CH(CH 3 ) 2 , —CH(CH 3 )CH 2 CH 3 , —CH 2 Ph or lower cycloalkyl;
(d) R 4 is CH 3 , ethyl, n-propyl, or i-propyl;
(e) R 5 is H;
(f) R 6 is H, —CH 3 , —CH 2 F, —CHF 2 , —CF 3 or —F;
(g) X is H, —OH, —OCH 3 , —F, —NH 2 or —N 3 ;
with the proviso that X cannot be OH when R 6 is —CH 3 or —CH 2 F;
(h) Y is —OH, —NH 2 , —OCH 3 or —OC(O)CH 3 ,
(i) R 10 is —NHR′ and R 11 is —NH 2 ;
(j) Z is N or —CR 12 ;
wherein R 12 is H, halogen, —OR′, —NH 2 , —NHR′, —NR′ 2 , —NO 2 , C 1-6 alkyl, —CO 2 R′, —CONH 2 , —CONHR′, —CONR′ 2 , —CH═CHCO 2 H or —CH═CHCO 2 R′;
(k) R′ is C 1-6 alkyl; and
(l) P* is a chiral phosphorus atom;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound has a formula:
3. A compound which is:
or a pharmaceutically acceptable salt thereof.