N4-ACYLCYTOSINE NUCLEOSIDES FOR TREATMENT OF VIRAL INFECTIONS
The present invention is directed to a method and composition of treating or preventing viral infections, in particular, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections, in human patients or other animal hosts, comprising the administration of N.sup.4-acyl-2′,3′-dideoxy-5-fluorocytidine or N.sup.4-acyl-2′,3′-didehyd-ro-2′,3′-dideoxy-5-fluorocytidine, and pharmaceutically acceptable salts, prodrugs, and other derivatives thereof.
1 - 17 . (canceled)
18 . A compound of formula (I):
or a pharmaceutically acceptable salt thereof, wherein
i) X is O, S, NR 5 , CH 2 , CHF or CF 2 ;
ii) Y is CH 2 , CHF or CF 2 ;
iii) R 1 is chosen from hydrogen, halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, CN, CF 3 , N 3 , NO 2 , aryl, heteroaryl and acyl;
iv) R 2 is chosen from alkenyl, alkynyl, cycloalkyl, aminoalkyl, hydroxyalkyl, haloalkyl, thioalkyl, aryl, heteroaryl, and C 6 H 4 R 6 where R 6 is chosen from halogen, CN, CF 3 , N 3 , NO 2 , alkyl, haloalkyl, aminoalkyl, alkoxy, thioalkyl, alkenyl, alkynyl, and aryl;
v) R 3 and R 3′ are chosen independently from H, halogen, CN, CF 3 , N 3 , NO 2 , alkyl, alkenyl, and alkynyl; and
vi) R 4 is H, phosphate, carbonyl substituted with alkyl, alkenyl, alkynyl, aryl, or other pharmaceutically acceptable leaving group, which, when administered in vivo, is capable of providing a compound wherein R 3 and R 3′ are H or phosphate, sulfonate ester, a lipid, an amino acid, a peptide, or cholesterol.
vii) R 5 is H, acyl, alkyl, alkenyl, alkynyl, or cycloalkyl.
19 . A pharmaceutical composition that includes an effective HIV or HBV treatment amount of a compound of claim 18 in a pharmaceutically acceptable carrier or diluent.
20 . A method for the treatment of a host infected with HIV that includes administering an effective amount of a compound of claim 18 in a pharmaceutically acceptable carrier.
21 . A method for the treatment of a host infected with HBV that includes administering an effective amount of a compound of claim 18 in a pharmaceutically acceptable carrier.
22 . A method for the treatment of a host infected with HIV that includes administering an effective amount of a compound of claim 18 in a pharmaceutically acceptable carrier in combination with another anti-HIV agent.
23 . A method for the treatment of a host infected with HBV that includes administering an effective amount of a compound of claim 18 in a pharmaceutically acceptable carrier in combination with another anti-HBV agent.
24 . A compound of claim 18 for use in the treatment of host infected with HIV.
25 . A compound of claim 18 for use in the treatment of a host infected with HBV infection.