Treatment of EBV and KHSV Infection and Associated Abnormal Cellular Proliferation

A method for treating a host with abnormal cellular proliferation or a cellular dysfunction, wherein the cell carries the Epstein-Barr virus or KHSV genome, comprising administering an effective amount of a compound of the general formula (I), (II) or (III):

• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• (i) X is O, S, NR4, CH2, CHF or CF2;
• ii) R1 is chosen from hydrogen, halogen (Cl, Br, I, F), alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, CN, CF3, N3, NO2, aryl, heteroaryl, heteroaryl, acyl or COR5 where R5 is chosen from one of H, OH, SH, alkyl, aminoalkyl, alkoxy, or thioalkyl;
• iii) R2 and R2′ are independently H, carbonyl substituted with a alkyl, alkenyl, alkynyl, aryl;
• benzyl, wherein the phenyl group is optionally substituted with one or more substituents;
• phosphate, phosphate ester, sulfonate ester including alkyl or aryl alkyl sulfonyl including methanesulfonyl;
• a lipid including a phospholipid;
• amino acid;
• peptide;
• cholesterol, or other pharmaceutically acceptable leaving group which, when administered in vivo, is capable of providing a compound wherein one or both of R2 and R2′ is H;
• iv) R3 is chosen from H, OH, halogen (F, Cl, Br, I), protected hydroxyl group or CH2OR4;
• v) R4 is independently H, acyl, alkyl, alkenyl, alkynyl or cycloalkyl;
• yl) Y is chosen from H, OH, halogen (F, Cl, Br, I), N3, CN, or OR2′;
• and
• vii) Z is 0 or S.

A method for treating a host with abnormal cellular proliferation or a cellular dysfunction, wherein the cell does not carry the EBV or KHSV genome, comprising

• (i) administering the EBV-TK or KHSV-TK gene to the cell or surrounding cells in a manner that allows the enzyme to be expressed in the cell, and then
• (ii) administering an effective amount of a compound of the general formula (I), (II) or (III):
• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• i) X is O, S, NR4, CH2, CHF or CF2;
• ii) R1 is chosen from hydrogen, halogen (Cl, Br, I, F), alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, CN, CF3, N3, NO2, aryl, heteroaryl, heteroaryl, acyl or COR5 where R5 is chosen from one of H, OH, SH, alkyl, aminoalkyl, alkoxy, or thioalkyl;
• iii) R2 and R2′ are independently H, carbonyl substituted with a alkyl, alkenyl, alkynyl, aryl;
• benzyl, wherein the phenyl group is optionally substituted with one or more substituents;
• phosphate, phosphate ester, sulfonate ester including alkyl or arylalkyl sulfonyl including methanesulfonyl;
• a lipid including a phospholipid;
• amino acid;
• peptide;
• cholesterol, or other pharmaceutically acceptable leaving group which, when administered in vivo, is capable of providing a compound wherein one or both of R2 and R2′ is H;
• iv) R3 is chosen from H, OH, halogen (F, Cl, Br, I), protected hydroxyl group or CH2OR4;
• v) R4 is independently H, acyl, alkyl, alkenyl, alkynyl or cycloalkyl;
• yl) Y is chosen from H, OH, halogen (F, Cl, Br, I), N3, CN, or OR2;
• and
• vii) Z is O or S.

A pharmaceutical composition comprising an effective amount to treat a cell carrying the Epstein-Barr virus or KHSV of a compound of the formula:

• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• i) X is O, S, NR4, CH2, CHF or CF2;
• ii) R1 is chosen from hydrogen, halogen (Cl, Br, I, F), alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, cycloalkyl, CN, CF3, N3, NO2, aryl, heteroaryl, heteroaryl, acyl or COR5 where R5 is chosen from one of H, OH, SH, alkyl, aminoalkyl, alkoxy, or thioalkyl;
• iii) R2 and R2′ are independently H, carbonyl substituted with a alkyl, alkenyl, alkynyl, aryl;
• benzyl, wherein the phenyl group is optionally substituted with one or more substituents;
• phosphate, phosphate ester, sulfonate ester including alkyl or aryl alkyl sulfonyl including methanesulfonyl;
• a lipid including a phospholipid;
• amino acid;
• peptide;
• cholesterol, or other pharmaceutically acceptable leaving group which, when administered in vivo, is capable of providing a compound wherein one or both of R2 and R2′ is H;
• iv) R3 is chosen from H, OH, halogen (F, Cl, Br, I), protected hydroxyl group or CH2OR4;
• v) R4 is independently H, acyl, alkyl, alkenyl, alkynyl or cycloalkyl;
• vi) Y is chosen from H, OH, halogen (F, Cl, Br, I), N3, CN, or OR2′;
• and
• vii) Z is 0 or S.