Methods and compositions for treating hepatitis C virus using 4'-modified nucleosides

A compound of Formula II:

• 20
• or a pharmaceutically acceptable salt or prodrug thereof, wherein:
• R1, R2 and R3 are independently H, mono-phosphate, di-phosphate, tri-phosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester;
• a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 and R3 are independently H or phosphate;
• Y is hydrogen, bromo, chloro, fluoro, iodo, OR4, NR4R5 or SR4;
• X1 is selected from the group consisting of H, alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, chloro, bromo, fluoro, iodo, OR4, NR4NR5 or SR4;
• and
• R4 and R5 are independently hydrogen, acyl, or alkyl.

A compound selected from Formulas III, IV and V, or a pharmaceutically acceptable salt or prodrug thereof, is provided:

• 21
• wherein:
• Base is a purine or pyrimidine base;
• R1, R2 and R3 are independently H;
• mono-phosphate, di-phosphate, tri-phosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester;
• a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 or R3 is independently H or phosphate;
• R6 is hydroxy, alkyl, azido, cyano, alkenyl, alkynyl, Br-vinyl, 2-Br-ethyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), CF3, chloro, bromo, fluoro, iodo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, —N(acyl)2;
• and
• X is O, S, SO2 or CH2.

A compound of Formula III, IV or V, or a pharmaceutically acceptable salt or prodrug thereof, is provided:

• 22
• wherein:
• Base is a purine or pyrimidine base;
• R1, R2 and R3 are independently hydrogen or phosphate;
• R6 is alkyl;
• and
• X is O, S, SO2 or CH2.

A compound of Formula III, IV or V, or a pharmaceutically acceptable salt or prodrug thereof, is provided:

• 23
• wherein:
• Base is a purine or pyrimidine base;
• R1, R2 and R3 are hydrogens;
• R6 is alkyl;
• and
• X is O, S, SO2 or CH2.

A compound of Formula III, IV or V, or a pharmaceutically acceptable salt or prodrug thereof, is provided:

• 24
• wherein:
• Base is a purine or pyrimidine base;
• R1, R2 and R3 are independently hydrogen or phosphate;
• R6 is alkyl;
• and
• X is O.

A compound of Formula IV, or its pharmaceutically acceptable salt or prodrug, is provided:

• 25
• wherein:
• Base is a purine or pyrimidine base;
• optionally substituted with an amine or cyclopropyl;
• and
• R1 and R2 are independently H;
• mono-phosphate, di-phosphate, tri-phosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester;
• a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1 or R2 is independently H or phosphate.

A compound of Formula VI, or a pharmaceutically acceptable salt or prodrug thereof:

• 26
• wherein:
• Base is a purine or pyrimidine base;
• R1 and R2 are independently H;
• mono-phosphate, di-phosphate, tri-phosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester;
• a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1 or R2 is independently H or phosphate;
• R6 is hydroxy, alkyl, azido, cyano, alkenyl, alkynyl, Br-vinyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), chloro, bromo, fluoro, iodo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, —N(acyl)2;
• R7 and R9 are independently hydrogen, OR2, hydroxy, alkyl, azido, cyano, alkenyl, alkynyl, Br-vinyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), chlorine, bromine, iodine, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, —N(acyl)2;
• R8 and R10 are independently H, alkyl, chlorine, bromine or iodine;
• alternatively, R7 and R9, R7 and R10, R8 and R9, or R8 and R10 can come together to form a pi bond;
• and
• X is O, S, SO2 or CH2.

A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of Formula I:

• 33
• or a pharmaceutically acceptable salt or prodrug thereof, together with a pharmaceutically acceptable carrier or diluent, wherein:
• R1, R2 and R3 are independently hydrogen, mono-phosphate, di-phosphate, tri-phosphate;
• a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester;
• a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 and R3 are independently hydrogen or phosphate;
• Y is hydrogen, bromo, chloro, fluoro, iodo, OR4, NR4R5 or SR4;
• X1 and X2 are independently selected from the group consisting of hydrogen, alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, chloro, bromo, fluoro, iodo, OR4, NR4NR5 or SR4;
• and
• R4 and R5 are independently hydrogen, acyl, or alkyl.

A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of Formula II:

• 34
• or a pharmaceutically acceptable salt or prodrug thereof, together with a pharmaceutically acceptable carrier or diluent, wherein:
• R1, R2 and R3 are independently H, mono-phosphate, di-phosphate, tri-phosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester;
• a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 and R3 are independently H or phosphate;
• Y is hydrogen, bromo, chloro, fluoro, iodo, OR4, NR4R5 or SR4;
• X1 is selected from the group consisting of H, alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, chloro, bromo, fluoro, iodo, OR4, NR4NR5 or SR4;
• and
• R4 and R5 are independently hydrogen, acyl, or alkyl.

A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound selected from Formulas III, IV and V, or a pharmaceutically acceptable salt or prodrug thereof, is provided:

• 35
• wherein:
• Base is a purine or pyrimidine base;
• R1, R2 and R3 are independently H;
• mono-phosphate, di-phosphate, tri-phosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester, a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 or R3 is independently H or phosphate;
• R6 is hydroxy, alkyl, azido, cyano, alkenyl, alkynyl, Br-vinyl, 2-Br-ethyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), CF3, chloro, bromo, fluoro, iodo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, —N(acyl)2;
• and
• X is O, S, SO2 or CH2.

A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of Formula VI, or a pharmaceutically acceptable salt or prodrug thereof:

• 36
• wherein:
• Base is a purine or pyrimidine base;
• R1 and R2 are independently H;
• mono-phosphate, di-phosphate, tri-phosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester, a lipid, including a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1 or R2 is independently H or phosphate;
• R6 is hydroxy, alkyl, azido, cyano, alkenyl, alkynyl, Br-vinyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), chloro, bromo, fluoro, iodo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, —N(acyl)2;
• R7 and R9 are independently hydrogen, OR2, hydroxy, alkyl, azido, cyano, alkenyl, alkynyl, Br-vinyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), chlorine, bromine, iodine, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, —N(acyl)2;
• R8 and R10 are independently H, alkyl , chlorine, bromine or iodine;
• alternatively, R7 and R9, R7 and R10, R8 and R9, or R8 and R10 can come together to form a pi bond;
• and
• X is O, S, SO2 or CH2.

A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of Formula I:

• 43
• or a pharmaceutically acceptable salt or prodrug thereof, in combination with one or more other antivirally effective agents, wherein:
• R1, R2 and R3 are independently H, mono-phosphate, di-phosphate, tri-phosphate;
• a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester, a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 and R3 are independently H or phosphate;
• Y is hydrogen, bromo, chloro, fluoro, iodo, OR4, NR4R5 or SR4;
• X1 and X2 are independently selected from the group consisting of H, alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, chloro, bromo, fluoro, iodo, OR4 NR4NR5 or SR4;
• and
• R4 and R5 are independently hydrogen, acyl, or alkyl.

A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of Formula IV:

• 44
• or a pharmaceutically acceptable salt or prodrug thereof, in combination with one or more other antivirally effective agents, wherein:
• R1, R2 and R3 are independently H, mono-phosphate, di-phosphate, tri-phosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester, a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 and R3 are independently H or phosphate;
• Y is hydrogen, bromo, chloro, fluoro, iodo, OR4, NR4R5 or SR4;
• X1 is selected from the group consisting of H, alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, chloro, bromo, fluoro, iodo, OR4, NR4NR5 or SR4;
• and
• R4 and R5 are independently hydrogen, acyl, or alkyl.

A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound selected from Formulas III, IV and V, or a pharmaceutically acceptable salt or prodrug thereof, is provided:

• 45
• wherein:
• Base is a purine or pyrimidine base;
• R1, R2 and R3 are independently H;
• phosphate mono-phosphate, di-phosphate, tr-iphosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester, a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 or R3 is independently H or phosphate;
• R6 is hydroxy, alkyl, azido, cyano, alkenyl, alkynyl, Br-vinyl, 2-Br-ethyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), CF3, chloro, bromo, fluoro, iodo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, —N(acyl)2;
• and
• X is O, S, SO2 or CH2.

A pharmaceutical composition for the treatment or prophylaxis of a hepatitis C virus in a host, comprising an effective amount of a compound of Formula VI, or a pharmaceutically acceptable salt or prodrug thereof:

• 46
• wherein:
• Base is a purine or pyrimidine base;
• R1 and R2 are independently H;
• phosphate mono-phosphate, di-phosphate, tri-phosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester;
• a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1 or R2 is independently H or phosphate;
• R6 is hydroxy, alkyl, azido, cyano, alkenyl, alkynyl, Br-vinyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), chloro, bromo, fluoro, iodo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, —N(acyl)2;
• R7 and R9 are independently hydrogen, OR2, hydroxy, alkyl, azido, cyano, alkenyl, alkynyl, Br-vinyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), chlorine, bromine, iodine, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, —N(acyl)2;
• R8 and R10 are independently H, alkyl, chlorine, bromine or iodine;
• alternatively, R7 and R9, R7 and R10, R8 and R9, or R8 and R10 can come together to form a pi bond;
• and
• X is O, S, SO2 or CH2.

A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula I:

• 53
• or a pharmaceutically acceptable salt or prodrug thereof, wherein:
• R1, R2 and R3 are independently H, mono-phosphate, di-phosphate, tri-phosphate;
• a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester;
• a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 and R3 are independently H or phosphate;
• Y is hydrogen, bromo, chloro, fluoro, iodo, OR4, NR4R5 or SR4;
• X1 and X2 are independently selected from the group consisting of H, alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, chloro, bromo, fluoro, iodo, OR4, NR4NR5 or SR4;
• and
• R4 and R5 are independently hydrogen, acyl, or alkyl.

A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula II:

• 54
• or a pharmaceutically acceptable salt or prodrug thereof, wherein:
• R1, R2 and R3 are independently H, mono-phosphate, di-phosphate, tri-phosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester;
• a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 and R3 are independently H or phosphate;
• Y is hydrogen, bromo, chloro, fluoro, iodo, OR4, NR4R5 or SR4;
• X1 is selected from the group consisting of H, alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, chloro, bromo, fluoro, iodo, OR4, NR4NR5 or SR4;
• and
• R4 and R5 are independently hydrogen, acyl, or alkyl.

A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound selected from Formulas III, IV and V, or a pharmaceutically acceptable salt or prodrug thereof, is provided:

• 55
• wherein:
• Base is a purine or pyrimidine base;
• R1, R2 and R3 are independently H;
• mono-phosphate, di-phosphate, tri-phosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester;
• a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 or R3 is independently H or phosphate;
• R6 is hydroxy, alkyl, azido, cyano, alkenyl, alkynyl, Br-vinyl, 2-Br-ethyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), CF3, chloro, bromo, fluoro, iodo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, —N(acyl)2;
• and
• X is O, S, SO2 or CH2.

A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula VI, or a pharmaceutically acceptable salt or prodrug thereof:

• 56
• wherein:
• Base is a purine or pyrimidine base;
• R1, R2 and R3 are independently H;
• mono-phosphate, di-phosphate, tri-phosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester;
• a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 or R3 is independently H or phosphate;
• R6 is hydroxy, alkyl, azido, cyano, alkenyl, alkynyl, Br-vinyl, 2-Br-ethyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), CF3, chloro, bromo, fluoro, iodo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, —N(acyl)2;
• and
• X is O, S, SO2 or CH2.

A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula I:

• 63
• or a pharmaceutically acceptable salt or prodrug thereof, in combination or alternation with one or more other antivirally effective agents, wherein:
• R1, R2 and R3 are independently H, mono-phosphate, di-phosphate, tri-phosphate;
• a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester;
• a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 and R3 are independently H or phosphate;
• Y is hydrogen, bromo, chloro, fluoro, iodo, OR4, NR4R5 or SR4;
• X1 and X2 are independently selected from the group consisting of H, alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, chloro, bromo, fluoro, iodo, OR4, NR4NR5 or SR4;
• and
• R4 and R5 are independently hydrogen, acyl, or alkyl.

A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula II:

• 64
• or a pharmaceutically acceptable salt or prodrug thereof, in combination or alternation with one or more other antivirally effective agents, wherein:
• R1, R2 and R3 are independently H, mono-phosphate, di-phosphate, tri-phosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester;
• a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 and R3 are independently H or phosphate;
• Y is hydrogen, bromo, chloro, fluoro, iodo, OR4, NR4R5 or SR4;
• X1 is selected from the group consisting of H, alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, chloro, bromo, fluoro, iodo, OR4, NR4NR5 or SR4;
• and
• R4 and R5 are independently hydrogen, acyl, or alkyl.

A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound selected from Formulas III, IV and V:

• 65
• or a pharmaceutically acceptable salt or prodrug thereof, in combination or alternation with one or more other antivirally effective agents, wherein:
• Base is a purine or pyrimidine base;
• R1, R2 and R3 are independently H;
• mono-phosphate, di-phosphate, tri-phosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester;
• a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 or R3 is independently H or phosphate;
• R6 is hydroxy, alkyl, azido, cyano, alkenyl, alkynyl, Br-vinyl, 2-Br-ethyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), CF3, chloro, bromo, fluoro, iodo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, —N(acyl)2;
• and
• X is O, S, SO2 or CH2.

A method for the treatment or prophylaxis of a hepatitis C virus infection in a host, comprising administering an anti-virally effective amount of a compound of Formula VI, or a pharmaceutically acceptable salt or prodrug thereof:

• 66
• or a pharmaceutically acceptable salt or prodrug thereof, in combination or alternation with one or more other antivirally effective agents, wherein:
• Base is a purine or pyrimidine base;
• R1, R2 and R3 are independently H;
• mono-phosphate, di-phosphate, tri-phosphate, a stabilized phosphate prodrug;
• acyl;
• alkyl;
• sulfonate ester;
• a lipid, a phospholipid;
• an amino acid;
• a carbohydrate;
• a peptide;
• a cholesterol;
• or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein R1, R2 or R3 is independently H or phosphate;
• R6 is hydroxy, alkyl, azido, cyano, alkenyl, alkynyl, Br-vinyl, 2-Br-ethyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), CF3, chloro, bromo, fluoro, iodo, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, —N(acyl)2;
• X is O, S, SO2 or CH2.
• R7 and R9 are independently hydrogen, OR2, hydroxy, alkyl (including lower alkyl), azido, cyano, alkenyl, alkynyl, Br-vinyl, —C(O)O(alkyl), —C(O)O(lower alkyl), —O(acyl), —O(lower acyl), —O(alkyl), —O(lower alkyl), —O(alkenyl), chlorine, bromine, iodine, NO2, NH2, —NH(lower alkyl), —NH(acyl), —N(lower alkyl)2, —N(acyl)2;
• R8 and R10 are independently H, alkyl, chlorine, bromine or iodine;
• alternatively, R7 and R9, R7 and R10, R8 and R9, or R8 and R10 can come together to form a pi bond;
• and
• X is O, S, SO2 or CH2.