Modified nucleosides for the treatment of viral infections and abnormal cellular proliferation
The disclosed invention is a composition for and a method of seating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug. This invention also provides an effective process to quantify the viral load, and in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase chain reaction (“RT-PCR”). Additionally, the invention discloses probe molecules that can fluoresce proportionally to the amount of virus present in a sample.
1. A method of treating a viral infection or abnormal cellular proliferation in a human exhibiting the viral infection or abnormal cellular proliferation, wherein the viral infection is not caused by Human Immunodeficiency Virus, comprising administering to the human an effective amount of a compound of the general formula (I-b)
or its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
D is hydrogen;
W 2 is N; and
wherein the compound of formula (I-b) is selected from one of the following:
X 1
X 2
W 1
R 2
R 2 ′
R 3
R 3 ′
OH
NH 2
N
H
OH
H
OH
OH
NH 2
CH
F
H
H
OH
NH-cyclohexyl
H
CH
H
H
H
H
NH 2
NH 2
N
H
OH
H
OH
NH 2
NH 2
CH
H
OH
H
OH
Cl
H
CH
F
H
H
H
Cl
I
CH
H
O—Ac
H
O—Ac
Cl
H
CH
H
OH
H
OH
Cl
H
CH
H
OH
H
H
NH 2
H
CH
H
OH
H
F.
2. The method of claim 1 wherein the viral infection is Flaviviridae.
3. The method of claim 1 wherein the viral infection is Orthomyxoviridae.
4. The method of claim 1 wherein the viral infection is Paramyxoviridae.
5. The method of claim 1 wherein the compound is selected from the group consisting of