US2003087873A1PendingUtilityA1
Modified nucleosides for the treatment of viral infections and abnormal cellular proliferation
Priority: Oct 18, 2000Filed: Oct 18, 2001Published: May 8, 2003
Est. expiryOct 18, 2020(expired)· nominal 20-yr term from priority
A61P 9/10A61P 43/00A61P 37/06A61P 37/02A61P 29/00A61P 35/02A61P 27/02A61P 35/00A61P 31/12A61P 31/14A61P 31/16A61P 3/12A61P 31/00C12Q 1/6895A61P 17/06A61P 17/12C07H 19/048A61K 31/7076C12Q 1/6809C07H 19/16A61P 19/02C07H 21/04A61P 17/00C07H 19/10C07H 19/06A61P 13/12C12Q 1/689C07H 19/20A61K 31/7064A61P 1/16A61K 31/706Y02A50/30
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Claims
Abstract
The disclosed invention is a composition for and a method of treating 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.
Claims
exact text as granted — not AI-modifiedWe claim:
1 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (I) or (II):
or its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D is hydrogen, alkyl, acyl, monophosphate, diphosphate, triphosphate, monophosphate ester, diphosphate ester, triphosphate ester, phospholipid or amino acid;
each W 1 and W 2 is independently CH or N;
each X 1 and X 2 is independently hydrogen, halogen (F, Cl, Br or I), NH 2 , NHR 4 , NR 4 R 4′ ,NHOR 4 ,NR 4 NR 4′ R 4″ , OH, O 4 , SH or SR 4 ;
each Y 1 is O, S or Se;
each Z is CH 2 or NH;
each R 1 and R 1′ is independently hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl, alkylaryl, halogen (F, Cl, Br or I), NH 2 , NHR 5 , NR 5 R 5′ , NHOR 5 , NR 5 NHR 5′ , NR 5 NR 5′ R 5″ , OH, OR 5 , SH, SR 5 , NO 2 , NO, CH 2 OH, CH 2 R 5′ , CO 2 H, CO 2 R 5 , CONH 2 , CONHR 5 , CON 5 R 5′ or CN;
each R 2 and R 2′ independently is hydrogen or halogen (F, Cl, Br or I), OH, SH, OCH 3 , SCH 3 , NH 2 , NHCH 3 , CH═CH 2 , CN, CH 2 NH 2 , CH 2 O H, CO 2 H.
each R 3 and R 3 independently is hydrogen or halogen (F, Cl, Br or I), OH, SH, OCH 3 , SCH 3 , NH 2 , NHCH 3 , CH 3 , C 2 H 5 , CH═CH 2 , CN, CH 2 NH 2 , CH 2 O H, CO 2 H.
each R 4 , R 4′ , R 4″ , R 5 , R 5′ and R 5″ independently is hydrogen, lower alkyl, lower alkenyl, aryl, or arylalkyl such as unsubstituted or substituted phenyl or benzyl;
such that for the nucleoside of the general formula (I) or (II) at least one of R 2 and R 2 is hydrogen and at least one of R 3 and R 3′ is hydrogen.
2 . The method of claim 1 , wherein the β-D nucleoside of the formula (I-a) is selected from one of the following:
X 1
Y 1
R 1
R 1′
R 2
R 2′
R 3
R 3′
NH 2
O
H
H
OH
H
H
OH
NH 2
O
H
H
OH
H
H
I
NH 2
O
H
H
OH
H
H
Cl
NH 2
O
H
H
OH
H
H
Br
NH 2
O
H
H
OH
H
H
S—CN
NH 2
O
H
H
OH
H
H
N 3
NH 2
O
H
H
H
Cl
H
OH
NH 2
O
H
H
H
Br
H
OH
NH 2
O
H
H
H
OH
Br
H
NH 2
O
H
H
H
OH
H
H
NH 2
O
H
H
H
OH
O—Ms
H
NH 2
O
H
H
H
OH
O—Ts
H
NH 2
O
H
H
O—Ms
H
H
OH
NH 2
O
H
H
Cl
H
H
OH
NH 2
O
D
D
OH
H
H
OH
NH 2
O
F
H
OH
H
H
OH
NH 2
O
F
H
H
OH
H
OH
NH 2
O
F
H
H
OH
H
H
NH 2
O
F
H
H
OH
Cl
H
NH 2
O
F
H
H
OH
Br
H
NH 2
O
F
H
H
Cl
H
OH
NH 2
O
F
H
H
OH
O—Ts
H
NH 2
O
F
H
H
OH
O—Ms
H
NH 2
O
Cl
H
H
OH
O—Ms
H
NH 2
O
Br
H
H
OH
O—Ms
H
NH 2
O
Br
H
H
OH
O—Ts
H
NH 2
O
Br
H
H
OH
Cl
H
NH 2
O
Br
H
H
OH
H
OH
NH 2
O
Br
H
OH
H
H
OH
NH 2
O
I
H
H
OH
O—Ms
H
NH 2
O
I
H
H
OH
Br
H
NH 2
O
I
H
H
OH
O—Ts
H
NH 2
O
I
H
H
Cl
H
OH
NH 2
O
I
H
Br
H
H
OH
NH 2
O
OH
H
OH
H
H
OH
NH 2
O
NH 2
H
H
OH
H
OH
NH 2
O
CH 3
H
H
OH
Cl
H
NH 2
NH
H
H
OH
H
H
OH
NH 2
S
H
H
H
Se-
H
H
phenyl
NH-(2-Ph-Et)
O
H
H
OH
H
H
OH
NH—COCH 3
O
H
H
OH
H
H
OH
NH—NH 2
O
H
H
OH
H
H
OH
NH—NH 2
O
F
H
OH
H
H
OH
NH—NH 2
O
CH 3
H
H
OH
H
OH
NH—OH
O
H
H
H
OH
H
OH
NH—OH
O
F
H
H
OH
H
OH
NH—OH
O
Br
H
H
OH
H
OH
NH—OH
O
I
H
H
OH
H
OH
NH—OH
O
H
H
OH
H
H
OH
OH
O
OH
H
OH
H
H
OH
OH
O
NH 2
H
H
OH
H
OH
OH
O
F
H
OH
H
H
OH
OH
O
F
H
H
O—Ts
H
OH
OH
O
F
H
H
O—Ms
H
O—Ms
OH
O
F
H
H
OH
H
OH
OH
O
F
H
H
OH
H
O—Ts
OH
O
F
H
H
H
H
OH
O—Et
O
H
H
H
O—Bz
H
O—Bz
S—CH 3
O
H
H
H
F
H
OH
SH
O
H
H
H
OH
H
OH
SH
O
F
H
H
OH
H
OH
N 3
O
H
H
H
H
H
H
NH-(2-Ph-Et)
O
H
H
H
OH
H
OH
OH
O
OH
H
H
OH
H
OH
OH
O
H
H
H
OH
H
H
or its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
3 . The method of claim 1 , wherein the β-D nucleoside of the 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
H
CH
H
OH
H
F
NH 2
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
NH 2
H
CH
H
OH
H
H
Cl
H
CH
H
OH
H
H
or its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
4 . The method of claim 1 , wherein the β-D nucleoside of the formula (II-a) is selected from one of the following:
X 1
Y 1
R 1
R 1′
R 2
R 3
NH-Bz-(m-NO 2 )
O
F
H
H
H
NH-Bz-(o-NO 2 )
O
F
H
H
H
NH 2
O
F
H
F
H
or its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
5 . The method of claim 1 , wherein the β-D nucleoside of the formula (II-b) is selected from one of the following:
X 1
X 2
W 1
R 2
R 3
Cl
H
CH
F
H
OH
H
CH
H
H
NH 2
F
CH
H
H
NH 2
F
CH
F
H
NH 2
H
CH
H
H
OH
NH 2
CH
H
H
OH
H
CH
H
H
or its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
6 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (V) or (VII):
or its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, W 1 , W 2 , X 1 , X 2 , Y 1 , Z, R 1 , R 1′ , R 1′ , R 2 , R 3 and R 3′ is the same as defined previously;
such that for the nucleoside of the general formula (V) or (VI), at least one of R 2 and R 2′ is hydrogen and at least one of R 3 and R 3′ is hydrogen.
7 . The method of claim 6 , wherein the β-D nucleoside of the formula (V-a) is selected from one of the following:
X 1
Y 1
R 1
R 1′
R 2
R 2′
R 3
R 3′
NH 2
O
F
H
H
OH
H
OH
OH
H
CH 3
H
H
H
H
H
OH
O
H
H
H
H
H
H
NH 2
O
H
H
H
OH
H
OH
NH 2
O
H
H
H
H
H
H
OH
O
F
H
H
OH
H
OH
NH 2
O
I
H
H
H
H
H
NH 2
O
I
H
H
OH
H
OH
NH 2
O
Cl
H
H
OH
H
OH
or its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
8 . The method of claim 6 , wherein the β-D nucleoside of the formula (VII-a) is selected from one of the following:
X 1
Y 1
R 1
R 1′
R 2
R 2′
R 3
R 3′
NH 2
O
H
H
H
OH
H
OH
NH 2
O
F
H
H
OH
H
OH
NH—OH
O
H
H
H
OH
H
OH
or its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
9 . The method of claim 6 , wherein the β-D nucleoside of the formula (VII-b) is selected from the following:
X 1
X 2
W 1
R 2
R 2′
R 3
R 3′
NH 2
H
CH
H
OH
H
OH
or its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
10 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (XI):
or its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, W 1 , W 2 , X 1 , X 2 , Y 1 , Z, R 1 , R 1′ , R 2 , R 2′ , R 3 and R 3′ is the same as defined previously;
each Z 1 and Z 2 independently is O, S, NR 6 or Se;
each R 6 is hydrogen, lower alkyl or lower acyl.
11 . The method of claim 10 , wherein the 5-D nucleoside of the formula (XI-a) is selected from one of the following:
X 1
Y 1
Z 1
Z 2
R 1
R 1
NH 2
O
O
O
H
H
NH 2
O
O
S
F
H
NH 2
O
O
O
F
H
or its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
12 . The method of claim 10 , wherein the E-D nucleoside of the formula (XI-b) is selected from one of the following:
X 1
X 2
W 1
Z 1
Z 2
Cl
H
CH
O
S
Cl
NH 2
CH
O
S
NH 2
F
CH
O
S
OH
H
CH
O
O
or its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
13 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (XIII):
or its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, R 1 , R 1′ , R 2 , R 2′ , R 3 and R 3′ is the same as defined previously;
each Y 2 is O, S, NH or NR;
each Y 3 is O, S, NH or NR 8 ;
each X 3 is OR 9 or SR 9 ; and
each R 7 , R 8 and R 9 is hydrogen, lower alkyl of C 1 -C 6 , arylalkyl or aryl;
such that for the nucleoside of the general formula (XIII-d), at least one of R 2 and R 2′ is hydrogen and at least one of R 3 and R 3′ is hydrogen.
14 . The method of claim 13 , wherein the β-D nucleoside of the formula (XIII-a) is selected from one of the following:
Y 2
Y 3
R 1
R 1′
R 2
R 2′
R 3
R 3′
O
O
F
H
H
OH
H
OH
or its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
15 . The method of claim 13 , wherein the β-D nucleoside of the formula (XIII-c) is selected from one of the following:
Y 2
Y 3
R 1
R 1′
R 3
R 3′
O
O
F
H
H
OH
O
O
F
H
H
O—Ms
NH
O
H
H
H
O—Ms
NH
O
H
H
H
O—Ac
NH
O
H
H
H
OH
NH
O
F
H
H
OH
NH
O
F
H
H
O—Ac
or its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
16 . The method of claim 13 , wherein the β-D nucleoside of the formula (XIII-d) is selected from the following:
Y 2
X 3
R 1
R 1′
R 2
R 2′
R 3
R 3′
O
O—CH 3
H
H
H
O—Ac
H
O—Ac
or its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
17 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (XIV):
or its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, X 1 , Y 1 , Z 1 , R 1 , R 2 , R 2′ , R 3 and R 3′ is the same as defined previously;
each L 1 is hydrogen, Cl or Br;
each L 2 is OH, OCH 3 , OC 2 H 5 , OC 3 H 7 , OCF 3 , OAc or OBz;
each Z 3 can be O or CH 2 .
18 . The method of claim 17 , wherein the β-D nucleoside of the formula (XIV) is selected from one of the following:
X 1
Y 1
R 1
R 1′
R 2
R 2′
R 3
R 3′
L 1
L 2
NH 2
O
NH—OH
OH
OH
H
H
OH
H
OH
OH
O
O
F
H
OH
H
OH
Cl
O—CH 3
OH
O
O
H
H
OH
H
OH
Br
O—CH 3
OH
O
O
F
H
OH
H
OH
Br
O—COCH 3
OH
O
O
F
H
OH
H
OH
Br
O—CH 3
OH
O
O
F
H
OH
H
OH
Br
O—Et
OH
O
O
Cl
H
OH
H
OH
Br
O—CH 3
or its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
19 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (XV):
or its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, W 1 , W 2 , X 1 , Y 1 , Z 3 , R 1 , R 1′ , R 2 , R 2′ , R 3 and R 3′ is the same as defined previously.
20 . The method of claim 19 , wherein the E-D nucleoside of the formula (XV-a) is defined as the following:
Y 1
Z 3
R 1
R 1′
R 2
R 2′
R 3
R 3′
O
O
H
H
H
OH
H
OH
its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
21 . The method of claim 19 , wherein the β-D nucleoside of the formula (XV-b) is defined as the following:
X 1
W 1
Z 3
R 2
R 2′
R 3
R 3′
NH 2
CH
O
H
OH
H
OH
its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
22 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (XVI):
or its β-L enantiomer or its pharmaceuticaily acceptable salt thereof, wherein:
each D, W 1 , X 1 , X 2 , Y 1 , Z, R 1 , R 2 , R 2′ , R 3 and R 3′ is the same as defined previously;
each W 3 is independently N, CH or CR 1 ;
each W 4 and W 5 is independently N, CH, CX 1 or CR 1 ; and
each Z 4 and Z 5 is independently NH or C(═Y 1 );
such that if Z 4 and Z 5 are covalently bound, then Z 4 is not C(═Y 1 ) when Z 5 is C(═Y 1 ); and
there are no more than three ring-nitrogens.
23 . The method of claim 22 , wherein the β-D nucleoside of the formula (XVI-a) is selected as one of the following:
W 3
Z 4
W 5
W 4
Z 5
R 2
R 2′
R 3
R 3′
CH
NCH 3
C—OH
N
C═O
H
OH
H
O—Ts
CH
NH
C—NH 2
N
C═O
H
OH
H
OH
CH
NH
C—NHAc
N
C═O
H
OH
H
OH
CH
NH
C—OH
N
C═O
H
OH
H
OH
CH
NCH 3
C—NH 2
N
C═O
H
OH
H
OH
CH
NH
C—NHBz
N
C═O
H
OH
H
OH
CH
C═O
C—NH 2
C—SH
NH
H
OH
H
OH
CH
NH
C—OH
N
C═O
H
Cl
H
OH
CH
NH
C—NH 2
N
C═O
H
Br
H
OH
its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
24 . The method of claim 22 , wherein the β-D nucleoside of the formula (XVI-c) is defined as the following:
W 3
Z 4
Z 5
W 4
R 2
R 2′
R 3
R 3′
CH
N—CH 3
C═O
N
H
OH
H
O—Ac
its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
25 . The method of claim 22 , wherein the β-D nucleoside of the formula (XVI-d) is defined as the following:
W 3
Z 4
Z 5
W 4
R 3
R 3′
CH
N
C═NH
N
H
OH
its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
26 . The method of claim 22 , wherein the β-D nucleoside of the formula (XVI-f) is defined as the following:
X 1
X 2
W 1
R 2
R 2′
R 3
R 3′
NH 2
H
N
H
OH
H
OH
its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
27 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (XVII):
or its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, W 1 , W 2 , X 1 , X 2 , Y 1 , Z 3 , R 1 , R 1′ , R 2 , R 24 , R 3 and R 3′ is the same as defined previously;
each X 4 and X 5 is independently hydrogen, halogen (F, Cl, Br or I), N 3 , NH 2 , NHR 8 , NR 8 RR OH, OR 8 , SH or SR; and
each R 8 and R 8′ is independently hydrogen, lower alkyl, lower alkenyl, aryl or arylalkyl, such as an unsubstituted or substituted phenyl or benzyl;
such that for the nucleoside of the general formula (XVII-a) or (XVII-b), X 4 is not OH or OR 8 .
28 . The method of claim 27 , wherein the β-D nucleoside of the formula (XVII-d) is defined as the following:
X 1
X 2
W 1
X 3
X 4
NH 2
F
CH
H
OH
its β-L-enantiomer or its pharmaceutically acceptable salt thereof.
29 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (XVIII):
or its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, W 1 , W 2 , X 1 , X 2 , Y 1 , R 1 R 1′ , R 2 , R 2′ , R 3 and R 3′ is the same as defined previously;
30 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (XIX):
or its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, R 1 , R 4 and R 4′ is the same as defined previously;
each R 9 is hydrogen, halogen (F, Cl, Br or I) or
each P 1 is hydrogen, lower alkyl, lower alkenyl, aryl, arylalkyl (such as an unsubstituted or substituted phenyl or benzyl), OH, OR 4 , NH 2 , NUR 4 or NR 4 R 4′ ; and
each P 2 and P 3 is independently hydrogen, alkyl, acyl, -Ms, -Ts, monophosphate, diphosphate, triphosphate, mono-phosphate ester, diphosphate ester, triphosphate ester, phospholipid or amino acid.
31 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula:
or its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein: each D and P 2 is the same as defined previously.
32 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (XX):
its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, P 1 , P 2 , P 3 , R 1 , R 4 , R 4′ and R 9 is the same as defined previously.
33 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (XXI):
its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein: each D, P 1 , P 2 , P 3 , R 1 , R 4 and R 4′ is the same as defined previously.
34 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula:
its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, P 2 and P 3 is the same as defined previously.
35 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (XXII):
its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, P 1 and R 1 is the same as defined previously.
36 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula:
its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
D is the same as defined previously.
37 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (XXIII):
its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, P 1 , P 2 , P 3 , R 1 , R 4 and R 4′ is the same as defined previously.
38 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administrating an effective amount of a compound of the general formula:
its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, P 2 , and P 3 , is the same as defined previously.
39 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthornyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula:
or its pharmaceutically acceptable salt thereof.
40 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula:
or its pharmaceutically acceptable salt thereof.
41 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula:
or its pharmaceutically acceptable salt thereof.
42 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (I) or (II):
or its pharmaceutically acceptable salt thereof.
43 . A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula:
or its pharmaceutically acceptable salt thereof.
44 . A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a compound according to any one of claims 1 - 29 .
45 . A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a β-D nucleoside of the formula (XIX):
its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, R 1 , R 4 and R 4′ is the same as defined previously;
each R 9 is hydrogen, halogen (F, Cl, Br or I) or OP 3 ;
each P 1 is hydrogen, lower alkyl, lower alkenyl, aryl, arylalkyl (such as an unsubstituted or substituted phenyl or benzyl), OH, OR 4 , NH 2 , NHR 4 or NR 4 R 4′ ; and
each P 2 and P 3 is independently hydrogen, alkyl, acyl, -Ms, -Ts, monophosphate, diphosphate, triphosphate, mono-phosphate ester, diphosphate ester, triphosphate ester, phospholipid or amino acid;
optionally in a pharmaceutically acceptable carrier.
46 . A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a E-D nucleoside of the formula:
its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D and P 2 is the same as defined previously;
optionally in a pharmaceutically acceptable carrier.
47 . A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a 1-D nucleoside of the formula (XX):
its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, P 1 , P 2 , P 3 , R 1 , R 4 , R 4′ and R 9 is the same as defined previously;
optionally in a pharmaceutically acceptable carrier.
48 . A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a β-D nucleoside of the formula (XXI):
its 1-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, P 1 , P 2 , P 3 , R 1 , R 4 and R 4′ is the same as defined previously;
optionally in a pharmaceutically acceptable camrer.
49 . A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a β-D nucleoside of the formula:
its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, P 2 and P 3 is the same as defined previously;
optionally in a pharmaceutically acceptable carrier.
50 . A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a β-D nucleoside of the formula (XXII):
its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, P 1 and R 1 is the same as defined previously;
optionally in a pharmaceutically acceptable carrier.
51 . A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a β-D nucleoside of the formula:
its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
D is the same as defined previously;
optionally in a pharmaceutically acceptable carrier.
52 . A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a β-D nucleoside of the formula (XXIII):
its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, P 1 , P 2 , P 3 , R 1 , R 4 and R 4′ is the same as defined previously;
optionally in a pharmaceutically acceptable carrier.
53 . A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a β-D nucleoside of the formula (XXIII) is the following:
its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein:
each D, P 2 and P 3 is the same as defined previously;
optionally in a pharmaceutically acceptable carrier.
54 . A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a nucleoside of the formula:
or its pharmaceutically acceptable salt thereof; optionally in a pharmaceutically acceptable carrier.
55 . A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a nucleoside of the formula:
or its pharmaceutically acceptable salt thereof; optionally in a pharmaceutically acceptable carrier.
56 . A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a nucleoside of the formula:
or its pharmaceutically acceptable salt thereof; optionally in a pharmaceutically acceptable carrier.
57 . A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a nucleoside of the formula:
or its pharmaceutically acceptable salt thereof; optionally in a pharmaceutically acceptable carrier.
58 . A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a nucleoside of the formula:
or its pharmaceutically acceptable salt thereof; optionally in a pharmaceutically acceptable carrier.Cited by (0)
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