Nucleotide mimics and their prodrugs
First Claim
1. A compound of Formula (I) which may be a D- or L-nucleotide:
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Accused Products
Abstract
The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.
-
Citations
50 Claims
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1. A compound of Formula (I) which may be a D- or L-nucleotide:
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 39, 47, 49, 50)
-
2. The compound defined in claim 1 of Formula (V):
-
3. The compound defined in claim 1 of Formula (VI):
-
4. The compound defined in claim 1 of Formula (VII):
-
5. The compound defined in claim 4
wherein X2 is O; - and
wherein X7 is SH, NH2, −
BH3M+, alkyl, aryl, alkylamino, or arylamino.
- and
-
6. The compound defined in claim 4
wherein X2 is O; - and
wherein X7 is selected from the group consisting of SH, NH2, −
BH3M+, R, and NHR.
- and
-
7. The compound defined in claim 1 of Formula (VIII):
-
8. The compound defined in claim 1 of Formula (VIII):
-
wherein X9 and X10 are selected independently from the group consisting of acylthioethoxy, acyloxymethoxy, 1,2-O-diacylglyceroxy, 1,2-O-dialkylglyceroxy, and 1-O-alkyl-2-O-acylglyceroxy
-
-
9. The compound defined in claim 1 of Formula (VIII):
-
10. The compound defined in claim 8 wherein at least one of X9 and X10 is 1,2-O-dialkylglyceryloxy.
-
11. The compound defined in claim 1 of Formula (IX):
-
12. The compound defined in claim 1 of Formula (IX):
-
13. The compound defined in claim 1 of Formula (X):
-
14. The compound defined in claim 1 of Formula (X):
-
39. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 1, a pharmaceutically acceptable salt thereof, optionally in combination with one or more other active ingredients and/or with a pharmaceutically acceptable carrier.
-
47. The compound of claim 1 where D is thymine.
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49. A method for the treatment of a microbial infection comprising administering a therapeutically effective amount of the compound defined in claim 1.
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50. A method for the treatment of a proliferative disorder comprising administering a therapeutically effective amount of the compound defined in claim 1.
-
2. The compound defined in claim 1 of Formula (V):
-
15. A compound of Formula (XVI):
- View Dependent Claims (16, 17, 18, 19, 20, 21, 22, 23, 24, 40, 43, 44, 45, 46)
-
16. The compound defined in claim 15 where Nu is selected from the group consisting of:
-
cytidine, uridine, 2′
-deoxycytidine,thymidine, 1-(β
-D-arabinofuranosyl)cytosine,1-(β
-D-arabinofuranosyl)uracil,1-(β
-D-arabinofuranosyl)thymine,3′
-azido-3′
-deoxythymidine,3′
-azido-2′
,3′
-dideoxyuridine,3′
-azido-2′
,3′
-dideoxycytidine,3′
-deoxythymidine,2′
,3′
-dideoxyuridine,2′
,3′
-dideoxycytidine,3′
-deoxy-2′
,3′
-didehydrothymidine,2′
,3′
-didehydro-2′
,3′
-dideoxyuridine,2′
,3′
-didehydro-2′
,3′
-dideoxycytidine,6-azauridine, 6-azathymidine, 6-azacytidine, 5-azacytidine, 5-fluorocytidine, 5-iodocytidine, 5-bromocytidine, 5-chlorocytidine, 5-fluorouridine, 5-iodouridine, 5-bromouridine, 5-chlorouridine, 2′
-C-methylcytidine,2′
-C-methyluridine,2′
-C-methylthymidine,2′
-deoxy-2′
-fluorocytidine,2′
-deoxy-2′
-fluorouridine,2′
-α
-fluorothymidine,2′
-deoxy-2′
-fluoroarabinocytidine,2′
-deoxy-2′
-fluoroarabinouridine,2′
-β
-fluorothymidine,2′
-O-methylcytidine,2′
-O-5-dimethyluridine,2′
-C-ethynylcytidine,2′
-C-ethynyluridine,2′
-C-ethynyl-5-methyluridine,3′
-C-ethynylcytidine,3′
-C-ethynyluridine,3′
-C-ethynyl-5-methyluridine,3′
-deoxycytidine,3′
-deoxyuridine,4′
-C-ethynylcytidine,4′
-C-ethynyluridine,4′
-C-ethynylthymidine,4′
-C-methylcytidine,4′
-C-methyluridine,4′
-C-methylthymidine,2′
-C-methyl-6-azauridine,2′
-C-methyl-5-fluorouridine,2′
-C-methyl-5-fluorocytidine,2′
-deoxy-6-azauridine,2′
-deoxy-5-fluorouridine,2′
-deoxy-5-fluorocytidine,2′
-deoxy-5-iodouridine,2′
-deoxy-5-iodocytidine,3′
-deoxy-6-azauridine,3′
-deoxy-5-fluorouridine,3′
-deoxy-5-iodouridine,3′
-deoxy-5-fluorocytidine,2′
,3′
-dideoxy-6-azauridine,2′
,3′
-dideoxy-5-fluorouridine,2′
,3′
-dideoxy-5-fluorouridine,2′
,3′
-dideoxy-5-iodocytidine,2′
,3′
-dideoxy-β
-L-cytidine,3′
-deoxy-β
-L-thymidine,2′
,3′
-dideoxy-5-fluoro-β
-L-cytidine,β
-L-thymidine,2′
-deoxy-β
-L-cytidine,β
-L-cytidine,β
-L-uridine,2′
,3′
-didehydro-2′
,3′
-dideoxy-β
-L-cytidine,2′
,3′
-didehydro-3′
-dideoxy-β
-L-thymidine,2′
,3′
-didehydro-2′
,3′
-dideoxy-β
-L-5-fluorocytidine,2′
-deoxy-2′
,2′
-difluorocytidine,2′
-deoxy-2′
(E)-fluoromethylenecytidine,2′
-deoxy-2′
(Z)-fluoromethylenecytidine,(−
)-2′
,3′
-dideoxy-3′
-thiacytidine,(+)-2′
,3′
-dideoxy-3′
-thiacytidine,1-β
-D-ribofuranosyl-1,2,4-triazole-3-carboxamide,1-β
-L-ribofuranosyl-1,2,4-triazole-3-carboxamide,1-β
-D-ribofuranosyl-1,3-imidazolium-5-olate,1-β
-L-ribofuranosyl-1,3-imidazolium-5-olate,1-β
-D-ribofuranosyl-5-ethynylimidazole-4-carboxamide,1-β
-L-ribofuranosyl-5-ethynylimidazole-4-carboxamide,1-(2-deoxy-2-fluoro-β
-D-arabinofuranosyl)-5-iodouracil,1-(2-deoxy-2-fluoro-β
-D-arabinofuranosyl)-5-iodocytosine,1-(2-deoxy-2-fluoro-β
-L-arabinofuranosyl)-5-methyluracil,1-β
-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil,E-5-(2-bromovinyl)-2′
-deoxyuridine,5-trifluoromethylthymidine, 1-β
-D-arabinofuranosyl-5-propynyluracil,1-(2-deoxy-2-fluoro-1-β
-D-arabinofuranosyl)-5-ethyluracil,3′
-deoxy-3′
-fluorothymidine,(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)cytosine, and (2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-5-fluorocytosine.
-
-
17. The compound defined in claim 15 of Formula (XVII):
-
18. The compound defined in claim 15 of Formula (XVII):
-
19. The compound defined in claim 17 where Nu is selected from the group consisting of:
-
cytidine, uridine, 2′
-deoxycytidine,thymidine, 1-(β
-D-arabinofuranosyl)cytosine,1-(β
-D-arabinofuranosyl)uracil,1-(β
-D-arabinofuranosyl)thymine,3′
-azido-3′
-deoxythymidine,3′
-azido-2′
,3′
-dideoxyuridine,3′
-azido-2′
,3′
-dideoxycytidine,3′
-deoxythymidine,2′
,3′
-dideoxyuridine,2′
,3′
-dideoxycytidine,3′
-deoxy-2′
,3′
-didehydrothymidine,2′
,3′
-didehydro-2′
,3′
-dideoxyuridine,2′
,3′
-didehydro-2′
,3′
-dideoxycytidine,6-azauridine, 6-azathymidine, 6-azacytidine, 5-azacytidine, 5-fluorocytidine, 5-iodocytidine, 5-bromocytidine, 5-chlorocytidine, 5-fluorouridine, 5-iodouridine, 5-bromouridine, 5-chlorouridine, 2′
-C-methylcytidine,2′
-C-methyluridine,2′
-C-methylthymidine,2′
-deoxy-2′
-fluorocytidine,2′
-deoxy-2′
-fluorouridine,2′
-α
-fluorothymidine,2′
-deoxy-2′
-fluoroarabinocytidine,2′
-deoxy-2′
-fluoroarabinouridine,2′
-β
-fluorothymidine,2′
-O-methylcytidine,2′
-O-5-dimethyluridine,2′
-C-ethynylcytidine,2′
-C-ethynyluridine,2′
-C-ethynyl-5-methyluridine,3′
-C-ethynylcytidine,3′
-C-ethynyluridine,3′
-C-ethynyl-5-methyluridine,3′
-deoxycytidine,3′
-deoxyuridine,4′
-C-ethynylcytidine,4′
-C-ethynyluridine,4′
-C-ethynylthymidine,4′
-C-methylcytidine,4′
-C-methyluridine,4′
-C-methylthymidine,2′
-C-methyl-6-azauridine,2′
-C-methyl-5-fluorouridine,2′
-C-methyl-5-fluorocytidine,2′
-deoxy-6-azauridine,2′
-deoxy-5-fluorouridine,2′
-deoxy-5-fluorocytidine,2′
-deoxy-5-iodouridine,2′
-deoxy-5-iodocytidine,3′
-deoxy-6-azauridine,3′
-deoxy-5-fluorouridine,3′
-deoxy-5-iodouridine,3′
-deoxy-5-fluorocytidine,2′
,3′
-dideoxy-6-azauridine,2′
,3′
-dideoxy-5-fluorouridine,2′
,3′
-dideoxy-5-fluorouridine,2′
,3′
-dideoxy-5-iodocytidine,2′
,3′
-dideoxy-β
-L-cytidine,3′
-deoxy-β
-L-thymidine,2′
,3′
-dideoxy-5-fluoro-β
-L-cytidine,β
-L-thymidine,2′
-deoxy-β
-L-cytidine,β
-L-cytidine,β
-L-uridine,2′
,3′
-didehydro-2′
,3′
-dideoxy-β
-L-cytidine,2′
,3′
-didehydro-3′
-dideoxy-β
-L-thymidine,2′
,3′
-didehydro-2′
,3′
-dideoxy-β
-L-5-fluorocytidine,2′
-deoxy-2′
,2′
-difluorocytidine,2′
-deoxy-2′
(E)-fluoromethylenecytidine,2′
-deoxy-2′
(Z)-fluoromethylenecytidine,(−
)-2′
,3′
-dideoxy-3′
-thiacytidine,(+)-2′
,3′
-dideoxy-3′
-thiacytidine,1-β
-D-ribofuranosyl-1,2,4-triazole-3-carboxamide,1-β
-L-ribofuranosyl-1,2,4-triazole-3-carboxamide,1-β
-D-ribofuranosyl-1,3-imidazolium-5-olate,1-β
-L-ribofuranosyl-1,3-imidazolium-5-olate,1-β
-D-ribofuranosyl-5-ethynylimidazole-4-carboxamide,1-β
-L-ribofuranosyl-5-ethynylimidazole-4-carboxamide,1-(2-deoxy-2-fluoro-β
-D-arabinofuranosyl)-5-iodouracil,1-(2-deoxy-2-fluoro-β
-D-arabinofuranosyl)-5-iodocytosine,1-(2-deoxy-2-fluoro-β
-L-arabinofuranosyl)-5-methyluracil,1-β
-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil,E-5-(2-bromovinyl)-2′
-deoxyuridine,5-trifluoromethylthymidine, 1-β
-D-arabinofuranosyl-5-propynyluracil,1-(2-deoxy-2-fluoro-1-β
-D-arabinofuranosyl)-5-ethyluracil,3′
-deoxy-3′
-fluorothymidine,(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)cytosine, and (2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-5-fluorocytosine.
-
-
20. The compound defined in claim 15 of Formula (XVIII):
-
21. The compound defined in claim 15 of Formula (XVIII):
-
22. The compound defined in claim 21 where Nu is selected from the group consisting of:
-
cytidine, uridine, 2′
-deoxycytidine,thymidine, 1-(β
-D-arabinofuranosyl)cytosine,1-(β
-D-arabinofuranosyl)uracil,1-(β
-D-arabinofuranosyl)thymine,3′
-azido-3′
-deoxythymidine,3′
-azido-2′
,3′
-dideoxyuridine,3′
-azido-2′
,3′
-dideoxycytidine,3′
-deoxythymidine,2′
,3′
-dideoxyuridine,2′
,3′
-dideoxycytidine,3′
-deoxy-2′
,3′
-didehydrothymidine,2′
,3′
-didehydro-2′
,3′
-dideoxyuridine,2′
,3′
-didehydro-2′
,3′
-dideoxycytidine,6-azauridine, 6-azathymidine, 6-azacytidine, 5-azacytidine, 5-fluorocytidine, 5-iodocytidine, 5-bromocytidine, 5-chlorocytidine, 5-fluorouridine, 5-iodouridine, 5-bromouridine, 5-chlorouridine, 2′
-C-methylcytidine,2′
-C-methyluridine,2′
-C-methylthymidine,2′
-deoxy-2′
-fluorocytidine,2′
-deoxy-2′
-fluorouridine,2′
-α
-fluorothymidine,2′
-deoxy-2′
-fluoroarabinocytidine,2′
-deoxy-2′
-fluoroarabinouridine,2′
-β
-fluorothymidine,2′
-O-methylcytidine,2′
-O-5-dimethyluridine,2′
-C-ethynylcytidine,2′
-C-ethynyluridine,2′
-C-ethynyl-5-methyluridine,3′
-C-ethynylcytidine,3′
-C-ethynyluridine,3′
-C-ethynyl-5-methyluridine,3′
-deoxycytidine,3′
-deoxyuridine,4′
-C-ethynylcytidine,4′
-C-ethynyluridine,4′
-C-ethynylthymidine,4′
-C-methylcytidine,4′
-C-methyluridine,4′
-C-methylthymidine,2′
-C-methyl-6-azauridine,2′
-C-methyl-5-fluorouridine,2′
-C-methyl-5-fluorocytidine,2′
-deoxy-6-azauridine,2′
-deoxy-5-fluorouridine,2′
-deoxy-5-fluorocytidine,2′
-deoxy-5-iodouridine,2′
-deoxy-5-iodocytidine,3′
-deoxy-6-azauridine,3′
-deoxy-5-fluorouridine,3′
-deoxy-5-iodouridine,3′
-deoxy-5-fluorocytidine,2′
,3′
-dideoxy-6-azauridine,2′
,3′
-dideoxy-5-fluorouridine,2′
,3′
-dideoxy-5-fluorouridine,2′
,3′
-dideoxy-5-iodocytidine,2′
,3′
-dideoxy-β
-L-cytidine,3′
-deoxy-β
-L-thymidine,2′
,3′
-dideoxy-5-fluoro-β
-L-cytidine,β
-L-thymidine,2′
-deoxy-β
-L-cytidine,β
-L-cytidine,β
-L-uridine,2′
,3′
-didehydro-2′
,3′
-dideoxy-β
-L-cytidine,2′
,3′
-didehydro-3′
-dideoxy-β
-L-thymidine,2′
,3′
-didehydro-2′
,3′
-dideoxy-β
-L-5-fluorocytidine,2′
-deoxy-2′
,2′
-difluorocytidine,2′
-deoxy-2′
(E)-fluoromethylenecytidine,2′
-deoxy-2′
(Z)-fluoromethylenecytidine,(−
)-2′
,3′
-dideoxy-3′
-thiacytidine,(+)-2′
,3′
-dideoxy-3′
-thiacytidine,1-β
-D-ribofuranosyl-1,2,4-triazole-3-carboxamide,1-β
-L-ribofuranosyl-1,2,4-triazole-3-carboxamide,1-β
-D-ribofuranosyl-1,3-imidazolium-5-olate,1-β
-L-ribofuranosyl-1,3-imidazolium-5-olate,1-β
-D-ribofuranosyl-5-ethynylimidazole-4-carboxamide,1-β
-L-ribofuranosyl-5-ethynylimidazole-4-carboxamide,1-(2-deoxy-2-fluoro-β
-D-arabinofuranosyl)-5-iodouracil,1-(2-deoxy-2-fluoro-β
-D-arabinofuranosyl)-5-iodocytosine,1-(2-deoxy-2-fluoro-β
-L-arabinofuranosyl)-5-methyluracil,1-β
-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil,E-5-(2-bromovinyl)-2′
-deoxyuridine,5-trifluoromethylthymidine, 1-β
-D-arabinofuranosyl-5-propynyluracil,1-(2-deoxy-2-fluoro-1-β
-D-arabinofuranosyl)-5-ethyluracil,3′
-deoxy-3′
-fluorothymidine,(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)cytosine, and (2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-5-fluorocytosine.
-
-
23. The compound defined in claim 15 of Formula (XIX):
-
24. The compound defined in claim 15 of Formula (XIX):
-
40. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 15, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable prodrug thereof, optionally in combination with one or more other active ingredients and/or with a pharmaceutically acceptable carrier.
-
43. The compound defined in claim 15,
wherein at least one of X7, X8 and/or X9 is − - BH3M+; and
at least one of X0, X5 or X6 is CY2.
- BH3M+; and
-
44. The compound defined in claim 43,
wherein at least one of X0, X5 or X6 is CF2. -
45. The compound defined in claim 43,
wherein X6 is CF2 or CCl2. -
46. The compound defined in claim 43,
wherein X7 is − - BH3M+.
-
16. The compound defined in claim 15 where Nu is selected from the group consisting of:
-
25. A compound of Formula (I) which may be a D- or L-nucleotide:
- View Dependent Claims (26, 27, 28, 29, 30, 31, 41)
-
26. The compound defined in claim 25 of Formula (VI):
-
27. The compound defined in claim 25 of Formula (VII):
-
28. The compound defined in claim 27
wherein X2 is O; - and
wherein X7 is selected from the group consisting of SH, NH2, −
BH3M+, alkyl, aryl, alkylamino, and arylamino.
- and
-
29. The compound defined in claim 27
wherein X2 is O; - and
wherein X7 is selected from the group consisting of SH, NH2, −
BH3M+, R, and NHR.
- and
-
30. The compound defined in claim 25 of Formula (VIII):
-
31. The compound defined in claim 25 of Formula (IX):
-
41. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 25, a pharmaceutically acceptable salt thereof, optionally in combination with one or more other active ingredients and/or with a pharmaceutically acceptable carrier.
-
26. The compound defined in claim 25 of Formula (VI):
-
32. A compound of Formula (XVI):
- View Dependent Claims (33, 34, 35, 36, 37, 38, 42)
-
33. The compound defined in claim 32 where Nu is selected from the group consisting of:
-
cytidine, uridine, 2′
-deoxycytidine,thymidine, 1-(β
-D-arabinofuranosyl)cytosine,1-(β
-D-arabinofuranosyl)uracil,1-(β
-D-arabinofuranosyl)thymine,3′
-azido-3′
-deoxythymidine,3′
-azido-2′
,3′
-dideoxyuridine,3′
-azido-2′
,3′
-dideoxycytidine,3′
-deoxythymidine,2′
,3′
-dideoxyuridine,2′
,3′
-dideoxycytidine,3′
-deoxy-2′
,3′
-didehydrothymidine,2′
,3′
-didehydro-2′
,3′
-dideoxyuridine,2′
,3′
-didehydro-2′
,3′
-dideoxycytidine,6-azauridine, 6-azathymidine, 6-azacytidine, 5-azacytidine, 5-fluorocytidine, 5-iodocytidine, 5-bromocytidine, 5-chlorocytidine, 5-fluorouridine, 5-iodouridine, 5-bromouridine, 5-chlorouridine, 2′
-C-methylcytidine,2′
-C-methyluridine,2′
-C-methylthymidine,2′
-deoxy-2′
-fluorocytidine,2′
-deoxy-2′
-fluorouridine,2′
-α
-fluorothymidine,2′
-deoxy-2′
-fluoroarabinocytidine,2′
-deoxy-2′
-fluoroarabinouridine,2′
-1-fluorothymidine,2′
-O-methylcytidine,2′
-O-5-dimethyluridine,2′
-C-ethynylcytidine,2′
-C-ethynyluridine,2′
-C-ethynyl-5-methyluridine,3′
-C-ethynylcytidine,3′
-C-ethynyluridine,3′
-C-ethynyl-5-methyluridine,3′
-deoxycytidine,3′
-deoxyuridine,4′
-C-ethynylcytidine,4′
-C-ethynyluridine,4′
-C-ethynylthymidine,4′
-C-methylcytidine,4′
-C-methyluridine,4′
-C-methylthymidine,2′
-C-methyl-6-azauridine,2′
-C-methyl-5-fluorouridine,2′
-C-methyl-5-fluorocytidine,2′
-deoxy-6-azauridine,2′
-deoxy-5-fluorouridine,2′
-deoxy-5-fluorocytidine,2′
-deoxy-5-iodouridine,2′
-deoxy-5-iodocytidine,3′
-deoxy-6-azauridine,3′
-deoxy-5-fluorouridine,3′
-deoxy-5-iodouridine,3′
-deoxy-5-fluorocytidine,2′
,3′
-dideoxy-6-azauridine,2′
,3′
-dideoxy-5-fluorouridine,2′
,3′
-dideoxy-5-fluorouridine,2′
,3′
-dideoxy-5-iodocytidine,2′
,3′
-dideoxy-β
-L-cytidine,3′
-deoxy-β
-L-thymidine,2′
,3′
-dideoxy-5-fluoro-β
-L-cytidine,β
-L-thymidine,2′
-deoxy-β
-L-cytidine,β
-L-cytidine,β
-L-uridine,2′
,3′
-didehydro-2′
,3′
-dideoxy-β
-L-cytidine,2′
,3′
-didehydro-3′
-dideoxy-β
-L-thymidine,2′
,3′
-didehydro-2′
,3′
-dideoxy-β
-L-5-fluorocytidine,2′
-deoxy-2′
,2′
-difluorocytidine,2′
-deoxy-2′
(E)-fluoromethylenecytidine,2′
-deoxy-2′
(Z)-fluoromethylenecytidine,(−
)-2′
,3′
-dideoxy-3′
-thiacytidine,(+)-2′
,3′
-dideoxy-3′
-thiacytidine,1-β
-D-ribofuranosyl-1,2,4-triazole-3-carboxamide,1-β
-L-ribofuranosyl-1,2,4-triazole-3-carboxamide,1-β
-D-ribofuranosyl-1,3-imidazolium-5-olate,1-β
-L-ribofuranosyl-1,3-imidazolium-5-olate,1-β
-D-ribofuranosyl-5-ethynylimidazole-4-carboxamide,1-β
-L-ribofuranosyl-5-ethynylimidazole-4-carboxamide,1-(2-deoxy-2-fluoro-β
-D-arabinofuranosyl)-5-iodouracil,1-(2-deoxy-2-fluoro-β
-D-arabinofuranosyl)-5-iodocytosine,1-(2-deoxy-2-fluoro-β
-L-arabinofuranosyl)-5-methyluracil,1-β
-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil,E-5-(2-bromovinyl)-2′
-deoxyuridine,5-trifluoromethylthymidine, 1-β
-D-arabinofuranosyl-5-propynyluracil,1-(2-deoxy-2-fluoro-1-β
-D-arabinofuranosyl)-5-ethyluracil,3′
-deoxy-3′
-fluorothymidine,(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)cytosine, and (2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-5-fluorocytosine.
-
-
34. The compound defined in claim 32 of Formula (XVII):
-
35. The compound defined in claim 34 where Nu is selected from the group consisting of:
-
cytidine, uridine, 2′
-deoxycytidine,thymidine, 1-(β
-D-arabinofuranosyl)cytosine,1-(β
-D-arabinofuranosyl)uracil,1-(β
-D-arabinofuranosyl)thymine,3′
-azido-3′
-deoxythymidine,3′
-azido-2′
,3′
-dideoxyuridine,3′
-azido-2′
,3′
-dideoxycytidine,3′
-deoxythymidine,2′
,3′
-dideoxyuridine,2′
,3′
-dideoxycytidine,3′
-deoxy-2′
,3′
-didehydrothymidine,2′
,3′
-didehydro-2′
,3′
-dideoxyuridine,2′
,3′
-didehydro-2′
,3′
-dideoxycytidine,6-azauridine, 6-azathymidine, 6-azacytidine, 5-azacytidine, 5-fluorocytidine, 5-iodocytidine, 5-bromocytidine, 5-chlorocytidine, 5-fluorouridine, 5-iodouridine, 5-bromouridine, 5-chlorouridine, 2′
-C-methylcytidine,2′
-C-methyluridine,2′
-C-methylthymidine,2′
-deoxy-2′
-fluorocytidine,2′
-deoxy-2′
-fluorouridine,2′
-α
-fluorothymidine,2′
-deoxy-2′
-fluoroarabinocytidine,2′
-deoxy-2′
-fluoroarabinouridine,2′
-β
-fluorothymidine,2′
-O-methylcytidine,2′
-O-5-dimethyluridine,2′
-C-ethynylcytidine,2′
-C-ethynyluridine,2′
-C-ethynyl-5-methyluridine,3′
-C-ethynylcytidine,3′
-C-ethynyluridine,3′
-C-ethynyl-5-methyluridine,3′
-deoxycytidine,3′
-deoxyuridine,4′
-C-ethynylcytidine,4′
-C-ethynyluridine,4′
-C-ethynylthymidine,4′
-C-methylcytidine,4′
-C-methyluridine,4′
-C-methylthymidine,2′
-C-methyl-6-azauridine,2′
-C-methyl-5-fluorouridine,2′
-C-methyl-5-fluorocytidine,2′
-deoxy-6-azauridine,2′
-deoxy-5-fluorouridine,2′
-deoxy-5-fluorocytidine,2′
-deoxy-5-iodouridine,2′
-deoxy-5-iodocytidine,3′
-deoxy-6-azauridine,3′
-deoxy-5-fluorouridine,3′
-deoxy-5-iodouridine,3′
-deoxy-5-fluorocytidine,2′
,3′
-dideoxy-6-azauridine,2′
,3′
-dideoxy-5-fluorouridine,2′
,3′
-dideoxy-5-fluorouridine,2′
,3′
-dideoxy-5-iodocytidine,2′
,3′
-dideoxy-β
-L-cytidine,3′
-deoxy-β
-L-thymidine,2′
,3′
-dideoxy-5-fluoro-β
-L-cytidine,β
-L-thymidine,2′
-deoxy-β
-L-cytidine,β
-L-cytidine,β
-L-uridine,2′
,3′
-didehydro-2′
,3′
-dideoxy-β
-L-cytidine,2′
,3′
-didehydro-3′
-dideoxy-β
-L-thymidine,2′
,3′
-didehydro-2′
,3′
-dideoxy-β
-L-5-fluorocytidine,2′
-deoxy-2′
,2′
-difluorocytidine,2′
-deoxy-2′
(E)-fluoromethylenecytidine,2′
-deoxy-2′
(Z)-fluoromethylenecytidine,(−
)-2′
,3′
-dideoxy-3′
-thiacytidine,(+)-2′
,3′
-dideoxy-3′
-thiacytidine,1-β
-D-ribofuranosyl-1,2,4-triazole-3-carboxamide,1-β
-L-ribofuranosyl-1,2,4-triazole-3-carboxamide,1-β
-D-ribofuranosyl-1,3-imidazolium-5-olate,1-β
-L-ribofuranosyl-1,3-imidazolium-5-olate,1-β
-D-ribofuranosyl-5-ethynylimidazole-4-carboxamide,1-β
-L-ribofuranosyl-5-ethynylimidazole-4-carboxamide,1-(2-deoxy-2-fluoro-β
-D-arabinofuranosyl)-5-iodouracil,1-(2-deoxy-2-fluoro-β
-D-arabinofuranosyl)-5-iodocytosine,1-(2-deoxy-2-fluoro-β
-L-arabinofuranosyl)-5-methyluracil,1-β
-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil,E-5-(2-bromovinyl)-2′
-deoxyuridine,5-trifluoromethylthymidine, 1-β
-D-arabinofuranosyl-5-propynyluracil,1-(2-deoxy-2-fluoro-1-β
-D-arabinofuranosyl)-5-ethyluracil,3′
-deoxy-3′
-fluorothymidine,(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)cytosine, and (2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-5-fluorocytosine.
-
-
36. The compound defined in claim 32 of Formula (XVIII):
-
37. The compound defined in claim 36 where Nu is selected from the group consisting of:
-
cytidine, uridine, 2′
-deoxycytidine,thymidine, 1-(β
-D-arabinofuranosyl)cytosine,1-(β
-D-arabinofuranosyl)uracil,1-(β
-D-arabinofuranosyl)thymine,3′
-azido-3′
-deoxythymidine,3′
-azido-2′
,3′
-dideoxyuridine,3′
-azido-2′
,3′
-dideoxycytidine,3′
-deoxythymidine,2′
,3′
-dideoxyuridine,2′
,3′
-dideoxycytidine,3′
-deoxy-2′
,3′
-didehydrothymidine,2′
,3′
-didehydro-2′
,3′
-dideoxyuridine,2′
,3′
-didehydro-2′
,3′
-dideoxycytidine,6-azauridine, 6-azathymidine, 6-azacytidine, 5-azacytidine, 5-fluorocytidine, 5-iodocytidine, 5-bromocytidine, 5-chlorocytidine, 5-fluorouridine, 5-iodouridine, 5-bromouridine, 5-chlorouridine, 2′
-C-methylcytidine,2′
-C-methyluridine,2′
-C-methylthymidine,2′
-deoxy-2′
-fluorocytidine,2′
-deoxy-2′
-fluorouridine,2′
-α
-fluorothymidine,2′
-deoxy-2′
-fluoroarabinocytidine,2′
-deoxy-2′
-fluoroarabinouridine,2′
-β
-fluorothymidine,2′
-O-methylcytidine,2′
-O-5-dimethyluridine,2′
-C-ethynylcytidine,2′
-C-ethynyluridine,2′
-C-ethynyl-5-methyluridine,3′
-C-ethynylcytidine,3′
-C-ethynyluridine,3′
-C-ethynyl-5-methyluridine,3′
-deoxycytidine,3′
-deoxyuridine,4′
-C-ethynylcytidine,4′
-C-ethynyluridine,4′
-C-ethynylthymidine,4′
-C-methylcytidine,4′
-C-methyluridine,4′
-C-methylthymidine,2′
-C-methyl-6-azauridine,2′
-C-methyl-5-fluorouridine,2′
-C-methyl-5-fluorocytidine,2′
-deoxy-6-azauridine,2′
-deoxy-5-fluorouridine,2′
-deoxy-5-fluorocytidine,2′
-deoxy-5-iodouridine,2′
-deoxy-5-iodocytidine,3′
-deoxy-6-azauridine,3′
-deoxy-5-fluorouridine,3′
-deoxy-5-iodouridine,3′
-deoxy-5-fluorocytidine,2′
,3′
-dideoxy-6-azauridine,2′
,3′
-dideoxy-5-fluorouridine,2′
,3′
-dideoxy-5-fluorouridine,2′
,3′
-dideoxy-5-iodocytidine,2′
,3′
-dideoxy-β
-L-cytidine,3′
-deoxy-β
-L-thymidine,2′
,3′
-dideoxy-5-fluoro-β
-L-cytidine,β
-L-thymidine,2′
-deoxy-β
-L-cytidine,β
-L-cytidine,β
-L-uridine,2′
,3′
-didehydro-2′
,3′
-dideoxy-β
-L-cytidine,2′
,3′
-didehydro-3′
-dideoxy-β
-L-thymidine,2′
,3′
-didehydro-2′
,3′
-dideoxy-β
-L-5-fluorocytidine,2′
-deoxy-2′
,2′
-difluorocytidine,2′
-deoxy-2′
(E)-fluoromethylenecytidine,2′
-deoxy-2′
(Z)-fluoromethylenecytidine,(−
)-2′
,3′
-dideoxy-3′
-thiacytidine,(+)-2′
,3′
-dideoxy-3′
-thiacytidine,1-β
-D-ribofuranosyl-1,2,4-triazole-3-carboxamide,1-β
-L-ribofuranosyl-1,2,4-triazole-3-carboxamide,1-β
-D-ribofuranosyl-1,3-imidazolium-5-olate,1-β
-L-ribofuranosyl-1,3-imidazolium-5-olate,1-β
-D-ribofuranosyl-5-ethynylimidazole-4-carboxamide,1-β
-L-ribofuranosyl-5-ethynylimidazole-4-carboxamide,1-(2-deoxy-2-fluoro-β
-D-arabinofuranosyl)-5-iodouracil,1-(2-deoxy-2-fluoro-β
-D-arabinofuranosyl)-5-iodocytosine,1-(2-deoxy-2-fluoro-β
-L-arabinofuranosyl)-5-methyluracil,1-β
-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil,E-5-(2-bromovinyl)-2′
-deoxyuridine,5-trifluoromethylthymidine, 1-β
-D-arabinofuranosyl-5-propynyluracil,1-(2-deoxy-2-fluoro-1-β
-D-arabinofuranosyl)-5-ethyluracil,3′
-deoxy-3′
-fluorothymidine,(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)cytosine, and (2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-5-fluorocytosine.
-
-
38. The compound defined in claim 32 Formula (XIX):
-
42. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 32, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable prodrug thereof, optionally in combination with one or more other active ingredients and/or with a pharmaceutically acceptable carrier.
-
33. The compound defined in claim 32 where Nu is selected from the group consisting of:
-
48. A compound having a formula selected from the group consisting of:
Specification
- Resources
-
Current AssigneeBiota Scientific Management Pty Limited (Vaxart, Inc.)
-
Original AssigneeBiota Scientific Management Pty Limited (Vaxart, Inc.)
-
InventorsJin, Yi, Wang, Guangyi, Prhavc, Marija, Leeds, Janet, Brooks, Jennifer, Ariza, Maria, Rajwanshi, Vivek, Fagan, Patrick, Bruice, Thomas, Boyle, Nicholas, Tucker, Kathleen, Cook, Phillip
-
Granted Patent
-
Time in Patent OfficeDays
-
Field of Search
-
US Class Current514/44.R
-
CPC Class CodesA61P 31/00 Antiinfectives, i.e. antibi...A61P 31/04 Antibacterial agentsA61P 31/12 AntiviralsA61P 31/18 for HIVA61P 35/00 Antineoplastic agentsC07H 19/04 Heterocyclic radicals conta...C07H 19/10 with the saccharide radical...C07H 19/14 Pyrrolo-pyrimidine radicalsC07H 19/20 with the saccharide radical...