US2004058893A1PendingUtilityA1
Antiviral nucleoside analogues
Est. expiryDec 23, 2018(expired)· nominal 20-yr term from priority
Inventors:Nghe Nguyen-Ba
A61P 31/20A61P 31/18A61P 31/12Y02P20/55C07D 473/00C07H 19/16C40B 40/00A61K 31/7076
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Claims
Abstract
In accordance with the present invention there is provided a nucleoside analogue of formula (I) or (Ia) which is useful as an antiviral agent.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A cis-nucleoside of formula (I):
and pharmaceutically acceptable salts thereof,
wherein:
n is 1 or 2
R 4 is chosen from H, COOH, CONH 2 , OH, SH, NH 2 , NO 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, COR a wherein R a is a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and COOR b wherein R b is a C 1-6 alkyl, C 2-6 alkenyl, or C 2-6 alkynyl;
R 3 is H or a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl;
X is chosen from H, monophosphate, diphosphate, triphosphate, carbonyl substituted with a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, or
wherein each Rc is indenpendently chosen from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl or an hydroxy protecting group; and
wherein said nucleoside is in the form of the (−) enantiomer, (+) enantiomer and mixtures thereof, including racemic mixtures.
2 . A nucleoside according to claim 1 wherein said nucleoside is present in the (−) form and is at least 95% free of the (+) form.
3 . A nucleoside according to claim 1 wherein said nucleoside is present in the (−) form and is at least 97% free of the (+) form.
4 . A nucleoside according to claim 1 wherein said nucleoside is present in the (−) form and is at least 99% free of the (+) form.
5 . A compound according to claim 1 wherein the hydroxy protecting group is chosen from acetyl-2-thioethyl ester, pivaloyloxymethyl ester or isopropyloxycarbonyloxymethyl ester.
6 . A compound according to claim 1 wherein X is H.,
7 . A compound according to claim 1 wherein n is 1.
8 . A compound according to claim 7 wherein R 3 is H or methyl or R 4 is H.
9 . A compound according to claim 7 wherein R 4 is H; COOH; CONH 2 ; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl or COOR b wherein R b is a C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl.
10 . A compound according to claim 7 wherein R 4 is H, COOH, or C 1-6 alkyl.
11 . A compound according to claim 7 wherein R 4 is methyl or ethyl.
12 . A compound according to claim 7 wherein R 4 is COOH.
13 . A compound according to claim 7 wherein R 3 and R 4 are H.
14 . The compound cis-2-hydroxymethyl-4-(2′-amino-6′-cyclopropylamino-purine-9′-yl)-1,3-dioxolane and pharmaceutically acceptable salts thereof.
15 . The compound cis-2-hydroxymethyl-4-(2′-amino-6′-cyclobutylamino-purine-9′-yl)-1,3-dioxolane and pharmaceutically acceptable salts thereof.
16 . The compound cis-2-hydroxymethyl-4-(2′-amino-6′-[1-carboxylic acid-cyclopropylamino]-purine-9′-yl)-1,3-dioxolane and pharmaceutically acceptable salts thereof.
17 . The compound (−)-(2R,4R)-2-hydroxymethyl-4-(2′-amino-6′-cyclopropylamino-purine-9′-yl)-1,3-dioxolane at least 97% free of the corresponding (+) enantiomer.
18 . The compound (+)-(2S,4S)-2-hydroxymethyl-4-(2′-amino-6′-cyclopropylamino-purine-9′-yl)-1,3-dioxolane at least 97% free of the corresponding (−) enantiomer.
19 . The compound (−)-(2R,4R)-2-hydroxymethyl-4-(2′-amino-6′-cyclobutylamino-purine-9′-yl)-1,3-dioxolane at least 97% free of the corresponding (+) enantiomer.
20 . The compound (+)-(2S,4S) -2-hydroxymethyl-4-(2′-amino-6′-cyclobutylamino-purine-9′-yl)-1,3-dioxolane at least 97% free of the corresponding (−) enantiomer.
21 . The compound (−)-(2R,4R)-2-hydroxymethyl-4-(2′-amino-6′-[1-carboxylic acid-cyclopropylamino]-purine-9′-yl)-1,3-dioxolane at least 97% free of the corresponding (+) enantiomer.
22 . The compound (+)-(2S,4S)-2-hydroxymethyl-4-(2′-amino-6′-[1-carboxylic acid-cyclopropylamino]-purine-9′-yl)-1,3-dioxolane at least 97% free of the corresponding (−) enantiomer.
23 . A combination useful for the treatment of viral infections comprising at least one compound according to anyone of claims 1 to 22 or pharmaceutically acceptable salts thereof comprising at least one further therapeutic agent chosen from nucleoside analogues; NNRTIs; or protease inhibitors.
24 . The combination of claim 23 wherein the nucleoside analogue is chosen from zidovudine, didanosine, zalcitabine, stavudine or lamivudine.
25 . The combination of claim 23 wherein the non-nucleoside reverse transcriptase inhibitor is chosen from nevirapine, delavirdine or efavirenz.
26 . The combination of claim 23 wherein the protease inhibitor is chosen from indinavir, nelfinavir, saquinavir or ritonavir.
27 . A compound according to anyone of claim 1 to 22 for use in medical therapy.
28 . A compound according to anyone of claim 1 to 22 for use in the treatment of viral infections.
29 . A compound according to anyone of claim 1 to 22 for use in the-treatment of HIV infection.
30 . A compound according to anyone of claim 1 to 22 for use in the treatment of HBV infection.
31 . A method for the treatment of viral infections comprising administering a therapeutically effective amount of a compound according to anyone of claims 1 to 22 to a subject in need of such treatment.
32 . The method according to claim 32 wherein the viral infection is an HIV infection.
33 . The method according to claim 32 wherein the viral infection is an HBV infection.
34 . A pharmaceutical formulation comprising at least one compound according to anyone of claims 1 to 22 together with at least one pharmaceutically acceptable carrier or excipient.Join the waitlist — get patent alerts
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