Combinations comprising VX478, zidovudine and/or 1592U89 for use in the treatment of HIV
AssigneeSmithKline Beecham Corporation
InventorsMartha Heider St. Clair, David Walter Barry
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Abstract
The present invention relates to therapeutic combinations of [3R*(1R*,2S*)]-[3[[(4-aminophenyl)sulphonyl](2-methylpropyl)-amino]-2-hydroxy-1-phenylmethyl)propyl]carbamic acid, tetrahydro-3-furanyl ester (141W94), 3′-azido-3′-deoxythymidine (zidovudine) and (1S,4R)-cis-4-[2-amino-6(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol (1592U89) which have anti-HIV activity. The present invention is also concerned with pharmaceutical compositions containing said combinations and their use in the treatment of HIV infections including infections with HIV mutants bearing resistance to nucleoside and/or non-nucleoside inhibitors.
Claims27
A synergistic combination comprising (a) 3S-[3R*(1R*,2S*)]-[3-[[(4-amino-phenyl)sulphonyl](2-methylpropyl)-amino]-2-hydroxy-1-phenylmethyl)propyl]-carbamic acid, tetrahydro-3-furanyl ester;
- (b) zidovudine;
- and (c) (1S,4R)-cis-4-[2-amino-6(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol, wherein the synergistic combination of (a):(b):(c) has a ratio of 1 to 20:1 to 20:
- to 1 to 10 by weight.
A synergistic combination comprising two compounds selected from the group consisting of 3S-[3R*(1R*,2S*)]-[3-[[(4-amino-phenyl)sulphonyl](2-methylpropyl)-amino]-2-hydroxy-1-phenylmethyl)propyl]-carbamic acid, tetrahydro-3-furanyl ester, zidovudine, and (1S,4R)-cis-4-[2-amino-6(cyclopropylamino)9H-purin-9-yl]-2-cyclopentene-1-methanol provided that the two synergistic compounds are not zidovudine and (1S,4R)-cis-4-[2-amino-6(cyclopropylamino) 9H-purin-9-yl]-2-cyclopentene-1-methanol.
A synergistic combination comprising (a) 3S-[3R*(1R*,2S*)]-[3-[[(4-amino-phenyl)sulphonyl](2-methylpropyl)-amino]-2-hydroxy-1-phenylmethyl)propyl]-carbamic acid, tetrahydro-3-furanyl ester or a physiologically functional derivative thereof;
- (b) zidovudine or a physiologically functional derivative thereof;
- and (c) (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl) (1H)-pyrimidin-2-one or a physiologically functional derivative thereof, wherein the synergistic combination of (a):(b):(c) has a ratio of 1 to 20:1 to 20:
- to 1 to 10 by weight.
A method for the treatment of an HIV infection in an infected animal, comprising:
- administering to said infected animal a therapeutically effective amount of a synergistic combination of active ingredients:
- (a) 3S-[3R*(1R*,2S*)]-[3-[[(4-amino-phenyl)sulphonyl](2-methylpropyl)-amino]-2-hydroxy-1-phenylmethyl)propyl]-carbamic acid, tetrahydro-3-furanyl ester;
- (b) zidovudine;
- and (c) (1s, 4R)-cis-4-[2-amino-6(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol, wherein the synergistic combination of (a):(b):(c) has a ratio of 1 to 20:1 to 20:
- to 1 to 10 by weight.
Patient pack comprising a synergistic combination of at least two active ingredients selected from the group consisting of 3S-[3R*(1R*,2S*)]-[3-[[(4-amino-phenyl)sulphonyl](2-methylpropyl)-amino]-2-hydroxy-1-phenylmethyl)propyl]-carbamic acid, tetrahydro-3-furanyl ester, zidovudine, and (1S,4R)-cis-4-[2-amino-6(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol and an information insert containing directions on the use of at least 3S-[3R*(1R*,2S*)]-[3-[[(4-amino-phenyl)sulphonyl](2-methylpropyl)-amino]-2-hydroxy-1-phenylmethyl)propyl]-carbamic acid, tetrahydro-3-furanyl ester and (1S,4R)-cis-4-[2-amino-6(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol together in synergistic combination.
Dependencies are inferred from the claim text.