Method of resolution and antiviral activity of 1,3-oxathiolane nucleoside enantiomers
AssigneeEmory University
InventorsDennis C. Liotta, Raymond F. Schinazi, Woo-Baeg Choi
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Abstract
A process for the resolution of a racemic mixture of nucleoside enantiomers that includes the step of exposing the racemic mixture to an enzyme that preferentially catalyzes a reaction in one of the enantiomers. The nucleoside enantiomer (−)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane is an effective antiviral agent against HIV, HBV, and other viruses replicating in a similar manner.
Claims45
A method for the resolution of a racemic mixture of nucleoside enantiomers, comprising the step of exposing the racemic mixture to an enzyme that preferentially catalyzes a reaction in one of the enantiomers.
The compound (−)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane.
The compound (+)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane.
A pharmaceutical composition consisting essentially of an effective amount to inhibit the replication of a virus in a human of a compound selected from the group consisting of (−)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, the monophosphate ester of (−)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, the diphosphate ester of (−)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, and the triphosphate ester of (−)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.
A pharmaceutical composition consisting essentially of an effective amount to inhibit the replication of a virus in a human of a compound selected from the group consisting of (+)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, the monophosphate ester of (+)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, the diphosphate ester of (+)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, and the triphosphate ester of (-+)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.
A method for inhibiting replication of HIV in cells comprising administering to a human an HIV inhibitory amount of a composition consisting essentially of a compound selected from the group consisting of (−)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, the monophosphate ester of (−)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, the diphosphate ester of (−)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, and the triphosphate ester of (−)-2-hydroxymethyl-5-(5-fluorocytosin)-1-yl)-1,3-oxathiolane, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.
A method for inhibiting replication of HIV in cells comprising administering to a human an HIV inhibitory amount of a composition consisting essentially of a compound selected from the group consisting of (+)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, the monophosphate ester of (+)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, the diphosphate ester of (+)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, and the triphosphate ester of (+)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.
A method for inhibiting the replication of HBV in cells comprising administering to a human an HBV inhibitory amount of a composition consisting essentially of a compound selected from the group consisting of (−)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, the monophosphate ester of (−)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, the diphosphate ester of (−)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, and the triphosphate ester of (−)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.
A method for inhibiting replication of HBV in cells comprising administering to a human an HBV inhibitory amount of a composition consisting essentially of a compound selected from the group consisting of (+)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, the monophosphate ester of (+)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, the diphosphate ester of (+)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, and the triphosphate ester of (+)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.