Antiviral phosphonomethoxy nucleotide analogs having increased oral bioavailability

USRE38333E1 · kind E1 · reissue

Assignee

• Gilead Sciences, Inc. · US

Inventors

• Murty N. Arimilli · Oak Ridge, US
• Kenneth C. Cundy · Redwood City, US
• Joseph P. Dougherty · New York, US
• Choung U. Kim · Redwood City, US
• Reza Oliyai · Burlingame, US
• Valentino J. Stella · Lawrence, US

Key dates

• Filing date: May 29, 2002
• Grant date: Nov 25, 2003
• Expiry date: May 29, 2022

Classification

• Technology area (CPC —): General

Abstract

Novel compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure —OC(R2)2OC(O)X(R)a, wherein R2 independently is H, C1-C12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR3 in which R3 is C1-C12 alkyl; X is N or O; R is independently H, C1-C12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro, —O—, —N═, —NR4—, —N(R4)2— or OR3, R4 independently is —H or C1-C8 alkyl, provided that at least one R is not H; and a is 1 or 2, with the proviso that when a is 2 and X is N, (a) two R groups can be taken together to form a carbocycle or oxygen-containing heterocycle, or (b) one R additionally can be OR3. The compounds are useful as intermediates for the preparation of antiviral compounds or oligonucleotides, or are useful for administration directly to patients for antiviral therapy of prophylaxis. Embod…