Antiviral phosphonomethoxy nucleotide analogs having increased oral bioavailability

US5977089A · kind A · utility

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: Nov 6, 1998
• Grant date: Nov 2, 1999
• Expiry date: Nov 6, 2018

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07F9/6512
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

Compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure --OC(R.sup.2).sub.2 OC(O)X(R).sub.a, wherein R.sup.2 independently is H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR.sup.3 in which R.sup.3 is C.sub.1 -C.sub.12 alkyl; X is N or O; R is independently H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro, --O--, --N.dbd., --NR.sup.4 --, --N(R.sup.4).sub.2 -- or OR.sup.3, R.sup.4 independently is --H or C.sub.1 -C.sub.8 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 OR.sup.3. The compounds are useful as intermediates for the preparation of antiviral compounds or oligonucleotides, or are useful for administration directly …