The present invention relates to purine derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.

The present invention provides novel crystalline forms of tenofovir alafenamide comprising tenofovir alafenamide and two different pharmaceutically acceptable acids, compositions and processes for the preparation thereof, and their use in the treatment of a human immunodeficiency virus (HIV) infection or a hepatitis B virus (HBV) infection.

Provided are prodrugs of various therapeutic agents that provide enhanced bioavailability of the therapeutic agent, and methods of treatment conditions in a subject by administration of the one or prodrugs. As provided herein a prodrug includes a therapeutic agent covalently attached to a cap, the cap having a structure according to formula (I) where: R.sup.1 is a branched or linear substituted or unsubstituted C2-C6 alkyl, alkenyl, or alkynl; X is —S(0).sub.2-; R.sup.2 is a branched or linear substituted or unsubstituted C4-C20 alkyl, alkenyl, or alkynyl; and R.sup.3 is —H, C3-C5 cycloalkyl, C3-C5 cycloheteroalkyl, —C(CH.sub.3).sub.3, —CF.sub.3, —C(CF.sub.3).sub.3, or a substituted or unsubstituted phenyl.

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Functionally-modified oligonucleotide analogues comprising modified intersubunit linkages and/or modified 3′ and/or 5′-end groups are provided. The disclosed compounds are useful for the treatment of diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.

The present invention provides a modified nucleic acid monomer compound having a specific backbone such as 2-ethylglycerol or methoxymethyl-1,3-propanediol backbone instead of a ribose or deoxyribose backbone of a nucleoside, and an oligonucleic acid analogue containing the monomer compound as at least one of building blocks. The oligonucleic acid analogue containing the nucleic acid monomer compound of the present invention allows provision of an oligonucleic acid analogue having excellent biological stability and/or target gene silencing activity.

Metaphosphate compounds can directly phosphorylate other compounds to provide easy synthetic access to phosphorylated compounds, including cyclic phosphate compounds.

Compounds that modulate the conversion of AMP to adenosine by 5′-nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5′-nucleotidase, ecto is also provided.

The invention relates to a novel lipidated oxoadenine compound of formula (I) and its use as a vaccine adjuvant and as a TLR7 and/or TLR8 agonist.

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Disclosed are compounds and compositions for inhibiting the expression of a pattern recognition receptor (e.g., STING), and methods of use thereof.

Provided are methods of preparing compounds and pharmaceutical compositions comprising a compound Formula VIII for treating Filoviridae virus infections. In one aspect, the compound of Formula VIII is formed from a reaction mixture comprising the compound of Formula IX, the compound of Formula X, a coupling agent such as magnesium chloride and a non-nucleophilic base such as diisopropylethylamine. The compound of Formula IX can be formed from a compound of Formula V and a cyanating agent. The compound of Formula V can be synthesized from a reaction mixture comprising a deprotonating agent such as phenylmagnesium chloride; a silylating agent such as chlorotrimethylsilane; a coupling agent such as isopropylmagnesium chloride, an additive such as LaCl.sub.3-2LiCl, LaCl.sub.3, CeCl.sub.3, NdCl.sub.3, or YCl.sub.3; a compound of Formula VI; and 7-iodopyrrolo[2,1-f][1,2,4]triazin-4-amine. The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.