Gilead Sciences, Inc.

John D Munger

John C Rohloff

Ernest J Prisbe

Choung U Kim

Matthew A Williams

Lawrence R McGee

Lijun Zhang

Kenneth M Kent

Michael J Postich

Daphne E Kelly

Mark D Matteucci

Robert J Jones

Daphne E St John

Lisa M Schultze

Sundaramoorthi Swaminathan

Murty N Arimilli

Jeff Pudlo

Lawrence V Manes

Thomas T K Lee

The present invention provides new synthetic methods and compositions. In particular, new methods of preparing intermediates useful in the synthesis of neuraminidase inhibitors and compositions useful as intermediates that are themselves useful in the synthesis of neuraminidase inhibitors are provided.

Preparation of cyclohexene carboxylate derivatives

The invention provides crystalline forms of adefovir dipivoxil and methods to prepare the crystals. The compositions and methods of the present invention have desirable properties for large scale synthesis of crystalline adefovir dipivoxil or for its formulation into therapeutic dosages. Invention compositions include an anhydrous crystal form of adefovir dipivoxil.

Nucleotide analog compositions

The present invention provides new synthetic methods and compositions. In particular, new methods of preparing intermediates such as those having formulas (I)-(IV), useful in the synthesis of neuraminidase inhibitors and compositions useful as intermediates that are themselves useful in the synthesis of neuraminidase inhibitors are provided.

Preparation of carbocyclic compounds

The invention provides a composition comprising bis(POC)PMPA and fumaric acid (1:1). The composition is useful as an intermediate for the preparation of antiviral compounds, or is useful for administration to patients for antiviral therapy or prophylaxis. The composition is particularly useful when administered orally. The invention also provides methods to make PMPA and intermediates in PMPA synthesis. Embodiments include lithium t-butoxide, 9-(2-hydroxypropyl) adenine and diethyl p-toluenesulfonylmethoxyphosphonate in an organic solvent such as DMF. The reaction results in diethyl PMPA preparations containing an improved by-product profile compared to diethyl PMPA made by prior methods.

Nucleotide analog composition and synthesis method

Oligomers are disclosed which have modified internucleotide linkages and can form triplex and duplex structures by binding to complementary nucleic acid sequences. The oligomers of the invention may be incorporated into carriers and may be constructed to have any desired sequence. Compositions of the invention can be used for diagnostic purposes in order to detect viruses or disease conditions.

Nuclease stable and binding competent oligomers and methods for their use

Oligonucleotide analogs are disclosed wherein one or more phosphodiester linkages between adjacent nucleotides are replaced by a backbone linkage resistant to nucleases. The modified oligonucleotides are capable of strong hybridization to target RNA or DNA. The oligomers of the invention may be used as diagnostic reagents to detect the presence or absence of the target DNA or RNA sequences to which they bind.

Modified internucleoside linkages having one nitrogen and two carbon

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Alviso, CA, United States of America

John D Munger