Gilead Sciences, Inc.

Syntex (u.s.a.) Inc.

Ernest J Prisbe

Lawrence R McGee

John C Rohloff

Murty N Arimilli

William A Lee

Robert J Jones

John D Munger

Choung U Kim

Matthew A Williams

Lijun Zhang

Norbert W Bischofberger

Kenneth M Kent

Michael J Postich

Petr Alexander

Michael S Louie

Daphne E Kelly

Kuei-Ying Lin

Julien P Verheyden

Daniel P McGee

Tomas Cihlar

John C Martin

Kenneth C Cundy

Gong-Xin He

Eugene J Eisenberg

Mark L Sparacino

Mark W Becker

Harlan H Chapman

Daphne E St John

Michael R Kernan

Hans Maag

Arnold J Gutierrez

Lisa M Schultze

G V Madhaven

G V Madhavan

Lawrence V Manes

Thomas T K Lee

Lawwrence R Mcgee

A novel method has led to the identification of novel mixed ester-amidates of PMPA for retroviral or hepadnaviral therapy, including compounds of structure (5a) having substituent groups as defined herein. Compositions of these novel compounds in pharmaceutically acceptable excipients and their use in therapy and prophylaxis are provided.

Prodrugs of phosphonate nucoleotide analogues

Nucleotide analogs characterized by the presence of an amidate linked amino acid or an ester linked group which is bonded to the phosphorus atom of phosphonate nucleotide analogs are disclosed. The analogs comprise a phosphoamidate or ester bond that is hydrolyzed in vivo to yield a corresponding phosphonate nucleotide analog. Methods and intermediates for their synthesis and use are described.

Nucleotide analogs

Prodrugs of phosphonate nucleotide analogues

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

Disclosed are methods for the dealkylation of phosphonate esters by use of trimethylchlorosilane as the dealkylating agent. In particular, this invention is directed to the discovery that high yields for the dealkylation of phosphonate esters can be achieved within relatively short reaction times by the use of trimethylchlorosilane provided that the dealkylation procedure occurs in a sealed vessel containing a compatible solvent.

Methods for the dealkylation of phosphonate esters

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

Nucleotide phosphonate esters characterized by the presence of an ester linked group which is bonded to the phosphorus atom of phosphonate nucleotide analogs are disclosed. The analogs comprise an ester bond that is hydrolyzed in vivo to yield a corresponding phosphonate nucleotide analog. Methods and intermediates for their synthesis and use are described.

In accordance with this invention novel compounds are provided that are selected from saturated and unsaturated pyrans and furans substituted with at least a phosphonate group and a heterocyclic base. These compounds are useful as antiinfectives, flame retardants, diagnostic oligonucleotides and immunogens.

Compounds and methods for making and using same

Growing community of inventors

Los Altos, CA, United States of America

Ernest J Prisbe