Isis Pharmaceuticals, Inc.

Acea Biosciences, Inc.

Valeant Pharmaceuticals North America

Valeant Research and Development

Ribapharm Inc.

Ibc Advanced Technologies, Inc.

Merck Sharp + Dohme Corp.

Ionis Pharmaceuticals, Inc.

Haoyun An

Phillip Dan Cook

Zhi Hong

Muthiah Manoharan

Xiao Xu

Stephanie Shaw

Martin A Maier

Thazha P Prakash

Xiaobo Wang

Balkrishen Bhat

P Dan Cook

Tingmin Wang

Yili Ding

Ronald L Bruening

David Brian Olsen

Jean-Luc Girardet

Yama A Abassi

Bryon J Tarbet

Malcolm Maccoss

Kanda Ramasamy

Clayton Harris

Krzysztof E Krakowiak

Biao Xi

Charles John Guinosso

Jim Zhen Wu

Robert L Orr

Nanhua Hugh Yao

Allister S Fraser

Pei-Pei Kung

Deborah F Johnson

Xiaopeng Mo

Weijian Zhang

Neelima Bhat

Becky Haly

Frank Rong

Shahul Nilar

Todd Appleby

William Ricketts

Suetying Chow

Lawrence C Kuo

Steven S Carroll

Robert L Lafemina

Marija Prhavc

Anne B Eldrup

Amy L Himmelberger

An improved method of preparing a sugar modified nucleoside analog includes a protocol in which a hydroxy group of a sugar is selectively deprotected and oxidized prior to nucleophilic modification of the corresponding carbonyl group. The modified sugar is then coupled to a heterocyclic base that is modified with a dual nucleophilic reagent in a further step that provides N6-modified adenosine analogs with high stereoselectivity.

Synthesis and use of 2'-substituted-N6-modified nucleosides

The present invention provides substituted di-, tri-, tetra- and penta-sulfide compounds and compositions, and methods of using the same for the treatment and/or prevention of a cell proliferative disorder. The present invention also provides methods for preparing trisulfide compounds and compositions.

Substituted organosulfur compounds and methods of using thereof

Novel compounds having a fused bicyclic heteroaromatic ring system substituted with a heteroaryl five-membered ring are disclosed. The compounds inhibit growth of a variety of types of cancer cells, and are thus useful for treating cancer. Efficacy of these compounds is demonstrated with a system for monitoring cell growth/migration, which shows they are potent inhibitors of growth and/or migration of cancer cells. In addition, compounds of the invention were shown to stop growth of tumors in vivo, and to reduce the size of tumors in vivo. Compositions comprising these compounds, and methods to use these compounds and compositions for treatment of cancers, are disclosed.

Heterocyclic compounds and uses as anticancer agents

The invention provides a synthetic and manufacturing process for the preparation of the anticancer drug, fluorapacin, bis(4-fluorobenzyl)trisulfide, and related trisulfide derivatives on large scale. Also provided are processes for the purification and isolation of fluorapacin having high purity and improved stability.

Synthetic process for anticancer drug fluorapacin and trisulfide derivatives

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A hydroxyalkylated heterocyclic base is prepared by reacting a heterocyclic base with an alkylene carbonate in dimethylacetamide as a solvent, wherein the hydroxyalkylated heterocyclic base is isolated from the solvent using isopropanol or tert-butylmethylether.

Synthesis for hydroxyalkylated heterocyclic bases

Various 2'-beta-methyl-6-substituted adenosine analogs (including 2,6-disubstituted adenosine, 8-aza-6-substituted adenosine, and 2-aza-6-substituted adenosine) are prepared by conventional and combinatorial library approaches. Contemplated compounds are particularly useful as therapeutic agents, and especially as antiviral agents.

2-beta -modified-6-substituted adenosine analogs and their use as antiviral agents

The invention provides substituted quinoxalines having the general formulas where R, R, R, and Rare, inter alia, alkyl, aryl, or heteroaryl groups; Z is NH or O; and X is, inter alia, COOH or CONH. The compounds of the invention have antiviral and immunomodulatory activity and are useful for treating infectious diseases, particularly viral infections.

Quinoxaline derivatives having antiviral activity

Substituted isothiazole compounds and compositions are provided, wherein particularly preferred compositions and methods are directed towards inhibition of various protein kinases (especially MEK and/or ERK). Consequently, particularly preferred methods include treatment of diseases associated with abnormality in MEK and/or ERK function.

Heterocyclic compounds and uses thereof

The present invention is directed to nucleoside monomers wherein the 3'-O atom is replaced with a methylene group. The present invention also provides oligomers comprising a plurality of such monomers which are linked by methylene phosphonate linkages. Further, methods of preparing monomers and oligomers according to the present invention are provided.

C3' -methylene hydrogen phosphonate oligomers and related compounds

A polymerase inhibitor has first moiety coupled to a second moiety via an optional linker in which the first moiety binds to an initiation nucleotide binding site of a polymerase and forms at least two hydrogen bonds with an RNA template strand that is associated with the polymerase, and in which the second moiety comprised a compound that binds to a site proximal to the nucleotide binding site of the polymerase and thereby increases the affinity of the polymerase inhibitor to the polymerase.

Inhibitors for de novo-RNA polymerases and methods of identifying targets for same

Conformationally restricted 2&prime;, 4&prime;-bridged nucleoside analogues are described herein. The compounds can be prepared by cyclization at C2&prime; and C4&prime; of nucleosides through a linker or linking molecule. These novel nucleosides have a desired, locked sugar pucker and are potentially useful as pharmaceutical ingredients, and especially for use in treatment of HCV.

Nucleosides having bicyclic sugar moiety

Compositions comprising novel chemical libraries are prepared. The compositions of the present invention are useful as antibacterial and other pharmaceutical agents and as intermediates for preparation of other pharmaceutical agents. In addition, compounds of the present invention are useful as research reagents.

Complex chemical libraries

The present invention is directed to nucleoside monomers wherein the 3&prime;-O atom is replaced with a methylene group. The present invention also provides oligomers comprising a plurality of such monomers which are linked by methylene phosphonate linkages. Further, methods of preparing monomers and oligomers according to the present invention are provided.

C3&prime;-methylene hydrogen phosphonate oligomers and related compounds

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Carlsbad, CA, United States of America

Haoyun An