Pfizer Corporation

Gilead Sciences, Inc.

Gilead Pharmasset LLC

Quest Software Inc.

Agouron Pharmaceuticals, Inc.

Robert William Scott

Nicole Suzanne White

Benjamin James Roberts

Denise A Colby

Andrew Anthony Martins

Bing Shi

Fang Wang

Robert Wayne Dugger

Erik Mogalian

David B Damon

David J Kucera

Martin Gerald Teresk

Justin Philip Vitale

Jared Wayne Evans

Kenneth Stanley Matthews

Alexandra Formella

Dustin S Siegel

John Alan Tucker

Xianghong Wang

Edward Doerffler

Bruce Ross

Willard Lew

Lars V Heumann

Michael Paul DeNinno

Hiroko Masamune

Robert Poling

Andrew W Waltman

Silvio A Campagna

Katrien Brak

Andrew C Stevens

Tiago Vieira

Robert Ronald Milburn

Pavel Robertovich Badalov

Sean Timothy Neville

Christopher Frederick Matthews

Andrei Chtchemelinine

Detian Gao

Mark Charles Whitcomb

Morin Mae Frick

Clarissa Tadeus

Mary Nielsen

Brittanie Hoang

Lydia Wolfe

Steven Donald Axt

Silvio Campagna

Chia-Yun Yu

Erik Rueden

Erick Rueden

Tiago Viera

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-2LiCl, LaCl, CeCl, NdCl, or YCl; 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.

Methods for the preparation of ribosides

The present disclosure provides processes for the preparation of a compound of formula I: which is useful as an antiviral agent. The disclosure also provides compounds that are synthetic intermediates to compounds of formula I.

Synthesis of antiviral compound

Amorphous and crystalline solid forms of the anti-HCV compound (1-{3-[6-(9,9-difluoro-7-{2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-9H-fluoren-2-yl)-1H-benzoimidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (Compound I) were prepared and characterized in the solid state:  Also provided are processes of manufacture and methods of using the amorphous and crystalline forms.

Solid forms of an antiviral compound

Methods for isolating 9-{(R)-2-[((S)&#x2014;{[(S)-1-(isopropoxycarbonyl)ethyl]amino}phenoxyphosphinyl)methoxy]propyl}adenine (compound 16): a method for preparing in high diastereomeric purity, intermediate compounds 13 and 15: and a method for preparing intermediate compound 12: 9-{(R)-2-[((S)&#x2014;{[(S)-1-(isopropoxycarbonyl)ethyl]amino}phenoxyphosphinyl)methoxy]propyl}adenine has anti-viral properties.

Methods for preparing anti-viral nucleotide analogs

Methods for isolating 9-{(R)-2-[((S)-{[(S)-1-(isopropoxycarbonyl)ethyl]amino}phenoxyphosphinyl)methoxy]propyl}adenine (compound 16): a method for preparing, in high diastereomeric purity, intermediate compounds 13 and 15: and a method for preparing intermediate compound 12: 9-{(R)-2-[((S)-{[(S)-1-(isopropoxycarbonyl)ethyl]amino}phenoxyphosphinyl)methoxy]propyl}adenine has anti-viral properties.

Amorphous and crystalline solid forms of the anti-HCV compound (1-{3-[6-(9,9-difluoro-7-{2-[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-9H-fluoren-2-yl)-1H-benzoimidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (Compound I) were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using the amorphous and crystalline forms.

Methods for isolating 9-{(R)-2-[((S)&#x2014;{[(S)-1-(isopropoxycarbonyl)ethyl]amino}phenoxyphosphinyl)methoxy]propyl}adenine (compound 16): a method for preparing, in high diastereomeric purity, intermediate compounds 13 and 15: and a method for preparing intermediate compound 12: 9-{(R)-2-[((S)&#x2014;{[(S)-1-(isopropoxycarbonyl)ethyl]amino}phenoxyphosphinyl)methoxy]propyl}adenine has anti-viral properties.

Amorphous and crystalline solid forms of the anti-HCV compound (1-{3-[6-(9,9-difluoro-7-{2 -[5-(2-methoxycarbonylamino-3-methyl-butyryl)-5-aza-spiro[2.4]hept-6-yl]-3H-imidazol-4-yl}-9H-fluoren-2-yl)-1H-benzoimidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carbonyl}-2-methyl -propyl)-carbamic acid methyl ester (Compound I) were prepared and characterized in the solid state: Also provided are processes of manufacture and methods of using the amorphous and crystalline forms.

The present invention relates to methods and compounds useful in the preparation of compounds of the formula (I). 

Methods for the preparation of HCV polymerase inhibitors

A protocol management system is capable of detecting certain message protocols and applying policy rules to the detected message protocols that prevent intrusion, or abuse, of a network's resources. In one aspect, a protocol message gateway is configured to apply policy rules to high level message protocols, such as those that reside at layer 7 of the ISO protocol stack.

Systems and methods for implementing protocol enforcement rules

Compounds of the formula: where the formula variables are as defined herein, are disclosed that advantageously inhibit or block the biological activity of the HIV protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with the HIV virus. Intermediates and synthetic methods for preparing such compounds are also described.

HIV protease inhibitors, compositions containing the same, their pharmaceutical uses, material for their synthesis

The present invention concerns processes for preparing compounds of formula (I-H), or a prodrug, pharmaceutically active metabolite, or pharmaceutically active salt or solvate thereof, which are useful as inhibitors of the HIV protease enzyme.

HIV protease inhibitors, compositions containing the same, their pharmaceutical uses and materials for their synthesis

A agonists, methods of using such A agonists and pharmaceutical compositions containing such A agonists. The A agonists are useful for the reduction of tissue damage resulting from tissue ischemia or hypoxia.

Compounds for the treatment of ischemia

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San Mateo, CA, United States of America

Robert William Scott