Metro International Biotech, LLC

Glaxosmithkline LLC

Glaxosmithkline Intellectual Property (No.2) Limited

Newsouth Innovations Pty Limited

Bruce G Szczepankiewicz

Robert B Perni

Jonathan N Kremsky

Karsten Koppetsch

James M McKearin

David J Livingston

Pui Yee Ng

Charles A Blum

Richard Dana Caldwell

David Andrew Sinclair

Jeremy S Disch

Brian H White

Christopher Oalmann

Ryan Michael Fox

Karl D Normington

Rebecca L Casaubon

William Henry Miller

Mateusz Pitak

Joseph Harris

Martin Bates

Jonathan Morris

Karen Lavery

Frank Preugschat

Hamish Toop

Matthew Baevsky

The present disclosure relates to crystalline solids comprising a compound of Formula (I), wherein R is n-propyl, and methods of making compounds of Formula (I) wherein R is C1-C4 alkyl or C2-C4 alkenyl. The present disclosure also relates to crystalline solids comprising a compound of Formula (II), The present disclosure further relates to methods of preparing the crystalline solids, and pharmaceutical preparations of the crystalline solids, and use of such pharmaceutical preparations in treatment of diseases and conditions.

Crystalline solids of nicotinic acid mononucleotide and esters thereof and methods of making and use

The invention relates to compounds and compositions for modulation of nicotinamide adenine dinucleotide (NAD+). The invention also relates to methods of making such compounds and compositions. The invention relates to pharmaceutical compositions containing one or more NAD+ modulating compounds as a first ingredient in combination with one or more active pharmaceutical ingredients. Further, the invention relates to methods of using such compounds or compositions to promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for treating diseases and/or improving cell and tissue survival.

Compositions comprising a phosphorus derivative of nicotinamide riboside and methods for modulation of nicotinamide adenine dinucleotide

The invention relates to compositions of nicotinamide mononucleotide derivatives and their methods of use. The invention also relates to methods of preparing nicotinamide mononucleotide derivatives. The invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinamide mononucleotide derivative. The invention relates to methods of using nicotinamide mononucleotide derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for treating diseases and improving cell and tissue survival.

Nicotinamide mononucleotide derivatives and their uses

The present disclosure relates to compounds and compositions for use in treating disease, such as viral infection. As disclosed herein, the compounds include an 'NMN-like' moiety linked to another moiety with biological activity upon administration. In some cases, the disease to be treated is infection with viruses. Such viruses include coronaviruses, such as SARS, MERS, or COVID-19, HIV, and viruses associated with hepatitis. Further, the invention relates to methods of using such compounds or compositions to promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD) in cells and tissues for treating diseases and/or improving cell and tissue survival.

Anti-viral compounds and methods of use

Provided herein are compounds of Formula (I) and their salts, and compositions comprising such compounds that are useful for increasing the amount of NADin cells. Also disclosed are methods of using the disclosed compounds and compositions for treating, for example, diseases or disorders related to aging or stress, diabetes, obesity, mitochondrial diseases, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing.

Nicotinamide riboside analogs, pharmaceutical compositions, and uses thereof

Compositions and methods for modulation of nicotinamide adenine dinucleotide

The present invention relates to novel substituted bridged urea compounds, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Substituted bridged urea analogs as sirtuin modulators

Provided herein are stereoisomerically pure ester and carbonate analogues of nicotinamide riboside and nicotinamide riboside hydride, and pharmaceutical compositions and uses thereof. The stereoisomerically pure ester and carbonate analogues of nicotinamide riboside and nicotinamide riboside hydride may be used to treat a disease or disorder that would benefit from increased NAD levels including a mitochondrial disease or disorder, insulin resistance, a metabolic syndrome, diabetes, obesity, for increasing insulin sensitivity in a subject, or to treat or prevent a skin condition. The compounds have general formulas (I) or (II): wherein Ris &#x2014;C(&#x2550;O)&#x2014;X&#x2014;(C-Cstraight chain or branched) alkyl or &#x2014;C(&#x2550;O)&#x2014;X&#x2014;(C-Cstraight chain or branched) alkenyl; each Ris independently selected from hydrogen, and a &#x2014;C(O)&#x2014;X&#x2014;(C-Cstraight chain or branched) alkyl or a &#x2014;C(O)&#x2014;X&#x2014;(C-Cstraight chain or branched) alkenyl; and X is a covalent bond or O.

Nicotinamide riboside analogs and pharmaceutical compositions and uses thereof

Provided herein are crystalline beta-D-nicotinamide riboside chloride compositions and methods of preparation and use thereof. Also provided are related pharmaceutical compositions and methods of use thereof. The crystalline beta-D-nicotinamide riboside chloride compositions may be used to treat a disease or disorder that would benefit from increased NAD levels including a mitochondrial disease or disorder, insulin resistance, a metabolic syndrome, diabetes, obesity, or for increasing insulin sensitivity in a subject.

Preparation and use of crystalline beta-D-nicotinamide riboside

The present invention relates to novel substituted bridged urea compounds of Formula (I): or a pharmaceutically acceptable salt thereof, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Provided herein are novel substituted bridged urea and related analogs and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent. 

Provided herein is a simple, one-step, non-enzymatic synthesis of O-Acetyl-ADP-ribose (OAADPR) from NAD and sodium acetate in acetic acid. The extension of this reaction to other carboxylic acids, demonstrates that the reaction between NAD, and NAD analogs produces mixtures of the corresponding 2'- and 3&#x2032;-carboxylic esters. Included are O-carboxyl-ADP-ribose compounds and corresponding methods of synthesis (e.g., O-propionyl-ADP-ribose, O-succinyl-ADP-ribose, O-malonyl-ADP-ribose), as well as non-adenosine nucleoside compounds.

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Cambridge, MA, United States of America

Bruce G Szczepankiewicz