Columbia University

Sloan-Kettering Institute for Cancer Research

Glaxosmithkline LLC

Les Laboratoires Servier

Armgo Pharma, Inc.

Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Glaxo Group Limited

Merck Hdac Research, LLC

Other

Aton Pharma, Inc.

Sandro Belvedere

Donald W Landry

Riccardo Giovannini

Thomas Allen Miller

David James Witter

Giuseppe Alvaro

Romano Di Fabio

Jiaming Yan

Victoria M Richon

Ronald C Breslow

Paul A Marks

Richard A Rifkind

Leland J Gershell

Shixian Deng

David Amantini

Joey Lee Methot

Daniele Andreotti

Christopher Hamblett

Nicole Villeneuve

Alessandro Falchi

Pascal Taulelle

Yael Webb

Marc Bertrand

David J Witter

The present disclosure relates to crystalline forms of the compound 4-[(7-methoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)yl)methyl]benzoic acid hemifumarate, pharmaceutical compositions comprising these compounds and uses thereof to treat diseases and conditions associated with Ryanodine Receptor (RyR) dysfunction, in particular cardiac and musculoskeletal disorders and diseases.

Crystalline forms of a Ryanodine receptor modulator and uses thereof

The invention provides a process for preparing a 2,3,4,5-tetrahydro[1,4]benzothiazepine of formula: by reacting a [2-(acylaminoethyl)thio]arene of formula with an aldehyde or a multimer thereof, and with an acid. The invention also provides for first reacting the [2-(acylaminoethyl)thio]arene with the aldehyde or multimer thereof and a base to form an [N-hydroxymethyl-2-[acylaminoethyl)thio]arene of formula then treating the [N-hydroxymethyl-2-(acylaminoethyl)thio]arene with the acid to form the 2,3,4,5-tetrahydro[1,4]benzothiazepine.

Process for preparing benzothiazepines from gamma-aminoalkylbenzenes

The present invention relates to 1,4-benzothiazepine derivatives and their use to treat conditions, disorders and diseases associated with ryanodine receptors (RyRs) that regulate calcium channel functioning in cells. The invention also discloses pharmaceutical compositions comprising the compounds and uses thereof to treat diseases and conditions associated with RyRs, in particular cardiac, musculoskeletal and central nervous system (CNS) disorders.

Agents for treating disorders involving modulation of ryanodine receptors

The present invention is directed to prodrugs of hydroxamic acid based histone deacetylase (HDAC) inhibitors, e.g., suberoylanilide hydroxamic acid (SAHA). The prodrugs are acylated derivatives having increased aqueous solubility and cellular permeability as compared with the free hydroxamic acid, and are useful for inhibiting HDACs, and for selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the prodrugs of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The prodrugs of the invention are also useful in the prevention and treatment of thioredoxin (TRX)-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases.

Histone deacetylase inhibitor prodrugs

This invention relates to imidazopyrazine substituted piperidine derivatives and their use as pharmaceuticals.

Imidazo[1,2-a]pyrazines as orexin receptor antagonists

A method of treatment of anxiety disorders which comprises administering to a host in need thereof an effective amount of a compound of formula (I): 

Pyridine derivatives and their use in the treatment of psychotic disorders

This invention relates to imidazopyrimidine substituted piperidine derivatives and their use as pharmaceuticals.

Imidazo[1,2-A]pyrimidines as orexin receptor antagonists

The present invention relates to a novel class of hydroxamic acid derivatives having a benzothiophene or thiophene backbone. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid compounds can also inhibit historic deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention are also useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases, The present invention further provides pharmaceutical compositions comprising the hydroxamic acid derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the hydroxamic acid derivatives in vivo.

Thiophene and benzothiophene hydroxamic acid derivatives

A pyridine derivative novel compounds of formula (I) or a pharmaceutically acceptable salt thereof where all variables are defined herein. The compounds are useful in the treatment of psychotic disorders.

The present invention relates to a novel class of hydroxamic acid derivatives having at least two aryl containing groups, at least one of which is a quinolinyl, isoquinolinyl or benzyl moiety, linked to the hydroxamic acid group through a methylene chain. The hydroxamic acid compounds can be used to treat cancer, for example, brain cancer. The hydroxamic acid compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention are also useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases.

Hydroxamic acid compounds and methods of use thereof

The invention relates to hydroxamic acid derivatives having carbamate linkage with the structural formula that are inhibitors of histone deacetylase (HDAC), and are useful in the prevention and/or treatment of cellular proliferative diseases, for example cancer, autoimmune, allergic and inflammatory diseases, diseases of the central nervous systems (CNS) such as neurodegenerative diseases, and in the prevention and/or treatment of restenosis.

Histone deacetylase inhibitors

This invention relates to hydroxamic acid derivatives having a urea linkage, that are inhibitors of histone deacetylase (HDAC), and are useful in the prevention and/or treatment of cellular proliferative diseases, for example cancer, autoimmune, allergic and inflammatory diseases, diseases of the central nervous system (CNS) such as neurodegenerative diseases, and in the prevention and/or treatment of restenosis.

There are provided according to the invention novel compounds of formula (I) or a pharmaceutically acceptable salt or solvate thereof: wherein all variables are defined herein. Also provided are pharmaceutical compositions containing the same and methods for their use in therapy.

This invention relates to hydroxamic acid derivatives having a sulfonamide linkage, that are inhibitors of histone deacetylase (HDAC), and are useful in the prevention and/or treatment of cellular proliferative diseases, for example cancer, autoimmune, allergic and inflammatory diseases, diseases of the central nervous system (CNS) such as neurodegenerative diseases, and in the prevention and/or treatment of restenosis.

Growing community of inventors

Verona, Italy

Sandro Belvedere