Tranzyme Pharma Inc.

Ocera Therapeutics, Inc.

Cyclenium Pharma Inc.

Mark L Peterson

Hamid R Hoveyda

Graeme Lovat Fraser

Kamel Benakli

Sylvie Beaubien

Luc Ouellet

Eric Marsault

Mahesh Ramaseshan

Éric Marsault

Sophie Beauchemin

Yves Dory

Pierre Deslongchamps

Carl St-Louis

Gérald Villeneuve

Daniel Fortin

Hamid Hoveyda

Ruoxi Lan

Amal Wahhab

Dwight Macdonald

Dwight MacDonald

Helmut Thomas

Luc Oullet

Daniel Dubé

Shigui Li

Luc Richard

Graeme Fraser

Daniel Dube

Robert Deziel

Zhigang Wang

Martin Brassard

Martin Vezina

Robert Dèziel

Martin Vézina

David Drutz

Gerald Villeneuve

Luc Quellet

Kamel Benkali

The present disclosure relates to novel macrocyclic compounds and libraries thereof containing heteroaryl moieties that are useful as research tools for drug discovery efforts. The present disclosure also relates to methods of preparing these compounds and libraries and methods of using these libraries, such as in high throughput screening. In particular, these libraries are useful for evaluation of bioactivity at existing and newly identified pharmacologically relevant targets, including G protein-coupled receptors, nuclear receptors, enzymes, ion channels, transporters, transcription factors, protein-protein interactions and nucleic acid-protein interactions. As such, these libraries can be applied to the search for new pharmaceutical agents for the treatment and prevention of a range of medical conditions.

Libraries of heteroaryl-containing macrocyclic compounds and methods of making and using the same

The present invention provides novel conformationally-defined macrocyclic compounds that can function as selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, bone disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

Macrocyclic ghrelin receptor modulators and methods of using the same

The present invention is directed to novel macrocyclic compounds of formula (I) and their pharmaceutically acceptable salts, hydrates or solvates: wherein R, R, R, R, R, R, n, m, p Z, Z, and Zare as described in the specification. The invention also relates to compounds of formula (I) which are antagonists of the motilin receptor and are useful in the treatment of disorders associated with this receptor and with or with motility dysfunction.

Intermediates for macrocyclic compounds

The present invention provides novel conformationally-defined macrocyclic compounds that can function as selective modulators of the ghrelin receptor (growth hormone sceretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, bone disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

The present invention is directed to novel macrocyclic compounds of formula (I) and their pharmaceutically acceptable salts, hydrates or solvates: wherein R, R, R, R, R, R, n, m, p Z, Z, and Zare as describe in the specification. The invention also relates to compounds of formula (I) which are antagonists of the motilin receptor and are useful in the treatment of disorders associated with this receptor and with or with motility dysfunction.

Novel spatially-defined macrocyclic compounds incorporating peptide bond surrogates are disclosed. Libraries of these macrocycles are then used to select one or more macrocycle species that exhibit a specific interaction with a particular biological target. In particular, compounds according to the invention are disclosed as agonists or antagonists of a mammalian motilin receptor and a mammalian ghrelin receptor.

Spatially-defined macrocycles incorporating peptide bond surrogates

Processes for intermediates for macrocyclic compounds

The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

Methods of using macrocyclic modulators of the ghrelin receptor

Novel spatially-defined macrocyclic compounds containing specific conformational control elements are disclosed. Libraries of these macrocycles are then used to select one or more macrocycle species that exhibit a specific interaction with a particular biological target. In particular, compounds according to the invention are disclosed as agonists or antagonists of a mammalian motilin receptor and a mammalian ghrelin receptor.

Spatially-defined macrocyclic compounds useful for drug discovery

Methods of treating cachexia with macrocyclic modulators of the ghrelin receptor

The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective agonists of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Such compounds are useful as medicaments for treatment and prevention of a range of medical conditions characterized by disturbed gastrointestinal motility including, but not limited to, post-surgical gastroparesis and post-operative ileus in combination with opioid-induced bowel dysfunction. These agents are effective for multiple disorders at dose levels equivalent to those required to treat a single disorder.

Methods of using macrocyclic agonists of the ghrelin receptor for treatment of gastrointestinal motility disorders

Growing community of inventors

Sherbrooke, Canada

Mark L Peterson