Macrocyclic ghrelin receptor antagonists and inverse...

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 5/12 (2006.01) A61K 38/12 (2006.01) A61P 1/14 (2006.01)

Patent

CA 2583345

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/or variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as antagonists or inverse 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, cardiovascular disorders, obesity and obesity-associated disorders, gastrointestinal disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

L'invention concerne des composés macrocycliques définis de manière conformationnelle s'étant révélés être des modulateurs sélectifs du récepteur de la ghréline (récepteur du sécrétagogue d'hormone de croissance, GHS-R1a et des sous-types, des isoformes et/ou des variants de ceux-ci). L'invention concerne des procédés de synthèse de composés selon l'invention. Ceux-ci sont utiles comme antagonistes ou agonistes inverses du récepteur de la ghréline et comme médicaments destinés au traitement et à la prévention d'une palette d'états médicaux comme, mais sans caractère restrictif, des troubles métaboliques et/ou endocriniens, des troubles cardio-vasculaires, l'obésité et des troubles associés à l'obésité, des troubles gastro-intestinaux, des troubles génétiques, des troubles hyperprolifératifs et des troubles inflammatoires.

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