title: Novel heterocyclic compounds as mGlu5 antagonists: WO2009015897.
abstract: Metabotropic glutamate receptor 5 (mGlu5) negative allosteric modulators (NAMs) have previously been implicated in a number of pathophysiological conditions, based on preclinical, and to some extent clinical, proof of concept for migraine, gastroesophageal reflux disease, Parkinson's disease and anxiety. In the past, the potential use of known mGlu5 antagonists for the treatment of lower urinary tract disorders was disclosed. In the patent evaluated herein, novel derivatives of 4-(prop-2-ynylidene)piperidine are described and claimed by Recordati Ireland Ltd, Ireland, as NAMs at mGlu5 for the treatment of lower urinary tract disorders. Selected compounds reported in this application were efficacious in the cystometry model of bladder dysfunction in conscious rats, and mGlu5 NAMs are, therefore, suggested to have potential for the treatment of lower urinary tract disorders.
authors.affiliation: Department of Medicinal Chemistry, Lundbeck Research USA, 215 College Road, Paramus, NJ 07652, USA. DADO@Lundbeck.com
authors.forename: Dario
authors.initials: D
authors.lastname: Doller
authors.forename: Guiying
authors.initials: G
authors.lastname: Li
authors.forename: Robbin M
authors.initials: RM
authors.lastname: Brodbeck
authors.forename: Christian
authors.initials: C
authors.lastname: Thomsen
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D004195:Disease Models, Animal; D015195:Drug Design; D006801:Humans; D010330:Patents as Topic; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D014570:Urologic Diseases / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D010880:Piperidines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate