Novel chromone oxime derivative and its use as allosteric modulator of metabotropic glutamate receptors

Abstract

The present invention provides a novel chromone oxime derivative of formula (I), which is a modulator of nervous system receptors sensitive to glutamate and, furthermore, presents an advantageously high brain penetration upon oral administration. The invention also relates to a pharmaceutical composition containing this compound, and to its use for the treatment or prevention of conditions associated with altered glutamatergic signalling and/or functions, or conditions which can be affected by alteration of glutamate level or signalling, particularly acute and chronic neurological and/or psychiatric disorders.

1 . A compound of the following formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or solvate thereof, wherein said compound has the (Z)-configuration at the oxime group comprised in formula (I). 
       
     
     
         2 . (canceled) 
     
     
         3 . The compound of  claim 1 , wherein the pharmaceutically acceptable salt is a hydrochloride salt. 
     
     
         4 . (canceled) 
     
     
         5 . A pharmaceutical composition comprising the compound or a pharmaceutically acceptable salt or solvate thereof, of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         6 - 21 . (canceled) 
     
     
         22 . A method of treating a condition associated with altered glutamatergic signalling and/or functions, or a condition which can be affected by alteration of glutamate level or signalling, the method comprising the administration of the compound or a pharmaceutically acceptable salt or solvate thereof, of  claim 1  to a subject in need thereof. 
     
     
         23 . The method of  claim 22 , wherein said condition associated with altered glutamatergic signalling and/or functions, or said condition which can be affected by alteration of glutamate level or signalling is selected from the group consisting of: dementias, parkinsonism and movement disorders, acute or chronic pain, anxiety disorders, schizophrenia, mood disorders, endocrine and metabolic diseases, diabetes, disorders of the endocrine glands, hypoglycaemia, and cancers. 
     
     
         24 . The method of  claim 23 , wherein said dementias are selected from the group consisting of: dementias of the Alzheimer's type (DAT); Alzheimer's disease; Pick's disease; vascular dementias; Lewy-body disease; dementias due to metabolic, toxic and deficiency diseases, including alcoholism, hypothyroidism, and vitamin B12 deficiency; AIDS-dementia complex; Creutzfeld-Jacob disease; and atypical subacute spongiform encephalopathy. 
     
     
         25 . The method of  claim 23 , wherein said parkinsonism and movement disorders are selected from the group consisting of: Parkinson's disease; multiple system atrophy; progressive supranuclear palsy; corticobasal degeneration; hepatolenticular degeneration; chorea, including Huntington's disease and hemiballismus; athetosis; dystonias, including spasmodic torticollis, occupational movement disorder, and Gilles de la Tourette syndrome; tardive or drug induced dyskinesias, including levodopa-induced dyskinesia; tremor; and myoclonus. 
     
     
         26 . The method of  claim 23 , wherein said anxiety disorders are selected from the group consisting of: panic disorders; phobias; obsessive-compulsive disorders; stress disorders, including post-traumatic stress disorder; and generalized anxiety disorders. 
     
     
         27 . The method of  claim 23 , wherein said mood disorders are selected from the group consisting of depressive disorders and bipolar disorders. 
     
     
         28 . The method of  claim 23 , wherein the method comprises orally administering said compound or a pharmaceutically acceptable salt or solvate thereof, to said subject. 
     
     
         29 . The method of  claim 23 , wherein said subject is a human. 
     
     
         30 . A method of treating Parkinson's disease, the method comprising the administration of the compound or a pharmaceutically acceptable salt or solvate thereof, of  claim 1  to a subject in need thereof. 
     
     
         31 . The method of  claim 30 , wherein the method comprises orally administering said compound or a pharmaceutically acceptable salt or solvate thereof, to said subject. 
     
     
         32 . The method of  claim 30 , wherein said subject is a human.