Analogs of pridopidine, their preparation and use

Abstract

This invention provides a composition comprising pridopidine or pharmaceutically acceptable salt thereof and at least one of compounds 1-8:or a pharmaceutically acceptable salt thereof; and to methods of use thereof.

What is claimed is: 
     
         1 . A method of treating, slowing the progression, lessening the decline, delaying onset of symptoms or slowing the progression of symptoms of a neurodegenerative or neurodevelopmental disease or disorder in a subject; wherein the method comprises administering a composition comprising pridopidine or a pharmaceutically acceptable salt thereof and at least one of Compounds 1-8 or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein the neurodegenerative disease or disorder is selected from the group consisting from Huntington Disease, prodromal/premanifest Huntington disease, Amyotrophic Lateral Sclerosis (ALS), Parkinson's Disease, Parkinson's Disease associated with glucocerebrosidase (GBA) deficiency, dystonia, cognitive disorder, dyskinesia, mild cognitive impairment (MCI), Alzheimer's Disease, age related memory loss, depression and anxiety, bacterial infections-induced depression, optic neuropathies including glaucoma, age-related macular degeneration (AMD), Leber's Hereditary Optic Neuropathy (LHON) and retinitis pigmentosa, mitochondrial disease or dysfunction, Wolfram disease and a viral infection; and wherein the neurodevelopmental disease or disorder is Rett syndrome and Fragile X Syndrome. 
     
     
         2 . The method of  claim 1 , wherein the method comprises treating, slowing the progression, lessening the decline, delaying onset of symptoms or slowing the progression of symptoms of Huntington disease, wherein the Huntington disease is an early stage Huntington disease. 
     
     
         3 . The method of  claim 1 , wherein the method comprises treating, slowing the progression, lessening the decline, delaying onset of symptoms or slowing the progression of symptoms of ALS. 
     
     
         4 . The method of  claim 1 , wherein the method comprises treating, slowing the progression, lessening the decline, delaying onset of symptoms or slowing the progression of symptoms of dystonia, wherein the dystonia is a severe dystonia. 
     
     
         5 . The method of  claim 1 , wherein the method treating, slowing the progression, lessening the decline, delaying onset of symptoms or slowing the progression of symptoms of Rett Syndrome. 
     
     
         6 . The method of  claim 1 , wherein the method comprises treating, slowing the progression, lessening the decline, delaying onset of symptoms or slowing the progression of symptoms of a mitochondrial disease or dysfunction, wherein the mitochondrial disease or dysfunction is Lysosomal Storage Disease (LSD), leukodystrophies or a vanishing white matter (VWM) disease. 
     
     
         7 . The method of  claim 1 , wherein the composition comprises pridopidine or a pharmaceutically acceptable salt thereof and at least one of compound 1, compound 4, pharmaceutically acceptable salt thereof or combination thereof. 
     
     
         8 . The method of  claim 1 , wherein the composition comprises pridopidine or a pharmaceutically acceptable salt thereof and compound 1 or pharmaceutically acceptable salt thereof. 
     
     
         9 . The method of  claim 1 , wherein the composition comprises pridopidine or a pharmaceutically acceptable salt thereof, compound 1 and compound 4 or pharmaceutically acceptable salt thereof. 
     
     
         10 . The composition of  claim 1 , wherein the composition comprises pridopidine salt, wherein the salt is hydrochloride, hydrobromide, nitrate, perchlorate, phosphate, sulphate, formate, acetate, aconate, ascorbate, benzenesulphonate, benzoate, cinnamate, citrate, embonate, enantate, fumarate, glutamate, glycolate, lactate, maleate, malonate, mandelate, methane-sulphonate, naphthalene-2-sulphonate, phthalate, salicylate, sorbate, stearate, succinate, tartrate or toluene-p-sulphonate salt. 
     
     
         11 . The method of  claim 1 , wherein the composition is an oral dosage unit comprising between 0.5-315 mg pridopidine. 
     
     
         12 . The method of  claim 11 , wherein the oral dosage unit form comprises between 0.5-10 mg pridopidine. 
     
     
         13 . The method of  claim 11 , wherein the oral dosage unit form comprises between 10-22.5 mg pridopidine. 
     
     
         14 . The method of  claim 11 , wherein the oral dosage unit form comprises between 22.5-45 mg pridopidine. 
     
     
         15 . The method of  claim 11 , wherein the oral dosage unit form comprises between 45-250 mg pridopidine. 
     
     
         16 . The method of  claim 15 , wherein the oral dosage unit form comprises between 45-135 mg pridopidine. 
     
     
         17 . The method of  claim 11 , wherein the oral dosage unit form comprises between 90-315 mg pridopidine. 
     
     
         18 . The method of  claim 1 , wherein the weight ratio between the pridopidine and at least one of compounds 1-8 is in the range of 1:0.001 to 1:0.1. 
     
     
         19 . The method of  claim 18 , wherein the weight ratio between the pridopidine and at least one of compounds 1-8 is in the range of 1:0.005 to 1:0.1. 
     
     
         20 . The method of  claim 19 , wherein the weight ratio between the pridopidine and at least one of compounds 1-8 is in the range of 1:0.001 to 1:0.005. 
     
     
         21 . The method of  claim 11 , wherein the oral dosage unit is formulated as a tablet, a capsule, a pill, powder, liquid solution or as a liquid suspension.