Novel derivatives of cholest-4-en-3-one oxime, pharmaceutical compositions containing them and preparation method

Abstract

The object of the invention is the use as a drug of a compound fitting formula I wherein X represents an oxygen atom or a ═N—OH group and R represents a group selected from or one of its esters and/or of its addition salts with pharmaceutically acceptable acids, particularly as a cytoprotective drug, preferentially a cardioprotective and/or neuroprotective drug, the compounds of formula I wherein R is R2, R3, R4, R5 or R6 as novel compounds as well as their preparation method and use.

1 . A compound of formula I 
       
         
           
           
               
               
           
         
         wherein X represents an oxygen atom or a ═N—OH group, and 
         R represents a group selected from 
       
       
         
           
           
               
               
           
         
       
       or one of its esters and/or its addition salts with pharmaceutically acceptable acids, with the proviso that the compound is not 3-oxyimino-cholest-4-en-6-one. 
     
     
         2 . The compound of  claim 1 , which is selected from the group consisting of 3-oxyimino-cholest-4,24-dien-6-one, 24-ethyl-3-oxyimino-cholest-4-en-6-one, 3-oxyimino-cholest-4,21-dien-6-one, 24-ethyl-3-oxyimino-cholest-4,21-dien-6-one, 24-methyl-3-oxyimino-cholest-4,21-dien-6-one, cholest-4-en-3,6-dioxime, cholest-4,24-dien-3,6-dioxime, 24-ethyl-cholest-4-en-3,6-dioxime, cholest-4,21-dien-3,6-dioxime, 24-ethyl-cholest-4,21-dien-3,6-dioxime, 24-methyl-cholest-4,21-dien-3,6-dioxime, one of its esters, and one of its addition salts with pharmaceutically acceptable acids. 
     
     
         3 . The compound of  claim 1 , which is selected from the group consisting of 3-oxyimino-cholest-4,24-dien-6-one, 24-ethyl-3-oxyimino-cholest-4-en-6-one, 3-oxyimino-cholest-4,21-dien-6-one, 24-ethyl-3-oxyimino-cholest-4,21-dien-6-one, 24-methyl-3-oxyimino-cholest-4,21-dien-6-one, one of its esters, and one of its additional salts with pharmaceutically acceptable acids. 
     
     
         4 . The compound of  claim 1 , which is 24-ethyl-3-oxyimino-cholest-4-en-6-one or one of its esters and/or its addition salts with pharmaceutically acceptable acids. 
     
     
         5 . A method for treating or inhibiting necrosis and/or pathological apoptosis and/or necroptosis, comprising administering the compound of  claim 1  to a patient in need thereof. 
     
     
         6 . A method for treating a pathology or trauma related to the degeneration or death of cells, comprising administering the compound of  claim 1  to a patient in need thereof. 
     
     
         7 . The method of  claim 6 , wherein the cells are cardiac cells and/or neurons and the death of the cells are natural or accidental. 
     
     
         8 . A method for treating diseases selected from the group consisting of:
 diseases of the bones, the joints, the connective tissue and cartilage;   muscular diseases such as muscular dystrophy;   diseases of the skin;   cardiovascular diseases;   circulatory diseases;   haematological and vascular diseases;   lung diseases including obstructive chronic diseases of the lungs;   diseases of the gastro-intestinal tract;   diseases of the liver;   diseases of the pancreas;   metabolic diseases;   diseases of the kidneys;   viral and bacterial infections;   severe intoxications;   degenerative diseases associated with the Acquired Immune Deficiency Syndrome (AIDS);   disorders associated with aging;   inflammatory diseases;   auto-immune diseases;   dental disorders;   ophthalmic diseases or disorders;   disorders of the audition tracts; and   diseases associated with mitochondria (mitochondrial pathologies), comprising administering to a patient in need thereof the compound of  claim 1 , or of one of its esters and/or its addition salts with pharmaceutically acceptable acids.   
     
     
         9 . A method for treating a neurodegenerative disease, comprising administering to a patient in need thereof the compound of as described in  claim 1 , or of one of its esters and/or of its addition salts with pharmaceutically acceptable acids. 
     
     
         10 . The method of  claim 9 , wherein the neurodegenerative disease is selected from the group consisting of Huntington's disease, hereditary or sporadic neurodegenerative chronic diseases, neuronal lesions related to aging, hereditary or lesional peripheral neuropathies, Charcot-Marie-Tooth's disease, diabetic neuropathies or those induced by anti-cancer treatments, epilepsies, traumas of the brain, the peripheral nerves or the spinal cord, ischemias of the brain or the spinal cord, hereditary, lesional or aging-related degenerations of sensorial neurons of vision, or degenerations of the optical nerve, hereditary, traumatic or aging-related degenerations of sensorial neurons of hearing, lobar atrophies, and vascular dementias, diseases and traumas related to the degeneration of motoneurons, spinal amyotrophies, in particular infantile spinal amyotrophies, multiple sclerosis; amyotrophic lateral sclerosis, traumas of the spinal cord, and traumas of the peripheral motor nerves. 
     
     
         11 . The method of  claim 9 , wherein the neurodegenerative disease is a spinal amyotrophy or amyotrophic lateral sclerosis. 
     
     
         12 . The method of  claim 11 , wherein the spinal amyotrophy is an infantile spinal amyotrophy. 
     
     
         13 . A pharmaceutical composition, comprising, as an active ingredient, a compound of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         14 . A compound of formula I 
       
         
           
           
               
               
           
         
         wherein X represents an oxygen atom or a ═N—OH group and 
         R represents a group selected from 
       
       
         
           
           
               
               
           
         
         as well as its esters and/or its addition salts with mineral or organic acids. 
       
     
     
         15 . The compound of  claim 14 , selected from the group consisting of 3-oxyimino-cholest-4,24-dien-6-one, 24-ethyl-3-oxyimino-cholest-4-en-6-one, 3-oxyimino-cholest-4,21-dien-6-one, 24-ethyl-3-oxyimino-cholest-4,21-dien-6-one, 24-methyl-3-oxyimino-cholest-4,21-dien-6-one, cholest-4,24-dien-3,6-dioxime, 24-ethyl-cholest-4-en-3,6-dioxime, cholest-4,21-dien-3,6-dioxime, 24-ethyl-cholest-4,21-dien-3,6-dioxime, and 24-methyl-cholest-4,21-dien-3,6-dioxime. 
     
     
         16 . A pharmaceutical composition, comprising, as an active ingredient, a compound of  claim 14  and a pharmaceutically acceptable excipient.