TREATMENT OF CNS DISEASES WITH sGC STIMULATORS

Abstract

The present disclosure relates to the use of stimulators of soluble guanylate cyclase (sGC), pharmaceutically acceptable salts thereof and pharmaceutical formulations or dosage forms comprising them, alone or in combination with one or more additional agents, for the treatment of various CNS diseases, wherein an increase in sGC stimulation, or an increase in the concentration of nitric oxide (NO), or cyclic guanosine 3′,5′-monophosphate (cGMP) or both, or an upregulation of the NO pathway is desirable.

1 .- 19 . (canceled) 
     
     
         20 . A method of reducing pain in a subject, comprising administering, alone or in combination therapy, a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof to the subject in need thereof, wherein the compound is selected from those depicted in Table I, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition or a dosage form comprising said compound or pharmaceutically acceptable salt thereof: 
       
         
           
                 
                 
                 
               
                   TABLE I 
                 
                     
                 
                     
                     
                   Compound 
                 
                     
                   Structure 
                   Number 
                 
                     
                 
                     
                   
                     
                       
                       
                           
                           
                       
                     
                   
                   I-5 
                 
                     
                 
                     
                   
                     
                       
                       
                           
                           
                       
                     
                   
                    I-2. 
                 
                     
                 
             
                
                
                
                
                
               
               
                
                
                
                
               
            
           
         
       
     
     
         21 . The method of  claim 20 , wherein the pain is acute pain, central pain syndrome, chemotherapy induced neuropathy and neuropathic pain, diabetic neuropathy, fibromyalgia, Inflammatory pain, neuropathic pain, neuropathic pain associated with a CNS disease, painful diabetic peripheral neuropathy, post-operative pain, tonic pain, visceral pain, or orphan pain. 
     
     
         22 . The method of  claim 21 , wherein the orphan pain is Acetazolamide-responsive myotonia, Autoerythrocyte sensitization syndrome, Autosomal dominant Charcot-Marie-Tooth disease type 2V, Autosomal dominant intermediate Charcot-Marie-Tooth disease with neuropathic pain, Autosomal recessive limb-girdle muscular dystrophy type 2A, Channelopathy-associated congenital insensitivity to pain, Chronic pain requiring intraspinal analgesia, Complex regional pain syndrome, Complex regional pain syndrome type 1, Complex regional pain syndrome type 2, Congenital insensitivity to pain with hyperhidrosis, Congenital insensitivity to pain with severe intellectual disability, Congenital insensitivity to pain-hypohidrosis syndrome, Diffuse palmoplantar keratoderma with painful fissures, Familial episodic pain syndrome, Familial episodic pain syndrome with predominantly lower limb involvement, Familial episodic pain syndrome with predominantly upper body involvement, Hereditary painful callosities, Hereditary sensory and autonomic neuropathy type 4, Hereditary sensory and autonomic neuropathy type 5, Hereditary sensory and autonomic neuropathy type 7, Interstitial cystitis, Painful orbital and systemic neurofibromas-marfanoid habitus syndrome, Paroxysmal extreme pain disorder, Persistent idiopathic facial pain, Qualitative or quantitative defects of calpain, and Tolosa-Hunt syndrome. 
     
     
         23 . The method of  claim 20 , wherein the pain is acute and tonic pain, neuropathic pain, inflammatory pain, post-operative pain, or visceral pain. 
     
     
         24 . The method of  claim 20 , wherein the pain is neuropathic pain. 
     
     
         25 . The method of  claim 24 , wherein the neuropathic pain is neuropathic pain with Multiple Sclerosis, neuropathic pain with shingles (herpes zoster), neuropathic pain with spine surgery.