Substituted pyrimidine derivatives

Abstract

The present invention relates to pyrimidine derivatives of the general formula I or salts thereof and their use.

1 . A compound having the general formula I: 
     
       
         
         
             
             
         
       
       wherein: q is 0 or 1;
 R 1  and R 2  are independently selected from the group consisting of hydrogen and optionally substituted aryl-C 1-6 -alk(en/yn)yl, provided that R 1  and R 2  are not both hydrogen, or R 1  and R 2  together with the nitrogen to which they are attached form a 5 to 7 membered ring optionally containing a further heteroatom; 
 R 3  and R 4  are independently selected from hydrogen, halogen, cyano, amino, C 1-6 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl, halo-C 1-6 -alk(en/yn)yl, halo-C 3-8 -cycloalk(en)yl, C 1-6 -alk(en/yn)yloxy, C 3-8 -Cycloalk(en)yloxy, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yloxy, halo-C 1-6 -alk(en/yn)yloxy, halo-C 3-8 -cycloalk(en)yloxy and halo-C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yloxy, provided that R 3  and R 4  are not both hydrogen; 
 R 5  is selected from the group consisting of C 1-10 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl, optionally substituted aryl-C 1-6 -alk(en/yn)yl and optionally substituted aryl; 
 
       or a pharmaceutically acceptable salt thereof. 
     
   
   
       2 . The compound according to  claim 1 , wherein q is 0. 
   
   
       3 . The compound according to  claim 1 , wherein q is 1. 
   
   
       4 . The compound according to  claim 1 , wherein R 1  and R 2  are independently selected from hydrogen and optionally substituted aryl-C 1-6 -alk(en/yn)yl, provided that R 1  and R 2  are not both hydrogen. 
   
   
       5 . The compound according to  claim 1 , wherein R 1  and R 2  taken together with the nitrogen to which they are attached form a 5 to 7 membered ring optionally containing a further hetero atom. 
   
   
       6 . The compound according to  claim 5 , wherein said further hetero atom is oxygen. 
   
   
       7 . The compound according to  claim 6 , wherein said ring is a 6 membered ring. 
   
   
       8 . The compound according to  claim 7 , wherein said ring is a morpholine ring. 
   
   
       9 . The compound according to  claim 1 , wherein R 3  and R 4  are independently selected from amino and C 1-6 -alk(en/yn)yl. 
   
   
       10 . The compound according to  claim 1 , wherein R 5  is selected from the group consisting of C 1-10 -alk(en/yn)yl, C 3-8 -cycloalk(en)yl-C 1-6 -alk(en/yn)yl, optionally substituted aryl-C 1-6 -alk(en/yn)yl and optionally substituted aryl. 
   
   
       11 . (canceled) 
   
   
       12 . A pharmaceutical composition comprising a compound according to  claim 1  in a therapeutically effective amount together with one or more pharmaceutically acceptable carriers or diluents. 
   
   
       13 . A method for increasing ion flow in a potassium channel of a mammal comprising administering to said mammal a therapeutically effective amount of a compound according to  claim 1 . 
   
   
       14 . A method of treatment of a disorder or disease being responsive to an increased ion flow in a potassium channel, comprising administering to a mammal a therapeutically effective amount of a compound according to  claim 1 . 
   
   
       15 . The method according to  claim 14 , wherein the disorder or disease to be treated is selected from the group consisting of seizure disorders, anxiety disorders, neuropathic pain and migraine pain disorders, cancer pain, neurodegenerative disorders, stroke, cocaine abuse, nicotine withdrawal, ethanol withdrawal and tinnitus. 
   
   
       16 . The method according to  claim 15  wherein the seizure disorders are selected from the group consisting of acute seizures, convulsions, status epilepticus, and epilepsy. 
   
   
       17 . The method according to  claim 15  wherein the anxiety disorders are selected from the group, consisting of anxiety and disorders and diseases related to panic attack, agoraphobia, panic disorder with agoraphobia, panic disorder without agoraphobia, agoraphobia without history of panic disorder, specific phobia, social phobia, obsessive-compulsive disorder, post-traumatic stress disorder, acute stress disorders, generalized anxiety disorder, anxiety disorder due to general medical condition, substance-induced anxiety disorder, separation anxiety disorder, adjustment disorders, performance anxiety, hypochondriacal disorders, anxiety disorder due to general medical condition and substance induced anxiety disorder. 
   
   
       18 . The method according to  claim 15  wherein the neuropathic pain and migraine pain disorders are selected from the group consisting of allodynia, hyperalgesic pain, phantom pain, neuropathic pain related to diabetic neuropathy, neuropathic pain related to trigeminal neuralgia and neupathic pain related to migraine. 
   
   
       19 . The method according to  claim 15  wherein the neurodegenerative disorders are selected from the group consisting of Alzheimer's disease, Huntington's chorea, multiple sclerosis, amyotrophic lateral sclerosis, Creutzfeld-Jakob's disease, Parkinson's disease, encephalopathies induced by AIDS or infection by rubella viruses, herpes viruses, borrelia or unknown pathogens, trauma-induced neurodegenerations, neuronal hyperexcitation states. 
   
   
       20 . The method according to  claim 14  wherein the disorder or disease to be treated is selected from the group consisting of bipolar disorders and attention deficit hyperactivity disorder. 
   
   
       21 . The method according to  claim 14  wherein the disorder or disease to be treated is insomnia. 
   
   
       22 . The method according to  claim 14  for the treatment of a disorder or disease being responsive to an increased ion flow in a potassium channel wherein the disorder or disease to be treated is selected from fibromyalgia, a motor disorder or motion disorder, spasms, myokymia and urinary incontinence. 
   
   
       23 . The compound according to  claim 9  wherein R 3  and R 4  are independently selected from amino and methyl.