Bumetanide analogs, compositions and methods of use

Abstract

The present invention provides bumetanide analogs and compositions comprising such analogs. The present invention also provides pharmaceutical compositions containing these bumetanide analogs and methods for their use. These analogs are believed useful for the treatment and/or prophylaxis of conditions that involve the Na+K+Cl− co-transporter or GABAA receptor.

1 - 194 . (canceled) 
     
     
         195 . A method of treating status epilepticus in a patient in need thereof comprising increasing pre-synaptic inhibition without depressing all GABA receptors by administering a compound of formula X: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein: 
         Y is sulfur; 
         Z is nitrogen; 
         each of R 8  and R 9  independently is hydrogen, alkyl, alkenyl, alkylcyano, alkylhalo, alkaryl, alkylheteroaryl, alkylheterocycloalkyl, alkylaminoalkyl, or alkylaminodialkyl; 
         or 
         R 8  and R 9  together with the atom to which they are attached, form a heterocycloalkyl group; and 
         R 10  is hydrogen or alkyl, 
         wherein the compound increases neuronal inhibition by acting at interneuron terminals and regulating neuronal firing. 
       
     
     
         196 . A method of treating status epilepticus in a patient in need thereof comprising increasing pre-synaptic inhibition without depressing all GABA receptors by administering a compound 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein the compound increases neuronal inhibition by acting at interneuron terminals and regulating neuronal firing. 
       
     
     
         197 . A method of treating status epilepticus in a patient in need thereof comprising increasing pre-synaptic inhibition without depressing all GABA receptors by administering a compound 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein the compound increases neuronal inhibition by acting at interneuron terminals and regulating neuronal firing.