Heterocyclic compounds, medicaments containing said compounds, use thereof and processes for the preparation thereof

Abstract

The present invention relates to compounds of general formula (I) and the tautomers and the salts thereof, particularly the pharmaceutically acceptable salts thereof with inorganic or organic acids and bases, which have valuable pharmacological properties, particularly an inhibitory effect on epithelial sodium channels, and the use thereof for the treatment of diseases, particularly diseases of the lungs and airways.

1 - 9 . (canceled) 
     
     
         10 . A method for the treatment of respiratory diseases and allergic diseases of the airways comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I) 
       
         
           
           
               
               
           
         
       
       wherein
 A denotes a bond or is selected from the group consisting of O, —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 —O—, —CH 2 —NR A1 — and —NR A1 —,
 wherein 
 
 R A1  denotes hydrogen or C 1-6 -alkyl, 
 B denotes 
 —CH 2 — or —CH 2 CH 2 —, or
 provided that A is not O or —NR A1 , B denotes a bond 
 
 D, E denote independently from each other a bond or —CH 2 —, 
 F denotes optionally substituted aryl, 
 or optionally substituted heteroaryl, 
 G denotes a group of formula (g.1), (g.2) or (g.3) 
 
       
         
           
           
               
               
           
         
         
           wherein 
           R 1  is selected from the group consisting of 
         
         hydrogen, C 1-6 alkyl, optionally substituted piperidinyl-CO—, 
         optionally substituted piperazinyl-CO—, R 1.1 —SO 2 —, R 1.2 —C 2-4 -alkyl-NH—CO—, H 3 C—NH—CO—, R 1.2.4 —O—CO—CH 2 —NH—CO—, R 1.2 —C 2-4 -alkyl-N(C 1-4 -alkyl)-CO—, H 3 C—N(C 1-4 -alkyl)-CO—, R 1.2.4 —O—CO—CH 2 —N(C 1-4 -alkyl)-CO—, R 1.3 —C 1-6 -alkyl-, R 1.4 —C 2-6 -alkyl-, optionally substituted phenyl-CH 2 —, C 1-6 -alkyl-O—CO—, R 1.4.3 —O—CO—CH 2 —, HO—CO—CH 2 — and HOSO 2 —CH 2 —, 
         R 1.5 —C 1-6 -alkyl-CO— and R 1.6 —C(NH)—, 
         wherein 
         R 1.1  is selected from the group consisting of C 1-4 -alkyl-, 
         H 2 NC(NH)NH—C 1-6 -alkyl-, R 1.2.1 R 1.2.2 N—C 1-4 -alkyl-, 
         R 1.2.1 R 1.2.2 R 1.2.3 N + —C 1-4 -alkyl, HOCO—C 1-4 -alkyl- and 
         C 1-3 -alkyl-OCO—C 1-4 -alkyl-, 
         R 1.2  is selected from the group consisting of hydrogen, H 2 NC(NH)NH—, R 1.2.1 R 1.2.2 N—, R 1.2.1 R 1.2.2 R 1.2.3 N + —, R 1.2.3 —HN—C(NR 1.2.3 )—NH—, R 1.2.4 —O—CO—, 
         R 1.2.5 —O—CO—NH— and HO—CO—, HOSO 2 —,
 wherein 
 R 1.2.1  denotes hydrogen or C 1-6 -alkyl, 
 R 1.2.2  denotes hydrogen or C 1-6 -alkyl, 
 
         or 
         R 1.2.1  and R 1.2.2  together form a 4- to 7-membered heterocyclic ring containing one N-atom, 
         R 1.2.3  denotes hydrogen or C 1-6 -alkyl, 
         R 1.2.4  denotes hydrogen or C 1-6 -alkyl, 
         R 1.2.5  denotes hydrogen or C 1-6 -alkyl, 
         R 1.3  is selected from the group consisting of hydrogen, C 1-6 -alkyl, C 1-6 -alkyl-O—, optionally substituted phenyl, R 1.3.1 R 1.3.2 N—, R 1.2.1 R 1.2.2 R 1.2.3 N + —, 
         R 1.2.3 —HN—C(NR 1.2.3 )—NH—, H 2 NC(NH)NH—, R 1.2.4 —O—CO—, HO—CO— and HOSO 2 —, 
         wherein
 R 1.3.1  denotes hydrogen or C 1-6 -alkyl, 
 R 1.3.2  denotes hydrogen or C 1-6 -alkyl, 
 or 
 R 1.3.1  and R 1.3.2  together form a 4- to 7-membered heterocyclic ring containing one N-atom, 
 
         R 1.4  is selected from the group consisting of hydrogen, R 1.4.1 R 1.4.2 N—, 
         R 1.4.1 R 1.4.2 R 1.4.3 N + —, H 2 N—C(NH)—NH—, R 1.4.3 —HN—C(NR 1.4.4 )—NH—, optionally substituted phenyl, R 1.4.3 —O—CO—, R 1.4.4 —O—CO—NH—, HO—CO— and HOSO 2 —, 
         wherein
 R 1.4.1  denotes hydrogen or C 1-6 -alkyl, 
 
         R 1.4.2  denotes hydrogen or C 1-6 -alkyl, 
         R 1.4.3  denotes hydrogen or C 1-6 -alkyl, 
         R 1.4.4  denotes hydrogen or C 1-6 -alkyl, 
         R 1.5  is selected from the group consisting of hydrogen, C 1-6 -alkyl-O—, 
         R 1.5.1 R 1.5.2 N—, R 1.5.2 R 1.5.3 N + —, H 2 N—C(NH)—NH—, optionally substituted phenyl, R 1.5.3 —O—CO—, R 1.5.4 —O—CO—NH—, HO—CO— and HOSO 2 —, 
         wherein
 R 1.5.1  denotes hydrogen or C 1-6 -alkyl, 
 
         R 1.5.2  denotes hydrogen or C 1-6 -alkyl, 
         R 1.5.3  denotes hydrogen or C 1-6 -alkyl, 
         R 1.5.4  denotes hydrogen or C 1-6 -alkyl, 
         R 1.6  denotes R 1.6.1 R 1.6.2 N—,
 wherein 
 R 1.6.1  denotes hydrogen or C 1-6 -alkyl; 
 R 1.6.2  denotes hydrogen or C 1-6 -alkyl; 
 
         R 1b  is selected from the group consisting of C 11-4 -alkyl, 
         R 1.4 —C 2-6 -alkyl-, optionally substituted phenyl-CH 2 —, R 1.4.3 —O—CO—CH 2 — and HO—CO—CH 2 — 
         R 1s  denotes C 1-6 -alkyl, 
         X −  denotes any anion forming a pharmaceutically acceptable salt, 
         L denotes a bridging group —CO—NH—C 2-6 -alkyl-NH—CO—, —COC 1-6 -alkyl-CO—, —C 2-6 -alkyl-, 
         forming a compound of formula (IC), 
         whereby the molecular entities of formula (IC) connected by L may be identical or different 
       
       
         
           
           
               
               
           
         
         R 5  denotes Cl or Br, 
       
       or a pharmacologically acceptable acid addition salt thereof.