2-(pyrazin-2-ylcarbonylaminomethyl) benzimidazolium compounds as epithelial sodium channel inhibitors

A compound of formula (I), or a tautomer thereof or a pharmacologically acceptable acid addition salt of the compound or the tautomer,

• wherein
• R3 is H or C1-C4-alkoxy;
• R4 is H or C1-C4-alkoxy;
• X is Cl or Br;
• and
• Z− is chloride, bromide, iodide, hydroxide, hydrogensulfate, sulfate, nitrate, phosphate, formate, acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate or p-toluenesulfonate;
• wherein the compound of formula (I) is characterized by a topological polar surface area value (TPSA) of at least 145;
• and
• wherein at least one of R1 and R2 is independently selected from a group of formula (A),
• wherein
• n is 1, 2 or 3, and
• Ra and Rb are independently selected from H, C1-C4-alkyl,
• wherein C1-C4-alkyl in the aforementioned moiety may carry a substituent selected from amino, C1-C4-alkylamino, di(C1-C4-alkyl)amino, hydroxy, C1-C4-alkoxy, C1-C4-alkoxycarbonylamino-, and C1-C4-alkoxycarbonyl(C1-C4-alkyl)amino-, or a 5- to 7-membered heterocycle containing 1 or 2 heteroatoms selected from O and N, wherein the 5- to 7-membered heterocycle may carry one substituent selected from C1-C4-alkyl and C1-C4-alkoxycarbonyl-;
• or wherein Ra and Rb together with the nitrogen they are attached to form a 5- to 7-membered heterocycle containing 1 or 2 heteroatoms selected from O and N, wherein the 5- to 7-membered heterocyclyl may carry one substituent selected from C1-C4-alkyl, amino, C1-C4-alkylamino, di(C1-C4-alkyl)amino, hydroxy, C1-C4-alkoxy, and C1-C4-alkoxycarbonyl-;
• and/or wherein at least one of R1 and R2 is independently selected from a group of formula (B),
• wherein Rc is selected from C1-C3-alkyl, C1-C2-alkoxy-C2-C3-alkyl-, hydroxy-C2-C3-alkyl-, and amino-C2-C3-alkyl-, and wherein * denotes the point of attachment;
• and/or wherein at least one of R1 and R2 is independently selected from
• wherein
• denotes the point of attachment;
• and
• the remaining substituent R1 or R2 may additionally be selected from C1-C3-alkyl, ω-fluoro-C2-C3-alkyl, 2-propenyl, dimethylaminocarbonylmethyl, and dimethylaminocarbonylpropyl;
• provided that if one of the substituents R1 or R2 is selected from C1-C3-alkyl the other substituent R1 or R2 is different from —(CH2—CH2—O)3H.