Long-term prevention and/or treatment of a disease by slo-1 inhibitors

A method of using a compound of formula I.1 or I.2

• in which:
• E1 is an aromatic bicyclic heterocycle substituted with at least one substitutent and wherein the aromatic bicyclic heterocycle is a ring system selected from the group consisting of
• a ring system consisting of two 5-membered rings,
• a ring system consisting of a 5-membered ring and a 6-membered ring, or
• a ring system consisting of two 6-membered rings;
• E2 is selected from the group consisting of
• an optionally substituted aromatic benzyl,
• an optionally substituted 6-membered heterocycle comprising 1, 2, 3 or 4 heteroatoms in form of N, and
• an optionally substituted bicyclic residue wherein the bicyclic residue is selected from the group consisting of
• a ring system consisting of two 5-membered rings,
• a ring system consisting of a 5-membered ring and a 6-membered ring, or
• a ring system consisting of two 6-membered rings;
• n is 0 or 1;
• R1 is selected from the group consisting of hydrogen, cyano, —CHO, —OH, C1-C6-alkyl, C1-C9-halogenoalkyl having 1 to 5 halogen atoms, C1-C4-alkoxy, C1-C4-halogenoalkoxy having 1 to 5 halogen atoms, C3-C6-cycloalkyl, C3-C6-halogenocycloalkyl having 1 to 5 halogen atoms, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-alkoxy-C1-C4-alkyl, C3-C6-cycloalkyl-C1-C3-alkyl, cyano-C1-C4-alkyl, —NH—C1-C4-alkyl, —N(C1-C4-alkyl)2, NH2—C1-C4-alkyl-, C1-C4-alkyl-NH—C1-C4-alkyl-, (C1-C4-alkyl)2N—C1-C4-alkyl-, C1-C4-alkyl-C(O)—, C1-C4-halogenoalkyl-C(O)— having 1 to 5 halogen atoms, C1-C4-alkoxy-C(O)—, benzyloxy-C(O)—, C1-C4-alkoxy-C1-C4-alkyl-C(O)—, —SO2—C1-C4-alkyl, —SO2—C1-C4-halogenoalkyl having 1 to 5 halogen atoms, amino-C1-C4-alkyl, C1-C4-alkylamino-C1-C4-alkyl, di-(C1-C4-alkyl)amino-C1-C4-alkyl, C1-C4-alkylcarbonyl, C1-C4-halogenoalkylcarbonyl having 1 to 5 halogen atoms, C1-C4-alkoxycarbonyl, benzyloxycarbonyl, C1-C4-alkoxy-C1-C4-alkylcarbonyl;
• and
• R is hydrogen, C1-C3 alkyl;
• or
• when E2 is E2_5
• R and R14 together with the atoms to which they are attached form a 5 or 6-carbon atoms containing unsaturated ring, wherein the unsaturated ring is optionally substituted with one or more C1-C3-alkyl, and/or wherein one or more of the ring-forming carbon atoms are optionally replaced by —NH—, —N═, ═N—, —O— or —S— or
• R and R14 together with the atoms to which they are attached form a 5 or 6-carbon atoms containing unsaturated ring, wherein the unsaturated ring is optionally substituted with one or more C1-C3-alkyl, and/or wherein one or more of the ring-forming carbon atoms are optionally replaced by —NH—, —N═, ═N—, —O— or —S—;
• wherein E2_5 is
• wherein
• R15 is independently hydrogen, halogen, C1-3 alkyl, C1-3 alkoxy, or NR15′R15″, wherein R15′ and R15″ are independently C1-3-alkyl;
• R16 is independently hydrogen, halogen, C1-3 alkyl, C1-3 alkoxy, or NR16′R16″, wherein R16′ and R16″ are independently C1-3-alkyl;
• R17 is independently hydrogen, C1-3 alkyl, C1-3 alkoxy, or NR17′R17″, wherein R17′ and R17″ are independently C1-3-alkyl;
• R18 is independently hydrogen, C1-3 alkyl, C1-3 alkoxy, or NR18′R18″, wherein R18′ and R18″ are independently C1-3-alkyl;
• or when E2 is E2_6
• R and R14 together with the atoms to which they are attached form a 5 or 6-carbon atoms containing non-aromatic ring, wherein the 5 or 6-carbon atoms containing ring is optionally substituted with one or more C1-3-alkyl or ═O, and/or wherein one or more of the ring forming carbon atoms are optionally replaced by —NH—, —N═, ═N—, —O—, —S(O)—, —S(O)2- or —S—, or R and R14 together with the atoms to which they are attached form a 5 or 6-carbon atoms containing aromatic ring, wherein the 5 or 6-carbon atoms containing ring is optionally substituted with one or more C1-3-alkyl, and/or wherein one or more of the ring forming carbon atoms are optionally replaced by —NH—, —N═, ═N—, —O— or —S—;
• wherein E2_6 is
• wherein
• A1 is N or CR15, wherein R15 is independently hydrogen, halogen,
• NR15′R15″, wherein R15′ and R15″ are independently C1-3-alkyl;
• A2 is N or CR16, wherein R16 is independently hydrogen, halogen,
• NR16R16″, wherein R16′ and R16″ are independently C1-3-alkyl;
• A3 is N or CR17, wherein R17 is independently hydrogen, halogen,
• NR17′R17″, wherein R17′ and R17 are independently C1-3-alkyl;
• A4 is N or CR18, wherein R18 is independently hydrogen, halogen
• NR18′R18″, wherein R18′ and R18″ are independently C1-3-alkyl;
• or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of the same,
• in the long-term prevention and/or treatment of a disease.