Substituted 6-amino-nicotinamides as KCNQ2/3 modulators

A substituted compound of formula (X):

• wherein
• X1 represents a C2-6-aliphatic residue, unsubstituted or mono- or polysubstituted;
• or a C3-6-cycloaliphatic residue or a 3 to 6 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted, and in each case optionally bridged via a C1-4 aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted;
• or represents OX6, wherein
• X6 represents a C1-6-aliphatic residue, unsubstituted or mono- or polysubstituted;
• or a C3-6-cycloaliphatic residue, unsubstituted or mono- or polysubstituted;
• X2, X3, X4 and X5 satisfy one of the clauses I, II or III below:
• I,
• X2 and X3 independently of one another represent H;
• F;
• Cl;
• Br;
• I;
• CN;
• CH2F;
• CHF2;
• CF3;
• OH;
• OCH2F;
• OCHF2;
• OCF3;
• SCF3;
• a C1-4-aliphatic residue, or an O—C1-4 aliphatic residue, wherein the C1-4 aliphatic residue may in each case be unsubstituted or mono- or polysubstituted;
• or a C3-6-cycloaliphatic residue or a 3 to 6 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted, with the proviso that at least one of X2 and X3 denotes H or at least one of X2 and X3 denotes CN;
• CH2F;
• CHF2;
• CF3;
• a C1-4-aliphatic residue, wherein the C1-4 aliphatic residue may be unsubstituted or mono- or polysubstituted;
• or a C3-6-cycloaliphatic residue or a 3 to 6 membered heterocycloaliphatic residue linked via a carbon atom, in each case unsubstituted or mono- or polysubstituted;
• X4 and X5 independently of one another represent H;
• CH2F;
• CHF2;
• CF3;
• a C1-4-aliphatic residue, wherein the C1-4 aliphatic residue may be unsubstituted or mono- or polysubstituted;
• or a C3-6-cycloaliphatic residue or a 3 to 6 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted;
• on the condition that if X4 and/or X5 denote(s) a 3 to 6 membered heterocycloaliphatic residue, the 3 to 6 membered heterocycloaliphatic residue is linked via a carbon atom,
• or
• II,
• X2 and X3
• and/or X4 and X5
• in pairs, in each case independently of one another, together with the carbon atom connecting them, form a C3-10-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted,
• and, if X2 and X3 together with the carbon atom connecting them do not form a C3-10-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted, then X2 and X3 each independently of one another represent H;
• F;
• Cl;
• Br;
• I;
• CN;
• CH2F;
• CHF2;
• CF3;
• OH;
• OCH2F;
• OCHF2;
• OCF3;
• SCF3;
• a C1-4-aliphatic residue, or an O—C1-4 aliphatic residue, wherein the C1-4 aliphatic residue may in each case be unsubstituted or mono- or polysubstituted;
• or a C3-6-cycloaliphatic residue or a 3 to 6 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted, with the proviso that at least one of X2 and X3 denotes H or at least one of X2 and X3 denotes CN;
• CH2F;
• CHF2;
• CF3;
• a C1-4-aliphatic residue, wherein the C1-4 aliphatic residue may be unsubstituted or mono- or polysubstituted;
• or a C3-6-cycloaliphatic residue or a 3 to 6 membered heterocycloaliphatic residue linked via a carbon atom, in each case unsubstituted or mono- or polysubstituted,
• and, if X4 and X5 together with the carbon atom connecting them do not form a C3-10-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted, then X4 and X5 each independently of one another represent H;
• CH2F;
• CHF2;
• CF3;
• a C1-4-aliphatic residue, wherein the C1-4 aliphatic residue may be unsubstituted or mono- or polysubstituted;
• or a C3-6-cycloaliphatic residue or a 3 to 6 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted;
• on the condition that if X4 and/or X5 denote(s) a 3 to 6 membered heterocycloaliphatic residue, the 3 to 6 membered heterocycloaliphatic residue is linked via a carbon atom,
• or
• III,
• X2 and X4 together with the carbon atoms connecting them, form a C3-10-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted,
• and X3 represents H;
• F;
• Cl;
• Br;
• I;
• CN;
• CH2F;
• CHF2;
• CF3;
• OH;
• OCH2F;
• OCHF2;
• OCF3;
• SCF3;
• a C1-4-aliphatic residue, or an O—C1-4 aliphatic residue, wherein the C1-4 aliphatic residue may in each case be unsubstituted or mono- or polysubstituted;
• or a C3-6-cycloaliphatic residue or a 3 to 6 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted;
• and X5 represents H;
• CH2F;
• CHF2;
• CF3;
• a C1-4-aliphatic residue, wherein the C1-4 aliphatic residue may be unsubstituted or mono- or polysubstituted;
• or a C3-6-cycloaliphatic residue or a 3 to 6 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted;
• on the condition that if X5 denotes a 3 to 6 membered heterocycloaliphatic residue, the 3 to 6 membered heterocycloaliphatic residue is linked via a carbon atom,
• wherein in X1-X6:
• an “aliphatic group” and an “aliphatic residue” can in each case be branched or unbranched, saturated or unsaturated,
• a “cycloaliphatic residue” and a “heterocycloaliphatic residue” can in each case be saturated or unsaturated,
• “mono- or polysubstituted” with respect to an “aliphatic group” and an “aliphatic residue” relates, with respect to the corresponding residues or groups, to the substitution of one or more hydrogen atoms each independently of one another by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, an NH(C1-4 aliphatic residue), an N(C1-4 aliphatic residue)2, a NH—C(═O)—C1-4 aliphatic residue, a N(C1-4-aliphatic residue)-C(═O)—C1-4 aliphatic residue, a NH—S(═O)2—C1-4 aliphatic residue, a N(C1-4-aliphatic residue)-S(═O)2—C1-4 aliphatic residue, ═O, OH, OCH2F, OCHF2, OCF3, a O—C1-4-aliphatic residue, a O—C(═O)—C1-4-aliphatic residue, SH, SCF3, a S—C1-4-aliphatic residue, S(═O)2OH, a S(═O)—C1-4-aliphatic residue, a S(═O)2—C1-4-aliphatic residue, a S(═O)2—O—C1-4-aliphatic residue, a S(═O)2—NH—C1-4-aliphatic residue, a S(═O)2—N(C1-4-aliphatic residue)2, CN, CH2F, CHF2, CF3, CHO, COOH, a C1-4-aliphatic residue, CH2OH, CH2—OCH3, C2H4—OH, C2H4—OCH3 CH2—CF3, a C(═O)—C1-4-aliphatic residue, a C(═O)—O—C1-4-aliphatic residue, a C3-6-cycloaliphatic residue, a 3 to 6 membered heterocycloaliphatic residue, C(═O)—NH2, a C(═O)—NH(C1-4 aliphatic residue), and a C(═O)—N(C1-4 aliphatic residue)2;
• “mono- or polysubstituted” with respect to a “cycloaliphatic residue” and a “heterocycloaliphatic residue” relates, with respect to the corresponding residues, to the substitution of one or more hydrogen atoms each independently of one another by at least one substituent selected from the group consisting of F, Cl, Br, I, NO2, NH2, an NH(C1-4 aliphatic residue), an N(C1-4 aliphatic residue)2, a NH—C(═O)—C1-4 aliphatic residue, a N(C1-4-aliphatic residue)-C(═O)—C1-4 aliphatic residue, a NH—S(═O)2—C1-4 aliphatic residue, a N(C1-4-aliphatic residue)-S(═O)2—C1-4 aliphatic residue, ═O, OH, OCH2F, OCHF2, OCF3, a O—C1-4-aliphatic residue, a O—C(═O)—C1-4-aliphatic residue, SH, SCF3, a S—C1-4-aliphatic residue, S(═O)2OH, a S(═O)—C1-4-aliphatic residue, a S(═O)2—C1-4-aliphatic residue, a S(═O)2—O—C1-4-aliphatic residue, a S(═O)2—NH—C1-4-aliphatic residue, a S(═O)2—N(C1-4-aliphatic residue)2, CN, CH2F, CHF2, CF3, CHO, COOH, a C1-4-aliphatic residue, CH2OH, CH2—OCH3, C2H4—OH, C2H4—OCH3 CH2—CF3, a C(═O)—C1-4-aliphatic residue, a C(═O)—O—C1-4-aliphatic residue, a C3-6-cycloaliphatic residue, a 3 to 6 membered heterocycloaliphatic residue, C(═O)—NH2, a C(═O)—NH(C1-4 aliphatic residue), and a C(═O)—N(C1-4 aliphatic residue)2;
• said compound being in the form of a free compound, the racemate, a mixture of enantiomers, diastereomers, or of enantiomers and diastereomers in any mixing ratio, or of an individual enantiomer or diastereomer, or in the form of a salt of physiologically acceptable acids or bases.