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US 8,618,129 B2Granted
Substituted 1-oxo-dihydroisoquinoline-3-carboxamides as KCNQ2/3 modulators
AssigneeGruenenthal GmbH
InventorsSven Kühnert, Gregor Bahrenberg, Achim Kless, Wolfgang Schröder
Life of this patent
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Abstract
The invention relates to substituted 1-oxo-dihydroisoquinoline-3-carboxamides, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.
Claims14
A substituted compound of formula (I):
- wherein
- R1 represents a C1-10-aliphatic residue, unsubstituted or mono- or polysubstituted;
- a C3-10-cycloaliphatic residue, unsubstituted or mono- or polysubstituted and optionally bridged via a C1-8 aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted;
- aryl or heteroaryl, in each case unsubstituted or mono- or polysubstituted and in each case optionally bridged via a C1-8 aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted;
- R2 represents F;
- Cl;
- Br;
- I;
- CN;
- CF3;
- C(═O)H;
- NO2;
- OCF3;
- SCF3;
- a C1-4-aliphatic residue, a C(═O)—C1-4 aliphatic residue, a C(═O)—O—C1-4 aliphatic residue, a C(═O)—NH—C1-4 aliphatic residue, a C(═O)—N(C1-4 aliphatic residue)2, wherein the C1-4 aliphatic residue may be in each case be unsubstituted or mono- or polysubstituted;
- a O—C1-4-aliphatic residue, a O—C(═O)—C1-4-aliphatic residue, a S—C1-4-aliphatic residue, a S(═O)2—C1-4-aliphatic residue, a S(═O)2—O—C1-4-aliphatic residue, wherein the C1-4 aliphatic residue may be in each case be unsubstituted or mono- or polysubstituted;
- 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;
- R3, R4, R5 and R6 each independently of one another represent H;
- F;
- Cl;
- Br;
- I;
- CN;
- CF3;
- C(═O)H;
- C(═O)—OH;
- C(═O)—NH2;
- SCF3;
- S(═O)2—OH;
- NO2;
- OCF3;
- a C1-4-aliphatic residue, a C(═O)—C1-4 aliphatic residue, a C(═O)—O—C1-4 aliphatic residue, a C(═O)—NH—C1-4 aliphatic residue, a C(═O)—N(C1-4 aliphatic residue)2, wherein the C1-4 aliphatic residue may be in each case be unsubstituted or mono- or polysubstituted;
- a O—C1-4-aliphatic residue, a O—C(═O)—C1-4-aliphatic residue, a S—C1-4-aliphatic residue, a S(═O)2—C1-4-aliphatic residue, a S(═O)2—O—C1-4-aliphatic residue, wherein the C1-4 aliphatic residue may be in each case be unsubstituted or mono- or polysubstituted;
- a NH(C1-4 aliphatic residue), a N(C1-4 aliphatic residue)2, a NH—C(═O)—C1-4 aliphatic residue, a NH—S(═O)2—C1-4-aliphatic residue, a N(C1-4 aliphatic residue)-C(═O)—C1-4 aliphatic residue, or a N(C1-4 aliphatic residue)-S(═O)2—C1-4 aliphatic residue, wherein the C1-4 aliphatic residue may in each case be unsubstituted or mono- or polysubstituted;
- 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;
- R7 represents a C1-10-aliphatic residue, unsubstituted or mono- or polysubstituted;
- a C3-10-cycloaliphatic residue or a 3 to 10 membered heterocycloaliphatic residue, in each case unsubstituted or mono- or polysubstituted and in each case optionally bridged via a C1-8 aliphatic group, which in turn may be unsubstituted or mono- or polysubstituted;
- on the condition that if R7 denotes a 3 to 10 membered heterocycloaliphatic residue, the 3 to 10 membered heterocycloaliphatic residue is linked via a carbon atom,
- in which an “aliphatic group” and “aliphatic residue” can in each case be branched or unbranched, saturated or unsaturated,
- in which a “cycloaliphatic residue” and a “heterocycloaliphatic residue” can in each case be saturated or unsaturated,
- in which “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, a NH—C(═O)—C1-4 aliphatic residue, a NH—S(═O)2—C1-4 aliphatic residue, OH, ═O, 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)2—C1-4-aliphatic residue, a S(═O)2—O—C1-4-aliphatic residue, a S(═O)2—NH—C1-4-aliphatic residue, CN, CF3, CHO, COOH, a C1-4-aliphatic residue, a C(═O)—C1-4-aliphatic residue, a C(═O)—O—C1-4-aliphatic residue, a C3-6-cycloaliphatic residue, C(═O)—NH2, a C(═O)—NH(C1-4 aliphatic residue), and a C(═O)—N(C1-4 aliphatic residue)2;
- in which “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 NH—S(═O)2—C1-4 aliphatic residue, ═O, OH, 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)2—C1-4-aliphatic residue, a S(═O)2—O—C1-4-aliphatic residue, a S(═O)2—NH—C1-4-aliphatic residue, CN, CF3, CHO, COOH, a C1-4-aliphatic residue, 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;
- in which “mono- or polysubstituted” with respect to “aryl” and a “heteroaryl” 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, an NH—C(═O)—C1-4 aliphatic residue, an NH—S(═O)2—C1-4 aliphatic residue, OH, 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)2—C1-4-aliphatic residue, a S(═O)2—O—C1-4-aliphatic residue, a S(═O)2—NH—C1-4-aliphatic residue, CN, CF3, C(═O)H, C(═O)OH, a C1-4-aliphatic residue, 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, benzyl, aryl, heteroaryl, 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, a racemate, an enantiomer, a diastereomer, a mixture of enantiomers or diastereomers in any mixing ratio, or of an individual enantiomer or diastereomer, or in the form of a salt of a physiologically acceptable acid or base.
43 more elements
Dependencies are inferred from the claim text.