Arylated furan- and thiophenecarboxamides, processes for their preparation, their use as medicaments, and pharmaceutical preparations comprising them

• US 6,982,279 B2
• Filed: 12/12/2001
• Issued: 01/03/2006
• Est. Priority Date: 12/12/2000
• Status: Expired due to Fees

• Current Assignee: Sanofi-Aventis Deutschland GmbH (Sanofi )
• Original Assignee: Aventis Pharma Deutschland GmbH (Sanofi )
• Inventors: Kleemann, Heinz-Werner, Brendel, Joachim, Peukert, Stefan, Hemmerle, Horst
• Primary Examiner(s): Lambkin, Deborah C.
• Application Number:
  US10/012,338
• Publication Number:
  US 20040068120A1
• Time in Patent Office: 1,483 Days
• Field of Search: 549/72, 549/71, 549/487, 549/484, 514/448, 514/471
• US Class Current: 514/448
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/34 having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
• CPC Class Codes: A61K 31/38 having sulfur as a ring hetero atom
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: C07D 307/68 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 333/38 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Abstract

Compounds of the formulae IA and Ib.
in which X, R(1), R(2), R(3), R(4), R(5), R(6), R(7), R(30) and R(31) have the meanings indicated in the claims, are very particularly suitable as novel antiarrhythmic active compounds, in particular for the treatment and prophylaxis of atrial arrhythmias, e.g. atrial fibrillation (AF) or atrial flutters.

Claims

1. A compound of the formula Ia or Ib,

or a pharmaceutically acceptable salt thereof,

in which:

X is oxygen or sulfur;

R(1) is C(O)OR(9), SO₂R(10), COR(11), C(O)NR(12)R(13) or C(S)NR(12)R(13);

R(9), R(10), R(11) and R(12)

independently of one another are C_xH_2x—

R(14);

x is 0, 1, 2, 3 or 4,

where x cannot be 0 if R(14) is OR(15) or SO₂Me;

R(14) is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 carbon atoms, CF₃, C₂F₅, C₃F₇, CH₂F, CHF₂, OR(15), SO₂Me, phenyl, naphthyl, biphenylyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms,

where phenyl, naphthyl, biphenylyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(15) is alkyl having 1, 2, 3, 4 or 5 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, CF₃ or phenyl, which is unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(13) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or CF₃;

R(2) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or CF₃;

R(3) is C_yH_2y—

R(l

     6);

y is 0, 1, 2, 3 or 4,

where y cannot be 0 if R(16) is OR(17) or SO₂Me;

R(16) is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 carbon atoms, CF₃, C₂F₅, C₃F₇, CH₂F, CHF₂, OR(17), SO₂Me, phenyl, naphthyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms,

where phenyl, naphthyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

 

R(17) is hydrogen, alkyl having 1, 2, 3, 4 or 5 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, CF₃, phenyl or 2-, 3- or 4-pyridyl,

where phenyl or 2-, 3- or 4-pyridyl is unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

or

R(3) is CHR(18)R(19);

R(18) is hydrogen or C_zH_2z—

R(16), where R(16) is defined as indicated above;

z is 0, 1, 2 or 3;

R(19) is COOH, CONH₂, CONR(20)R(21), COOR(22) or CH₂OH;

R(20) is hydrogen, alkyl having 1, 2, 3, 4 or 5 carbon atoms, C_vH_2v—

CF₃ or C_wH_2w-phenyl,

where the phenyl ring is unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

v is 0, 1, 2 or 3;

w is 0, 1, 2 or 3;

R(21) is hydrogen or alkyl having 1, 2, 3, 4 or 5 carbon atoms;

R(22) is alkyl having 1, 2, 3, 4 or 5 carbon atoms;

R(4) is hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or CF₃;

or

R(3) and R(4)

together are a chain of 4 or 5 methylene groups, of which one methylene group can be replaced by —

O—

, —

S—

, —

NH—

, —

N(methyl)- or —

N(benzyl)-;

R(5), R(6) and R(7)

independently of one another are hydrogen, F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino;

R(30) and R(31)

independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;

or

R(30) and R(31)

together are oxygen or a chain of 2 methylene groups.

2. A compound of the formula Ia or Ib as claimed in claim 1, or a pharmaceutically acceptable salt thereof, in which:

X is oxygen or sulfur;

R(1) is C(O)OR(9), SO₂R(10), COR(11) or C(O)NR(12)R(13);

R(9), R(10), R(11) and R(12)

independently of one another are C_xH_2x—

R(14);

x is 0, 1, 2, 3 or 4,

where x cannot be 0 if R(14) is OR(15)

R(14) is alkyl having 1, 2, 3, 4, carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9 carbon atoms, CF₃, OR(15), phenyl, naphthyl, biphenylyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms,

where phenyl, naphthyl, biphenylyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

 

R(15) is alkyl having 1, 2, 3, 4 or 5 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, CF₃ or phenyl, which is unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(13) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or CF₃;

R(2) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or CF₃;

R(3) is C_yH_2y—

R(¹⁶);

y is 0, 1, 2, 3 or 4,

where y cannot be 0 if R(16) is OR(17) or SO₂Me;

R(16) is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8 or 9 carbon atoms, CF₃, OR(17), SO₂Me, phenyl, naphthyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms,

where phenyl, naphthyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

 

R(17) is hydrogen, alkyl having 1, 2, 3, 4 or 5 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, CF₃, phenyl or 2-, 3- or 4-pyridyl,

where phenyl or 2-, 3- or 4-pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

or

R(3) is CHR(18)R(19);

R(18) is hydrogen or C_zH_2z—

R(16), where R(16) is defined as indicated above;

z is 0, 1, 2 or 3;

R(19) is CONH₂, CONR(20)R(21), COOR(22) or CH₂OH;

R(20) is hydrogen, alkyl having 1, 2, 3, 4 or 5 carbon atoms, C_vH_2v—

CF₃ or C_wH_2w-phenyl,

where the phenyl ring is unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

v is 0, 1, 2 or 3;

w is 0, 1, 2 or 3;

R(21) is hydrogen or alkyl having 1, 2, 3, 4 or 5 carbon atoms;

R(22) is alkyl having 1, 2, 3, 4 or 5 carbon atoms;

R(4) is hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or CF₃;

R(5), R(6) and R(7)

independently of one another are hydrogen F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino;

R(30) and R(31)

independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;

or

R(30) and R(31)

are a chain of 2 methylene groups.

3. A compound of the formula Ia or Ib as claimed in claim 1, or a pharmaceutically acceptable salt thereof, in which:

X is oxygen or sulfur;

R(1) is C(O)OR(9), SO₂R(10), COR(11) or C(O)NR(12)R(13);

R(9), R(10), R(11) and R(12)

independently of one another are C_xH_2x—

R(14);

x is 0, 1, 2, 3 or 4,

where x cannot be 0 if R(14) is OR(15);

R(14) is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 carbon atoms, CF₃, C₂F₅, C₃F₇, CH₂F, CHF₂, OR(15), phenyl, naphthyl, biphenylyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms,

where phenyl, naphthyl, biphenylyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

 

R(15) is alkyl having 1, 2, 3, 4 or 5 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, CF₃ or phenyl, which is unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(13) is hydrogen;

R(2) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;

R(3) is CHR(18)R(19);

R(18) is hydrogen or C_zH_2z—

R(16),

R(16) is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8 or 9 carbon atoms, CF₃, OR(17), SO₂Me, phenyl, naphthyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms,

where phenyl, naphthyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(17) is hydrogen, alkyl having 1, 2, 3, 4 or 5 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, CF₃, phenyl or 2-, 3- or 4-pyridyl,

where phenyl or 2-, 3- or 4-pyridyl is unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

z is 0, 1, 2 or 3;

R(19) is CONH₂, CONR(20)R(21), COOR(22) or CH₂OH;

R(20) is hydrogen, alkyl having 1, 2, 3, 4 or 5 carbon atoms, C_vH_2v—

CF₃ or C_wH_2w-phenyl,

where the phenyl ring is unsubstituted or substituted having 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

 

v is 0, 1, 2 or 3;

 

w is 0, 1, 2 or 3;

R(21) is hydrogen or alkyl having 1, 2, 3, 4 or 5 carbon atoms;

R(22) is alkyl having 1, 2, 3, 4 or 5 carbon atoms;

R(4) is hydrogen, alkyl having 1 or 2 carbon atoms

R(5), R(6) and R(7)

independently of one another are hydrogen F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino;

R(30) and R(31)

independently of one another are hydrogen or methyl.

4. A compound of the formula Ia or Ib as claimed in claim 1, or a pharmaceutically acceptable salt thereof, in which:

X is oxygen or sulfur;

R(1) is C(O)OR(9), SO₂R(10), COR(11) or C(O)NR(12)R(13);

R(9), R(10), R(11) and R(12)

independently of one another are C_xH_2x—

R(14);

x is 0, 1, 2, 3 or 4,

R(14) is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 carbon atoms, CF₃, C₂F₅, C₃F₇, CH₂F, CHF₂, SO₂Me, phenyl, naphthyl, biphenylyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms,

where phenyl, naphthyl, biphenylyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(13) is hydrogen;

R(2) is hydrogen or methyl;

R(3) is C_yH_2y—

R(16);

y is 0, 1, 2, 3 or 4;

where y cannot be 0 if R(16) is OR(17);

R(16) is alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 carbon atoms, CF₃, C₂F₅, C₃F₇, CH₂F, CHF₂, OR(17), SO₂Me, phenyl, naphthyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms,

where phenyl, naphthyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(17) is hydrogen, alkyl having 1, 2, 3, 4 or 5 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, CF₃, phenyl or 2-, 3- or 4-pyridyl,

where phenyl or 2-, 3- or 4-pyridyl is unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(4) is hydrogen or alkyl having 1 or 2 carbon atoms;

R(5), R(6) and R(7)

independently of one another are hydrogen F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino;

R(30) and R(31)

independently of one another are hydrogen or methyl.

5. A compound of the formula Ia or Ib as claimed in claim 1, or a pharmaceutically acceptable salt thereof, in which:

R(1) is C(O)OR(9), SO₂R(10), COR(11) or C(O)NR(12)R(13);

R(9), R(10), R(11) and R(12)

independently of one another are C_xH_2x—

R(14);

x is 0, 1, 2 or 3;

R(14) is alkyl having 1, 2, 3 or 4 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, 8 or 9 carbon atoms, CF₃, phenyl or pyridyl,

where phenyl and pyridyl are unsubstituted or substituted by 1 or 2 substituents chosen from F, Cl, Br, I, CF₃, OCF₃, OH, alkyl having 1, 2, 3, and alkoxy having 1 or 2 carbon atoms;

R(13) is hydrogen;

R(2) is hydrogen;

R(3) is C_yH_2y—

R(¹⁶);

y is 0, 1 or 2;

R(16) is alkyl having 1, 2 or 3 carbon atoms, cycloalkyl having 5 or 6 carbon atoms, CF₃, phenyl or pyridyl,

where phenyl and pyridyl are unsubstituted or substituted by 1 or 2 substituents chosen from F, C₁, CF₃, OCF₃, alkyl having 1, 2 or 3 carbon atoms and alkoxy having 1 or 2 carbon atoms;

R(4) is hydrogen;

R(5), R(6) and R(7)

independently of one another are hydrogen F, C₁, CF₃, CN, COOMe, CONH₂, COMe, NH₂, OH, alkyl having 1, 2 or 3 carbon atoms, or alkoxy having 1 or 2 carbon atoms;

R(30) and R(31)

independently of one another are hydrogen or methyl.

6. A compound of the formula Ia or Ib as claimed in claim 1, or a pharmaceutically acceptable salt thereof, in which:

X is oxygen or sulfur;

R(1) is C(O)OR(9) or COR(11);

R(9) and R(11)

independently of one another are C_xH_2x—

R(14);

x is 0, 1, 2 or 3;

R(14) is cycloalkyl having 5 or 6 carbon atoms or phenyl,

where phenyl is unsubstituted or substituted by 1 or 2 substituents chosen from F, Cl, Br, I, CF₃, OCF₃, OH, alkyl having 1, 2, 3 and alkoxy having 1 or 2 carbon atoms;

R(2) is hydrogen;

R(3) is C_yH_2y—

R(16);

y is 0, 1 or 2;

R(16) is alkyl having 1, 2 or 3 carbon atoms, cycloalkyl having 5 or 6 carbon atoms, phenyl or pyridyl,

where phenyl and pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents chosen from F, C₁, CF₃, alkyl having 1, 2 or 3 carbon atoms and alkoxy having 1 or 2 carbon atoms;

R(4) is hydrogen;

R(5), R(6) and R(7)

independently of one another are hydrogen F, Cl, alkyl having 1, 2 or 3 carbon atoms or alkoxy having 1 or 2 carbon atoms;

R(30) and R(31)

are hydrogen.

7. A pharmaceutical composition, comprising at least one compound as claimed in claim 1 and one or more pharmaceutically acceptable vehicles and additives.

8. A pharmaceutical composition as claimed in claim 7, which further comprises one or more other pharmacological active compounds.

9. A method for the therapy of cardiac arrhythmia which can be eliminated by action potential prolongation, which comprises administering to a host in need of the therapy an effective amount of one or more compounds as claimed in claim 1.

10. A method for the therapy of reentry arrhythmia, which comprises administering to a host in need of the therapy an effective amount of one or more compounds as claimed in claim 1.

11. A method for the therapy of supraventricular arrhythmia, which comprises administering to a host in need of the therapy an effective amount of one or more compounds as claimed in claim 1.

12. A method for the therapy of atrial fibrillation or atrial flutters, which comprises administering to a host in need of the therapy an effective amount of one or more compounds as claimed in claim 1.

13. A method for the termination of atrial fibrillation or atrial flutters, which comprises administering to a host in need of the therapy an effective amount of one or more compounds as claimed in claim 1.

14. A pharmaceutical composition as claimed in claim 7, which further comprises at least one IK_r channel blocker.

15. A pharmaceutical composition as claimed in claim 7, which further comprises at least one IK_s channel blocker.

16. A pharmaceutical composition as claimed in claim 7, which further comprises at least one beta blocker.