Anthranilamides with heteroarylsulfonyl side chain, process of preparation, and use
This invention encompasses anthranilamides with heteroarylsulfonyl side chain, process for their preparation, their use as medicament or diagnostic aid, and pharmaceutical preparations containing them. Compounds of formula I, in which R1 to R7 have the meanings stated in the claims, act on the Kv1.5 potassium channel and inhibit a potassium current which is referred to as the ultra-rapidly activating delayed rectifier in the atrium of the human heart. They are therefore suitable as novel antiarrhythmic ingredients, such as for the treatment and prophylaxis of atrial arrhythmias, e.g. atrial fibrillation (AF) or atrial flutter.
1. A compound of formula I
in which R1 is:
where A is —C n H 2n — and n=0, 1, 2, 3, 4, or 5;
D is a bond or —O—;
E is —C m H 2m — and m=0, 1, 2, 3, 4, or 5;
R8 is hydrogen, alkyl having 1, 2, 3, or 4 carbon atoms, or C p H 2p —R14 where p is 0, 1, 2, 3, 4, or 5 and where R14 is phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, Br, I, CF 3 , OCF 3 , NO 2 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R9 is hydrogen or alkyl having 1, 2, 3, 4, 5, or 6 carbon atoms;
R10 is hydrogen, alkyl having 1, 2, 3, or 4 carbon atoms, phenyl, naphthyl or heteroaryl, where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, Br, I, CF 3 , OCF 3 , NO 2 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R11 is cycloalkyl having 3, 4, 5, or 6 carbon atoms, phenyl, naphthyl, thienyl, furyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl or cinnolinyl, where phenyl, naphthyl, thienyl, furyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl are unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, Br, I, CF 3 , OCF 3 , NO 2 , CN, COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R12 is alkyl having 1, 2, 3, or 4 carbon atoms, alkynyl having 1, 2, 3, or 4 carbon atoms, cycloalkyl having 3, 4, 5, or 6 carbon atoms, phenyl, naphthyl or heteroaryl where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, Br, I, CF 3 , OCF 3 , NO 2 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R13 is C p H 2p —R14;
R15 is cycloalkyl having 3, 4, 5, 6, 7, or 8 carbon atoms;
R2 is hydrogen or alkyl having 1, 2, 3, or 4 carbon atoms;
R3 is heteroaryl, where heteroaryl is unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, Br, I, CF 3 , OCF 3 , NO 2 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R4, R5, R6, and R7 are, independently of one another, hydrogen, F, Cl, Br, I, CF 3 , OCF 3 , NO 2 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, or methylsulfonylamino;
and the pharmaceutically acceptable salts thereof.
2. A compound of formula I as claimed in claim 1 , in which:
R1 is
wherein
A is —C n H 2n — and n is 0, 1, 2, or 3;
E is —C m H 2m — and m is 0, 1, 2, or 3;
R8 is hydrogen, alkyl having 1, 2, or 3 carbon atoms, or C p H 2p —R14 where p is 0, 1, 2, or 3 and where R14 is phenyl, naphthyl or heteroaryl, where phenyl, naphthyl or heteroaryl are unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R9 is hydrogen or alkyl having 1, 2, 3, or 4 carbon atoms;
R10 is hydrogen, alkyl having 1, 2, or 3 carbon atoms, phenyl, naphthyl or heteroaryl, where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R11 is phenyl, naphthyl, thienyl, furyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl where phenyl, naphthyl, thienyl, furyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl or cinnolinyl are unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R2 is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
R3 is heteroaryl where heteroaryl is unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R4, R5, R6, and R7 are, independently of one another, hydrogen, F, Cl, CF 3 , OCF 3 , CN, COMe, OH, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, or methylsulfonylamino;
and the pharmaceutically acceptable salts thereof.
3. A compound of formula I as claimed in claim 1 , in which:
R1 is
where
A is —C n H 2n — and n is 0 or 1;
E is —C m H 2m — and m is 0 or 1;
R8 is hydrogen, alkyl having 1, 2, or 3 carbon atoms, or C p H 2p —R14 where p is 0 or 1 and where R14 is phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl or heteroaryl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R9 is hydrogen, methyl, or ethyl;
R10 is hydrogen, alkyl having 1, 2, or 3 carbon atoms, phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl, and heteroaryl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R11 is phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl, where phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R2 is hydrogen, methyl, or ethyl;
R3 is heteroaryl, where heteroaryl is unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R4, R5, R6, and R7 are, independently of one another, hydrogen, F, Cl, CF 3 , OCF 3 , CN, COMe, OH, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, or methylsulfonylamino;
and the pharmaceutically acceptable salts thereof.
4. A compound of formula I as claimed in claim 1 , in which
R1 is
where
A is —C n H 2n — and n is 0 or 1;
E is —C m H 2m — and m is 0 or 1;
R8 is hydrogen, alkyl having 1, 2, or 3 carbon atoms, or C p H 2p —R14 where p is 0 or 1 and where R14 is phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl or heteroaryl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, methyl, methoxy, dimethylamino, sulfamoyl, and methylsulfonyl;
R9 is hydrogen, methyl, or ethyl;
R10 is hydrogen, alkyl having 1, 2, or 3 carbon atoms, phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl or heteroaryl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, methyl, methoxy, ethoxy, dimethylamino, sulfamoyl, and methylsulfonyl;
R11 is phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl or cinnolinyl, where phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, methyl, methoxy, ethoxy, dimethylamino, sulfamoyl, and methylsulfonyl;
R2 is hydrogen;
R3 is heteroaryl, where heteroaryl is unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, methyl, methoxy, ethoxy, dimethylamino, sulfamoyl, and methylsulfonyl;
R4 is hydrogen, F, Cl, CF 3 , methyl, or methoxy;
R5 is hydrogen, F, Cl, CF 3 , methyl, methoxy, COMe, OCF 3 , CN, or OH;
R6 is hydrogen, F, Cl, CF 3 , methyl, or methoxy;
R7 is hydrogen, F, Cl, CF 3 , methyl, ethyl, methoxy, or OH;
and the pharmaceutically acceptable salts thereof.
5. A compound of formula I as claimed in claim 1 , in which:
R1 is
where A is —C n H 2n — and n is 0, 1, 2, or 3;
D is a bond or —O—;
E is —C m H 2m — and m is 0, 1, 2, or 3;
R8 is hydrogen, alkyl having 1, 2, or 3 carbon atoms, or C p H 2p —R14 where p is 0, 1, 2, or 3 and where R14 is phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R9 is hydrogen or alkyl having 1, 2, 3, or 4 carbon atoms;
R11 is phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl where phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl are unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R12 is alkyl having 1, 2, or 3 carbon atoms, alkynyl having 1, 2, or 3 carbon atoms, cycloalkyl having 3, 4, 5, or 6 carbon atoms, phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R2 is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
R3 is heteroaryl, where heteroaryl is unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R4, R5, R6, and R7 are, independently of one another, hydrogen, F, Cl, CF 3 , OCF 3 , CN, COMe, OH, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, or methylsulfonylamino;
and the pharmacologically acceptable salts thereof.
6. A compound of formula I as claimed in claim 1 , in which:
R1 is
where A is —C n H 2n — and n is 0 or 1;
D is a bond or —O—;
E is —C m H 2m — and m is 0 or 1;
R8 is hydrogen, alkyl having 1, 2, or 3 carbon atoms, or C p H 2p —R14 where p is 0 or 1 and where R14 is phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R9 is hydrogen, methyl, or ethyl;
R11 is phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl, where phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R12 is alkyl having 1, 2, or 3 carbon atoms, ethynyl, cyclopropyl, phenyl, naphthyl, or heteroaryl where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R2 is hydrogen, methyl, or ethyl;
R3 is heteroaryl, where heteroaryl is unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R4, R5, R6, and R7 are, independently of one another, hydrogen, F, Cl, CF 3 , OCF 3 , CN, COMe, OH, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, or methylsulfonylamino;
and the pharmacologically acceptable salts thereof.
7. A compound of formula I as claimed in claim 1 in which:
R1 is
where A is —C n H 2n — and n is 0 or 1;
D is a bond or —O—;
E is —C m H 2m — and m is 0 or 1;
R8 is hydrogen, alkyl having 1, 2, or 3 carbon atoms, or C p H 2p —R14 where p is 0 or 1 and where R14 is phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl or heteroaryl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, methyl, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R9 is hydrogen, ethyl, or methyl;
R11 is phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl, where phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, methoxy, ethoxy, dimethylamino, sulfamoyl, and methylsulfonyl;
R12 is alkyl having 1, 2, or 3 carbon atoms, ethynyl, cyclopropyl, phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R2 is hydrogen;
R3 is heteroaryl, where heteroaryl is unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, methyl, methoxy, ethoxy, dimethylamino, sulfamoyl, and methylsulfonyl;
R4 is hydrogen, F, Cl, CF 3 , methyl, or methoxy;
R5 is hydrogen, F, Cl, CF 3 , methyl, methoxy, COMe, OCF 3 , CN, or OH;
R6 is hydrogen, F, Cl, CF 3 , methyl, or methoxy;
R7 is hydrogen, F, Cl, CF 3 , methyl, methoxy, or OH;
and the pharmacologically acceptable salts thereof.
8. A compound of formula I as claimed in claim 1 , in which:
R1 is
where A is —C n H 2n — and n=0, 1, 2, or 3;
D is a bond or —O—;
E is —C m H 2m — and m is 0, 1, 2, or 3;
R9 is hydrogen or alkyl having 1, 2, 3, or 4 carbon atoms;
R10 is hydrogen, alkyl having 1, 2, or 3 carbon atoms, phenyl, naphthyl, or heteroaryl where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R11 is phenyl, naphthyl, thienyl, furanyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl, where phenyl, naphthyl, thienyl, furanyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl or cinnolinyl are unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R13 is C p H 2p —R14 where p is 0, 1, 2, or 3 and where R14 is phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R2 is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
R3 is heteroaryl, where heteroaryl is unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R4, R5, R6, and R7 are, independently of one another, hydrogen, F, Cl, CF 3 , OCF 3 , CN, COMe, OH, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, or methylsulfonylamino;
and the pharmaceutically acceptable salts thereof.
9. A compound of formula I as claimed in claim 1 in which:
R1 is
where A is —C n H 2n — and n is 0 or 1;
D is a bond or —O—;
E is —C m H 2m — and m is 0 or 1;
R9 is hydrogen, methyl, or ethyl;
R10 is hydrogen, alkyl having 1, 2, or 3 carbon atoms, phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, alkyl having 1, 2, 3, or 4 carbon atoms, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R11 is phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl, where phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R13 is C p H 2p —R14 where p is 0 or 1 and where R14 is phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R2 is hydrogen, methyl, or ethyl;
R3 is heteroaryl, where heteroaryl is unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R4, R5, R6, and R7 are, independently of one another, hydrogen, F, Cl, CF 3 , OCF 3 , CN, COMe, OH, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, or methylsulfonylamino;
and the pharmaceutically acceptable salts thereof.
10. A compound of formula I as claimed in claim 1 in which
R1 is
where A is —C n H 2n — and n is 0 or 1;
D is a bond or —O—;
E is —C m H 2m — and m is 0 or 1;
R9 is hydrogen, methyl, or ethyl;
R10 is hydrogen, alkyl having 1, 2, or 3 carbon atoms, phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, methyl, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R11 is phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl, where phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, or cinnolinyl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, methyl, methoxy, ethoxy, dimethylamino, sulfamoyl, and methylsulfonyl;
R13 is C p H 2p —R14 where p is 0 or 1 and where R14 is phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, methoxy, ethoxy, dimethylamino, sulfamoyl, and methylsulfonyl;
R2 is hydrogen;
R3 is heteroaryl, where heteroaryl is unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, methoxy, ethoxy, dimethylamino, sulfamoyl, and methylsulfonyl;
R4 is hydrogen, F, Cl, CF 3 , methyl, or methoxy;
R5 is hydrogen, F, Cl, CF 3 , methyl, methoxy, COMe, OCF 3 , CN, or OH;
R6 is hydrogen, F, Cl, CF 3 , methyl, methoxy, or OH;
R7 is hydrogen, F, Cl, CF 3 , methyl, ethyl, methoxy, or OH;
and the pharmaceutically acceptable salts thereof.
11. A compound of formula I as claimed in claim 1 , in which:
R1 is
where A is —C n H 2n — and n=0, 1, 2, or 3;
R8 is hydrogen, alkyl having 1, 2, or 3 carbon atoms, or C p H 2p —R14 where p is 0, 1, 2, or 3 and where R14 is phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R15 is cycloalkyl having 3, 4, 5, 6, or 7 carbon atoms;
R2 is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
R3 is heteroaryl, where heteroaryl is unsubstituted or substituted by 1, 2, or 3 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COOMe, CONH 2 , COMe, NH 2 , OH, alkyl having 1, 2, 3, or 4 carbon atoms, alkoxy having 1, 2, 3, or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R4, R5, R6, and R7 are, independently of one another, hydrogen, F, Cl, CF 3 , OCF 3 , CN, COMe, OH, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, or methylsulfonylamino;
and the pharmaceutically acceptable salts thereof.
12. A compound of formula I as claimed in claim 1 in which:
R1 is
where A is —C n H 2n — and n is 0 or 1;
R8 is hydrogen, alkyl having 1, 2, or 3 carbon atoms, or C p H 2p —R14 where p is 0 or 1 and where R14 is phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R15 is cycloalkyl having 3, 4, 5, 6, or 7 carbon atoms;
R2 is hydrogen, methyl, or ethyl;
R3 is heteroaryl, where heteroaryl is unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, and methylsulfonylamino;
R4, R5, R6, and R7 are, independently of one another, hydrogen, F, Cl, CF 3 , OCF 3 , CN, COMe, OH, alkyl having 1, 2, 3, or 4 carbon atoms, methoxy, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl, or methylsulfonylamino;
and the pharmaceutically acceptable salts thereof.
13. A compound of formula I as claimed in claim 1 in which:
R1 is
where A is —C n H 2n — and n is 0 or 1;
R8 is hydrogen, alkyl having 1, 2, or 3 carbon atoms, or C p H 2p —R14 where p is 0 or 1 and where R14 is phenyl, naphthyl, or heteroaryl, where phenyl, naphthyl, or heteroaryl are unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, methyl, methoxy, ethoxy, dimethylamino, sulfamoyl, and methylsulfonyl;
R15 is cycloalkyl having 3, 4, 5, 6, or 7 carbon atoms;
R2 is hydrogen;
R3 is heteroaryl, where heteroaryl is unsubstituted or substituted by 1 or 2 substituents selected from F, Cl, CF 3 , OCF 3 , CN, COMe, methyl, methoxy, ethoxy, dimethylamino, sulfamoyl, or methylsulfonyl;
R4 is hydrogen, F, Cl, CF 3 , methyl, or methoxy;
R5 is hydrogen, F, Cl, CF 3 , methyl, methoxy, COMe, OCF 3 , CN, or OH;
R6 is hydrogen, F, Cl, CF 3 , methyl, methoxy, or OH;
R7 is hydrogen, F, Cl, CF 3 , methyl, ethyl, methoxy, or OH;
and the pharmaceutically acceptable salts thereof.
14. A pharmaceutical composition comprising:
one or more compounds of claim 1 ; and
one or more pharmaceutically acceptable carriers or additives.
15. A method of treatment or prevention of K + channel-mediated diseases comprising administering a compound of claim 1 to a subject in need thereof.
16. A method of treatment or prevention of cardiac arrhythmias comprising administering a compound of claim 1 to a subject in need thereof.
17. A method of treatment or prevention of reentry arrhythmias comprising administering a compound of claim 1 to a subject in need thereof.
18. A method of treatment or prevention of supraventricular arrhythmias comprising administering a compound of claim 1 to a subject in need thereof.
19. A method of treatment or prevention of atrial fibrillation or atrial flutter comprising administering a compound of claim 1 to a subject in need thereof.
20. A pharmaceutical composition comprising:
one or more compounds of claim 1 ; and
one or more pharmaceutically acceptable carriers or additives; and
a beta-blocker.