US 6,184,221 B2Granted

Sulfonamide-substituted compounds, processes for their preparation, their use as a medicament or diagnostic, and medicament comprising them

AssigneeHoechst Marion Roussel Deutschland GmbH

InventorsUwe Gerlach, Hans Jochen Lang, Klaus Weidmann, Joachim Brendel

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Abstract

Compounds of the formula I having the meanings of the substituents indicated in the claims are outstandingly active substances for the production of medicaments for the prophylaxis and for the therapy of cardiovascular disorders, in particular arrhythmias, for the treatment of ulcers of the gastrointestinal region or for the treatment of diarrheal illnesses.

Claims28

Dependent claims

A compound of formula I:

in which:
R(1) and R(2) independently of one another are hydrogen, CF3, C2F5, C3F7, alkyl having 1, 2, 3, 4, 5, or 6 carbon atoms, or phenyl,
wherein said phenyl is unsubstituted or substituted by 1 or 2 identical or different substituents that are F, Cl, Br, I, CF3, methyl, methoxy, sulfamoyl, or methylsulfonyl;
or
R(1) and R(2) together are an alkylene chain having 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms;
where one CH2 group of the alkylene chain can be replaced by —O—, —CO—, —S—, —SO—, —SO2—, or —NR(10)—;
R(10) is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
R(3) is R(12)—CaH2a[NR(13)]m—;
R(12) is hydrogen or cycloalkyl having 3, 4, 5, 6, 7, or 8 carbon atoms, CF3, C2F5, or C3F7;
a is zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
m is zero or 1;
R(13) is hydrogen or alkyl having 1, 2, 3, 4, 5, or 6 carbon atoms;
or
R(12) and R(13) together are an alkylene chain having 4, 5, 6, 7, or 8 carbon atoms,
where one CH2 group of the alkylene chain can be replaced by —O—, —[SOzero, 1 or 2]—, —CO—, or —NR(10)—;
R(10) is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
R(4) is R(14)—CrH2r;
r is zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;
R(14) is hydrogen, cycloalkyl having 3, 4, 5, 6, 7, or 8 carbon atoms, piperidyl, 1-pyrrolidinyl, N-morpholino, N-methylpiperazino, CF3, C2F5, C3F7, pyridyl, thienyl, imidazolyl, or phenyl,
wherein said phenyl is unsubstituted or substituted by 1 or 2 identical or different substituents that are F, Cl, Br, I, CF3, methyl, methoxy, sulfamoyl, methylsulfonyl, or methylsulfonylamino;
where one CH2 group of the group CrH2r can be replaced by —O—, —CH═CH—, —C≡C—, —CO—, —CO—O—, —CO—NR(11)—, —[SOzero, 1, or 2]—, or —NR(11)—;
R(11) is hydrogen or —(CaH2a)—R(10);
where one CH2 group of the group CaH2a can be replaced by —O—, —CH═CH—, —C≡C—, —CO—, —CO—O—, —O—CO—, —S—, —SO—, —SO2—, —NR(10)—, or —CONR(10)—;
R(10) is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
a is zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
or
R(3) and R(4) together are an alkylene chain having 3, 4, 5, 6, 7, or 8 carbon atoms, where one CH2 group of the alkylene chain can be replaced by —O—, —[SOzero, 1, or 2]—, —CO—, or —NR(11)—;
R(11) is hydrogen or —(CaH2a)—R(10),
where one CH2 group of the group CaH2a can be replaced by —O—, —CH═CH—, —C≡C—, —CO—, —CO—O—, —O—CO—, —S—, —SO—, —SO2—, NR(10)—, or —CONR(10)—;
R(10) is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
a is zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
R(5) and R(6) together are
—CR(15)═CR(16)—CR(17)═N—,
—CR(15)═CR(16)—N═CR(17)—,
—CR(15)═N—CR(17)═N—,
—CR(15)═N—N═CR(17)—,
—N═CR(16)—CR(17)═N—, or
—S—CR(15)═CR(16)—;
R(15), R(16) and R(17) independently of one another are hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, or 4 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, or 8 carbon atoms, CN, CF3, C2F5, C3F7, N3, NO2, —CONR(19)R(21), —COOR(21),
R(22)—CsH2s—Z—, or phenyl,
wherein said phenyl is unsubstituted or substituted by 1 or 2 identical or different substituents that are F, Cl, Br, I, CF3, methyl, methoxy, sulfamoyl, or methylsulfonyl;
R(19) is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
R(21) is hydrogen, methyl, ethyl, phenyl, or —CuH2u—NR(19)R(20);
wherein said phenyl is unsubstituted or substituted by 1 or 2 identical or different substituents that are F, Cl, Br, I, CF3, methyl, methoxy, sulfamoyl, or methylsulfonyl;
R(20) is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
u is 2 or 3;
R(22) is hydrogen, cycloalkyl having 3, 4, 5, 6, 7, or 8 carbon atoms, —COOR(21), CONR(19)R(21), thienyl, imidazolyl, pyridyl, quinolyl, isoquinolyl, piperidyl, 1-pyrrolidinyl, N-morpholino, N-methylpiperazino, CF3, C2F5, C3F7, or phenyl,
wherein said phenyl is unsubstituted or substituted by 1 or 2 identical or different substituents that are F, Cl, Br, I, CF3, methyl, methoxy, sulfamoyl, or methylsulfonyl;
s is zero, 1, 2, 3, 4, 5, or 6;
Z is —[S(O)zero, 1, or 2]—, —CO—, —SO(zero, 1, or 2)—NR(11)—, —SO2—O—, —O—, —NR(11)— or —[CO—NR(11)]—;
R(7) is hydrogen, hydroxyl, alkoxy having 1, 2, 3, or 4 carbon atoms, acyloxy having 1, 2, 3, or 4 carbon atoms, Cl, Br, F, or alkyl having 1, 2, 3, or 4 carbon atoms;
R(8) is hydrogen or alkyl having 1, 2, 3, 4, 5, or 6 carbon atoms;
or a physiologically tolerable salt of a compound of formula I.

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Dependencies are inferred from the claim text.

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Abstract

A compound of formula I:

in which:
R(1) and R(2) independently of one another are hydrogen, CF3, C2F5, C3F7, alkyl having 1, 2, 3, 4, 5, or 6 carbon atoms, or phenyl,
wherein said phenyl is unsubstituted or substituted by 1 or 2 identical or different substituents that are F, Cl, Br, I, CF3, methyl, methoxy, sulfamoyl, or methylsulfonyl;
or
R(1) and R(2) together are an alkylene chain having 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms;
where one CH2 group of the alkylene chain can be replaced by —O—, —CO—, —S—, —SO—, —SO2—, or —NR(10)—;
R(10) is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
R(3) is R(12)—CaH2a[NR(13)]m—;
R(12) is hydrogen or cycloalkyl having 3, 4, 5, 6, 7, or 8 carbon atoms, CF3, C2F5, or C3F7;
a is zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
m is zero or 1;
R(13) is hydrogen or alkyl having 1, 2, 3, 4, 5, or 6 carbon atoms;
or
R(12) and R(13) together are an alkylene chain having 4, 5, 6, 7, or 8 carbon atoms,
where one CH2 group of the alkylene chain can be replaced by —O—, —[SOzero, 1 or 2]—, —CO—, or —NR(10)—;
R(10) is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
R(4) is R(14)—CrH2r;
r is zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;
R(14) is hydrogen, cycloalkyl having 3, 4, 5, 6, 7, or 8 carbon atoms, piperidyl, 1-pyrrolidinyl, N-morpholino, N-methylpiperazino, CF3, C2F5, C3F7, pyridyl, thienyl, imidazolyl, or phenyl,
wherein said phenyl is unsubstituted or substituted by 1 or 2 identical or different substituents that are F, Cl, Br, I, CF3, methyl, methoxy, sulfamoyl, methylsulfonyl, or methylsulfonylamino;
where one CH2 group of the group CrH2r can be replaced by —O—, —CH═CH—, —C≡C—, —CO—, —CO—O—, —CO—NR(11)—, —[SOzero, 1, or 2]—, or —NR(11)—;
R(11) is hydrogen or —(CaH2a)—R(10);
where one CH2 group of the group CaH2a can be replaced by —O—, —CH═CH—, —C≡C—, —CO—, —CO—O—, —O—CO—, —S—, —SO—, —SO2—, —NR(10)—, or —CONR(10)—;
R(10) is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
a is zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
or
R(3) and R(4) together are an alkylene chain having 3, 4, 5, 6, 7, or 8 carbon atoms, where one CH2 group of the alkylene chain can be replaced by —O—, —[SOzero, 1, or 2]—, —CO—, or —NR(11)—;
R(11) is hydrogen or —(CaH2a)—R(10),
where one CH2 group of the group CaH2a can be replaced by —O—, —CH═CH—, —C≡C—, —CO—, —CO—O—, —O—CO—, —S—, —SO—, —SO2—, NR(10)—, or —CONR(10)—;
R(10) is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
a is zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
R(5) and R(6) together are
—CR(15)═CR(16)—CR(17)═N—,
—CR(15)═CR(16)—N═CR(17)—,
—CR(15)═N—CR(17)═N—,
—CR(15)═N—N═CR(17)—,
—N═CR(16)—CR(17)═N—, or
—S—CR(15)═CR(16)—;
R(15), R(16) and R(17) independently of one another are hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, or 4 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7, or 8 carbon atoms, CN, CF3, C2F5, C3F7, N3, NO2, —CONR(19)R(21), —COOR(21),
R(22)—CsH2s—Z—, or phenyl,
wherein said phenyl is unsubstituted or substituted by 1 or 2 identical or different substituents that are F, Cl, Br, I, CF3, methyl, methoxy, sulfamoyl, or methylsulfonyl;
R(19) is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
R(21) is hydrogen, methyl, ethyl, phenyl, or —CuH2u—NR(19)R(20);
wherein said phenyl is unsubstituted or substituted by 1 or 2 identical or different substituents that are F, Cl, Br, I, CF3, methyl, methoxy, sulfamoyl, or methylsulfonyl;
R(20) is hydrogen or alkyl having 1, 2, or 3 carbon atoms;
u is 2 or 3;
R(22) is hydrogen, cycloalkyl having 3, 4, 5, 6, 7, or 8 carbon atoms, —COOR(21), CONR(19)R(21), thienyl, imidazolyl, pyridyl, quinolyl, isoquinolyl, piperidyl, 1-pyrrolidinyl, N-morpholino, N-methylpiperazino, CF3, C2F5, C3F7, or phenyl,
wherein said phenyl is unsubstituted or substituted by 1 or 2 identical or different substituents that are F, Cl, Br, I, CF3, methyl, methoxy, sulfamoyl, or methylsulfonyl;
s is zero, 1, 2, 3, 4, 5, or 6;
Z is —[S(O)zero, 1, or 2]—, —CO—, —SO(zero, 1, or 2)—NR(11)—, —SO2—O—, —O—, —NR(11)— or —[CO—NR(11)]—;
R(7) is hydrogen, hydroxyl, alkoxy having 1, 2, 3, or 4 carbon atoms, acyloxy having 1, 2, 3, or 4 carbon atoms, Cl, Br, F, or alkyl having 1, 2, 3, or 4 carbon atoms;
R(8) is hydrogen or alkyl having 1, 2, 3, 4, 5, or 6 carbon atoms;
or a physiologically tolerable salt of a compound of formula I.

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