DE19730326A1 - New N-substituted sulphonamide or sulphamide compounds - Google Patents

Abstract

N-(Bicyclic aryl or heteroaryl)-sulphonamide or sulphamide derivatives of formula (I) and their salts are new: X = O, S, SO, SO2, NR7, CR'8R"8 or C=O; R7 = H or -CaH2a-R9, where one CH2 is optionally replaced by O, CH=CH, C?=C, CO, CO2, OCO, S, SO, SO2, NR10 or CONR10; R10 = H or A; a = 0-8; R9 = H, CF3, C2F5, C3F7, 3-8 C cycloalkyl, NMe2, NEt2, 1-piperidyl, pyrrolidino, morpholino or 4-methyl-piperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl (the latter four all optionally substituted by 1 or 2 F, Cl, Br, I, CF3, NO2, CN, NH2, OH, Me, Et, OMe, NMe2, SO2NH2, SO2Me and NHSO2Me); or R1+R7 = bond; R'8 = H, CF3, C2F5, C3F7, 1-6 C alkyl or phenyl (optionally substituted by 1 or 2 F, Cl, Br, I, CF3, NO2, CN, NH2, OH, Me, Et, OMe, NMe2, SO2NH2, SO2Me and NHSO2Me); R"8 = H, A, OR10, CO2R10 or COR10; R10 = H or A; or R'8+R1 or R"8+R1 = bond if Y = N; Y = N or CR11; R11 = H or A; R1, R2 = H, CF3, C2F5, C3F7, F, Cl, OMe, 1-6 C alkyl or phenyl (optionally substituted by 1 or 2 F, Cl, Br, I, CF3, NO2, CN, NH2, OH, Me, Et, OMe, NMe2, SO2NH2, SO2Me and NHSO2Me); or CR1R2 = 2-10 C alkylene chain; R3 = R12-CnH2n-N(R13)- or R12-CnH2n-, where one CH2 of CnH2n is optionally replaced by O, CO, S, SO, SO2 or R'10; R'10 = H, Me or Et; R12 = H, Me, 3-8 C cycloalkyl, CF3, C2F5 or C3F7; n = 0-10; R13 = H or 1-6 C alkyl; or R12+R13 = bond if n \- 3; or R3+R4 = 3-8 C alkylene chain, where one CH2 is optionally replaced by O, CO, S, SO, SO2 or NR'10; R4 = R14-CrH2r-, where one CH2 of CrH2r is optionally replaced by O, CH=CH, C?=C, CO, CO2, OCO, S, SO, SO2, NR"10 or CONR"10; R"10 = H or A; R14 = Me, CF3, C2F5, C3F7, 3-8 C cycloalkyl, OH, CO2H, NR23R24, 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl or 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl (the latter four all optionally substituted by 1 or 2 F, Cl, Br, I, CF3, NO2, CN, NH2, OH, Me, Et, OMe, NMe2, SO2NH2, SO2Me and NHSO2Me); R23, R24 = H or A; or NR23R24 = (CH2)k, where one CH2 is optionally replaced by O, S, NH, NMe or N(CH2Ph); k = 4 or 5; r = 0-20; R5+R6 = -CR15=CR16CR17=CR18-, -CR15=CR16CR17=N-, -CR15=CR16N=CR18-, -CR15=N-CR17=N-, -CR15=NN=CR18-, -N=CR16CR17=N- or -SCR15=CR16-, all bonded in either direction; R15-R18 = H, F, Cl, Br, I, 1-5C alkyl, 3-8 C cycloalkyl, CN, CF3, C2F5, C3F7, N3, NO2, -Z-CsH2s-R22, thienyl or phenyl (optionally substituted by 1 or 2 F, Cl, Br, I, CF3, NO2, CN, NH2, OH, Me, Et, OMe, NMe2, SO2NH2, SO2Me and NHSO2Me); Z = O, CO, CO2, OCO, S, SO, SO2, SO2O, SO2NR'"10, NR'"10 or CONR'"10; R'"10 = H or A; s = 0-6; R22 = H, CF3, C2F5, C3F7, 3-8 C cycloalkyl, NR19R20, CO2R21, 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl or 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl or phenyl (the latter six all optionally substituted by 1 or 2 F, Cl, Br, I, CF3, NO2, CN, NH2, OH, Me, Et, OMe, NMe2, SO2NH2, SO2Me and NHSO2Me); R19, R20 = H or A; or NR19R20 = (CH2)k, where one CH2 is optionally replaced by O, S, NH, NMe or N(CH2Ph); R21 = H or A; and A = 1-3 C alkyl; provided that Y is not CR11 if X = O.

Description

The invention relates to compounds of the formula I

wherein X, Y, R (1), R (2), R (3), R (4), R (5) and R (6) have the meanings given below, their preparation and their use, in particular in medicaments . The compounds influence the potassium channel or the I _Ks channel opened by cyclic adenosine monophosphate (cAMP) and are outstandingly suitable as active pharmaceutical ingredients, for example for the prophylaxis and therapy of cardiovascular diseases, in particular arrhythmias, for the treatment of ulcers of the gastrointestinal tract. Area or to treat diarrhea.

In drug chemistry, the class of 4-Acylaminochroman derivatives worked intensively, with some corresponding Chromene derivatives have been described. The most prominent representative of this class is the cromakalim of formula A, an example of a chromene is the compound of Formula B (J. Chem. Soc. Perkin Trans. 1, 1991, 63-70).  

Cromakalim and other related 4-acylaminochrome an derivatives are compounds with a relaxing effect on smooth muscle organs, so that they are used to lower the increased blood pressure due to vascular muscle relaxation and in the treatment of asthma due to the relaxation of the smooth muscles of the airways. All these preparations have in common that they act on the cellular level, for example of smooth muscle cells, and there lead to the opening of certain ATP-sensitive K⁺ channels. The increase in negative charge in the cell (hyperpolarization) induced by the emergence of K⁺ ions counteracts the increase in the intracellular Ca ² ⁺ concentration and thus cell activation via secondary mechanisms, which z. B. leads to muscle contraction.

The compounds of formula I according to the invention differ structurally from these acylamino derivatives, inter alia, by the replacement of the acylamino group by a sulfonylamino function. While the cromakalim (formula A) and the chromium derivative of the formula B and analog acylamino compounds act as openers of ATP-sensitive K⁺ channels, the compounds of the formula I according to the invention with the sulfonylamino structure, however, have no opening action on this K⁺ (ATP) - Channel, but surprisingly a strong and specific blocking (closing) effect on a K⁺ channel, which is opened by cyclic adenosine monophosphate (cAMP) and differs fundamentally from the mentioned K⁺ (ATP) channel. Recent studies show that this K⁺ (cAMP) channel identified on colon tissue is very similar, perhaps even identical, to the I _Ks channel identified on the heart muscle. In fact, for the compounds of the formula I according to the invention, a strong blocking action on the I _Ks channel in guinea pig cardiomyocytes as well as on the I _sK channel expressed in Xenopus oocytes could be demonstrated. As a result of this blocking of the K⁺ (cAMP) channel or the I _Ks channel, the compounds according to the invention develop pharmacological effects of high therapeutic utility in the living organism.

In addition to the above-mentioned cromakalim or acylaminochroman derivatives are also compounds with 4-sulfonylaminochroman structure in the literature described, which differ both in structure and in biological Effect clearly of the compounds of the formula according to the invention differentiate. So in EP-A-315 009 Chroman derivatives with 4-Phenylsulfonylaminostruktur described, which are characterized by antithrombotic and distinguish antiallergic properties. In EP-A-389 861 and JP 01294677 are 3-hydroxychroman or chromene derivatives with a cyclic 4-sulfonylamino group described (e.g. Compound C), which has an activation of the K⁺ (ATP) channel are said to act as antihypertensives. In EP-A-370 901 3-hydroxychrome and / or chromene derivatives with a 4-sulfonylamino group, where the remaining valence of the N atom carries a hydrogen atom, which is described via CNS effects. Other 4-sulfonylaminochroman derivatives are described in Bioorg. Med. Chem. Lett. 4 (1994), 769-773: "N-sulfonamides of benzopyran related potassium channel openers: conversion of glyburyde insensitive smooth muscle relaxants to potent smooth muscle contractors ".

The present invention relates to compounds of the formula I

in which mean:
X -O-, -S-, -SO-, -SO ₂ -, -NR (7) -, -CR (8a) R (8b) - or -CO-;
R (7) is hydrogen or - (C _a H _2a ) -R (9), where a CH ₂ group from the group C _a H _2a can be replaced by -O-, -CH = CH-, -C∼C- , -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, NR (10) - or -CONR (10) -;
R (10) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
a zero, 1, 2, 3, 4, 5, 6, 7 or 8;
R (9) hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, dimethylamino, diethylamino, 1-piperidyl, 1-pyrrolidinyl, 4- Morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl, where pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
or
R (7) together with R (1) is a bond;
R (8a) is hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or phenyl which is unsubstituted or substituted by 1 or 2 substituents from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (8b) is hydrogen, alkyl having 1, 2 or 3 carbon atoms, -OR (10), -COOR (10), CO-R (10);
R (10) is hydrogen or alkyl having 1, 2 or 3 carbon atoms,
or
one of the radicals R (8a) or R (8b) together with R (1) forms a bond if Y is N;
YN or CR (11);
R (11) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (1) and R (2) independently of one another are hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , F, Cl, methoxy, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or phenyl , which is unsubstituted or substituted with 1 or 2 substituents, selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
or
R (1) and R (2) together form an alkylene chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms;
R (3) R (12) -C _n H _2n -NR (13) - or R (12) -C _n H _2n -, whereby a CH ₂ group in the groups C _n H _2n can be replaced by -O -, -CO-, -S-, -SO-, -SO ₂ - or -NR (10a) -;
R (10a) is hydrogen, methyl or ethyl;
R (12) is hydrogen, methyl, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, CF ₃ , C ₂ F ₅ or C ₃ F ₇ ;
n zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R (13) is hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms;
or
R (12) and R (13) together form a bond if n is not less than 3;
or
R (3) together with R (4) is an alkylene chain with 3, 4, 5, 6, 7 or 8 carbon atoms, a CH ₂ group of the alkylene chain being -O-, -CO-, -S-, - SO-, -SO ₂ - or -NR (10a) - can be replaced;
R (10a) is hydrogen, methyl or ethyl;
R (4) R (14) -C _r H _2r , where a CH ₂ group from the group C _r H _2r can be replaced by -O-, -CH = CH-, -C∼C-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (14) methyl, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, -OH, -COOH, -NR (23) R (24 ), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl, where pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (23) and R (24) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
or
R (23) and R (24) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
r zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;
R (5) and R (6) together form a group
-CR (15) = CR (16) -CR (17) = CR (18) -,
-CR (15) = CR (16) -CR (17) = N-,
-CR (15) = CR (16) -N = CR (18) -,
-CR (15) = N-CR (17) = N-,
-CR (15) = NN = CR (18) -,
-N = CR (16) -CR (17) = N- or
-S-CR (15) = CR (16) -,
both directions of linkage are possible;
R (15), R (16), R (17) and R (18) independently of one another are hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4 or 5 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, -CN, -CF ₃ , -C ₂ F ₅ , -C ₃ F ₇ , -N ₃ , -NO ₂ , -ZC _s H _2s -R (22) , Thienyl or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino , Sulfamoyl, methylsulfonyl and methylsulfonylamino;
Z -O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -SO ₂ -O-, -SO ₂ NR (10c), - NR (10c) - or -CONR (10c) -;
R (10c) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
s zero, 1, 2, 3, 4, 5 or 6;
R (22) hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, -NR (19) R (20), -COOR (21 ), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl or phenyl, where pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (19) and R (20) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
or
R (19) and R (20) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
R (21) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
however, Y cannot simultaneously be CR (11) and X can equal O;
as well as their physiologically acceptable salts.

Compounds of the formula I are preferred in which:
X -O-, -S-, -SO-, -SO_2nd-, -NR (7) -, -CR (8a) R (8b) - or -CO-;
R (7) is hydrogen or - (C_aH_2a) -R (9), being a CH_2nd-Group of group C_aH_2a can be replaced by -O-, -CH = CH-, -C = -C-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO_2nd-, -NR (10) - or -CONR (10) -;
R (10) Hydrogen or alkyl having 1, 2 or 3 carbon atoms;
a zero, 1, 2, 3, 4, 5, 6, 7 or 8;
R (9) hydrogen, CF._3rd, C_2ndF₅, C_3rdF₇, Cycloalkyl with 3, 4, 5, 6, 7 or 8 Carbon atoms, dimethylamino, diethylamino, 1-piperidyl, 1- Pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, Thienyl, imidazolyl or phenyl, where pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted by 1 or 2 Substituents selected from the group consisting of from F, Cl, Br, I, CF_3rd, NO_2nd, CN, NH_2nd, OH, methyl, ethyl,  Methoxy, dimethylamino, sulfamoyl, methylsulfonyl and Methylsulfonylamino;
R (8a) Hydrogen, CF._3rd, C_2ndF₅, C_3rdF₇, Alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms or phenyl, that is unsubstituted or substituted with 1 or 2 Substituents selected from the group consisting of F, Cl, Br, I, CF._3rd, NO_2nd, CN, NH_2nd, OH, methyl, ethyl, methoxy, Dimethylamino, sulfamoyl, methylsulfonyl and Methylsulfonylamino;
R (8b) hydrogen, alkyl having 1, 2 or 3 carbon atoms, -OR (10), -COOR (10), -CO-R (10);
R (10) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
Y N or CR (11);
R (11) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (1) and R (2) independently hydrogen, CF_3rd, C_2ndF₅, C_3rdF₇, Alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms or phenyl, which is unsubstituted or substituted with 1 or 2 substituents, selected from the group consisting of F, Cl, Br, I, CF_3rd, NO_2ndCN NH_2nd, OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, Methylsulfonyl and methylsulfonylamino;
or
R (1) and R (2) together an alkylene chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms;
R (3) R (12) -C_nH_2n-NR (13) - or R (12) -C_nH_2n-, being a CH_2ndGroup in groups C_nH_2n can be replaced by -O-, -CO-, -S-, -SO-, -SO_2nd- or -NR (10a) -;
R (10a) is hydrogen, methyl or ethyl;
R (12) Hydrogen, methyl, cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, CF._3rd, C._2ndF₅ or C_3rdF₇;
 n zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R (13) Hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms;
or
R (12) and R (13) together a bond if n is not less than 3;
or
R (3) together with R (4) is an alkylene chain with 3, 4, 5, 6, 7 or 8 carbon atoms, being a CH_2nd-Group of the alkylene chain by -O-, -CO-, -S-, -SO-, -SO_2nd- or -NR (10a) - can be replaced;
R (10a) is hydrogen, methyl or ethyl;
R (4) R (14) -C_rH_2r, being a CH_2nd-Group of group C_rH_2r can be replaced by -O-, -CH = CH-, -C∼C-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO_2nd-, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (14) Methyl, CF._3rd, C_2ndF₅, C_3rdF₇, Cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, -OH, -COOH, -NR (23) R (24), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl, wherein pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group Group consisting of F, Cl, Br, I, CF_3rd, NO_2nd, CN, NH_2nd, Oh Methyl, ethyl, methoxy, dimethylamino, sulfamoyl, Methylsulfonyl and methylsulfonylamino;
R (23) and R (24) independently of one another hydrogen or alkyl with 1, 2 or 3 Carbon atoms;
or
R (23) and R (24) together a chain of 4 or 5 methylene groups, of  which a CH_2ndGroup by -O-, -S-, -NH-, -N (CH_3rd) - or -N (benzyl) - can be replaced;
r zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;
R (5) and R (6) together a group
-CR (15) = CR (16) -CR (17) = CR (18) -,
-CR (15) = CR (16) -CR (17) = N-,
-CR (15) = CR (16) -N = CR (18) -,
-CR (15) = N-CR (17) = N-,
-CR (15) = N-N = CR (18) -,
-N = CR (16) -CR (17) = N- or
-S-CR (15) = CR (16) -,
both directions of linkage are possible;
R (15), R (16), R (17) and R (18) independently of one another hydrogen, F, Cl, Br, I, alkyl with 1, 2, 3.4 or 5 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, -CN, -CF_3rd, -C_2ndF₅, -C_3rdF₇, -N_3rd, -NO_2nd, -Z-C_sH_2s-R (22), thienyl or phenyl, that is unsubstituted or substituted with 1 or 2 Substituents selected from the group consisting of F, Cl, Br, I, CF._3rd, NO_2nd, CN, NH_2nd, OH, methyl, ethyl, methoxy, Dimethylamino, sulfamoyl, methylsulfonyl and Methylsulfonylamino;
Z -O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO_2nd-, -SO_2nd-O-, -SO_2ndNR (10c), -NR (10c) - or -CONR (10c) -;
R (10c) Hydrogen or alkyl having 1, 2 or 3 carbon atoms;
s zero, 1, 2, 3, 4, 5 or 6;
R (22) Hydrogen, CF._3rd, C_2ndF₅, C_3rdF₇, Cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, -NR (19) R (20), -COOR (21), 1-piperidyl, 1-  Pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, Thienyl, imidazolyl, quinolyl, isoquinolyl or phenyl, where pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl and phenyl are unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of from F, Cl, Br, I, CF_3rd, NO_2nd, CN, NH_2nd, OH, methyl, ethyl, Methoxy, dimethylamino, sulfamoyl, methylsulfonyl and Methylsulfonylamino;
R (19) and R (20) independently of one another hydrogen or alkyl with 1, 2 or 3 carbon atoms;
or
R (19) and R (20) together a chain of 4 or 5 methylene groups, one of which is CH_2nd-Group by -O-, -S-, -NH-, -N (CH_3rd) - or -N (benzyl) - can be replaced;
R (21) is hydrogen or alkyl having 1, 2 or 3 carbon atoms; however, Y cannot simultaneously be CR (11) and X can equal O; as well as their physiologically acceptable salts.

Compounds of the formula I are also preferred, in which:
X -NR (7) - or -CR (8a) R (8b) -;
R (7) together with R (1) is a bond;
R (8b) is hydrogen, alkyl having 1, 2 or 3 carbon atoms, -OR (10), -COOR (10), -CO-R (10);
R (10) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (8a) together with R (1) is a bond;
YN; or CR (11) if X has the meaning of NR (7);
R (11) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (1) together with R (7) or R (8a) is a bond;
R (2) is hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , F, Cl, methoxy, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or phenyl which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (3) R (12) -C _n H _2n -NR (13) - or R (12) -C _n H _2n -, whereby a CH ₂ group in the groups C _n H _2n can be replaced by -O -, -CO-, -S-, -SO-, -SO ₂ - or -NR (10a) -;
R (10a) is hydrogen, methyl or ethyl;
R (12) is hydrogen, methyl, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, CF ₃ , C ₂ F ₅ or C ₃ F ₇ ;
n zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R (13) is hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms;
or
R (12) and R (13) together form a bond if n is not less than 3;
or
R (3) together with R (4) is an alkylene chain with 3, 4, 5, 6, 7 or 8 carbon atoms;
R (4) R (14), C _r H _2r , where a CH ₂ group from the group C _r H _2r can be replaced by -O-, -CH = CH-, -C∼C-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (14) methyl, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, -OH, -COOH, -NR (23) R (24 ), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl or imidazolyl, pyridyl, thienyl and imidazolyl being unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (23) and R (24) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
or
R (23) and R (24) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
r zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;
R (5) and R (6) together form a group
-CR (15) = CR (16) -CR (17) = CR (18) - or -S-CR (15) = CR (16) -, in each case both linking directions are possible;
R (15), R (16), R (17) and R (18) independently of one another are hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4 or 5 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, -CN, -CF ₃ , -C ₂ F ₅ , -C ₃ F ₇ , -N ₃ , -NO ₂ , ZC _s H _2s -R (22), Thienyl or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, Sulfamoyl, methylsulfonyl and methylsulfonylamino;
Z -O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -SO ₂ -O-, -SO ₂ NR (10c), - NR (10c) - or -CONR (10c) -;
R (10c) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
s zero, 1, 2, 3, 4, 5 or 6;
R (22) hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, -NR (19) R (20), -COOR (21 ), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl or phenyl, where pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (19) and R (20) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
or
R (19) and R (20) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
R (21) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
as well as their physiologically acceptable salts.

Compounds of the formula I are particularly preferred, in which:

X -O-, -S-, -SO-, -SO ₂ -, -NR (7) -, -CR (8a) R (8b) - or -CO-;
R (7) is hydrogen or - (C _a H _2a ) -R (9), where a CH ₂ group from the group C _a H _2a can be replaced by -O-, -CH = CH-, -C∼C- , -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -NR (10) - or -CONR (10) -;
R (10) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
a zero, 1, 2, 3, 4, 5, 6, 7 or 8;
R (9) hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, dimethylamino, diethylamino, 1-piperidyl, 1-pyrrolidinyl, 4- Morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl, where pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (8a) is hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or phenyl which is unsubstituted or substituted by 1 or 2 substituents from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (8b) is hydrogen, alkyl having 1, 2 or 3 carbon atoms, -OR (10), -COOR (10), -CO-R (10);
R (10) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
YN or CR (11);
R (11) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (1) and R (2) independently of one another are hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
or
R (1) and R (2) together form an alkylene chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms;
R (3) R (12) -C _n H _2n -NR (13) - or R (12) -C _n H _2n -, whereby a CH ₂ group in the groups C _n H _2n can be replaced by -O -, -CO-, -S-, -SO-, -SO ₂ - or -NR (10a) -;
R (10a) is hydrogen, methyl or ethyl;
R (12) is hydrogen, methyl, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, CF ₃ , -C ₂ F ₅ or C ₃ F ₇ ;
n zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R (13) is hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms;
or
R (12) and R (13) together form a bond if n is not less than 3;
or
R (3) together with R (4) is an alkylene chain with 3, 4, 5, 6, 7 or 8 carbon atoms, a CH ₂ group of the alkylene chain being -O-, -CO-, -S-, - SO-, - SO ₂ - or -NR (10a) - can be replaced;
R (10a) is hydrogen, methyl or ethyl;
R (4) R (14) -C _r H _2r , where a CH ₂ group from the group C _r H _2r can be replaced by -O-, -CH = CH-, -C∼C-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (14) methyl, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, -OH, -COOH, -NR (23) R (24 ), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl, where pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (23) and R (24) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
or
R (23) and R (24) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
r zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;
R (5) and R (6) together form a group -CR (15) = CR (16) -CR (17) = CR (18) -;
R (15), R (16), R (17) and R (18) independently of one another are hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4 or 5 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, -CN, -CF ₃ , -C ₂ F ₅ , -C ₃ F ₇ , -N ₃ , -NO ₂ , -ZC _s H _2s -R (22) , Thienyl or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino , Sulfamoyl, methylsulfonyl and methylsulfonylamino;
Z -O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -SO ₂ -O-, -SO ₂ NR (10c), - NR (10c) - or -CONR (10c) -;
R (10c) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
s zero, 1, 2, 3, 4, 5 or 6;
R (22) hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, -NR (19) R (20), -COOR (21 ), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl or phenyl, where pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (19) and R (20) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
or
R (19) and R (20) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
R (21) is hydrogen or alkyl having 1, 2 or 3 carbon atoms; however, Y cannot simultaneously be CR (11) and X can equal O; as well as their physiologically acceptable salts.

Compounds of the formula I are very particularly preferred, in which:
X -O-, -S-, -SO-, -SO ₂ -, -NR (7) - or -CR (8a) R (8b) -;
R (7) is hydrogen or - (C _a H _2a ) -R (9), where a CH ₂ group from the group C _a H _2a can be replaced by -O-, -CO-, -CO-O-, - SO ₂ - or -NR (10) -;
R (10) is hydrogen or alkyl having 1 or 2 carbon atoms;
a zero, 1, 2, 3 or 4;
R (9) hydrogen, CF ₃ cycloalkyl with 5 or 6 carbon atoms, pyridyl, thienyl, imidazolyl or phenyl, where pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F , Cl, Br, I, CF ₃ NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (8a) is hydrogen, CF ₃ , alkyl having 1, 2, 3 or 4 carbon atoms or phenyl which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF. ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (8b) is hydrogen, alkyl having 1, 2 or 3 carbon atoms;
YN or CR (11);
R (11) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (1) and R (2) independently of one another are CF ₃ , alkyl having 1, 2, 3 or 4 carbon atoms or phenyl which is unsubstituted or substituted by 1 or 2 substituents, selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
or
R (1) and R (2) together form an alkylene chain with 2, 3, 4, 5 or 6 carbon atoms;
R (3) R (12) -C _n H _2n -NR (13) - or R (12) -C _n H _2n -;
R (12) methyl or CF ₃ ;
n zero, 1, 2, 3, 4 or 5;
R (13) is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
or
R (3) together with R (4) is an alkylene chain with 3 or 4 carbon atoms, whereby a CH ₂ group of the alkylene chain can be replaced by -CO-;
R (4) R (14) -C _r H _2r , where a CH ₂ group from the group C _r H _2r can be replaced by -O-, -CO-, -CO-O, -O-CO-, - S-, -SO-, -SO ₂ -, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1 or 2 carbon atoms;
R (14) methyl, CF ₃ , cycloalkyl with 3, 4, 5, 6 or 7 carbon atoms, -OH, -COOH, -NR (23) R (24), 1-piperidyl, 1-pyrrolidinyl, 4- Morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl, where pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (23) and R (24) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms;
or
R (23) and R (24) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
r zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R (5) and R (6) together form a group -CR (15) = CR (16) -CR (17) = CR (18) -;
R (15), R (16), R (17) and R (18) independently of one another hydrogen, F, Cl, alkyl with 1, 2 or 3 carbon atoms, -CN, -CF ₃ , -NO ₂ , - ZC _s H _2s -R (22), thienyl or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
Z -O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, SO ₂ -, -SO ₂ -O-, -SO ₂ NR (10c), -NR (10c) - or -CONR (10c) -;
R (10c) is hydrogen or alkyl having 1 or 2 carbon atoms;
s zero, 1, 2, 3, or 4;
R (22) is hydrogen, CF ₃ , cycloalkyl having 5 or 6 carbon atoms, -NR (19) R (20), -COOR (21), pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl or phenyl, where pyridyl, thienyl , Imidazolyl, quinolyl, isoquinolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy , Dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (19) and R (20) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms;
or
R (19) and R (20) together form a chain of 4 or 5 methylene groups, of which one CH ₂ group can be replaced by -O-, -S-, -NH- or -N (CH ₃ ) -;
R (21) is hydrogen or alkyl having 1 or 2 carbon atoms; however, Y cannot simultaneously be CR (11) and X can equal O; as well as their physiologically acceptable salts.

Compounds of the formula I are particularly preferred, in which:
X -CR (8a) R (8b) -;
R (8a) hydrogen;
R (8b) hydrogen;
Y CR (11);
R (11) hydrogen;
R (1) and R (2) independently of one another alkyl having 1, 2 or 3 carbon atoms;
or
R (1) and R (2) together form an alkylene chain with 4 or 5 carbon atoms;
R (3) R (12) -C _n H _2n -;
R (12) methyl;
n zero, 1 or 2;
R (4) R (14) -C _r H _2r , where a CH ₂ group from the group C _r H _2r can be replaced by -O-, -CO-, -CO-O-, -O-CO-, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1 or 2 carbon atoms;
R (14) methyl, CF ₃ , cycloalkyl having 3, 4, 5 or 6 carbon atoms, -NR (23) R (24), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, pyridyl, thienyl, imidazolyl or Phenyl, wherein pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
R (23) and R (24) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms;
r zero, 1, 2, 3, 4, 5, 6, 7 or 8;
R (5) and R (6) together form a group -CR (15) = CR (16) -CR (17) = CR (18) -;
R (15), R (16), R (17) and R (18) independently of one another are hydrogen, F, Cl, alkyl having 1 or 2 carbon atoms, -CN, -CF ₃ , -NO ₂ , -ZC _s H _2s -R (22) or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
Z -O-, -CO-, -CO-O-, -O-CO-, -SO ₂ -, -SO ₂ -O-, -SO ₂ NR (10c), -NR (10c) - or -CONR (10c) -;
R (10c) is hydrogen or methyl;
s zero, 1, 2, 3, or 4;
R (22) is hydrogen, CF ₃ , cycloalkyl having 5 or 6 carbon atoms, -NR (19) R (20) or phenyl which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl , CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
R (19) and R (20) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms;
as well as their physiologically acceptable salts.

Compounds of the formula I are also particularly preferred, in which:
X -O-, -NR (7) - or -CR (8a) R (8b) -;
R (7) is hydrogen or - (C _a H _2a ) -R (9);
a zero, 1, 2, 3 or 4;
R (9) is hydrogen or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , methyl, methoxy, sulfamoyl and methylsulfonyl;
R (8a) hydrogen;
R (8b) hydrogen;
YN;
R (1) and R (2) independently of one another alkyl having 1, 2 or 3 carbon atoms;
or
R (1) and R (2) together form an alkylene chain with 4 or 5 carbon atoms;
R (3) R (12) -C _n H _2n -;
R (12) methyl;
n zero, 1 or 2;
R (4) R (14) -C _r H _2r ,
wherein a CH ₂ group of the group C _r H _2r can be replaced by -O-, -CO-, -CO-O-, -O-CO-, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1 or 2 carbon atoms;
R (14) methyl, CF ₃ , cycloalkyl having 3, 4, 5 or 6 carbon atoms, -NR (23) R (24), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, pyridyl, thienyl, imidazolyl or Phenyl, wherein pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
R (23) and R (24) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms;
r zero, 1, 2, 3, 4, 5, 6, 7 or 8;
R (5) and R (6) together form a group -CR (15) = CR (16) -CR (17) = CR (18) -;
R (15), R (16), R (17) and R (18) independently of one another hydrogen, F, Cl, alkyl with 1 or 2 carbon atoms, -CN, -CF ₃ -NO ₂ , ZC _s H _2s -R (22) or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
Z -O-, -CO-, -CO-O-, -O-CO-, -SO ₂ -, -SO ₂ -O-, -SO ₂ NR (10c), -NR (10c) - or -CONR (10c) -;
R (10c) is hydrogen or methyl;
s zero, 1, 2, 3, or 4;
R (22) is hydrogen, CF ₃ , cycloalkyl having 5 or 6 carbon atoms, -NR (19) R (20) or phenyl which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl , CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
R (19) and R (20) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms;
as well as their physiologically acceptable salts.

Compounds of the formula I in which:
X -NR (7) -, -S-, -SO- or -SO ₂ -;
R (7) is hydrogen or - (C _a H _2a ) -R (9);
a zero, 1, 2, 3 or 4;
R (9) is hydrogen or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , methyl, methoxy, sulfamoyl and methylsulfonyl;
Y CR (11);
R (11) hydrogen;
R (1) and R (2) independently of one another alkyl having 1, 2 or 3 carbon atoms;
or
R (1) and R (2) together form an alkylene chain with 4 or 5 carbon atoms;
R (3) R (12) -C _n H _2n -;
R (12) methyl;
n zero, 1 or 2;
R (4) R (14) -C _r H _2r ,
wherein a CH ₂ group of the group C _r H _2r can be replaced by -O-, -CO-, -CO-O-, -O-CO-, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1 or 2 carbon atoms;
R (14) methyl, CF ₃ , cycloalkyl having 3, 4, 5 or 6 carbon atoms, -NR (23) R (24), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, pyridyl, thienyl, imidazolyl or Phenyl, wherein pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
R (23) and R (24) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms;
r zero, 1, 2, 3, 4, 5, 6, 7 or 8;
R (5) and R (6) together form a group -CR (15) = CR (16) -CR (17) = CR (18) -;
R (15), R (16), R (17) and R (18) independently of one another are hydrogen, F, Cl, alkyl having 1 or 2 carbon atoms, -CN, -CF ₃ , -NO ₂ , -ZC _s H _2s -R (22) or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
Z -O-, -CO-, -CO-O-, -O-CO-, -SO ₂ -, -SO ₂ -O-, -SO ₂ NR (10c), -NR (10c) - or -CONR (10c) -;
R (10c) is hydrogen or methyl;
s zero, 1, 2, 3, or 4;
R (22) is hydrogen, CF ₃ , cycloalkyl having 5 or 6 carbon atoms, -NR (19) R (20) or phenyl which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl , CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
R (19) and R (20) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms;
as well as their physiologically acceptable salts.

Alkyl residues and alkylene residues can be straight-chain or branched. This also applies to the alkylene radicals of the formulas C _a H ₂₃ , C _n H _2n and C _s H _2s . Alkyl residues and alkylene residues can also be straight-chain or branched if they are substituted or contained in other residues, e.g. B. in an alkoxy group or in an alkyl mercapto group or in a fluorinated alkyl group. Examples of alkyl radicals are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3,3-dimethylbutyl, heptyl, octyl, Nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl. The divalent residues derived from these residues, e.g. B. methylene, 1,1-ethylene, 1,2-ethylene, 1,1-propylene, 1,2-propylene, 2,2-propylene, 1,3-propylene, 1,4-butylene, 1,5- Pentylene, 2,2-dimethyl-1,3-propylene, 1,6-hexylene, etc. are examples of alkylene radicals. Examples of acyl radicals are formyl, acetyl, propionyl, n-butyryl or isobutyryl.

Monosubstituted phenyl radicals can be in the 2-, 3- or 4-position be substituted, disubstituted in the 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-position. The same applies to thienyl, pyridyl and imidazolyl radicals. Thienyl residues can be in the 2- or the 3-position, pyridyl radicals in the 2-, 3- or 4-position, imidazolyl radicals be bound in the 1-, 2-, 4- or 5-position. When a residue is disubstituted the substituents can be the same or different.

If the radicals R (1) and R (2) together form an alkylene chain, these radicals form a ring with the carbon atom carrying them, which has a carbon atom in common with the 6-ring in the formula I, so there is a spiro compound . If R (1) and one of the radicals R (7), R (8a) or R (8b) together represent a bond, there is a double bond between the groups X and CR (1) R (2), so that the 6th -Ring is aromatic. If R (12) and R (13) together represent a bond, the group R (12) -C _n H _2n -NR (13) - preferably represents a nitrogen heterocycle bonded via a nitrogen atom. If R (12) and R (13) together represent a bond and the group R (12) -C _n H _2n -NR (13) - stands for a nitrogen heterocycle bonded via a nitrogen atom, this nitrogen heterocycle is preferably a 4-ring or a larger ring than a 4-ring, e.g. B. a 5-ring, 6-ring or 7-ring. The bivalent radicals, which stand for R (5) and R (6), together with the corresponding carbon atoms of the 6-ring in formula I form a fused aromatic ring, e.g. B. a benzene, pyridine, pyrimidine, pyrazine, pyridazine or thiophene ring. For linking the common group for R (5) and R (6) both directions of linking are possible, so that, for. B. in the event that R (5) and R (6) together mean -S-CR (15) = CR (16) -, a thiophene ring is fused, in which the sulfur at both the position of R (6) as can also be at the position of R (5).

Contain the compounds of formula I one or more acidic or basic Groups or one or more basic heterocycles, so are those corresponding physiologically or toxicologically tolerable salts subject of the invention, in particular the pharmaceutically usable salts. So can the compounds of formula I, the acidic groups, e.g. B. one or more COOH Groups, for example as alkali metal salts, preferably sodium or Potassium salts, or as alkaline earth metal salts, e.g. B. calcium or magnesium salts, or as ammonium salts, e.g. B. as salts with ammonia or organic amines or amino acids can be used. Compounds of formula I, the one or several basic, d. H. protonatable, wearing groups or one or more Containing basic heterocyclic rings can also be in the form of their physiological compatible acid addition salts with inorganic or organic acids are used, for example as hydrochlorides, phosphates, sulfates, Methanesulfonates, acetates, lactates, maleinates, fumarates, malates, gluconates etc. The compounds of the formula I contain acidic and basic groups at the same time in the molecule, besides the salt forms described also include inner salts, so-called betaines to the invention. Salts can be obtained from the compounds of the Formula I can be obtained by customary processes, for example by Combination with an acid or base in a solvent or dispersant or also by anion exchange from other salts.

With appropriate substitution, the compounds of formula I can be substituted into stereoisomeric forms are present. Contain the compounds of formula I or  several centers of asymmetry, so these can independently the S configuration or the R configuration. All belong to the invention possible stereoisomers, e.g. B. enantiomers or diastereomers, and mixtures of two or more stereoisomeric forms, e.g. B. enantiomers and / or Diastereomers, in any ratio. Enantiomers e.g. B. are in enantiomerically pure form, both as left-handed and right-handed antipodes, and also in the form of mixtures of the two enantiomers in different Ratios or in the form of racemates are the subject of the invention. At Both the cis form and the trans form are present in a cis / trans isomerism and mixtures of these forms are the subject of the invention. The production of if desired, individual stereoisomers can be separated by Mixture by conventional methods or z. B. by stereoselective synthesis respectively. In the presence of mobile hydrogen atoms, the present includes Invention also all tautomeric forms of the compounds of formula I.

The compounds of formula I can be prepared by different chemical processes, which are also the subject of the present invention. For example, a compound of formula I is obtained by

• a) a compound of formula II,
  in which R (1), R (2), R (5), R (6), X and Y have the meanings given above and L is a nucleofugic leaving group, in particular F, Cl, Br, I, methanesulfonyloxy or p-toluenesulfonyloxy, means reacted in a manner known per se with a sulfonamide or its salt of the formula III,
  wherein R (3) and R (4) have the meanings given above and M represents hydrogen or preferably a metal equivalent, particularly preferably lithium, sodium or potassium;
  or that one
• b) a compound of formula IV
  wherein R (1), R (2), R (4), R (5), R (6), X and Y have the meanings given above, with a sulfonic acid derivative of the formula V.
  implements, wherein R (3) has the meanings given above and W is a nucleofugic leaving group, such as. B. fluorine, bromine, 1-imidazolyl, but especially chlorine;
  or that one
• c) a compound of formula VI
  wherein R (1), R (2), R (3), R (5), R (6), X, Y and M have the meanings given above, in a manner known per se in the sense of an alkylation reaction with an alkylating agent Implement Formula VII,
  R (4) -L VII
  wherein R (4) has the meanings given above with the exception of hydrogen and L has the meanings given above;
  or that one
• d) in a compound of formula I.
  wherein R (1) to R (6), X and Y have the meanings given, in at least one of the positions R (15), R (16), R (17), R (18) of the ring system R (5) - R (6) carries out an electrophilic substitution reaction if this position means hydrogen.

Procedure a) corresponds to the nucleophilic substitution of a leaving group in a reactive bicyclic compound of the formula II by a sulfonamide or one of its salts of the formula III. Because of the higher nucleophilicity and higher reactivity of a sulfonamide present in the salt form, when using a free sulfonamide (formula III, M = H) it is preferred to first generate a sulfonamide salt (formula III, M = metal cation) from this by the action of a base. If a free sulfonamide (formula III, M = H) is used, the sulfonamide can be deprotonated to the salt in situ. Bases are preferably used which are themselves not or only slightly alkylated, such as. B. sodium carbonate, potassium carbonate, sterically hindered amines, e.g. B. dicyclohexylamine, N, N-dicyclohexyl-ethylamine, or other strong nitrogen bases with low nucleophilicity, for example DBU (diazabicycloundecene), N, N ', N''' - triisopropylguanidine etc. However, other commonly used bases for the reaction can also be used are used, such as potassium tert-butoxide, sodium methylate, alkali metal bicarbonates, alkali metal hydroxides such as LiOH, NaOH or KOH, or alkaline earth metal hydroxides such as C _a (OH) ₂ .

The process is preferably carried out in a solvent, particularly preferably in polar organic solvents such as B. Dimethylformamide (DMF), dimethylacetamide (DMA), dimethyl sulfoxide (DMSO), tetramethyl urea (TMU), Hexamethylphosphoric triamide (HMPT), tetrahydrofuran (THF), dimethoxyethane (DME) or other ethers, or for example in a hydrocarbon such as toluene or in a halogenated hydrocarbon such as chloroform or Methylene chloride etc. It can also be used in polar protic solvents to be worked such. B. in water, methanol, ethanol, isopropanol, Ethylene glycol or its oligomers and their corresponding semi-ethers or also their ethers. The reaction can also take place in mixtures of these solvents be performed. However, the reaction can also be completely without Solvents are carried out. The reaction is preferred in one Temperature range from -10 to + 140 ° C, particularly preferably in the range from 20 to 100 ° C carried out. Procedure a) can also be carried out in a favorable manner Phase transfer catalysis conditions are carried out.

The compounds of the formula II are obtained by methods known from the literature, for example from the corresponding 4-oxo compounds of the formula X,

wherein R (1), R (2), R (5), R (6), X and Y have the meanings given above, or their tautomeric form (formula II, L = -OH) by the action of an inorganic acid halide, such as POCl ₃ , PCl ₃ , PCl ₅ , SOCl ₂ , SOBr ₂ , COCl ₂ or mixtures thereof. The use of catalytically active additives, such as DMF when using SOCl ₂ or N, N-dimethylaniline when using POCl _{3, has} proven successful in many cases. It is advantageous to work in a solvent which is sufficiently inert to these halogenating, high-energy reagents, such as, for example, in toluene or a halogenated hydrocarbon such as, for. B. in chloroform, methylene chloride or in one of the liquid halogenating agents themselves, preferably in POCl _3rd

Procedure b) describes the known and frequently used reaction of a reactive Sulfonyl compound of the formula V, in particular a chlorosulfonyl compound (W = Cl), with an amino derivative of the formula IV to give the corresponding sulfonamide derivative   23289 00070 552 001000280000000200012000285912317800040 0002019730326 00004 23170 of formula I. The reaction can in principle be carried out without a solvent, however, in most cases, such reactions are carried out using a Solvent carried out.

The reaction is preferably carried out using a polar one Solvent preferably in the presence of a base, which itself is advantageous as Solvent can be used, e.g. B. when using triethylamine, especially of pyridine and its homologues. Also used Solvents are, for example, water, aliphatic alcohols, e.g. B. methanol, Ethanol, isopropanol, sec. Butanol, ethylene glycol and its monomers and oligomeric monoalkyl and dialkyl ethers, tetrahydrofuran, dioxane, dialkylated amides like DMF, DMA, as well as TMU and HMPT. You work at one temperature from 0 to 160 ° C, preferably from 20 to 100 ° C.

The amino derivatives of the formula IV are obtained in a manner known per se, preferably by reacting the reactive compounds of the formula II with R (1), R (2), R (5), R (6), X, Y and L in of the meaning given, either with ammonia or an amine of the formula XI

R (4) -NH ₂ XI

with R (4) in the meaning given.

Procedure c) represents the known alkylation reaction of a sulfonamide or one of its salts VI with an alkylating agent of the formula VII Reaction analogy with procedure a) apply to procedure c) which already reaction conditions described in detail under procedure a).

The preparation of the sulfonamide derivatives VI and their precursors have already been described in procedure b). The preparation of the alkylating agents VII follows Analogous regulations of the literature or as described under procedure a), preferably from the corresponding hydroxy compounds (formula VII with L equal to -OH).

Procedure d) describes the further chemical conversion of the invention Compounds of formula I in other compounds of formula I by electrophilic Substitution reactions in one or more of those with R (15) to R (18) designated positions of the ring system R (5) -R (6), each hydrogen mean.

Preferred substitution reactions are

• 1. the aromatic nitration for the introduction of one or more nitro groups, the in subsequent reactions, some or all of them are reduced to amino groups can. The amino groups can in turn in subsequent reactions other groups are converted, for example in a Sandmeyer reaction, e.g. B. for the introduction of cyano groups;
• 2. the aromatic halogenation especially for the introduction of chlorine, bromine or iodine;  
• 3. the chlorosulfonation, e.g. B. by the action of chlorosulfonic acid Introduction of a chlorosulfonyl group that is used in subsequent reactions in others Groups can be converted, e.g. B. in a sulfonamide group;
• 4. the Friedel-Crafts acylation reaction to introduce an acyl residue or one Sulfonylrestes by the action of the corresponding acid chlorides in the presence a Lewis acid as a Friedel-Crafts catalyst, preferably in the presence of anhydrous aluminum chloride.

All procedures may be appropriate, some To temporarily protect the reaction steps of functional groups in the molecule. Such Protection group techniques are familiar to those skilled in the art. Choosing one Protection group for eligible groups and the procedures for their Introduction and spin-off are described in the literature and can if necessary, be adapted to the individual case without difficulty.

It has already been said that the compounds of the formula I surprisingly have a strong and specific blocking (closing) action on a K⁺ channel which is opened by cyclic adenosine monophosphate (cAMP) and is fundamentally different from the well-known K⁺ (ATP) channel differs, and that this K⁺ (cAMP) channel identified on colon tissue is very similar, perhaps even identical, to the I _Ks channel identified on the heart muscle. A strong blocking effect on the I _Ks channel in guinea pig cardiomyocytes as well as on the I _sK channel expressed in Xenopus oocytes was _{demonstrated for the compounds according to the invention} . As a result of this blocking of the K⁺ (cAMP) channel or the I _Ks channel, the compounds according to the invention develop pharmacological effects of high therapeutic utility in the living organism and are outstandingly suitable as active pharmaceutical ingredients for the therapy and prophylaxis of various clinical pictures.

Thus, the compounds of formula I according to the invention are new Active ingredient class of potent inhibitors of stimulated gastric acid secretion. The Compounds of the formula I are therefore valuable active pharmaceutical ingredients for therapy and prophylaxis of gastric and intestinal ulcers, for example the duodenum. They are also suitable due to their strong gastric secretion-inhibiting effect as excellent therapeutic agents Therapy and prophylaxis of reflux esophagitis.

The compounds of the formula I according to the invention are also notable for have an antidiarrheal effect and are therefore used as active pharmaceutical ingredients Therapy and prophylaxis of diarrheal diseases suitable.

The compounds of formula I according to the invention are also suitable as Active pharmaceutical ingredients for the therapy and prophylaxis of cardiovascular diseases. In particular, they can be used for the therapy and prophylaxis of all types of arrhythmias used, including atrial, ventricular and supraventricular Arrhythmias, especially cardiac arrhythmias caused by action potential Extension can be fixed. They can be used specifically for Therapy and prophylaxis of atrial fibrillation (atrial fibrillation) and atrial Flutter (atrial flutter) and for therapy and prophylaxis of reentry Arrhythmias and to prevent sudden cardiac death as a result of Ventricular fibrillation.

Although numerous antiarrhythmic substances are already on the market, there is no compound that is really satisfactory in terms of effectiveness, range of use and side effect profile, so that there is still a need to develop improved antiarrhythmics. The effect of numerous known antiarrhythmics of the so-called class III is based on an increase in the myocardial refractory period by extending the duration of the action potential. This is essentially determined by the extent of repolarizing K⁺ currents that flow out of the cell via various K⁺ channels. Of particular importance is the so-called "delayed rectifier" I _K , of which two subtypes exist, a quickly activated I _Kr and a slowly activated I _Ks . Most known class III antiarrhythmics block predominantly or exclusively I _Kr (e.g. dofetilide, d-sotalol). However, it has been shown that these compounds have an increased proarrhythmic risk at low or normal heart rates, arrhythmias which are referred to as torsades de pointes "being observed in particular (DM Roden;" Current Status of Class III Antiarrhythmic Drug Therapy "; (J. Cardiol. 72 (1993), 44B-49B), however, with higher heart rates or stimulation of the β-receptors, the action potential prolonging effect of the I _Kr blockers is significantly reduced, which is attributed to the fact that under these conditions The I _{Ks contributes} more to repolarization For these reasons, the substances according to the invention which act as I _Ks blockers have significant advantages over the known I _Kr blockers. In the meantime it has also been described that a correlation between I _Ks channel-inhibitory Effect and the prevention of life-threatening cardiac arrhythmias, such as, for example, by β-adrenergic H. hyper stimulation are triggered (e.g. BTJ Colatsky, CH Follmer and CF Starmer; "Channel Specificity in Antiarrhythmic Drug Action; Mechanism of potassium channel block and its role in suppressing and aggravating cardiac arrhythmias"; Circulation 82: 2235-2242 (1990); AE Busch, K. Malloy, WJ Groh, MD Varnum, JP Adelman and J. Maylie; "The novel class III antiarrhythmics NE-10064 and NE-10133 inhibit I _sK channels in xenopus oocytes and I _Ks in guinea pig cardiac myocytes"; Biochem. Biophys. Res. Commun. 202: 265-270 (1994).

In addition, the connections contribute to a significant improvement in Heart failure, especially congestive heart failure (congestive heart Failure), advantageously in combination with contraction-promoting (positive inotropic) active ingredients, e.g. B. Phosphodiesterase inhibitors.

Despite the therapeutically useful advantages that can be achieved by blocking the _IC , very few compounds have been described so far that inhibit this subtype of the "delayed rectifier". The developing substance azimilide also has a blocking effect on the I _Ks , but mainly blocks the I _Kr (selectivity 1:10). In WO-A-95/14470 the use of benzodiazepines as selective blockers of the claimed I _Ks. Further I _Ks blockers are described in FEBS Letters 396 (1996), 271-275: "Specific blockade of slowly activating I _sK channels by chromanols..." and Pflügers Arch.- Eur. J. Physiol. 429 (1995), 517-530: "A new class of inhibitors of cAMP-mediated CI secretion in rabbit colon, acting by the reduction of cAMP-activated K⁺ conductance". However, the potency of the 3-hydroxychromanols mentioned there is lower than that of the compounds of the formula I according to the invention. In addition, the compounds of the formula I according to the invention have the advantage over the 3-hydroxychromanols that the sulfonamide function is not on a chiral carbon atom, so that, in contrast to the known compounds, no complex enantioselective synthesis or resolution is required to produce a uniform active ingredient.

The compounds of formula I according to the invention and their physiological compatible salts can thus on the animal, preferably on the mammal, and especially in humans as a medicine on its own, in mixtures used with each other or in the form of pharmaceutical preparations become. The present invention also relates to the compounds of Formula I and its physiologically tolerable salts for use as medicaments, their use in the therapy and prophylaxis of the diseases mentioned and their use in the manufacture of medicines therefor and from Drugs with a K Kanal channel blocking effect. Furthermore, the subject of present invention pharmaceutical preparations as an active ingredient an effective dose of at least one compound of formula I and / or one physiologically acceptable salt thereof in addition to usual, pharmaceutical contain impeccable carriers and auxiliary substances. The pharmaceutical Preparations normally contain 0.1 to 90 percent by weight of the Compounds of formula I and / or their physiologically acceptable salts. The The pharmaceutical preparations can be prepared in a manner known per se respectively. For this purpose, the compounds of formula I and / or their physiological  compatible salts together with one or more solid or liquid pharmaceutical excipients and / or excipients and, if desired, in Combination with other active pharmaceutical ingredients in a suitable Dosage form or dosage form brought, which then as a drug in the Human medicine or veterinary medicine can be used.

Medicaments, the compounds of formula I according to the invention and / or their contain physiologically acceptable salts, can be administered orally, parenterally, e.g. B administered intravenously, rectally, by inhalation or topically, the preferred application in individual cases, e.g. B. the respective appearance of the treating disease, is dependent.

Which excipients are suitable for the desired pharmaceutical formulation is familiar to the specialist on the basis of his specialist knowledge. In addition to solvents, Gelling agents, suppository bases, tablet excipients and others Active substance carriers can, for example, antioxidants, dispersants, Emulsifiers, defoamers, flavoring agents, preservatives, Solubilizers, means of achieving a depot effect, buffer substances or Dyes are used.

The compounds of formula I can also be combined with other active pharmaceutical ingredients in order to achieve an advantageous therapeutic effect. In the treatment of cardiovascular diseases, advantageous combinations with cardiovascular active substances are possible. Such combination partners which are advantageous for cardiovascular diseases include, for example, other antiarrhythmics, such as class I, class II or class III antiarrhythmics, such as, for example, I _Kr channel blockers, e.g. B. dofetilide, or further blood pressure lowering substances such as ACE inhibitors (for example enalapril, captopril, ramipril), angiotensin antagonists, K, channel activators, and alpha and beta receptor blockers, but also sympathomimetic and adrenergic compounds, and Na⁺ / H⁺-Exchange inhibitors, calcium channel antagonists, phosphodiesterase inhibitors and other positive inotropic substances, such as. B. digitalis glycosides, or diuretics. Combinations with antibiotic substances and with antiulcer agents are also advantageous, for example with H ₂ antagonists (for example ranitidine, cimetidine, famotidine, etc.), in particular when used for the treatment of gastrointestinal disorders.

For an oral form of use, the active compounds with the for it suitable additives, such as carrier stabilizers or inert Diluent, mixed and by the usual methods in the appropriate Dosage forms brought, such as tablets, coated tablets, capsules, aqueous, alcoholic or oily solutions. As inert carriers such. B. gum arabic, Magnesia, magnesium carbonate, potassium phosphate, milk sugar, glucose or starch, especially corn starch can be used. The preparation can be both done as dry as well as wet granules. As an oily carrier or as Solvents are, for example, vegetable or animal oils, such as Sunflower oil or cod liver oil. As a solvent for aqueous or alcoholic Solutions come z. B. water, ethanol or sugar solutions or mixtures of which, into consideration. Other auxiliaries, also for other forms of application, are e.g. B. Polyethylene glycols and polypropylene glycols.

For subcutaneous or intravenous administration, the active compounds, if desired with the usual substances such as solubilizers, Emulsifiers or other auxiliaries, in solution, suspension or emulsion brought. The compounds of formula I and their physiologically tolerable salts can also be lyophilized and the resulting lyophilizates z. B. for Manufacture of injection or infusion preparations can be used. As Solvents come e.g. B. water, physiological saline or alcohols, e.g. As ethanol, propanol, glycerol, into consideration, as well as sugar solutions such as Glucose or mannitol solutions, or mixtures of the different mentioned solvents.

As a pharmaceutical formulation for administration in the form of aerosols or sprays are suitable e.g. B. solutions, suspensions or emulsions  Active ingredients of formula I or their physiologically tolerable salts in one pharmaceutically acceptable solvents, such as in particular ethanol or Water, or a mixture of such solvents. The wording can follow Also needs other pharmaceutical auxiliaries such as surfactants, emulsifiers and stabilizers and a propellant gas. Such a preparation contains the active ingredient usually in a concentration of about 0.1 to 10, in particular from about 0.3 to 3 percent by weight.

The dosage of the active ingredient to be administered of the formula I or physiologically acceptable salts depend on the individual case and are as usual adapt to the circumstances of the individual case for an optimal effect. So hangs they naturally depend on the frequency of administration and on the potency and Duration of action of the compounds used for therapy or prophylaxis, but also on the type and severity of the disease to be treated and on Gender, age, weight and individual responsiveness of the person to be treated Humans or animals and whether acute or prophylactic therapy is used. The daily dose of a compound of the formula I is usually: Administration to a patient weighing approximately 75 kg 0.001 mg / kg Body weight up to 100 mg / kg body weight, preferably 0.01 mg / kg body weight up to 20 mg / kg body weight. The dose can be administered in the form of a single dose be or in several, e.g. B. two, three or four single doses. Especially in the treatment of acute cases of irregular heartbeat, For example, in an intensive care unit, parenteral administration can also be used by injection or infusion, e.g. B. by intravenous continuous infusion, advantageous be.

The compounds of formula I and their physiologically tolerable salts selectively inhibit K⁺ (cAMP) channels or I _Ks channels. Due to this property, they can be used as active pharmaceutical ingredients in human medicine and veterinary medicine as well as a scientific tool or as an aid for biochemical examinations in which an influence on potassium channels is intended, as well as for diagnostic purposes, e.g. B. in the in vitro diagnostics of cell or tissue samples. Furthermore, as already mentioned above, they can be used as intermediates for the production of further active pharmaceutical ingredients.

Experimental part List of abbreviations

DMA N, N-dimethylacetamide
DMSO dimethyl sulfoxide
EE ethyl acetate
Mp melting point
RT room temperature
THF tetrahydrofuran

example 1 4- (N-ethylsulfonyl-N-methyl) amino-2-phenylquinazoline

A solution of 0.67 g (5.5 mmol) of ethylsulfonic acid-N-methylamide in 10 was added to a slurry of 0.165 g (5 mmol) of sodium hydride (as an 80% dispersion in oil) in 10 ml of anhydrous DMA under an argon protective gas atmosphere ml of anhydrous DMA added dropwise. The mixture was allowed to stir at room temperature for 4 hours and then a suspension of 1.2 g (5 mmol) of 4-chloro-2-phenylquinazoline in 10 ml of anhydrous DMA was added to this solution in portions, and the reaction mixture was allowed to stir at room temperature for 3 days. The solvent was distilled off under reduced pressure, the residue was stirred with water and the microcrystalline substance was filtered off. After washing with water and drying in an air stream, the product was recrystallized from diisopropyl ether.
Colorless crystals, mp 128-130 ° C.

Example 2 3-chloro-1- (N-ethylsulfonyl-N-methyl) amino-isoquinoline

To a slurry of 0.22 g (7.6 mmol) sodium hydride (as 80% Dispersion in oil) in 5 ml of anhydrous DMA was Protective gas atmosphere a solution of 0.62 g (5 mmol) of ethylsulfonic acid-N- methylamide added dropwise in 10 ml of anhydrous DMA. It was left for 1 hour Stir room temperature, then added 1.09 g (5.5 mmol) of 1.3- Dichloroisoquinoline, stirred at RT overnight and then at 80 ° C. for a further 8 h. The Solvent was distilled off under reduced pressure, the residue with The water is stirred and the solid which has precipitated is filtered off with suction. After cleaning the Crude product by chromatography on silica gel were 0.34 g of 3-chloro-1- (N- obtained ethylsulfonyl-N-methyl) amino-isoquinoline; F.p. 116-118 ° C.

Example 3 7-chloro-4- (N-ethylsulfonyl-N-methyl) amino-quinoline

To a slurry of 0.22 g (7.6 mmol) sodium hydride (as 80% Dispersion in oil) in 10 ml of anhydrous DMA was Protective gas atmosphere a solution of 0.62 g (5 mmol) of ethylsulfonic acid-N- methylamide added dropwise in 10 ml of anhydrous DMA. It was left for 1 hour Stir room temperature, then added 1.09 g (5.5 mmol) of 4,7-dichloroquinoline and heated to 120 ° C for 6 h. The solvent was removed under reduced pressure  distilled off, the residue stirred with water and the precipitated solid aspirated. After purification of the crude product by chromatography on silica gel 0.08 g of 7-chloro-4- (N-ethylsulfonyl-N-methyl) amino-quinoline was obtained; F.p. 273 ° C.

Example 4 4- (N-ethylsulfonyl-N-methyl) amino-2,2-dimethyl-2H-benzo [e] [1,3] oxazine a) 4-Chloro-2,2-dimethyl-2H-benzo [e] [1,3] oxazine

5.3 g (30.0 mmol) 2,2-dimethyl-2,3-dihydro-benzo [e] [1,3] oxazin-4-one, 5.8 ml (45.0 mmol) of N, N-dimethylaniline and 2.2 ml (24 mmol) of phosphorus oxytrichloride were dissolved in 100 ml of absolute toluene dissolved and refluxed for 3 hours on a water separator heated. The toluene phase was then decanted off with 20% cold NaOH Solution and 2N hydrochloric acid washed. After drying was on Oil pump vacuum removed the solvent and 5.3 g of product was obtained as an oil.

b) 4- (N-ethylsulfonyl-N-methyl) amino-2,2-dimethyl-2H-benzo [e] [1,3] oxazine

To a suspension of 150 mg (3.6 mmol) sodium hydride (60%) in 7 ml Dimethylacetamide was 405 mg (3.3 mmol) of ethylsulfonic acid methylamide admitted. After 30 min, 600 mg (3 mmol) of 4-chloro-2,2-dimethyl-2H- benzo [e] [1,3] oxazin in 6 ml DMA and stirred for 24 hours at 80 ° C. After Dilution with ethyl acetate was filtered off from the solid and the solvents in  High vacuum removed. After chromatography with heptane / ethyl acetate 4/1, 35 mg of the product obtained as an oil.

Claims (23)

1. Compounds of the formula I
in which mean:
X -O-, -S-, -SO-, -SO ₂ -, -NR (7) -, -CR (8a) R (8b) - or -CO-;
R (7) is hydrogen or (C _a H _2a ) -R (9), where a CH ₂ group from the group C _a H _2a can be replaced by -O-, -CH = CH-, -C∼C-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, NR (10) - or -CONR (10) -;
R (10) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
a zero, 1, 2, 3, 4, 5, 6, 7 or 8;
R (9) hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, dimethylamino, diethylamino, 1-piperidyl, 1-pyrrolidinyl, 4- Morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl, where pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
or
R (7) together with R (1) is a bond;
R (8a) is hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or phenyl which is unsubstituted or substituted by 1 or 2 substituents from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (8b) is hydrogen, alkyl having 1, 2 or 3 carbon atoms, -OR (10), -COOR (10), CO-R (10);
R (10) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
or one of the radicals R (8a) or R (8b) together with R (1) forms a bond if Y is N;
YN or CR (11);
R (11) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (1) and R (2) independently of one another are hydrogen CF ₃ , C ₂ F ₅ , C ₃ F ₇ , F, Cl, methoxy, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or phenyl, which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino ;
or
R (1) and R (2) together form an alkylene chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms;
R (3) R (12) -C _n H _2n -NR (13) - or R (12) -C _n H _2n -, whereby a CH ₂ group in the groups C _n H _2n can be replaced by -O -, -CO-, -S-, -SO-, -SO ₂ - or -NR (10a) -;
R (10a) is hydrogen, methyl or ethyl;
R (12) is hydrogen, methyl, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, CF ₃ , C ₂ F ₅ or C ₃ F ₇ ;
n zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R (13) is hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms;
or
R (12) and R (13) together form a bond if n is not less than 3;
or
R (3) together with R (4) is an alkylene chain with 3, 4, 5, 6, 7 or 8 carbon atoms, a CH ₂ group of the alkylene chain being -O-, -CO-, -S-, - SO-, -SO ₂ - or -NR (10a) - can be replaced;
R (10a) is hydrogen, methyl or ethyl;
R (4) R (14) -C _r H _2r , where a CH ₂ group from the group C _r H _2r can be replaced by -O-, -CH = CH-, -C∼C-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (14) methyl, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, -OH, -COOH, -NR (23) R (24 ), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl, where pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (23) and R (24) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
or
R (23) and R (24) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
r zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;
R (5) and R (6) together form a group
-CR (15) = CR (16) -CR (17) = CR (18) -,
-CR (15) = CR (16) -CR (17) = N-,
-CR (15) = CR (16) -N = CR (18) -,
-CR (15) = N-CR (17) = N-,
-CR (15) = NN = CR (18) -,
N = CR (16) -CR (17) = N- or
-S-CR (15) = CR (16) -,
both directions of linkage are possible;
R (15), R (16), R (17) and R (18) independently of one another are hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4 or 5 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, -CN, -CF ₃ , -C ₂ F ₅ , -C ₃ F ₇ , -N ₃ , -NO ₂ , -ZC _s H _2s -R (22) , Thienyl or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino , Sulfamoyl, methylsulfonyl and methylsulfonylamino;
Z -O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -SO ₂ -O-, -SO ₂ NR (10c), - NR (10c) - or -CONR (10c) -;
R (10c) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
s zero, 1, 2, 3, 4, 5 or 6;
R (22) hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, -NR (19) R (20), -COOR (21 ), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl or phenyl, where pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (19) and R (20) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
or
R (19) and R (20) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
R (21) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
however, Y cannot simultaneously be CR (11) and X can equal O;
as well as their physiologically acceptable salts. 2. Compound of formula I according to claim 1, in which:
X -O-, -S-, -SO-, -SO ₂ -, -NR (7) -, -CR (8a) R (8b) - or -CO-;
R (7) hydrogen or (C _a H _2a ) -R (9) where a CH ₂ group from the group C ₈ H _2a can be replaced by -O-, -CH = CH-, -C-in - C -, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -NR (10) - or -CONR (10) -;
R (10) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
a zero, 1, 2, 3, 4, 5, 6, 7 or 8;
R (9) hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, dimethylamino, diethylamino, 1-piperidyl, 1-pyrrolidinyl, 4- Morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl, where pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (8a) is hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or phenyl which is unsubstituted or substituted by 1 or 2 substituents from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (8b) is hydrogen, alkyl having 1, 2 or 3 carbon atoms, -OR (10), -COOR (10), -CO-R (10);
R (10) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
YN or CR (11);
R (11) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (1) and R (2) independently of one another are hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
or
R (1) and R (2) together form an alkylene chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms; R (3) R (12) -C _n H _2n -NR (13) - or R (12) -C _n H _2n -, whereby a CH ₂ group in the groups C _n H _2n can be replaced by -O -, -CO-, -S-, -SO-, -SO ₂ - or -NR (10a) -;
R (10a) is hydrogen, methyl or ethyl;
R (12) is hydrogen, methyl, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, CF ₃ , C ₂ F ₅ or C ₃ F ₇ ;
n zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R (13) is hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms;
or
R (12) and R (13) together form a bond if n is not less than 3;
or
R (3) together with R (4) is an alkylene chain with 3, 4, 5, 6, 7 or 8 carbon atoms, a CH ₂ group of the alkylene chain being -O-, -CO-, -S-, - SO-, -SO ₂ - or -NR (10a) - can be replaced;
R (10a) is hydrogen, methyl or ethyl;
R (4) R (14) -C _r H _2r , where a CH ₂ group from the group C _r H _2r can be replaced by -O-, -CH = CH-, -C∼C-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (14) methyl, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, -OH, -COOH, -NR (23) R (24 ), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl, where pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (23) and R (24) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
or
R (23) and R (24) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
r zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;
R (5) and R (6) together form a group
-CR (15) = CR (16) -CR (17) = CR (18) -,
-CR (15) = CR (16) -CR (17) = N-,
-CR (15) = CR (16) -N = CR (18) -,
-CR (15) = N-CR (17) = N-,
-CR (15) = NN = CR (18) -,
-N = CR (16) -CR (17) = N- or
-S-CR (15) = CR (16) -,
both directions of linkage are possible;
R (15), R (16), R (17) and R (18) independently of one another are hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4 or 5 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, -CN, -CF ₃ , -C ₂ F ₅ , -C ₃ F ₇ , -N ₃ , -NO ₂ , -ZC _s H _2s -R (22) , Thienyl or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino , Sulfamoyl, methylsulfonyl and methylsulfonylamino;
Z -O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -SO ₂ -O-, -SO ₂ NR (10c), - NR (10c) - or -CONR (10c) -;
R (10c) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
s zero, 1, 2, 3, 4, 5 or 6;
R (22) hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, -NR (19) R (20), -COOR (21 ), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl or phenyl, where pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethyiamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (19) and R (20) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
or
R (19) and R (20) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
R (21) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
however, Y cannot be equal to CR (11) and X equal to O at the same time. 3. Compound of formula I according to claims 1 or 2, in which:
X -O-, -S-, -SO-, -SO ₂ -, -NR (7) -, -CR (8a) R (8b) - or -CO-;
R (7) is hydrogen or - (C _a H _2a ) -R (9), where a CH ₂ group from the group C _a H _2a can be replaced by -O-, -CH = CH-, -C∼C- , -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -NR (10) - or -CONR (10) -;
R (10) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
a zero, 1, 2, 3, 4, 5, 6, 7 or 8;
R (9) hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, dimethylamino, diethylamino, 1-piperidyl, 1-pyrrolidinyl, 4- Morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl, where pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (8a) is hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or phenyl which is unsubstituted or substituted by 1 or 2 substituents from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (8b) is hydrogen, alkyl having 1, 2 or 3 carbon atoms, -OR (10), -COOR (10), -CO-R (10);
R (10) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
YN or CR (11);
R (11) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (1) and R (2) independently of one another are hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ ,, NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
or
R (1) and R (2) together form an alkylene chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms;
R (3) R (12) -C _n H _2n -NR (13) - or R (12) -C _n H _2n -, whereby a CH ₂ group in the groups C _n H _2n can be replaced by -O -, -CO-, -S-, -SO-, -SO ₂ - or -NR (10a) -;
R (10a) is hydrogen, methyl or ethyl;
R (12) is hydrogen, methyl, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, CF ₃ , -C ₂ F ₅ or C ₃ F ₇ ;
n zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R (13) is hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms;
or
R (12) and R (13) together form a bond if n is not less than 3;
or
R (3) together with R (4) is an alkylene chain with 3, 4, 5, 6, 7 or 8 carbon atoms, a CH ₂ group of the alkylene chain being -O-, -CO-, -S-, - SO-, -SO ₂ - or -NR (10a) - can be replaced;
R (10a) is hydrogen, methyl or ethyl;
R (4) R (14) -C _r H _2r , where a CH ₂ group from the group C _r H _2r can be replaced by -O-, -CH = CH-, -C∼C-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (14) methyl, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, -OH, -COOH, -NR (23) R (24 ), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl, where pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (23) and R (24) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
or
R (23) and R (24) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
r zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;
R (5) and R (6) together form a group -CR (15) = CR (16) -CR (17) = CR (18) -;
R (15), R (16), R (17) and R (18) independently of one another are hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4 or 5 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, -CN, -CF ₃ , -C ₂ F ₅ , -C ₃ F ₇ , -N ₃ , -NO ₂ , -ZC _s H _2s -R (22) , Thienyl or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino , Sulfamoyl, methylsulfonyl and methylsulfonylamino;
Z -O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -SO ₂ -O-, -SO ₂ NR (10c), - NR (10c) - or -CONR (10c) -;
R (10c) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
s zero, 1, 2, 3, 4, 5 or 6;
R (22) hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, -NR (19) R (20), -COOR (21 ), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl or phenyl, where pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (19) and R (20) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
or
R (19) and R (20) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
R (21) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
however, Y cannot be equal to CR (11) and X equal to O at the same time. 4. A compound of formula I according to claims 1 to 3, in which:
X -O-, -S-, -SO-, -SO ₂ -, -NR (7) - or -CR (8a) R (8b) -;
R (7) is hydrogen or - (C _a H _2a ) -R (9), where a CH ₂ group from the group C _a H _2a can be replaced by -O-, -CO-, -CO-O-, - SO ₂ - or -NR (10) -;
R (10) is hydrogen or alkyl having 1 or 2 carbon atoms;
a zero, 1, 2, 3 or 4;
R (9) is hydrogen, CF ₃ , cycloalkyl with 5 or 6 carbon atoms, pyridyl, thienyl, imidazolyl or phenyl, where pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (8a) is hydrogen, CF ₃ , alkyl having 1, 2, 3 or 4 carbon atoms or phenyl which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF. ₃ NO ₂ , CN, NH ₂ OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (8b) is hydrogen, alkyl having 1, 2 or 3 carbon atoms;
YN or CR (11);
R (11) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (1) and R (2) independently of one another are CF ₃ , alkyl having 1, 2, 3 or 4 carbon atoms or phenyl which is unsubstituted or substituted by 1 or 2 substituents, selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
or
R (1) and R (2) together form an alkylene chain with 2, 3, 4, 5 or 6 carbon atoms;
R (3) R (12) -C _n H _2n -NR (13) - or R (12) -C _n H _2n -;
R (12) methyl or CF ₃ ;
n zero, 1, 2, 3, 4 or 5;
R (13) is hydrogen or alkyl having 1, 21 3 or 4 carbon atoms;
or
R (3) together with R (4) is an alkylene chain with 3 or 4 carbon atoms, whereby a CH ₂ group of the alkylene chain can be replaced by -CO-;
R (4) R (14) -C _r H _2r , where a CH ₂ group from the group C _r H _2r can be replaced by -O-, -CO-, -CO-O, -O-CO-, - S-, -SO-, -SO ₂ -, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1 or 2 carbon atoms;
R (14) methyl, CF ₃ , cycloalkyl with 3, 4, 5, 6 or 7 carbon atoms, -OH, -COOH, -NR (23) R (24), 1-piperidyl, 1-pyrrolidinyl, 4- Morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl, where pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (23) and R (24) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms;
or
R (23) and R (24) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
r zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R (5) and R (6) together form a group -CR (15) = CR (16) -CR (17) = CR (18) -;
R (15), R (16), R (17) and R (18) independently of one another hydrogen, F, Cl, alkyl with 1, 2 or 3 carbon atoms, -CN, -CF ₃ , -NO ₂ , - ZC _s H _2s -R (22), thienyl or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
Z -O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -SO ₂ -O-, -SO ₂ NR (10c), - NR (10c) - or -CONR (10c) -;
R (10c) is hydrogen or alkyl having 1 or 2 carbon atoms;
s zero, 1, 2, 3, or 4;
R (22) hydrogen, CF ₃ , cycloalkyl with 5 or 6 carbon atoms, -NR (19) R (20), -COOR (21), pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl or phenyl, whereby pyridyl, thienyl , Imidazolyl, quinolyl, isoquinolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy , Dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (19) and R (20) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms;
or
R (19) and R (20) together form a chain of 4 or 5 methylene groups, of which one CH ₂ group can be replaced by -O-, -S-, -NH- or -N (CH ₃ ) -;
R (21) is hydrogen or alkyl having 1 or 2 carbon atoms;
however, Y cannot be equal to CR (11) and X equal to O at the same time. 5. A compound of formula I according to claims 1 to 4, in which:
X -CR (8a) R (8b) -;
R (8a) hydrogen;
R (8b) hydrogen;
Y CR (11);
R (11) hydrogen;
R (1) and R (2) independently of one another alkyl having 1, 2 or 3 carbon atoms;
or
R (1) and R (2) together form an alkylene chain with 4 or 5 carbon atoms;
R (3) R (12) -C _n H _2n -;
R (12) methyl;
n zero, 1 or 2;
R (4) R (14) -C _r H _2r , where a CH ₂ group from the group C _r H _2r can be replaced by -O-, -CO-, -CO-O-, -O-CO-, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1 or 2 carbon atoms;
R (14) methyl, CF ₃ , cycloalkyl having 3, 4, 5 or 6 carbon atoms, -NR (23) R (24), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, pyridyl, thienyl, imidazolyl or Phenyl, wherein pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
R (23) and R (24) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms;
r zero, 1, 2, 3, 4, 5, 6, 7 or 8;
R (5) and R (6) together form a group -CR (15) = CR (16) -CR (17) = CR (18) -;
R (15), R (16), R (17) and R (18) independently of one another are hydrogen, F, Cl, alkyl having 1 or 2 carbon atoms, -CN, -CF ₃ , -NO ₂ , -ZC _s H _2s -R (22) or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
Z -O-, -CO-, -CO-O-, -O-CO-, -SO ₂ -, -SO ₂ -O-, -SO ₂ NR (10c), -NR (10c) - or -CONR (10c) -;
R (10c) is hydrogen or methyl;
s zero, 1, 2, 3, or 4;
R (22) is hydrogen, CF ₃ , cycloalkyl having 5 or 6 carbon atoms, -NR (19) R (20) or phenyl which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl , CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
R (19) and R (20) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms. 6. A compound of the formula I as claimed in claims 1 to 4, in which:
X -O-, -NR (7) - or -CR (8a) R (8b) -;
R (7) is hydrogen or - (C _a H _2a ) -R (9);
a zero, 1, 2, 3 or 4;
R (9) is hydrogen or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , methyl, methoxy, sulfamoyl and methylsulfonyl;
R (8a) hydrogen;
R (8b) hydrogen;
YN;
R (1) and R (2) independently of one another alkyl having 1, 2 or 3 carbon atoms;
or
R (1) and R (2) together form an alkylene chain with 4 or 5 carbon atoms;
R (3) R (12) -C _n H _2n -;
R (12) methyl;
n zero, 1 or 2;
R (4) R (14) -C _r H _2r , where a CH ₂ group from the group C _r H _2r can be replaced by -O-, -CO-, -CO-O-, -O-CO-, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1 or 2 carbon atoms;
R (14) methyl, CF ₃ , cycloalkyl having 3, 4, 5 or 6 carbon atoms, -NR (23) R (24), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, pyridyl, thienyl, imidazolyl or Phenyl, wherein pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
R (23) and R (24) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms;
r zero, 1, 2, 3, 4, 5, 6, 7 or 8;
R (5) and R (6) together form a group -CR (15) = CR (16) -CR (17) = CR (18) -;
R (15), R (16), R (17) and R (18) independently of one another are hydrogen, F, Cl, alkyl having 1 or 2 carbon atoms, -CN, -CF ₃ , -NO ₂ , -ZC _s H _2s -R (22) or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
Z -O-, -CO-, -CO-O-, -O-CO-, -SO ₂ -, -SO ₂ -O-, -SO ₂ NR (10c), -NR (10c) - or -CONR (10c) -;
R (10c) is hydrogen or methyl;
s zero, 1,2,3, or 4;
R (22) is hydrogen, CF ₃ cycloalkyl having 5 or 6 carbon atoms, -NR (19) R (20) or phenyl which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
R (19) and R (20) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms. 7. Compound of formula I according to claims 1 to 4, in which:
X -NR (7) -, -S-, -SO- or -SO ₂ -; R (7) is hydrogen or - (C _a H _2a ) -R (9);
a zero, 1, 2, 3 or 4;
R (9) is hydrogen or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , methyl, methoxy, sulfamoyl and methylsulfonyl;
Y CR (11);
R (11) hydrogen;
R (1) and R (2) independently of one another alkyl having 1, 2 or 3 carbon atoms;
or
R (1) and R (2) together form an alkylene chain with 4 or 5 carbon atoms;
R (3) R (12) -C _n H _2n -;
R (12) methyl;
n zero, 1 or 2;
R (4) R (14) -C _r H _2r , where a CH ₂ group from the group C _r H _2r can be replaced by -O-, -CO-, -CO-O-, -O-CO-, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1 or 2 carbon atoms;
R (14) methyl, CF ₃ , cycloalkyl having 3, 4, 5 or 6 carbon atoms, -NR (23) R (24), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, pyridyl, thienyl, imidazolyl or Phenyl, wherein pyridyl, thienyl, imidazolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
R (23) and R (24) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms;
r zero, 1, 2, 3, 4, 5, 6, 7 or 8;
R (5) and R (6) together form a group -CR (15) = CR (16) -CR (17) = CR (18) -;
R (15), R (16), R (17) and R (18) independently of one another are hydrogen, F, Cl, alkyl having 1 or 2 carbon atoms, -CN, -CF ₃ , -NO ₂ , -ZC _s H _2s -R (22) or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
Z -O-, -CO-, -CO-O-, -O-CO-, -SO ₂ -, -SO ₂ -O-, -SO ₂ NR (10c), -NR (10c) - or -CONR (10c) -;
R (10c) is hydrogen or methyl;
s zero, 1, 2, 3, or 4;
R (22) is hydrogen, CF ₃ , cycloalkyl having 5 or 6 carbon atoms, -NR (19) R (20) or phenyl which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl , CF ₃ , OH, methyl, methoxy, sulfamoyl and methylsulfonyl;
R (19) and R (20) independently of one another are hydrogen or alkyl having 1 or 2 carbon atoms. 8. A compound of formula I according to claim 1, in which:
X -NR (7) - or -CR (8a) R (8b) -;
R (7) together with R (1) is a bond;
R (8b) is hydrogen, alkyl having 1, 2 or 3 carbon atoms, -OR (10), -COOR (10), -CO-R (10);
R (10) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (8a) together with R (1) is a bond;
YN; or CR (11) if X has the meaning of NR (7);
R (11) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (1) together with R (7) or R (8a) is a bond;
R (2) hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , F, Cl, methoxy, alkyl with 1,2, 3, 4, 5 or 6 C atoms or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (3) R (12) -C _n H _2n -NR (13) - or R (12) -C _n H _2n -, whereby a CH ₂ group in the groups C _n H _2n can be replaced by -O -, -CO-, -S-, -SO-, -SO ₂ - or -NR (10a) -;
R (10a) is hydrogen, methyl or ethyl;
R (12) is hydrogen, methyl, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, CF ₃ , C ₂ F ₅ or C ₃ F ₇ ;
n zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
R (13) is hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms;
or
R (12) and R (13) together form a bond if n is not less than 3;
or
R (3) together with R (4) is an alkylene chain with 3, 4, 5, 6, 7 or 8 carbon atoms;
R (4) R (14) -C _r H _2r , where a CH ₂ group from the group C _r H _2r can be replaced by -O-, -CH = CH-, -C∼C-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -NR (10b) - or -CONR (10b) -;
R (10b) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R (14) methyl, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, -OH, -COOH, -NR (23) R (24 ), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl or imidazolyl, pyridyl, thienyl and imidazolyl being unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (23) and R (24) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
or
R (23) and R (24) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
r zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;
R (5) and R (6) together form a group -CR (15) = CR (16) -CR (17) = CR (18) - or -S-CR (15) = CR (16) -, respectively both linking directions are possible;
R (15), R (16), R (17) and R (18) independently of one another are hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4 or 5 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, -CN, -CF ₃ , -C ₂ F ₅ , -C ₃ F ₇ , -N ₃ , -NO ₂ , -ZC _s H _2s -R (22) , Thienyl or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino , Sulfamoyl, methylsulfonyl and methylsulfonylamino;
Z -O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -SO ₂ -O-, -SO ₂ NR (10c), - NR (10c) - or -CONR (10c) -;
R (10c) is hydrogen or alkyl having 1, 2 or 3 carbon atoms;
s zero, 1, 2, 3, 4, 5 or 6;
R (22) hydrogen, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms, -NR (19) R (20), -COOR (21 ), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl or phenyl, where pyridyl, thienyl, imidazolyl, quinolyl, isoquinolyl and phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (19) and R (20) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
or
R (19) and R (20) together form a chain of 4 or 5 methylene groups, one of which is a CH ₂ group through -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl ) - can be replaced;
R (21) is hydrogen or alkyl having 1, 2 or 3 carbon atoms. 9. A process for the preparation of compounds of formula I according to one or more of claims 1 to 8, characterized in that

• a) a compound of formula II,
  wherein R (1), R (2), R (5), R (6), X and Y have the meanings given in claims 1 to 8 and L is a nucleofugal leaving group, reacted with a sulfonamide or its salt of the formula III,
  wherein R (3) and R (4) have the meanings given in claims 1 to 8 and M represents hydrogen or preferably a metal equivalent;
  or that one
• b) a compound of formula IV
  wherein R (1), R (2), R (4), R (5), R (6), X and Y have the meanings given in claims 1 to 8, with a sulfonic acid derivative of the formula V.
  implements, wherein R (3) has the meanings given in claims 1 to 8 and W represents a nucleofugal leaving group;
  or that one
• c) a compound of formula VI
  wherein R (1), R (2), R (3), R (5), R (6), X, Y and M have the meanings given in Claims 1 to 8 or under a), with an alkylating agent Formula VII,
  R (4) -L VII
  wherein R (4) has the meanings given in Claims 1 to 8 with the exception of hydrogen and L has the meanings given under a);
  or that one
• d) in a compound of formula I.
  wherein R (1) to R (6), X and Y have the meanings given in claims 1 to 8, in at least one of the positions R (15), R (16), R (17), R (18) of Ringsystems R (5) -R (6) carries out an electrophilic substitution reaction if this position means hydrogen.

10. Compounds of formula I according to one or more of claims 1 to 8 and their physiologically acceptable salts for use as medicines. 11. Pharmaceutical preparation containing at least an effective amount a compound of formula I according to one or more of claims 1 to 8 and / or a physiologically acceptable salt thereof as an active ingredient  with pharmaceutically acceptable carriers and additives and optionally one or more other pharmacological agents. 12. Use of a compound of formula I according to one or more of the Claims 1 to 8 and / or a physiologically acceptable salt thereof Manufacture of a drug with K⁺-channel blocking effect for therapy and prophylaxis of K⁺-channel mediated diseases. 13. Use of a compound of formula I according to one or more of the Claims 1 to 8 and / or a physiologically acceptable salt thereof Manufacture of a medicament for inhibiting gastric acid secretion. 14. Use of a compound of formula I according to one or more of the Claims 1 to 8 and / or a physiologically acceptable salt thereof Manufacture of a medicament for the therapy or prophylaxis of ulcer Stomach or intestinal area. 15. Use of a compound of formula I according to one or more of the Claims 1 to 8 and / or a physiologically acceptable salt thereof Manufacture of a medicament for therapy or prophylaxis of the Reflux esophagitis. 16. Use of a compound of formula I according to one or more of the Claims 1 to 8 and / or a physiologically acceptable salt thereof Manufacture of a medicament for the therapy or prophylaxis of Diarrhea. 17. Use of a compound of formula I according to one or more of the Claims 1 to 8 and / or a physiologically acceptable salt thereof Manufacture of a medicament for the therapy or prophylaxis of all types of Arrhythmias, including atrial, ventricular, and supraventricular Arrhythmias.   18. Use of a compound of formula I according to one or more of the Claims 1 to 8 and / or a physiologically acceptable salt thereof Manufacture of a medicament for the therapy or prophylaxis of Cardiac arrhythmias, which are remedied by action potential extension can. 19. Use of a compound of formula I according to one or more of the Claims 1 to 8 and / or a physiologically acceptable salt thereof Manufacture of a medicament for the therapy or prophylaxis of atrial fibrillation or atrial flutter. 20. Use of a compound of formula I according to one or more of the Claims 1 to 8 and / or a physiologically acceptable salt thereof Manufacture of a medicament for the therapy or prophylaxis of reentry Arrhythmias or to prevent sudden cardiac death as a result of Ventricular fibrillation. 21. Use of a compound of formula I according to one or more of the Claims 1 to 8 and / or a physiologically acceptable salt thereof Manufacture of a medicament for the therapy of heart failure, in particular the Congestive heart failure. 22. Use of a compound of formula I according to one or more of the Claims 1 to 8 and / or a physiologically acceptable salt thereof Blocking the potassium channel caused by cyclic adenosine monophosphate (cAMP) is opened. 23. Use of a compound of formula I according to one or more of the Claims 1 to 8 and / or a physiologically acceptable salt thereof Manufacture a drug to inhibit the stimulated Gastric acid secretion, for the therapy or prophylaxis of gastric ulcers or  of the intestinal area, reflux esophagitis, of diarrheal diseases, for Therapy or prophylaxis of arrhythmias, including atrial, ventricular and supraventricular arrhythmias, atrial fibrillation and atrial flutter and of Reentry arrhythmias, or to prevent sudden cardiac death as a result of Ventricular fibrillation.