Inhibitors kqt1 channels to obtain drugs for the treatment of diseases caused by helminths and ectoparasites

 

(57) Abstract:

The invention relates to pharmaceutical industry and relates to inhibitors lks-channel simultaneous action as inhibitors KQT1 channel to obtain drugs for the treatment of diseases caused by helminths and ectoparasites, while inhibitors KQT1 channel have high selectivity and are non-toxic to warm-blooded animals and humans. 1 C. p. F.-ly, 1 table.

The invention relates to inhibitors KQT1 channels to obtain drugs for the treatment of diseases caused by helminths and ectoparasites.

Parasitic diseases are widely spread and cause people and animals with a wide range of pathological phenomena, which range from minor disorders to severe, even fatal diseases. Currently known many parasitic diseases that threaten the health and lives of people, as well as domestic and useful animals.

Besides, in the world there is a tendency to weakening of the immune systems of millions of people. This circle of people so massively affected modern parasites that every year there are Milli is considered exotic parasites. The reason for this is that continuing an increasingly strong tendency to travel in close to the hygienic conditions of these countries is the loss of a sense of hygiene hazard. Along with protection of human health requires the protection of animals and disposal of animals from calling a parasitic disease suffering and pain. The reasons are primarily in relation to the useful animals when under adverse conditions of keeping and feeding animals (for example, when certain forms of mass of the animal) especially prevalent parasitic diseases, which lead to a decrease in performance quantitative (amount of meat, including eggs, time of operation) or qualitative (quality meat and wool) type. A lot of damage, which cause the parasites to humans and animals, makes it desirable control over them, if not inevitable, in the interests of health and agriculture.

The use of chemical substances, known for its activity against certain parasites or large groups of parasites and toxicologically acceptable to the host (human, animal), is even more important.

On the spectrum of distinguished destwidth, effective against insect insecticide, effective against mites blossom; the last two groups unite under the definition of ectoparasitic drugs. Increase resistance to medicinal substances which are favorable to long-term and intensive use in modern mass animal or the appearance of sometimes strong side effects, particularly with long-term medical treatment of the person, which must be held for a long time in the tropics or subtropics, as well as the high cost of preventive/therapeutic chemicals do we need to search for other classes of substances with acceptable cost, with a different mechanism of action and tolerability.

In the framework of the invention found that the inhibition KQT1 channel represents a new solution with fatal outcome in respect of helminths and ectoparasites. The present invention relates therefore to the use of blockers of cell KQT1-channel, which are helminths and ectoparasites, to obtain drugs for the treatment of vertebrate animals and people affected by worms or parasites. These KQT1-blockers applicable as their activities.

Unexpectedly, it was shown that inhibitors lks-channel can substantially block KQT1 channel. Thus, inhibitors lks-channels with their blocking activity against KQT1 channel suitable for receiving medicines for the treatment of diseases caused by helminths and ectoparasites.

In the case of inhibitors lks-channel we are talking about biologically active substances, which for the first time in the last 10 years has attracted interest from this point of view. Meanwhile, described the numerous applications of this class of biologically active substances, such as their use as medications for the treatment of cardiac arrhythmias, treatment of ulcers by inhibiting the secretion of gastric juice, therapy of diseases associated with diarrhea, the treatment of Meniere's disease etc., of Particular importance for therapeutic applications lks-blockers has their antiarrhythmic action.

Antiarrhythmic effect of blockers lks-channels based on the elongation of the flat phase of the cardiac cells, especially under conditions of stimulation of the sympathetic division of the autonomic nervous system. Slow repolarization is a recognized anti-arrhythmic principle of the so-called antiaritmichesky is but it was installed, that lks-inhibitors act as KQT1-blockers and affect the viability of helminths and ectoparasites, the invention relates to the use described in the following patents blockers lks-channels as valuable therapeutic agents for the treatment of lesions of humans and vertebrate animals with worms and parasites and related diseases, as well as to obtain plant protection for combating pathogenic for plants Arthropoda, molluscs and nematodes.

Suitable compounds for use according to the invention are, among others, compounds selected from those described in the following descriptions to patents and literary sources.

1) EP 807629 (NOAH 96/F119)

Romany formula I

where R(1) and R(2) denote independently from each other hydrogen, CpF2p+1, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl, methylsulfonylamino and methylsulfonyl;

p is 1, 2 or 3,

or R(1) and R(2) denote, together alkylenes chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms;

R(3) denotes R(9)-CnH2nm is zero or 1;

R(11) denotes hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(11) denotes together with R(9) alkylenes group 1, 2, 3, 4, 5, 6, 7 or 8 C-atoms

one of CH2-group groupnH2nmay be replaced by-O-, -SOqor-NR(10);

q is zero, 1 or 2;

R(10) denotes hydrogen, methyl or ethyl;

R(4) denotes R(12)-CrH2r;

R(12) denotes hydrogen, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, piperidyl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CpF2p+1, pyridyl, thienyl, imidazolyl or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl, methylsulfonyl and methylsulfonylamino;

r is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20,

one of CH2group group CrH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -SOq- or-NR(10)-;

q is zero, 1 or 2;

R(10) denotes hydrogen, methyl or ethyl;

R(5), R(6) R(7) and R(8) denote independently from each other hydrogen, F, Cl, Br, I, alkyl with 1, 2, 3 or 4 C-atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -CN, phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl;

R(13) and R(14) denote independently from each other hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(15) denotes hydrogen, methyl, ethyl, phenyl or-CuH2u-NR(13)R(14);

u is 2 or 3;

R(16) denotes hydrogen, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -COOR(15), thienyl, imidazolyl, pyridyl, hinely, ethanolic, piperidyl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CtF2f+1or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl or methylsulfonyl;

s - zero, 1, 2, 3, 4, 5 or 6;

t is 1, 2 or 3;

Y denotes SOq, -CO-, -SO2-NR(10)-, -O-, -NR(10)- or-CO-NR(10),

moreover, however, R(6) cannot be F3or-OC2F5,

and their physiologically acceptable salts;

2)ER 847 996 (NOAH 96/F341)

The compounds of formula I

where X represents-O-, -S-, -SO-, -SO2-, -NR(7)-, -CR(8a)R(8b)- or-CO-;

R(7) denotes hydrogen or - (CaH2a) -R (9),

one CHR(10) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

and zero, 1, 2, 3, 4, 5, 6, 7 or 8;

R(9) denotes hydrogen, CF3WITH2F5WITH3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, dimethylaminopropyl, diethylaminopropyl, 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl,

moreover, pyridyl, thienyl, imidazolyl and phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

or R(7) and R(1) together represent a bond;

R(8a) denotes hydrogen, CF3C2F5C3F7, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(8b) denotes hydrogen, alkyl with 1, 2 or 3 C-atoms, OR(10), -COOR(10), CO-R(10);

R(10) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms

R(11) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(1) and R(2) denote independently from each other hydrogen, CF3C2F5WITH3F7, F, CL, methoxy group, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino,

or R(1) and R(2) denote, together alkylenes chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms;

R(3) denotes R(12)-CnH2n-NR(13) R(12)-CnH2n-, and CH2-group groupnH2nmay be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(10a)-;

R(10a) denotes hydrogen, methyl or ethyl;

R(12) denotes hydrogen, methyl, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, CF3WITH2F5or3F7;

n - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

R(13) denotes hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(12) R(13) together represent a bond, when n is not less than 3,

or R(3) and R(4) together represent alkylenes chain with 3, 4, 5, 6, 7 or 8 C-atoms

one of CH2the alkyl group is ethyl;

R(4) denotes R(14)-CrH2r,

one of CH2-group grouprH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, -NR(10b) -, or-CONR(10b)-;

R(10b) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(14) denotes methyl, CF3C2F5WITH3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -OH, -COOH, -NR(23)R(24), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl,

moreover, pyridyl, thienyl, imidazolyl and phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(23) R(24) denote independently from each other hydrogen or alkyl with 1, 2 or 3 C-atoms

or R(23) R(24) together represent a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

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) R(6) together represent the group

-CR(15)=CR(16)-CR(17)=CR(18)-,

-CR(15)=CR(16)-CR(17)=N-

-CR(15)=CR(16)-N=CR(18)-,

-CR (the Deposit accession;

R(15) R(16) R(17) R(18) denote independently from each other 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, -CF3, -C2F5- 3F7,

-N3, -NO2, -Z-CsH2s-R(22), thienyl or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

Z represents-O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, -SO2-O-, -SO2NR(10c), -NR(10c) -, or-CONR(10c)-;

R(10c) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

s - zero, 1, 2, 3, 4, 5 or 6;

R(22) denotes hydrogen, CF3C2F5WITH3F7cycloalkyl 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, hinely, ethanolic or phenyl,

moreover, pyridyl, thienyl, imidazolyl, hinely, ethanolic and phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl or alkyl with 1, 2 or 3 C-atoms

or R(19) R(20) together represent a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

R(21) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms

moreover, however, cannot be simultaneously Y is CR(11) and X is equal to O

and their physiologically acceptable salts;

3) EP 857724 (NOAH 97/F 024)

The compounds of formula I

where X is -[S(O)zero, 1 or 2]-, -NR(9)-, - [CR(9) R(23)]- or-CO-;

R(9) denotes hydrogen or -(CnH2n)-R(10);

n - zero, 1, 2, 3, 4, 5, 6, 7 or 8;

R(10) denotes hydrogen, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, piperidyl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CF3C2F5or3F7,

one of CH2-group groupnH2nmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -[SOzero, 1 or 2]- or-NR(11)-;

R(11) denotes hydrogen, methyl or ethyl

or R(10) denotes pyridyl, thienyl, imidazolyl or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl, methylsulfate, alkyl with 1, 2 or 3 C-atoms, HE, O-alkyl with 1, 2 or 3 C-atoms, COOH, COO-alkyl with 1, 2 or 3 C-atoms or-CO-R(24);

R(24) denotes hydrogen, methyl or ethyl;

R(1) and R(2) denote independently from each other hydrogen, CF3C2F5WITH3F7, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl,

or R(1) and R(2) denote, together alkylenes chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms;

R(3) denotes R(12)-CaH2a[NR(13)]m-;

R(12) denotes hydrogen or cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, CF3C2F5or3F7;

and zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

m is zero or 1;

R(13) denotes hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(12) R(13) denote

together alkylenes group 4, 5, 6, 7 or 8 C-atoms

one of CH2Groupe alkalinous group may be replaced by-O-, -[SOzero, 1 or 2]-, -CO - or-NR(11)-;

R(11) denotes hydrogen, methyl or ethyl;

R(4) denotes R(14)-CrH2r;

r is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,farinograph, N-methylpiperazine, CF3C2F5WITH3F7, pyridyl, thienyl, imidazolyl or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl, methylsulfonyl and methylsulfonylamino;

one of CH2-group grouprH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -CO-, NR(11)-, -[SOzero, 1 or 2]- or-NR(11)-,

or R(3) and R(4) together represent alkylenes chain with 3, 4, 5, 6, 7 or 8 C-atoms

one of CH2group alkalinous chain may be replaced by-O-, -[SOzero, 1 or 2]-, -CO - or-NR(11)-;

R(5) R(6) together represent-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)-;

R(15) R(16) R(17) R(18) denote independently from each other hydrogen, F, Cl, Br, I, alkyl with 1, 2, 3 or 4 C-atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, CN, CF3C2F5C3F7N3, NO2, -CONR(19)R(20), -COOR(21), R (22)-CsH2s-Z -, or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and the CLASS="ptx2">R(21) denotes hydrogen, methyl, ethyl, phenyl or-CuH2u-NR(19)R(20);

u is 2 or 3,

and phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl or methylsulfonyl;

R(22) denotes hydrogen, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -COOR(21), thienyl, imidazolyl, pyridyl, hinely, ethanolic, piperidyl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CF3C2F5or C3F7or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl or methylsulfonyl;

s - zero, 1, 2, 3, 4, 5 or 6;

Z represents-S(O)zero, 1 or 2]-, -CO-, -SO2-NR(11)-, -SO2-O-, -O-, -NR(11)- or -[CO-NR(11)]-;

R(7) denotes hydrogen, a hydroxy-group, alkoxygroup with 1, 2, 3 or 4 C-atoms, alloctype with 1, 2, 3 or 4 C-atoms, Cl, Br, F, alkyl with 1, 2, 3 or 4 C-atoms;

R(8) denotes hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

and their physiologically acceptable salts;

4) EP 860440 (NOAH 97/F033)

Derivatives chromane formula I

where R(1) and R(2) independently represent other="ptx2">which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl,

or R(1) and R(2) denote, together alkylenes chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms;

R(A) denotes a hydroxy-group, alkanoyloxy with 1, 2, 3, 4, 5 or 6 C-atoms or alkylsulfonates with 1, 2, 3, 4, 5 or 6 C-atoms;

R(B) denotes hydrogen

or R(a) and R(B) together represent a bond;

R(3) denotes R(9)-CnH2n[NR(11)]m-;

R(9) denotes hydrogen or cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms;

n - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

m is zero or 1;

R(11) denotes hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(11) and R(9) represent together alkylenes group 1, 2, 3, 4, 5, 6, 7 or 8 C-atoms

one of CH2group group CnH2nmay be replaced by-O-, SOzero, 1 or 2- or-NR(10);

R(10) denotes hydrogen, methyl or ethyl;

R(4) denotes R(12)-CrH2r;

R(12) denotes hydrogen, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, piperidyl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CF3C2F5WITH3F7, pyridyl, what if 2 substituents, selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl, methylsulfonyl and methylsulfonylamino;

r - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20,

one CH2-rpynna grouprH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, SOzero, 1 or 2- or-NR(10)-;

R(5), R(6) R(7) and R(8) denote independently from each other hydrogen, F, Cl, Br, I, alkyl with

1, 2, 3, 4, 5 or 6 C-atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -CN, -CF3, -C2F5- 3F7, -N3, -NO2, -CONR(13)R(14), -COOR(15), R (16)-CsH2s-Y -, or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl;

R(13) and R(14) denote independently from each other hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(15) denotes hydrogen, methyl, ethyl, phenyl or-CuH2u-NR(13)R(14);

u is 2 or 3;

R(16) denotes hydrogen, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -COOR(15), thienyl, imidazolyl, pyridyl, hinely, ethanolic, piperidyl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CF3C2F5C3F7VG, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl;

s - zero, 1, 2, 3, 4, 5 or 6;

Y represents-S-, -SO-, -SO2-, -CO-, -SO2-NR(10)-, -O-, -NR(10)- or-CO-NR(10),

however, provided that two of substituents R(5), R(6) R(7) and R(8) are not hydrogens,

and their physiologically acceptable salts;

5) EP 861836 (NOAH 97/F038)

The compounds of formula I

where X1 represents-O-, -S-, -SO-, -SO2-, -CR(1)R(2)-, -NR(6)-, -CO -, or-CR(1)R(7)-;

R(1) and R(2) denote independently from each other hydrogen, CF3C2F5WITH3F7, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl, which is unsubstituted or substituted by 1 or substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl of sulfamoyl, methylsulfonyl and methylsulfonylamino,

or R(1) and R(2) denote, together alkylenes chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms;

R(6) denotes hydrogen or CnH2n-R(8),

one of CH2-group groupnH2nmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, -NR(9) -, or-CONR(9)-;

R(9) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

n is zero, 1, 2, 3, or 8 C-atoms, dimethylaminopropyl, diethylaminopropyl, 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl,

moreover, pyridyl, thienyl, imidazolyl and phenyl is not substituted or is substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

X2 represents-CR(1)R(2)- or-CR(2)R(10)-

or x2 if X3 and X1 mean-CR(1)R(2)-, also means-O-, -S-, -SO-, -SO2- or-NR(6)-,

at the same time balances R(1), R(2) and R(6) have the meanings specified for X1, but regardless of the values of the residues in X1;

R(10) denotes together with R(7) communication;

X3 represents-CR(1)R(2)-

or X3, if x2 and X4 mean-CR(1)R(2)-, also means-O-, -S-, -SO-, -SO2- or-NR(6)-, with the remains of R(1), R(2) and R(6) have the meanings specified for X1, but regardless of the values of the residues in X1;

X4 represents-CR(1)R(2)-, -NR(6)-, -NR(11)-, -CH(OR(30)) or CR(2)R(11)-, with the remains of R(1), R(2) and R(6) have the meanings specified for X1, but regardless of the values of the residues in X1;

R(30) denotes hydrogen, alkyl with 1, 2 or 3 C-atoms or acyl of 1, 2, 3 or 4 C-atoms;

R(11) denotes together with R(5) with the simultaneous mean N;

the residues R(12) denote independently from each other 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, CF3WITH2F5WITH3F7N3, NO2, -Z-CmH2m-R(13) or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

Z represents-O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, -NO2NR(14)-, -NR(14) -, or-CONR(14)-;

R(14) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

m - zero, 1, 2, 3, 4, 5 or 6;

R(13) denotes hydrogen, CF3C2F5WITH3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -NR(15)R(16), -CONR(15)R(16), -OR(30a), phenyl, thienyl or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C - atoms

and phenyl, thienyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(15) R(16) denote independently on the SCP, one of CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

R(30a) denotes hydrogen, alkyl with 1, 2 or 3 C-atoms or acyl of 1, 2, 3 or 4 C-atoms;

or Y1 and Y2 together represent the atoms S and each of Y3 and Y4-CR(12)-;

the residues R(12) independently of one another, as defined in Y1, Y2, Y3, Y4;

R(3) denotes R(17) -CxH2x-NR(18) R(17) -CxH2x,

one of CH2-groupxH2groups can be

replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(19)-;

R(19) denotes hydrogen, methyl or ethyl;

R(17) denotes hydrogen, methyl, cycloalkyl with 3, 4, 5,

6, 7 or 8 C-atoms, CF3C2F5or3F7;

x - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

R(18) denotes hydrogen or alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C - atoms

or R(18) and R(17) together represent a bond, if x is not less than 3,

or R(3) denotes a phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino,

or R(3) together with R(4) denote Alki the s-O-, -CO-, -S-, -SO - or-SO2-;

R(4) means-CrH2r-R(20),

one of CH2group group CrH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, -NR(21) -, or-CONR(21)-;

R(21) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

r - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;

R(20) denotes hydrogen, methyl, CF3C2F5C3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -NR(22)R(23), phenyl, thienyl or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C-atoms

and phenyl, thienyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(22) R(23) denote independently from each other hydrogen or alkyl with 1, 2 or 3 C-atoms

or R(22) R(23) together represent a chain of 4 or 5 methylene groups, in which one CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

R(5) denotes hydrogen or together with R(11) communications

in all their stereoisomeric forms and mixtures in any aspect] is s I

where R(1) and R(2) denote independently from each other hydrogen, CF3C2F5WITH3F7, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl,

or R(1) and R(2) denote, together alkylenes chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms

one of CH2group alkalinous chain may be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(10)-;

R(10) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(3) denotes R(12)-CaH2a[NR(13)]m-;

R(12) denotes hydrogen or cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, CF3C2F5or3F7;

and zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

m is zero or 1;

R(13) denotes hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(12) or R(13) denote together alkylenes group 4, 5, 6, 7 or 8 C-atoms

one of CH2group alkalinous group may be replaced by-O-, -[SOzero, 1 or 2]-, -CO - or-NR(10)-;

R(10) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(4) denotes R(14)-CrH2r;

r is ohms, piperidyl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CF3C2F5WITH3F7, pyridyl, thienyl, imidazolyl or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl, methylsulfonyl and methylsulfonylamino,

one of CH2-group grouprH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -CO-NR(11)-, -[SOzero, 1 or 2]- or-NR(11)-;

R(11) denotes hydrogen or -(CandH2A)-R(10),

one of CH2-group groupandH2Amay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, NR(10) -, or-CONR(10)-,

R(10) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms

or R(3) and R(4) together represent alkylenes chain with 3, 4, 5, 6, 7 or 8 C-atoms, one of CH2group alkalinous chain may be replaced by-O-, -[SOzero, 1 or 2]-, -CO - or-NR(11)-;

R(11) denotes hydrogen or - (CaH2a) -R(10),

one of CH2group group CaH2amay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, NR(10) -, or-CONR(10)-;

R(10) denotes hydrogen 2">-CR(15)=N-CR(17)=N-

-CR(15)=N-N=CR(17)-,

-N=CR(16)-CR(17)=N - or

-S-CR(15)=CR(16)-;

R(15) R(16) and R(17) denote independently from each other hydrogen, F, Cl, Br, I, alkyl with 1, 2, 3 or 4 C-atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, CN, CF3C2F5WITH3F7N3, NO2, -CONR(19)R(21), -COOR(21), R(22) -CsH2s-Z -, or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl;

R(19) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(21) denotes hydrogen, methyl, ethyl, phenyl or-CuH2u-NR(19)R(20),

and phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl;

R(20) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

u is 2 or 3;

R(22) denotes hydrogen, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -COOR(21), CONR(19)R(21), thienyl, imidazolyl, pyridyl, hinely, ethanolic, piperidyl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CF3C2F5C3F7or phenyl,

which is unsubstituted or substituted by 1 or 2 mixing Hanila;

s - zero, 1, 2, 3, 4, 5 or 6;

Z represents-S(O)zero, 1 or 2]-, -CO-, -SO(zero, 1 or 2)-NR(11)-, -SO2-O-, -O-, -NR(11)- or -[CO-NR(11)]-;

R(7) denotes hydrogen, a hydroxy-group, alkoxygroup with 1, 2, 3 or 4 C-atoms, alloctype with 1, 2, 3 or 4 C-atoms, Cl, Br, F, alkyl with 1, 2, 3 or 4 C-atoms;

R(8) denotes hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

and their physiologically acceptable salts;

7) HMR 97/L223 EP-OS 905131

The compounds of formula I

where R(1) and R(2) denote independently from each other hydrogen, CF3C2F5WITH3F7, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino,

or R(1) and R(2) denote, together alkylenes chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms;

R(3) denotes R(10)-CnH2n-NR(11) - or R(10)-CnH2n-,

one of CH2-group b groups CnH2nmay be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(12a);

R(12a) denotes hydrogen, methyl or ethyl;

R(10)>

n - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

R(11) denotes hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(10) R(11) together represent a bond, when n is not less than 3;

R(4) denotes R(13) -CrH2r-Z-CqH2q-;

q is 0, 1,2,3,4,5, 6, 7 or 8;

r is 0, 1, 2, 3, 4, 5, 6, 7 or 8;

Z represents-CO-NR(14)-,

-OCO-NR(14)-,

-O-CxH2x-O-,

-O-CxH2x-NR(14)-,

-O-CxH2x-CO-O,

-CO-O-CxH2x-O -, or

-CO-O-CxH2x-NR(14)-,

and in each case it is possible to both directions of the connection;

x is 2,3 or 4;

R(14) denotes hydrogen, alkyl with 1, 2 or 3 C-atoms, -CyH2y-OR(12b), -CyH2y-NR(12b)2;

R(12b) denotes hydrogen, methyl or ethyl;

y is 2 or 3;

R(13) denotes N, CF3C2F5C3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -NR(15)R(16), -CONR(15)R(16), -C(=NR(17))NR(15)R(16) is OR(17), -COOR(17), phenyl, or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms,

and phenyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, Dimity oznachaet independently from each other hydrogen, alkyl with 1, 2, 3 or 4 C-atoms or-CzH2z-phenyl,

and phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, CF3, NO2CN, HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl, aminosulfonyl and methylsulfonylamino,

or R(15) R(16) together represent a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

R(17) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(5), R(6) R(7) and R(8) denote independently from each other 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, -CF3, -C2F5, -C3F7, -N3, -NO2, -Y-CsH2s-R(18) or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

Y represents-O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, -SO2-O-, -SO2NR(10c)-, NR(10c) -, or-CONR(10c)-;

R(10c) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

moreover, pyridyl, thienyl, imidazolyl, hinely, ethanolic and phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(21) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(9) denotes hydrogen, OR(10d) or OCOR(10d);

R(10d) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

In denotes hydrogen

or R(9) and together represent a bond,

and their physiologically acceptable salts;

8) HMR 97/L224-EP-OS 906911

The compounds of formula I

where R(1) and R(2) denote independently from each other hydrogen, CF3WITH2F5C3F7, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino R(10)-CnH2n-NR(11)- or R(10)-CnH2n-,

one of CH2-group groupnH2nmay be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(12a);

R(12a) denotes hydrogen, methyl or ethyl;

R(10) denotes hydrogen, methyl, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, CF3C2F5or3F7;

n - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

R(11) denotes hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(10) R(11) together represent a bond, when n is not less than 3,

or R(3) together with R(4) denote alkylenes chain with 3, 4, 5, 6, 7 or 8 C-atoms

one of CH2group alkalinous chain may be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(12a);

R(12a) denotes hydrogen, methyl or ethyl;

R(4) denotes R(13)-CrH2r,

one of CH2group group CrH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, -NR(14) -, or-CONR(14)-;

R(14) denotes hydrogen, alkyl with 1, 2 or 3 C-atoms, -CyH2y-OR(12b), -CyH2y-NR(12b)2;

R(12b) denotes hydrogen, methyl or ethyl;

y is 2 or 3;

R(13) denotes N, CF3C2F5WITH3F7, cycloalkane,

and phenyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(15) R(16) denote independently from each other hydrogen or alkyl with 1, 2, 3 or 4 C-atoms

or R(15) R(16) together represent a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

R(17) denotes hydrogen, alkyl with 1, 2 or 3 C-atoms, - CxH2xOR(12c);

R(12c) denotes hydrogen, methyl or ethyl;

x is 2 or 3;

r - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;

at least one of the substituents R(5), R(6) R(7) and R(8) denote-Y-CsH2s-R(18), thienyl, furyl or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C-atoms

thienyl, furyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, methylaminopropyl, dimethylaminopropyl, etilenovomu, diethylaminopropyl, sulfato the UB>-O-, -SO2NR(12d)-, -NR(12d) -, or-CONR(12d)-,

moreover, the accession to the benzene nucleus of each time going through the atom, standing left;

R(12d) denotes hydrogen, methyl or ethyl;

s is 1, 2, 3, 4, 5 or 6;

R(18) denotes a substituted phenyl which contains one or two substituent selected from the group consisting of NO2, CN, NH2N (methyl)2HE, ethyl, -COOH, -Sometime - Couetil, -CONH2, -CON(methyl)2,

or R(18) denotes a substituted N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, which contains one or 2 substituent selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino,

or R(18) denotes-OR(19), -SO2R(19), -NR(19)R(20), -CONR(19)R(20);

R(19) R(20) denote independently of each other CtH2t-R(21);

t - zero, 1, 2, 3, 4, 5 or 6;

R(21) denotes hydrogen, CF3C2F5WITH3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, NR(22)R(23), -OR(24), phenyl, thienyl or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C-atoms

and phenyl, thienyl and N-containing heterocycle unsubstituted or substituted 1 Il is, is lexigraphy, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(22) R(23) denote independently from each other hydrogen, alkyl with 1, 2 or 3 C-atoms

or R(22) R(23) together represent a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

R(24) denotes hydrogen, alkyl with 1, 2 or 3 C-atoms;

and any of the substituents R(5), R(6) R(7) and R(8) that have not yet been stated previously, independently from each other 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, CF3, NO2, OR(12e) or NR(12e)R(12f);

R(12e) and R(12f) denote independently from each other hydrogen or alkyl with 1, 2, 3 or 4 C-atoms;

R(9) denotes hydrogen, OR(12g) or OCOR(12g);

R(12g) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

In denotes hydrogen

or R(9) and together represent a bond,

and their physiologically acceptable salts;

9) HMR 97/L232-EP 913396

The compounds of formula I

where R(5) is in one of these 5, 6, 7, and 8 positions and where R(1) and R(2) denote independently from each other hydrogen, CF3C2F5WITH3F7, alkyl with 1, 2, 3, 4, 5 �standing from F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino,

or R(1) and R(2) denote, together alkylenes chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms;

R(3) denotes R(10) -CnH2n-NR (11) - or R(10) -CnH2n-,

one of CH2-group Huppah CnH2nmay be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(12a);

R(12a) denotes hydrogen, methyl or ethyl;

R(10) denotes hydrogen, methyl, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, CF3C2F5or3F7;

n - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

R(11) denotes hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(10) R(11) together represent a bond, when n is not less than 3,

or R(3) together with R(4) denote alkylenes chain with 3, 4, 5, 6, 7 or 8 C-atoms

one CH2group alkalinous chain may be

replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(12a);

R(12a) denotes hydrogen, methyl or ethyl;

R(4) denotes R(13)-CrH2r,

one of CH2-group grouprH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2- orfrom> C2F5C3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, NR(15)R(16), phenyl, or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C-atoms

and phenyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(15) R(16) together represent a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(methyl) -, or-N(benzyl)-;

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) denotes a-Y-CsH2s-R(18) or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

Y represents-O-, -S - or-NR(10c)-;

R(10c) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

s is 1, 2, 3, 4, 5, 6, 7 or 8;

R(18) denotes hydrogen, CF3WITH2F5WITH3H7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -COOR(21), NR(15a)R(1i thienyl unsubstituted or substituted by 1 or 2 substituents, selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(15a) and R(16a) together represent a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(methyl) -, or-N(benzyl)-;

R(21) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(6) denotes OR(10d) or OCOR(10d);

R(10d) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

In denotes hydrogen

or R(6) and together represent a bond,

and their physiologically acceptable salts;

10) HMR 97/L235-EP 915087

The compounds of formula I

where R(1) and R(2) denote independently from each other hydrogen, CF3, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(2) and R(9) together represent a bond,

or R(2) denotes-OR(10a), if X is-CR(22)R(23);

R(10a) represents hydrogen, acetyl or alkyl with 1, 2 or 3 C-atoms;

R(3) denotes R(10b)-CnH2n-NR(11) - or R(10b) -CnH2n-,

one of CH2-group groupnH2nmay be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(12a);

R(12a) denotes hydrogen, methyl or ethyl;

R(10b) denotes methyl, Tsiklauri 10;

R(11) denotes hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(10b) and R(11) together represent a bond, if n is greater than 2,

or R(3) together with R(4) denotes alkylenes chain with 3, 4, 5, 6, 7 or 8 C-atoms

one CH2group alkalinous chain may be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(12a);

R(12a) denotes hydrogen, methyl or ethyl;

R(4) denotes R(13)-CrH2r,

one of CH2-group grouprH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, -NR(14) -, or-CONR(14)-;

R(14) denotes hydrogen, alkyl with 1, 2 or 3 C-atoms, -CyH2y-OR(12b), CyH2y-NR(12b) 2;

R(12b) denotes hydrogen, methyl or ethyl;

y is 2 or 3;

R(13) denotes CH3, CF3C2F5C3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -NR(15)R(16), -CONR(15)R(16) is OR(17), -COOR(17), phenyl, or N-containing heterocycle c 1, 2, 3, 4, 5, 6, 7, 8 or 9 C-atoms

and phenyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and ptx2">or R(15) R(16) together represent a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

R(17) denotes hydrogen, alkyl with 1, 2 or 3 C-atoms, -CzH2zOR(12c);

R(12c) denotes hydrogen, methyl or ethyl;

z is 2 or 3;

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), R(6) R(7) and R(8) denote independently from each other 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, -CF3- 2F5- 3F7, -N3, -NO2, -Y-CsH2s-R(18), phenyl, thienyl, furyl or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C-atoms

and phenyl, thienyl, furyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

Y represents-O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, -O-SO2-, -SO2NR(10c) -, or-CONR(10c)-,

moreover, the accession to the basic skeleton each time going through the atom, standing left;

R(10c) denotes hydrogen Il 2F5WITH3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, OR(21), -COOR(21), -NR(15a)R(16a), -CONR(15a)R(16a), phenyl, or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C-atoms

and phenyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(15a) and R(16a) denote independently from each other hydrogen or alkyl with 1, 2, 3 or 4 C-atoms

or R(15a) and R(16a) together represent a chain of 4 or 5 methylene groups, of

which one CH2group can be replaced by-O-,

-S-, -NH-, -N(CH3)- or-N(benzyl)-;

R(21) denotes hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(9) denotes hydrogen or together with R(2) communication;

X represents-CR(22)R(23)-, -O-, -NR(24)-, -S-, -SO-, -SO2-;

R(22) R(23) denote independently from each other hydrogen, CF3, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms;

R(24) denotes hydrogen, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, m is CLASS="ptx2">and their physiologically acceptable salts;

11) WO 96 05827, WO 96 40146, WO 96 05839, WO 95 14671, WO 97 49690, WO 95 14676, WO 95 14695, WO 95 14471, WO 98 00406, WO 97 48686, US 5633251, WO 96 40653.

Compounds of the formula

where And denotes thienyl, pyridyl, phenyl, unsubstituted or

substituted;

X denotes O, S,=N-NH2,=N-OH, H2;

Y denotes O, NCN, N2;

Z denotes a linear or branched alkyl, alkenyl, unsubstituted or substituted phenyl, cycloalkyl,

moreover, one or more CH2-groups may be replaced by O, S, NH or a bond;

R1 denotes phenyl, unsubstituted or substituted, alkyl or cycloalkyl, mono - or bicyclic a heterocycle, indanyl;

R2 denotes phenyl, unsubstituted or substituted alkyl, cycloalkyl, 2 - or 3-furyl, N-mono - or bis-alkyl;

R3 denotes H, alkyl, unsubstituted or substituted N(CH3)2HE or foralkyl;

R4 denotes H, alkyl which may be interrupted by one or two oxygen atoms;

or their pharmaceutically acceptable salts;

12) WO 95 14694, WO 95 14472

Compounds of the formula

where And denotes 2 - or 3-membered chain which consists of C-atoms, but in which can be one noticeably linear or branched alkyl or alkenyl, which is unsubstituted or substituted by phenyl, cycloalkyl and in which one or more CH2-groups may be replaced by O, S, NH or a bond, or N-alkyl or N-phenyl;

R1 denotes phenyl, unsubstituted or substituted, alkyl or cycloalkyl, mono - or bicyclic a heterocycle;

R2 denotes phenyl, unsubstituted or substituted;

or R2 denotes alkyl, cycloalkyl, 2 - or 3-furyl, N-mono - or bis-alkyl,

or its pharmaceutically acceptable salt;

13) WO 95 14473

Compounds of the formula

where R1 denotes phenyl, unsubstituted or substituted,

or R1 denotes alkyl or cycloalkyl, mono - or bicyclic a heterocycle, indanyl;

R2 and R3 represent independently from each other alkyl, which is unsubstituted or

substituted by phenyl,

or R2 and R3 denote cycloalkyl,

or R2 and R3 together represent Azazel;

R4 denotes alkyl, unsubstituted or substituted phenyl,

or R4 denotes phenyl or foralkyl;

R5 denotes H or alkyl,

or their pharmaceutically acceptable salts;

14) WO 96 40655, WO 96 40656, WO 96 40653, WO 96 40654

Compounds of the formula

where X is Oh or H2;

R1 denotes alkyl, t is ptx2">or Z denotes alkenyl, cycloalkyl, cycloalkenyl or connection;

R2 denotes phenyl, unsubstituted or substituted,

or R2 denotes cycloalkyl, unsubstituted or substituted;

R3 represents alkyl, cycloalkyl, foralkyl or oxazolidinyl alkyl,

or their pharmaceutically acceptable salts;

15) WO 93 04061

Compounds of the formula

where X denotes a saturated or unsaturated 5-, 6 - or 7-Chennai a heterocycle or carbocycle;

R - link, heteroatom, carbonyl, heterocyclic ring, carbocyclic ring, alkyl, alkenyl, alkoxygroup, alkylamino, arylalkyl, alloctype, acyl, alloctype or aceraminophen;

Y is substituted or unsubstituted, saturated or unsaturated 5-, 6 or 7-membered heterocyclic or carbocyclic ring or link;

R1, R2 and R3 independently of each other Cl, F, Br, NH2, CF3HE SO3N, CH3SO2NH, COOH, alkoxygroup, alkyl, alkoxycarbonyl, hydroxyalkyl, carboxyethyl, aminoalkyl, aceraminophen or alloctype;

L means alkylamino, alkynylamino, alkylamino, alkynylamino or allmenalp,

in which the nitrogen is linked to the nitrogen l or heteroalkyl;

And substituted or unsubstituted, saturated or unsaturated alkyl or heteroalkyl or substituted or unsubstituted 5-, 6 - or 7-membered heterocycle;

R5 is alkyl;

or their pharmaceutically acceptable salts;

16) WO 9837068

Compounds of the formula

where X denotes O, S, NH, NR, C-CN, N-OR, N-NO2;

Y is a bond, -C=C - or NH;

R1 is alkyl, alkenyl, quinil, aryl, cycloalkyl, heterocycle, or (heterocycle)alkyl;

R2 is aryl or heterocycle;

or their pharmaceutically acceptable salts;

17) WO 9514695

Compounds of the formula

where R1 represents halogen, alkyl, alkenyl, quinil, cycloalkyl, aryl, (aryl)alkenyl, alkoxygroup, O-alkenyl, O-aryl, O-alkyl, (heterocycle), COO-alkyl, alkanoyl, WITH the amino group, substituted by an amino group, alkyl-CO-amino group, the alkyl substituted amino group, NHCO-alkyl, NHCO-aryl, NHCO-alkyl, (heterocycle), N(alkyl)CO-alkyl, N(alkyl)-aryl, N(alkyl)-heterocycle, N-(alkyl)CO-alkyl, (heterocycle);

R2 is hydrogen, alkyl, halogen, aryl, alkoxygroup, amino group, substituted amino group;

R3 means oxoprop, the hydroxy-group, alkoxygroup, O-CO-alkyl, O-CO-aryl, O-CO-heterocycle, NOH, NO-alkyl, N-amino group, N-substituted an amino group, N-NHCONH-alkyl, heterocycle;

R4 is hydrogen, alkyl, alkyl(CO-alkyl), alkyl(COO-alkyl)

or R3 and R4 together with the atom to which they are bound, a 5 - to 7-membered ring which can contain up to three heteroatoms O, N or S;

R5 is hydrogen, alkyl, alkenyl, alkyl, (heterocycle) alkyl-NHCO(alkyl), alkyl-NHCO(aryl), alkyl-NHCO(alkylglycerols);

n is 0, 1 or 2,

or their pharmaceutically acceptable salts.

Preferred compounds are described in the following publications.

1) EP 807629 (NOAH 96/F119)

Romany formula I

where R(1) and R(2) denote independently from each other hydrogen, CpF2p+1, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl, methylsulfonylamino and methylsulfonyl;

p is 1, 2 or 3,

or R(1) and R(2) denote, together alkylenes chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms;

R(3) denotes R(9)-CnH2n[NR(11)]m-;

R(9) is hydrogen or cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms;

n - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

m is zero or 1;

R(11) is hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(11) together with R(9) - alkit to be replaced by-O-, -SOqor-NR(10);

q is zero, 1 or 2;

R(10) is hydrogen, methyl or ethyl;

R(4) denotes R(12)-CrH2r;

R(12) denotes hydrogen, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, piperidyl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CpF2p+1, pyridyl, thienyl, imidazolyl or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl, methylsulfonyl and methylsulfonylamino;

r is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20,

one of CH2group group CrH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -SOq- or-NR(10)-;

q is zero, 1 or 2;

R(10) is hydrogen, methyl or ethyl;

R(5), R(6) R(7) and R(8) independently from each other hydrogen, F, Cl, Br, I, alkyl with 1, 2, 3 or 4 C-atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -CN, -CF3, -C2F5- 3F7, -N3, -NO2, -CONR(13)R(14), - COOR(15), R(16)-CsH2s-Y -, or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl;

R(13) and R(14) - independently researched>H2u-NR(13)R(14);

u is 2 or 3;

R(16) is hydrogen, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, - COOR(15), thienyl, imidazolyl, pyridyl, hinely, ethanolic, piperidyl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CtF2t+1or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl or methylsulfonyl;

s - zero, 1, 2, 3, 4, 5 or 6;

t = 1, 2, or 3;

Y denotes SOq, -CO-, -SO2-NR(10)-, -O-, -NR(10)- or-CO-NR(10),

moreover, however, R(6) cannot be F3or-OC2F5,

and their physiologically acceptable salts;

2)EP 847996 (NOAH 96/F341)

The compounds of formula I

where X represents-O-, -S-, -SO-, -SO2-, NR(7)-, -CR(8a)R(8b)- or-CO-;

R(7) is hydrogen or -(CaH2a)-R(9),

one of CH2-group groupandH2Amay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, NR(10)- or-CONR(10)-;

R(10) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

and zero, 1, 2, 3, 4, 5, 6, 7 or 8;

R(9) is hydrogen, CF3C2F5C3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, dimethylaminopropyl, diethylaminopropyl is 2">moreover, pyridyl, thienyl, imidazolyl and phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino,

or R(7) and R(1) - together connection;

R(8a) is hydrogen, CF3C2F5WITH3F7, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(8b) is hydrogen, alkyl with 1, 2 or 3 C-atoms, OR(10), -COOR(10), CO-R(10);

R(10) is hydrogen or alkyl with 1, 2 or 3 C-atoms

or the remainder R(8a) or R(8b) together with R(1) - connection, if Y has the value of N;

Y is N or CR(11);

R(11) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(1) and R(2) independently from each other hydrogen, CF3C2F5C3F7, F, Cl, methoxy group, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or

phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, CL, Br, I, CF3 is and methylsulfonylamino,

or R(1) and R(2) - together Allenova chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms;

R(3) denotes R(12)-CnH2n-NR(13) R(12)-CnH2n-,

and CH2-group b groups CnH2nmay be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(10a)-;

R(10a) is hydrogen, methyl or ethyl;

R(12) is hydrogen, methyl, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, CF3C2F5or3F7;

n - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

R(13) is hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(12) R(13) - together relationship, if n is not less than 3,

or R(3) and R(4) together Allenova chain with 3, 4, 5, 6, 7 or 8 C-atoms, and one CH2group alkalinous chain may be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(10a)-;

R(10a) is hydrogen, methyl or ethyl;

R(4) denotes R(14)-CrH2r,

one of CH2group group CrH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, -NR(10b) -, or-CONR(10b)-;

R(10b) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(14) - methyl, CF3C2F5WITH3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -OH, -COOH, -NR(23)R(24), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, teenbestiality, selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(23) R(24) - independently from each other hydrogen or alkyl with 1, 2 or 3 C-atoms

or R(23) R(24) along a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

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) R(6) - together 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)-,

with both directions of the connection;

R(15) R(16) R(17) R(18) - independently from each other 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, -CF3, -C2F5- 3F7, -N3, -NO2, -Z-CsH2s-R(22), thienyl or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and ptx2">R(10c) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

s - zero, 1, 2, 3, 4, 5 or 6;

R(22) - hydrogen, CF3C2F5WITH3F7cycloalkyl 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, hinely, ethanolic or phenyl,

moreover, pyridyl, thienyl, imidazolyl, hinely, ethanolic and phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(19) R(20) independently from each other hydrogen or alkyl with 1, 2 or 3 C-atoms

or R(19) R(20) along a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

R(21) is hydrogen or alkyl with 1, 2 or 3 C-atoms

moreover, however, cannot be simultaneously Y is CR(11) and X is equal to O

and their physiologically acceptable salts;

3) EP 857724 (NOAH 97/F 024)

The compounds of formula I

where X is -[S(O)zero, 1 or 2]-, NR(9)-, - [CR (9) R(23)]- or-CO-;

R(9) is hydrogen or - (CnHl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CF3C2F5or3F7,

one of CH2group group CnH2nmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -[SOzero, 1 or 2]- or-NR(11)-;

R(11) is hydrogen, methyl or ethyl,

or R(10) - pyridyl, thienyl, imidazolyl or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl, methylsulfonyl and methylsulfonylamino,

or R(9) together with R(1) - connection;

R(23) is hydrogen, alkyl with 1, 2 or 3 C-atoms, HE, O-alkyl with 1, 2 or 3 C-atoms, COOH, COO-alkyl with 1, 2 or 3 C-atoms or-CO-R(24);

R(24) is hydrogen, methyl or ethyl;

R(1) and R(2) independently from each other hydrogen, CF3C2F5WITH3F7, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl,

or R(1) and R(2) - together Allenova chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms;

R(3) denotes R(12)-CaH2a[NR(13)]m-;

R(12) is hydrogen or CICL, 9 or 10;

m is zero or 1;

R(13) is hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(12) R(13) together Allenova group 4, 5, 6, 7 or 8 C-atoms

one of CH2group alkalinous group may be replaced by-O-, -[SOzero, 1 or 2]-, -CO - or - NR(11)-;

R(11) is hydrogen, methyl or ethyl;

R(4) denotes R(14)-CrH2r;

r is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;

R(14) is hydrogen, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, piperidyl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CF3C2F5WITH3F7, pyridyl, thienyl, imidazolyl or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl, methylsulfonyl and methylsulfonylamino,

one of CH2group group CrH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-,

-CO-NR(11)-, -[SOzero, 1 or 2]- or-NR(11)-,

or R(3) and R(4) together Allenova chain with 3, 4, 5, 6, 7 or 8 C-atoms, one of CH2group alkalinous chain may be replaced by-O-, -[SOzero, 1 or 2]-, -CO - or-NR(11)-;

R(5) R(6) - together-CR(15)=CR(16)-CR(17)=CR(18), separately from each other hydrogen, F, Cl, Br, I, alkyl with 1, 2, 3 or 4 C-atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, CN, CF3C2F5WITH3F7N3, NO2, -CONR(19)R(20), -COOR(21), R (22)-CsH2s-Z -, or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl;

R(19) R(20) independently from each other hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(21) is hydrogen, methyl, ethyl, phenyl or-CuH2u-NR(19)R(20);

u is 2 or 3;

and phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl or methylsulfonyl;

R(22) - hydrogen, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -COOR(21), thienyl, imidazolyl, pyridyl, hinely, ethanolic, piperidyl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CF3C2F5WITH3F7or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl or methylsulfanyl;

s - zero, 1, 2, 3, 4, 5 or 6;

Z represents-S(O)zero, 1 or 2]-, -CO-, -SO2-, celoxica with 1, 2, 3 or 4 C-atoms, CL, Br, F, alkyl with 1, 2, 3 or 4 C-atoms;

R(8) is hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

and their physiologically acceptable salts;

4) EP 860440 (NOAH 97/F033)

Derivatives chromane formula I

where R(1) and R(2) denote independently from each other hydrogen, CF3C2F5C3F7, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl,

or R(1) and R(2) - together Allenova chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms;

R(A) is a hydroxy - group, alkanoyloxy with 1, 2, 3, 4, 5 or 6 C-atoms or alkylsulfonates with 1, 2, 3, 4, 5 or 6 C-atoms;

R(B) is hydrogen or R(A) and R(B) - together connection;

R(3) denotes R(9)-CnH2n[NR(11)]m-;

R(9) is hydrogen or cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms;

n - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

m is zero or 1;

R(11) is hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(11) and R(9) - together Allenova group 1, 2, 3, 4, 5, 6, 7 or 8 C-atoms

one of CH2-group groupnH2ncan be replaced>The2r;

R(12) is hydrogen, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, piperidyl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CF3C2F5C3F7, pyridyl, thienyl, imidazolyl or phenyl,

moreover, pyridyl, thienyl, imidazolyl or phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl, methylsulfonyl and methylsulfonylamino;

r - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20,

one of CH2-group grouprH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -SOzero, 1 or 2- or-NR(10)-;

R(5), R(6) R(7) and R(8) independently from each other hydrogen, F, Cl, Br, I, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -CN, -CF3, -C2F5- 3F7, -N3, -NO2, -CONR(13)R(14), -COOR(15), R (16) -CsH2s-Y -, or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl;

R(13) and R(14) - independently from each other hydrogen or alkyl with 1, 2

or 3 C-atoms;

R(15) is hydrogen, methyl, ethyl, what Mami, -COOR(15), thienyl, imidazolyl, pyridyl, hinely, ethanolic, piperidyl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CF3C2F5WITH3F7or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl;

s - zero, 1, 2, 3, 4, 5 or 6;

Y represents-S-, -SO-, -SO2, -CO-, -SO2-NR(10)-, -O-, -NR(10)- or-CO-NR(10),

however, provided that two of substituents R(5), R(6) R(7) and R(8) are not hydrogens,

and their physiologically acceptable salts;

5) EP 861836 (NOAH 97/F038)

The compounds of formula I

where X1 represents-O-, -S-, -SO-, -SO2-, -CR(1)R(2)-, -NR(6)-, -CO -, or - CR(1)R(7)-;

R(1) and R(2) independently from each other hydrogen, CF3C2F5WITH3F7, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino,

or R(1) and R(2) - together Allenova chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms;

R(6) vadney on-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, -NR(9) -, or-CONR(9)-;

R(9) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

n - zero, 1, 2, 3, 4, 5, 6, 7 or 8;

R(8) is hydrogen, CF3C2F5C3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, dimethylaminopropyl, diethylaminopropyl, 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl or phenyl,

moreover, pyridyl, thienyl, imidazolyl and phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

X2 represents-CR(1)R(2)- or-CR(2)R(10)-

or x2 if X3 and X1 mean-CR(1)R(2), also denotes-O-, -S-, -SO-, -SO2- or-NR(6)-,

at the same time balances R(1), R(2) and R(6) have the meanings specified for X1, but regardless of the values of the residues in X1;

R(10) together with R(7) - connection;

X3 represents-CR(1)R(2)-

or X3, if x2 and X4 mean-CR(1) R(2),- O-, -S-, -SO-, -SO2- or-NR(6)-,

at the same time balances R(1), R(2) and R(6) have the meanings specified for X1, but regardless of the values of the residues in X1;

X4 represents-CR(1)R(2)-, -NR(6)-, -NR(ll)-, -CH(OR(30))- or - C is in X1;

R(30) is hydrogen, alkyl with 1, 2 or 3 C-atoms or acyl of 1, 2, 3 or 4 C-atoms;

R(11) together with R(5) - connection;

Y1, Y2, Y3 and Y4 is independently from each other-CR(12)- or N

with a maximum of 2 groups Y1, Y2, Y3 and Y4 are simultaneously mean N;

the residues R(12) independently from each other 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, CF3C2F5WITH3F7N3, NO2, -Z-CmH2m- R(13) or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

Z represents-O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, -SO2NR(14)-, -NR(14) -, or-CONR(14)-;

R(14) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

m - zero, 1, 2, 3, 4, 5 or 6;

R(13) is hydrogen, CF3C2F5C3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -NR(15)R(16), -CONR(15)R(16), -OR(30a), phenyl, thienyl or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C-atoms

and phenyl, thienyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of methylsulfonyl and methylsulfonylamino;

R(15) R(16) - independently from each other hydrogen or alkyl with 1, 2 or 3 C-atoms

or R(15) R(16) along a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

R(30a) is hydrogen, alkyl with 1, 2 or 3 C-atoms or acyl of 1, 2, 3 or 4 C-atoms

or Y1 and Y2 together the S atom and each of Y3 and Y4-CR(12)-;

the residues R(12) independently from each other, as defined in Y1, Y2, Y3, Y4;

R(3) denotes R(17) -CxH2x-NR(18) R(17)-CxH2x-,

one of CH2-groupxH2-groups may be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(19)-;

R(19) is hydrogen, methyl or ethyl;

R(17) is hydrogen, methyl, ethyl, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, CF3C2F5or3F7;

x - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

R(18) is hydrogen or alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C-atoms

or R(18) and R(17) - together relationship, if x is not less than 3,

or R(3) - phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino is the SCP alkalinous chain may be replaced by-O-, -CO-, -S-, -SO - or-SO2-;

R(4) means-CrH2r-R(20),

one of CH2-group grouprH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, -NR(21) -, or-CONR(21)-;

R(21) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

r - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;

R(20) is hydrogen, methyl, CF3C2F5WITH3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -NR(22)R(23), phenyl, thienyl or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C-atoms

and phenyl, thienyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(22) R(23) - independently from each other hydrogen or alkyl with 1, 2 or 3 C-atoms

or R(22) R(23) along a chain of 4 or 5 methylene groups,

in which one CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

R(5) is hydrogen or together with R(11) communications

in all their stereoisomeric forms and mixtures in any ratio, and their physiologically pianisimo from each other hydrogen, CF3C2F5C3F7, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl,

or R(1) and R(2) - together Allenova chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms

one of CH2group alkalinous chain may be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(10)-;

R(10) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(3) denotes R(12)-CaH2a[NR(13)]m-;

R(12) is hydrogen or cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, CF3C2F5or3F7;

and zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

m is zero or 1;

R(13) is hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(12) R(13) together Allenova group 4, 5, 6, 7 or 8 C-atoms

one of CH2group alkalinous group may be replaced by-O-, -[SOzero, 1 or 2]-, -CO - or-NR(10)-;

R(10) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(4) denotes R(14)-CrH2r;

r - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;

R(14) is hydrogen, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, piperidyl, 1-pyrrolidineethanol or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl, methylsulfonyl and methylsulfonylamino,

one of CH2-group grouprH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -CO-NR(11)-, -[SOzero, 1 or 2]- or-NR(11)-;

R(11) is hydrogen or -(CaH2a)-R(10),

one of CH2-group groupandH2Amay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, NR(10) -, or-CONR(10)-;

R(10) is hydrogen or alkyl with 1, 2 or 3 C-atoms

or R(3) and R(4) together Allenova chain with 3, 4, 5, 6, 7 or 8 C-atoms

one of CH2group alkalinous chain may be replaced by-O-, -[SOzero,1 or 2]-, -CO - or-NR(11)-;

R(11) is hydrogen or -(CandH2A)-R(10),

one of CH2-group groupandH2Amay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, NR(10) -, or-CONR(10)-;

R(10) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(5) R(6) - -CR(15)=CR(16)-CR(17)=N-

-CR(15)=CR(16)-N=CR(17)-,

-CR(15)=N-CR(17)=N-

-CR(15)=N-N=CR(17)-,

-N=CR(16)-CR(17)=N - or

-S-CR(15)=CR(16)-;

R(15) R(16) and R(17) - independently of the SUB>5WITH3F7N3, NO2, -CONR(19)R(21), -COOR(21), R (22)-CsH2s-Z -, or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl;

R(19) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(21) is hydrogen, methyl, ethyl, phenyl or-CuH2u-NR(19)R(20),

and phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl;

R(20) is hydrogen or alkyl with 1, 2 or 3 C - atoms;

u is 2 or 3;

R(22) - hydrogen, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -COOR(21), CONR(19)R(21), thienyl, imidazolyl, pyridyl, hinely, ethanolic, piperidyl, 1-pyrrolidinyl, N-morpholinopropan, N-methylpiperazine, CF3C2F5C3F7or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl and methylsulfonyl;

s - zero, 1, 2, 3, 4, 5 or 6;

Z represents-S(O)zero, 1 or 2]-, -CO-, -SO(zero, 1 or 2)-NR(11)-, -SO2-O-, -O-, -NR(11)- or -[CO-NR(11)]-;

R(7) is hydrogen, hydrox the Mami;

R(8) is hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

and their physiologically acceptable salts;

7) HMR 97/L223 EP-OS 905131

The compounds of formula I

where R(1) and R(2) denote independently from each other hydrogen, CF3C2F5C3F7, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino,

or R(1) and R(2) - together Allenova chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms;

R(3) denotes R(10)-CnH2n-NR(11) - or R(10) -CnH2n-,

one of CH2-group groupnH2nmay be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(12a);

R(12a) is hydrogen, methyl or ethyl;

R(10) is hydrogen, methyl, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, CF3C2F5or3F7;

n - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

R(11) is hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(10) R(11) - together relationship, if n is not less than 3;

R(4) denotes R(13) -CrH2r-Z-CqH2q-;

q R is -O-CxH2x-O-,

-O-CxH2x-NR(14)-,

-O-CxH2-CO-O

-CO-O-CxH2x-O -, or

-CO-O-CxH2x-NR(14)-,

and in each case it is possible to both directions of the connection;

x is 2, 3 or 4;

R(14) is hydrogen, alkyl with 1, 2 or 3 C-atoms, -CyH2y-OR(12b), -CyH2y-NR(12b);

R(12b) is hydrogen, methyl or ethyl;

y is 2 or 3;

R(13) N, CF3C2F5WITH3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -NR(15)R(16), -CONR(15)R(16), -C(=NR(17))NR(15)R(16) is OR(17), -COOR(17), phenyl, or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms,

and phenyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl, aminosulfonyl and methylsulfonylamino;

R(15) R(16) - independently from each other hydrogen, alkyl with 1, 2, 3 or 4 C-atoms or-CzH2z-phenyl,

and phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, CF3, NO2CN, HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, selfile 5 methylene groups, one of CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

R(17) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(5), R(6) R(7) and R(8) independently from each other 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, -CF3, -C2F5- 3F7, -N3, -NO2, -Y-CsH2s-R(18) or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

Y represents-O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2-, -SO2-O-, -SO2NR(10c)-, -NR(10c) -, or-CONR(10c)-;

R(10c) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

s - zero, 1, 2, 3, 4, 5 or 6;

R(18) is hydrogen, CF3C2F5C3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -COOR(21), 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl, 4-methylpiperazin-1-yl, pyridyl, thienyl, imidazolyl, hinely, ethanolic or phenyl,

moreover, pyridyl, thienyl, imidazolyl, hinely, ethanolic and phenyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CFR(21) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(9) is hydrogen OR(10d) or OCOR(10d);

R(10d) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

In - hydrogen

or R(9) and - together relationship,

and their physiologically acceptable salts;

8) HMR 97/L224-EP-OS 906911

The compounds of formula I

where R(1) and R(2) denote independently from each other hydrogen, CF3C2F5WITH3F7, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino,

or R(1) and R(2) - together Allenova chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms;

R(3) denotes R(10)-CnH2n-NR(11)- or R(10) -CnH2n-,

one of CH2-group groupnH2nmay be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(12a);

R(12a) is hydrogen, methyl or ethyl;

R(10) is hydrogen, methyl, cycloalkyl with 3, 4, 5, 6, 7, or 8

C-atoms, CF3C2F5or C3F7;

n - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

R(11) is hydrogen or alkyl with 1, 2 is the first chain 3, 4, 5, 6, 7 or 8 C-atoms

one of CH2group alkalinous chain may be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(12a);

R(12a) is hydrogen, methyl or ethyl;

R(4) denotes R(13)-CrH2r,

one of CH2-group grouprH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2, -NR(14) -, or-CONR(14)-;

R(14) is hydrogen, alkyl with 1, 2 or 3 C-atoms, -CyH2y-OR(12b), -CyH2y-NR(12b)2;

R(12b) is hydrogen, methyl or ethyl;

y is 2 or 3;

R(13) - N, CF3WITH2F5WITH3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -NR(15)R(16), -CONR(15)R(16) is OR(17), -COOR(17), phenyl, or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C-atoms

and phenyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(15) R(16) - independently from each other hydrogen or alkyl with 1, 2, 3 or 4 C-atoms

or R(15) R(16) along a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, R(12c) - hydrogen, methyl or ethyl;

x is 2 or 3;

r - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;

at least one of the substituents R(5), R(6) R(7) and R(8) denotes

-Y-CsH2s-R(18), thienyl, furyl or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C-atoms

thienyl, furyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, methylaminopropyl, dimethylaminopropyl, etilenovomu, diethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

Y represents-O-, -CO-, -O-CO-, -S-, -SO-, -SO2-, -SO2-O-, -SO2NR(12d)-, -NR(12d) -, or-CONR(12d)-,

moreover, the accession to the benzene nucleus of each time going through the atom, standing left;

R(12d) is hydrogen, methyl or ethyl;

s is 1, 2, 3, 4, 5 or 6;

R(18) substituted phenyl which contains one or two substituent selected from the group consisting of NO2, CN, NH2N(methyl)2HE, ethyl, -COOH, -COO-methyl, COO-ethyl, -CONH2, -CON(methyl)2,

or R(18) - substituted N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, which contains 1 and is lexigraphy, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino,

or R(18) denotes-OR(19), -SO2R(19), -NR(19)R(20), -CONR(19)R(20);

R(19) R(20) independently of each other CtH2t-R(21);

t - zero, 1, 2, 3, 4, 5 or 6;

R(21) is hydrogen, CF3C2F5WITH3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, NR(22)R(23), -OR(24), phenyl, thienyl or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C-atoms

and phenyl, thienyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(22) R(23) - independently from each other hydrogen, alkyl with 1, 2 or 3 C-atoms

or R(22) R(23) along a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

R(24) is hydrogen, alkyl with 1, 2 or 3 C-atoms

and any of the substituents R(5), R(6) R(7) and R(8), which have not yet fallen under the earlier definition data, independently from each other 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, CFR(9) is hydrogen OR(12g) or OCOR(12g);

R(12g) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

In - hydrogen

or R(9) and - together relationship,

and their physiologically acceptable salts;

9) HMR 97/L232-EP 913396

The compounds of formula I

where R(5) is in one of these 5, 6, 7 and 8 of the terms and

where R(1) and R(2) denote independently from each other hydrogen, CF3C2F5WITH3F7, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino,

or R(1) and R(2) - together Allenova chain with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C-atoms;

R(3) denotes R(10)-CnH2n-NR(11) - or R(10)-CnH2n-,

one CH2-group HuppahnH2nmay be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(12a);

R(12a) is hydrogen, methyl or ethyl;

R(10) is hydrogen, methyl, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, CF3C2F5or3F7;

n - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

R(11) is hydrogen or alkyl ANOVA chain with 3, 4, 5, 6, 7 or 8 C-atoms

one of CH2group alkalinous chain may be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(12a);

R(12a) is hydrogen, methyl or ethyl;

R(4) denotes R(13)-CrH2r,

one CH2group group CrH2rmay be replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO2or NR(14)-;

R(14) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(13) - CH3, CF3C2F5WITH3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, NR(15)R(16), phenyl, or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C-atoms

and phenyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(15) R(16) along a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(methyl)- or N(benzyl)-;

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) denotes a-Y-CsH2s-R(18) or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from GCI, sulfamoyl, methylsulfonyl and methylsulfonylamino;

Y represents-O-, -S - or-NR(10c)-;

R(10c) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

s is 1, 2, 3, 4, 5, 6, 7 or 8;

R(18) is hydrogen, CF3C2F5C3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -COOR(21), NR(15a)R(16a), unsubstituted N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, phenyl or thienyl,

moreover, the phenyl and thienyl unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, methyl, metoxygroup, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(15a) and R(16a) along a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(methyl)- or N(benzyl)-;

R(21) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(6) denotes OR(10d) or OCOR(10d);

R(10d) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

In - hydrogen;

or R(6) and link together,

and their physiologically acceptable salts, or

10. HMR 97/L235-EP 915087

The compounds of formula I

where R(1) and R(2) denote independently from each other hydrogen, CF3, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(2) and R(9) - together relationship,

and the mean R(10b) -CnH2n-NR(11)- or R(10b)-CnH2n-,

one of CH2-group b groups CnH2nmay be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(12a);

R(12a) is hydrogen, methyl or ethyl;

R(10b) - methyl, cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, CF3WITH2F5or3F7;

n - zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

R(11) is hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C-atoms

or R(10b) and R(11) - together relationship, if n is greater than 2,

or R(3) together with R(4) - Allenova chain with 3, 4, 5, 6, 7 or 8 C-atoms

one of CH2group alkalinous chain may be replaced by-O-, -CO-, -S-, -SO-, -SO2- or-NR(12a);

R(12a) is hydrogen, methyl or ethyl;

R(4) denotes R(13)-CrH2r,

one of CH2-group grouprH2rcan be

replaced by-O-, -CH=CH-, -SS-, -CO-, -CO-O-,

-O-CO-, -S-, -SO-, -SO2-, -NR(14) -, or-CONR (14)-;

R(14) is hydrogen, alkyl with 1, 2 or 3 C-atoms, -CyH2y-OR(12b), -CyH2y-NR(12b)2;

R(12b) is hydrogen, methyl or ethyl;

y is 2 or 3;

R(13) - CH3, CF3WITH2F5WITH3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, -NR(15)R(16), -CONR(15)R(16) is OR(17), -COOR(17), phenyl, or N-provided is shifted 1 or 2 substituents, selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(15) R(16) - independently from each other hydrogen or alkyl with 1, 2, 3 or 4 C-atoms

or R(15) R(16) along a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

R(17) is hydrogen, alkyl with 1, 2 or 3 C-atoms, -CzH2zOR(12c);

R(12c) is hydrogen, methyl or ethyl;

z is 2 or 3;

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), R(6) R(7) and R(8) independently from each other 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, -CF3, -C2F5- 3F7, -N3, -NO2, -Y-CsH2s-R(18), phenyl, thienyl, furyl or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C-atoms

and phenyl, thienyl, furyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino prisoedinenie to the main skeleton each time going through the atom, standing left;

R(10c) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

s - zero, 1, 2, 3, 4, 5 or 6;

R(18) is hydrogen, methyl, CF3C2F5WITH3F7cycloalkyl with 3, 4, 5, 6, 7 or 8 C-atoms, OR(21), -COOR(21), -NR(15a)R(16a), -CONR(15a)R(16a), phenyl, or N-containing heterocycle with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C-atoms

and phenyl and N-containing heterocycle unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF3, NO2, CN, NH2HE, methyl, ethyl, metoxygroup, dimethylaminopropyl, sulfamoyl, methylsulfonyl and methylsulfonylamino;

R(15a) and R(16a) - independently from each other hydrogen or alkyl with 1, 2, 3 or 4 C-atoms

or R(15a) and R(16a) along a chain of 4 or 5 methylene groups, of which one CH2group can be replaced by-O-, -S-, -NH-, -N(CH3)- or-N(benzyl)-;

R(21) is hydrogen or alkyl with 1, 2 or 3 C-atoms;

R(9) is hydrogen or together with R(2) communication;

X represents-CR(22)R(23)-, -O-, -NR(24)-, -S-, -SO-, -SO2-;

R(22) R(23) - independently from each other hydrogen, CF3, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms;

R(24) is hydrogen, alkyl with 1, 2, 3, 4, 5 or 6 C-atoms or phenyl,

which is unsubstituted or substituted by 1 or 2 substituents selected from the group which, is sulfamoyl, methylsulfonyl and methylsulfonylamino,

and their physiologically acceptable salts.

Unless otherwise stated, the alkyl and alkenyl denote a linear or branched (C1-C4)-alkyl or-alkenyl; alkoxygroup denotes a (C1-C4)-alkoxygroup; cycloalkyl indicates (WITH3-C8-cycloalkyl; aryl denotes a (C6-C12) -aryl; heteroaryl denotes furanyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolin, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazoles, hinely, ethanolic, phthalazine, honokalani, hintline and cinnoline; acyl denotes a (C1-C4)-CO or (C6-C12)-aryl -, or heteroaryl-WITH; galactography or halogen means F, Cl, Br; heterostropha has the values specified for heteroaryl, but also partially or completely gidrirovannah.

The present invention describes the use of a new class of biologically active substances - blockers lks-channels as therapeutic agents against pathogenic for humans and animals endo - and ectoparasites. The effects of these blockers is based on antihelminthic and EC thus lead to loss of function of the pharyngeal muscles, which is indispensable for the meal; this mechanism of action leads, finally, to death by starvation parasites. Blockers lks-channel active against pathogenic for humans and animals trematodes (Fasciola hepatica, Fasciolopsis buski, Fasciola gigantica, Fascioioides magna, Dicrocoelium dendriticum plerocercoids, Opisthorchis felineus, Clonorchis sinensis, Paragonimus westermanni, Paragonimus kellikotti, Schistosoma haematobium, Schistosoma japonicum, Schistosoma mansoni) and pathogenic for humans and animals nematodes that belong to the family Trichuridae, Trichinelidae, Strongyloididae, Ancylostomatidae, Strongylidae, Trichostrongylidae, Metastrongylidae, Oesophagostomatidae, Dictyocaulidae, Protostrongylidae, Angiostrongylidae, Oxyuridae, Ascaridae, Toxocaridae, Dracunculidae, Habronematidae and Filariidae; moreover, the range of actions blockers lks feeds also covers pathogenic for human and animal ectoparasites, which belong to the class Arachnida (family: Argasidae, Ixodidae, Dermanyssidae, Demodicidae, Sarcoptidae, Psoroptidae, Varroidae) and to the class of insects covering childbirth lice (Anoplura, Mallophaga), flies and fleas.

The active substance is applicable under conditions of good endurance plants and low toxicity for warm-blooded to combat pathogenic to plants, animals, pests, in particular insects, arachnids, nematodes and molluscs, especially preferred for controlling insects and arachnids, which are encountered in CE. is no active against normally sensitive and resistant species and all or individual stages of development. To the abovementioned pests include the following:

Detachment of ticks, for example, Acarus siro, Argas spp., Eriophyes ribis, Phyllocoptruta oleivora, Tarsonemus spp., Bryobia praetiosa, Panonychus spp., Tetranychus spp., Eotetranychus spp., Oligonychus spp., Eutetranychus spp.

Isopods of the genus, for example, Oniscus asselus, Armadium vulgare, Porcellio scaber.

From the order of, for example, Blaniulus guttulatus.

From troop Gubanova, for example, Geopnilus carpophagus, Scutigera spp.

From squad Simpel, for example, Scutigerella immaculata.

From a squadron of stinkwood, for example, Lepisma saccharina. Detachment of springtails, for example, Onychiurus armatus.

From the order Orthoptera, for example Blatta orientalis, Periplaneta americana, Leucophaea madeirae, Blatella germanica, Acheta domesticus, Gryllotalpa spp., Locusta migratoria migratorioides, Melanoplus differentialis, Schistocerca gregaria.

From a squadron of termites, for example, Reticulitermes spp.

Detachment of lice, for example, Phylloera vastatrix. Pemphigus spp., Pediculus humanus corporis, Haematopinus spp., Linognathus spp.

From a squadron of Phaedo, for example, Trichodectess pp., Damalinea spp.

From the order of Puzanova, for example, Hercinothrips femoralis, Thrips tabaci, Frankliniella spp.

From the order Heteroptera, for example Eurygaster spp., Dysdercus intermedius, Piesma quadrata, Cimex lectularius, Rhodnius prolixus, Triatoma spp.

From squad ranarridh, osiphum avenae, Myzus spp., Phorodon humuli, Rhopalosiphum padi, Empoasca spp., Euscelus bilobatus, Nephotettix cincticeps, Lecanium corni, Saissetia oleae, Laodelphax striatellus, Nilaparvata lugens, Aonidiella aurantii, Aspidiotus hederae, Pseudococcus spp., Psylla spp.

From the order Lepidoptera, for example, Pectinophora gossypiella, Bupalus piniarius, Cheimatobia brumata, Lithocolletis blancardella, Hyponomeuta padella, Plutella maculipennis, Malacosoma neustria, Euproctis chrysorrhoea, Lymantria spp., Bucculatrix thurberiella, Phyllocnistis citrella, Agrotis spp., Euxoa spp., Feltia spp., Earias insulana, Heliothis spp., Laphygma exigua, Mamestra brassicae, Panolis flammea, Prodenia litura, Spodoptera spp., Trichoplusia ni, Caprocapsa pomonella, Pieris spp., Chilo spp., Pyrausta nubilalis, Ephestia kuehniella, Galleria mellonella, Cacoecia podana, Capua reticulana, Choristoneura fumiferana, Clysia ambiguella, Homona magnanima, Tortrix viridana.

From the order Coleoptera, for example, Anobium punctatum, Rhizopertha dominica, Bruchidius obtectus, Acanthoscelides obtectus, Hylotrupes bajulus, Agelastica alni, Leptinotarsa decemlineata, Phaedon cochleariae, Diabrotica spp., Psylloides chrysocephala, Epilachna varivestis, Atomaria spp., Oryzaephilus surinamensis, Anthonumus spp., Sitophilus spp., Otiorrhynchus sulcatus, Cosmopolites sordidus, Ceuthorrynchus assimilis, Hypera postica, Dermestes spp., Trogoderma, Anthrenus spp., Attagenus spp., Lyctus spp., Meligethes aeneus, Ptinus spp., Niptus hololeucus, Gibbium psylloides, Tribolium spp., Tenebrio molitor, Agriotes spp., Conoderus spp., Melolontha melolontha, Amphimallon solstitialis, Costelytra zealandica, Lissorhoptus spp.

From the order Hymenoptera, for example Diprion spp., Hoplocampa spp., Lasius spp., Monomorium pharaonis, Vespa spp.

From the order Diptera, for example Aedes spp., Anopheles spp., Culex spp., Drosophila melanogaster, Musca spp., Fannia spp., Calliphora erythrocephala, Cuterebra spp., Hypobosca spp., Stomoxys spp., Oestrus spp., Tabanus spp., Tannia opsis, Ceratophyllus spp.

From the order of Arachnida, for example Scorpio maurus, Latrodectus mactans.

From the class of gastropods, e.g., Deroceras spp., Arion spp., Lymnaea spp., Galba spp., Succinea spp., Biomphalaria spp., Bulinus spp., Oncomelania spp.

Class shell-bearing mollusks, for example, Dreissena spp.

To parasitic plant nematodes, which according to the invention can be treated include, for example, parasitic on the roots of soil nematodes, such as the genus Meloidogyne (Wurzelgallennematoden as Meloidogyne incognita, Meloidogyne hapla and Meloidogyne javanica), Heterodera and Globodera (catabrosa nematodes, as Globodera rostochiensis, Globodera pallida, Heterodera trifolii) and the genera Radopholus (as Rhadopholus similis), Pratylenchus (as Pratylenchus neglectus, Pratylenchus penetrans and Pratylenchus curvitatus), Tylenchulus (as Tylenchulus semipenetrans), Tylenchorhynchus (as Tylenchorhynchus dubius and Tylenchorhynchus claytoni), Rotylenchus (as Rotylenchus robustus), Heliocotylenchus (as Haliocotylenchus multicinctus), Belonoaimus (as Belonoaimus longicaudatus), Longidorus (as Longidorus elongatus), Trichodorus (as Trichodorus primitivus) and Xiphinema (as Xiphinema index).

Next, using the proposed compounds are able to deal with genera of nematodes Ditylenchus (stem parasites, such as Ditylenchus dipsaci and Ditylenchus destructor), Aphelenchoides (leaf nematodes, such as Aphelenchoides ritzemabosi) and Anguina (flower nematodes, such as Anguina tritici).

The invention relates also to the means, in particular insecticidal, agarici is 2">The means according to the invention contain the active substances of the formula (I) is usually from 1 to 95 wt.%.

They can be formed in various ways, once agreed their biological and/or physicochemical parameters.

As possible ready preparative forms, we are primarily talking about powders for spraying (WP), emulsifiable concentrates (EC), aqueous solutions (BP), emulsions, spray solutions, dispersions on an oil or water-based (D), suspoemulsions (SE), powdered media (PS), stain the granules in the form of micro-sputtered, suction and adsorption granular materials, dispersible in water and granules (WG), ULV formulations, microcapsules, waxes or baits.

These individual types of songs in principle known and described, for example, in "Chemische Technologie", volume 7, C. Hauser publishing house Munich, 4. Aufl. 1986; van Falkenberg, "Pesticides Formulations", Marcel Dekker, N. Y., 2nd ed, 1972-1973; K. Martens, "Spray Drying Handbook", 3rd ed. 1979, G. Goodwin Ltd. London.

The tools needed for the finished preparative forms, such as inert materials, surfactants, solvents and other additives are also known and described, for example, in Watkins, "Handbook of Insecticide Dust Diluents and Carriers" 2-y ed., Darland Books, and Emulsifiers Annual", MC Publ. Corp., Ridgewood N. J.; Sisley and Wood, "Encyclopedia of Surface Active Agents", Chem. Publ. Co. Inc., N. Y. 1964; " ", Wiss. Verlagsgesell., Stuttgart 1967; Winnacker-, "Chemische Technologie", volume 7, C. Hausen Verlag, Munich, 4. Aufl. 1986.

On the basis of these compositions is also possible to get a combination with other pesticidal substances, fertilizers and/or plant growth regulators, for example, in the form of preparations or in the form of tank mixes. Sprayable powders are uniformly dispersible drugs, which along with the active substance contains in addition to a diluent or inert substance, also a binder, for example polyoxyethylene alkyl phenol, polyoxyethylene fatty alcohol, an alkyl - or algebrasolver, and a dispersant, such as sodium salt ligninsulfonate acid, sodium salt of 2,2'-dynafilter-6,6'-disulfonic acid.

Emulsifiable concentrates are obtained by dissolving the biologically active substance in an organic solvent, for example butanol, cyclohexanone, dimethylformamide, xylene or high-boiling aromatic compounds or hydrocarbons, with the addition of one or more emulsifiers. As emulsifiers can be, for example, used a calcium salt alkylarylsulfonates acid, such as dodecylbenzenesulphonate esters, simple polyglycolide ethers of fatty alcohols, condensation products of propylene oxide and ethylene oxide, simple alkalemia polyethers, esters of fatty acids with sorbitan esters of fatty acids with polyoxyethylenesorbitan or esters of polyoxyethylenesorbitan.

Pulverized funds obtained by grinding the active substance with finely powdered solid substances, for example talc, natural clays like kaolin, bentonite, pyrophyllites, or diatomaceous earth. The granules can be produced either by spraying the active substance capable of adsorption of granulated inert material or by applying a concentrate of the active substance with adhesive means, for example polyvinyl alcohol, sodium polyacrylate or mineral oils, to the surface of the media, such as sand, kaolinites or granulated inert material. Suitable active substances can also be granulated by the way, normal to obtain granular fertilizer, if desired in a mixture with fertilizers.

In sprayable powders the concentration of the active substance is usually about 10 to 90 wt.%, the remainder to 100% consists of the usual components of the finished formulation. In emulsifiable conc preparative form usually contains from 5 to 20 wt.% the active substance, spray solutions about 2 to 20 wt.%. In the case of granules, the active substance depends partly on whether the active compound is liquid or solid and which used excipients for granulation, fillers, etc.

In addition, these compositions active substances, if necessary, contain the usual means of improving adhesion, wetting agents, dispersing agents, emulsifiers, agents, improving penetration, solvents, fillers or carriers.

For the application presented in the standard form of concentrates, if necessary, diluted in the usual way, for example, in the case of sprayed powders, emulsifiable concentrates, dispersions and partly also of microgranules, water. Powdered and granular compositions, as well as the spray solution before use, usually no longer diluted with other inert substances.

Depending on external conditions such as temperature, humidity, etc. vary with the required standards of consumption. They can range, for example, between 0.0005 and 10.0 kg/ha or more of active substance, but preferably they are between 0.001 and 5 kg/ha

Biologically act is different from these compounds ready forms in mixtures with other active substances, such as insecticides, attractants, sterilizing, acaricides, nematicides, fungicides, plant growth regulators or herbicides.

The means of pest control include, for example, phosphoric esters, carbamates, esters of carboxylic acids, formamidines, tin compounds, substances produced by microorganisms, and others. Preferred components of the mixtures are the following:

1) from the group of phosphorus compounds

Arafat, azamethiphos, azinphos-ethyl, azinphosmethyl, bromophos, bromophos-ethyl, cadusafos (F-67825), chlorethoxyfos, Chlorfenvinphos, chlormephos, chlorpyrifos, chlorpyrifos-methyl, demeton, demeton-S-methyl, demeton-S-methylsulfone, dialifos, diazinon, dichlorvos, dicrotophos, dimethoate, disulfoton, EPN, ethion, ethoprophos, etrimfos, famphur, fenamiphos, fenitrothion, fensulfothion, fenthion, fonofos, formation, fosthiazate (ASC-66824), heptenophos, isazofos, isocial, isoxathion, Malathion, methacrifos, metamidophos, mitigation, salicion, mevinphos, monocrotophos, naled, omethoate, oxydemeton-methyl, parathion, parathion-methyl, pentat, Fort, fosalan, phosfolan, fastcars (BAS-301), phosmet, phosphamidon, phoxim, pirimiphos, pirimiphos-ethyl, pirimiphos-methyl, profenofos, propafol, propetamphos, prothiofos, parksafe, trichlorfon, vamidothion;

2) from the group of the carbamates

alanylons (CA-135), aldicarb, 2-second-butylphenylmethyl (VRMS), carbaryl, carbofuran, carbosulfan, cloethocarb, benfuracarb, ethiofencarb, furathiocarb, HCN-801, isoprocarb, methomyl, 5-methyl-meta-kumanivtsi(methyl)carbamate, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, 1-methylthio(ethylenediamino)-N-methyl-N-(morpholinothio)carbamate (UC 51717), triazamate;

3) from the group of esters of carboxylic acids

acrinathrin, allethrin, alphamethrin, beta-cypermethrin, 5-benzyl-3-furylmethyl-(E),(1R)-CIS-2,2-dimethyl-3-(2-oxathiolan-3-ylidenemethyl)cyclopropanecarboxylate, beta-cyfluthrin, beta-cypermethrin, bioallethrin, bioallethrin(S)-cyclopentolate, bioresmethrin, lifenet, (RS)-1-cyano-1-(6-phenoxy-2-pyridyl)methyl(1RS)-TRANS-3-(4-tert-butylphenyl)-2,2-dimethylcyclo-propanecarboxylate (NCI 85193), cicloprofen, cyfluthrin, cigalotrin, Caitrin, cypermethrin, cyphenothrin, deltamethrin, empenthrin, esfenvalerate, fenfluthrin, fenpropathrin, fenvalerate, flucythrinate, flumethrin, fluvalinate (D-isomer), imiprothrin (S-41311), lambda cigalotrin, permethrin, Petrin ((R-isomer), prallethrin, pyrethrin (natural product), resmethrin, tefluthrin, tetramethrin, theta-cypermethrin (TD-2344), tralomethrin, from the group of compounds of tin

cyhexatin, fenbutatin;

6) other

the abamectin, ABG-9008; acetamiprid, Anagrapha falcitera, AKD-1022, AKD-3059, ANS-118, Bacillus thuringiensis, Beauveria bassianea, bensultap, bifenazate (D-2341), binapacryl, BJL-932, bromopropylate, BTG-504, BTG-505, buprofezin, camphechlor, cartap, Chlorobenzilate, chlorfenapyr, chlorfluazuron, 2-(4-chlorophenyl)-4,5-diphenylthiophene (UBI-T 930), chlorphenesin, chromafenozide (ANS-118), CG-216, CG-217, CG-234, A-184699, (2-naphthylethylenediamine) ether cyclopropanecarbonyl acid (Rol2-0470), cyromazine, dialogen (thiamethoxam), diafenthiuron, ethyl ester of N-(3,5-dichloro-4-(1,1,2,3,3,3-hexamer-1 propyloxy)phenyl)carbarnoyl)-2-chlorobenzenamine acid, DDT, dicofol, difluorobenzene, N-(2,3-dihydro-3-methyl-1,3-thiazol-2-ilidene)-2,4-ilidene)-2,4-xylidene, dinobuton, dinocap, giovanola, DPX-062, amaneciendo (MK-244), endosulfan, ethiprole (sulfation), etofenprox, etoxazole (YI-5301), fenazaquin, fenoxycarb, fipronil, flumet (Florentin, SZI-121), a simple 2-fluoro-5-(4-(4-ethoxyphenyl)-4-methyl-1-pentyl)diphenyl ether (MTI 800), granulosa and Poligrafiya nuclei (cells), fenpyroximate, benthiocarb, flibanserin, flucycloxuron, flufenoxuron, pluginpac (ICI-A5683), propoxyphen, gamma-HCH, halogenated (RH-0345), halftracks (MTI-732), hexaflumuron (DE-473), hexythiazox, HOI-9004, hydramethylnon (AC 217300), who, RH-2485), milbemectin, NC-196, neergard, nitenpyram (TI-304), 2-nitro methyl-4,5-dihydro-6N-thiazin (DS 52618), 2-nitro methyl-3,4-dihydrodiol (SD 35651), 2-nitromethylene-1,2-diazinon-3-ylcarbamate (WL 108477), pyriproxyfen (S-71639), NC-196, NC-111, NNI-9768, novaluron MCW-275), OK-9701, OK-9601, OK-9602, propargite, pymetrozine, pyridaben, pyrimidifen (SU-8801), RH-0345, RH-2485, RYI-210, S 1283, S-1833, SB7242, SI-8601, selflove, Salamatin (CG-177), spinosad, SU-9118, tebufenozide, tebufenpyrad (MK-239), teflubenzuron, returneesin (MTI-446), tetradifon, tetrasul, thiacloprid, thiocyclam, TI-435, tolpinrud (OMI-88), Tiamat (RH-7988), triflumuron, verboten, vertalec, (mycotal), YI-5301.

The content of biologically active substances prepared application forms prepared from the commercially available standard compounds, can vary from 0,00000001 to 95 wt.% the active substance, preferably between 0.00001 and 1 wt.%.

The application is carried out according to conventional methods, depending on the form of application.

The proposed active substances of the formula (I) are applicable against endo - and ectoparasites in the veterinary field or the field of animal welfare.

The application of the proposed active substances is well known manner as by oral administration in the form of, for example, PL is ylenia (sprays), pouring (pour-on and spot-on and dusting, and by parenteral administration in the form of, for example, injection.

Accordingly, proposed according to the invention used compounds particularly useful for the keeping of livestock (e.g. cattle, sheep, pigs and poultry, such as chickens, geese, and so on). In a preferred form of embodiment of the invention the new compounds administered to the animals, if necessary, in suitable compositions (cf. above) and if necessary with drinking water or feed. Because the selection is active with faeces, it is possible in this way it is very easy to hamper the development of insects in the feces of animals. Suitable dosages and compositions, in particular, depend on the type and stage of development of useful animal and also from the degree of destruction and can be easily identified and installed in the usual way. The new compounds can be administered to cattle, for example, in doses of from 0.01 to 100 mg/kg body weight.

Used according to the invention compounds also exhibit a wide fungicidal effect. Already in the plant tissue successfully fight penetrating fungal pathogens. This is particularly important in the conventional fungicides. Action spectrum of the active compounds covers various economic important phytopathogenic fungi, such as Plasmopara viticola, Phytophthora infestans, Erysiphe graminis, Piricularia oryzae, Pyrenophora teres, Leptosphaerea nodorum, Pellikularia sasakii and Puccinia recondita.

Compounds according to the invention is also applicable for use in technical fields, for example, as a means to protect the wood, as preservatives in paints, in cooling lubricants for metal processing or as preservatives in oils for sverlova and cutting works.

Offer active substances can be used in commercially available ready-made forms, either individually or in combination with other known from the literature fungicides.

As known from the literature fungicides, which can be combined with compounds of the formula I, should be named the following products: Aldemar, andapril, anilazine, AZOXYSTROBIN, azaconazole, vases 450F, benalaxyl, Benadryl, benomyl, beloxepin, binapacryl, Bion (CGA-245704), bitertanol, bromuconazole, butiaba, captafol, Captan, carbendazim, carboxin, cropropamide, CGA 173506, having cymoxanil, tsyprokonazolu, cyprodinil, zipform, diplomatarium, dichlofluanid, dichlorotin, diclobutrazol, dickiedina, dithianon, dodemont, Dodin, edifenphos, epoxiconazol, ethirimol, etridiazole, famoxadone, (DPX-JE874), fenarimol, fenbuconazole, fanforum, fenhexamid, fenpiclonil, fenpropidin, fenpropimorph, fentiazac, pentahydroxy, verison (TF 164), fluazinam, fluoroskan, fludyoksonil flamethower (RPA-403397), fluquinconazole, perimed, flusilazol, glucolipid, flutolanil, flutriafol, folpet, postillonne, fuberidazole, parallaxis, vorconizole, parameter (S-82658), pharmacyclics, guazatine, hexaconazole, imazalil, kabekona, ipconazole, iprobenfos, iprodion, isoprothiolane, KNF 317, kresoxim-methyl (BAS-490F), copper compounds, such as oxychloride si, si-oxen, the oxide of si, MANCOZEB, MANEB, mepanipyrim (KIFD 3535), mepronil, metalaxyl, metalaxyl-M (CGA-329351), metconazole, metasurfaces, mefenoxam, etaminophen (SSF-126), metamyosyn (phenominalrose, SSF-126), MON 24000, MON-6550, MON-41100, myclobutanil, nabam, nitratenitrogen, nuarimol, furac, OK-9601, OK-9603, oxadixyl, oxycarboxin, penconazole, pencycuron, PP 969, polyoxin, provenzal, propineb, prochloraz, procymidone, propamocarb, propiconazol, protocorm, percarbonic, pyrazophos, pirivenas, Pyrimethanil, pyroquilon, quinoxyfen (DE-795), rabenasolo, RH-7592, RH-7281, sulfur, spiroxamine, SSF-109, tebuconazole, tet is waned, triadimefon, triadimenol, triazoxide, Trichoderma harzianum (DHF-471), tricyclazole, tridemorph, triflumizole, triforine, triflumizole (UCC-A815), triticonazole, validamycin, vinclozolin, XRD 563, zineb, dodecylsulfonate sodium, sodium dodecyl sulphate, C13/C15-certifiedhealthnut sodium, zetostearilovy sodium, sulfosuccinate dictinary, isopropylnaphthalene sodium, methyltrimethoxysilane sodium, chloride, cetyltrimethylammonium, salts of long chain primary, secondary or tertiary amines, alkyldiphenylamine, laurylamine bromide, ethoxylated fatty Quaternary amines, chloride, alkyldimethylbenzylammonium and 1-hydroxyethyl-2-alkylimidazole.

The above-mentioned components of the combinations are known biologically active substances, which are mostly described in The Pesticide Manual (editor Clive Tomlin), 11th edition (1997), Crop Protection Publications/ISBN 1-901396-11-8 795.

The content of active substance in ready-made applications, made from the commercially available formulations can vary within wide limits, the concentration of active substance in the form of application may range from 0.0001 to 95 wt.% the active substance, preferably between 1 and 50 wt.%. The application is normal what sevanam 10 wt. parts of the active substance and 90 wt. parts of talc as inert substance and grinding in an impact mill.

b) Easily dispersible in water wettable powder is obtained by mixing 25 wt. parts of active substance, 65 wt. parts kalisoderjasimi quartz as inert substance, 10 wt. parts of the potassium salt ligninsulfonate acid and 1 wt. part of the sodium salt oleoylethanolamide acid as socialseo and disperging tools and grinding in a pin mill.

c) Easily dispersible in water dispersion concentrate is obtained by mixing 40 wt. parts of the active substance with a 7 wt. parts of Palmyra sulfonterol acid, 2 wt. parts of the sodium salt ligninsulfonate acid and 51 wt. part of water and grinding in a ball mill to a particle size less than 5 microns.

a) Emulsifiable concentrate can receive from 15 wt. parts of active substance, 75 wt. parts of cyclohexane as solvent and 10 wt. parts atsetilirovanie of Nonylphenol (10 EO) as emulsifier.

e) Granules able to get out of 2-15 wt. parts of the active substance and an inert carrier, such as attapulgite, granulated pumice and/or quartz dog who beat him on the surface of the granules attapulgite, to dry and carefully stir. Moreover, the weight fraction of the sprayed powder is about 5% and inert carrier about 95% of the finished granulate.

To test the activity of the blocker lks-channel KQT1 channel was conducted electrophysiological studies on frog oocytes that Express KQT1-channel (specific lks-channel nematode Caenorhabditis elegans). Adult female frogs (Xenopus laevis) umemulo and selected from ovarian oocytes of all stages of maturity. Egg stages V and VI were sorted; using nanometrology injector inserted into the micromanipulator, each egg was injected 10 ng of mRNA specific for KQT1. After 1-4 days enriched KQT1-channels expressed, so that could be measured appropriate threads. For measuring slowly activated potassium flow at constant intracellular conditions, the method was used the voltage at the terminals of the two microelectrodes (Voltage Clamp-Methode). It is based on the fact that I work with 2 intracellular microelectrodes; the first electrode measures the membrane potential relative to the reference electrode, which serves as the second electrode. To initiate the flow, it is necessary to maintain the desired potential. During measurement ustanavli zoologicheskogo measurement consists of Sathaye oscillating table for experimental animal, which is fixed to a specially prepared measuring chamber 2 micromanipulator, each with pre-amplifier and the holder of the microelectrodes and the stereomicroscope.

All measurement surrounded by a Faraday cage to minimize electrical interference during measurement. Oocytes during measurement washed ND-96 buffer solution. To activate dependent voltage lks-channel membrane of oocytes depolarized surge voltage constant potential (-80 mV) to 0 mV and maintaining this state for 10 seconds before recovering constant potential. The temporary conclusion of the measurement Protocol is repeated all 45 C. During the phase of depolarization was measured by slowly activated potassium channel. Blocking the channel, the effect of different lks-blockers was tested at concentrations of 100, 10, 1 and 0.1 μm; the measured amplitude of the flow without the influence of the drug compared with the amplitudes of the flow under the influence of the drug served as a measure of activity blocker lks-channel and were expressed as percent inhibition or IC50. Depending on the structure of the blocker lks-channel at 10 μm concentrations were determined the values of inhibition of 90% or value IC50<2 μm.

To verify the validity of blockers lks feeds on worms conducted a sample in vitro (test for larval development) with larvae of Ascaridia galli. Fertilized eggs of A. galli were surface sterilized by treatment with 5% sodium hypochlorite solution and after removal of this solution is mechanically opened by means of a rotating glass pellets (5 mm). Theatric L2-larvae enriched by way of enrichment of larvae were made in a special nutrient medium (HP-2 medium), and incubated at 41P and 10% CO2. Larvae were incubated (41P, 10% CO248 hours after slipping in the tablet for micrometrology (96 wells) 5 days with medical medium (200 μl) at concentrations(200, 100, 50....0,1 mg/ml). During the 5-day period of incubation daily controlled using a microscope and observed the motility, morphology and viability. After medical treatment culture of larvae incubated 48 hours with neutral red at a concentration of 0.16%; after removal of neutral red on changing CIM way as an indicator of viability. Drug treatment of larvae blockers lks-channels at concentrations of 200, 100, 50 and 25 mg/ml leads to 100% mortality.

The action of blockers lks-channels against ectoparasites were tested in samples of larvae of fleas (cat fleas, Ctenocephalides felis). 5 mg of the substance was dissolved in 0.5 ml of acetone and stirred to a 500 mg portion of blood. After evaporation of the solvent, 2 g of quartz sand mixed with the treated portions of the blood thus to obtain concentrations of 1000, 500, 250, 100'clock N. m To mixtures of treated units of blood and quartz sand was added drug sample or control solution 15 flea eggs, which are then incubated at C and high humidity. The development of larvae, hatching and development to adult stages controlled in 3-5 days and watched the speed of killing. Depending on the doses could watch larvicide effect 100% in comparison with the control solution.

It is fundamentally important in the processing of helminths and ectoparasites to distinguish therapeutic, meta and preventive measures; these different processing methods require special galenic ready preparative forms. These are ready preparative forms of obespechivayushchego, these are distinguished by their extension release "support" and "policyrule releasing the balls". The first differ further by slowly releasing the balls", which are by their decreasing speed of release and continuous release beads, which are so in their remaining uniform module release. "Policyrule releasing the balls, on the contrary, release the active substance from several hours to days. Along with technology releases, which includes also the microencapsulation of active substances and which enjoys increasing popularity in veterinary medicine, the usual are "spot on" and "pour on" ready formulation for topical application to animals; the state of the art is the use of tablets, pastes or solutions for injection and neck bandages that contain the medicinal product in relation to, for example, ectoparasites.

1. Inhibitors lks-channel simultaneous action as inhibitors KQTl channel to obtain drugs for the treatment of diseases caused by helminths and ectoparasites, wherein the following compounds:EN, 6-cyano-4-TRANS-(N-ethylsulfonyl-M-methylamino)-3-hydroxy-2,2-DIMETHYLPROPANE, 7-chloro-4-N-ethylsulfonyl-N-methylamino-6-fluoro-2,2-DIMETHYLPROPANE, 6,7-dichloro-4-[N-ethylsulfonyl-N-(4,4,4-trifloromethyl)amino]-2,2-DIMETHYLPROPANE, 2-[econsultancy-(6-fluoro-2,2-dimethyl-chroman-4-yl)-amino]-N-pyridin-4-yl-ndimethylacetamide, N-(2-dimethylamino-ethyl)-2-[econsultancy-(6-fluoro-2,2-dimethyl-chroman-4-yl) -amino]-ndimethylacetamide, N-[2-(benzyl-methyl-amino)-ethyl]-2-[econsultancy-(6-fluoro-2,2-dimethyl-chroman-4-yl)-amino]-ndimethylacetamide, (3R,4S)-(+)-N-[3-hydroxy-2,2-dimethyl-6-(4,4,4-triptoreline)-chroman-4-yl]-N-methyl-methanesulfonamide, (3S,4R)-(-)-N-[3-hydroxy-2,2-dimethyl-6-(4,4,4-triptoreline)-chroman-4-yl]-N-methyl-methanesulfonamide, or N-[2,2-dimethyl-6-(4,4,4-triptoreline)-2H-chromen-4-yl]-N-methyl-methanesulfonamide, as well as their physiologically compatible salts.

2. Application under item (1 inhibitors lks-channel simultaneous action as inhibitors KQTl channel to obtain drugs for the treatment of diseases caused by helminths.

 

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