UA77042C2 - Substituted 4-tetrahydroquinolines, use thereof as medicament, a medicament containing them - Google Patents

Abstract

The invention relates to compounds of formula (I), wherein Rl - R9 which have the meaning as cited in the claims, are extremely suitable as antihypertensives for reducing or preventing ischemically induced injuries, as medicaments for operative intervention for the treatment of is-chemics of the nervous system, strokes and swelling of the brain, shocks, disturbed respiratory functions, for the treatment of snorers, as a laxative, as agents against parasites, for the prevention of gallstones, as antiatherosclerotic agents, agents against diabetic late complications, cancer, fibrotic diseases, endothelial dysfunctions, organ hypertrophia and hyperplasia. Said compounds are also inhibitors of the cellular sodium-proton-antiporters, they influence serum lipoproteins and can be used in the prophylaxis of and for the regression ot'-atherosclerotic alterations.

Description

Description of the invention

The invention relates to the compound of the formula (): pednodeschya their breath i Shchi

She is also a member of the National Academy of Sciences

Same Same I with ge -y uk yi - -g hu In here Yasya a. tv BE ne What are you 74 h i niah I ; I am a child of PEE and Dr SHEU si MyEtOST i min Tue: and p. "aEtEka where:

KL, K2, KZ and K4, independently of each other, mean H, P, SI, Vg, I, CM, MO», OH, MN», SaNzahi» SadNodd-1» s

OSHNam, SOOMK10, OSOKITO, SOKT0 or O,-(CHo)u-phenyl; o a and 5 in the groups CaNoani and OSNouiya, independently of each other, mean 1, 2, C, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by P-atoms; da means 3, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by P-atoms;

K10 means H or CoNosyai; c c means 1, 2, C, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by H-atoms; " x means zero or 1; y means zero, 1, 2, C or 4; (ав) and the phenyl ring in the О,-(СНо)у-phenyl group is unsubstituted or substituted by 1-3 substituents, which select from them groups consisting of РЕ, СИ, Вг, СМ, МО», ОН, МН» or SaNzdchi; a means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; or -

K, K2, KZ Her K4, independently of each other, mean heteroaryl, and the ring may contain 0, 1, 2, C or 4 nitrogen atoms, 0 or 1 oxygen atom or 0 or 1 sulfur atom; or "

КИ, К2, КЗ and К4, independently of each other, mean СОМК11К12 or МК11К12;

K11 and K12, independently of each other, mean H, SeNoeni, StNot-1; t c e means 1,2, 3,4, 5,6, 7 or 8; ch gg means 3, 4, 5, 6, 7 or 8, » and in the groups SeNoech1 and StNotp-1 one or more H-atoms can be replaced by P-atoms and one or more СНо-groups can be replaced by О or МК13 ;

КИЗ means H or StNovi; - and Her means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms; -1 or

КИЗ and one СНо group of the К11 or К12 radical, together with the nitrogen atom to which they are connected, form a 5- or («c) b-membered cycle; 50 of them or

K11 and K12, together with the nitrogen atom to which they are connected, form a 5-, 6-, or 7-ene ring;

Ko) or

K11 and K12, independently of each other, mean СОК14, С5К14 or 50214;

K14 means SoNadyai; d means 1, 2, 3, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by E-atoms and o one or more СНо-groups can be replaced by O or MK13; or eat) КИ, К2, КЗ and К4, independently of each other, mean -0,-5О)-К15, and also means zero or 1; 6o0 | means zero, 1 or 2;

K15 means SKNokii, OH, OSINami or MK17K18;

K means 1, 2, 3, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by E-atoms; 1 means 1, 2, C, 4, 5, 6, 7 or 8, and one or more H atoms can be replaced by E atoms;

K17 and K18, independently of each other, mean H or StpNotchi1; 65 t means 1, 2, C, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced in the StyaNoti group

E atoms and one or more СНо groups can be replaced by О, СО, С5 or MK19;

K19 stands for H or SuNodchi; n means 1, 2, C or 4; moreover, in SaNor-4, one or more H-atoms can be replaced by E-atoms; or

K17 and K18, together with the nitrogen atom to which they are connected, form a 5-, 6- or 7-lene cycle; or

K19 and the СНо group of the K17 or K18 radical, together with the nitrogen atom to which they are connected, form a 5- or b--linked ring; 70 and, however, always K2 should not mean H;

K5 stands for H, SeNorni, SevNovv, SOK2O or BOZ2O; p means 1,2, 3,4,5, 6, 7 or 8; c5 means 3, 4, 5, 6, 7 or 8; k20 means SaNgodni; d means 1,2, 3,4,5,6, 7 or 8, and in the groups SeNoria, SevNove-1 and SaNodnia one or more H-atoms can be replaced by P-atoms and one or more СНо-groups can be replaced on O or MK21;

K21 stands for H or SNachi; r means 1, 2, C or 4; moreover, in SINAg-i, one or more H-atoms can be replaced by P-atoms;

Kb means H, E, SI, Vg, Y, SeNaovchn, SdaNzda-1, OH, oOSsSNaya or osSoOng2; z ii, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8; ad means 3, 4, 5, 6, 7 or 8, and in SeNovch1; In SaaNoda-1 and OSINo3-ya, one or more H-atoms can be replaced by E-atoms; high school

K22 means Sun Nights; и means 1, 2, C or 4; (8) and in SuNoun, one or more H-atoms can be replaced by P-atoms;

К7, КВ and КУ, independently of each other, mean -О,-50,,-К23;

M means zero or 1; c z o m means zero, 1 or 2;

Kk23 means SppNoppyai» SttNott-1, OH, OSrrNorr-i or MK25KO26; - пп and пр, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8; o tt means 3,4, 5, 6, 7 or 8, and in SppNoppyayai; SttNottoi, ON Her OSrrNorr-i. OSrrNors one or more H-atoms can be - replaced by E-atoms; uh-

K25 and K26, independently of each other, mean H, CM or С,Нао»н1, С,»Но»»1; 7 means 1, 2, 3, 4, 5, 6, 7 or 8; 77 means 3, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by E-atoms and in C,H2,-14 one or more H-atoms can be replaced by P-atoms and one or several СНо-groups can be replaced by 0, СО, С5 or MK27; in c K27 means H or SaaNodachi;

And aa means 1, 2, Z or 4; and in SaaNodaz-1 ONE or several H-atoms can be replaced by E-atoms; or

K25 and K26 together with the nitrogen atom to which they are connected form a 5-, 6- or 7-ene ring, -I or

K27 and one СНо-group of the radical K25 or K26 together with the nitrogen atom to which they are connected form a 5- or - b--lene cycle; about or

K?7, KV and KU, independently of each other, mean MK32СОМКЗО, MK32С5КЗО or MK325О0бКЗО; o KZO means H, SooNossiai» SuNouu.1, pyrrolidinyl or piperidinyl, in the rings of which one CH o-group can be

Iz is replaced by O or MK33;

KZ2 and K33, independently of each other, mean H or SuNorn4; рр means 2 or 3; 5B ss means 1, 2, 3, 4, 5, 6, 7 or 8; uu means 3, 4, 5, 6, 7 or 8; (F) and means 1, 2, 3, 4, 5, 6, 7 or 8; moreover, in SiNi, one or more H-atoms can be replaced by P-atoms, and in the groups СосНоссяя and СуНоуу1 one or more H-atoms can be replaced by P-atoms and one or more СНо-groups can be replaced by МКЗ1 and one СНо -group can be replaced by 0;

KZ1 means H, SKNokknyi, SOKb5 or 50565;

KK means 1, 2, C or 4; and one or more H-atoms can be replaced by E-atoms;

Kb5 means H, SuhKohkhchi; 65 xx means 1, 2, C or 4, and one or more H-atoms may be replaced by P-atoms; or

KZ1 together with one СНо group of the KZO radical forms a 5-, 6-, or 7-lene ring; or

KZO means a 5- or b-lene heteroaryl with 1, 2, 3 or 4 nitrogen atoms, 0 or 1 sulfur atoms and 0 or 1 oxygen atoms, which is unsubstituted or substituted up to three times with substituents selected from the group consisting of RE, SI, Vg, Ii SooNorsochmi; MA7OK71;

KO and K71, independently of each other, mean H, SuuNotsuichya and SOK72;

K72 stands for H, SL/Nouchi; oo, shi and mu, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8; 70 and in SooNooogi groups; One or more H-atoms can be substituted in CtsSNHOcs or SuU/NouUi

E-atoms; or

K7, KV and KU, independently of each other, mean H, RE, SI, Vg, I, MO", SM, OH, MN", SeeNoveni". Court Nodu-1"

OsSyaNoti, MK4OKA1, SOMK4AOK4A1, SOOKA42, SOK42 or OSOKA2; ee and I, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8; mly means 3, 4, 5, 6, 7 or 8; moreover, in the groups SeeNovech1, SuluNoudu-1, and OSyaNovya, one or more H-atoms can be replaced

E-atoms;

K40 and K41 mean H, SeNon, or C(IMN)MN";

HER means 1, 2, Z, 4, 5, 6, 7 or 8; moreover, in the group SeNon-yai one or more H-atoms can be replaced by P-atoms and one or more

СНо-groups can be replaced by O or MK44;

K44 means H or C.5Noduni; yes means 1, 2, 3, 4, 5, 6, 7 or 8; c and in the C39Nodd group one or more H-atoms can be replaced by P-atoms and K44 together with one

The СНо group of the K40 or КА41 radical and the nitrogen atom with which they are connected can form a 5- or b--lens i) cycle; or

K4O and K41, together with the nitrogen atom to which they are connected, form a 5- or b--linked ring;

K42 means H or SfNonniai; c z o n means 1, 2, 3, 4, 5, 6, 7 or 8; moreover, one or more H-atoms can be replaced by P-atoms in the SynNonnia group; - moreover, however, two substituents from the group K7, КВ and КУ simultaneously cannot mean ОН or ОСН3 о and at least one of the residues К7, К8 or КО must be selected from the group consisting of

Somko Ka1, -0.50.23, MK32СОк30, MK32С5К30 and MA3250.0К30; - as well as to their pharmaceutically acceptable salts and trifluoroacetates. uh-

Preferred compounds of formula (I), where:

КИ, К2, КЗ and К4, independently of each other, mean H, PE, SI, Vg, I, CM, MO», OH, MH», CaNoa»i, cycloalkyl with 3, 4, 5 or 6 C atoms , OSNnoyuyi, SOOK10; a and 6, independently of each other, mean 1, 2, C or 4, and one or more H-atoms may be replaced by E-atoms; with c K10 means H or SoNosyai, . c means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; and" or

КИ, К2, КЗ and К4, independently of each other, are 5- or b-lene heteroaryl selected from

A group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl and -I oxazolyl; or - КИ, К2, КЗ and К4, independently of each other, mean СОМК11К12 or МК11К12; o K11 and K12, independently of each other, mean H, SeNoeni, StNot-1; e means 1, 2, C or 4; pi gg means 3, 4, 5 or 6,

Moreover, in the SeNzechi and StNaorg.-1 groups, one or more H-atoms can be replaced by E-atoms; or

K11 and K12, independently of each other, mean hydroxyethyl, M,M-dimethylaminoethyl, M,M-diethylaminoethyl, pyrrolidinoethyl, M-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or (F) K1T1 and K12, together with the nitrogen atom to which they are connected, form a pyrrolidine, piperidine, or M-methylpiperazine, piperazine or morpholine ring; or in K11 and K12, independently of each other, mean SOK14, SZK14, SOMNI14, SZMNK14 or 5ОЖ14;

K14 means SoNadyai; 9 means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; or

КИ, К2, КЗ and К4, independently of each other, mean О5ОЗН, ЗОЗН, 502К15, and 65 К15 means SKNokya1, OSINami or MK17К18;

K means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms;

Y means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms;

K17 and K18, independently of each other, mean H, СТНот:и, in which the first is bound to the nitrogen atom

The CH»o group is replaced by CO and the second СНо group is replaced by MK19; t means 1, 2, 3, 4 or 5, and one or more H-atoms can be replaced in the group X

E-atoms;

K19 stands for H or SuNodchi; n means 1, 2, C or 4; moreover, in SiNop1 one or more H-atoms can be replaced by P-atoms; 70 or

K17 and K18, together with the nitrogen atom to which they are connected, form a 5- or b--lene cycle; moreover, however, always K2 should not mean H;

K5 means H, SrNora; p means 1, 2, C or 4; and in SrNaorya one or more H-atoms can be replaced by P-atoms;

Kb means H, SeNovyi, OSINo3nya or OSOK22; z and i, independently of each other, mean 1, 2, З or 4; moreover, in SeNovcha and OS, Nanya, one or more H-atoms can be replaced by P-atoms;

K22 means Sun Nights; и means 1, 2, C or 4; and in С, |Na)c-4 one or more H-atoms can be replaced by E-atoms;

K?7, KV and KU, independently of each other, mean OZOZN, 5OZN or GOD; k23 means SppNaoppya1» SttNott-1i» OSrrNorr-i or MK25KO; пп and пр, independently of each other, mean 1, 2, Z, 4 or 5; сч тт means 3, 4, 5 or 6, and in SppNoppya» SttNaott-i and OSrrNorr-i one or more H-atoms can be replaced by P-atoms; and)

K25 and K26, independently of each other, mean Н, СМ, С., Н2,-1, and the first one bound to the nitrogen atom

The СНо group is replaced by СО or С5 and the second СНо group is replaced by MK27; 7 means 1, 2, 3, 4, 5 or 6; c zo and in C,H2,-41 one or more H-atoms can be replaced by P-atoms;

K27 means H or SaaNzodachni, - aa means 1, 2, Z or 4; and in SaaNodaz-1 ONE or several H-atoms can be replaced by E-atoms; or -

K25 and K26, together with the nitrogen atom to which they are connected, form a 5- or b--linked ring, i- or

K27 and one СНо-group of the radical K25 or K26 together with the nitrogen atom to which they are connected form a 5- or b--linked ring; or "

K?7, KV and KU, independently of each other, mean MK32SOKZO, MK32S5KZO or MK32505K30; with c KZO means H, OH, SeONosya, SuNouU, pyrrolidinyl or piperidinyl, in the cycles of which one СО group can be replaced by O or MK33; with KZ2 and K33, independently of each other, mean H or SuNorn4; ss means 1, 2, 3, 4, 5, 6, 7 or 8; uu means 3, 4, 5 or 6; - And n means 1, 2, C or 4; moreover, in SiNon-y one or several H-atoms can be replaced by P-atoms and in the groups SooNossya1 and SuuNouui

Sh- one or more H-atoms can be replaced by P-atoms and one or more СНо-groups can be replaced by МКЗ1 and one СНо-group can be replaced by 0;

KZ1 means H, SKNokknyi, SOKb5 or 50565; pi KK means 1, 2, C or 4;

And one or more H-atoms can be replaced by E-atoms;

Кб5 means Н, СххНоххчи; xx means 1, 2, C or 4, and one or more H-atoms may be replaced by P-atoms; 5B or

KZ1, together with one СНо group of the KZO radical and the nitrogen atom with which they are connected, form a 5- or (Ф) b--lene cycle; ka or

KZO means a 5- or b-lene heteroaryl selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thienyl, thiazolyl, and oxazolyl, which are unsubstituted or substituted up to three times with substituents selected from the group consisting of E, SI, Vg, I, SooNosochi; MAK7OK71;

K?O and K71, independently of each other, mean H, SuuNotsu-i or SOK?72;

K72 stands for H, SL/Nouchi; оо, ши and мм, independently of each other, mean 1, 2, З or 4; 65 and in SooNooogi groups; One or more H-atoms can be replaced in SusNHysium or SuU/Nuyuyy

E-atoms; or

K7, KV and KU, independently of each other, mean H, RE, SI, Vg, I, MO", SM, ОН, МН", SeeNovechi" of Court Nodu-1;

OsSeNoti, MK4OK41, СОМК4ОКА1, СООК42, СОКаЯ2 or OSOKA2; ee and I, independently of each other, mean 1, 2, Z or 4; mly means 3, 4, 5 or 6; moreover, in the groups SeeNovech1, SuluNoudu-1, and OSyaNovya, one or more H-atoms can be replaced

E-atoms;

K40 and K41 mean H, SeNon, or C(IMN)MN";

HER means 1, 2, Z, 4, 5, 6, 7 or 8; 70 and one or more H-atoms can be replaced by E-atoms in the SeNon-yai group; or

K4O and K41, independently of each other, are selected from the group consisting of hydroxyethyl,

M,M-dimethylaminoethyl, M,M-diethylaminoethyl, pyrrolidinoethyl, M-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or

K40 Its K41 together with the nitrogen atom to which they are connected form a ring selected from the group consisting of pyrrolidine, piperidine, M-methylpiperazine, piperazine and morpholine;

K42 means H or SfNonniai; pi means 1, 2, C or 4; moreover, one or more H-atoms can be replaced by E-atoms in the Sennon group; and, however, two substituents from the group K7, КВ and КУ at the same time cannot mean ОН or ОСН3 and at least one of the residues К7, К8 or КО must be selected from the group consisting of

Somko Ka1, -0.50.23, MK32СОк30, MK32С5К30 and MA3250.0К30; as well as their pharmaceutically acceptable salts and trifluoroacetates. high school

Compounds of formula (I) are especially preferred, where:

КИ, К2, КЗ and К4, independently of each other, mean Н, РЕ, СИ, Вг, ОН, МН», СаНза-4, cycloalkyl with 3, 4, 5 (8) or 6 C-atoms, ОШНовчл; a and 6 in the groups СаНоа-и and ОСХНоюй, independently of each other, mean 1, 2, З or 4, and one or more H-atoms can be replaced by P-atoms; with zo or

КИ, К2, КЗ and К4, independently of each other, mean МК11К12; "

K11 and K12, independently of each other, mean H, SeNoeni, StNot-1; о е means 1, 2, C or 4; гг means 3, 4, 5 or 6, c. moreover, in the SeNzechi and StNaorg.-1 groups, one or more H-atoms can be replaced by E-atoms; or

K11 and K12 together with the nitrogen atom to which they are connected form a ring selected from the group consisting of pyrrolidine, piperidine, M-methylpiperazine, piperazine and morpholine; or "

K11 and K12, independently of each other, mean SOK14, SZK14, SOMNI14, SZMNK14 or 5ОЖ14; with c K14 means SoNadyai; . 9 means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; and" or

КИ, К2, КЗ and К4, independently of each other, mean О5ОЗН, ЗОЗН, 502515;

K15 means SKNok-ya, or MK17K18; -And K means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms;

K17 and K18, independently of each other, mean H or StpNotchi1; - t means 1, 2, 3, 4 or 5, and one or more H-atoms can be replaced by E-atoms in the group of the following; or

K17 and K18, together with the nitrogen atom to which they are connected, form a 5- or b--lene cycle; pi and, however, always K2 should not mean H;

He K5 means methyl or trifluoromethyl;

Kb means H;

K?7, KV and KU, independently of each other, mean OZOZN, 5OZN or GOD; 5B K23Z means SppNopp-y 8bo MK25K26; пп means 1, 2, Z, 4 or 5;

Ф) and in SdpNopp«-1 one or more H-atoms can be replaced by E-atoms; ka K25 and K26, independently of each other, mean Н, СМ or С,Н2,-41, IN WHICH the first is bound to the nitrogen atom

The СНо group is replaced by СО or С5 and the second СНо group is replaced by MK27; 60 7 means 1, 2, 3, 4, 5 or 6; and in C,H2,-41 one or more H-atoms can be replaced by P-atoms;

K27 means H or SaaNodachi; aa means 1, 2, C or 4; and in SaaNodaz-1 ONE or several H-atoms can be replaced by E-atoms; 65 or

K25 and K26, together with the nitrogen atom to which they are connected, form a 5- or b--ene ring,

or

K27 and one СНо-group of the radical K25 or K26 together with the nitrogen atom to which they are connected form a 5- or b--linked ring; or

K?7, KV and KU, independently of each other, mean MK32SOKZO, MK32S5KZO or MK32505K30;

KZO means H, OH, SeosNossni» Suuuguu-1 pPyrrolidinyl or piperidinyl, in the rings of which one СНо-group can be replaced by O or MK33;

KZ2 and KZZ mean H, methyl or CE"; 70 cc means 1, 2, 3, 4, 5, 6, 7 or 8; uu means 3, 4, 5 or 6; moreover, in the groups SooNossni and Suuuguu.1 one or more H-atoms can be replaced by P-atoms and one or more СНо-groups can be replaced by MKZ1 and one СНо-group can be replaced by 0;

KZ1 means H, methyl, ethyl, CEz, СНоСЕ», acetyl, propionyl, methanesulfonyl or ethanesulfonyl; or

KZ1, together with one СНо group of the KZO radical and the nitrogen atom with which they are connected, form a 5- or b--linked cycle; or

KZO means pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl which are 2o unsubstituted or substituted with up to three substituents selected from the group consisting of KE, SI, methyl, ethyl, trifluoromethyl, MH", MH- acetyl; or

K7, KV and KU, independently of each other, mean H, E, SI, OH, MN", SeeNovech1". Sumu Nomlu-1;. OSyaNoni,

MAK4OKa1, SOMKAOKAT, SOOKa2 or OSOKA42; ee and I, independently of each other, mean 1, 2, Z or 4; сч млы means 3, 4, 5 or 6; moreover, in the groups SeeNovech1, SuluNomlu-1 and OSvkNoyani, one or more H-atoms can be replaced i)

E-atoms;

K40 and K41 mean H, SeNon, or C(IMN)MN";

Her means 1, 2, Z or 4; c zo and in the SeNon group one or more H-atoms can be replaced by E-atoms; or -

K4O and K4a1, independently of each other, mean hydroxyethyl, M,M-dimethylaminoethyl, M,M-diethylaminoethyl, o pyrrolidinoethyl, M-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or

K4O and K41, together with the nitrogen atom to which they are connected, form pyrrolidine, piperidine, etc.

M-methylpiperazine, piperazine or morpholine ring; Cha

K42 means H or SfNonniai; pi means 1, 2, C or 4; moreover, one or more H-atoms can be replaced by E-atoms in the Sennon group; and, however, two substituents from the group K7, КВ and КУ at the same time cannot mean ОН or ОСН3 " and at least one of the residues К7, К8 or КО must be selected from the group consisting of с СсОоМ4ОоКат1, -0.50, ,К23, MK32СокЗ0, MKZ32С5ЗО and MK3250О,ЛК30; as well as their pharmaceutically acceptable salts and

And trifluoroacetates. and?" Compounds of formula (I) are most preferred, where:

КИ, К2, КЗ and К4, independently of each other, mean H, E, CI, Bg, OH, MH", CaNoach-i, cycloalkyl with 3, 4, 5 or 6 C-atoms, ОЧНорин; - I a and 5 in the groups СаНоани and ОСНоюія, independently of each other, mean 1, 2, З or 4, and one or more H-atoms can be replaced by P-atoms;

Sh- or o КИ, К2, КЗ and К4, independently of each other, mean МК11К12;

K11 and K12, independently of each other, mean H, SeNoeni, StNot-1; pi e means 1, 2, C or 4;

Из гг means 3, 4, 5 or 6, and in the SeNzechi and StNaorg.-1 groups one or more H-atoms can be replaced by E-atoms; or

K11 and K12 together with the nitrogen atom to which they are connected form a ring selected from the group consisting of pyrrolidine, piperidine, M-methylpiperazine, piperazine and morpholine;

F) or ka K11 and K12, independently of each other, mean SOK14, SZK14, SOMNI14, SZMNK14 or 5ОЖ14;

K14 means SoNadyai; in 9 means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; or

КИ, К2, КЗ and К4, independently of each other, mean О5ОЗН, ЗОЗН, 50215;

K15 means SKNok-i or MK17K18;

K means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms; 65 K17 and K18, independently of each other, mean H or StpNotchi1; t means 1, 2, 3, 4 or 5, and one or more H-atoms can be replaced in the group X

E-atoms; or

K17 and K18, together with the nitrogen atom to which they are connected, form a 5- or b--lene cycle; moreover, however, always K2 should not mean H;

K5 means methyl or trifluoromethyl;

Kb means H;

K?7, KV and KU, independently of each other, mean OZOZN, 5OZN or GOD;

K2Z means SapNodpp-yai, or MK25KO26; пп means 1, 2, Z, 4 or 5; 70 and in SdpNopp-1 one or more H-atoms can be replaced by P-atoms;

K25 and K26, independently of each other, mean Н, СМ or С,Н2,-41, IN WHICH is bound to the nitrogen atom the first

The СНо group is replaced by СО or С5 and the second СНо group is replaced by MK27; 7 means 1, 2, 3, 4, 5 or 6; and in С,Н2о,-4 one or more H-atoms can be replaced by E-atoms;

K27 means H or SaaNodachi; aa means 1, 2, C or 4; and in SaaNodaz-1 ONE or several H-atoms can be replaced by E-atoms; or

K25 and K26, together with the nitrogen atom to which they are connected, form a 5- or b--len ring, or

K27 and one СНо-group of the radical K25 or K26 together with the nitrogen atom to which they are connected form a 5- or b--linked ring; or

K?7, KV and KU, independently of each other, mean MK32SOKZO, MK32S5KZO or MK32505K30; high school

KZO means H, OH, SeoNosya, SuuNouu, pyrrolidinyl or piperidinyl, in the rings of which one СНо group can be replaced by O or MK33; (8)

KZ2 and K33 mean H, methyl or CE"; ss means 1, 2, 3, 4, 5, 6, 7 or 8; uu means 3, 4, 5, 6; c zo and in the groups SosNossyai and SuuNouu-1 one or more H-atoms can be replaced by P-atoms and one or more СНо-groups can be replaced by MKZ1 and one СНо-group can be replaced by 0; -

KZ1 means H, methyl, ethyl, СЕ5, СНоСЕ»3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl; about or

КЗ1 together with one СНо group of the КЗО radical and the nitrogen atom to which they are connected form a 5- or и-б--lene cycle; cha or

KZO means pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl which are unsubstituted or substituted with up to three substituents selected from the group consisting of PE, Si, methyl, ethyl, trifluoromethyl, MH, MH-acetyl ; "or in c K7, KV and KU, independently of each other, mean H, E, SI, ОН, МН", SeeNovech1". Sumu Nomlu-1;. OSyaNoni,

AND MAK4OKa1, SOMKAOKAT, SOOKa2 or OSOKA42; and? ee and I, independently of each other, mean 1, 2, Z or 4; mly means 3, 4, 5 or 6; moreover, in the groups SeeNovech1, SuluNoudu-1, and OSyaNovya, one or more H-atoms can be replaced by -I E-atoms;

K40 and K41 mean H, SeNoavnya, or C(IMN)IMN"; - Her means 1, 2, Z or 4; and in the SeNon-yai group, one or more H atoms can be replaced by E atoms; or pi K4O and K41, independently of each other, mean hydroxyethyl, M,M-dimethylaminoethyl, M,M-diethylaminoethyl,

He pyrrolidinoethyl, M-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or

K4O and K41 together with the nitrogen atom to which they are connected form a pyrrolidine, piperidine, 2-M-methylpiperazine, piperazine or morpholine cycle;

K42 means H or SfNonniai; (F) pi means 1, 2, C or 4; moreover, one or more H-atoms can be replaced by E-atoms in the Sennon group; and, however, two substituents from the group K7, КВ and КУ at the same time cannot mean ОН or ОСН3 60 and at least one of the residues К7, К8 or КУ must be selected from the group consisting of -0,50,К23,

MK32СО30, MK32С5К30 and MK325О0бКЗО; as well as their pharmaceutically acceptable salts and trifluoroacetates.

The most preferred compounds are: 1). M-I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|acetamide; 65 2) 4-(6,8-dichloro-2-methyl -1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; 3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide;

4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M,M-dimethylbenzenesulfonamide; 5) 4-(4-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline; 6) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid; 7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-ethylbenzamide; 8). 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-propylbenzamide; 9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-(2-dimethylaminoethyl)benzamide; 10) 6,8-dichloro-2-methyl-4-(4-morpholin-4-ylphenyl)-1,2,3,4-tetrahydroisoquinoline; 113. I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|diethylamine; 70 12) 6,8-dichloro-2-methyl-4-(4-piperidin-1-ylphenyl)-1,2,3,4-tetrahydroisoquinoline; 13). 6,8-dichloro-2-methyl-4-(4-pyrrolidin-1-ylphenyl)-1,2,3,4-tetrahydroisoquinoline; 14). 6,8-dichloro-2-methyl-4-I(4-(4-methylpiperazin-1-yl)phenyl)-1,2,3,4-tetrahydroisoquinoline; 15) 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 16). 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenylamine; 17). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-3-propylurea; 18). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylthiourea; 19). 1-I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-ethylurea; 20). M-(4-(6-methanesulfonyl-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|acetamide; 21). h-(4-(2,6,β-trimethyl-1,2 ,3,4-tetrahydroisoquinolin-4-yl)uphenyl)acetamide; 2235. M-I4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylacetamide; 23). M-I4-(8-chloro-2-methyl-b-pyrrolidin-1-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide; 24). M-I4-(8-chloro-2-methyl-6-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide; 25). M-4-18-chloro-2-methyl-6-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydroisoquinolin-4-yl|phenyl)acetamide; 26). M-4-18-chloro-6-cyclopropylmethylamino)-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ylphenyl)acetamide; ch 27) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid; 28) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxy-M-methylbenzamide; (8) 29) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-ethyl-2-hydroxybenzamide; 30) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinol-4-yl)-M-(2-dimethylaminoethyl)-2-hydroxybenzamide; 31). Mch-I5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoylguanidine; from 32). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|acetamide; 33) 3-(6,8-dichloro-2-methyl-1,2, 3,4-tetrahydroisoquinoline-4-iluphenylamine; "34) 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenylamine; about 35). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 36) Ch-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; i- 37) 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|pentanoic acid amide; i- 38). h-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylisobutyramide; 39). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-2,2-dimethylpropionamide; 40) I4-(6,8-dichloro-2-methyl -1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide cyclopropanecarboxylic acid; 41) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of cyclobutanecarboxylic acid; 42) Cyclopentanecarboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; from p. 43). chCh-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)-2,2,2-trifluoroacetamide; . 44) 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide 1-acetylpiperidine-4-carboxylic acid acids; 45). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|nicotinamide; 46) H-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl)methanesulfonamide; -I 47) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of ethanesulfonic acid; 48) M'M'-dimethylamino-H-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|sulfamide;

Sh- 49) h-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; at 50). Ch-IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; 51) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|pentanoic acid amide; ve 52). h-13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylisobutyramide;

Ge 53). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2,2-dimethylpropionamide; 54) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of cyclopropanecarboxylic acid; 55) Cyclobutanecarboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 56) Cyclopentanecarboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 57). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-2,2,2-trifluoroacetamide;

F) 58) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide 1M-acetylpiperidine-4-carboxylic acid; 59). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|nicotinamide; in 60) M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; 61). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenylamide ethanesulfonic acid; 62). M',M'-dimethylamino-M-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|sulfamide; 63). M-(2-( 6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|propionamide; 64). h-(2-(6,8-dichloro-2-methyl-1,2 ,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; 66) h-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylisobutyramide;

67). M-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2,2-dimethylpropionamide; 68) (2-(6,8-dichloro Cyclopropanecarboxylic acid -2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 69) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4 -yl)uphenyl|amide of cyclobutanecarboxylic acid; 79) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide of cyclopentanecarboxylic acid; 71). M-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-2,2,2-trifluoroacetamide; 72) (2-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide of 1-acetylpiperidine-4-carboxylic acid; 73). M-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; 70 74) (2-(6,8-dichloro-2-methyl -1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl|amide of ethanesulfonic acid; 75) M'M'-dimethylamino-M-(2-(6,8-dichloro-2-methyl-1,2, 3,4-tetrahydroisoquinolin-4-iluphenyl|sulfamide; 76). 1-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-Z 77). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylurea; 79). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-33-methylthiourea; 80)

M-15-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoxcholin-4-yl)uphenylsulfamoyl|-4-methylthiazol-2-ilyacetamide; 81)

M-15-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenylsulfamoyl|-4-methylthiazol-2-yl)acetamide; 82). |4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide of 1,2-dimethyl-1H-imidazole-4-sulfonic acids; 83). 1,2-dimethyl-1H-imidazole-4-sulfonic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 84) |4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide sc dv 3-chloro-1,3-dimethyl-1H-pyrazole-4 - sulfonic acids; 85). I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide and) 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid; 86). (4-(6,8-dichloro-2-methyl-1,2,34-tetrahydroisoquinoline-4-iluphenyl)amide 5-bromothiophene-2-sulfonic acid; 87). I3-(6,8-dichloro-2-methyl -1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide 5-bromothiophene-2-sulfonic acid; c zo 88). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-C,C,C-trifluoromethanesulfonamide; 89). M-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-C,C,C-trifluoromethanesulfonamide; - 90) (4-(6, 2,2,2-trifluoroethanesulfonic acid 8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide; o 91). 2,2,2-trifluoroethanesulfonic acid 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide; 92). M-ethyl-M'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonylurea; i- 93). 2-chloro-5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; i- 94) 2-methyl-4-phenyl-β6,8-bistrifluoromethyl-1,2,3,4-tetrahydroisoquinoline; 95). 2-amino-IM-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide; 96). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-methylaminoacetamide; 97). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-dimethylaminoacetamide; 98) 2-amino-M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|propionamide; from p. 99). 2-amino-M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; . 100) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 2,6-diaminohexanoic acid; and?" 101) Pyrrolidine-2-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl amide; 102). chCh-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenylisonicotinamide; 103) I4-(6,8-dichloro-2-methyl-1,2,3, 4-tetrahydroisoquinoline-4-yl)uphenylamide of 1H-pyrrole-3-carboxylic acid; -I 104) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1H-pyrrole-2-carboxylic acid; 105) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1-methylpiperidine-4-carboxylic acid; o 106) 1,4-dimethyl-1H-pyrrole-2-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; ve 107) 4-nitro-1H-pyrrole-2-carbonate 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide

From acid; 108). 2,5-dimethyl-1H-pyrrole-3-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 109) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1H-imidazole-4-carboxylic acid; 110). 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide

F) 1-methanesulfonylpiperidine-4-carboxylic acid; ka 111). 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 3,5-dimethyl-1H-pyrazole-4-carboxylic acid; in 112) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1H-pyrazole-4-carboxylic acid; 113). 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide

C-trifluoromethyl-1H-pyrazole-4-carboxylic acid; 114). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-methylaminoacetamide; 115). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-dimethylaminoacetamide; 65 116). 2-amino-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 117). 2-amino-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|butyramide;

118) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 2,6-diaminohexanoic acid; 119) Pyrrolidine-2-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl-iamide; 120). h-IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenylisonicotinamide; 121) I3-(6,8-dichloro-2-methyl-1,2,3, 4-tetrahydroisoquinoline-4-yl)uphenylamide of 1H-pyrrole-3-carboxylic acid; 122) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1H-pyrrole-2-carboxylic acid; 123) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1-methylpiperidine-4-carboxylic acid; 124) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide 70 of 1,4-dimethyl-1H-pyrrole-2-carboxylic acid; 125) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 4-nitro-1H-pyrrole-2-carboxylic acid; 126) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 2,5-dimethyl-1H-pyrrole-3-carboxylic acid; 127) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1H-imidazole-4-carboxylic acid; 128) 1-methanesulfonylpiperidine-4-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 129) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 3,5-dimethyl-1H-pyrazole-4-carboxylic acid; 130) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1H-pyrazole-4-carboxylic acid; 131). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide

C-trifluoromethyl-1H-pyrazole-4-carboxylic acid; 132). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-ethylthiourea; 133). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-ethylthiourea; Article 134). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-ethylthiourea; 135) 3-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; (8) 136) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 4-methylpiperazine-1-carboxylic acid; 137) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of piperidine-1-carboxylic acid; c zo 138) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; 139) Pyrrolidine-1-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl amide; - 140) 3-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)|-1,1-diethylurea; at 141). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; 142). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)urea; i- 143). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-(tetrahydrofuran-3-yl)urea; i- 144). 1-I3-(6,8-dichloro-2-methyl-1,2Da4a-tetrahydroisoquinolin-4-yl)phenyl|-3-(tetrahydropyran-4-yl)urea; 145) 3-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1-methyl-1-(1-methylpiperidin-4-yl)urea ; 146) 3-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1-3-dimethylaminopropyl)-1-methylurea; from p. 147). 3-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1--2-dimethylaminoethyl)-1-methylurea; and?" 148). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-3-(3-dimethylaminopropyl)urea; 149) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-(2-methoxyethyl)urea; 150). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-pyridin-3-ylurea; -I 151). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-pyridin-4-ylurea; 152) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 4-methylpiperazine-1-carboxylic acid; o 153). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; 154). 3-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; pi 155). 3-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)|-1,1-diethylurea;

He 156) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide piperidine-1-carboxylic acid; 157) (2-(6,8-dichloro Morpholine-4-carboxylic acid -2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 158) (2-(6,8-dichloro-2-methyl-1,2,3,4 -tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-1-carboxylic acid; 159). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)urea; 160) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide of 4-methylpiperazine-1-carboxylic acid (F, acid; ka 161) I4-( Pyrrolidine-1-carboxylic acid 6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl-iamide; 162). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; at 163). 3-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; 164) 3-I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-1,1-diethyl urea; 165). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)urea; 166) I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of piperidine-1-carboxylic acid; 167) I4-(6,8-dichloro- 2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; 65 168). M-I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|formamide; 169)|4-(6,8-dichloro-2-methyl-1 ,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamine;

170). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,3-dimethylurea; 171). 4-methylpiperazine-1-carboxylic acid 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|methylamide; 172). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1,3,3-trimethylurea; 173) I4-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of piperidine-1-carboxylic acid; 174) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Imethylamide of morpholine-4-carboxylic acid; 175) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of pyrrolidine-1-carboxylic acid; 70 176) 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)-1-methylurea; 177). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-3,3-diethyl-1-methylurea; 178). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|formamide; 179) I3-(6,8-dichloro-2-methyl-1,2, 3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamine; 180) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of pyrrolidine-1-carboxylic acid; 181) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of piperidine-1-carboxylic acid; 182). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1,3,3-trimethylurea; 183) 1-I3-(6,8-dichloro -2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,3-dimethylurea; 184) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl-methylamide of morpholine-4-carboxylic acid; 185). I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of 4-methylpiperazine-1-carboxylic acid; 186) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)-1-methylcarbamide; Article 187). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-3,3-diethyl-1-methylurea; 188) 2-dimethylaminoethyl ether i)

13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 189) 2-dimethylaminoethyl ether

I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; c zo 190) 2-dimethylaminoethyl ether (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; - 191) methyl ester of 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylcarbamic acid; o 192) ethyl ester of 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|carbamic acid; 193) isopropyl ether of 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylcarbamic acid; i- 194) 2,2-dimethylpropyl ether i-

13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 195) methyl ester of 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylcarbamic acid; 196) isopropyl ether (4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylcarbamic acid; 197) 2,2-dimethylpropyl ether "

I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; from p. 198) ethyl ether |4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|carbamic acid; . 199). (K)-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; and?" 200). (5)-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; 201). (kK)-1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylurea; 202). (5)-1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylurea; -I 203). M-III-(6,8-difluoro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|acetamide; 204). 4-(3-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline;

Sh- 205). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-3-(2-hydroxyethyl)urea; o 206) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid ethyl ether; 207) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid; ve as well as their pharmaceutically acceptable salts.

Ge In the highest degree, compounds from the group: 1) are preferred. M-I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|acetamide; 2) 4-(6,8-dichloro-2-methyl- 1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; 3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; 4). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylthiourea;

F) 5). 1-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylurea; ka 6). M-I4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylacetamide; 7). Mch-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide; at 8). M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 9) I4-(6,8-dichloro-2-methyl-1 ,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide of 1-acetylpiperidine-4-carboxylic acid; 10).chCh-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|methanesulfonamide; 11) 14-(6,8-dichloro-2-methyl-1 ,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of ethanesulfonic acid; 65 12). MM'-dimethylamino--I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|sulfamide; 13).h-IZ-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide;

14). mch-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/phenyl|butyramide; 15). mch-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylisobutyramide; 16) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide cyclopropanecarboxylic acid; 17) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of cyclobutanecarboxylic acid; 18). h-IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-2,2,2-trifluoroacetamide; 19) IZ-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide of 1-acetylpiperidine-4-carboxylic acid; 20). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|nicotinamide; 70 21). Mch-13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl)methanesulfonamide; 22) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of ethanesulfonic acid; 23) M'M'-dimethylamino-IM-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|sulfamide; 24) (2-(6 Cyclopropanecarboxylic acid ,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide; 25) (2-(6,8-dichloro-2-methyl-1,2,3,4 -tetrahydroisoquinolin-4-yl)uphenyl|amide of 1-acetylpiperidine-4-carboxylic acid /5 ACID; 26). 1-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-ethylurea; 27). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylthiocarbamide; 28). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-ethylurea; 29). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-methylthiourea; 30)

M-15-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenylsulfamoyl|-4-methylthiazol-2-yl)acetamide; 31). 1,2-dimethyl-1H-imidazole-4-sulfonic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 32). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-C,C,C-trifluoromethanesulfonamide; Art. 33). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-C,C,C-trifluoromethanesulfonamide; 34) M-ethyl-M'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonylurea; i) 35). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-dimethylaminoacetamide; 36) (4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 2,6-diaminohexanoic acid; 37) I4-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1H-pyrrole-3-carboxylic acid; c zo 38) 1-methylpiperidine-4-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; - 39) |4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide o 1-methanesulfonylpiperidine-4-carboxylic acid; 40) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1H-pyrazole-4-carboxylic acid; i- 41). h-IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-methylaminoacetamide; i- 42). h-13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-dimethylaminoacetamide; 43). 2-amino-M-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 44). 2-amino-M-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/phenyl|butyramide; 45) I3-(6,8-dichloro- 2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 2,6-diaminohexanoic acid; 46) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1-methylpiperidine-4-carboxylic acid; . 47) IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl]amide of 1H-imidazole-4-carboxylic acid; and?" 48). 1-Methanesulfonylpiperidine-4-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide; 49) 13-(6,8-dichloro-2-methyl-1D,3,4-tetrahydroisoquinolin-4-yl)uphenylamide -I 3,5-dimethyl-1H-pyrazole-4-carboxylic acid; 50) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1H-pyrazole-4-carboxylic acid; - 51). 3-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,1-dimethylurea; o 52) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide 4-methylpiperazine-1-carbon

Acids; ve 53) Piperidine-1-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide;

Ge 54) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; 55) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-1-carboxylic acid; 56) 3-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)-1,1-diethylurea; 57). 1-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-33-methylurea; 58). 1-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)urea;

F) 59). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-(tetrahydrofuran-z-yl)urea; ka 60) /1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-(tetrahydropyran-4-yl)urea; 61) in 3-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1-methyl-1-(1-methylpiperidin-4-yl) urea; 62) 3-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1--3-dimethylaminopropyl)-1-methylurea; 63) 3-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1--2-dimethylaminoethyl)-1-methylurea; 65 64) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-3-"3-dimethylaminopropyl)urea; 65). 1-IZ3-( 6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl()|-3-(2-methoxyethyl)urea;

66). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-pyridin-3-ylurea; 67). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-pyridin-4-ylurea; 68) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide 4-methylpiperazine-1-carbon

ACIDS; 69). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-33-methylurea; 70). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)urea; 71) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 4-methylpiperazine-1-carboxylic acid; 70 72). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-33-methylurea; 73). 3-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,1-dimethylurea; 74). 3-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)-1,1-diethylurea; 75) 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)urea; 76) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; 77). M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|formamide; 78). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|formamide; 79). 1-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,3,3-trimethylurea; 80) 1-I3-(6 ,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,3-dimethylurea; 81) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of morpholine-4-carboxylic acid; 82). I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|methylamide of 4-methylpiperazine-1-carboxylic acid; 83) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)-1-methylurea; 84) 2-dimethylaminoethyl ether

13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 85) 2-dimethylaminoethyl ether i)

I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 86) 2-dimethylaminoethyl ether (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; c zo 87) methyl ester of 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/phenylcarbamic acid; 88) (K or 5)-M-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylimethanesulfonamide; - 89) (K or 5)- 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylurea; o 90). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl1-3-(2-hydroxyethyl)urea; and their pharmaceutically acceptable salts. uh-

Further, the invention relates to the use of compounds of the formula (I) for the preparation of a medicinal product for the treatment of diseases that can be influenced by inhibiting the sodium-proton exchange of the PI subtype (NEP), where:

KI, K2, KZ and K4, independently of each other, mean H, RE, SI, Vg, I, SM, MO", OH, MN", SaNzachi, SadNada-i

ОСНон, СООМ10, ОСОК10, СОКТ0 or О,-(СНо)у-phenyl; « a and 5 in the groups СаНоани and ОСНоюня, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8, and n) с one or more H-atoms can be replaced by P-atoms; . da means 3, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by P-atoms; and 10 means H or SeNosi; c means 1, 2, C, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by H-atoms; x means zero or 1; - And y means zero, 1, 2, Z or 4; and the phenyl ring in the O,-(CH»)/-phenyl group is unsubstituted or substituted by 1-3 substituents selected from the group consisting of РЕ, СИ, Вг, СМ, МО», ОН, МН» or СаНздчи; o and means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; or pi KIT, K2, KZ and K4, independently of each other, mean heteroaryl, and as ring atoms can

Z contains 0, 1, 2, 3 or 4 nitrogen atoms, 0 or 1 oxygen atom or 0 or 1 sulfur atom; or

КИ, К2, КЗ and К4, independently of each other, mean СОК11К12 or МК11К12;

K11 and K12, independently of each other, mean H, SeNoeni, StNot-1; e means 1,2, 3,4, 5,6, 7 or 8; (F) гг means 3, 4, 5, 6, 7 or 8, and in the SeNoech1 and StNotp-1 groups, one or more H-atoms can be replaced by P-atoms and one or more СНо-groups can be replaced by О or MK13; 60 KIZ means H or XiaNov4;

It means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; or

КИЗ and one СНо group of the К11 or К12 radical, together with the nitrogen atom to which they are connected, form a 5- or b--linked cycle; or 65 K11 and K12, together with the nitrogen atom to which they are connected, form a 5-, 6- or 7-lene cycle; or

K11 and K12, independently of each other, mean СОК14, С5К14 or 50214;

K14 means SoNadyai; d means 1, 2, 3, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by E-atoms and one or more СНо-groups can be replaced by O or MK13; or

КИ, К2, КЗ and К4, independently of each other, mean -0,-5О)-К15, and also means zero or 1; means zero, 1 or 2; 70 K15 means SKNokii, OH, OSINami or MK17K18;

K means 1, 2, 3, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by E-atoms;

Y means 1, 2, C, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by E-atoms;

K17 and K18, independently of each other, mean H or StpNotch1, t means 1, 2, 3, 4, 5, 6, 7 or 8, and in the group StNotin one or more H-atoms can be replaced

E atoms and one or more СНо groups can be replaced by О, СО, С5 or MK19;

K19 stands for H or SuNodchi; n means 1, 2, C or 4; moreover, in SaNor-4, one or more H-atoms can be replaced by E-atoms; or

K17 and K18, together with the nitrogen atom to which they are connected, form a 5-, 6- or 7-lene cycle; or

K19 and one СНо group of the K17 or K18 radical together with the nitrogen atom to which they are connected form a 5- or b--linked cycle;

K5 stands for H, SeNorni, SevNovv, SOK2O or BOZ2O; сч о means 1, 2, Z, 4, 5, 6, 7 or 8; c5 means 3, 4, 5, 6, 7 or 8; (8) and in SrNorai and Se5Novv-1 one or several H-atoms can be replaced by P-atoms; k20 means SaNzdyai; d means 1,2, 3,4,5,6, 7 or 8, with zo and in the C3Nod group one or more H-atoms can be replaced by P-atoms and one or more

CH»e-groups can be replaced by O or MK21; -

K21 means H or; o r means 1, 2, C or 4; moreover, in SINAg-i, one or more H-atoms can be replaced by P-atoms; in.

Kb means H, E, SI, Vg, Y, SeNaovchn, SdaNzda-1, OH, oOSsSNaya or osSoOng2; rch- z iy, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8; ad means 3, 4, 5, 6, 7 or 8, and in SeNovch1; In SaaNoda-1 and OSINo3-ya, one or more H-atoms can be replaced by E-atoms;

K22 means Sun Nights; « и means 1, 2, Z or 4; in c and in C, |Na)c-4 one or more H-atoms can be replaced by E-atoms;

К7, КВ and КУ, independently of each other, mean -О,-50,,-К23; with M means zero or 1; m means zero, 1 or 2; k23 means SppNaoppya1» SttNott-i OH, OSrrNorr-i or MK25K26; - And пп and пр, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8; tt means 3, 4, 5, 6, 7 or 8, and in SppNoppya» SttNaott-i and OSrrNorr-i one or more H-atoms can be replaced by P-atoms; o K25 and K26, independently of each other, mean Н, СМ or С,Нао»н1, С,»Но»»1; 7 means 1, 2, 3, 4, 5, 6, 7 or 8; pi 77 means 3, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by E-atoms and

He in С,Н2,-14 one or more H-atoms can be replaced by P-atoms and one or more СНо-groups can be replaced by 0, СО, С5 or К27;

K27 means H or SaaNodachi; 5B aa means 1, 2, Z or 4; and in SaaNodaz-1 ONE or several H-atoms can be replaced by E-atoms;

Ф) either K25 and K26 together with the nitrogen atom to which they are connected form a 5-, 6- or 7-membered ring, or in K27 and one СНо group of the K25 or K26 radical together with the nitrogen atom, with by which they are connected, form a 5- or b--linked cycle; or

K?7, KV and KU, independently of each other, mean MK32СОМКЗО, MK32С5КЗО or MK325О0бКЗО;

KZO means H, SooNossiai» SuNouu.1, pyrrolidinyl or piperidinyl, in the cycles of which one CH o-group can be replaced by O or MK33;

KZ2 and K33, independently of each other, mean H or SuNorn4;

рр means 2 or 3; ss means 1, 2, 3, 4, 5, 6, 7 or 8; uu means 3, 4, 5, 6, 7 or 8; and means 1, 2, 3, 4, 5, 6, 7 or 8; moreover, in SuNonch one or more H atoms can be replaced by P atoms and in SesNosni and SuNouu 1 groups one or more H atoms can be replaced by P atoms and one or more СНо groups can be replaced by МКЗ1 and one СНо- the group can be replaced by 0;

KZ1 means H, SKNokknyi, SOKb5 or 50565; 70 KK means 1, 2, C or 4; and one or more H-atoms can be replaced by E-atoms;

Кб5 means Н, СххНоххчи; xx means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms; or

KZ1 together with one СНо group of the KZO radical forms a 5-, 6-, or 7-lene ring; or

KZO means a 5- or b-lene heteroaryl with 1, 2, 3 or 4 nitrogen atoms, 0 or 1 sulfur atoms and 0 or 1 oxygen atoms, which is unsubstituted or substituted up to three times with substituents selected from the group consisting of E, SI, Vg, I. SooNooozi, MAK7OK71;

KO and K71, independently of each other, mean H, SuuNotsuichya and SOK72;

K72 stands for H, SL,/Nowuchi oo, shi and mu, independently of each other, stand for 1, 2, 3, 4, 5, 6, 7 or 8; and in SooNooogi groups; One or more H-atoms can be substituted in CtsSNHOcs or SuU/NouUi

E-atoms; or

K7, KV and KU, independently of each other, mean H, E, SI, Vg, I, MO", SM, OH, MN", SeeNovech1;. Court Nodu- 1, (8)

OsSeNovi, MK4OKa1, SOMK4OKA1, SOOK42, SOKaYa2 or OSOKA2; ee and I, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8; mly means 3, 4, 5, 6, 7 or 8; with zo and in the groups SeeNovech1, SuluNoudu-1 and OSyaNovya one or more H-atoms can be replaced

E-atoms; "

K40 and K41 mean H, SeNon, or C(IMN)MN"; at

HER means 1, 2, Z, 4, 5, 6, 7 or 8; moreover, in the SeNon group, one or more H-atoms can be replaced by P-atoms, and one or more SNeo-corpses can be replaced by O- or MKA44; Cha

K44 means H or C.5Noduni; yes means 1, 2, 3, 4, 5, 6, 7 or 8; moreover, in the C3uNgdud group, one or more H-atoms can be replaced by P-atoms; or "

K4O and K41, together with the nitrogen atom to which they are connected, form a 5- or b--linked ring; with c K42 means H or SfNonniai; n means 1, 2, 3, 4, 5, 6, 7 or 8; ;" moreover, one or more H-atoms can be replaced by P-atoms in the SnNonn group; as well as their pharmaceutically acceptable salts.

Preferred use of compounds of formula (I), where: -I КИ, К2, КЗ and К4, independently of each other, mean Н, РЕ, СИ, Вг, И, СМ, МО», ОН, МН», СаНоа»и, cycloalkyl with 3, 4, 5 or 6 C-atoms, OXN, SOOK10; - a and 6, independently of each other, mean 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms;

K10 means H or CoNosyai; pi c means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms;

With or

KI, К2, КЗ and К4, independently of each other, mean 5- or b--lene heteroaryl selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl and oxazolyl; or (F) КИ, К2, КЗ and К4, independently of each other, mean СОМК11К12 or МК11К12; ka K11 and K12, independently of each other, mean H, SeNoeni, StNot-1; e means 1, 2, C or 4; 60 gg means 3, 4, 5 or 6, and in the SeNzechi and StNaorg.-1 groups one or more H-atoms can be replaced by E-atoms; or

K11 and K12, independently of each other, mean hydroxyethyl, M,M-dimethylaminoethyl, M,M-diethylaminoethyl, pyrrolidinoethyl, M-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; 65 or

K1T1 and K12, together with the nitrogen atom to which they are connected, form pyrrolidine, piperidine,

M-methylpiperazine, piperazine or morpholine ring; or

K11 and K12, independently of each other, mean SOK14, SZK14, SOMNI14, SZMNK14 or 5ОЖ14;

Kt14 means CaNod1; 9 means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; or

КИ, К2, КЗ and К4, independently of each other, mean О5ОЗН, ЗОЗН, 502К15, and

K15 means SKNokya1, OSINa»nii or MK17K18; 70 K means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms;

Y means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms;

K17 and K18, independently of each other, mean H, СТНот:и, in which the first is bound to the nitrogen atom

The CH»o group is replaced by CO and the second СНо group is replaced by MK19; t means 1, 2, 3, 4 or 5, and one or more H-atoms can be replaced in the group СТНоти

E-atoms;

K19 stands for H or SuNodchi; n means 1, 2, C or 4; moreover, in SaNor-4, one or more H-atoms can be replaced by E-atoms; or

K17 and K18, together with the nitrogen atom to which they are connected, form a 5- or b--lene cycle;

KB stands for H, SeNaorai» SezNovv-1; p means 1, 2, C or 4; c5 means 3, 4, 5 or 6, and in SeNoray and SeNovv-1 one or more H-atoms can be replaced by P-atoms; high school

Kb means H, SeNovyi, OSINo3nya or OSOK22; z and i, independently of each other, mean 1, 2, З or 4; (8) moreover, in SeNovch and OSINany, one or more H-atoms can be replaced by E-atoms;

K22 means Sun Nights; и means 1, 2, C or 4; c zo and in C, |Na)c-4 one or more H-atoms can be replaced by E-atoms;

К7, КВ and КУ, independently of each other, mean ОБОЗН, ЗОЗН or 5ОБК23; "k23 means SppNaoppya1" SttNott-1i" OSrrNorr-i or MK25KO; o пп and пр, independently of each other, mean 1, 2, 3, 4 or 5; tt means 3, 4, 5 or 6, c. and in SppNoppya» SttNaott-i and OSrrNorr-i one or more H-atoms can be replaced by P-atoms; uh-

K25 and K26, independently of each other, mean Н, СМ, С, Н2/»-1, and the first one bound to the nitrogen atom

The СНо group is replaced by СО or С5 and the second СНо group is replaced by MK27; 7 means 1, 2, 3, 4, 5 or 6; and in C,H2,-41 one or more H-atoms can be replaced by P-atoms; "

K27 means H or SaaNodachi; in c aa means 1, 2, Z or 4; . and in SaaNodaz-1 ONE or several H-atoms can be replaced by E-atoms; and" or

K25 and K26, together with the nitrogen atom to which they are connected, form a 5- or β-ene ring, or -I K27 and one СНо group of the radical K25 or K26 together with the nitrogen atom to which they are connected, form a 5- or b-linked cycle; - or about K?7, KV and KU, independently of each other, mean MK32SOKZO, MK32S5KZO or MK32505K30;

KZO means H, OH, SeONosya, SuNouU, pyrrolidinyl or piperidinyl, in the rings of which one CO group can be replaced by O or MK33;

He KZ2 and K33, independently of each other, mean H or SuNorn4; ss means 1, 2, 3, 4, 5, 6, 7 or 8; uu means 3, 4, 5 or 6; 5B n means 1, 2, C or 4; moreover, in SiNonch one or several H-atoms can be replaced by P-atoms and in the groups SosNossyai and SuuNouul

F) one or more H-atoms can be replaced by E-atoms and one or more СНо-groups can be replaced by МКЗ1 and one СНо-group can be replaced by 0;

MAKZ1 means H, SKNokkayayi, SOKb5 or 50265; 60 KK means 1, 2, Z or 4; and one or more H-atoms can be replaced by E-atoms;

Кб5 means Н, СххНоххчи; xx means 1, 2, C or 4, and one or more H-atoms may be replaced by P-atoms; or 65 KZ1, together with one СНо group of the KZO radical and the nitrogen atom with which they are connected, form a 5- or b--lene cycle;

or

KZO means a 5- or b-lene heteroaryl selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thienyl, thiazolyl and oxazolyl, which are unsubstituted or substituted up to three times with substituents selected from the group , which consists of RE, SI, Vg, I, SooNosochzi", MA7OK7 1;

K?O and K71, independently of each other, mean H, SuuNotsu-i or SOK?72;

K72 stands for H, SL/Nouchi; оо, ши and мм, independently of each other, mean 1, 2, З or 4; and in SooNooogi groups; In SzshNHYotsii or SuU/Nouuii one or more H-atoms can be replaced by 70 E-atoms; or

K7, KV and KU, independently of each other, mean H, E, SI, Vg, I, MO", SM, OH, MN", SeeNovech1;. Court Nodu- 1,

OsSeNoti, MK4OK41, СОМК4ОКА1, СООК42, СОКаЯ2 or OSOKA2; ee and I, independently of each other, mean 1, 2, Z or 4; mly means 3, 4, 5 or 6; moreover, in the groups SeeNovech1, SuluNoudu-1, and OSyaNovya, one or more H-atoms can be replaced

E-atoms;

K40 and K41 mean H, SeNon, or C(IMN)MN";

HER means 1, 2, Z, 4, 5, 6, 7 or 8; moreover, one or more H-atoms can be replaced by E-atoms in the SeNon-yai group; or

K4O and K41, independently of each other, are selected from the group consisting of hydroxyethyl,

M,M-dimethylaminoethyl, M,M-diethylaminoethyl, pyrrolidinoethyl, M-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or

K40 Its K41, together with the nitrogen atom to which they are connected, form a cycle selected from the group i) consisting of pyrrolidine, piperidine, M-methylpiperazine, piperazine and morpholine;

K42 means H or SfNonniai; pi means 1, 2, C or 4; c zo and in the SenNon group one or more H-atoms can be replaced by E-atoms; as well as their pharmaceutically acceptable salts. -

Especially preferred is the use of compounds of formula (I), where: o

КИ, К2, КЗ and К4, independently of each other, mean Н, РЕ, СИ, Вг, ОН, МН», СаНза-4, cycloalkyl with 3, 4, 5 or 6 C-atoms, ОСНоя; - a and 6 in the groups СаНоай and ОСНоййяй, independently of each other, mean 1, 2, З or 4, and one or several H-atoms can be replaced by P-atoms; or

КИ, К2, КЗ and К4, independently of each other, mean МК11К12;

K11 and K12, independently of each other, mean H, SeNoeni, StNot-1; "e" means 1, 2, C or 4; in c gg means 3, 4, 5 or 6, . moreover, in the SeNzechi and StNaorg.-1 groups, one or more H-atoms can be replaced by E-atoms; "" or

K11 and K12 together with the nitrogen atom to which they are connected form a ring selected from the group consisting of pyrrolidine, piperidine, M-methylpiperazine, piperazine and morpholine; - And or

K11 and K12, independently of each other, mean SOK14, SZK14, SOMNI14, SZMNK14 or 5ОЖ14; - K14 means SoNadyai; o 9 means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; or pi КИ, К2, КЗ and К4, independently of each other, mean О5ОЗН, 5ОЗН, 50215;

Ge K15 means SKNokya1 SuluNoulu-i or MK17K18;

K means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms;

K17 and K18, independently of each other, mean H or StpNotchi1; t means 1, 2, 3, 4 or 5, and one or more H-atoms can be replaced in the group X

E-atoms;

Ф) or ka K17 and K18, together with the nitrogen atom to which they are connected, form a 5- or b--linked ring;

KB stands for H, SeNaorai» SezNovv-1; 60 p means 1, 2, Z or 4; c5 means 3, 4, 5 or 6, and in SeNortO and Se5Nove-1 one or more H-atoms can be replaced by P-atoms;

Kb means H, СНу";

K?7, KV and KU, independently of each other, mean OZOZN, 5OZN or GOD; 65 K23Z means SppNopp-i 8bo MK25K26; pp means 1, 2, 3, 4 or 5;

moreover, in SdpNoppya1 ONE or several H-atoms can be replaced by E-atoms;

K25 and K26, independently of each other, mean Н, СМ or С,Н2,-41, IN WHICH is bound to the nitrogen atom the first

The СНо group is replaced by СО or С5 and the second СНо group is replaced by MK27; 7 means 1, 2, 3, 4, 5 or 6; and in C,H2,-41 one or more H-atoms can be replaced by P-atoms;

K27 means H or SaaNodachi; aa means 1, 2, C or 4; and in SaaNodaz-1 ONE or several H-atoms can be replaced by E-atoms; 70 or

K25 and K26, together with the nitrogen atom to which they are connected, form a 5- or b--len ring, or

K27 and one СНо-group of the radical K25 or K26 together with the nitrogen atom to which they are connected form a 5- or b--linked ring; or

K?7, KV and KU, independently of each other, mean MK32SOKZO, MK32S5KZO or MK32505K30;

KZO means H, OH, SesNosyai, SuNouul, pyrrolidinyl or piperidinyl, in the rings of which one CH o-group can be replaced by O or MKZ33;

KZ2 and KZZ mean H, CH" or CE"; ss means 1, 2, 3, 4, 5, 6, 7 or 8; uu means 3, 4, 5 or 6; moreover, in the groups SosNossyai and SuuNouu-1 one or more H-atoms can be replaced by P-atoms and one or more СНо-groups can be replaced by MKZ1 and one СНо-group can be replaced by 0;

KZ1 means H, methyl, ethyl, СЕ5, СНоСЕ»3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl; or

KZ1, together with one СНо group of the KZO radical and the nitrogen atom with which they are connected, form a 5- or i) b-lene cycle; or

KZO means pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl, which are unsubstituted or substituted with up to three substituents selected from the group consisting of KE, SI, methyl, ethyl, trifluoromethyl, MH, MH -acetyl; - or o

K7, KV and KU, independently of each other, mean H, E, SI, OH, MN", SeeNovech1". Sumu Nomlu-1;. OSyaNoni,

MAK4OKa1, SOMKAOKAT, SOOKa2 or OSOKA42; - ее and Я, independently of each other, mean 1, 2, Z or 4; ate means 3, 4, 5 or 6; moreover, in the groups SeeNovech1, SuluNoudu-1, and OSyaNovya, one or more H-atoms can be replaced

E-atoms;

K40 and K41 mean H, SeNon, or C(IMN)MN"; "

Her means 1, 2, Z or 4; in c and in the group SeNon-yai one or more H-atoms can be replaced by E-atoms; or from K4O and K41, independently of each other, mean hydroxyethyl, M,M-dimethylaminoethyl, M,M-diethylaminoethyl, pyrrolidinoethyl, M-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or

K4O and K41 together with the nitrogen atom to which they are connected form a pyrrolidine, piperidine, -I M-methylpiperazine, piperazine or morpholine cycle;

K42 means H or SfNonniai; - pi means 1, 2, C or 4; and in the SnNon group, one or more H-atoms can be replaced by P-atoms; as well as their pharmaceutically acceptable salts. o In a higher degree preferred use of compounds that are selected from the group consisting of

Ge 1). Mch-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|acetamide; 2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; 3). 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; 4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M,M-dimethylbenzenesulfonamide; 5). 4-(4-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline; (F) 6) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid; ka 7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-ethylbenzamide; 8). 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-propylbenzamide; in 9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-(2-dimethylaminoethyl)benzamide; 10) 6,8-dichloro-2-methyl-4-(4-morpholin-4-ylphenyl)-1,2,3,4-tetrahydroisoquinoline; 113. I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|diethylamine; 12) 6,8-dichloro-2-methyl-4-(4-piperidin-1-ylphenyl)-1,2,3,4-tetrahydroisoquinoline; 13). 6,8-dichloro-2-methyl-4-(4-pyrrolidin-1-ylphenyl)-1,2,3,4-tetrahydroisoquinoline; 65 14). 6,8-dichloro-2-methyl-4-(4-(4-methylpiperazin-1-yl)phenyl|-1,2,3,4-tetrahydroisoquinoline; 15) 6,8-dichloro-2-cyclopropyl-4 -phenyl-1,2,3,4-tetrahydroisoquinoline;

16). 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine; 17). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-propylurea; 18). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylthiourea; 19). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-ethylurea; 20). M-(4-(6-methanesulfonyl-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|acetamide; 21). Mch-I4-(2,6,8-trimethyl-1,2, 3,4-tetrahydroisoquinolin-4-iluphenyl|acetamide; 2235. h-I4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|acetamide; 23 ). M-I4-(8-chloro-2-methyl-6-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|acetamide; 25). M-4-18-chloro-2-methyl-6-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydroisoquinolin-4-yl|phenyl)acetamide; 26). M-(4-(3-chloro-6--(cyclopropylmethylamino)-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl|phenyl)acetamide; 27) 5-(6,8-dichloro- 2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid; 28) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxy-M-methylbenzamide; 29) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-ethyl-2-hydroxybenzamide; 30) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-(2-dimethylaminoethyl)-2-hydroxybenzamide; 31). Mch-I5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoylguanidine; 32). M-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide; 33) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine; 34) 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine; 35). M-I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|propionamide; 36). M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; 37) I4-(6,8-dichloro-2-methyl-1 ,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|pentanoic acid amide; 38). h-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylisobutyramide; Article 39). -(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2,2-dimethylpropionamide; 40) I4-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl|cyclopropanecarboxylic acid amide; i) 41) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of cyclobutanecarboxylic acid; 42) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of cyclopentanecarboxylic acid; 43). M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-2,2,2-trifluoroacetamide; c zo 44) I4-(6, 8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1-acetylpiperidine-4-carboxylic acid; - 45). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|nicotinamide; o 46) M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|imethanesulfonamide; 47) I4-(6,8-dichloro-2- ethanesulfonic acid methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; i- 48) M'M'-dimethylamino-H-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|sulfamide; i- 49). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 50). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; 51) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pentanoic acid; 52). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylisobutyramide; "53). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2,2-dimethylpropionamide; from p 54) Cyclopropanecarboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; . 55) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Iamide of cyclobutanecarboxylic acid; and?" 56) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of cyclopentanecarboxylic acid; 57). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iso)phenyl)-2,2,2-trifluoroacetamide; 58) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide of 1-acetylpiperidine-4-carboxylic acid; 59). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|nicotinamide;

Sh-60) Ch-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; at 61). I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl/uphenyl|ethanesulfonic acid amide; 62). M'M'-dimethylamino-M-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|sulfamide; ve 63). M-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|propionamide;

Ge 64) M-(2-(6,8-dichloro-2-methyl-1,2,354-tetrahydroisoquinolin-4-yl)/phenyl|butyramide; 65) (2-(6,8-dichloro-2-methyl- 1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|pentanoic acid amide; 66) M-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4- yl)uphenylisobutyramide; 67). Mch-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2,2-dimethylpropionamide; 68) (2-(6,8-dichloro Cyclopropanecarboxylic acid -2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide;

F) 69) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Iamide of cyclobutanecarboxylic acid; ka 79) (2-(6,8-dichloro -2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|cyclopentanecarboxylic acid amide; 71)..h-(2-(6,8-dichloro-2-methyl-1,2,3 ,4-tetrahydroisoquinolin-4-iluphenyl)|-2,2,2-trifluoroacetamide; in 72) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl) uphenyl|iamide of 1-acetylpiperidine-4-carboxylic acid; 73). Mch-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; 74) (2-(6,8-dichloro-2-methyl- 1,2,3,4-tetrahydroisoquinolin-4-yl/uphenyl|ethanesulfonic acid amide; 75) MM'-dimethylamino-M-(2-(6,8-dichloro-2-methyl-1,2,3,4- tetrahydroisoquinoline-4-iluphenyl|sulfamide; 65 76). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-3-ethylurea; 77 ). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-methylthiourea;

78). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-3-ethylurea; 79). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-methylthiourea;

M-15-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylsulfamoyl|-4-methylthiazol-2-yl)iacetamide; 81)

M-15-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylsulfamoyl|-4-methylthiazol-2-yl)iacetamide; 82) 1,2-dimethyl-1H-imidazole-4-sulfonic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide; 70 83). 1,2-dimethyl-1H-imidazole-4-sulfonic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide; 84) |4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid amide ; 85). I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide 75 -chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid; 86). 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl 5-bromothiophene-2-sulfonic acid; 87). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl 5-bromothiophene-2-sulfonic acid; 88). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-C,C,C-trifluoromethanesulfonamide; 89). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-C,C,C-trifluoromethanesulfonamide; 90) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide 2,2,2-trifluoroethanesulfonic acid; 91). I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide 2,2,2-trifluoroethanesulfonic acid; 92). M-ethyl-M'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonylurea; 93) 2-chloro-5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; 94) 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine; ch 95) 6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 96) 4-(8-amino-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenol; i) 97) 8-methoxy-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 98). 2-(8-amino-2-ethyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenol; 99). 2-(8-amino-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenol; c zo 100) 5-(8-amino-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-methoxyphenol; 101) 2-methyl-8-nitro-4-phenyl-1,2,3,4-tetrahydroisoquinoline; - 102). 4-(8-amino-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzene-1,2-diol; o 103) 2,8-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 104) 4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline; i- 105). 4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine; i- 106) 4-(2,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine; 107). 4-(3-chlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine; 108) 2,4-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 109) 2-butyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine; 110). M-(2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)lacetamide; from p. 111). 7-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; . 112). 8-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; and? 113) 2,6-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 114) 6b-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 115) b-methoxy-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; -I 116) 2-ethyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 117) 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; - 118) 6,8-dichloro-2-ethyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; at 119). 4-(4-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline; 120) 2-methyl-4-phenyl-b,8-bistrifluoromethyl-1,2,3,4-tetrahydroisoquinoline; pi 121) 6,8-dichloro-2-isopropyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline;

Ge 122) 5,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 123) 6,8-dichloro-4-(4-fluorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline; 124) 6,8-dichloro-2-methyl-4-p-tolyl-1,2,3,4-tetrahydroisoquinoline; 125) 5,6-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 126) 6,7-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline;

F) 127) 8-bromo-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; ka 128) 6,8-dichloro-4-(4-chlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline; 129) 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; at 130). 2-amino-M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|acetamide; 131). h-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-methylaminoacetamide; 132)..Mch-I4-(6,8- dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-2-dimethylaminoacetamide; 133). 2-amino-M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 134). 2-amino-M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; 65 135) 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 2,6-diaminohexanoic acid; 136) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-2-carboxylic acid;

137). h-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylisonicotinamide; 138) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 1H-pyrrole-3-carboxylic acid; 139) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 1H-pyrrole-2-carboxylic acid; 140) 1-methylpiperidine-4-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide; 141). 1,4-dimethyl-1H-pyrrole-2-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 142) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 4-nitro-1H-pyrrole-2-carbon

R where it is 143). 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 2,5-dimethyl-1H-pyrrole-3-carboxylic acid; 144) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl amide of 1H-imidazole-4-carboxylic acid; 145). 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 1-methanesulfonylpiperidine-4-carboxylic acid; 146) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 3,5-dimethyl-1H-pyrazole-4-carboxylic acid; 147) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1H-pyrazole-4-carboxylic acid; 148) 4-(6,8-dichloro-2-methyl-1,2,3L-tetrahydroisoquinolin-4-yl)phenyl|amide

C-trifluoromethyl-1H-pyrazole-4-carboxylic acid; 149). h-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-methylaminoacetamide; 150). h-13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-dimethylaminoacetamide; 151). 2-amino-M-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 152). 2-amino-M-I3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; ch 153) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 2,6-diaminohexanoic acid; 154) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-2-carboxylic acid; i) 155). h-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylisonicotinamide; 156) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1H-pyrrole-3-carboxylic acid; 157) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1H-pyrrole-2-carboxylic acid; c zo 158) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide of 1-methylpiperidine-4-carboxylic acid; - 159). I13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide o 1,4-dimethyl-1H-pyrrole-2-carboxylic acid; 160) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide 4-nitro-1H-pyrrole-2-carbonic

With ACIDS; chapter 161). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 2,5-dimethyl-1H-pyrrole-3-carboxylic acid; 162) 1H-imidazole-4-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl Iiamide; 163). 1-methanesulfonylpiperidine-4-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; from p. 164) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide. 3,5-dimethyl-1H-pyrazole-4-carboxylic acid; and?" 165) 1H-pyrazole-4-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylilamide; 166) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide

C-trifluoromethyl-1H-pyrazole-4-carboxylic acid; -I 167). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylthiourea; 168). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylthiourea;

Sh- 169). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylthiourea; at 170). 3-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; 171) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide of 4-methylpiperazine-1-carboxylic acid;

He 172) Piperidine-1-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide; 173) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; 174) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-1-carboxylic acid; 175) 3-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-1,1-diethylurea; 176). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea;

F) 177). 1-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3--2-dimethylaminoethyl)urea; ka 178). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-(tetrahydrofuran-3-yl)urea; 179) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-(tetrahydropyran-4-yl)urea; 60 180) 3-IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1-methyl-1-(1-methylpiperidin-4-yl)urea; 181) 3-IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1-(3-dimethylaminopropyl)-1-methylcarbamide; 182) 65 3-I3 -(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1--2-dimethylaminoethyl)-1-methylurea; 183). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--3-dimethylaminopropyl)urea;

184). 1-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-(2-methoxyethyl)urea; 185). 1-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-pyridin-3-ylurea; 186). 1-3-(6,8-dichloro-2-methyl-1,2,33,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-pyridin-4-ylurea; 187) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|4-methylpiperazine-1-carboxylic acid amide; 188). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; 189). 3-(2-(6,8-dichloro-2-methyl-1,2,3Z54-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; 190). 3-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-1,1-diethylurea; 70 191) (2-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|piperidine-1-carboxylic acid amide; 192) (2-(6,8-dichloro-2-methyl-1,2 ,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; 193) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide pyrrolidine-1-carboxylic acid; 194). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3--2-dimethylaminoethyl)urea; 195) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 4-methylpiperazine-1-carboxylic /5 ACID; 196) (pyrrolidine-1-carboxylic acid 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 197). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; 198). 3-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; 199) 3-(4-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,1-diethylurea; 200). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)urea; 201) Piperidine-1-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl iamide; 202) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; 203). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|formamide; 204) (|4-(6,8-dichloro-2-methyl-1, 2,3,4-tetrahydroisoquinolin-4-yl)phenyl|methylamine; ch 205). 1-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,3-dimethylurea; 206) |4-(6,8-dichloro -2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl|methylamide and) 4-methylpiperazine-1-carboxylic acid; 207). 1-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,3,3-trimethylurea; 208) I4-(6,8- dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide piperidine-1-carbonate

From Acid; 209) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of morpholine-4-carboxylic acid; o 2190) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of pyrrolidine-1-carboxylic acid; - 211) part of 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)-1-methylurea; 212). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-3,3-diethyl-1-methylurea; 213). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Iformamide; 214) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|methylamine; 215) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of pyrrolidine-1-carboxylic acid; . 216) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of piperidine-1-carbonate and? acids; 217). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,3,3-trimethylurea; 218). 1-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,3-dimethylurea; -I 219) IZ-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of morpholine-4-carboxylic acid;

Sh-220) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl|methylamide o 4-methylpiperazine-1-carboxylic acid; 221) and 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)-1-methylurea;

Ge 222) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl/|-3,3-diethyl-1-methylurea; 223) 2-dimethylaminoethyl ether

13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 224) of 2-dimethylaminoethyl ether

I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid;

F) 225) 2-dimethylaminoethyl ether of (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 226) methyl ether (IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenylcarbamic acid; in 227) ethyl ether IZ3-(6,8-dichloro- 2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylcarbamic acid; 228) isopropyl ether of 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)carbamic acid; 229) of 2,2-dimethylpropyl ether

13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 65 230) methyl ether (4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl Icarbamic acid; 231) isopropyl ether I4-(6,8-dichloro- 2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)carbamic acid; 232) of 2,2-dimethylpropyl ether

I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 233) ethyl ether of 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylcarbamic acid; 234). (K)-M-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; 235) (5)-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; 236). (K)-1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylurea; 237) (5)-1-( 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-3-ethylurea; 70 238). M-III-(6,8-difluoro-2-methyl -1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide; 239) 4-(3-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline; 240) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)|-3-(2-hydroxyethyl)urea; 241) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid ethyl ether; 242) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid; and also from their pharmaceutically acceptable salts.

Most preferred are compounds selected from the group consisting of 1). Mch-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|acetamide; 2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; 3). 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; 4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid; 5) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-ethylbenzamide; 6). 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-propylbenzamide; 7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-(2-dimethylaminoethyl)benzamide; 8) 6,8-dichloro-2-methyl-4-(4-morpholin-4-ylphenyl)-1,2,3,4-tetrahydroisoquinoline; ch 9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenylamine; 10). 1-I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylthiourea; i) 113). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-ethylurea; 123. h-I4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide; 13). 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid; from 14). 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-(2-dimethylaminoethyl)-2-hydroxybenzamide; 15). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|acetamide; - 16). 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine; at 17). 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine; 18). M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 1-19) I4-(6,8-dichloro-2-methyl) -1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1-acetylpiperidine-4-carboxylic acid; 20) M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Imethanesulfonamide; 21) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of ethanesulfonic acid; 22) M'M'-dimethylamino-H-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|sulfamide; « 23). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; from p. 24). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|butyramide; . 25). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylisobutyramide; and?" 26) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl-iamide of cyclopropanecarboxylic acid; 27) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of cyclobutanecarboxylic acid; 28). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-2,2,2-trifluoroacetamide; -I 29) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1-acetylpiperidine-4-carboxylic acid;

Sh- 30) M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|nicotinamide; at 31). h-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; 32) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl/uphenyl|ethanesulfonic acid amide; ve 33). M',M'-dimethylamino-M-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|sulfamide;

Ge 34) I(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl amide of cyclopropanecarboxylic acid; 35) (2-(6,8-dichloro-2- methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1-acetylpiperidine-4-carboxylic acid; 36) 1-IZ3-(6,8-dichloro-2-methyl-1,2,3 ,4-tetrahydroisoquinolin-4-yl)phenyl)|-3-ethylurea; 37). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-methylthiourea;

F) 38). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-3-ethylurea; ka 39). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-methylthiourea; 40) in M-05-I3-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenylsulfamoyl)-4-methylthiazol-2-yl)acetamide; 41). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide 1,2-dimethyl-1H-imidazole-4-sulfonic acid; 42). h-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-C,C,C-trifluoromethanesulfonamide; 43). hCh-IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-C,C,C-trifluoromethanesulfonamide; 65 44) M-ethyl-M'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonylurea; 45). N-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-dimethylaminoacetamide;

46) 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl amide of 2,6-diaminohexanoic acid; 47) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 1H-pyrrole-3-carboxylic acid; 48) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1-methylpiperidine-4-carbon

ACIDS; 49) |4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide of 1-methanesulfonylpiperidine-4-carboxylic acid; 50) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Iamide of 1H-pyrazole-4-carboxylic acid; 51). Mch-13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-methylaminoacetamide; 70 52). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-dimethylaminoacetamide; 53). 2-amino-M-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 54). 2-amino-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; 55) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 2,6-diaminohexanoic acid; 56) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide 1-methylpiperidine-4-carboxylic acid; 57) IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1H-imidazole-4-carboxylic acid; 58). 1-methanesulfonylpiperidine-4-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide; 59) 3,5-dimethyl-1H-pyrazole-4-carboxylic acid 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide; 60) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Iamide of 1H-pyrazole-4-carboxylic acid; 61). 3-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; 62) IZ-(6,8-dichloro- 4-methylpiperazine-1-carboxylic acid 2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide; c 63) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of piperidine-1-carboxylic acid; 64) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; i) 65) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-1-carboxylic acid; 66) 3-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-1,1-diethylurea; 67). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-methyl urea; c zo 68) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3--2-dimethylaminoethyl)urea; 69) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-3-(tetrahydrofuran-3-yl)urea; - 70). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-(tetrahydropyran-4-yl)urea; o 71) 3-IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1-methyl-1-(1-methylpiperidin-4-yl)urea; 1-12) - 3-IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1-(3-dimethylaminopropyl)-1-methylurea; 73) 3 -I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1--2-dimethylaminoethyl)-1-methylurea; 74). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-"3-dimethylaminopropyl)urea; "75). 1-I3-( 6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-3-(2-methoxyethyl)urea; from p. 76). 1-I3-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)|-3-pyridin-3-ylurea; 77). 1-I3-(6,8-dichloro-2-methyl- 1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)|-Z-pyridin-4-ylurea; and? 78) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|4-methylpiperazine-1-carboxylic acid amide; 79). 1-(2- (6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; -I 80. 1-(2-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3--2-dimethylaminoethyl)carbamide; 81) I4-(6,8-dichloro-2-methyl-1,2,3, 4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 4-methylpiperazine-1-carboxylic acid; o 82). 1-(4-(6,8-dichloro-2-methyl-1,2,3,4- tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; 83). 3-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1 ,1-dimethylcarbamide; 84).3-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-1,1-diethylcarbamide;

Ge 85). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3--2-dimethylaminoethyl)urea; 86) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; 87). M-I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|formamide; 88). I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)methylamine; 89). M-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|formamide;

F) 90). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)methylamine; ka 91). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,3,3-trimethylurea; 92). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,3-dimethylurea; in 93) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of morpholine-4-carboxylic acid; 94). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)methylamide of 4-methylpiperazine-1-carboxylic acid; 95) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)-1-methylurea; 65 96) of 2-dimethylaminoethyl ether

13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid;

97) of 2-dimethylaminoethyl ether

I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 98) 2-dimethylaminoethyl ether (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 99) methyl ether (3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenylcarbamic acid; 100) (K or 5)-M-I(3- (6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; 101) (K or 5)-1-(2-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylurea; 102). 1-I(I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl/|-3-(2-hydroxyethyl)urea; 70 103) ethyl ether of 3-( 6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid; 104) 3-(6,8-dichloro-2-methyl-1,2,3,4- tetrahydroisoquinolin-4-yl)benzoic acid; and also from their pharmaceutically acceptable salts.

If the compounds of formula (I) contain one or more asymmetric centers, they can be in both the 5- and the K-configuration. Compounds can exist in the form of optical isomers, in the form of diastereomers, in the form of racemates or in the form of their mixtures.

These alkyl residues, respectively, partially or fully fluorinated alkyl residues can be both linear and branched. The groups СаНга-1 and their analogues up to Су/Ноул mean either the corresponding alkenyls, cycloalkyls, cycloalkylalkyls, or alkylcycloalkyls.

Heteroaryls especially include 2- or 3-thienyl, 2- or 3-furyl, 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or

B-imidazolyl, 1-, 3-, 4- or b5-pyrazolyl; 1,2,3-triazol-1-, -4- or -5-yl; 1,2,4-triazol-1-, -3- or -5-yl; 1- or B-tetrazolyl, 2-, 4- or bB-oxazolyl, 3-, 4- or b5-isoxazolyl, 1,2,3-oxadiazol-4- or -5-yl, 1,2,4-oxadiazole -3- or -5-yl, 1,3,4-oxadiazol-2-yl or -5-yl, 2-, 4- or B5-thiazolyl, 3-, 4- or

B-isothiazolyl, 1,3,4-thiadiazol-2- or -5-yl, 1,2,4-thiadiazol-3- or -5-yl, 1,2,3-thiadiazol-4- or -5- il, 2-,

C-or 4-pyridyl, 2-, 4-, 5- or b-pyrimidinyl, 3- or 4-pyridazinyl, pyrazinyl, 1-, 2-, 3-, 4-, 5-, 6- or c 7- indolyl, 1-, 2-, 4- or 5B-benzimidazolyl, 1-, 3-, 4-, 5-, b6- or 7-indazolyl, 2-, 3-, 4-, 5-, 6-, 7 - or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7- or b8-isoquinolyl, 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl, 3-, 4-, 5-, 6-, 7-(8) or 8-cinolinyl, 2-, 3-, 5-, 6-, 7- or 8-quinoxalinyl, 1-, 4-, 5-, 6-, 7- or 8-phthalazinyl. Further, they include the corresponding M-oxides of these compounds, for example, 1-oxy-2-, -3- or -4-pyridyl.

At the same time, 5- or b-membered heterocycles are preferred. Particularly preferred are imidazolyl, pyrazolyl, pyrrolyl, isotriazolyl, tetrazolyl, thiazolyl and oxazolyl.

СНе-groups also include terminal СН3-groups in the alkyl chain, which are considered СНо-Н-groups. -

The methods of obtaining the used compounds are also described. at

Thus, the substances described in this case can be obtained starting from benzylamines of the formula (IM) as precursors. In turn, they can be synthesized, if they are not commercially available, by standard methods from the corresponding benzyl chlorides or bromides of the formula (1): | J. vk v ne sya et DK kv NE n per UNe DYBKN V SK

НЯ их х х д Ох к-t и g ше: V or y. kt ml

Uh shcha pe

In Devi -1 se yan, bek y o SHCI M i" 20 Thus obtained benzylamines of the formula (IM) are alkylated in a manner known to a specialist with the help of the corresponding substituted alpha-bromoacetophenones of the formula (M).

F) name) 60 b5

:uvyuyh

TV Me y y re that M o» san

TYA: also: with . es t y Zh.

BE st NV Y en de u Ya a i p i ih z VEK. 70 OB Kn in sia shi still shk

To OK HA for ko EK na. Alpha-bromoacetophenones of the formula (M) can be obtained by methods known from the literature from the corresponding acetophenones as precursors by bromination. By reducing the carbonyl group in the compound of the formula (MI) and subsequent acid-catalyzed cyclization of the corresponding alcohols of the formula (MI) | see Teigapedgtop 2o 1eshsh, 30, 5837 (1989); Oh Roger Rgosed Ipb, 27, 513 (19953) tetrahydroisoquinolines of formula (1) can be obtained by known methods. Stu Pn

Bere A govyh BE Z zsenn svo s o S also in IN: ee.

Drink and do what the village brings

Es ІІі en i r: zey soup, drink SAN u nyanya dya ev zo -d ! M CHE i what schi. ro VN: shk svo ZY b shki « pd Ne tur ru UM VE zhen

Bine in Wischa o some Nya zr Kt a; you do not,

En Ya Kt nim B ol kstnY z Bel av! y ve m even trent t kaglu, « shk - s Mra - | p I E i Y. Ma e vi i V (av) Min Z y vysh ish Sche i STI ek rt nave)

From Kk 55. Shh - !

In the case of Kb, which does not mean H, the desired compounds of formula (I) can be obtained, for example, from iodides (F) of formula (MI) by a halogen-metal exchange reaction and subsequent nucleophilic action of the intermediate

GI of an organolithium compound on a carbonyl group (see Spet. RNagt. Vyi., 43, 1543 (1995). 60 b5

On. - STILL

EN shin s Ya t hg: JHE seashe Mdnaoi zh: : N dance re kvi

Sho i: uh VE OS mesh i nene che shynny ee YaIvai x kV; that YAVI Ba know

Uh Z r FU td- Ks ut VANEK. -:-sntuas ovo tone U about mother-in-law you pcs

DAK Y, acti ben; ET TAZA PNI MILI AJ ay t y t Ta 70 da in «r Uk z

Shik t nad: ynj ev a, lk ar i her B. wash in

VN Yava and KT ShZY LEN in Meri o

Goal

M

The synthesized tertiary alcohols can be converted into other derivatives by known methods.

To obtain branched alkyl analogs of formula (I), the corresponding ethers of diphenylacetic acid of formula (X) are alkylated in the alpha position by known methods. The desired products of the formula (XI) can be converted by standard methods into the corresponding amides of the formula (XI), which according to a reaction analogous to

Ristes-Zrepadieg, are converted into the desired tetrahydroisoquinolines of formula (I), see Tei(hapeadgop, 43, 439 (1987);

Spent Rpagt. Vii, 33, 340 (1985)). sword ke ly b J zd vil s

I Y de --x Still I sadi a nni shko: Kf a HORSE dogs: ZK: o two I sleep NN Z Z

Iii 3 eI u o sk ze z au Eva i s ev DE sia ani snah MAN dno be

B) M ry shin eЖ B: den sya sh yi I pe I sv v: a re g Where khol yatya N pali Z SCHE tka ry sce SHA Dn olyutnto ! a o: -KE on y t t zkssni Ne kt s: Bov st zd iks that Y . Cysts Den same glass MTK dya PE TNK Ya yati shchi chshchrh Bo Uare eh SO carried and oinishchii sno te 5 y V 1 s KI «v

Kvi 5. from the article about HOW to eat and et syu Dt KN

ZB same E same ; y- r MORE - 2 s i kk meh sid: p y t Bk g :» t; pi it with -i same sake t

Ek - («c) EY of 50 In the descriptions of applications UMO 01/32624 and MO 01/32625, compounds of type (I) are described as reuptake inhibitors of norepinephrine, dopamine, and serotonin. However, these patent applications only protect compounds in which K1 to) and K2 can only be H. In the case of the compounds proposed according to the invention, however, it is indicated that at least K2 does not mean H. Further, by means of one of the compounds, that are proposed according to the invention, could not reveal any inhibitory properties against the described receptors, so that the described compounds, both structurally and in terms of their pharmacological properties, clearly differ from the compounds described in the specified patent applications.

Next, compounds of type (I) according to the description of the application EP 1113007 are described as agonists and antagonists of estrogen. It has been found that the compounds proposed according to the invention do not show activity against the indicated receptors, so that the consequence of the structural difference of the compounds proposed according to the invention is clearly 60 other pharmacological properties.

It has been shown that the compounds of formula (I) are exceptional inhibitors of sodium-hydrogen metabolism (NSM), especially sodium-hydrogen metabolism of subtype C (NSM).

Due to these properties, the compounds are suitable for the treatment of diseases caused by oxygen deficiency. Due to their pharmacological properties, the compounds are exceptionally suitable as antiarrhythmic drugs with a cardioprotective component for the prevention and treatment of heart attacks, as well as for the treatment of angina pectoris, and they prophylactically inhibit or strongly reduce pathophysiological processes in the event of ischemic induced damage, especially in the event of ischemic induced cardiac arrhythmias . Due to their protective effects against pathological and ischemic conditions, the compounds of formula (I) used according to the invention, due to the inhibition of the cellular mechanism of Ma"/H"-exchange, can be used as medicinal agents for the treatment of all acute and chronic ischemia-induced injuries or induced primary or secondary diseases due to this.This refers to their use as drugs in the case of surgical interventions, for example in organ transplants, and the compounds can be used both to protect the organs in the donor before and during the extraction, to protect the extracted organs, e.g. when treated with or stored in saline electrolyte solutions, 70 and when transferred into the recipient's body.The compounds are also valuable, protective drugs in angioplasty operations, for example, in the case of the heart, as well as in the case of peripheral vessels Due to their protective effect, it is relatively ischemic induced damage, the compounds are also suitable as drugs for the treatment of ischemia of the nervous system, especially of the central nervous system, for example, for the treatment of stroke or brain edema. Moreover, the compounds of formula (I) used according to the invention are also suitable for the treatment of various forms of shock, such as, for example, allergic, cardiogenic, hypovolemic and bacterial shock.

Further, the compounds induce improvement of the respiratory impulse and are therefore used to treat conditions of the respiratory system in the case of the following clinical conditions and diseases: impaired central respiratory impulse (eg, central sleep apnea, sudden infant death syndrome, postoperative hypoxia), mMuscular disorders breathing, respiratory failure after long-term artificial ventilation, respiratory failure during adaptation to high altitudes, obstructive and mixed form of sleep apnea, acute and chronic lung diseases with hypoxia and hypercapnia. In addition, the compounds increase the muscle tone of the upper respiratory tract, so that snoring is suppressed.

The combination of an MNE inhibitor with a carbonic anhydrase inhibitor (such as, for example, acetazolamide), and the latter leads to metabolic acidosis and, due to this, increases respiratory activity, is preferable due to the increased effect and reduced introduction of the biologically active substance. and)

It has been shown that the compounds used in accordance with the invention have a moderate laxative effect and therefore can be used as a laxative or in the case of threatened constipation, and the prevention of ischemic damage caused by obstructions in the intestinal tract is particularly advantageous. Ge

Next, there is an opportunity to prevent the formation of gallstones.

Moreover, the compounds of formula (I), used according to the invention, are characterized by a strong M inhibitory effect on cell proliferation, for example, fibroblast proliferation and smooth muscle cell proliferation. aw!

Therefore, the compounds of formula (I) are considered as valuable therapeutic agents in the case of diseases in which cellular proliferation is the primary or secondary cause, and as a result they can be used as - antiatherosclerotic agents, agents against diabetic late complications, cancers, fibrotic diseases such as fibrosis lungs, liver fibrosis or kidney fibrosis, hypertension and organ hyperplasia, especially with prostatic hyperplasia or prostatic hypertrophy.

The compounds used according to the invention are effective inhibitors of the cellular sodium-proton antiport (Ma/H-exchange), which in the case of numerous diseases (essential hypertension, atherosclerosis, diabetes, etc.) is increased in cells accessible to measurements, as, for example, in erythrocytes, platelets or leukocytes. The compounds used according to the invention are therefore suitable as exceptional and simple scientific means, for example, as diagnostic means for determining and recognizing certain forms of hypertension, as well as atherosclerosis, diabetes, proliferative diseases, etc. Moreover, the compounds formulas (I) are suitable for preventive therapy to prevent the genesis of high blood pressure, for example, essential hypertension.

In addition, it was found that MNE inhibitors have a beneficial effect on serum lipoproteins. -I It is well known that for the occurrence of atherosclerotic changes in blood vessels, especially coronary heart disease, a significant risk factor is very high concentrations of lipoproteins in the blood, so-called hyperlipoproteinemia. 7 For the prevention and regression of atherosclerotic changes, extreme importance is attached to the reduction of elevated av! content of serum lipoproteins. The compounds used according to the invention can therefore be used for the prevention and regression of atherosclerotic changes, as they eliminate the causal risk factor. Due to this protection of blood vessels in relation to the syndrome of endothelial dysfunction, the compounds of formula (I) are valuable medicinal

With means for the prevention and treatment of coronary spasms, atherogenesis and atherosclerosis, left ventricular hypertrophy and dilated cardiomyopathy, and thrombotic diseases.

These compounds are therefore mainly used to obtain a medicinal product for the prevention and treatment of sleep apnea and muscle-related breathing disorders; to obtain a medicinal product for the prevention and treatment of snoring; to receive a drug to reduce

F, blood pressure; to obtain a medicinal product for the prevention and treatment of diseases that are provoked by ischemia and reperfusion of central and peripheral organs, such as acute renal failure, stroke, endogenous shock states, intestinal diseases, etc.;; to obtain a medicinal product for the treatment of diabetic late damage and chronic kidney diseases, especially any inflammation of the kidneys (nephritis) associated with increased protein/albumin excretion; to obtain a medicinal product for the treatment of ectoparasites in human medicine and veterinary medicine; to obtain a medicinal product for the treatment of the indicated diseases in combination with blood pressure-lowering substances, mainly with angiotensin-converting enzyme (ACE) inhibitors, with diuretics and saluretics, such as furosemide, hydrochlorothiazide, 65 pseudoaldosterone antagonists and aldosterone antagonists; with adenosine receptor modulators, especially with adenosine receptor activators (Ag2-agonists); and with angiotensin receptor antagonists.

According to the invention, the introduction of sodium-proton exchange inhibitors of the formula (I) is proposed as a new type of drugs for reducing the elevated level of lipids in the blood, as well as the combination of sodium-proton exchange inhibitors with blood pressure-lowering and/or lipid-lowering drugs.

Medicinal products containing compounds of formula (I) can be administered orally, parenterally, intravenously, rectally, transdermally or by inhalation, the preferred route of administration depending on the relevant clinical picture of the disease. The compounds of formula (I) can be used individually or together with galenic excipients, both in veterinary medicine and in human medicine.

What excipients are suitable for the desired finished form of the medicinal product is known to the skilled person on the basis of 70 his special knowledge. Along with solvents, gelling agents, suppository bases, auxiliary substances for obtaining tablets and other carriers of biologically active substances, for example, antioxidants, dispersants, emulsifiers, antifoams, substances that adjust taste, preservatives, substances that promote dissolution, or dyes can be used.

For oral administration, the active substances are mixed with suitable admixtures, such as carriers, stabilizers or inert diluents, and brought into suitable administration forms, such as tablets, dragees, detachable capsules, aqueous, alcohol or oil solutions, by conventional means. As inert carriers can be used, for example, gum arabic, magnesia, magnesium carbonate, potassium phosphate, milk sugar, glucose or starch, especially corn starch. At the same time, preparation of the drug can be carried out both in the form of dry and in the form of wet granules. As oil carriers or solvents are used, for example, vegetable oils or 2o animal oils, such as sunflower oil or fish oil.

For subcutaneous or intravenous administration, the active compounds, if desired, together with substances customary for this purpose, such as solubilizers, emulsifiers or other excipients, are brought into the form of a solution, suspension or emulsion. As solvents, for example, water, physiological sodium chloride solution or alcohols, such as ethanol, propanol, glycerin, as well as sugar solutions, such as glucose or mannitol solutions, or a mixture of various specified solvents are used.

As a pharmaceutical composition for use in the form of aerosols or sprays, for example, solutions, i) suspensions or emulsions of the biologically active substance of formula (I) in a pharmaceutically acceptable solvent, especially such as ethanol or water, or mixtures of such solvents are suitable.

The composition, if necessary, may also contain other pharmaceutical excipients, such as surfactants, emulsifiers and stabilizers, as well as a propellant. Such a composition contains a biologically active substance in a concentration usually from about O0.19 omas. up to 1095 mass, especially from - approximately 0.39 mass. to Zoomas. at

The dosage of the biologically active substance of the formula (I), which is introduced, and the frequency of administration depend on the strength and duration of the action of the compounds used; in addition, from the type and intensity of the disease being treated, and also from the sex, age, weight and individual sensitivity of the mammal being treated. uh-

On average, the daily dose of the compound of formula (I) at a patient weight of approximately 75 kg is at least 0.001 mg/kg, preferably 0.01 mg/kg, up to a maximum of 1 mg/kg, preferably 1 mg/kg of body weight. In acute outbreaks of the disease, for example, immediately after a myocardial infarction, even higher and, above all, more frequent dosages may be necessary, for example, up to 4 single doses per day. Especially with intravenous administration, for example, in the case of a patient with a heart attack in the intensive care unit, up to 200 Ωg per day may be required.

Descriptions of experiments and examples: List of abbreviations used: ;"

And the retention time

TFOK (TRA) Trifluoroacetic acid - and HPLC High performance liquid chromatography

Eq. Equivalent - IsM5 Liquid chromatography with mass spectrometry

And av | Me (M) Mass spectrometry

SI Chemical ionization t- E5, EBI Ionization by electron sputtering

From THF (TNE) Tetrahydrofuran tot O-(Cutoxycarbonyl)cyanomethylamino|-M,M,M',M'-tetramethyluronium tetrafluoroborate

DMSO (0M50) Dimethyl sulfoxide

Abs. Absolute 7egv. Decomposition

IF) DMF(OME) Dimethylformamide ime)

General part in The retention times (Ku) indicated below refer to | CM5 measurements with the following parameters:

Method A: stationary phase: MegeKk RigozrNeg; From a micron; 2x55mm mobile phase: 9595 H2O (0.0595 TFOC)-»9595 acetonitrile; 4 min.; 9595 acetonitrile; 1.5 min.-»595 acetonitrile; Ihv.; O.5 ml/min.; 302 65 Method B: stationary phase: MegeKk RigozrNeg; From a micron; 2x55mmM mobile phase: Okhv. 9095 Ng2O (0.0595 TFOK); 2.5 min. - 9595 acetonitrile; 9595 acetonitrile up to Z,Zhv.; 1095 acetonitrile 3.4 min.; ml/min

Method B1: stationary phase: UM, )'zrpege OO NBO; 4 microns; 2x20mm moving phase Cover. 9095 H2gO (0.0595 TOOK); 1.9 min. - 9595 acetonitrile; 9595 acetonitrile up to 2.4 min.; 1095 acetonitrile 2.45 min.; ml/min

Method C: stationary phase Megek GiSpgoSap 55-2 Rygovreg ZTAK KR 18e mobile phase solvent A: acetonitrile/water 90:1040.596 HSOOH solvent B: acetonitrile/water 10:9040.5956 HSOOH flow rate: O.7Bml/min. time (min.) solvent B (901 0.00 95.0 0.50 95.0 1.75 50 425 50 4.50 95.0 5.00 95.0 stopping time: 6.20 min. temperature: 40

Method 0 stationary phase Megsk KR18 RigozrNeg ziag, 55x2mm, grain size Z microns mobile phase solvent A: acetonitrile 0.0896 NCOOH solvent B: hydrogenO.195 NCOOH flow rate: O.45ml/min. s time (min) solvent B (901 о о 95 5 5 7 5 сч зо 8 95 9 5 « temperature: room temperature Ha»)

Example 1

IM-(4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|acetamide)

A « rosi sa s 5 and plaku g an KK egA-Tsy and her - 0 Mivoatny. and. is And I bake: NO («c) ! She I and She to r I; that) Intermediate 1: 2,4-dichlorobenzylmethylamine

Obtained by methods known from the literature |9U. Honey. Spet., 27, 1111 (1984)).

Intermediate 2: M-I(4--2-bromoacetyl)phenyl|acetamide

Synthesized in a known expert manner by bromination of M-(4-acetylphenyl)acetamide. o The starting compound (0.25 bmol) is added to 30 ml of acetic acid and at a temperature of 602C a solution of 39.9 g (1.b0eq.) of bromine in bOml of acetic acid is attached. After 1.5 hours, it is left to cool to room temperature, and the reaction mixture is poured with ice water. The precipitate is filtered off under vacuum, washed with water and dried, and the title compound (m.p.: 19290) is isolated, because Intermediate 3: M-14-(2-(2,4-dichlorobenzylamino)acetyl|phenyl)acetamide 37.1 g (0.195 mol) of intermediate product 1 is added to 40 Oml of dioxane and mixed with a solution of 100 g (0.234 mol) of intermediate product 2 in bbOml of dioxane. Add 134 ml of triethylamine and stir for 4 hours at room temperature. After standing overnight, the precipitate is filtered off and the filtrate is concentrated in vacuo. The residue is treated with ethyl acetate, washed with Manso solution and HO, dried over magnesium sulfate and concentrated. The oily residue formed in this case is triturated with a mixture of ethyl acetate and diethyl ether, and Zbg intermediate product C is obtained in the form of a crystalline solid (eg:

115-11720).

Intermediate 4: M-(4-(2-(2,4-dichlorobenzylamino)-1-hydroxyethyl|phenyl)acetamide

Zbg (0.099 mol) of intermediate C is dissolved in 500 ml of methanol and mixed with 7.8 g (equiv.) of sodium borohydride at a temperature of 02C. It is additionally stirred for 30 minutes at a temperature of 02 and during the next hour at room temperature. For processing, the reaction mixture is concentrated and the residue is partitioned between sodium chloride and ethyl acetate. The aqueous phase is separated, the pH-O value is set and extracted twice with ethyl acetate. The combined organic phases are dried over magnesium sulfate and concentrated. The raw product obtained in this way can be further processed without further purification.

IM-(4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|acetamide 20 g (0.054 mol) of intermediate compound 4 is dissolved in 250 ml of dichloromethane and at a temperature of 09 drops mixed with 250 ml of concentrated NeZO). Stir for 2 hours at 02C and for 1 hour at room temperature. For processing, the reaction mixture is added to ice water and the precipitate is filtered off under vacuum. By drying the organic phase and concentrating, a crude product is obtained, which is triturated with diisopropyl ether, and 11.7 g of the title compound is isolated as a crystalline solid (m.p.: 205-2062C).

By: M-I4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|acetamide hydrochloride

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A sample (10 mg) of the title compound from example 1 is suspended in 1 ml of 2N HCl and mixed with such an amount of tetrahydrofuran that a clear solution is formed. Concentrate in a vacuum, the residue is triturated with diethyl ether and filtered in a vacuum, after which the title compound is obtained as a crystalline solid (K-3.807 min. (method A); m.p.: 12592 upon decomposition).

Example 2 - ha: (3-4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide hydrochloride 26: (9-3-(6,8-Dichloro- 2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide hydrochloride 2c: (-)-4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4- yl)benzenesulfonamide acetate " du 24: (7-3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide acetate - with part of as in V sh. gYa Same s - I and where I Sri

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NK, Yerenya o S

Intermediate 1: 2,4-dichlorobenzylmethylamine

Obtained by methods known from the literature |9U. Honey. Spet., 27, 1111 (1984)).

Intermediate product 2: 2-(2,4-dichlorobenzyl)methylamino)-1-phenylethanone bB Intermediate product 1 is introduced into interaction with 2-bromo-1-phenylethanone according to the method described in example 1, for intermediate product 3. Similar treatment and purification on silica gel lead to the target alkylation product in good yield as a yellowish oil (K .-4.188 min. (method A); MS (СІ7)-308.2/310.2).

Intermediate 3: 2-(2,4-dichlorobenzyl)methylamino|-1-phenylethanol

Intermediate product 2, according to the method described in example 1 for intermediate product 4, is reduced using sodium borohydride. After monitoring the progress of the reaction shows complete conversion, concentrate and treat the residue with ethyl acetate. Wash twice with water, dry over magnesium sulfate and remove the solvent. The crude product obtained with a quantitative yield can be further subjected to transformation without further purification (K,-4.14 Ohv. (method A); MS (SI")-310.2/312.2).

Intermediate 4: 6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline 20 g (64.5 mmol) of intermediate C is dissolved in 55 ml of dichloromethane and cooled to room temperature. This solution is added to 5 bml of pre-cooled concentrated NBO, and then stirred for two hours at room temperature. Extract three times with dichloromethane. The combined organic phases 75 are dried over magnesium sulfate and concentrated. The oily crude product is purified on silica gel, and intermediate product 4 is obtained with a yield of 5395 (K,-4.444 min. (method A); MS (SI")-292.2/294.2). da: (-)-6, 8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline trifluoroacetate 46: (1)-6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline trifluoroacetate

Intermediate 4 is separated in the chiral phase by HPLC into both enantiomers.

Column with chiral phase SpPigaIrak OB, 250x4, bsm; solvent: n-heptane/isopropanol 7:3-0.1 TFOK; volumetric flow rate: Tml/min.;

Re (()-enantiomer/4a)-9.340 Ohv.;

Ec ((4)-enantiomer/45)-20.327xV. ch 29 ha: (i)-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide hydrochloride Ge) 26: (3)-3-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide hydrochloride

A suspension of 500 mg (1.7 mmol) of intermediate product 4a in 1 Oml of dichloromethane at a temperature of 09C is added to 1.2 ml of chlorosulfonic acid. Stir for 1 hour at 02C and for the next hour at room temperature. Add 5 ml of chlorosulfonic acid and stir for another hour at room temperature. For processing, place on ice and set the value to pH-8 with the help of MansSO»z. Extract "Zh" three times with ethyl acetate. The combined organic phases are dried over sodium sulfate and the solvent is removed. In this way, the raw product obtained in 20 ml of a concentrated solution of MNaz is heated at a temperature of 902 for three hours. After complete conversion, the reaction solution is concentrated and the residue is partitioned between water and - and ethyl acetate. The organic phase is separated, and the aqueous phase is extracted again with ethyl acetate. The combined organic phases are dried over sodium sulfate and the solvent is removed in vacuo. Further chromatography on silica gel gives 3335 mg of a mixture of compounds of examples 2a and 265 in the form of a yellowish amorphous solid. Further purification using preparative HPLC yielded 212 mg of the para-substituted compound 2a indicated in the title, as well as 58 mg of the meta-isomer 26. « 20 Preparative HPLC conditions: column with chiral phase SpPigaIrak A5, 250x4, bmm; c solvent: n-heptane/(ethanol/methanol/acetonitrile in a ratio of 20:1.5:0.5:0.5; :c" volumetric flow rate: Tml/min.;

KE, (main fraction)-14.145 min. (-»2a);

K, (side fraction)-11.623 min. (-»26). -i Both fractions are dissolved in mixtures of methanol and 2N HCl and subjected to freeze-drying, and the compounds 2a and 25 specified in the title can be obtained in the form of crystalline solids. - (Bk2a)-3.63 Ohv. (method A); MS(2a28)(E5B)-371.3/373.3 (M'NUu412.3/414.3 (M'SNZUSM); Ru25)-3.668 min. (c) (method A); MS(25)(E5)-371.3/373.3 (M"NU412.3/414.3 (M'ASNZSM)). 50 of them 2s: (-)-4-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl/benzenesulfonamide acetate 2a: (-)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl) )benzenesulfonamide acetate that) The synthesis of the compound indicated in the title is carried out according to the method described in case 2a/265, and intermediate product 45 is used as the starting compound. Purification and separation from the target meta-isomer is carried out under the following conditions: a column with a chiral phase SpPigaIrak A5, 250x4, 6/12 mm; o solvent: acetonitrile; volume flow rate: Tml/min.; ime) KE, (main fraction)-4.394 min (-»2s);

K, (side fraction)-4,130 Ohv. (-»29). for Purified products are treated with a 10906 solution of acetic acid and subjected to freeze-drying, and the target acetates are obtained in the form of slightly yellowish solids. (K(2s)-3.656 min. (method A);

MS(E5)-371.1/373.1. (M'-NU412,1/414,1. (M'SNUSM); B24)-1.562 min. (method B); MOSC(E5")-371.1/373.1 (M'Nul12.1/414.1 (M'ASNaUSM)).

Example C bo 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M,M-dimethylbenzenesulfonamide hydrochloride

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6b,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (intermediate product 4, example 2) is introduced in b/bml of chlorosulfonic acid in portions. Then it is stirred for an hour at a temperature of 409. After that, the reaction mixture is cooled to room temperature and mixed with a mixture of water and ice. The resulting precipitate is filtered off under vacuum and treated with ethyl acetate, the obtained ethyl acetate phase after washing with a saturated sodium chloride solution is dried over magnesium sulfate. By further concentration, 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/benzenesulfonyl chloride is obtained in the form of a solid crude product, part of which (150 mg) is introduced in portions directly into a cooled at a temperature of 10 C, a solution of dimethylamine (bml; approximately 4095 parts in water). The resulting suspension is then stirred at this temperature for 1.5 hours. After that, it is mixed with water and ice, extracted three times with ethyl acetate, Ge) the combined ethyl acetate phases are washed with saturated sodium chloride solution and dried over magnesium sulfate.

The residue is treated with water, mixed with 2N NOI and freeze-dried. The crude product thus obtained is then purified by preparative HPLC.

Conditions: stationary phase: Megsk Rygozrpeg KR18 (10μM), 250хх25MMm; "And mobile phase: 9095 NoO (0.0595 TFOK). 59095 acetonitrile; 4 Covering; volumetric flow rate: 25 ml/min.

Fractions containing the product are combined, acetonitrile is removed in a rotary evaporator, the aqueous phase is washed with a saturated solution of potassium carbonate and then extracted three times with ethyl acetate. The combined ethyl acetate phases are washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated. The residue is treated with water, mixed with 2N NOI and freeze-dried. Obtained - 8Omg of a light solid, consisting of approximately 8095 of the target compound and approximately 2095 of the regioisomer (P-4.00 Ohv. (method A); MS(SI")-399.1).

Example 4 "20 da: "6,b'dichloro-a-methyl-1,2,3,E-tetrahydroisoquinoline-p-yl)-benzenesulfonamide hydrochloride -o c or, dike MO 2" no

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Intermediate product 1: 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonyl chloride and F) At a temperature of 0°C Immol 6,8-dichloro-2-methyl-4- phenyl-1,2,3,4-tetrahydroisoquinoline (intermediate product 4, as in example 2) is added to a mixture of chlorosulfonic acid and stirred for 3 hours at room temperature. For processing, the reaction mixture is placed on ice, with the help of a solution of MassonH, the pH value is set to 7-8 and 60 is extracted twice with ethyl acetate. The combined ethyl acetate phases are dried over sodium sulfate and concentrated in a rotary evaporator. Thus, the raw product obtained without further purification is further subjected to transformation.

Intermediate 2: 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide

C19mg of intermediate product 1 is suspended in bml of 2596 ammonia solution and heated to a temperature of 9026. After 3 hours, it is diluted with water and extracted with ethyl acetate. The organic phase is separated and dried over sodium sulfate, and 165 mg of the title compound is obtained.

4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)y-benzenesulfonamide hydrochloride 145 mg of intermediate product 2 is suspended in 1 bml of diethyl ether and mixed with 1 ml of a solution of NOSI in diethyl ether. After stirring for 30 minutes at room temperature, the precipitate is filtered off under vacuum and dried, thus obtaining 1 Zbmg of hydrochloride in the form of a yellowish solid. 4р: 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide acetate se KI ms ve BO

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Pan and Drew sg 255 mg of Intermediate 2, Example 8, are mixed with 5 ml of glacial acetic acid and 500 ml of water are added.

After filtering out difficult-to-dissolve components, they are subjected to freeze-drying, thus obtaining 250 mg of the compound indicated in the title. high school

Example 5 4-(4-Bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolinhydrochloride and) as:

OK shchi she ze full: owls o r. | - c Intermediate 1: 1-(4-bromophenyl)-1-(2,4-dichlorobenzyl)methylamino|-ethanone (2,4-Dichlorobenzyl)methylamine (see example 1, intermediate 1) and 2-bromo- 1-(4-bromophenyl)ethanone is injected. and?" in an interaction similar to that described in example 1 for the intermediate product of the method. After similar treatment and chromatography on silica gel, the alkylation product can be isolated with a yield of 6995.

Intermediate product 2: 1-(4-bromophenyl)-2-((2,4-dichlorobenzyl) methylamino|ethanol -I Analogously to the method described in example 1 for intermediate product 4, intermediate product 1 is reduced to the corresponding alcohol with the help of 2 equivalents of Mavn , which can be allocated with an output of 8695.

Sh- Intermediate product 3: 4-(4-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline about 5.45 g (14, Ommol) 1-(4-bromophenyl)- 2-((2,4-dichlorobenzyl)-methylamino|ethanol is added to 15 ml of dichloromethane and mixed with 15 ml of concentrated H.ZO4 for 5 minutes at a temperature of 09C. After stirring for 2 hours at room temperature, the reaction mixture is placed on ice and made alkaline with of Mmaon solution. Extract three times with dichloromethane. The combined organic phases are dried over magnesium sulfate and concentrated.

For further purification, the residue is chromatographed on silica gel, thus obtaining 2.0 mg of the title compound in the form of a yellowish oil. 4-(4-Bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline hydrochloride

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Zb0Omg of 4-(4-Bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline in 2N HCl is stirred at room temperature. The precipitate that has fallen out is filtered under vacuum and dried.

Example 6 4-16,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid and

SDS:

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2) 5.57 g (15 mmol) of 4-(4-Bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (example 5, intermediate - product 3) ) is dissolved in 150 ml of a mixture of absolute dimethylformamide and benzene (in a ratio of 1:1). After the solution is degassed in an argon atmosphere, 1.18 g (4.5 mmol) of triphenylphosphine and 1.17 g (3 mmol) of Ca(HSO) are added.

After a new purge with argon, 867 mg (0.75 mmol) of Ra|P(Св6Н5в)зI4 are added and carbon monoxide is introduced into the solution. Stir at a temperature of 1202C. After six hours at a temperature of 1202 and holding overnight in an argon atmosphere, 867 mg (0.75 mmol) of Ra(GR(C in H5)z3) are added again and stirred for the next eight hours at a temperature of 1202C, and carbon monoxide is introduced into the solution. After a new exposure during the night, add 135 mg of Rasi" and leave to react under the same conditions. For processing, the solvent is removed under vacuum and the residue is treated with ethyl acetate. It is extracted three times with 2N Mahon solution. In the combined aqueous phases, the pH value is set with the help of HCl and extracted three times with ethyl acetate. The organic phases are dried over magnesium sulfate and the solvent is removed. The residue is purified on silica gel using a mixture of dichloromethane and methanol, while obtaining 42 mg of the title compound (K,-4.025 min. (method A); this. MSc(SI)-336.1/338.1). - and Example 7 about 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-ethylbenzamide trifluoroacetate and M su p sx cm

F. ok Elven veshn ro Her 60 Yam ze 146mg (0.4Zmmol) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/benzoic acid (see . example 6) is dissolved in 5 ml of dimethylformamide and mixed with 1.0 equivalent of triethylamine. At a temperature of 02, a solution of 141 mg (04 Zmmol) of TOTO in Zml of dimethylformamide is added. Stir for 30 minutes at a temperature of 02C, and also for 30 minutes at room temperature. This solution is then added at 09C to a solution of 0.28ml of a 2M solution of ethylamine and 0.0bml (0.04Zmmol) of triethylamine in xXml of dimethylformamide and the reaction mixture is stirred for three hours at room temperature. For processing, the solvent is distilled off in a vacuum, the residue is treated with ethyl acetate and washed twice with KOH solution and once with water.

The organic phase is dried over sodium sulfate and concentrated. For further purification, chromatography on silica gel (dichloromethane/methanol in the ratio 95:5) is performed. By further purification using preparative HPLC (acetonitrile/water/trifluoroacetic acid), the target amide carboxylic acid is obtained in the form of trifluoroacetate. (B,-4.169 min. (method A); MS(SI)-363.3/365.3).

Example 8 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-propylbenzamide trifluoroacetate, which is present in well with P servrtret sova i i de se vo sv z 5 v de I zh kh i yi

Starting from n-propylamine and 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid (see example 6), the title compound can be obtained as described in example 7 by the method (P-1.881 min. (method B); MS(SI")377.3/379.3). c

Example 9 about 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-(2-dimethylaminoethyl)benzamide trifluoroacetate ze zt ZE I: 2 in I as ; - і і: о і хе м о Ше іх denne 5 дк жк і і - і z І vne Se " ke littya, sk 20 і with rn - s "B ;" Obtained similarly to the method of example («/7, starting from 0/0 of the compound of example 6 |i

of M1,M1-dimethylethane-1,2-diamine, by TOTO-mediated combination reaction (KK /-1.44 Ohv. (method B);

MO (SIU406,3/408,3). -I Example 10 -I 6,8-dichloro-2-methyl-4-(4-morpholin-4-ylphenyl)-1,2,3,4-tetrahydroisoquinolinetrifluoroacetate

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B: And ptpdyut se. with "Pet Lech 5" of Me and Pi and 45 mg (14 mmol) of Св2СО5, 6.5 mg (0.03 mmol) of palladium acetate, and also 28 mg (0.045 mmol) of 2,2-bis(idiphenylphosphino)-1,1-binaphthyl put in 5 ml of absolute toluene. In an argon atmosphere, add a solution of 0.104 ml (1.2 mmol) of morpholine in 2.5 ml of absolute dimethylformamide, as well as a solution of 371 mg (1.0 mmol)

4-(4-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline in 2.5 ml of absolute toluene and stirred for 9 hours at a temperature of 100 C. For processing, remove the solvent, the residue treated with dichloromethane and filtered from the insoluble part. After concentration of the filtrate by chromatography of the selected residue on silica gel (dichloromethane/methanol in a ratio of 95:5), 350 mg of the target morpholine derivative are obtained. After further purification by preparative HPLC, 1bOmg of the corresponding trifluoroacetate can be isolated as a colorless solid.

Example 11 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-diethylaminetrifluoroacetate with Shk E

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Starting from diethylamine and 4-(4-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetraisoquinoline (example 5, intermediate product 3), follow the same method described in example 10. The duration of the reaction is 2 days at 20 °C at a temperature of 1002, using three times the amount of palladium catalyst and phosphine ligand.

By means of preparative HPLC, the target trifluoroacetate can be isolated in the form of a colorless solid. at

Example 12 6,8-dichloro-2-methyl-4-(4-piperidin-1-ylphenyl)-1,2,3,4-tetrahydroisoquinoline trifluoroacetate v. Ha

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Kz Similarly to the method described in example 10, the target piperidine derivative can be obtained starting from piperidine and 4-(4-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (example 5, intermediate 3).

Example 13 6,8-dichloro-2-methyl-4-(4-pyrrolidin-4-ylphenyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride

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The reaction is carried out similarly to the method described in example 10, starting from pyrrolidine and 4-(4-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (example 5, intermediate product 3). After 20 chromatographic purification, the obtained product is treated with a mixture of dimethylsulfoxide and acetonitrile, and a precipitate is formed, which is filtered off, dissolved in 2N NOS and subjected to freeze-drying, thus obtaining the compound specified in the title as a colorless solid.

Example 14 6,8-dichloro-2-methyl-4-I(4-(4-methyltperazin-1-yl)phenyl|-1,2,3,4-tetrahydroisoquinoline trifluoroacetate with 25 X o 30 food "

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By introducing into the interaction M-methylpiperazine and 4-(4-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (example 5, intermediate product 3) according to - described in example 10 method, the title compound is obtained as a colorless solid. -| Example 15 about 6,8-Dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline trifluoroacetate

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Intermediate 1: cyclopropyl-(2,4-dichlorobenzyl)amine in 5.25 g (ZOmmol) of 2,4-dichlorobenzaldehyde is added to 140 ml of methanol and a solution of 1.71 g (ZOmmol) cyclopropylamine is added at room temperature. Stir at room temperature for 40 minutes and then mix in portions with 1.42g (37.5mmol) of Mavn. After standing overnight, the solvent is removed and the residue is treated with 2N NA. Extract twice with ethyl acetate. The aqueous phase is basified with Mahon and extracted again twice with ethyl acetate. The organic phases are dried over magnesium sulfate and

Concentrate. Thus, the crude product obtained in the form of a slightly yellowish oil can be subjected to further transformation without further purification.

Intermediate 2: 2-|cyclopropyl-(2,4-dichlorobenzyl)amino)|-1-phenylethanone

Intermediate product 1 in the presence of triethylamine in dioxane is introduced into the interaction with alpha-bromoacetophenone according to the method described in example 1 for intermediate product C. For processing, the solvent is distilled off and/or the residue is treated with ethyl acetate. Wash twice with water and twice with 2N HCl, dry over magnesium sulfate and concentrate. The raw product obtained in this way can be further processed without further purification.

Intermediate 3: 2-|(cyclopropyl-(2,4-dichlorobenzyl)amino)|-1-phenylethanol

Intermediate product 2, similar to the method described in example 1 for intermediate product 4, is restored by 7/5 using MavVN". For treatment, concentrate and partition the residue between 1N HCl and ethyl acetate. The aqueous phase is separated and extracted again with ethyl acetate. The combined organic phases are dried over magnesium sulfate and the solvent is removed in vacuo. 6,8-Dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline trifluoroacetate

Intermediate product C (1.9 g) is dissolved in 10 ml of dichloromethane without further purification and, according to the method described in example 1, is cyclized with the help of concentrated NaSO). For processing, the reaction mixture is placed on ice. The organic phase is separated, and the aqueous phase is extracted again with dichloromethane. The combined organic phases are dried over magnesium sulfate and the solvent is removed. Chromatography on silica gel (n-heptane/oethyl acetate in the ratio 5:1-53:1) yields 200 mg of yellowish oil, which is subjected to further purification by preparative HPLC. At the same time, 184 mg of the compound indicated in the title is obtained in the form of trifluoroacetate. with

Example 16 va: (-)-M-I(4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylacetamide o 166: Sk)-n-I( 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)acetamide

СХ them shcha ey x Z «I (ee be y- eh nya y g E kh y ZI

Ks eh m she shk « g; and from here I have sons

500 mg of the compound specified in the title of example 1 is separated on the chiral phase, and approximately 250 mg of both enantiomeric acetamides 16ba and 1665 are obtained. - Column with a chiral phase SpPigaIrak 00, 250x4 bmm; -I solvent: acetonitrile; volumetric flow rate: Tml/min.; o CC )-enantiomer/1ba) 5.856 min.; iz 70 VI(v)-enantiomer/165)-8.613 min.

Example 17 4-(6,8-dichloro-2-methyl-1 2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine hydrochloride m

Be Y stump m kN

Hn z SCHE: ID nin 65 y s yiv and Ya

Intermediate 1: 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine

30 g (8.mmol) /M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|idacetamide (example 1) is dissolved in 100 ml of 2095 solutions of sodium methylate and refluxed during

Four hours. The following 2.0 g (294 mmol) of solid sodium methylate are added and refluxed for another three hours. For treatment, the solvent is removed under vacuum, the residue is treated with 200 ml of water and extracted twice with dichloromethane. The combined organic phases are dried over magnesium sulfate and concentrated. For further purification, chromatography on silica gel (ethyl acetate/heptane in a 1:1 ratio) is performed, and aniline is obtained with a quantitative yield in the form of a yellowish oil. 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine hydrochloride 200 mg (0.65 mmol) 4-(6,8-dichloro-2-methyl-1,2 . The clear solution is concentrated under vacuum. The residue is triturated in diethyl ether, filtered under vacuum and dried, and 208 mg of the desired hydrochloride can be isolated.

Example 18

M-Ethyl-M'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonylcarbamide hydrochloride . i i pe N |.

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1 tomole //4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl) benzenesulfonamide (example 4, (from intermediate product 2) in 15 ml of anhydrous acetone is mixed with 350 mg ( 2.5 equiv.) of KSO" and stirred at room temperature for 1.5 hours. At room temperature, a solution of 2. equiv. of ethyl isocyanate in a little acetone is added and the solution is heated to the boiling point with a reflux condenser. For treatment, concentrated (r. vacuum, the residue is treated with water and extracted twice with ethyl acetate. The aqueous phase is acidified with BN NOA and the precipitate is filtered off under vacuum. Washing with ethyl acetate and drying under vacuum gives the title compound in good yield.

Example 19 "1-14-(6,8-dichloro-2-methyl-1 22,3,4-tetrahydroisoquinolin-4-yl)-phenyl|-3-propylurea with c ZB

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IV B

To a solution of 500 mg (1.63 mmol) of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine (see

GF) example 17) in 15 ml of toluene with stirring add a solution of 0.17 g (2.0 mmol) of n-propyl isocyanate in 7 toluene. After standing for one hour at a temperature of 40 oC, add the following 0.17 g of n-propyl isocyanate and stir for one hour at a temperature of 802C. For processing, the solvent is removed and the residue is triturated with water and diethyl ether. After drying, 50 mg of the target n-propylurea is obtained. 19a:. 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-propylcarbamide hydrochloride b5

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SNI dan yar - Ba: pure 45mg of 1-I4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-33-propylurea is dissolved in a mixture with 2n NOI of tetrahydrofuran. The clear solution is concentrated under vacuum, the residue is triturated with diethyl ether and filtered under vacuum. After drying, 47 mg of the target hydrochloride are obtained.

Example 20 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylthiourea

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YET more E h;E

Starting from 500 mg (1.633 mmol) of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine (see example 17) and 220 mg (33, 00 mmol) of methyl isothiocyanate, similarly to the method described in example 19, 245 mg of the target thiourea can be isolated.

Example 21 "1-I4-(6,8-dichloro-2-methyl-1,2.3,4-tetrahydroisoquinolin-4-yl)phenyl|-33-ethylurea -

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Obtained similarly to the method described in example 19, starting from B50mg (1.633mmol) of two 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine and 284mg (4mmol) ethyl isocyanate. o 21a: 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylcarbamide hydrochloride ime) 60 b5

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Conversion to the corresponding hydrochloride is carried out similarly to the method described in example 19a.

Example 22

M-(4-(6-Methanesulfonyl-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)acetamide

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Intermediate 1: (4-methanesulfonylbenzyl)methylamine -

Synthesized in a manner known to a specialist, starting from 1-bromomethyl-4-methanesulfonylbenzene and methylamine. at

The compound specified in the title is obtained similarly to example 1, starting from Kk! (4-methanesulfonylbenzyl)methylamine (intermediate 1) and. M-(4-(-2-bromoacetyl)phenyl|iacetamide (example 1, intermediate product 2).

Example 23

IM-(4-(2,6,8-Trimethyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylacetamide

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Starting from (2,4-dimethylbenzyl)methylamine, which can be obtained from 1-bromomethyl-2,4-dimethylbenzene and methylamine in a manner known to those skilled in the art, and M-(4-(2-bromoacetyl)phenyl)acetamide (Example 1, intermediate product 2), the synthesis is carried out similarly to example 1.

Example 24

IM-(4-(6-Bromo-8-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|acetamide

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Based on (4-bromo-2-chlorobenzyl)methylamine, which can be obtained in a known manner from 4-bromo-1-bromomethyl-2-chlorobenzene and methylamine, and M-I (4--2-bromoacetyl)phenyl|iacetamide (example 1, intermediate product 2) carry out the synthesis similarly to example 1.

Example 25

M-I4-(8-Chloro-2-methyl-b-pyrrolidin-1-yl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|acetamide)

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Sol w Ivt 1.02 g (333.12 mmol) C8v2CO3, 88 mg (0.04 MmmMmol) palladium acetate, as well as Zb, mg (0.Obmmol) y-2,2-bisidiphenylphosphino)-1,1-binaphthyl in an argon atmosphere add 5 ml of absolute toluene to b. At room temperature, add a solution of 512 mg (1.3 mmol)

IM-I(I4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iacetamide (example 24) in 4 ml of absolute dimethylformamide, as well as a solution of 111 mg ( 1.5 mmol) of pyrrolidine in 4 ml of dimethylformamide and heated " for 7 hours at a temperature of 10020. For workup, the solvent is removed in vacuo and the residue is treated with dichloromethane. The insoluble components are filtered off and the filtrate is concentrated. From the residue by chromatography on silica gel using a mixture dichloromethane and methanol, while "" Zbomg of the compound indicated in the title of the example can be isolated. 25a: M-I4-(8-Chloro-2-methyl-6-pyrrolidin-1-yl-1,2,3,4-tetrahydroisoquinoline -4-yl)/phenyl|iacetamide hydrochloride - their composition and composition

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Dissolve 20 mg of /M-(4-(8-Chloro-2-methyl-b-pyrrolidin-1-yl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)acetamide in 20 ml of a solution of NCI in ethanol, stir for 30 minutes minutes at room temperature and concentrate.

The residue is treated with water and freeze-dried.

Example 26 65 IM-(4-(8-Chloro-2-methyl-6-morpholin-1-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylacetamide trifluoroacetate

-

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Ka and Vr r

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It is obtained similarly to the method described in example 25, based on

IM-I(I4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenylacetamide (example 24) and morpholine. After chromatographic separation on silica gel, further purification is carried out by preparative HPLC.

Example 27

M-14-(I-Chloro-2-methyl-6-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydroisoquinolin-4-yl|phenyl)iacetamide shen more

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It is obtained similarly to the method described in example 25, based on Kk!

IM-I(I4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|acetamide (example 24) and M-methylpiperazine. 2t7a: « du M -4-(B-Chloro-2-methyl-6-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-4-yl|phenyl)acetamide hydrochloride with

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ЧК» E. MAY t vik o y mivy y Yan Gy: what) y ge 220mg M-4-I(8-Chloro-2-methyl-6-(4-methylpiperazin-1-yl)-1,2,3 ,4-tetrahydroisoquinolin-4-ylphenyl)acetamide and dissolve. in a small amount of methanol, dilute with 2n NH! and subjected to freeze-drying to obtain 226 mg of the target hydrochloride. (F) Example 28 ka M-14-(Y-Chloro-6--'cyclopropylmethylamino)-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl|phenylacetamide hydrochloride 60 b5 -BO0-

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It is obtained similarly to the method described in example 25, based on Kk!

IM-I(I4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylacetamide (example 24) and

C-cyclopropylmethylamine. After chromatographic separation on silica gel, further purification is carried out by preparative HPLC. The purified compound is dissolved in other NSI, diluted with water and dried by freezing.

Example 29 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid

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Intermediate 1: 5-acetyl-2-hydroxybenzoic acid ethyl ester

Obtained in a known manner from 5-acetyl-2-hydroxybenzoic acid by an acid-catalyzed esterification reaction.

Intermediate 2: 5-(2-bromoacetyl)-2-hydroxybenzoic acid ethyl ester

It is obtained by known methods from the ethyl ether of 5-acetyl-2-hydroxybenzoic acid similarly to the method described in example 1 for intermediate product 2.

Intermediate C: ethyl ether - with 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid "from ethyl ether 5-(2 -bromoacetyl)-2-hydroxybenzoic acid and 2,4-dichlorobenzylmethylamine" (see example 1, intermediate product 1) synthesize the compound indicated in the title according to the method described in example 1. 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid - and b,vg (1 mmol) ethyl ether - 5-(6,8- dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid is saponified in a mixture of ethanol and 2N KOH solutions in a manner known to a specialist, while obtaining 5.4 g of free acid. (ав) 29а: Sodium salt of 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid: synthesis of 70 ee "re SE "PYASHTE efe still Sho oy visi and te o MNK in: t t vi y i dochav Not sn 60 Ki? Pod 352mMg (Immol) 5-(6,8-dichloro-2-methyl-1,2,3 ,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid is dissolved in 10ml of 0.1M Mahon solution, diluted with water and subjected to freeze-drying, thereby obtaining 375mg of the compound indicated in the title.

Example 30 65 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxy-M-methylbenzamide trifluoroacetate

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SHI with PE ee

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Starting from 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid, the title compound can be obtained by a TOTIO-mediated reaction with methylamine similar to 75 described in example 7 of the method.

Example 31 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-ethyl-2-hydroxybenzamide trifluoroacetate with SVI

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Kk os I attempt:; "with V

Starting from 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid, the title compound can be obtained by TOTO-mediated reaction with ethylamine similarly And the method described in example 7. "in)

Example 32 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-(2-dimethylaminoethyl)-2-hydroxybenzamide trifluoroacetate

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Starting from 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid, the title compound can be obtained by mediated tot reaction with

М1,М1-dimethylethane-1,2-diamine, similarly to the method described in example 7. Example 33

He M-(5-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoyl|guanidin shi rya rea y Z ШЭ Ш Ш Ш Ш.

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To a solution of 2.39 g (25 mmol) of guanidine hydrochloride in 1.5 ml of absolute dimethylformamide, add 2.52 g of 65 potassium tert-butylate and stir for 45 minutes at room temperature. Add a solution of 95 mg (2.5 mmol) of 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid ethyl ether (example 29, intermediate 3) in 10 ml of absolute dimethylformamide and stirred for four hours at room temperature. After no further increase in conversion can be established, the precipitate is filtered off under vacuum and the solvent is removed under vacuum. The residue is treated with 2N NH and extracted twice with dichloromethane. The aqueous phase is adjusted to a pH of approximately 10 with KOH, and the target acylguanidine precipitates as a colorless precipitate. By vacuum filtration and drying, 79 mg of the title compound are obtained.

Example 34

M-I3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|acetamide 70 ml

She y y o zi u Ka he: t ee: ke p!

Ki

The target meta-acetanilide is obtained similarly to the synthesis described in example 1, based on

M-(3-acetylphenyl)acetamide and 2,4-dichlorobenzylmethylamine (example 1, intermediate 1), according to four similar stages. Gee!

Example 35 about 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine shk

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Cleavage of the acetyl group from "

IM-IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iacetamide (example 34) is carried out according to the method described in example 17 for intermediate product 1 in the presence sodium methyl atu. From c Example 36 and » 2-(6,8-dichloro-2-methyl-2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine c pk g

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Intermediate 1: M-(2-(2-bromoacetyl)phenyl)acetamide 3g (0.175 mol) of M-(2-acetylphenyl)acetamide (obtained by acylation of 2-aminoacetophenone with acetyl chloride according to Etsegwipeg A|Poiv, dZitrate Oepiv M ., Teggapeagop, 48, 29, 5991-6010 (1992) | dissolve in 200 ml of glacial acetic acid. Add 127 ml of 3390 solution of HBg in glacial acetic acid and then slowly add 8.75 ml (0.175 mol) of bromine at room temperature. The mixture is stirred overnight at room temperature and, while stirring, is added to 1.5 L of ice water, the precipitated product is filtered off under vacuum, additionally washed well with ice water and dried under vacuum. According to HPLC and NMR, the crude product contains a small 60 amount of starting material and dibrominated product, however, for further conversion it is sufficiently pure (about 8595-na purity).Yield: 43Zg.

Intermediate 2: M-(2-2-((2,4-dichlorobenzyl)methylamino|acetyl)phenyl)acetamide 12.4 g (65.24 mmol) of 2,4-dichloro-M-methylbenzylamine (example 1, intermediate 1 ) is dissolved in 200 ml of dioxane. 19.96 g of crude product of preliminary bromination, also dissolved in 65 ml of dioxane in 200 ml, and 45 ml of triethylamine are added to the resulting solution. The mixture is stirred overnight at room temperature and then filtered. The filtrate is evaporated, the residue is treated with ethyl acetate and washed with saturated sodium bicarbonate solution and sodium chloride solution, dried over sodium sulfate and concentrated in a rotary evaporator. The crude product (20.4 g), according to NMR, is pure enough for further conversion.

Intermediate product 3: M-(2-2-((2,4-dichlorobenzyl)methylamino|-1-hydroxyethylphenyl)acetamide 20g (approximately 5Omol) of the crude product obtained at the previous stage is dissolved in 200ml of methanol and cooled in an ice bath to temperature "59 C. 4.3 g (109 mmol) of sodium borohydride is added in portions to the resulting solution with good mixing, so that the internal temperature does not exceed 10260.

Then it is additionally stirred for another 30 minutes in an ice bath and for 1 hour at room temperature. After standing overnight, the mixture is evaporated, the residue is treated with ethyl acetate, washed 70 times with water and once with sodium chloride solution, dried over sodium sulfate and concentrated in a rotary evaporator. The crude product (19.4 g) is further subjected to transformation without further purification.

Intermediate product 4: 1-(2-aminophenyl)-2-(2,4-dichlorobenzyl)methylamino|ethanol 10g of the raw product obtained at the previous stage is dissolved in 300ml of methanol. Add 200 ml of concentrated hydrochloric acid and stir for 10 hours at a temperature of 50 °C. Leave 75 to cool, the reaction mixture is poured into water and with the help of 2095 MasonH solution, the pH value is set to 10-12. The product is extracted with ethyl acetate, the combined extracts are washed with sodium chloride solution, dried over sodium sulfate and evaporated. The raw product (9.9 g) contains a little sodium chloride, which, however, does not interfere with further transformation. 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine 9.9 g of the crude product obtained at the previous stage is dissolved in 35 ml of chloroform. When cooling in an ice bath, add 123 ml of concentrated sulfuric acid. It is additionally stirred for 2 hours in an ice bath, then the temperature is slowly raised to room temperature and, finally, heated overnight at a temperature of 50 °C. The cooled mixture is poured onto ice and alkalized with sodium hydroxide solution (pH»10). The organic phase is separated, the aqueous phase is additionally extracted 2 times with dichloromethane, the combined organic phases are washed with He water and Masi solution, dried over sodium sulfate and evaporated. (5)

General method of obtaining the compounds of examples 37-77 154 mg (0.5 mmol) of the target compounds from example 35, example 36 or example 17, intermediate 1, are added to bml of dichloromethane and mixed with 0.07 bml (0.55 mmol) of triethylamine. At a temperature of 09, a solution of 1.1 equivalents (O0.55 mmol) of acid chloride in bOml of dichloromethane is added and stirred overnight with thawing. For processing, filter and remove the solvent. The residue is dissolved in 20 ml of ethyl acetate and washed once with a 590% solution of MansSoOz, as well as with a 595% solution of Masi, and dried.

After removing the solvent, final purification is carried out by preparative HPLC. | "c) cha i - - s . and? -I -I («c) sh»

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J. Be - B. University of E. shk I Her - NN NI NKY i EN MN U KN p their SHYZHYA, I I: MZHK Aste dk. 45 tei zd yunlinyan nt si - 7 aa. Example 78 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl|-3-ethyl urea trifluoroacetate

Z x ШЧе яш 50 Take de dao ne pi xx Kovi Es ; 1 Z.

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Mona TD ZNEH 60 ry their mother

I

0.355 mmol of the compound of example 35 is dissolved in bml of anhydrous acetonitrile and mixed with 0.39 mmol of ethyl isocyanate. After standing overnight with removal of moisture, the solvent is removed and the crude product b5 e : e is purified by preparative HPLC to give the title compound as a colorless solid.

Example 79 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylthiourea trifluoroacetate fast

Ш ША Ще ": ШЙ EE a - shck Coffees and rai dut s y h y

Also

Me ekot vna en 70 | G y sho ev More EI B V Ko t Z HER in the spring

And that's what I'm in

Mecca Anna

I and di te i sheche

Based on the compound of example C5 and methyl isothiocyanate according to the method described in example 78, the compound specified in the title is synthesized.

Example 80 1-(2-16,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)|-3-ethylurea

MET, s; scha she sch

TE sei ke Shnasnokh SA se (o)

Another Psa kV "in that ey pe Ko Shi

NYA goes pai Y i Nv: gu si ish shi shi o azh a t ia od ! one! ! pi and -

Proceeding from the compound of example Zb and ethyl isocyanate, a method similar to example 78 is followed. For processing, the precipitate formed is filtered under vacuum and washed with acetonitrile, thus obtaining the target ethyl urea in the form of a colorless solid.

Example 81 "du 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylthiourea trifluoroacetate with i: CH deco sat i, tk ; Z ii her ; s still KEN "a h Zhe x I i vy 5 Z -I -y ge, - shva "rya shu B sti -1 Be: AY her Resleyakh Shchy en, deya y:

Мект пери s ШЭ... with the included weight of PTS: и3 70 ysloy det: ZK KN,

Io "Ve tey

The compound of example 36 and methyl isothiocyanate are introduced into the interaction in a manner similar to that described in example 78 of the method. 99 Example 82

HF) Hydrochloride 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide ethanesulfonic acid ime) 60 b5

Mi: pas sei la ay b: a SE: KDD g y shchen 2 sk . 56.

She ee asya y o v dany 0000 Sya re UT to SN IY first ay vih y te ki ia dIZH yi : 5 i tia

MNK to sew 0 NVK, lion act let mon

307.1 mg (1 mmol) of the compound of example 35 is dissolved in 1 ml of pyridine and mixed with 0.19 g (1.5 mmol) of ethanesulfonyl chloride and a catalytic amount of 4-dimethylaminopyridine (OMAR) at a temperature of 02C.

Stir at room temperature. For processing, the solvent is removed in vacuo, the residue is treated with ethyl acetate and washed with water. The organic phase is dried over magnesium sulfate and concentrated. The crude product is chromatographed on silica gel. The thus obtained sulfonamide is dissolved in a mixture of tetrahydrofuran and 2N NOI and concentrated again in a vacuum, thus obtaining 208 mg of the target hydrochloride.

Example 83 p

M-I3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl)methanesulfonamide hydrochloride o

I am; their

I nn a oh y shi SHY sia ak NE se YAN "DO NOT PEBAZH ey sun nok Z

WHAT ARE WE?

Mo ni pai oh i s den shk | "c) a gift. and and what

NO and, 0 pounds By NK

Ah Sha -

DO NOT EXPERIENCE TEN WITH EXPERIMENTAL EDUCATION

SHK uky SCHE and ak yah tya - 2, "with SAD" Proceeding from the compound of example 35 and methanesulfonyl chloride, follow the method described similarly in example 82.

Example 84

Che Hydrochloride (|4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide ethanesulfonic acid -i ("c) sh"

Ko) ime) 60 b5 sh i ZE Uteya seti ok from Mt for

In the vein of IR

Ve tn 70 Ii skh s ro

I am so

Ir ie sv still Sbegyai Yan still essay -- check you edict t, li She

She

Based on the compound of example 17, intermediate product 1, and ethanesulfonyl chloride, follow the method described similarly in example 82. with

Example 85 o

IM-(4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl|Imethanesulfonamide hydrochloride and De

Kobeya o schev yan z0 min i va. re

K. I "

From about the same where 5 and - 7 and | : eat, but even t hN and 5 t that x « da Es and chas re oo zha:

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J

-i and o Based on the compound of example 17, intermediate product 1, and methanesulfonyl chloride, follow the method described similarly in example 82. d» Example 86 "from 8ba: (-)-M-I3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylacetamide 86r: OO ()-M- I3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylacetamide

F) ime) 60 b5 o own and IZ Vk , : I with I: still g y

SYA palav Kut peso -h i ste Shayan nya s ai De shyneh

2.0 g of the compound specified in the title of Example 34 is separated on the chiral phase, and approximately 1.0 g of both enantiomeric acetamides 86ba and 866B are obtained.

A column with a chiral phase SpPigairak AYUON/Z1; 250x4, bmm; solvent: acetonitrile; volumetric flow rate: Tml/min.;

P-)-enantiomer/8ba)-5.541 min.; sch d )-enantiomer/865)-7.033Хх8в.

General method of obtaining the compounds of examples 87-98 Ge) 1 c0mmol of 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine (example 17, intermediate product 1), respectively, 3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine (Example 35) is added to 1 Oml of pyridine and at a temperature of 0°C a solution of 1.2 equivalents of the corresponding anhydride chloride, 20 mg acid (see Table 2) in 5 ml of dichloromethane. Stir at room temperature. Depending on the development of the reaction, add a catalytic amount of OMAR and, if necessary, raise the temperature of the Ж reaction to 502С, until no further increase in conversion can be established. For processing, it is concentrated and the residue is distributed between ethyl acetate and a saturated solution of Manso with. The organic phase is separated and once again washed with a saturated solution of MansSoOz and water, dried over sodium sulfate and concentrated. For in After further purification, the resulting crude product is chromatographed on silica gel. To convert the obtained food products into the corresponding hydrochlorides, the substances are dissolved in 2N HCI or an ethanolic solution of HCI and the solvent is removed, thereby obtaining the target HCI salts.

When purified by preparative HPLC, the corresponding products are obtained in the form of trifluoroacetates. " - with . and? -I -I («c) drive 50

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General method of synthesis of the compounds of examples 99-110 in Preparation of the amine component 4.00 mmol of aromatic aldehyde (see Table 3) together with 8.0 mmol of aliphatic amine (see Table 3) in methanol are stirred for 2 hours at room temperature and then, depending from the course of the reaction, mixed in portions with 0.67-2.0 equivalents of MavN 5. After standing overnight at room temperature, the solvent is removed and the residue is treated with other NS. Extract with dichloromethane. In the 65 aqueous phase, the pH value is set from 11 to 12 with the help of Mahon and extracted again with dichloromethane.

The organic phases are dried over magnesium sulfate and concentrated in a rotary evaporator. Further purification is carried out by chromatography on silica gel or by preparative HPLC.

Obtaining the bromoketone component

Bromoketone components are synthesized by methods known from the literature, based on commercially available acetophenones, by bromine treatment in glacial acetic acid, similar to the method of example 1 for intermediate 2.

Based on the amine and bromoketone components indicated in Table C, the compounds of examples 100-111 can be obtained similarly to the synthesis described in example 1 (alkylation of the amine component with the help of the bromoketone component, further reduction with the help of Mavn, and further, mediated by NZO,X 7/o / Cyclization).

The obtained tetrahydroisoquinolines can be converted into the corresponding salts in a manner known to the expert.

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V. chic and nn vno nn their av! General method of obtaining the compounds of examples 111-124. 0.358 mmol of the acids specified in Table 4 are dissolved in 50 ml of dimethylformamide and 0.221 ml (1.30 mmol) of diisopropylethylamine is added. At a temperature of 09, a solution of 128 mg (0.390 mmol) of LTTE in one ml of dimethylformamide is added. After mixing with a solution of 100 mg

Kk" (0.325 mmol) of the amine component specified in Table 4 in 2 ml of dimethylformamide is stirred at room temperature overnight. For processing, it is filtered from insoluble components and additionally washed with 20 ml of ethyl acetate. The filtrate is washed twice with saturated Manso solution, and once with Massey's 5905 solution, dried and concentrated. o From raw products that still contain Bos protective groups, protective groups are removed without further purification (see below: the general method of removing Bos protective groups) In the case of components not protected by Bos groups, after their isolation, preparative HPLC is performed, with this gives the target compounds of the examples in the form of trifluoroacetates. 60 General method of obtaining compounds of examples 125-147 0O.358mm mol of the acids indicated in Table 4 are dissolved in 1ml of dimethylformamide and 0.221ml (1.30mmol) of diisopropylethylamine is added. At a temperature of 09C, it is mixed with 151 mg (0.975 mmol) of diethylcarbodiimide, a solution of 132 mg (0.975 mmol) of M-hydroxybenzotriazole (NOVO) in one ml of dimethylformamide, as well as 20 mg (0.162 mmol) of 4-dimethylaminopyridine (OMAR). After sprinkling the solution of the amine 65 component indicated in Table 4 in 2 ml of dimethylformamide, stir at room temperature overnight. For processing, it is filtered from insoluble components and additionally washed with 20 ml of ethyl acetate.

The filtrate is washed twice with a saturated solution of ManHsSoO", and once with a 595% Massey solution, dried and concentrated.

Raw products that still contain Bos-protecting groups are deprotected without further purification (see below: general technique for cleavage of Bos-protecting groups). In the case of components not protected by Boc groups, after their isolation, preparative HPLC is performed, while the target compounds of the examples are obtained in the form of trifluoroacetates.

General technique for cleavage of anti-antibody groups

The obtained raw products in bml of a 10956 solution of trifluoroacetic acid in dichloromethane are stirred 7/0 for one hour at room temperature. Then it is concentrated in a vacuum and the residue is purified by preparative HPLC, and the target compounds of the examples are obtained in the form of trifluoroacetates. ani koh kn ooo K r i vn, i o o v v v V i i i Osi v V v:

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Example 148 "1-(2-(6,8-dichloro-2-methyl-1 2,3,4-tetrahydroisoquinolin-4-yl)-phenyl|-3-ethylthiourea hydrochloride t0 ich n- aa ey li pa IC shchi 3 : soya, o : | aha knizhn: vrakyty ih ssiytya -I k i I BUM ie

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95 mg of 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine (compound of example Zb) is added to 4 ml of acetonitrile and, with stirring, 27 mg of ethyl isothiocyanate. After standing for 15 hours at room temperature, the solvent is removed in vacuo and the residue is purified by preparative HPLC.

Trifluoroacetate obtained in this way is treated with water and alkalized with K»CO3. Aqueous phase

HF) is extracted with ethyl acetate. The organic phase is separated, dried over magnesium sulfate and concentrated. The residue is treated with dilute hydrochloric acid and subjected to freeze-drying, and Zbmg of the title compound is obtained. in Example 149 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-ethylthiourea hydrochloride b5

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Bomg of 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine (compound of example 17, intermediate 1) is added to 4 ml of tetrahydrofuran and mixed with 14 mg of ethyl isothiocyanate. After boiling with a reverse 7/5 refrigerator for 2 hours, the reaction solution is concentrated and heated for 2 hours at a temperature of 8520. The crude product thus obtained is purified by preparative HPLC. Further treatment of the thus obtained trifluoroacetate as described in Example 148, after freeze-drying, gives ZZmg of the target hydrochloride.

Example 150 1-I3-(6,8-dichloro-2-methyl-1 2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-ethylthiourea trifluoroacetate

BA valo in SHE zhk SHU y: i " I Ne Ge 7 chi "a TI i: Z TE ren eh kar ke NK y Ii zi " 5Omg 3-(6,8-dichloro-2-methyl-1,2,3 ,4-tetrahydroisoquinolin-4-yl)uphenylamine (compound of example 35) is dissolved in 3 ml of tetrahydrofuran and mixed with 14 mg of ethyl isothiocyanate while stirring. After refluxing for 2 hours, the reaction solution is concentrated and heated for 2 hours at a temperature of 8590. Thus, the crude product obtained is purified by preparative HPLC, and bbmg of the title compound is obtained.

Example 151 3-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl|-1,1-dimethylcarbamide hydrochloride i5; there is v. 7 KI. decoys

GE Intermediate 1: 4-nitrophenyl ether hydrochloride

3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylylcarbamic acid

350 mg of /3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine (compounds of example 35) are dissolved in 17 ml of dichloromethane and mixed with 2300 mg of 4 -nitrophenyl ether of chloroformic acid. After 4.5 hours. add the following 0.1 equivalents (2 mg) of 4-nitrophenyl ether (F) of chloroformic acid and stir the solution overnight. For processing, the sediment that has fallen is filtered and

The GI is washed with dichloromethane. The title compound obtained in this way can be subjected to further transformation without further purification. in 3-IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,1-dimethylurea hydrochloride

35 mg of 4-nitrophenyl ether hydrochloride

I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|carbamic acid (intermediate product 1) is suspended in 3.5 ml of dichloromethane and, with stirring, a solution of 3,/ mg of dimethylamine in ml of dichloromethane. After 1 hour, dilute with dichloromethane and wash with an aqueous solution of K»CO3. The organic 65 phase is separated and washed twice with a saturated solution of CoCO3, dried over magnesium sulfate and concentrated. The residue is treated with diluted hydrochloric acid and freeze-dried,

and 29 mg of the title compound are obtained.

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Intermediate 1: 4-nitrophenyl ether hydrochloride (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|carbamic acid 200 mg 2-(6,8-dichloro -2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine (compound of example 36) is dissolved in 10 ml of dichloromethane and mixed with 131 mg of 4-nitrophenyl ether of chloroformic acid with stirring.

After 3.5 hours, the precipitate that has formed is filtered off under vacuum and washed with dichloromethane. The thus obtained crude product is recrystallized from dichloromethane, thus obtaining 159 mg of the title compound.

Hydrochloride (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)| 4-methylpiperazine-1-carboxylic acid amide with 15 mg of 4-nitrophenyl ether hydrochloride g) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|carbamic acid suspended in 2 ml of dichloromethane and mixed with a solution of 3.2 mg of 1-methylpiperazine in 1 ml of dichloromethane. After 1 hour, dilute with dichloromethane and wash with an aqueous solution of K»CO3. The organic phase is separated and washed twice with a saturated solution of COCO3, dried over magnesium sulfate and concentrated The residue is treated with dilute hydrochloric acid and subjected to freeze-drying, thus obtaining 1 mg of the compound indicated in "g" of the title.

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Intermediate 1: 4-nitrophenyl ether hydrochloride

I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/phenyl|carbamic acid 200 mg 4-(6,8-dichloro-2-methyl-1,2, 3,4-tetrahydroisoquinolin-4-yl)uphenylamine (compound of example 17, intermediate 1) is dissolved in 1 ml of dichloromethane and mixed with 131 mg of 4-nitrophenyl ether with xchloroformic acid under stirring. After 4.5 hours, the sediment that has fallen out is filtered under vacuum and washed with dichloromethane. The crude product thus obtained is recrystallized twice from dichloromethane, and 254 mg of the title compound is obtained.

Hydrochloride I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)| of 4-methylpiperazine-1-carboxylic acid amide with 15 mg of 4-nitrophenyl ether hydrochloride

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CSR". The organic phase is separated and washed twice with a saturated solution of K»oCO3, dried over magnesium sulfate and concentrated. The residue is treated with dilute hydrochloric acid and subjected to drying or freezing, and 1 mg of the title compound is obtained.

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Y o ss: Y NK BYA r y

GE - Dake And I - from. i

And, and: Yay r her and h: pe g i pry sty ee pe z i Be tn reno I

N vy zom i s s aku: U I ee ky E

I "V vyg and I Shk tu M: I;

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Example 184

IM-(4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|formamide hydrochloride) sleep inn I with)

200 mg of 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine (compound of example 17, intermediate 1) is dissolved in 1 ml of formic acid and boil under reflux for 15 minutes.

After standing overnight, the mixture is added to a mixture of water and ice and extracted twice with ethyl acetate.

The combined organic phases are dried over magnesium sulfate and concentrated. The residue is treated with dichloromethane and washed with a saturated solution of ManHsSoO»z. The phases are separated and the aqueous phase is extracted three more times with dichloromethane. By drying the organic phases (Mo5O)4) and distilling off the solvent, 167 mg of crude product is obtained. 1 mg of the product is dissolved in diluted HCl and freeze-dried, and 11 mg of the title compound is obtained.

Example 185

14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl|methylamine hydrochloride

BE Be etc

I and Z! rea szhaya Yai dr go

E i and pallets av)

Karlu 7- E: cha nt n vv y i

1500 mg of M-(4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl) formamide (compound of example 184): from" is dissolved in 2.5 ml of tetrahydrofuran and at a temperature of 5022 in an argon atmosphere is added to a solution of 0.45 ml of a 1 M solution of lithium aluminum hydride in tetrahydrofuran in 2.5 ml of tetrahydrofuran. Boil with a reflux refrigerator for 1 hour. After standing overnight, add at at a temperature of 50 C, the following - and 0.22 ml of a 1 M solution of lithium aluminum hydride and refluxed for the next hour. For processing, the solvent is removed and the residue is distributed between dichloromethane and an aqueous solution of NOSI. The phases are separated and the aqueous phase is extracted three times with dichloromethane. The combined organic phases are dried over magnesium sulfate and concentrated. Further purification is carried out by preparative HPLC. Thus obtained

The product is treated with Manso solution and extracted with dichloromethane. By drying the organic phase over - magnesium sulfate, 8Omg of the free base is obtained. Tomg bases are treated with a diluted solution of NSI and

GE is freeze-dried, and 1mg of the title compound is obtained.

Example 186 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,3-dimethylcarbamide hydrochloride

F) name) 60 b5

Se ki Z as z. that

NV I ar with I : m more

Mo. SN de VEK 0. Z

And

The compound specified in the title is obtained according to the method described in example 151, based on

14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamine (Example 185), 4-nitrophenylchloroformate and methylamine (2Oml, 2M solution in tetrahydrofuran), and obtain Umg of the target hydrochloride.

Similarly to the methodology of example 186, based on Kk!

14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamine (example 185), 4-nitrophenylchloroformate and the corresponding amine components, the following compounds are obtained: c (8 ) s « «c) cha m. shi s z -I -I («c) iz 50

Co.)

F) name) 60 b5

There is

In their SECT

MAVKA

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ТЕ я З -Щ Э Х и ; yar Not YET NK, i

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VKA AK KE YAN Navy PC VN ve i KN V («c)

Example 194 M

M-III-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/phenylformamide and m : ЖЕ «Ж

Ii:

Kt ey o g "

B i d i ya y shi x g i- So . to her BD ch de va es M re Y y t E idu oy Oko cho y svya s t h (7 ay F

Z DY z KE i penary j st ZY Kon Sov - coupling of bOOmg 3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine (compound of example 35) dissolve VE in 24 ml of formic acid and boil under reflux for 15 minutes. After aging

Overnight, the reaction mixture is added to a mixture of ice water and a saturated solution of Manso)" and extracted three times with dichloromethane. The combined organic phases are dried over magnesium sulfate and concentrated to obtain 588 mg of the title compound.

Example 195 o IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamine hydrochloride ime) 60 b5

Pi: t mishku Yan dev d sn Ma a i yi Zk ; from tya y y in Sv t y fran zation i Ma» ia

Be

CO with 588 mg of 0 M-(3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenylroramide) (compound of example 194) 75 is dissolved in 10 ml of tetrahydrofuran and at a temperature of 5023 in an argon atmosphere is added to a solution of 1.8 ml of a 1 M solution of lithium aluminum hydride in tetrahydrofuran and refluxed for 1 hour.

After standing overnight, add the next 2 ml of 1 M solution of lithium aluminum hydride at a temperature of 502C and boil under reflux for the next 30 minutes. For processing, mix with ice and the aqueous phase is extracted four times with ethyl acetate. The combined organic phases are dried over magnesium sulfate and concentrated. Further purification is carried out by preparative HPLC. The thus obtained product is treated with Manso solution and extracted with ethyl acetate. Drying of the organic phase over magnesium sulfate gives 27Omg of the free base. 45 mg of this base is treated with a diluted solution of NSI and freeze-dried, and 45 mg of the title compound is obtained.

According to the method described in example 151, based on Kk! se |3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Imethylamine (example 195), 4-nitrochloroformate o and the corresponding amine components, the following compounds are obtained: s " "c) cha m. - s . and? -I -I («c) sh»

Co.)

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Mk EK akny KK leni shkh EEEENNI Z y ---

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KO et oeh Y "Shk ee BE non Kk - i

NEK B; About: Also:

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Example 204

Hydrochloride of 2-dimethylaminoethyl ether "

13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylcarbamic acid is not: : I I -

JE s, ME AK te pyti ev Z I - zi seose VN: - VYN still ch y I U x oreh a! And And | |;

More blue rih an from the seam! ЖЭя - I se How: session paz kro tn : yara tre ВХ y I ak -I ІВ і рі ! 15 хх B сх: ИЙ (ав) dey DA, pe ikh et pl

And t» 5. th

When stirring («| in an argon atmosphere, 15 mg of 4-nitrophenyl ether hydrochloride

3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl|carbamic acid (see example 151, intermediate 1) is suspended in 1.5 ml of dichloromethane and mixed with a solution of Zmg of 2-dimethylaminoethanol in about 0.bBml of dichloromethane and stirred for b hours. After standing overnight, water, dichloromethane and saturated Manso solution are added and the organic phase is separated. The dichloromethane phase is washed three times with a saturated solution of MnSO 3 , dried over magnesium sulfate, and the solvent is removed under vacuum. The thus obtained crude product is purified by preparative HPLC. The fractions containing the product are concentrated and partitioned at 60° between ethyl acetate and a saturated solution of Manso with. The organic phase is separated, dried over magnesium sulfate and concentrated. The residue is treated with dilute hydrochloric acid and freeze-dried to obtain 5 mg of the title compound.

Similarly, starting from the hydrochloride of 4-nitrophenyl ether

14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)carbamic acid and hydrochloride 65 4-nitrophenyl ether (|2-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|carbamic acid, the corresponding isomers are obtained: 2-dimethylaminoethyl ether hydrochloride

I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)carbamic acid and hydrochloride of 2-dimethylaminoethyl ether (2-(6,8-dichloro-2-methyl -1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)carbamic acid. " Mi re Y M my g aeri zhi I Z shchaOny a TE mi in 33 g. per se ikh ke Te KU zh ! u MEZHA Ki ihz, Be N| Kaya yat ve BT E r: interna ZE yulysh J shk not zeevo day oi: dk soplulnv SHE r

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From Z for Ps avsv

Z I I t I 75 Z 54 r er what Ne nya I,

I; i x and 53 s

Z os oyuazha A r v sen her t tane KE

I c re V

M uses the 5th base of the letter and letter

E S tn, you J. pln them in u y. and not KE in «a Yan Ko I A G ha Z te, ME in s 2 І A і х BE і (8) with і:

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D 1 pile Z and lm G:; -at

Ma p Kol Be V i juice of veins in z---iV --e E E-025 sg - y vus ly o ne VEN t OS ShTA et "» Example 207 " Hydrochloride of methyl ether I3-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|carbamic acid same pa: 75 so MK: 5 I -I kap BA s I Ku y iya suki nene oi x TYA ta Se in

What |! And him. iy y TE I ss KD o She snk shЯ i ps 20 | where t. zano

SM she shh zol k v kny hAp her sister-

Ko) ОИ and

Тец Ж t kn Vot z tk MALANKA: BALA kavttnu ey o kl siya ka in an atmosphere of argon and with stirring 15 mg of 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl )uphenylamine (Example 35) is added to 1.5 ml of dichloromethane, and 1 is mixed with a solution of 4.6 mg of methyl chloroformate in 0.5 ml of dichloromethane. After stirring for 6 hours and standing overnight, add the next 2.3 mg of methyl chloroformate and stir for 5 hours. For processing, the solvent is removed, the residue is treated with dilute hydrochloric acid and freeze-dried, thereby obtaining 20 mg of the title compound.

Similarly, leaving Kk! corresponding anilines - 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine, respectively, b5 4-(6,8-dichloro-2-methyl-1, 2,3,4-tetrahydroisoquinolin-4-yl)uphenylamine - the following carbamates can be obtained:

according to euvyra Shk

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I am in this world

Тех г ны: т B Я ЯЯХК Я з i: tys и я 75 ШЭ и ех MILE Z

Z t si I

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Example 215 where 215a: (t)-M-(3-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|methanesulfonamide hydrochloride 21560: (-)-M-I3- (6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide hydrochloride 60 b5 re z З за B

Ki l DN v ias Din, MI dev nai

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R NE et 18 sk s. E: with is Ky

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Bach х PO I: хи Еков В я

About mg of racemic M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|methanesulfonamide (see example 83)) is separated into enantiomers by preparative HPLC on a chiral phase.

SpigaIrak AB chiral phase column, 20 microns; 250x50mm; solvent: heptane-ethanol:methanol in a ratio of 10:1:1; volumetric flow rate: 5Oml/min.

The obtained enantiomers are dissolved in dilute hydrochloric acid and subjected to freeze-drying, and the title compounds 215a and 2156 are obtained. The purity of the enantiomers is determined using

HPLC on a chiral phase.

Column with chiral phase SpPigaIrak AO-N/Z1; 250x4, bmm; solvent: heptane-ethanol:methanol in a ratio of 10:1:1; volume flow rate: Tml/min.;

K, (the first eluted enantiomer)-6.84 min., 10095th enantiomer excess; and)

Ex (second eluted enantiomer) - 8.02 min., 10095th enantiomer excess.

Example 216 21va: (g)-1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylcarbamide hydrochloride c zo 216r: (- )-1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)-3-ethylcarbamide hydrochloride шШШ: desk z al shcha i tv, -, I don't have A Z and i

TYA shk o vy iz SE I y : ev; Be :3 et li oaKi, p y She i

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316 mg of racemic 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-33-ethylurea 15 (compounds of example 80) are separated into enantiomers by preparative HPLC on a chiral phase. - Column with chiral phase SpigaIrak OO, 20 microns; 250хх5Оммм; solvent: heptane-ethanol: isopropanol in a ratio of 50:2:1; 0.390 diethylamine; -| volumetric flow rate: 5Oml/min. o Enantiomers are separately subjected to further purification by preparative HPLC. The obtained products are distributed between a saturated solution of Manso with and ethyl acetate, the organic phase is separated, dried over

It is removed with magnesium sulfate and the solvent. By dissolving the residues in dilute hydrochloric acid and drying with freezing, 337 mg of the eluted first and 58 mg of the eluted second enantiomer are obtained. The purity of the enantiomers is determined by analytical HPLC.

Column with chiral phase SpPigaIrak 00-20; 250x4 BMM; solvent: heptane:ethanol:isopropanol in a ratio of 50:2:1 (0.395 diethylamine); volumetric flow rate: Tml/min.;

HF) K, (the first eluted enantiomer) - 9.22 min., 10095th enantiomer excess; 7 K, (second eluted enantiomer) - 9.96 min., 9896th enantiomer excess.

Example 217 in IM-III-(6,8-Difluoro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|acetamide hydrochloride b5 aromatic as

C Modne, I to her

Bi wai ; that's how SHO 5 is

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AND

Intermediate 1: 2,4-difluorobenzylmethylamine

Starting from 2,4-difluorobenzaldehyde, 2,4-difluorobenzylmethylamine can be obtained in a manner known to a specialist (see example 1, intermediate 1).

IM-IZ-(6,8-Difluoro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-acetamide hydrochloride

Starting from M-(3-acetylphenyl)acetamide and 2,4-difluorobenzylmethylamine (intermediate product 1), it is possible to obtain the compound indicated in the title as described in example 1 by synthesis.

Example 218 4-(3-Bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolinhydrochloride ka v Ya i shh I v a th "

On Monday

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Kz

Based on 2,4-dichlorobenzylmethylamine (see example 1) and 2-bromo-1-(3-bromophenyl)ethanone as an alkylating agent, the title compound can be obtained by the synthesis described in example 1. -

Example 219 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)-3-(2-hydroxyethyl)carbamide

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He 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl|carbamic acid (compound of example 151, intermediate product 1) is dissolved in 15 ml of absolute dimethylformamide and at temperature 09C is mixed with a solution of 67.2 mg (1.1 mmol) of 2-aminoethanol in 1 ml of dimethylformamide. Stir for three hours at room temperature and then remove the solvent under vacuum. The residue was partitioned between ethyl acetate and saturated Massey solution. The organic phase is separated, and the aqueous phase is extracted two more times with ethyl acetate. iF) The combined organic phases are washed with a saturated solution of ManHsSoO»z, dried over magnesium sulfate and co-concentrated. Chromatography on silica gel (dichloromethane/methanol) gives 265 mg of the title compound. in Example 220

Ethyl ether of 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid b5

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Obtained in a known manner from 3-acetylbenzonitrile by saponification of the nitrile group.

Intermediate 2: ethyl ester of 3-acetylbenzoic acid

Obtained in a known manner from intermediate product 1.

Intermediate 3: 3-(2-bromoacetyl)benzoic acid ethyl ester

It is synthesized from the ethyl ether of 3-acetylbenzoic acid (intermediate product 2) similarly to the method described in example 1 for intermediate product 2.

Ethyl ether of 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid with

It is possible to follow the synthesis described in example 1, starting from the ethyl ether of 3-(2-bromoacetyl)benzoic acid (intermediate 3) and 2,4-dichlorobenzylmethylamine (example 1, intermediate 1), while after the reaction of alkylation, reduction and cyclization reactions yield 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid ethyl ester.

Example 221 with 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/benzoic acid "

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After drying, 304 mg of the title compound is obtained as a colorless solid.

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Pharmacological data

Test description «

In this test, the restoration of the intracellular pH value (pH ;) after acidification, which is used in the case of normally functioning sodium-hydrogen exchange (NHE), as well as in conditions with the absence of bicarbonate, was established. For this, the pH was determined. with the help of the pH-sensitive fluorescent dye VSCE and (2,7-bis(2-carboxyethyl)-5,6-carboxyfluorescein) (Sairbiospet; the precursor VSCE-AM is used). "» Cells were first loaded with VSESE. VSEE fluorescence was determined using a spectrometer "Kaiyo RiIpogezsepse bZresigoteifeg (Rpoiop TesppoYodu Ipiegpaiopa!, Zotshii VgypemzhiskK, M.9U., USA) at excitation wavelengths of 505 nm and 44 Ohm and emission wavelength of 535 nm and using calibration curves - and converted to pH; Cells were incubated in MN.SiI-buffer (pH-74) (MNACI-buffer: 115mM Mass, 20mM MH, CsI, 5mM KSI, 1mM Sasi), 1mM Mo950O, 20mM Nerez, 5mM glucose, mg/ml and bovine serum albumin; with the help of a 1M solution of MaOH, the value of pH-/7a) is determined. aw! Intracellular acidification was induced by adding 975 μl of a buffer that does not contain MH SI (see below) to 25 μl aliquots of cells incubated in MH.SI-buffer. The further speed of pH recovery was recorded by the sk at MNE! two minutes, with MNE2 five minutes and with MNEZ three minutes. To calculate the inhibitory capacity

Among the test substances, cells were studied primarily in buffers in which complete pH recovery or no pH recovery occurred at all. To completely restore the pH (10090), the cells were incubated in

to the Ma"-containing buffer (133.8 mM Mas, 4.7 mM KSI, 1.225 mM Sas, 125 mM Mosi", 0.97 mM Ma»HPO,, 0.23 mM 5B manPo,, 5 mM Nerevz, 5 mM glucose; using 1M solution MasonN set the pH value to 7.0).

HF) determination of the value of 095 cells were incubated in a buffer that does not contain Ma"-ions (133.8 mM choline chloride, 4.7 mM yuyu KSI, 1.25 mM Sasi", 1.25 mM Masi", 0.97 mM CoHPO, 0.23 mM KNoRO, 5 mM Nerevz, 5 mM glucose; with the help of 1 M MasonN solution, the pH value is set to 7.0). The tested substances were introduced into the Ma"-containing buffer.

Recovery of the intracellular pH value in the case of each concentration of the tested substance 60 was expressed as a percentage of the maximum recovery. From the values of pH recovery expressed in percentages, using the Zidt-Rioi program, the ISvo value (concentration that causes 5095-no inhibition) of the corresponding substance for individual subtypes of MNE was calculated.

The results

Table 14 b5

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Ann is just ni po and writes with it ni po om 11 nene ni no psi niist li ni po i tu 1 plInigU i NI PO oyu 1011 ma | Tue 11 Sep with

Claims (1)

The formula of the invention o) 1. 4-Phenyltetrahydroisoquinolines of formula (1): where: с КИ, К2, КЗ and К4, independently of each other, mean Н, РЕ, СИ, Вг, И, СМ, МО», ОН, МН», СаНзачи, СадНада - and « ОСНон, СОКИТО, OSOMК10, СОК1О or O,-(СНо)у-phenyl; a and 5 in the groups САНоани and ОСНов.я, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8, and (Ф one or several H-atoms can be replaced by P-atoms; yes means 3, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by P-atoms; K10 means H or CoNosyai; - c means 1, 2, C, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by H-atoms; x means zero or 1; y means zero, 1, 2, З or 4; " and the phenyl ring in the O,-(CHo)y-phenyl group is unsubstituted or substituted with 1-3 substituents selected from the group consisting of E, SI, Bg, CM, MO", OH, MH" or CaHzdchi; - c and means 1, 2, C or 4, and one or more H -atoms can be replaced by E-atoms; и or "» КИ, К2, КЗ and К4, independently of each other, mean heteroaryl, and the ring can contain 0, 1, 2, З or 4 nitrogen atoms, 0 or 1 atom oxygen or 0 or 1 sulfur atom; or - and КИ, К2, КЗ and К4, independently of each other, mean СОМК11К12 or МК11К12; -1 К11 и К1 2, independently of each other, mean H, SeNoeni, StNot-1; e means 1,2, 3,4, 5,6, 7 or 8; (ав) гг means 3, 4, 5, 6, 7 or 8, and in the groups SeNoechi and StNaokt-1 and one or more H-atoms can be replaced by E-atoms and one or t». 2, several СНо-groups can be replaced by O or MK13; that) KIZ means H or StiNovi; It means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms; or КИЗ and one СНо-group of the K11 or K12 radical, together with the nitrogen atom to which they are connected, form a 5- or b--linked cycle; o or eat) K11 and K12 together with the nitrogen atom to which they are connected form a 5-, 6- or 7-ene ring; or 6o0 K11 and K12, independently of each other, mean SOK14, C5K14 or 50214; K14 means SoNadyai; d means 1, 2, 3, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by E-atoms and one or more СНо-groups can be replaced by O or MK13; or 65 КИ, К2, КЗ and К4, independently of each other, mean -0,-50)-К15, and also means zero or 1; means zero, 1 or 2; K15 means SKNokyaya, ON, OSINa»ya or MK17K18; K means 1, 2, 3, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by E-atoms; Y means 1, 2, C, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by E-atoms; K17 and K18, independently of each other, mean H or StpNotchi1; t means 1, 2, З, 4, 5, 6, 7 or 8, and in the group СтяНоти one or more H-atoms can be replaced by E-atoms and one or more СНо-groups can be replaced by О, СО, С5 or MK19; K19 stands for H or SuNodchi; 70 n means 1, 2, C or 4; moreover, in SaNor-4, one or more H-atoms can be replaced by E-atoms; or K17 and K18, together with the nitrogen atom to which they are connected, form a 5-, 6- or 7-lene ring; or K19 and the СНо group of the K17 or K18 radical together with the nitrogen atom to which they are connected form a 5- or b--linked cycle; moreover, however, always K2 should not mean H; K5 stands for H, SeNorni, SevNovv, SOK2O or BOZ2O; p means 1,2, 3,4,5, 6, 7 or 8; c5 means 3, 4, 5, 6, 7 or 8; k20 means SaNzdyai; d means 1,2, 3,4,5,6, 7 or 8, and in the groups SeNoria, SevNove-1 and SaNodnia one or more H-atoms can be replaced by P-atoms and one or more СНо-groups can be replaced on O or MK21; c K21 means H or SNachi; r means 1, 2, C or 4; (8) moreover, in SINAch4, one or more H-atoms can be replaced by E-atoms; Kb means H, E, SI, Vg, Y, SeNovachya, SdaNzda-1, OH, oOSsSNaya or osSoOng2; z ii, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8; c zoad means 3, 4, 5, 6, 7 or 8, and in SeNovch1; In SaaNoda-1 and OSINo3-ya, one or more H-atoms can be replaced by E-atoms; " K22 stands for Sun Nights; о и means 1, 2, З or 4; and in С, |Na)c-4 one or more H-atoms can be replaced by E-atoms; in. К7, КВ and КУ, independently of each other, mean -О,-50,,-К23; i-m means zero or 1; m means zero, 1 or 2; k23Z means SppNaoppya1» SttNott-i» OH, OSrrNorr-i or MK25K26; пп and пр, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8; " tt means 3, 4, 5, 6, 7 or 8, in c and in SppNoppya" SttNaott-i and OSrrNorr-i one or more H-atoms can be replaced by P-atoms; . K25 and K26, independently of each other, mean H, CM or С,Нао»н1, С,»Но»»1; and? 72 means 1, 2, 3, 4, 5, 6, 7 or 8; 77 means 3, 4, 5, 6, 7 or 8, and one or more H atoms may be replaced by E atoms and in C,H2/.-1 one or more H atoms may be replaced by P atoms, and one or more СНо-groups can be replaced by 0, СО, С5 or MK27; K27 means H or SaaNodachi; - aa means 1, 2, C or 4; and in SaaNodaz-1 ONE or several H-atoms can be replaced by E-atoms; or ve K25 and K26, together with the nitrogen atom to which they are bound, form a 5-, 6-, or 7-ene ring, or He K27 and one СНо group of the K25 or K26 radical together with the nitrogen atom with which they connected, form a 5- or b--linked cycle; or K?7, KV and KU, independently of each other, mean MK32СОМКЗО, MK32С5КЗО or MK325О0бКЗО; KZO means H, SooNossiai» SuNouu.1, pyrrolidinyl or piperidinyl, in the rings of which one CH o-group can be (F) replaced by O or MK33; ka KZ2 and K33, independently of each other, mean H or SuNorn4; рр means 2 or 3; 60 cc means 1, 2, 3, 4, 5, 6, 7 or 8; uu means 3, 4, 5, 6, 7 or 8; and means 1, 2, 3, 4, 5, 6, 7 or 8; moreover, in SuNonch one or more H-atoms can be replaced by P-atoms and in SesNossni and SuNouu 1 groups one or more H-atoms can be replaced by P-atoms, and one or more СНо-groups can be replaced by МКЗ1 and one The СНо group can be replaced by 0; KZ1 means H, SKNokknyi, SOKb5 or 50565; KK means 1, 2, C or 4; and one or more H-atoms can be replaced by E-atoms; Кб5 means Н, СххНоххчи; xx means 1, 2, C or 4, and one or more H-atoms may be replaced by P-atoms; or KZ1 together with one СНо group of the KZO radical forms a 5-, 6-, or 7-lene cycle; or KZO means a 5- or b-lene heteroaryl with 1, 2, 3 or 4 nitrogen atoms, 0 or 1 sulfur atoms and 0 or 1 7/0 oxygen atoms, which is unsubstituted or substituted up to three times with substituents selected from the group , which consists of RE, SI, Vg, I, SooNooozi, MAK7OK1; KO and K71, independently of each other, mean H, SuuNotsuichya and SOK72; K72 stands for H, SL/Nouchi; oo, shi and mu, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8; and in SooNooogi groups; One or more H-atoms can be replaced by E-atoms in CtshNHYotsii or SuU/Nouuii; or K7, KV and KU, independently of each other, mean H, RE, SI, Vg, I. MO", SM, ON, MN", SeeNoveni". Sumu Nodu-1 OsSeNoti, MK4OK41, СОМК4ОКА1, СООК42, СОКаЯ2 or OSOKA2; ee and I, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8; mly means 3, 4, 5, 6, 7 or 8; moreover, in the groups SeeNovech1, SuluNoudu-1, and OSyaNovya, one or more H-atoms can be replaced by E-atoms; K40 and K41 mean H, SeNon, or C(IMN)MN"; сч ІИ means 1, 2, Z, 4, 5, 6, 7 or 8; moreover, in the SeNon group, one or more H-atoms can be replaced by P-atoms and one or more i) CH»e-groups can be replaced by O or MKA44; K44 means H or C.5Noduni; 9a means 1, 2, 3, 4, 5, 6, 7 or 8; c zo and in the C39Nodd group, one or more H-atoms can be replaced by P-atoms, and K44, together with one SNeo group of the K40 or KA1 radical and the nitrogen atom to which they are bound, can form 5- or b- -lenny - cycle, av or K4O and K41, together with the nitrogen atom to which they are connected, form a 5- or b--lenny cycle; и- K42 means H or SfNonniai; cha n means 1, 2, 3, 4, 5, 6, 7 or 8; moreover, one or more H-atoms can be replaced by E-atoms in the Sennon group; and, however, two substituents from the group K7, КВ and КУ at the same time cannot mean ОН or ОСН", and at least one of the residues К7, К8 or КО must be selected from the group consisting of " СОМеаОКат1, -0,50,К23 , MK32СО30, MKZ2О5IAZO and MK32ОБКЗО; in c as well as their pharmaceutically acceptable salts and trifluoroacetates. . 2. Compounds of formula (I) according to claim 1, where: и? КИ, К2, КЗ and К4, independently of each other, mean Н, РЕ, СИ, Вг, И, СМ, МО», ОН, МН», СаНоази, cycloalkyl with 3, 4, 5 or 6 C-atoms, ОСНО :i, SOOK10; a and 6, independently of each other, mean 1, 2, C or 4, and one or more H-atoms can be -I replaced by E-atoms; K10 means H or CoNosyai; - c means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; o or KI, K2, KZ and K4, independently of each other, are 5- or b--heteroaryl selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl and He oxazolyl ; or КИ, К2, КЗ and К4, independently of each other, mean СОМК11К12 or МК11К12; K11 and K12, independently of each other, mean H, SeNoeni, StNot-1; e means 1, 2, C or 4; (F) gg means 3, 4, 5 or 6, and in the SeNzechi and StNaorg.-1 groups, one or more H-atoms can be replaced by E-atoms; or in K11 and K12, independently of each other, mean hydroxyethyl, M,M-dimethylaminoethyl, M,M-diethylaminoethyl, pyrrolidinoethyl, M-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or KT1 and K12, together with the nitrogen atom to which they are connected, form a pyrrolidine, piperidine, M-methylpiperazine, piperazine or morpholine cycle; 65 or K11 and K12, independently of each other, mean SOK14, SZK14, SOMNI14, SZMNK14 or 5ОЖ14; K14 means SoNadyai; 9 means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; or КИ, К2, КЗ and К4, independently of each other, mean О5ОЗН, ЗОЗН, 502К15, and К15 means SKНокя1, ОСИНа»нии or МК17К18; K means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms; Y means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms; K17 and K18, independently of each other, mean H, СТНот:и, in which the first is bound to the nitrogen atom 7/0. The ЕNeo group is replaced by СО and the second СНо group is replaced by MK19; t means 1, 2, 3, 4 or 5, and one or more H-atoms can be replaced by E-atoms in the group of C; K19 stands for H or SuNodchi; n means 1, 2, C or 4; moreover, in SaNor-4, one or more H-atoms can be replaced by E-atoms; or K17 and K18, together with the nitrogen atom to which they are connected, form a 5- or b--linked ring; moreover, however, always K2 should not mean H; K5 means H, SrNora; p means 1, 2, C or 4; and in SrNaorya one or more H-atoms can be replaced by P-atoms; Kb means H, SeNovyi, OSINo3nya or OSOK22; z and i, independently of each other, mean 1, 2, З or 4; moreover, in SeNovcha and OS, Nanya, one or more H-atoms can be replaced by P-atoms; sch K22 means Sun Nights; и means 1, 2, C or 4; (8) and in SuNoun, one or more H-atoms can be replaced by P-atoms; K?7, KV and KU, independently of each other, mean ОЗОЗН, 5ОЗН or 5ОзК23; k23 means SppNaoppya1» SttNott-1i» OSrrNorr-i or MK25KO; c зо пп and пр, independently of each other, mean 1, 2, 3, 4 or 5; tt means 3, 4, 5 or 6, and in SppNoppyai SttNott-i and OSrrNorr-i one or more H-atoms can be replaced by P-atoms; o K25 and K26, independently of each other, mean Н, СМ, С, Н2/»-1, and the first СНо group connected to the nitrogen atom is replaced by СО or С5 and the second СНо group is replaced by MK27; i- 7 means 1, 2, 3, 4, 5 or 6; and in C,H2,-41 one or more H-atoms can be replaced by P-atoms; K27 means H or SaaNodachi; aa means 1, 2, C or 4; and in SaaNodaz-1 ONE or several H-atoms can be replaced by E-atoms; " or in c K25 and K26, together with the nitrogen atom to which they are connected, form a 5- or b-membered ring, or K27 and one СНо group of the K25 or K26 radical together with the nitrogen atom to which they are connected form 5- or и? b-membered cycle; or K?7, KV and KU, independently of each other, mean MK32SOKZO, MK32S5KZO or MK32505K30; -And KZO means H, OH, SeoNosyaya, SuuNouu, pyrrolidinyl or piperidinyl, in the cycles of which one СНо group can be replaced by O or MK33; - KZ2 and K33, independently of each other, mean H or SuNorn4; o ss means 1, 2, 3, 4, 5, 6, 7 or 8; uu means 3, 4, 5, 6; pi n means 1, 2, C or 4; Moreover, in SiNonch one or more H-atoms can be replaced by P-atoms and in SosNossyai and SuNouul groups one or more H-atoms can be replaced by P-atoms, and one or more СНо-groups can be replaced by MKZ1, and one The СНо group can be replaced by 0; KZ1 means H, SKNokknyi, SOKb5 or 50565; KK means 1, 2, C or 4; F) and one or more H-atoms can be replaced by E-atoms; ka Кб5 means Н, СххНоххчи; xx means 1, 2, C or 4, and one or more H-atoms may be replaced by P-atoms; 60 or KZ1 together with one СНо group of the KZO radical and the nitrogen atom to which they are bound form a 5- or b--linked cycle; or KZO means a 5- or b-lene heteroaryl selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thienyl, thiazolyl, and oxazolyl, which are unsubstituted or substituted up to three times with substituents selected from from the group consisting of E, SI, Vg, I, SooNosozi, MAK7OK71; K?O and K71, independently of each other, mean H, SuuNotsu-i or SOK?72; K72 stands for H, SL/Nouchi; оо, ши and мм, independently of each other, mean 1, 2, З or 4; and in SooNooogi groups; One or more H-atoms can be replaced by E-atoms in CtshNHYotsii or SuU/Nouuii; or K7, KV and KU, independently of each other, mean H, RE, SI, Vg, I. MO", SM, ON, MN", SeeNoveni". Sumu Nodu-1 OsSeNoti, MK4OK41, СОМК4ОКА1, СООК42, СОКаЯ2 or OSOKA2; 70 ee and I, independently of each other, mean 1,2, Z or 4; mly means 3, 4, 5 or 6; moreover, in the groups SeeNovech1, SuluNoudu-1, and OSyaNovya, one or more H-atoms can be replaced by E-atoms; K40 and K41 mean H, SeNosya or C(IMN)IMN"; HER means 1, 2, Z, 4, 5, 6, 7 or 8; moreover, one or more H-atoms can be replaced by E-atoms in the SeNon-yai group; or K4O and K41, independently of each other, are selected from the group consisting of hydroxyethyl, M,M-dimethylaminoethyl, M,M-diethylaminoethyl, pyrrolidinoethyl, M-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or K40 and K41 together with the nitrogen atom to which they are connected form a ring selected from the group consisting of pyrrolidine, piperidine, M-methylpiperazine, piperazine and morpholine; K42 means H or SfNonniai; c pi means 1, 2, C or 4; moreover, one or more H-atoms can be replaced by E-atoms in the Sennon group; i) moreover, however, two substituents from the group K7, K8 and KU at the same time cannot mean OH or OSN" and at least one of the residues K7, K8 or KU must be selected from the group consisting of СОМК4ОКаЯ1, -О,50,К23 , MK32СО30, MKk32С5КЗО and MK325ОБКЗО; as well as their pharmaceutically acceptable salts and trifluoroacetates. c zo 3. Compounds of formula (I) according to claim 1 or 2, where: КИ, К2, КЗ и К4, independently of each other, mean Н, Е, СИ, Вг, ОН, МН», СаНоач-и, cycloalkyl with With, 4, 5, or 6 carbon atoms, OXNoya; o a and 5 in the groups СаНоани and ОСНоюія, independently of each other, mean 1, 2, З or 4, and one or more H-atoms can be replaced by P-atoms; in. or и- КИ, К2, КЗ and К4, independently of each other, mean МК11К12; K11 and K12, independently of each other, mean H, SeNoeni, StNot-1; e means 1, 2, C or 4; гг means 3, 4, 5 or 6, and in the SeNzechi and StNaorg.-1 groups, one or more H-atoms can be replaced by E-atoms; with or K11 and K12, together with the nitrogen atom to which they are connected, form a cycle, which is chosen from the group, which is? consists of pyrrolidine, piperidine, M-methylpiperazine, piperazine and morpholine; or K11 and K12, independently of each other, mean SOK14, SZK14, SOMNI14, SZMNK14 or 5ОЖ14; -And K14 means SoNadyai; 9 means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; - or about КИ, К2, КЗ and К4, independently of each other, mean О5ОЗН, ЗОЗН, 50215; K15 means SKNok-i or MK17K18; pi K means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms; Ge K17 and K18, independently of each other, mean H or StpNotchi1; t means 1, 2, 3, 4 or 5, and one or more H-atoms can be replaced by E-atoms in the group of C; 5B or K17 and K18, together with the nitrogen atom to which they are connected, form a 5- or b--ene cycle; (F) moreover, however, always K2 should not mean H; ka K5 means methyl or trifluoromethyl; Kb means H; in K?7, KV and KU, independently of each other, mean OZOZN, 5OZN or GOD; K23Z means SppNopp-i 8bo MK25K26; пп means 1, 2, Z, 4 or 5; moreover, in SdpNoppya1 ONE or several H-atoms can be replaced by E-atoms; K25 and K26, independently of each other, mean Н, СМ or С,Н2,-41, IN WHICH the first 65 СНо group connected to the nitrogen atom is replaced by СО or С5 and the second СНо group is replaced by MK27; 7 means 1, 2, 3, 4, 5 or 6; and in C,H2,-41 one or more H-atoms can be replaced by P-atoms; K27 means H or SaaNodachi; aa means 1, 2, C or 4; and in SaaNodaz-1 ONE or several H-atoms can be replaced by E-atoms; or K25 and K26 together with the nitrogen atom to which they are bonded form a 5- or b-membered ring, or K27 and one СНо group of the radical K25 or K26 together with the nitrogen atom to which they are bonded, form a 5- or b-linked cycle; 70 or K?7, KV and KU, independently of each other, mean MK32SOKZO, MK32S5KZO or MK32505K30; KZO means H, OH, SeoNosya, SuuNouu, pyrrolidinyl or piperidinyl, in the rings of which one СНо group can be replaced by O or MK33; KZ2 and K33 mean H, methyl or CE"; ss means 1, 2, 3, 4, 5, 6, 7 or 8; uu means 3, 4, 5, 6; moreover, in the SeooNossyai and SuuN»ouu1i groups, one or more H-atoms can be replaced by P-atoms and one or more СНо-groups can be replaced by MKZ1, and one СНо-group can be replaced by 0; KZ1 means H, methyl, ethyl, СЕ5, СНоСЕ»3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl; or KZ1, together with one СНо group of the KZO radical and the nitrogen atom to which they are bound, form a 5- or b--linked cycle; or KZO means pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl, which are unsubstituted or substituted with up to three substituents selected from the group consisting of EC, Si, methyl, ethyl, trifluoromethyl, MH", MH-acetyl; i) or K7, K8 and KU, independently of each other, mean H, E, SI, OH, MN", SeeNovech1". Sumu Knowlu1;. OSyaNonaya, MAK4OKa1, SOMKAOKAT, SOOKa2 or OSOKA42; с зо ее and Я, independently of each other, mean 1, 2, З or 4; mly means 3, 4, 5 or 6; "and in SeeNove-1 groups; SumNoazh-y OceNoty one or more H-atoms can be replaced by E-atoms; K40 and K41 mean H, SeNon, or C(IMN)MN"; - Her means 1, 2, Z or 4; and in the SeNon group, one or more H atoms can be replaced by E atoms; or K4O and K41, independently of each other, mean hydroxyethyl, M,M-dimethylaminoethyl, M,M-diethylaminoethyl, pyrrolidinoethyl, M-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; « or in c К4О and К41 together with the nitrogen atom to which they are connected form a pyrrolidine, piperidine, М-methylpiperazine, piperazine or morpholine cycle; and 42 means H or SenNonnchy; pi means 1, 2, C or 4; moreover, one or more H-atoms can be replaced by E-atoms in the Sennon group; - And at the same time, two substituents from the group K7, K8 and KU at the same time cannot mean ОН or ОсСН" with at least one of the residues 7, К8 or KU must be selected from the group consisting of СОМК4ОКА1, -О,5ODK2З, ш- MK32СО30, Mk32С5K30 and MK325О0лКZO; as well as their pharmaceutically acceptable salts and trifluoroacetates. 4. Compounds of formula (I) according to claims 1-3, where: π КИ, К2, КЗ and К4, independently of each other, mean Н, Е, СИ, Вг, ОН, МН», СаНза-и, cycloalkyl with З , 4, 5 with or 6 C-atoms, OXNoya; a and 6 in the groups СаНоа-і and ОСНой-і independently of each other mean 1, 2, З or 4, and one or more H-atoms can be replaced by P-atoms; 5B or КИ, К2, КЗ and К4, independently of each other, mean МК11К12; F) K11 and K12, independently of each other, mean H, SeNoechni; StNog-1; ka e means 1, 2, C or 4; гг means 3, 4, 5 or 6, and in the SeNzechi and StNaorg.-1 groups one or more H-atoms can be replaced by E-atoms; or K11 and K12 together with the nitrogen atom to which they are connected form a ring selected from the group consisting of pyrrolidine, piperidine, M-methylpiperazine, piperazine and morpholine; or 65 K11 and K12, independently of each other, mean SOK14, SZK14, SOMNI14, SZMNK14 or 5ОЖ14; K14 means SoNadyai; 9 means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; or КИ, К2, КЗ and К4, independently of each other, mean О5ОЗН, ЗОЗН, 50215; K15 means SKNok-i or MK17K18; K means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms; K17 and K18, independently of each other, mean H or StpNotchi1; t means 1, 2, 3, 4 or 5, and one or more H-atoms can be replaced by E-atoms in the group of C; 70 or K17 and K18 together with the nitrogen atom to which they are connected form a 5- or b--linked ring; at the same time, however, always K2 should not mean H; K5 means methyl or trifluoromethyl; Kb means H; K?7, KV and KU, independently of each other, mean OZOZN, 5OZN or GOD; K23Z means SppNopp-i 8bo MK25K26; пп means 1, 2, Z, 4 or 5; moreover, in SdpNoppya1 ONE or several H-atoms can be replaced by P-atoms; K25 and K26, independently of each other, mean Н, СМ or С,Н2,-41, IN WHICH the first СНео group connected to the nitrogen atom is replaced by СО or С5 and the second СНо group is replaced by MK27; 7 means 1, 2, 3, 4, 5 or 6; and in C,H2,-41 one or more H-atoms can be replaced by P-atoms; K27 means H or SaaNodachi; aa means 1, 2, C or 4; c and in SaaNodaz-1 ONE or several H-atoms can be replaced by E-atoms; or about K25 and K26 together with the nitrogen atom to which they are bound form a 5- or b-membered ring, or K27 and one СНо group of the radical K25 or K26 together with the nitrogen atom to which they are bound , form a 5- or b-linked cycle; c zo or K7, KV and KU, independently of each other, mean MK32СОКЗ0, MK32С5Н430 or MK32505К30; " KZO means H, OH, SeONosya, SuNouU, pyrrolidinyl or piperidinyl, in the rings of which one СНо-group can be replaced by O or MK33; KZ2 and KZZ mean H, methyl or CE"; in. ss means 1, 2, 3, 4, 5, 6, 7 or 8; cha uu means 3, 4, 5 or 6; moreover, in the SeooNossyai and SuuN»ouu1i groups, one or more H-atoms can be replaced by P-atoms and one or more СНо-groups can be replaced by MKZ1, and one СНо-group can be replaced by 0; KZ1 means H, methyl, ethyl, СЕ5, СНоСЕ»3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl; « or in c KZ1, together with one СНо-group of the KZO radical and the nitrogen atom with which they are bound, form a 5- or Й b--ene cycle; and" or KZO means pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl, which are unsubstituted or substituted with up to three substituents selected from the group consisting of EC, C, -I methyl, ethyl, trifluoromethyl, MH", MH-acetyl; or sh- K7, K8 and KU, independently of each other, mean H, E, SI, OH, MH", SeeNovech1". Sumu Noulu1;. OSyaNonaya, o Me4OoKA1, SOMK4OKA1, SOOKAYA2 or OSOKA42 ; ee and Y, independently of each other, mean 1, 2, C or 4; pi mly means 3, 4, 5 or 6; Ge, and in the groups SeeNovech1, SuluNoudu-1 and OSyaNovia one or more H-atoms can be replaced E-atoms; K40 and K41 mean H, SeNon.y or C(IMH)MH"; 5B Her means 1, 2, З or 4; and in the group SeNon-ya one or more H-atoms can be replaced by E-atoms ; F) or ka K4O and K41, independently of each other, mean hydroxyethyl, M,M-dimethylaminoethyl, M,M-diethylaminoethyl, pyrrolidinoethyl, M-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; 60 or K4O and K41 together with the nitrogen atom to which they are connected form a pyrrolidine, piperidine, M-methylpiperazine, piperazine or morpholine cycle; K42 means H or SfNonniai; pi means 1, 2, C or 4; 65 and one or more H-atoms can be replaced by E-atoms in the Sennon group; at the same time, however, two substituents from the group K7, K8 and KU at the same time cannot mean OH or OSNU3 and at least one of the residues K7, K8 or KU must be selected from the group consisting of -0.50, К23, МК32СО30, Мк32С5К30 and MK325О0бКЗО; as well as their pharmaceutically acceptable salts and trifluoroacetates. 5. The compound of formula (I) according to claim 1, selected from the group consisting of 1). Mch-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|acetamide; 2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; 3). 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; 4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M,M-dimethylbenzenesulfonamide; 70 5). 4-(4-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline; 6) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid; 7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-ethylbenzamide; 8). 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-propylbenzamide; 9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-(2-dimethylaminoethyl)benzamide; 10) 6,8-dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline; 113. I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|diethylamine; 12). 6,β-dichloro-2-methyl-4-(4-piperidin-1-ylphenyl)-1,2,3,4-tetrahydroisoquinoline; 13). 6,8-dichloro-2-methyl-4-(4-pyrrolidin-1-ylphenyl)-1,2,3,4-tetrahydroisoquinoline; 14). 6,8-dichloro-2-methyl-4-(4-(4-methylpiperazin-1-yl)phenyl|-1,2,3,4-tetrahydroisoquinoline; 15) 6,8-dichloro-2-cyclopropyl-4 -phenyl-1,2,3,4-tetrahydroisoquinoline; 16). 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine; 17). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-propylurea; 18). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylthiourea; 19). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-ethylurea; high school 20). M-(4-(6-methanesulfonyl-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|acetamide); 21). Mch-I4-(2,6,8-trimethyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|acetamide; i) 2235. h-I4-(6-bromo-8-chloro-2-methyl- 1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|acetamide; 23) M-I4-(8-chloro-2-methyl-b-pyrrolidin-1-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)acetamide; 24). M-I4-(8-chloro-2-methyl-6-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|acetamide; from 25). M-14-(3-chloro-2-methyl-6-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydroisoquinolin-4-yl|phenyl)acetamide; 26) 4-14-(8-chloro-6-(cyclopropylmethylamino)-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ylphenyl)acetamide; - 27) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid; o 28) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxy-M-methylbenzamide; 29) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-ethyl-2-hydroxybenzamide; in. 30) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-(2-dimethylaminoethyl)-2-hydroxybenzamide; uh- 31). Mch-I5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoylguanidine; 32). M-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide; 33) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine; 34) 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine; " 35). M-I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|propionamide; from p. 36). M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; . 37) I4-(6,8-dichloro-2-methyl- 1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|pentanoic acid amide; and?" 38). -I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl) isobutyramide; 39). -(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2,2-dimethylpropionamide; 40) I4-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl|cyclopropanecarboxylic acid amide; -I 41) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of cyclobutanecarboxylic acid; 42) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of cyclopentanecarboxylic acid; Sh- 43). M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-2,2,2-trifluoroacetamide; o 44) I4-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1-acetylpiperidine-4-carboxylic acid; in 45). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|nicotinamide; Ge 46) M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Imethanesulfonamide; 47) I4-(6,8-dichloro-2- ethanesulfonic acid methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 48) M', M' -dimethylamino--I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|sulfamide; 49). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 50). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; F) 51) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pentanoic acid; ka 52). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylisobutyramide; 53). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2,2-dimethylpropionamide; in 54) cyclopropanecarboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 55) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Iamide of cyclobutanecarboxylic acid; 56) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of cyclopentanecarboxylic acid; 57). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)|-2,2,2-trifluoroacetamide; 58) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1-acetylpiperidine-4-carboxylic acid; 59). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|nicotinamide; 60) Ch-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; 61). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl/uphenyl)iamide of ethanesulfonic acid; 62). M',M'-dimethylamino-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|sulfamide; 63). M-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|propionamide; 64). M-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; 65) (2-(6,8-dichloro-2-methyl- 1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|pentanoic acid amide; 66) M-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4- il)uphenylisobutyramide; 67). Mch-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2,2-dimethylpropionamide; 70 68) (2-(6,8- Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of cyclopropanecarboxylic acid; 69) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline- 4-yl)uphenyl|Iamide of cyclobutanecarboxylic acid; 79) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide of cyclopentanecarboxylic acid; 71). 6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide 1-acetylpiperidine-4-carboxylic acid /5 ACID; 73). Mch-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; 74) (2-(6,8-dichloro-2-methyl- 1,2,3,4-tetrahydroisoquinolin-4-yl/uphenyl|iamide of ethanesulfonic acid; 75) M',M'-dimethylamino-m-(2-(6,8-dichloro-2-methyl-1,2,3 ,4-tetrahydroisoquinoline-4-iluphenyl|sulfamide; 76). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-3-ethylurea; 77). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-methylthiourea; 78). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-3-ethylurea; 79). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-methylthiourea; 80) M-15-(4-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfamoyl|-4-methylthiazol-2-yl)acetamide; ch 81) that M-15-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylsulfamoyl|-4-methylthiazol-2-yl)iacetamide; i) 82) 1,2-dimethyl-1H-imidazole-4-sulfonic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl iamide; 83). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide with 1,2-dimethyl-1H-imidazole-4-sulfonic acid; 84) |4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide - 5-chloro-1,3-dimethyl-1H-pyrazole-4- sulfonic acids; o 85)(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide 5-chloro-1,3-dimethyl-1H-pyrazole-4- sulfonic acids; 86). 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl 5-bromothiophene-2-sulfonic acid; uh- 87). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl 5-bromothiophene-2-sulfonic acid; 88) Ch-I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-C,C,C-trifluoromethanesulfonamide; 89)Ch-IZ- (6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-C,C,C-trifluoromethanesulfonamide; 90) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide 2,2,2-trifluoroethanesulfonic acid; " 91). I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide 2,2,2-trifluoroethanesulfonic acid; from p. 92). M-ethyl-M'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonylurea; . 93) 2-chloro-5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; and?" 94) 2-methyl-4-phenyl-b,8-bistrifluoromethyl-1,2,3,4-tetrahydroisoquinoline; 95). 2-amino-M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|acetamide; 96) M-I(4-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-methylaminoacetamide; -I 97). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-dimethylaminoacetamide; 98) 2-amino-M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|propionamide; Sh- 99) 2-amino-M-I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; about 100) I4-(6 2,6-diaminohexanoic acid ,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide; 101) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-2-carboxylic acid; ve 1023. chCh-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylisonicotinamide; Ge 103) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 1H-pyrrole-3-carboxylic acid; 104) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 1H-pyrrole-2-carboxylic acid; 105) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1-methylpiperidine-4-carboxylic 5B ACID; 106) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide (F) 1,4-dimethyl-1H-pyrrole-2-carboxylic acid; ka 107) 4-nitro-1H-pyrrole-2-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl iamide; at 108). 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 2,5-dimethyl-1H-pyrrole-3-carboxylic acid; 109) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl Iiamide of 1H-imidazole-4-carboxylic acid; 110). I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1-methanesulfonylpiperidine-4-carboxylic acid; 65 111). 114-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 3,5-dimethyl-1H-pyrazole-4-carboxylic acid; 112) 1H-pyrazole-4-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylilamide; 113). 3-trifluoromethyl-1H-pyrazole-4-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 114). 115). h-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-dimethylaminoacetamide; 116) 2-amino-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|propionamide; 117). 2-amino-M-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; 118) I3-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide of 2,6-diaminohexanoic acid; 70 119) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-2-carboxylic acid; 120). hCh-IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylisonicotinamide; 121) 1H-pyrrole-3-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylilamide; 122) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1H-pyrrole-2-carboxylic acid; 123) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1-methylpiperidine-4-carboxylic acid; 124) 1,4-dimethyl-1H-pyrrole-2-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 125) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide of 4-nitro-1H-pyrrole-2-carboxylic acid; 126) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 2,5-dimethyl-1H-pyrrole-3-carboxylic acid; 127) 1H-imidazole-4-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl Iiamide; 128). 1-methanesulfonylpiperidine-4-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; ch 129) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 3,5-dimethyl-1H-pyrazole-4-carboxylic acid; (8) 130) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl amide of 1H-pyrazole-4-carboxylic acid; 131). 3-trifluoromethyl-1H-pyrazole-4-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; page 132). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylthiourea; 133). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylthiourea; - 134). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylthiourea; o 135) 3-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; 136) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 4-methylpiperazine-1-carboxylic acid; part 137) piperidine-1-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl iamide; 138) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; 139) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-1-carboxylic acid; 140). 3-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-1,1-diethylurea; « 141). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; with c 142)1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3--2-dimethylaminoethyl)urea; . 143). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-(tetrahydrofuran-3-yl)urea; and?" 144). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-(tetrahydropyran-4-yl)urea; - And 146) -1 3-IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1-(3-dimethylaminopropyl)-1-methylurea; 147) o 3-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1-2-dimethylaminoethyl)-1-methylurea; 148). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--3-dimethylaminopropyl)urea; in 149). 1-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-(2-methoxyethyl)urea; Ge 150). 1-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-pyridin-3-ylurea; 151). 1-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-pyridin-4-ylurea; 152) (2-(6, 8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 4-methylpiperazine-1-carboxylic acid 5B ACID; 153). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; F) 154). 3-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; ka 155) 3-(2-(6, 8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)|-1,1-diethylurea; 156) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of piperidine-1-carboxylic acid; in 157) (2-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; 158) (2-(6,8-dichloro-2-methyl-1,2,3 ,4-tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-1-carboxylic acid; 159). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3--2-dimethylaminoethyl)urea; 160) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 4-methylpiperazine-1-carboxylic acid; 65 161) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-1-carboxylic acid; 162). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; 163). 3-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; 164). 3-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,1-diethylurea; 165). 1-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3--2-dimethylaminoethyl)urea; 166) Piperidine-1-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl iamide; 167) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; 168). M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/phenyl|formamide; 169) |4-(6,8-dichloro-2-methyl -1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)methylamine; 170). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,3-dimethylurea; 70 171). I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of 4-methylpiperazine-1-carboxylic acid; 172). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1,3,3-trimethylurea; 173) I4-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of piperidine-1-carboxylic acid; 174) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of morpholine-4-carboxylic acid; 175) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of pyrrolidine-1-carboxylic acid; 176) 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)-1-methylurea; 177). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl/|-3,3-diethyl-1-methylurea; 178). M-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/phenyl|formamide; 179) 13-(6,8-dichloro-2-methyl- 1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)methylamine; 180) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of pyrrolidine-1-carboxylic acid; 181) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of piperidine-1-carboxylic acid; 182) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,3,3-trimethylurea; 183) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,3-dimethylurea; c zo 184) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of morpholine-4-carboxylic acid; - 185). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide o 4-methylpiperazine-1-carboxylic acid; 186) 1-1-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)-1-methylurea; i- 187). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl/|-3,3-diethyl-1-methylurea; 188) 2-dimethylaminoethyl ether IZ-( 6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 189) 2-dimethylaminoethyl ether of 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; from p. 190) of 2-dimethylaminoethyl ether. (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; and?" 191) methyl ester of 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenylcarbamic acid; 192) ethyl ester of 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|carbamic acid; 193) isopropyl ether of 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)carbamic acid -I; 194) 2,2-dimethylpropyl ester of 3-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; o 195) 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenylcarbamic acid methyl ester; 196) isopropyl ether of 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)carbamic acid; Ge 197) 2,2-dimethylpropyl ether of 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 198) ethyl ether |4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|carbamic acid; 199). (K)-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; 200) (5)-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl| methanesulfonamide; F) 201). (K)-1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylurea; ka 202). (5)-1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-3-ethylurea; 203). M-IZ-(6,8 -difluoro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)| acetamide; at 204). 4-(3-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline; 205). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)|-3-(2-hydroxyethyl)urea; 206) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid ethyl ether; 207) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid; 65 as well as their pharmaceutically acceptable salts. 6. The compound of formula (I) according to claim 1, selected from the group consisting of 1). M-I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-ylphenyl|acetamide; 2) 4-(6,8-dichloro-2-methyl-1, 2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; 3). 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; 4). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-3-methylthiourea; 5). 1-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylurea; 6). Ch-I4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide; 7). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|acetamide; 8). M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 70 9) |4-(6,8-dichloro-2-methyl -1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1-acetylpiperidine-4-carboxylic acid; 10).M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl|Imethanesulfonamide; 11) 14-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide ethanesulfonic acid; 12). M,M'-dimethylamino-1H-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|sulfamide; 13). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 14). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; 15). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylisobutyramide; 16) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide cyclopropanecarboxylic acid; 17) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of cyclobutanecarboxylic acid; 18). M-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-2,2,2-trifluoroacetamide; 19) IZ-(6,8- 1-acetylpiperidine-4-carboxylic acid dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide; 20). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|nicotinamide; 21). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|imethanesulfonamide; ch 22) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of ethanesulfonic acid; 23) M,M'-dimethylamino-M-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/phenyl|sulfamide; i) 24) (2 -(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl|cyclopropanecarboxylic acid amide; 25) (2-(6,8-dichloro-2-methyl-1 ,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1-acetylpiperidine-4-carboxylic acid; page 26). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylurea; 27). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-3-methylthiourea; - 28). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylurea; o 29). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-methylthiourea; v. 30) - M-15-(3-( 6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenylsulfamoyl)|-4-methylthiazol-2-ilyacetamide; 31). 1,2-Dimethyl-1H-imidazole-4-sulfonic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide; 32). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-C,C,C-trifluoromethanesulfonamide; " 33). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-C,C,C-trifluoromethanesulfonamide; from p. 34). M-ethyl-M'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl) benzenesulfonylurea; . 35). M-I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-dimethylaminoacetamide; i? 36) I4-(6,8-dichloro -2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 2,6-diaminohexanoic acid; 37) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1H-pyrrole-3-carboxylic acid; 38) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1-methylpiperidine-4-carboxylic acid; 39) 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl]amide of 1-methanesulfonylpiperidine-4-carboxylic acid; o 40) 1H-pyrazole-4-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylilamide; 41). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-2-methylaminoacetamide; and 42) h-13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-dimethylaminoacetamide; Ge 43) 2-amino-M-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|propionamide; 44). 2-amino-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; 45) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl amide of 2,6-diaminohexanoic acid; 46) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide of 1-methylpiperidine-4-carboxylic acid; F) 47) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 1H-imidazole-4-carboxylic acid; ka 48). 1-methanesulfonylpiperidine-4-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; in 49) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 3,5-dimethyl-1H-pyrazole-4-carboxylic acid; 50) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Iamide of 1H-pyrazole-4-carboxylic acid; 51). 3-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; 52) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 4-methylpiperazine-1-carboxylic acid; 53) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of piperidine-1-carboxylic acid; 54) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; 55) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-1-carboxylic acid; 56) 3-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-1,1-diethylurea; 57). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; 58) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)urea; 59) 1-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-3-(tetrahydrofuran-3-yl)urea; 60) /1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-(tetrahydropyran-4-yl)urea; 61) 70 3-IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1-methyl-1-(1-methylpiperidin-4-yl)urea; 62) 3-IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1-(3-dimethylaminopropyl)-1-methylcarbamide; 63) 3-I3- (6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1-2-dimethylaminoethyl)-1-methylurea; 64) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-"3-dimethylaminopropyl)urea; 65). 1-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-(2-methoxyethyl)urea; 66) 1-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-3-pyridin-3-ylurea; 67) 1-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-iluphenyl)|-3-pyridin-4-ylurea; 68) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 4-methylpiperazine-1-carboxylic 2o ACID; 69). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; 70). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3--2-dimethylaminoethyl)urea; 71) 4-methylpiperazine-1-carboxylic acid 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide; with 723. 1-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; 73). 3-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; and) 74). 3-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-1,1-diethylurea; 75) 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3--2-dimethylaminoethyl)urea; 76) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; from 77). M-i(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|formamide; 78). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|formamide; - 79). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,3,3-trimethylurea; at 80). 1-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,3-dimethylurea; 81) 3-(6,8-dichloro -2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)| methylamide of morpholine-4-carboxylic acids; part 82) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)| 4-methylpiperazine-1-carboxylic acid methylamide; 83) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)-1-methylurea; « 84) 2-dimethylaminoethyl ether of 3-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; . 85) 2-dimethylaminoethyl ether and? I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 86) 2-dimethylaminoethyl ether (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; -I 87) methyl ether (3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenylcarbamic acid; 88) (K or 5)-M-I( 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; Sh-89) (K or 5)-1-(2-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)|-3-ethylurea; at 90). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl/|-3-(2-hydroxyethyl)urea; and also from their pharmaceutically acceptable salts. ve 7 The use of the compound of formula (I), as well as its pharmaceutically acceptable salts, for the preparation of a medicinal product for the treatment of diseases that can be influenced by inhibition of sodium-proton exchange of the IP subtype (MNEZ), where: КИ, К2, КЗ and К4, independently one from one, mean H, PE, SI, Vg, I, CM, MO", OH, MH", SaNzachi, SadNada-i OShNorvn, SOOK10, OSOMK10, SOK10 or O,-(CHa)u-phenyl; and and 5 in the groups CaNoani and OxNoyia, independently of each other, are 1, 2, C, 4, 5, 6, 7 or 8, and (F) one or more H atoms may be replaced by P atoms; each represents 3, 4, 5, 6, 7 or 8, and one or more H-atoms may be replaced by P-atoms; K10 means H or CoNosyai; voc means 1, 2, C, 4, 5, 6, 7 or 8, and one or more H atoms may be replaced by H atoms; x means zero or 1; y means zero, 1, 2, C or 4; and ф the enyl ring in the O,-(CH")/-phenyl group is unsubstituted or substituted by 1-3 substituents selected from the group consisting of E, SI, Bg, CM, MO,, OH, MH" or CaHzdchi; 65 and means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; or КИ, К2, КЗ and К4, independently of each other, mean heteroaryl, and the ring may contain 0, 1, 2, З or 4 nitrogen atoms, 0 or 1 oxygen atom or 0 or 1 sulfur atom; or КИ, К2, КЗ and К4, independently of each other, mean СОМК11К12 or МК11К12; K11 and K12, independently of each other, mean H, SeNoeni, StNot-1; e means 1,2, 3,4, 5,6, 7 or 8; гг means 3, 4, 5, 6, 7 or 8, while in the SeNoechi and StNot-1 groups, one or more H-atoms can be replaced by P-atoms, and one or more CHo-groups can be replaced by O or MK13; КИЗ means H or XiaNov4; It means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms; or КИЗ and one СНо group of the К11 or К12 radical, together with the nitrogen atom to which they are connected, form a 5- or b--linked cycle; or K11 and K12, together with the nitrogen atom to which they are connected, form a 5-, 6- or 7-ene ring; or K11 and K12, independently of each other, mean SOK14, C5K14 or 50214; K14 means SoNadyai; d means 1, 2, 3, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by E-atoms and one or more СНо-groups can be replaced by O or MK13; or КИ, К2, КЗ and К4, independently of each other, mean -0,-5О)-К15, and сч и means zero or 1; means zero, 1 or 2; (8) K15 means SKNok-y, OH, OSINa»yaya or MK17K18; K means 1, 2, 3, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by E-atoms; Y means 1, 2, C, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by E-atoms; c zo K17 and K18, independently of each other, mean H or StpNotchi1; t means 1, 2, З, 4, 5, 6, 7 or 8, and in the StNotini group one or more H-atoms can be replaced by E-atoms and one or more СНо-groups can be replaced by О, СО, C5 or MK19; o K19 means H or SuNodchi; n means 1, 2, C or 4; in. moreover, in SaNor-4, one or more H-atoms can be replaced by E-atoms; i- or K17 and K18, together with the nitrogen atom to which they are connected, form a 5-, 6- or 7-ene ring; or K19 and the СНо group of the K17 or K18 radical, together with the nitrogen atom to which they are connected, form a 5- or « b--lens cycle; in c K5 means H, SeNorni, SevNovv, SOK2O or BOZH2O; And p means 1,2, 3,4,5, 6, 7 or 8; and? vz means Z, 4, 5, 6, 7 or 8; and in SrNorai and Se5Novv-1 one or several H-atoms can be replaced by P-atoms; k20 means SaNzdyai; -I d means 1,2, 3,4,5,6, 7 or 8, and in the C3Nod group one or more H-atoms can be replaced by P-atoms and one or more Sh-СНо-groups can be replaced on O or MK21; o K21 means H or SNachi; r means 1, 2, C or 4; and in SINAg-i, one or more H-atoms can be replaced by P-atoms; Kz Kb means H, E, SI, Vg, Y, SeNovachya, SaaNgda-1, OH, AUTUMN or osSoOng2; z ii, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8; ad means 3, 4, 5, 6, 7 or 8, and in SeNovch1; In SaaNoda-1 and OSINo3-ya, one or more H-atoms can be replaced by E-atoms; K22 means Sun Nights; (F) and means 1, 2, C or 4; and in C, |Na)c-4 one or more H-atoms can be replaced by E-atoms; К7, КВ and КУ, independently of each other, mean -О,-50,,-К23; 60 m means zero or 1; m means zero, 1 or 2; k23Z means SppNaoppya1» SttNott-i» OH, OSrrNorr-i or MK25K26; пп and пр, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8; tt means 3, 4, 5, 6, 7 or 8, 65 and in SppNoppya» SttNaott-i and OSrrNorr-i one or more H-atoms can be replaced by P-atoms; K25 and K26, independently of each other, mean H, CM or С,Нао»н1, С,»Но»»1; 7 means 1, 2, 3, 4, 5, 6, 7 or 8; 77 means 3, 4, 5, 6, 7 or 8, and one or more H-atoms can be replaced by P-atoms and in С,Но; 1 one or more H-atoms can be replaced by P-atoms, and one or more СНо-groups can be replaced by О, СО, С5 or МК27; K27 means H or SaaNodachi; aa means 1, 2, C or 4; and in SaaNodaz-1 ONE or several H-atoms can be replaced by E-atoms; or 70 K25 and K26 together with the nitrogen atom to which they are connected form a 5-, 6- or 7-membered ring, or K27 and one СНо group of the radical K25 or K26 together with the nitrogen atom to which they are connected are linked, form a 5- or b--linked cycle; or K7, KV and KU, independently of each other, mean MK32СОКЗ0, MK32С5Н430 or MK32500530; KZO means H, SooNossiai» SuNouu.1, pyrrolidinyl or piperidinyl, in the rings of which one CH o-group can be replaced by O or MK33; KZ2 and K33, independently of each other, mean H or SuNorn4; рр means 2 or 3; ss means 1, 2, 3, 4, 5, 6, 7 or 8; uu means 3, 4, 5, 6, 7 or 8; and means 1, 2, 3, 4, 5, 6, 7 or 8; and in SiNonch one or more H-atoms can be replaced by P-atoms and in SosNossyai and SuNouul groups one or more H-atoms can be replaced by P-atoms, and one or more СНо-groups can be replaced by MKZ1, and one СНо -group can be replaced by 0; сч КЗ1 means Н, СКНоккний, СОКб5 or 50565; KK means 1, 2, C or 4; (8) and one or more H-atoms can be replaced by E-atoms; Кб5 means Н, СххНоххчи; xx means 1, 2, C or 4, and one or more H-atoms may be replaced by P-atoms; c zo or KZ1 together with one СНо group of the KZO radical forms a 5-, 6- or 7-ene ring; - or o KZO means a 5- or b--lene heteroaryl with 1, 2, 3 or 4 nitrogen atoms, 0 or 1 sulfur atoms and 0 or 1 oxygen atoms, which is unsubstituted or substituted up to three times by substituents selected from the group, which - Zv consists of E, SI, Vi, I, SooNosoni; MA7OK 1; и- КО и К71, independently of each other, mean H, SuuNotsuichya and SOK72; K72 stands for H, SL/Nouchi; oo, Shi and mu, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8; moreover, one or more H-atoms can be replaced by P-atoms in the groups СооНооози» СциНоцини or С.,/Ноууни; " or in c K7, KV and KU, independently of each other, mean H, RE, SI, Vg, I. MO", SM, ОН, МН", SeeNoveni". Sumu Nodu-1 and OsSeNoti, MK4OK41, СОМК4ОКА1, СООК42, СОКаЯ2 or OSOKA2; and? ee and I, independently of each other, mean 1, 2, 3, 4, 5, 6, 7 or 8; mly means 3, 4, 5, 6, 7 or 8; moreover, in the groups SeeNovech1, SuluNoudu-1, and OSyaNovya, one or more H-atoms can be replaced by -I E-atoms; K40 and K41 mean H, SeNon, or C(IMN)MN"; - HER means 1, 2, Z, 4, 5, 6, 7 or 8; and in the SeNon-yai group, one or more H-atoms can be replaced by P-atoms and one or more SNeg-corpses can be replaced by O or MKa44; pi K44 means H or C.5Noduni; From 9a means 1, 2, 3, 4, 5, 6, 7 or 8; moreover, in the SouNoddia group, one or more H-atoms can be replaced by P-atoms, and K44, together with the СНо-group of the K40 or K41 radical and the nitrogen atom to which they are bound, can form a 5- or 5B β-ene cycle ; or Ф) К4О and К41 together with the nitrogen atom to which they are connected form a 5- or b--linked cycle; ka K42 means H or SfNonniai; n means 1, 2, 3, 4, 5, 6, 7 or 8; moreover, one or more H-atoms can be replaced by E-atoms in the Sennon group. 8. Application according to claim 7, which differs in that compounds of the formula (I) are used, where КИ, К2, КЗ and К4, independently of each other, mean Н, РЕ, СИ, Вг, И, СМ, МО», ОН , MH», CaNodni cycloAlkyl with 3, 4, 5 or 6 C-atoms, ОСНоюии, СООК10; a and 6, independently of each other, mean 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; K10 means H or CoNosyai; c means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; or KI, К2, КЗ and К4, independently of each other, mean 5- or b--lene heteroaryl selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl and oxazolyl; or КИ, К2, КЗ and К4, independently of each other, mean СОМК11К12 or МК11К12; K11 and K12, independently of each other, mean H, SeNoeni, StNot-1; 70 e means 1, 2, C or 4; гг means 3, 4, 5 or 6, and in the SeNzechi and StNaorg.-1 groups one or more H-atoms can be replaced by E-atoms; or C11 and C12, independently of each other, mean hydroxyethyl, M,M-dimethylaminoethyl, M,M-diethylaminoethyl, pyrrolidinoethyl, M-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or KT1 and K12, together with the nitrogen atom to which they are connected, form a pyrrolidine, piperidine, M-methylpiperazine, piperazine or morpholine cycle; or K11 and K12, independently of each other, mean SOK14, SZK14, SOMNI14, SZMNK14 or 5ОЖ14; K14 means SoNadyai; 9 means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; or КИ, К2, КЗ and К4, independently of each other, mean О5ОЗН, ЗОЗН, 502К15, and сч К15 means SKНокя1, ОСИНа»нии or МК17К18; K means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms; (8) Y means 1, 2, C or 4, and one or more H-atoms may be replaced by P-atoms; КИ17 and К18, independently of each other, mean Н, СУНот:.і In which the first СН»о group connected to the nitrogen atom is replaced by CO and the second СНо group is replaced by MK19; s zo t means 1, 2, 3, 4 or 5, and in the group of SyuNotii one or more H-atoms can be replaced by E-atoms; "K19 stands for H or SuNodchi; o n means 1, 2, C or 4; moreover, in SaNor-4, one or more H-atoms can be replaced by E-atoms; in. or M. K17 and K18, together with the nitrogen atom to which they are connected, form a 5- or b--linked ring; KB stands for H, SeNaorai» SezNovv-1; p means 1, 2, C or 4; c5 means 3, 4, 5 or 6, and in SeNoray and SeNovv-1 one or more H-atoms can be replaced by P-atoms; with c Kb means H, SeNovyi, OSINo3nya or OSOK22; . z and i, independently of each other, mean 1, 2, З or 4; and in SeNovcha and OS, Nanya, one or more H-atoms can be replaced by P-atoms; K22 stands for SuNozzi1; и means 1, 2, C or 4; - And in C, |Na)c-4, one or more H-atoms can be replaced by E-atoms; K?7, KV and KU, independently of each other, mean OZOZN, 5OZN or GOD; sh- k23 means SppNaoppya1» SttNott-1i» OSrrNorr-i or MK25KO; o пп and пр, independently of each other, mean 1, 2, 3, 4 or 5; tt means 3, 4, 5 or 6, and in SppNoppya» SttNaott-i and OSrrNorr-i one or more H-atoms can be replaced by P-atoms; He K25 and K26, independently of each other, mean Н, СМ or С,Н2,-1, and the first СНо group connected to the nitrogen atom is replaced by СО or С5 and the second СНо group is replaced by MK27; 7 means 1, 2, 3, 4, 5 or 6; and in C,H2,-41 one or more H-atoms can be replaced by P-atoms; K27 means H or SaaNodachi; (F) aa means 1, 2, C or 4; and in SaaNodaz-1 ONE or several H-atoms can be replaced by E-atoms; or in K25 and K26, together with the nitrogen atom to which they are bound, form a 5- or b-membered ring, or K27 and one СНо group of the radical K25 or K26 together with the nitrogen atom to which they are bound , form a 5- or b-linked cycle; or K?7, KV and KU, independently of each other, mean MK32SOKZO, MK32S5KZO or MK32505K30; 65 KZO means H, OH, SeoNosya, SuuNouu, pyrrolidinyl or piperidinyl, in the rings of which one СНо group can be replaced by O or MK33; KZ2 and K33, independently of each other, mean H or SuNorn4; ss means 1, 2, 3, 4, 5, 6, 7 or 8; uu means 3, 4, 5 or 6; n means 1, 2, C or 4; moreover, in SuNonchi one or more H-atoms can be replaced by P-atoms and in SesNosni and SuNouu 1 groups one or more H-atoms can be replaced by P-atoms, and one or more СНо-groups can be replaced by MKZ1, and one The СНо group can be replaced by 0; KZ1 means H, SKNokknyi, SOKb5 or 50565; 70 KK means 1, 2, C or 4; and one or more H-atoms can be replaced by E-atoms; Кб5 means Н, СххНоххчи; xx means 1, 2, C or 4, and one or more H-atoms may be replaced by P-atoms; or KZ1, together with one СНо group of the KZO radical and the nitrogen atom to which they are bound, form a 5- or b--linked cycle; or KZO means a 5- or b-lene heteroaryl selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thienyl, thiazolyl, and oxazolyl, which are unsubstituted or substituted 2o up to three times with substituents selected from from the group consisting of RE, SI, Vg, I, SooNosochmi" MA7OK?7 1; K?O and K71, independently of each other, mean H, SuuNotsu-i or SOK?72; K72 stands for H, SL/Nouchi; оо, ши and мм, independently of each other, mean 1, 2, З or 4; and in SooNooogi groups; One or more H-atoms can be replaced by E-atoms in SzshNHYotsii or SuU/Nouuii; or i) K7, KV and KU, independently of each other, mean H, RE, SI, Vg, I, MO», SM, OH, MN», SeeNoveni» Sh Ngoudu-1, OsSeNoti, MK4OK41, SOMK4OKA1, SOOK42, SOKAYA2 or OSOKA2; ee and I, independently of each other, mean 1, 2, Z or 4; c zo mly means 3, 4, 5 or 6; moreover, in the groups SeeNoven1i, SmlmNomlu-1 and OSyaNoyani, one or more H-atoms can be replaced by - E-atoms; o K40 and K41 mean H, SeNon.i or C(IMN)MN"; HER means 1, 2, Z, 4, 5, 6, 7 or 8; in. moreover, one or more H-atoms can be replaced by E-atoms in the SeNon-yai group; y- or K4O and K41, independently of each other, are selected from the group consisting of hydroxyethyl, M,M-dimethylaminoethyl, M,M-diethylaminoethyl, pyrrolidinoethyl, M-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; " or in c K40 and K41, together with the nitrogen atom to which they are connected, form a cycle that is selected from the group that . consists of pyrrolidine, piperidine, M-methylpiperazine, piperazine and morpholine; and 42 means H or SenNonnchy; pi means 1, 2, C or 4; moreover, one or more H-atoms can be replaced by E-atoms in the Sennon group. - and 9. The application according to claim 7, which differs in that in formula (I) КИ, К2, КЗ and К4, independently of each other, mean Н, Е, СИ, Вг, ОН, МН», СаНза-4и, cycloalkyl with 3, 4, 5 C- or 6 C-atoms, OXNoya; o a and 6 in the groups СаНоа-і and ОСНой.і independently of each other mean 1, 2, З or 4, and one or more H-atoms can be replaced by P-atoms; ве or Ге КИ, К2, КЗ and К4, independently of each other, mean МК11К12; K11 and K12, independently of each other, mean H, SeNoeni, StNot-1; e means 1, 2, C or 4; 5B gg means 3, 4, 5 or 6, and in the SeNzechi and StNaorg.-1 groups one or more H-atoms can be replaced by E-atoms; Ф) or ka КИ 1 и К12 together with the nitrogen atom to which they are connected form a cycle selected from the group consisting of pyrrolidine, piperidine, M-methylpiperazine, piperazine and morpholine; 60 or K11 and K12, independently of each other, mean SOK14, SZK14, SOMNI14, SZMNK14 or 5ОЖ14; K14 means SoNadyai; 9 means 1, 2, C or 4, and one or more H-atoms can be replaced by E-atoms; or 65 КИ, К2, КЗ and К4, independently of each other, mean О5ОЗН, ЗОЗН, 50215; K15 means SKNok-i or MK17K18; K means 1, 2, C or 4, and one or more H-atoms can be replaced by P-atoms; K17 and K18, independently of each other, mean H or StpNotchi1; t means 1, 2, 3, 4 or 5, and one or more H-atoms can be replaced by E-atoms in the group of C; or K17 and K18, together with the nitrogen atom to which they are connected, form a 5- or b--linked cycle; KB stands for H, SeNaorai» SezNovv-1; p means 1, 2, C or 4; 70 in5 means 3, 4, 5 or 6, and in SeNoray and SezNovv-1 one or more H-atoms can be replaced by P-atoms; Kb means H, СНу"; K?7, KV and KU, independently of each other, mean OZOZN, 5OZN or GOD; K23 means SapNopp-ya or MK25K26; пп means 1, 2, Z, 4 or 5; moreover, in SdpNoppya1 ONE or several H-atoms can be replaced by E-atoms; K25 and K26, independently of each other, mean Н, СМ or С,Н2,-41, IN WHICH the first СНо group connected to the nitrogen atom is replaced by СО or С5 and the second СНо group is replaced by MK27; 7 means 1, 2, 3, 4, 5 or 6; and in C,H2,-41 one or more H-atoms can be replaced by P-atoms; K27 means H or SaaNodachi; aa means 1, 2, C or 4; and in SaaNodaz-1 ONE or several H-atoms can be replaced by E-atoms; or with K25 and K26, together with the nitrogen atom to which they are bound, form a 5- or b-membered ring, or K27 and one СНо group of the radical K25 or K26 together with the nitrogen atom to which they are bound , form a 5- or i) b-lens cycle; or K7, KV and KU, independently of each other, mean MK32SOKZ0, MK32S5430 or MK32502130; c zo KZO means H, OH, SeoNosyaya, SuuNouu, pyrrolidinyl or piperidinyl, in the cycles of which one СHO group can be replaced by O or MK33; "KZ2 and KZZ mean H, CH" or CE"; o ss means 1, 2, 3, 4, 5 or 6; uu means 3, 4, 5, 6, 7 or 8; in. moreover, in the groups SosNossyai and SuuNouu-1 one or more H-atoms can be replaced by P-atoms and one or several СНо-groups can be replaced by MKZ1 and one СНо-group can be replaced by 0; KZ1 means H, methyl, ethyl, СЕ5, СНоСЕ»3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl; or KZ1, together with one СНо group of the KZO radical and the nitrogen atom with which they are bound together, form a 5- or « b--lene cycle; in c or KZO stands for pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl, or oxazolyl, what are they? unsubstituted or substituted with up to three substituents selected from the group consisting of EC, Si, methyl, ethyl, trifluoromethyl, MH", MH-acetyl; or -I K7, K8 and KU, independently of each other, mean H, E, SI, OH, MN", SeeNovech1". Sumu Knowlu1;. OSyaNonaya, MAK4OKa1, SOMKAOKAT, SOOKa2 or OSOKA42; - ее and Я, independently of each other, mean 1, 2, Z or 4; o mly means 3, 4, 5 or 6; moreover, in the groups SeeNovech1, SuluNoudu-1, and OSyaNovya, one or more H-atoms can be replaced by pi E-atoms; He K40 and K41 mean H, SeNon.i or C(IMN)MN"; Her means 1, 2, Z or 4; moreover, one or more H-atoms can be replaced by E-atoms in the SeNon-yai group; 5B or K4O and K41, independently of each other, mean hydroxyethyl, M,M-dimethylaminoethyl, M,M-diethylaminoethyl, (F) pyrrolidinoethyl, M-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; ka or K4O and K41 together with the nitrogen atom to which they are connected form a pyrrolidine, piperidine, boron M-methylpiperazine, piperazine or morpholine cycle; K42 means H or SfNonniai; pi means 1, 2, C or 4; moreover, one or more H-atoms can be replaced by E-atoms in the Sennon group. 10. Application according to claim 7, which is characterized by the fact that the compounds of formula (I) are selected from the group consisting of 65 1). Mch-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|acetamide; 2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; 3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl) benzenesulfonamide; 4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M,M-dimethylbenzenesulfonamide; 5). 4-(4-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline; 6) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid; 7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-ethylbenzamide; 8). 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-propylbenzamide; 9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-(2-dimethylaminoethyl)benzamide; 10) 6,8-dichloro-2-methyl-4-(4-morpholin-4-ylphenyl)-1,2,3,4-tetrahydroisoquinoline; 70 113. I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|diethylamine; 12). 6,β-dichloro-2-methyl-4-(4-piperidin-1-ylphenyl)-1,2,3,4-tetrahydroisoquinoline; 13). 6,8-dichloro-2-methyl-4-(4-pyrrolidin-1-ylphenyl)-1,2,3,4-tetrahydroisoquinoline; 14). 6,8-dichloro-2-methyl-4-(4-(4-methylpiperazin-1-yl)phenyl|-1,2,3,4-tetrahydroisoquinoline; 15) 6,8-dichloro-2-cyclopropyl-4 -phenyl-1,2,3,4-tetrahydroisoquinoline; 16). 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine; 17). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-propylurea; 18). 1-I4-(6,8-dichloro-2-methyl-1, 2, 3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylthiourea; 19). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-ethylurea; 20). M-(4-(6-methanesulfonyl-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|acetamide); 21). Mch-I4-(2,6,8-trimethyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|acetamide; 2235. h-I4-(6-bromo-8-chloro-2-methyl-1, 2,3,4-tetrahydroisoquinolin-4-yl)phenyl|acetamide; 23). M-I4-(8-chloro-2-methyl-b-pyrrolidin-1-yl-1,2,3,4-tetrahydroisoquinolin-4-yl) phenylacetamide; 24). M-I4-(8-chloro-2-methyl-6-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|acetamide; 25). M-4-18-chloro-2-methyl-6-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydroisoquinolin-4-yl|phenyl)acetamide; high school 26). M-(4-(3-chloro-6--(cyclopropylmethylamino)-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl|phenyl)acetamide; 27) 5-(6,8-dichloro- 2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid; (8) 28) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxy-M-methylbenzamide; 29) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-ethyl-2-hydroxybenzamide; 30) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-(2-dimethylaminoethyl)-2-hydroxybenzamide; from 31). Mch-I5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoylguanidine; 32). M-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide; - 33) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine; o 34) 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine; 35). M-I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|propionamide; i- 36). M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; i- 37) I4-(6,8-dichloro-2-methyl -1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|pentanoic acid amide; 38). M-(4-(6,8-dichloro-2-methyl-1, 2, 3,4-tetrahydroisoquinolin-4-yl)phenylisobutyramide; 39). -(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2,2-dimethylpropionamide; 40) I4-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl|iamide of cyclopropanecarboxylic acid; 41) 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of cyclobutanecarboxylic acid; from p 42) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of cyclopentanecarboxylic acid; . 43). M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-2,2,2-trifluoroacetamide; i?» 44) I4-(6 ,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1-acetylpiperidine-4-carboxylic acid; 45). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|nicotinamide; -I 46) M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Imethanesulfonamide; 47) I4-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide ethanesulfonic acid; Sh- 48) M'M'-dimethylamino-H-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|sulfamide; o 49). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 50). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; and 51) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pentanoic acid; Ge 52). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylisobutyramide; 53). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2,2-dimethylpropionamide; 54) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of cyclopropanecarboxylic acid; 55) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Iamide of cyclobutanecarboxylic acid; 56) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of cyclopentanecarboxylic acid; F) 57). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)|-2,2,2-trifluoroacetamide; ka 58) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide of 1-acetylpiperidine-4-carboxylic acid; at 59). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|nicotinamide; 60) h-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; 61). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl/uphenyl)iamide of ethanesulfonic acid; 62). M'M'-dimethylamino-M-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|sulfamide; 63). M-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|propionamide; 65 64). M-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; 65) (2-(6,8-dichloro-2-methyl- 1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|pentanoic acid amide; 66) M-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylisobutyramide; 67). Mch-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2,2-dimethylpropionamide; 68) (2-(6,8-dichloro -2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of cyclopropanecarboxylic acid; 69) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4 -yl)uphenyl|Iamide of cyclobutanecarboxylic acid; 79) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide of cyclopentanecarboxylic acid; 71). 723. |2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Iamide of 1-acetylpiperidine-4-carboxylic acid; 70 73). Mch-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; 74) (2-(6,8-dichloro-2-methyl- 1,2,3,4-tetrahydroisoquinolin-4-yl/uphenyl|iamide of ethanesulfonic acid; 75) MM'-dimethylamino-M-(2-(6,8-dichloro-2-methyl-1,2,3,4- tetrahydroisoquinoline-4-iluphenyl|sulfamide; 76). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-3-ethylurea; 77) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-methylthiourea; 78). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-3-ethylurea; 79). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-methylthiourea; 80) M-15-(4-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfamoyl|-4-methylthiazol-2-yl)acetamide; 81) 20. M-5-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-iluphenylsulfamoyl)-4-methylthiazol-2-yl)acetamide; 82) 1,2-dimethyl-1H-imidazole-4-sulfonic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide; 83). 1,2-Dimethyl-1H-imidazole-4-sulfonic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide; ch 84) |4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide 5-chloro-1,3-dimethyl-1H-pyrazole-4- sulfonic acids; and) 85). I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid; 86). 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl 5-bromothiophene-2-sulfonic acid; from 87). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl 5-bromothiophene-2-sulfonic acid; 88). M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-C,C,C-trifluoromethanesulfonamide; - 89). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-C,C,C-trifluoromethanesulfonamide; o 90) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide 2,2,2-trifluoroethanesulfonic acid; 91). I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide 2,2,2-trifluoroethanesulfonic acid; uh- 92). M-ethyl-M'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl) benzenesulfonylurea; i- 93) 2-chloro-5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide; 94) 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine; 95) 6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 96) 4-(8-amino-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenol; 97) 8-methoxy-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; from p. 98). 2-(8-amino-2-ethyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenol; . 99). 2-(8-amino-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenol; and?" 100) 5-(8-amino-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)2-methoxyphenol; 101) 2-methyl-8-nitro-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 102). 4-(8-amino-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzene-1,2-diol; -I 103) 2,8-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 104) 4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline; Sh- 105). 4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine; o 106) 4-(2,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine; 107). 4-(3-chlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine; pi 108) 2,4-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; Ge 109) 2-butyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine; 110). M-(2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-yl)lacetamide; 111). 7-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 112). 8-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 113) 2,6-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; F) 114) 6b-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; ka 115) b-methoxy-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 116) 2-ethyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; in 117) 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 118) 6,8-dichloro-2-ethyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 119). 4-(4-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline; 120) 2-methyl-4-phenyl-b,8-bistrifluoromethyl-1,2,3,4-tetrahydroisoquinoline; 121) 6,8-dichloro-2-isopropyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 65 122) 5,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 123) 6,8-dichloro-4-(4-fluorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline; 124) 6,8-dichloro-2-methyl-4-p-tolyl-1,2,3,4-tetrahydroisoquinoline; 125) 5,6-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 126) 6,7-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 127) 8-bromo-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 128) 6,8-dichloro-4-(4-chlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline; 129) 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline; 130). 2-amino-M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|acetamide; 131). h-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-methylaminoacetamide; 70 132)..Mch-I4-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-dimethylaminoacetamide; 133) 2-amino-M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 134). 2-amino-M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; 135) 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 2,6-diaminohexanoic acid; 136) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-2-carboxylic acid; 137). h-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylisonicotinamide; 138) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 1H-pyrrole-3-carboxylic acid; 139) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 1H-pyrrole-2-carboxylic acid; 140) 1-methylpiperidine-4-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide; 141). 1,4-dimethyl-1H-pyrrole-2-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 142) 4-nitro-1H-pyrrole-2-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl iamide; 143). 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 2,5-dimethyl-1H-pyrrole-3-carboxylic acid; 144) 1H-imidazole-4-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl Iiamide; i) 145). I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1-methanesulfonylpiperidine-4-carboxylic acid; 146). 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide with 3,5-dimethyl-1H-pyrazole-4-carboxylic acid; 147) 1H-pyrazole-4-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl Iiamide; - 148). 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide o 3-trifluoromethyl-1H-pyrazole-4-carboxylic acid; 149). h-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-methylaminoacetamide; 1-150). h-13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-dimethylaminoacetamide; i- 151) 2-amino-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl| propionamide; 152). 2-amino-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; 153) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 2,6-diaminohexanoic acid; 154) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-2-carboxylic acid; 155). h-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylisonicotinamide; from p 156) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1H-pyrrole-3-carboxylic acid; . 157) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1H-pyrrole-2-carboxylic acid; and?" 158) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide of 1-methylpiperidine-4-carboxylic acid; 159). 113-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide-1,4-dimethyl-1H-pyrrole-2-carboxylic acid; 160) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl iamide of 4-nitro-1H-pyrrole-2-carboxylic acid; at 161). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 2,5-dimethyl-1H-pyrrole-3-carboxylic acid; ve 162) 1H-imidazole-4-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl Iiamide; Ge 163). I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 1-methanesulfonylpiperidine-4-carboxylic acid; 164) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of 3,5-dimethyl-1H-pyrazole-4-carboxylic acid; 165) 1H-pyrazole-4-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylilamide; F) 166) 3-trifluoromethyl-1H-pyrazole-4-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; 167). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylthiourea; in 168). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylthiourea; 169) 1-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylthiourea; 170). 3-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; 171) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide of 4-methylpiperazine-1-carboxylic acid; 65 172) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of piperidine-1-carboxylic acid; 173) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; 174) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-1-carboxylic acid; 175) 3-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-1,1-diethylurea; 176). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; 177). 1-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3--2-dimethylaminoethyl)urea; 178). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-(tetrahydrofuran-3-yl)urea; 179) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-(tetrahydropyran-4-yl)urea; 180) 3-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1-methyl-1-(1-methylpiperidin-4-yl)urea; 70 181) 3-IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1-(3-dimethylaminopropyl)-1-methylcarbamide; 182) 3-I3- (6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1-2-dimethylaminoethyl)-1-methylurea; 183). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--3-dimethylaminopropyl)urea; 184). 1-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-(2-methoxyethyl)urea; 185). 1-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-pyridin-3-ylurea; 186) 1-(3-( 6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-pyridin-4-ylurea; 187) (2-(6,8-dichloro-2-methyl -1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 4-methylpiperazine-1-carboxylic acid; 188). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; 189) 3-(2-(6,8-dichloro 190). 3-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-1,1-diethylurea; 191) (2-(6,8- dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of piperidine-1-carboxylic acid; 192) (2-(6,8-dichloro-2-methyl-1,2, 3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; ch 193) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide pyrrolidine-1-carboxylic acid; 194). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3--2-dimethylaminoethyl)urea; i) 195) 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide of 4-methylpiperazine-1-carboxylic acid; 196) (pyrrolidine-1-carboxylic acid 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide; page 197). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; 198). 3-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; - 199) 3-(4-(6, 8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,1-diethylurea; about 200). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)urea; 201) Piperidine-1-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl iamide; i- 202) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; i- 203). M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Iformamide; 204) (|4-(6,8-dichloro-2-methyl -1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|methylamine; 205). 1-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,3-dimethylurea; 206) |4-(6,8-dichloro -2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl|methylamide of 4-methylpiperazine-1-carboxylic acid; from p. 207). 1-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,3,3-trimethylurea; . 208) I4-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of piperidine-1-carbon and? acids; 209) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of morpholine-4-carboxylic acid; -I 2190) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of pyrrolidine-1-carboxylic acid; Sh-213) about 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)-1-methylurea; 212). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-3,3-diethyl-1-methylurea; in 213). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Iformamide; Ge 214) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|methylamine; 215) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of pyrrolidine-1-carboxylic acid; 216) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of piperidine-1-carboxylic acid; F) 217). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,3,3-trimethylurea; ka 218). 1-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,3-dimethylurea; 219) 3-(6,8-dichloro -2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide morpholine-4-carboxylic acid; 220) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl|methylamide of 4-methylpiperazine-1-carboxylic acid; 221) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)-1-methylurea; 65 222) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl/|-3,3-diethyl-1-methylurea; 223) 2-dimethylaminoethyl ether 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 224) 2-dimethylaminoethyl ether of 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 225) 2-dimethylaminoethyl ether (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 226) methyl ether (IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenylcarbamic acid; 227) ethyl ether IZ3-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylcarbamic acid; 228) isopropyl ether IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)carbamine P where it is 229) 2,2-dimethylpropyl ether IZ-(6, 8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 230) methyl ether (4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl Icarbamic acid; 231) isopropyl ether I4-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)carbamic /5 ACID; 232) 2,2-dimethylpropyl ether of 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 233) ethyl ether of 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylcarbamic acid; 234) (K)-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl| methanesulfonamide; 235)(5)-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl| methanesulfonamide; 236). (K)-1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylurea; 237) (5)-1-( 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-3-ethylurea; 238). M-III-(6,8-difluoro-2-methyl- 1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide; 239) 4-(3-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline; ch 240) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)|-3-(2-hydroxyethyl)urea; 241) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid ethyl ether; i) 242) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid; and also from their pharmaceutically acceptable salts. 11. Application according to claim 7, which is characterized by the fact that the compounds of formula (I) are selected from the group consisting of clause 1). Mch-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|acetamide; 2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl) benzenesulfonamide; - 3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl) benzenesulfonamide; o 4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid; 5) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-ethylbenzamide; in. 6). 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-propylbenzamide; i-7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-(2-dimethylaminoethyl)benzamide; 8) 6,8-dichloro-2-methyl-4-(4-morpholin-4-ylphenyl)-1,2,3,4-tetrahydroisoquinoline; 9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenylamine; 10). 1-I(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylthiourea; « 113). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-ethylurea; from p. 123. h-I4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)acetamide; . 13). 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoic acid; and? 14). 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-M-(2-dimethylaminoethyl)-2-hydroxybenzamide; 15). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|acetamide; 16). 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine; -And 17). 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamine; 18). M-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; Sh-19) |4-(6,8-dichloro-2- methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide of 1-acetylpiperidine-4-carboxylic acid; 20) M-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Imethanesulfonamide; and 21) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of ethanesulfonic acid; Ge 22) M'M'-dimethylamino-1H-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|sulfamide; 23). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 24). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|butyramide; 25). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylisobutyramide; 26) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenyl-iamide of cyclopropanecarboxylic acid; F) 27) IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of cyclobutanecarboxylic acid; ka 28). M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-2,2,2-trifluoroacetamide; 29) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide of 1-acetylpiperidine-4-carboxylic acid; 30) M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|nicotinamide; 31). h-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; 32) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl/uphenyl) ethanesulfonic acid; 33). M',M'-dimethylamino-M-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|sulfamide; 65 34) I(2-(6 ,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of cyclopropanecarboxylic acid; 35) |2-(6,8-dichloro-2-methyl-1,2,3,4 -tetrahydroisoquinolin-4-yl)uphenyl|Iamide of 1-acetylpiperidine-4-carboxylic acid; 36) 1-IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl) uphenyl)|-3-ethylurea; 37). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-methylthiourea; 38). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-3-ethylurea; 39). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-methylthiourea; 40) M-15-(3-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfamoyl|-4-methylthiazol-2-yl)acetamide; 41) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide 1,2-dimethyl-1 70 H-imidazole-4-sulfonic acid; 42). h-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-C,C,C-trifluoromethanesulfonamide; 43). hCh-IZ-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-C,C,C-trifluoromethanesulfonamide; 44) M-ethyl-M'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl) benzenesulfonylurea; 45) 4-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-dimethylaminoacetamide; 46) I4-(6,8-dichloro- 2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylylamide of 2,6-diaminohexanoic acid; 47) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 1H-pyrrole-3-carboxylic acid; 48) 1-methylpiperidine-4-carboxylic acid 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl-iamide; 49) |4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|amide of 1-methanesulfonylpiperidine-4-carboxylic acid; 50) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Iamide of 1H-pyrazole-4-carboxylic acid; 51). Mch-13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-methylaminoacetamide; 52). M-III-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-2-dimethylaminoacetamide; 53). 2-amino-M-I(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|propionamide; 54). 2-amino-M-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|butyramide; 55) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamide of 2,6-diaminohexanoic acid; (8) 56) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide of 1-methylpiperidine-4-carboxylic acid; 57) IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide of 1H-imidazole-4-carboxylic acid; from page 58). 1-methanesulfonylpiperidine-4-carboxylic acid 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide; - 59) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl-iamide o 3,5-dimethyl-1H-pyrazole-4-carboxylic acid; 60) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|Iamide of 1H-pyrazole-4-carboxylic acid; uh- 61). 3-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; i-62) IZ-(6,8- 4-methylpiperazine-1-carboxylic acid dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|iamide; 63) 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of piperidine-1-carboxylic acid; 64) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; 65) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of pyrrolidine-1-carboxylic acid; from p. 66) 3-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-1,1-diethylurea; . 67). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; and?" 68) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3--2-dimethylaminoethyl)urea; 69) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-3-(tetrahydrofuran-3-yl)urea; 70). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-(tetrahydropyran-4-yl)urea; 71) and 3-IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1-methyl-1-(1-methylpiperidin-4-yl)urea; 72) about 3-IZ3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl|-1-(3-dimethylaminopropyl)-1-methylurea; 73) in 20 3 -I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1--2-dimethylaminoethyl)-1-methylurea; Ge 74). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-"3-dimethylaminopropyl)urea; 75). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl/|-3-(2-methoxyethyl)urea; 76). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)|-3-pyridin-3-ylurea; 77). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl)|-3-pyridin-4-ylurea; 78) (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|4-methylpiperazine-1-carboxylic acid (F, acid; ka 79). 1 -(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; 80). 1-(2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3--2-dimethylaminoethyl)urea; in 81) 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl]amide of 4-methylpiperazine-1-carboxylic acid; 82). 1-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3-methylurea; 83). 3-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-1,1-dimethylurea; 84). 3-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)|-1,1-diethylurea; 65 85). 1-I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3--2-dimethylaminoethyl)urea; 86) I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenylamide of morpholine-4-carboxylic acid; 87). M-I (4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|formamide; 88). I4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)methylamine; 89). M-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|formamide; 90). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)methylamine; 91). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,3,3-trimethylurea; 92). 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-1,3-dimethyl urea; 93) I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methylamide of morpholine-4-carboxylic acid; 94). 13-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)methylamide 70 of 4-methylpiperazine-1-carboxylic acid; 95) 1-I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|-3--2-dimethylaminoethyl)-1-methylurea; 96) 2-dimethylaminoethyl ester of 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 97) 2-dimethylaminoethyl ether of 14-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 98) 2-dimethylaminoethyl ether (2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl)carbamic acid; 99) methyl ether (3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)/uphenylcarbamic acid; 100) (K or 5)-M-I(3- (6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)uphenyl|methanesulfonamide; 101) (K or 5)-1-(2-(6,8-dichloro-2 -methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl|-3-ethylurea; 102). 1-I(I3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline-4-iluphenyl/|-3-(2-hydroxyethyl)urea; 103) ethyl ether 3-(6 ,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzoic acid; 104) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline -4-yl)benzoic acid; as well as from their pharmaceutically acceptable salts. 12. Application of the compound of formula (I) according to claim 7 for obtaining a medicinal product for the treatment or i) prevention of respiratory impulse disorders. 13. Use of the compound of formula (I) according to claim 7 for the preparation of a medicinal product for the treatment or prevention of breathing disorders, especially sleep-related breathing disorders, such as sleep apnea. 14. Use of the compound of formula (I) according to claim 7 for the preparation of a medicinal product for the treatment or prevention of snoring. at 15. Use of the compound of formula (I) according to claim 7 for the preparation of a medicinal product for the treatment or prevention of acute and chronic kidney diseases, especially acute renal failure and chronic renal failure. uh- 16. Use of the compound of formula (I) according to claim 7 for the preparation of a medicinal product for the treatment or prevention of intestinal function disorders. 17. Use of the compound of formula (I) according to claim 7 to obtain a medicinal product for the treatment or prevention of biliary function disorders. " 18. Use of the compound of formula (I) according to claim 7 to obtain a medicinal product for the treatment or prevention of ischemic conditions of the peripheral and central nervous system and stroke. . 19. Use of the compound of formula (I) according to claim 7 to obtain a medicinal product for treatment or prevention of ischemic conditions of peripheral organs and limbs. 20. Use of the compound of formula (I) according to claim 7 for the preparation of a medicinal product for the treatment of shock states. 21. Use of the compound of formula (I) according to claim 7 for obtaining a medicinal product for use in -I surgical operations and organ transplants. 22. Application of the compound of formula (I) according to claim 7 for obtaining a medicinal product for preservation and storage of Ш-grafts for surgical procedures. o 23. Use of the compound of formula (I) according to claim 7 for the preparation of a medicinal product for the treatment of diseases, the primary or secondary cause of which is cell proliferation. ve 24. Use of the compound of formula (I) according to claim 7 for the preparation of a medicinal product for the treatment or prevention of disorders of fat metabolism. 25. Use of the compound of formula (I) according to claim 7 for the preparation of a medicinal product for the treatment or prevention of ectoparasite damage. 26. Medicinal product containing an effective amount of the compound of formula (I) according to claim 1. F) Official Bulletin "Industrial Property". Book 1 "Inventions, useful models, topographies of integrated circuits", 2006, M 10, 15.10.2006. State Department of Intellectual Property of the Ministry of Education and Science of Ukraine. 60 b5