HRP20040507A2 - Substituted 4-phenyltetrahydroisoquinoline methods - Google Patents

Substituted 4-phenyltetrahydroisoquinoline methods

Info

Publication number
HRP20040507A2
HRP20040507A2 HR20040507A HRP20040507A HRP20040507A2 HR P20040507 A2 HRP20040507 A2 HR P20040507A2 HR 20040507 A HR20040507 A HR 20040507A HR P20040507 A HRP20040507 A HR P20040507A HR P20040507 A2 HRP20040507 A2 HR P20040507A2
Authority
HR
Croatia
Prior art keywords
methyl
dichloro
phenyl
tetrahydroisoquinolin
tetrahydro
Prior art date
Application number
HR20040507A
Other languages
Croatian (hr)
Inventor
Hofmeister Armin
Heinelt Uwe
Jochen Lang Hans
Bleich Markus
Wirth Klaus
Gekle Michael
Original Assignee
Aventis Pharma Deutschland Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Aventis Pharma Deutschland Gmbh filed Critical Aventis Pharma Deutschland Gmbh
Publication of HRP20040507A2 publication Critical patent/HRP20040507A2/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/16—Central respiratory analeptics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • C07D217/18—Aralkyl radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Pulmonology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Nutrition Science (AREA)
  • Obesity (AREA)
  • Surgery (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Indole Compounds (AREA)

Description

Izum se odnosi na spojeve formule I The invention relates to compounds of formula I

[image] [image]

u kojoj where

R1, R2, R3 i R4 međusobno neovisno predstavljaju H, F, Cl, Br, J, CN, NO2, OH, NH2, CaH2a+1, CqqH2qq-1, OCbH2b+1, COOR10, OCOR10, COR10 ili Ox-(CH2)y-fenil; R1, R2, R3 and R4 independently represent H, F, Cl, Br, J, CN, NO2, OH, NH2, CaH2a+1, CqqH2qq-1, OCbH2b+1, COOR10, OCOR10, COR10 or Ox-(CH2 )y-phenyl;

a i b u skupinama CaH2a+1 i OCbH2b+1 su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; a and b in the groups CaH2a+1 and OCbH2b+1 are independently 1, 2, 3, 4, 5, 6, 7 or 8, whereby one or more H atoms can be replaced by F atoms;

qq je 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; qq is 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms;

R10 je H ili CCH2c+1; R10 is H or CCH2c+1;

c je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma smije biti zamijene s F atomima; c is 1, 2, 3, 4, 5, 6, 7 or 8, whereby one or more H atoms may be replaced by F atoms;

x je nula ili 1; x is zero or 1;

y je nula, 1, 2, 3 ili 4; y is zero, 1, 2, 3 or 4;

pri čemu fenilni prsten u skupini Ox-(CH2)y-fenil nije supstituiran ili je supstituiran s 1-3 supstituenta odabrana iz skupine koju čine F, Cl, Br, CN, NO2, OH, NH2 ili CdH2d+1, wherein the phenyl ring in the Ox-(CH2)y-phenyl group is not substituted or is substituted with 1-3 substituents selected from the group consisting of F, Cl, Br, CN, NO2, OH, NH2 or CdH2d+1,

d je 1, 2, 3, ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili d is 1, 2, 3, or 4, wherein one or more H atoms may be replaced by F atoms; or

R1, R2, R3 i R4 međusobno neovisno predstavljaju heteroaril, pri čemu u prstenu može biti nula, 1, 2, 3 ili 4 N atoma, nula ili 1 atom kisika ili nula ili 1 S atom; ili R 1 , R 2 , R 3 and R 4 independently represent heteroaryl, whereby the ring may contain zero, 1, 2, 3 or 4 N atoms, zero or 1 oxygen atom or zero or 1 S atom; or

R1, R2, R3 i R4 međusobno neovisno predstavljaju CONR11R12 ili NR11R12; R 1 , R 2 , R 3 and R 4 independently represent CONR 11 R 12 or NR 11 R 12 ;

R11 i R12 međusobno neovisno predstavljaju H, CeH2e+1, CrrHrr-1; R11 and R12 independently represent H, CeH2e+1, CrrHrr-1;

e je 1, 2, 3, 4, 5, 6, 7 ili 8, e is 1, 2, 3, 4, 5, 6, 7 or 8,

rr je 3, 4, 5, 6, 7, ili 8, rr is 3, 4, 5, 6, 7, or 8,

pri čemu u skupinama CeH2e+1 i CrrH2rr-1 jedan ili više H atoma smije biti zamijenjeno F atomima i jedna ili više CH2 skupina može biti zamijenjeno s F atomima O ili s NR13; whereby in the groups CeH2e+1 and CrrH2rr-1 one or more H atoms may be replaced by F atoms and one or more CH2 groups may be replaced by F atoms O or by NR13;

R13 je H ili CfH2f+1; R13 is H or CfH2f+1;

F je 1, 2, 3, ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili F is 1, 2, 3, or 4, wherein one or more H atoms may be replaced by F atoms; or

R13 i jedna CH2 skupina iz R11 ili R12 zajedno s N atomom, na koji su one povezane, tvore 5- ili 6-člani prsten; ili R13 and one CH2 group from R11 or R12 together with the N atom, to which they are attached, form a 5- or 6-membered ring; or

R11 i R12 zajedno s N atomom na koji su one povezane tvore 5-, 6- ili 7-člani prsten; ili R11 and R12 together with the N atom to which they are attached form a 5-, 6- or 7-membered ring; or

R11 i R12 međusobno neovisno predstavljaju COR14, CSR14 ili SO2R14; R 11 and R 12 independently represent COR 14 , CSR 14 or SO 2 R 14 ;

R14 je CgH2g+1; R14 is CgH2g+1;

g je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s F atomima O ili s NR13; ili g is 1, 2, 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms and one or more CH 2 groups may be replaced by F atoms O or by NR 13 ; or

R1, R2, R3 i R4 su međusobno neovisno –Oh-SOjR15, pri čemu R1, R2, R3 and R4 are mutually independently -OH-SOjR15, wherein

h je nula ili 1, h is zero or 1,

j je nula, 1 ili 2; j is zero, 1 or 2;

R15 je CkH2k+1, OH, OClH2l+1 ili NR17R18; R15 is CkH2k+1, OH, OClH21+1 or NR17R18;

k je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; k is 1, 2, 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms;

l je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; l is 1, 2, 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms;

R17 i R18 međusobno neovisno predstavljaju H ili CmH2m+1; R17 and R18 independently represent H or CmH2m+1;

m je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu u skupini CmH2m+1 jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s O, CO, CS ili NR19; m is 1, 2, 3, 4, 5, 6, 7 or 8, whereby in the group CmH2m+1 one or more H atoms can be replaced by F atoms and one or more CH2 groups can be replaced by O, CO, CS or NR19;

R19 je H ili CnH2n+1; R19 is H or CnH2n+1;

n je 1, 2, 3 ili 4; n is 1, 2, 3 or 4;

pri čemu u skupini CnH2n+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili whereby in the group CnH2n+1 one or more H atoms can be replaced by F atoms; or

R17 i R18 zajedno s N atomom na koji su one povezane tvore 5-, 6- ili 7-člani prsten; ili R17 and R18 together with the N atom to which they are attached form a 5-, 6- or 7-membered ring; or

R19 i jedna CH2 skupina iz R17 ili R18 zajedno s N atomom na koji su one povezane tvore 5- ili 6-člani prsten; R19 and one CH2 group from R17 or R18 together with the N atom to which they are attached form a 5- or 6-membered ring;

pri čemu, međutim, R2 mora uvijek biti različit od H, where, however, R2 must always be different from H,

R5 je H, CpH2p+1, CssH2ss-1, COR20 ili SO2R20; R5 is H, CpH2p+1, CssH2ss-1, COR20 or SO2R20;

p je 1, 2, 3, 4, 5, 6, 7 ili 8, p is 1, 2, 3, 4, 5, 6, 7 or 8,

ss je 4, 5, 6, 7 ili 8, ss is 4, 5, 6, 7 or 8,

R20 je CqH2q+1; R20 is CqH2q+1;

q je 1, 2, 3, 4, 5, 6, 7 ili 8, q is 1, 2, 3, 4, 5, 6, 7 or 8,

pri čemu u skupinama CpH2p+1, CssH2ss-1 i CqH2q+1 jedan ili više H atoma može biti zamijenjeno s F atomima, i jedna ili više CH2 skupina može biti zamijenjeno s O ili NR21; wherein in the groups CpH2p+1, CssH2ss-1 and CqH2q+1 one or more H atoms can be replaced by F atoms, and one or more CH2 groups can be replaced by O or NR21;

R21 je H ili CrH2r+1; R21 is H or CrH2r+1;

r je 1, 2, 3 ili 4; r is 1, 2, 3 or 4;

pri čemu u skupini CrH2r+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in the group CrH2r+1 one or more H atoms can be replaced by F atoms;

R6 je H, F, Cl, Br, I, CsH2s+1, CddH2dd-1, OH, OCtH2t+1 ili OCOR22; R6 is H, F, Cl, Br, I, CsH2s+1, CddH2dd-1, OH, OCtH2t+1 or OCOR22;

s i t su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8; s and t are independently 1, 2, 3, 4, 5, 6, 7 or 8;

dd je 3, 4, 5, 6, 7 ili 8, pri čemu u skupinama CsH2s+1, CddH2dd-1 i OCtH2t+1 jedan ili više H atoma može biti zamijenjeno s F atomima; dd is 3, 4, 5, 6, 7 or 8, whereby in the groups CsH2s+1, CddH2dd-1 and OCtH2t+1 one or more H atoms can be replaced by F atoms;

R22 je CuH2u+1; R22 is CuH2u+1;

u je 1, 2, 3 ili 4; u is 1, 2, 3 or 4;

pri čemu u skupini CuH2u+1 jedan ili više H atoma može biti zamijenjeno s F atomima: where in the group CuH2u+1 one or more H atoms can be replaced by F atoms:

R7, R8 i R9 su međusobno neovisno -Ov-SOw-R23; R7, R8 and R9 are mutually independently -Ov-SOw-R23;

v je nula ili 1; v is zero or 1;

w je nula, 1 ili 2; w is zero, 1 or 2;

R23 je CnnH2nn+1, CmmH2mm-1, OH, OCppH2pp+1 ili NR25R26; R23 is CnnH2nn+1, CmmH2mm-1, OH, OCppH2pp+1 or NR25R26;

nn i pp su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8, nn and pp are independently 1, 2, 3, 4, 5, 6, 7 or 8,

mm je 3, 4, 5, 6, 7 ili 8, mm is 3, 4, 5, 6, 7 or 8,

pri čemu u skupinama CnnH2nn+1, CmmH2mm-1 i OCppH2pp+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in the groups CnnH2nn+1, CmmH2mm-1 and OCppH2pp+1 one or more H atoms can be replaced by F atoms;

R25 i R26 su međusobno neovisno H, CN ili CzH2z+1, CzzH2zz-1; R25 and R26 are mutually independently H, CN or CzH2z+1, CzzH2zz-1;

z je 1, 2, 3, 4, 5, 6, 7 ili 8; z is 1, 2, 3, 4, 5, 6, 7 or 8;

zz je 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; i zz is 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms; and

u skupini CzH2z+1 jedan ili više H atoma može biti zamijenjeno s F atomima; i jedna ili više CH2 skupina može biti zamijenjeno s O, CO, CS ili s NR27; in the group CzH2z+1 one or more H atoms can be replaced by F atoms; and one or more CH 2 groups may be replaced by O, CO, CS or by NR 27 ;

R27 je H ili CaaH2aa+1; R27 is H or CaaH2aa+1;

aa je 1, 2, 3 ili 4; aa is 1, 2, 3 or 4;

pri čemu u skupini CaaH2aa+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili whereby in the group CaaH2aa+1 one or more H atoms can be replaced by F atoms; or

R25 i R26 zajedno s N atomom na koji su oni povezani tvore 5-, 6- ili 7-člani prsten, ili R25 and R26 together with the N atom to which they are attached form a 5-, 6- or 7-membered ring, or

R27 i jedna CH2 skupina iz R25 ili R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; ili R27 and one CH2 group from R25 or R26 together with the N atom to which they are attached form a 5- or 6-membered ring; or

R7, R8 i R9 su međusobno neovisno NR32COR30, NR32CSR30 ili NR32SObbR30; R7, R8 and R9 are independently NR32COR30, NR32CSR30 or NR32SObbR30;

R30 je H, CccH2cc+1, CyyH2yy-1, pirolidinil ili piperidinil, u kojim prstenovima jedna CH2 skupina može biti zamijenjena s O ili s NR33; R30 is H, CccH2cc+1, CyyH2yy-1, pyrrolidinyl or piperidinyl, in which rings one CH2 group can be replaced by O or by NR33;

R32 i R33 su međusobno neovisno H ili ChH2h+1; R32 and R33 are mutually independently H or ChH2h+1;

bb je 2 ili 3; bb is 2 or 3;

cc je 1, 2, 3, 4, 5, 6, 7 ili 8; cc is 1, 2, 3, 4, 5, 6, 7 or 8;

yy je 3, 4, 5, 6, 7 ili 8; yy is 3, 4, 5, 6, 7 or 8;

h je 1, 2, 3, 4, 5, 6, 7 ili 8, h is 1, 2, 3, 4, 5, 6, 7 or 8,

pri čemu u skupini ChH2h+1 jedan ili više H atoma smije biti zamijenjeno s F atomima, a u skupinama CccH2cc+1 i CyyH2yy-1 jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s NR31 i jedna CH2 skupina može biti zamijenjena s O; where in the group ChH2h+1 one or more H atoms may be replaced by F atoms, and in the groups CccH2cc+1 and CyyH2yy-1 one or more H atoms may be replaced by F atoms and one or more CH2 groups may be replaced by NR31 and one CH2 group can be replaced by O;

R31 je H, C,ckH2kk+1, COR65 ili SO2R65; R31 is H, C,ckH2kk+1, COR65 or SO2R65;

kk je 1, 2, 3, ili 4; kk is 1, 2, 3, or 4;

pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; wherein one or more H atoms may be replaced by F atoms;

R65 je H, CxxH2xx+1; R65 is H, CxxH2xx+1;

xx je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili xx is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or

R31 zajedno s jednom CH2 skupinom iz R30 tvori 5-, 6-ili 7-člani prsten; ili R31 together with one CH2 group from R30 forms a 5-, 6- or 7-membered ring; or

R30 je 5- ili 6-člani heteroaril s 1, 2, 3 ili 4 N atoma, s nula ili 1 S atomom i nula ili 1 O atomom, koji nije supstituiran ili je supstituiran s do tri supstituenta odabrana iz skupine koju čine F, Cl Br, I, CooH2oo+1, NR70R71; R30 is a 5- or 6-membered heteroaryl with 1, 2, 3 or 4 N atoms, with zero or 1 S atom and zero or 1 O atom, which is unsubstituted or substituted with up to three substituents selected from the group consisting of F, Cl Br, I, CooH2oo+1, NR70R71;

R70 i R71 su međusobno neovisno H, CuuH2uu+1 i COR72; R70 and R71 are independently H, CuuH2uu+1 and COR72;

R72 je H, CwH2w+1; R72 is H, CwH2w+1;

oo, uu i vv su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8; oo, uu and vv are independently 1, 2, 3, 4, 5, 6, 7 or 8;

pri čemu u skupinama CooH2oo+1, CuuH2uu+1 i CwH2w+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili whereby in the groups CooH2oo+1, CuuH2uu+1 and CwH2w+1 one or more H atoms may be replaced by F atoms; or

R7, R8 i R9 su međusobno neovisno H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 ili OCOR42, R7, R8 and R9 are independently H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42,

ee i ff su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8; ee and ff are independently 1, 2, 3, 4, 5, 6, 7 or 8;

ww je 3, 4, 5, 6, 7 ili 8; ww is 3, 4, 5, 6, 7 or 8;

pri čemu u skupinama CeeH2ee+1, CwwH2ww-1 i OCffH2ff+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in the groups CeeH2ee+1, CwwH2ww-1 and OCffH2ff+1 one or more H atoms can be replaced by F atoms;

R40 i R41 su H, CttH2tt+1 ili C(NH)NH2; R40 and R41 are H, CttH2tt+1 or C(NH)NH2;

tt je 1, 2, 3, 3, 4, 5, 6, 7 ili 8; tt is 1, 2, 3, 3, 4, 5, 6, 7 or 8;

pri čemu u skupini CttH2tt+1 jedan ili više H atoma smije biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s O ili NR44; wherein in the group CttH2tt+1 one or more H atoms may be replaced by F atoms and one or more CH2 groups may be replaced by O or NR44;

R44 je H ili CggH2gg+1; R44 is H or CggH2gg+1;

gg je 1, 2, 3, 4, 5, 6, 7 ili 8; gg is 1, 2, 3, 4, 5, 6, 7 or 8;

pri čemu u skupini CggH2gg+1 jedan ili više H atoma može biti zamijenjeno s F atomima i R44 zajedno s jednom (CH2) skupinom iz R40 ili R41 i N atomom na koji su one zajedno povezane mogu tvoriti 5 ili 6-člani prsten; ili whereby in the group CggH2gg+1 one or more H atoms can be replaced by F atoms and R44 together with one (CH2) group from R40 or R41 and the N atom to which they are connected together can form a 5- or 6-membered ring; or

R40 i R41 s N atomom na koji su oni povezani tvore 5-ili 6-člani prsten; R40 and R41 with the N atom to which they are attached form a 5- or 6-membered ring;

R42 je H ili ChhH2hh+1; R42 is H or ChhH2hh+1;

hh je 1, 2, 3, 4, 5, 6, 7 ili 8; hh is 1, 2, 3, 4, 5, 6, 7 or 8;

pri čemu u skupini ChhH2hh+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in the group ChhH2hh+1 one or more H atoms can be replaced by F atoms;

pri čemu, međutim, dva supstituenta iz skupina R7, R8 i R9 ne smiju biti istovremeno OH ili OCH3, i whereby, however, two substituents from groups R7, R8 and R9 must not be simultaneously OH or OCH3, and

pri čemu najmanje jedan od ostataka R7, R8 ili R9 mora biti odabran iz skupine koju čine CONR40R41, -OvSOwR23, NR32COR30, NR32CSR30 i NR32SObbR30; wherein at least one of the residues R7, R8 or R9 must be selected from the group consisting of CONR40R41, -OvSOwR23, NR32COR30, NR32CSR30 and NR32SObbR30;

kao i njihove farmacetski podnošljive soli i trifluor-acetate. as well as their pharmaceutically acceptable salts and trifluoroacetates.

Prednost se daje spojevima formule I, u kojoj Preference is given to compounds of formula I, in which

R1, R2, R3 i R4 međusobno neovisno predstavljaju H, F, Cl, Br, I, CN, NO2, OH, NH2, CaH2a+1, cikloalkil s 3, 4, 5 ili 6 C atoma, OCbH2b+1, COOR10; R1, R2, R3 and R4 independently represent H, F, Cl, Br, I, CN, NO2, OH, NH2, CaH2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms, OCbH2b+1, COOR10;

a i b su međusobno neovisno 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; a and b are independently 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms;

R10 je H ili CcH2c+1; R10 is H or CcH2c+1;

c je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili c is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or

R1, R2, R3 i R4 su međusobno neovisno 5- ili 6-člani heteroaril odabran iz skupine koju čine piridil, imidazolil, pirazolil, pirolil, triazolil, tetrazolil, tiazolil i oksazolil; ili R 1 , R 2 , R 3 and R 4 are independently 5- or 6-membered heteroaryl selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl and oxazolyl; or

R1, R2, R3 i R4 su međusobno neovisno CONR1R12 ili NR11R12; R 1 , R 2 , R 3 and R 4 are mutually independently CONR 1 R 12 or NR 11 R 12 ;

R11 i R12 su međusobno neovisno H, CeH2e+1, CrrH2rr-1; R11 and R12 are mutually independently H, CeH2e+1, CrrH2rr-1;

e je 1, 2, 3 ili 4, e is 1, 2, 3 or 4,

rr je 3, 4, 5 ili 6, rr is 3, 4, 5 or 6,

pri čemu u skupinama CeH2e+1 i CrrH2rr-1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili whereby in the groups CeH2e+1 and CrrH2rr-1 one or more H atoms may be replaced by F atoms; or

R11 i R12 su međusobno neovisno hidroksietil, N,N-di-metilaminoetil, N,N-dietilaminoetil, pirolidinoetil, N-metilpiperazinoetil, piperazinoetil, morfolinoetil ili piperidinoetil; ili R11 and R12 are mutually independently hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or

R11 i R12 zajedno s N atomom na koji su oni povezani tvore pirolidinski, piperidinski, N-metilpiperazinski, piperazinski ili morfolinski prsten; ili R11 and R12 together with the N atom to which they are attached form a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring; or

R11 i R12 su međusobno neovisno COR14, CSR14, CONHR14, CSNHR14 ili SO2R14; R 11 and R 12 are independently COR 14 , CSR 14 , CONHR 14 , CSNHR 14 or SO 2 R 14 ;

R14 je CgH2g+1; R14 is CgH2g+1;

g je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili g is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or

R1, R2, R3 i R4 su međusobno neovisno OSO3H, SO3H, SO2R15, pri čemu R1, R2, R3 and R4 are mutually independently OSO3H, SO3H, SO2R15, wherein

R15 je CkH2k+1, OClH2l+1 ili NR17R18; R15 is CkH2k+1, OClH21+1 or NR17R18;

k je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; k is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms;

l je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; l is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms;

R17 i R18 su međusobno neovisno H, CmH2m+1, u kojem prva CH2 skupina povezana na dušik može biti zamijenjena sa CO, a druga CH2 skupina povezana na dušik može biti zamijenjena s NR19; R17 and R18 are independently H, CmH2m+1, wherein the first CH2 group attached to the nitrogen can be replaced by CO and the second CH2 group attached to the nitrogen can be replaced by NR19;

m je 1, 2, 3, 4 ili 5, pri čemu u skupini CmH2m+1 jedan ili više H atoma može biti zamijenjeno s F atomima; m is 1, 2, 3, 4 or 5, whereby in the group CmH2m+1 one or more H atoms can be replaced by F atoms;

R19 je H ili CnHn+1; R 19 is H or CnHn+1;

n je 1, 2, 3 ili 4; n is 1, 2, 3 or 4;

pri čemu u skupini CnH2n+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili whereby in the group CnH2n+1 one or more H atoms can be replaced by F atoms; or

R17 i R18 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; R17 and R18 together with the N atom to which they are attached form a 5- or 6-membered ring;

pri čemu, međutim, R2 mora uvijek biti različit od H, where, however, R2 must always be different from H,

R5 je H, CpH2p+1; R5 is H, CpH2p+1;

p je 1, 2, 3 ili 4; p is 1, 2, 3 or 4;

pri čemu u CpH2p+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in CpH2p+1 one or more H atoms can be replaced by F atoms;

R6 je H, CsH2s+1, OCtH2t+1 ili OCOR22; R6 is H, CsH2s+1, OCtH2t+1 or OCOR22;

s i t su međusobno neovisno 1, 2, 3 ili 4; s and t are independently 1, 2, 3 or 4;

pri čemu u CsH2s+1 i OCtH2t+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in CsH2s+1 and OCtH2t+1 one or more H atoms can be replaced by F atoms;

R22 je CuH2u+1; R22 is CuH2u+1;

u je 1, 2, 3 ili 4; u is 1, 2, 3 or 4;

pri čemu u CuH2u+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in CuH2u+1 one or more H atoms can be replaced by F atoms;

R7, R8 i R9 su međusobno neovisno OSO3H, SO3H ili SO2R23; R 7 , R 8 and R 9 are mutually independently OSO 3 H, SO 3 H or SO 2 R 23 ;

R23 je CnnH2nn+1, CmmH2mm-1, OCppH2pp+1 ili NR25R26; R23 is CnnH2nn+1, CmmH2mm-1, OCppH2pp+1 or NR25R26;

nn i pp su međusobno neovisno 1, 2, 3, 4 ili 5, nn and pp are independently 1, 2, 3, 4 or 5,

mm je 3, 4, 5 ili 6, mm is 3, 4, 5 or 6,

pri čemu u CnnH2nn+1, CmmH2mm-1 i OCppH2pp+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in CnnH2nn+1, CmmH2mm-1 and OCppH2pp+1 one or more H atoms can be replaced by F atoms;

R25 i R26 su međusobno neovisno H, CN ili CzH2z+1, u kojem prva CH2 skupina povezana na dušik može biti zamijenjena sa CO ili CS, a druga CH2 skupina povezana na dušik može biti zamijenjena s NR27; R25 and R26 are independently H, CN or CzH2z+1, wherein the first CH2 group attached to the nitrogen may be replaced by CO or CS and the second CH2 group attached to the nitrogen may be replaced by NR27;

z je 1, 2, 3, 4, 5 ili 6; z is 1, 2, 3, 4, 5 or 6;

pri čemu u CzH2z+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in CzH2z+1 one or more H atoms can be replaced by F atoms;

R27 je H ili CaaH2aa+1; R27 is H or CaaH2aa+1;

aa je 1, 2, 3 ili 4; aa is 1, 2, 3 or 4;

pri čemu u CaaH2aa+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili where in CaaH2aa+1 one or more H atoms can be replaced by F atoms; or

R25 i R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten, ili R25 and R26 together with the N atom to which they are attached form a 5- or 6-membered ring, or

R27 i jedna CH2 skupina iz R25 ili R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; ili R27 and one CH2 group from R25 or R26 together with the N atom to which they are attached form a 5- or 6-membered ring; or

R7, R8 i R9 su međusobno neovisno NR32COR30, NR32CSR30 ili NR32SO2R30; R7, R8 and R9 are independently NR32COR30, NR32CSR30 or NR32SO2R30;

R30 je H, OH, CccH2cc+1, CyyH2yy-1; pirolidinil ili piperidinil, u kojim prstenovima jedna CH2 skupina može biti zamijenjena s O ili NR33; R30 is H, OH, CccH2cc+1, CyyH2yy-1; pyrrolidinyl or piperidinyl, in which rings one CH2 group may be replaced by O or NR33;

R32 i R33 su međusobno neovisno H ili ChH2h+1; R32 and R33 are mutually independently H or ChH2h+1;

cc je 1, 2, 3, 4, 5, 6, 7 ili 8; cc is 1, 2, 3, 4, 5, 6, 7 or 8;

yy je 3, 4, 5, 6; yy is 3, 4, 5, 6;

h je 1, 2, 3 ili 4; h is 1, 2, 3 or 4;

pri čemu u ChH2h+1 jedan ili više H atoma smije biti zamijenjeno s F atomima, a u skupinama CccH2cc+1 i CyyH2yy-1 jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s NR31, i jedna CH2 skupina može biti zamijenjena s O; whereby in ChH2h+1 one or more H atoms may be replaced by F atoms, and in the groups CccH2cc+1 and CyyH2yy-1 one or more H atoms may be replaced by F atoms and one or more CH2 groups may be replaced by NR31, and one CH2 group can be replaced by O;

R31 je H, CkkH2kk+1, COR65 ili SO2R65; R31 is H, CkkH2kk+1, COR65 or SO2R65;

kk je 1, 2, 3, ili 4; kk is 1, 2, 3, or 4;

pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; wherein one or more H atoms may be replaced by F atoms;

R65 je H, CxxH2xx+1; R65 is H, CxxH2xx+1;

xx je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili xx is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or

R31 zajedno s jednom CH2 skupinom iz R30 i N atomom na koji su oni zajedno povezani tvore 5- ili 6-člani prsten; ili R31 together with one CH2 group from R30 and the N atom to which they are connected form a 5- or 6-membered ring; or

R30 je 5- ili 6-člani heteroaromat odabran iz skupine koju čine piridil, imidazolil, pirazolil, pirolil, triazolil, tetrazolil, tienil, tiazolil i oksazolil, koji nisu supstituirani ili su supstituirani s do tri supstituenta odabrana iz skupine koju čine F, Cl, Br, I, CooH2oo+1, NR70R71, R30 is a 5- or 6-membered heteroaromatic selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thienyl, thiazolyl and oxazolyl, which are unsubstituted or substituted with up to three substituents selected from the group consisting of F, Cl , Br, I, CooH2oo+1, NR70R71,

R70 i R71 su međusobno neovisno H, CuuH2uu+1 ili COR72; R70 and R71 are mutually independently H, CuuH2uu+1 or COR72;

R72 je H, CwH2w+1; R72 is H, CwH2w+1;

oo, uu i vv su međusobno neovisno 1, 2, 3 ili 4; oo, uu and vv are independently 1, 2, 3 or 4;

pri čemu u skupinama CooH2oo+1, CuuH2uu+1 i CwH2w+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili whereby in the groups CooH2oo+1, CuuH2uu+1 and CwH2w+1 one or more H atoms may be replaced by F atoms; or

R7, R8 i R9 su međusobno neovisno H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 ili OCOR42; R7, R8 and R9 are independently H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42;

ee i ff su međusobno neovisno 1, 2, 3 ili 4; ee and ff are independently 1, 2, 3 or 4;

ww je 3, 4, 5 ili 6, ww is 3, 4, 5 or 6,

pri čemu u skupinama CeeH2ee+1, CwwH2ww-1 i OCffH2ff+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in the groups CeeH2ee+1, CwwH2ww-1 and OCffH2ff+1 one or more H atoms can be replaced by F atoms;

R40 i R41 su H, CttH2tt+1 ili C(NH)NH2; R40 and R41 are H, CttH2tt+1 or C(NH)NH2;

tt je 1, 2, 3, 4, 5, 6, 7 ili 8; tt is 1, 2, 3, 4, 5, 6, 7 or 8;

pri čemu u skupinama CttH2tt+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili whereby in the groups CttH2tt+1 one or more H atoms may be replaced by F atoms; or

R40 i R41 su međusobno neovisno odabrani iz niza koji čine hidroksietil, N,N-dimetilaminoetil, N,N-dietilamino-etil, pirolidinoetil, N-metilpiperazinoetil/ piperazino-etil, morfolinoetil ili piperidinoetil; ili R40 and R41 are independently selected from the group consisting of hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl/piperazinoethyl, morpholinoethyl or piperidinoethyl; or

R40 i R41 zajedno s N atomom na koji su oni povezani tvore prsten odabran iz skupine koju čine pirolidin, piperidin, N-metilpiperazin, piperazin i morfolin; R40 and R41 together with the N atom to which they are attached form a ring selected from the group consisting of pyrrolidine, piperidine, N-methylpiperazine, piperazine and morpholine;

R42 je H ili ChhH2hh+1; R42 is H or ChhH2hh+1;

hh je 1, 2, 3 ili 4; hh is 1, 2, 3 or 4;

pri čemu u skupini ChhH2hh+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in the group ChhH2hh+1 one or more H atoms can be replaced by F atoms;

pri čemu, međutim, dva supstituenta iz skupina R7, R8 i R9 ne smiju biti istovremeno OH ili OCH3, i whereby, however, two substituents from groups R7, R8 and R9 must not be simultaneously OH or OCH3, and

pri čemu najmanje jedan od ostataka R7, R8 ili R9 mora biti odabran iz skupine koju čine CONR40R41, -OvSOwR23, NR32COR30, NR32CSR30 i NR32SObbR30; wherein at least one of the residues R7, R8 or R9 must be selected from the group consisting of CONR40R41, -OvSOwR23, NR32COR30, NR32CSR30 and NR32SObbR30;

kao i njihovim farmaceutski podnošljivim solima i trifluor-acetatima. as well as their pharmaceutically acceptable salts and trifluoroacetates.

Posebnu prednost se daje spojevima formule I, u kojoj Particular preference is given to compounds of formula I, in which

R1, R2, R3 i R4 su međusobno neovisno H, F, Cl, Br, OH, NH2, CaH2a+1, cikloalkil s 3, 4, 5 ili 6 C atoma, R1, R2, R3 and R4 are independently H, F, Cl, Br, OH, NH2, CaH2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms,

a i b u skupinama CaH2a+1 i OCbH2b+1 su međusobno neovisno 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili a and b in the groups CaH2a+1 and OCbH2b+1 are independently 1, 2, 3 or 4, whereby one or more H atoms can be replaced by F atoms; or

R1, R2, R3 i R4 su međusobno neovisno NR11R12; R 1 , R 2 , R 3 and R 4 are independently NR 11 R 12 ;

R11 i R12 su međusobno neovisno H, CeH2e+1, CrrH2rr-1; R11 and R12 are mutually independently H, CeH2e+1, CrrH2rr-1;

e je 1, 2, 3 ili 4, e is 1, 2, 3 or 4,

rr je 3, 4, 5 ili 6, rr is 3, 4, 5 or 6,

pri čemu u skupinama CeH2e+1 i CrrH2rr-1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili whereby in the groups CeH2e+1 and CrrH2rr-1 one or more H atoms may be replaced by F atoms; or

R11 i R12 zajedno s N atomima na koje su oni povezani tvore prsten odabran iz skupine koju čine pirolidin, piperidin, N-metilpiperazin, piperazin i morfolin; ili R11 and R12 together with the N atoms to which they are attached form a ring selected from the group consisting of pyrrolidine, piperidine, N-methylpiperazine, piperazine and morpholine; or

R11 i R12 su međusobno neovisno COR14, CSR14, CONHR14, CSNHR14 ili SO2R14; R 11 and R 12 are independently COR 14 , CSR 14 , CONHR 14 , CSNHR 14 or SO 2 R 14 ;

R14 je CgH2g+1; R14 is CgH2g+1;

g je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili g is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or

R1, R2, R3 i R4 su međusobno neovisno OSO3H, SO3H, SO2R15; R1, R2, R3 and R4 are mutually independently OSO3H, SO3H, SO2R15;

R15 je ChH2k, CkH2k+1 ili NR17R18; R15 is ChH2k, CkH2k+1 or NR17R18;

k je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; k is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms;

R17 i R18 su međusobno neovisno H ili CmH2m+1; R17 and R18 are mutually independently H or CmH2m+1;

m je 1, 2, 3, 4 ili 5, pri čemu u skupini CmH2m+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili m is 1, 2, 3, 4 or 5, whereby in the group CmH2m+1 one or more H atoms can be replaced by F atoms; or

R17 i R18 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; R17 and R18 together with the N atom to which they are attached form a 5- or 6-membered ring;

pri čemu, međutim, R2 mora uvijek biti različit od H; wherein, however, R 2 must always be different from H;

R5 je metil ili trifluoremetil; R 5 is methyl or trifluoromethyl;

R6 je H; R 6 is H;

R7, R8 i R9 su međusobno neovisno OSO3H, SO3H ili SO2R23; R 7 , R 8 and R 9 are mutually independently OSO 3 H, SO 3 H or SO 2 R 23 ;

R23 je CnnH2nn+1 ili NR25R26; R23 is CnnH2nn+1 or NR25R26;

nn je 1, 2, 3, 4 ili 5, nn is 1, 2, 3, 4 or 5,

pri čemu u CnnH2nn+1 jedan ili više H atoma može biti zamijenjeno s F atomima; where in CnnH2nn+1 one or more H atoms can be replaced by F atoms;

R25 i R26 su međusobno neovisno H, CN ili CzH2z+1, u kojem prva CH2 skupina povezana na dušik može biti zamijenjena sa CO ili CS, a druga CH2 skupina povezana na dušik može biti zamijenjena s NR27; R25 and R26 are independently H, CN or CzH2z+1, wherein the first CH2 group attached to the nitrogen may be replaced by CO or CS and the second CH2 group attached to the nitrogen may be replaced by NR27;

z je 1, 2, 3, 4, 5 ili 6; z is 1, 2, 3, 4, 5 or 6;

pri čemu u CzH2z+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in CzH2z+1 one or more H atoms can be replaced by F atoms;

R27 je H ili CaaH2aa+1; R27 is H or CaaH2aa+1;

aa je 1, 2, 3 ili 4; aa is 1, 2, 3 or 4;

pri čemu u CaaH2aa+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili where in CaaH2aa+1 one or more H atoms can be replaced by F atoms; or

R25 i R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten, ili R25 and R26 together with the N atom to which they are attached form a 5- or 6-membered ring, or

R27 i jedna CH2 skupina iz R25 ili R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; ili R27 and one CH2 group from R25 or R26 together with the N atom to which they are attached form a 5- or 6-membered ring; or

R7, R8 i R9 su međusobno neovisno NR32COR30, NR32CSR30 ili NR32SO2R30; R7, R8 and R9 are independently NR32COR30, NR32CSR30 or NR32SO2R30;

R30 je H, OH, CccH2cc+1, CyyH2yy-1, pirolidinil ili piperidinil, u kojim prstenovima jedna CH2 skupina može biti zamijenjena s O ili NR33; R30 is H, OH, CccH2cc+1, CyyH2yy-1, pyrrolidinyl or piperidinyl, in which rings one CH2 group may be replaced by O or NR33;

R32 i R33 su H, metil ili CF3; R32 and R33 are H, methyl or CF3;

cc je 1, 2, 3, 4, 5, 6, 7 ili 8; cc is 1, 2, 3, 4, 5, 6, 7 or 8;

yy 3, 4, 5, 6; yy 3, 4, 5, 6;

pri čemu u skupinama CccH2cc+1 i CyyH2yy-1 jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s NR31, i jedna CH2 skupina može biti zamijenjena s O; wherein in the groups CccH2cc+1 and CyyH2yy-1 one or more H atoms can be replaced by F atoms and one or more CH2 groups can be replaced by NR31, and one CH2 group can be replaced by O;

R31 je H, metil, etil, CF3, CH2CF3, acetil, propionil, metansulfonil ili etansulfonil; ili R31 is H, methyl, ethyl, CF3, CH2CF3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl; or

R31 zajedno s jednom CH2 skupinom iz R30 i N atomom na koji su one zajedno povezane tvore 5- ili 6-člani prsten; ili R31 together with one CH2 group from R30 and the N atom to which they are connected form a 5- or 6-membered ring; or

R30 je piridil, imidazolil, pirazolil, pirolil, triazolil, tetrazolil, tiazolil ili oksazolil, koji nisu supstituirani ili su supstituirani s najviše 3 supstituenta odabrana iz skupine koju čine F, Cl, metil, etil, trifluor-metll, NH2, NH-acetil; ili R30 is pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl, which are unsubstituted or substituted with at most 3 substituents selected from the group consisting of F, Cl, methyl, ethyl, trifluoromethyl, NH2, NH-acetyl ; or

R7, R8 i R9 su međusobno neovisno H, F, Cl, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42 ili OCOR42, R7, R8 and R9 are independently H, F, Cl, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42 or OCOR42,

ee i ff su međusobno neovisno 1, 2, 3 ili 4; ee and ff are independently 1, 2, 3 or 4;

ww je 3, 4, 5 ili 6, ww is 3, 4, 5 or 6,

pri čemu u skupinama CeeH2ee+1, CwwH2ww-1 i OCffH2ff+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in the groups CeeH2ee+1, CwwH2ww-1 and OCffH2ff+1 one or more H atoms can be replaced by F atoms;

R40 i R41 su H, CttH2tt+1 ili C(NH)NH2; R40 and R41 are H, CttH2tt+1 or C(NH)NH2;

tt je 1, 2, 3 ili 4; tt is 1, 2, 3 or 4;

pri čemu u skupini CttH2tt+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili whereby in the group CttH2tt+1 one or more H atoms may be replaced by F atoms; or

R40 i R41 su međusobno neovisno hidroksietil, N,N-dimetilaminoetil, N,N-dietilaminoetil, pirolidinoetil, N-metilpiperazinoetil, piperazinoetil, morfolinoetil ili piperidinoetil; ili R40 and R41 are mutually independently hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or

R40 i R41 zajedno s N atomom na koji su oni povezani tvore pirolidinski, piperidinski, N-metilpiperazinski, piperazinski ili morfolinski prsten; R40 and R41 together with the N atom to which they are attached form a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;

R42 je H ili ChhH2hh+1; R42 is H or ChhH2hh+1;

hh je 1, 2, 3 ili 4; hh is 1, 2, 3 or 4;

pri čemu u skupini ChhH2hh+1, jedan ili više H atoma može biti zamijenjeno s F atomima; wherein in the group ChhH2hh+1, one or more H atoms can be replaced by F atoms;

pri čemu, međutim, dva supstituenta iz skupina R7, R8 i R9 ne smiju biti istovremeno OH ili OCH3, i whereby, however, two substituents from groups R7, R8 and R9 must not be simultaneously OH or OCH3, and

pri čemu najmanje jedan od ostataka R7, R8 ili R9 mora biti odabran iz skupine koju čine CONR40R41, -OvSOwR23, NR32COR30, NR32CSR30 i NR32SObbR30; wherein at least one of the residues R7, R8 or R9 must be selected from the group consisting of CONR40R41, -OvSOwR23, NR32COR30, NR32CSR30 and NR32SObbR30;

kao i njihovim farmaceutski podnošljivim solima i trifluor-acetatima. as well as their pharmaceutically acceptable salts and trifluoroacetates.

Posve posebnu prednost daje se spojevima formule I, u kojoj Particular preference is given to compounds of formula I, in which

R1, R2, R3 i R4 su međusobno neovisno H, F, Cl, Br, OH, NH2, CaH2a+1, cikloalkil s 3, 4, 5 ili 6 C atoma, OCbH2b+1; R1, R2, R3 and R4 are independently H, F, Cl, Br, OH, NH2, CaH2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms, OCbH2b+1;

a i b u skupinama CaH2a+1 i OCbH2b+1 su međusobno neovisno 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili a and b in the groups CaH2a+1 and OCbH2b+1 are independently 1, 2, 3 or 4, whereby one or more H atoms can be replaced by F atoms; or

R1, R2, R3 i R4 su međusobno neovisno NR11R12; R 1 , R 2 , R 3 and R 4 are independently NR 11 R 12 ;

R11 i R12 su međusobno neovisno H, CeH2e+1, CrrH2rr-1; R11 and R12 are mutually independently H, CeH2e+1, CrrH2rr-1;

e je 1, 2, 3 ili 4, e is 1, 2, 3 or 4,

rr je 3, 4, 5 ili 6, rr is 3, 4, 5 or 6,

pri čemu u skupinama CeH2e+1 i CrrH2rr-1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili whereby in the groups CeH2e+1 and CrrH2rr-1 one or more H atoms may be replaced by F atoms; or

R11 i R12 zajedno s N atomom na koji su oni povezani tvore prsten odabran iz skupine koju čine pirolidin, piperidin, N-metilpiperazin, piperazin i morfolin; ili R11 and R12 together with the N atom to which they are attached form a ring selected from the group consisting of pyrrolidine, piperidine, N-methylpiperazine, piperazine and morpholine; or

R11 i R12 su međusobno neovisno COR14, CSR14, CONHR14, CSNHR14 ili SO2R14; R 11 and R 12 are independently COR 14 , CSR 14 , CONHR 14 , CSNHR 14 or SO 2 R 14 ;

R14 je CgH2g+1; R14 is CgH2g+1;

g je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili g is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or

R1, R2, R3 i R4 su međusobno neovisno OSO3H, SO3H, SO2R15; R1, R2, R3 and R4 are mutually independently OSO3H, SO3H, SO2R15;

R15 je CkH2k+1 ili NR17R18; R15 is CkH2k+1 or NR17R18;

k je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; k is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms;

R17 i R18 su međusobno neovisno H ili CmH2m+1; R17 and R18 are mutually independently H or CmH2m+1;

m je 1, 2, 3, 4 ili 5, pri čemu u skupini CmH2m+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili m is 1, 2, 3, 4 or 5, whereby in the group CmH2m+1 one or more H atoms can be replaced by F atoms; or

R17 i R18 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; R17 and R18 together with the N atom to which they are attached form a 5- or 6-membered ring;

pri čemu, međutim, R2 mora uvijek biti različit od H; wherein, however, R 2 must always be different from H;

R5 je metil ili trifluoremetil; R 5 is methyl or trifluoromethyl;

R6 je H; R 6 is H;

R7, R8 i R9 su međusobno neovisno OSO3H, SO3H ili SO2R23; R 7 , R 8 and R 9 are mutually independently OSO 3 H, SO 3 H or SO 2 R 23 ;

R23 je CnnH2nn+1 ili NR25R26; R23 is CnnH2nn+1 or NR25R26;

nn je 1, 2, 3, 4 ili 5, nn is 1, 2, 3, 4 or 5,

pri čemu u CnnH2nn+1 jedan ili više H atoma može biti zamijenjeno s F atomima; where in CnnH2nn+1 one or more H atoms can be replaced by F atoms;

R25 i R26 su međusobno neovisno H, CN ili CzH2z+1, u. kojem prva CH2 skupina povezana na dušik može biti zamijenjena sa CO ili CS, a druga CH2 skupina povezana na dušik može biti zamijenjena NR27; R25 and R26 are independently H, CN or CzH2z+1, in which the first CH2 group attached to the nitrogen can be replaced by CO or CS, and the second CH2 group attached to the nitrogen can be replaced by NR27;

z je 1, 2, 3, 4, 5 ili 6; z is 1, 2, 3, 4, 5 or 6;

pri čemu u CzH2z+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in CzH2z+1 one or more H atoms can be replaced by F atoms;

R27 je H ili CaaH2aa+1; R27 is H or CaaH2aa+1;

aa je 1, 2, 3 ili 4; aa is 1, 2, 3 or 4;

pri čemu u CaaH2aa+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili where in CaaH2aa+1 one or more H atoms can be replaced by F atoms; or

R25 i R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten, ili R25 and R26 together with the N atom to which they are attached form a 5- or 6-membered ring, or

R27 i jedna CH2 skupina iz R25 ili R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; ili R27 and one CH2 group from R25 or R26 together with the N atom to which they are attached form a 5- or 6-membered ring; or

R7, R8 i R9 su međusobno neovisno NR32COR30, NR32CSR30 ili NR32SO2R30; R7, R8 and R9 are independently NR32COR30, NR32CSR30 or NR32SO2R30;

R30 je H, OH, CccH2cc+1, CyyH2yy-1, pirolidinil ili piperidinil, u kojim prstenovima jedna CH2 skupina može biti zamijenjena O ili NR33; R30 is H, OH, CccH2cc+1, CyyH2yy-1, pyrrolidinyl or piperidinyl, in which rings one CH2 group may be replaced by O or NR33;

R32 i R33 su H, metil ili CF3; R32 and R33 are H, methyl or CF3;

cc je 1, 2, 3, 4, 5, 6, 7 ili 8; cc is 1, 2, 3, 4, 5, 6, 7 or 8;

yy je 3, 4, 5 ili 6; yy is 3, 4, 5 or 6;

pri čemu u skupinama CccH2cc+1 i CyyH2yy-1 jedan više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s NR31, i jedna CH2 skupina može biti zamijenjena s O; wherein in the groups CccH2cc+1 and CyyH2yy-1 one or more H atoms can be replaced by F atoms and one or more CH2 groups can be replaced by NR31, and one CH2 group can be replaced by O;

R31 je H, metil, etil, CF3, CH3CF3, acetil, propionil, metansulfonil ili etansulfonil; ili R31 is H, methyl, ethyl, CF3, CH3CF3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl; or

R31 zajedno s jednom CH2 skupinom iz R30 i N atomom na koji su oni zajedno povezani tvore 5-ili 6-člani prsten; ili R31 together with one CH2 group from R30 and the N atom to which they are connected form a 5- or 6-membered ring; or

R30 je piridil, imidazolil, pirazolil, pirolil, triazolil, tetrazolil, tiazolil ili oksazolil, koji nisu supstituirani ili su supstituirani s najviše 3 supstituenta odabrana iz skupine koju čine F, Cl, metil, etil, trifluor-metil, NH2, NH-acetil; ili R30 is pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl, which are unsubstituted or substituted with at most 3 substituents selected from the group consisting of F, Cl, methyl, ethyl, trifluoromethyl, NH2, NH-acetyl ; or

R7, R8 i R9 su međusobno neovisno H, F, Cl, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR4OR41, CONR40R41, COOR42 ili COR42, R7, R8 and R9 are independently H, F, Cl, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR4OR41, CONR40R41, COOR42 or COR42,

ee i ff su međusobno neovisno 1, 2, 3 ili 4; ee and ff are independently 1, 2, 3 or 4;

ww je 3, 4, 5 ili 6, ww is 3, 4, 5 or 6,

pri čemu u skupinama C2eeH2ee+1, CwwH2ww-1 i OCffH2ff+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in the groups C2eeH2ee+1, CwwH2ww-1 and OCffH2ff+1 one or more H atoms can be replaced by F atoms;

R40 i R41 su H, CttH2tt+1 ili C(NH)NH2; R40 and R41 are H, CttH2tt+1 or C(NH)NH2;

tt je 1, 2, 3 ili 4; tt is 1, 2, 3 or 4;

pri čemu u skupini CttH2tt+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili whereby in the group CttH2tt+1 one or more H atoms may be replaced by F atoms; or

R40 i R41 su međusobno neovisno hidroksietil, N,N-dimetilaminoetil, N,N-dietilaminoetil, pirolidinoetil, N-metilpiperazinoetil, piperazinoetil, morfolinoetil ili piperidinoetil; ili R40 and R41 are mutually independently hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or

R40 i R41 zajedno s N atomom na koji su oni povezani tvore pirolidinski, piperidinski, N-metilpiperazinski, piperazinski ili morfolinski prten; R40 and R41 together with the N atom to which they are attached form a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;

R42 je H ili ChhH2hh+1; R42 is H or ChhH2hh+1;

hh je 1, 2, 3 ili 4; hh is 1, 2, 3 or 4;

pri čemu u skupini ChhH2hh+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in the group ChhH2hh+1 one or more H atoms can be replaced by F atoms;

pri čemu, međutim, dva supstituenta iz skupina R7, R8 i R9 ne smiju biti istovremeno OH ili OCH3, i whereby, however, two substituents from groups R7, R8 and R9 must not be simultaneously OH or OCH3, and

pri čemu najmanje jedan od ostataka R7, R8 ili R9 mora biti odabran iz skupine koju čine -OvSOwR23, NR32COR30, NR32CSR30 i NR32SObbR30; wherein at least one of the residues R7, R8 or R9 must be selected from the group consisting of -OvSOwR23, NR32COR30, NR32CSR30 and NR32SObbR30;

kao i njihovim farmaceutski podnošljivim solima i trifluoracetatima. as well as their pharmaceutically acceptable salts and trifluoroacetates.

Posve naročitu i posebnu prednost imaju spojevi: Compounds have a very particular and special advantage:

1) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 1) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide;

2) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-benzolsulfonamid; 2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-benzenesulfonamide;

3) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-benzolsulfonamid; 3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-benzenesulfonamide;

4) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N,N-dimetil-benzol-sulfonamid; 4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N,N-dimethyl-benzene-sulfonamide;

5) 4-(4-bromfenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin; 5) 4-(4-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline;

6) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-benzojeva kiselina; 6) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-benzoic acid;

7) 4-(6,8-diklor-2-metil)-1,2,3,4-tetrahidroizokinolin-4-il)-N-etil-benzamid; 7) 4-(6,8-dichloro-2-methyl)-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-ethyl-benzamide;

8) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-propil-benzamid; 8) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-propyl-benzamide;

9) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-(2-dimetilaminoetil)-benzamid; 9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-(2-dimethylaminoethyl)-benzamide;

10) 6,8-diklor-2-metil-4-(4-morfolin-4-il-fenil)-1,2,3,4-tetrahidroizokinolin; 10) 6,8-dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;

11) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-dietil-amin; 11) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-diethyl-amine;

12) 6,8-diklor-2-metil-4-(4-piperidin-1-il-fenil)-1,2,3,4-tetahidroizokinolin; 12) 6,8-dichloro-2-methyl-4-(4-piperidin-1-yl-phenyl)-1,2,3,4-tetahydroisoquinoline;

13) 6,8-diklor-2-metil-4-(4-pirolidin-1-il-fenil)-1,2,3,4-tetrahidroizokinolin; 13) 6,8-dichloro-2-methyl-4-(4-pyrrolidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;

14) 6,8-diklor-2-metil-4-[4-(4-metil-piperazin-1-il)-fenil]-1,2,3,4-tetrahidroizokinolin; 14) 6,8-dichloro-2-methyl-4-[4-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydroisoquinoline;

15) 6,8-diklor-2-ciklopropil-4-fenil-1,2,3,4-tetrahidroizokinolin; 15) 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline;

16) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin; 16) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;

17) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-propil-urea; 17) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-propyl-urea;

18) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 18) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea;

19) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea; 19) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;

20) N-[4-(6-metansulfonil-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 20) N-[4-(6-methanesulfonyl-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;

21) N-[4-(2,6,8-trimetil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 21) N-[4-(2,6,8-trimethyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide;

22) N-[4-(6-brom-8-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-1l}-fenil]-acetamid; 22) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-1l}-phenyl]-acetamide;

23) N-[4-{8-klor-2-metil-6-pirolidin-1-il-1,2,3,4-tetra-hidroizokinolin-4-il)-fenil]-acetamid; 23) N-[4-{8-chloro-2-methyl-6-pyrrolidin-1-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide;

24) N-[4-(8-klor-2-metil-6-morfolin-4-il-1,2,3,4-tetra-hidroizokinolin-4-il)-fenil]-acetamid; 24) N-[4-(8-chloro-2-methyl-6-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide;

25) N-{4-[8-klor-2-metil-6-(4-metil-piperazin-1-il)-1,2,3,4-tetrahidro-izokinolin-4-il]-fenil}-acetamid; 25) N-{4-[8-chloro-2-methyl-6-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}- acetamide;

26) N-{4-[8-klor-6-(ciklopropilmetil-amino)-2-metil-1,2,3,4-tetrahidroizokinolin-4-il]-fenil}-acetamid; 26) N-{4-[8-chloro-6-(cyclopropylmethyl-amino)-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl]-phenyl}-acetamide;

27) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-2-hidroksi-benzojeva kiselina; 27) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxy-benzoic acid;

28) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-2-hidroksi-N-metil-benzamid; 28) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxy-N-methyl-benzamide;

29) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-etil-2-hidroksi-benzamid; 29) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-ethyl-2-hydroxy-benzamide;

30) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-(2-dimetilamino-etil)-2-hidroksi-benzamid; 30) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-2-hydroxy-benzamide;

31) N-[5-(6, δ-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-2-hidroksibenzoil]-gvanidin; 31) N-[5-(6,δ-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoyl]-guanidine;

32) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 32) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide;

33) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenilamin; 33) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenylamine;

34) 2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenilamin; 34) 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenylamine;

35) N-[4-{6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 35) N-[4-{6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide;

36) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-butiramid; 36) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;

37) pentanska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 37) pentanoic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

38) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 38) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide;

39) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2-dimetil-propionamid; 39) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;

40) ciklopropankarbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 40) cyclopropanecarboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

41) ciklobutankarbonska kiselina-[4-(6,diklor-2-metil-1,2,3, 4-tetrahidroizokinolin-4-il)-fenil]-amid; 41) cyclobutanecarboxylic acid-[4-(6,dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

42) ciklopentankarbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 42) cyclopentanecarboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

43) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2,2-trifluoracetamid; 43) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2,2-trifluoroacetamide;

44) 1-acetil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 44) 1-acetyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide;

45) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-nikotinamid; 45) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-nicotinamide;

46) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metansulfonamid; 46) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methanesulfonamide;

47) etansulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 47) ethanesulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

48) N',N'-dimetilamino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 48) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;

49) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 49) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide;

50) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-butiramid; 50) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-butyramide;

51) pentanska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 51) pentanoic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

52) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 52) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide;

53) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2-dimetil-propionamid; 53) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;

54) ciklopropankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 54) cyclopropanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

55) ciklobutankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 55) cyclobutanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

56) ciklopentankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil-amid; 56) cyclopentanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl-amide;

57) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin 4-il)-fenil]-2,2,2-trifluoracetamid; 57) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline 4-yl)-phenyl]-2,2,2-trifluoroacetamide;

58) 1-acetil-piperidin-4-karbonska kiselina-[3-(6,8-di-klor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 58) 1-acetyl-piperidine-4-carboxylic acid-[3-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

59) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-nikotinamid; 59) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-nicotinamide;

60) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 60) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide;

61) etansulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 61) ethanesulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

62) N',N'-dimetilamino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-sulfamid; 62) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-sulfamide;

63) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 63) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide;

64) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenilj-butiramid; 64) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenylj-butyramide;

65) pentanska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 65) pentanoic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

66) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 66) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide;

67) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2-dimetil-propionamid; 67) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;

68) ciklopropankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 68) cyclopropanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

69) ciklobutankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 69) cyclobutanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

70) ciklopentankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 70) cyclopentanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

71) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2,2-trifluoracetamid; 71) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2,2-trifluoroacetamide;

72) 1-acetil-piperidin-4-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 72) 1-acetyl-piperidine-4-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

73) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 73) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide;

74) etansulfonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 74) ethanesulfonic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

75) N',N'-dimetilamino-N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-sulfamid; 75) N',N'-dimethylamino-N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-sulfamide;

76) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 76) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea;

77) 1-[3-(6,δ-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 77) 1-[3-(6,δ-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea;

78) 1-[2-(6,δ-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 78) 1-[2-(6,δ-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea;

79) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinotin-4-il)-feni ]-3-metil-tiourea; 79) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinotin-4-yl)-phenyl]-3-methyl-thiourea;

80) N-{5-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilsulfamoil]-4-metil-tiazol-2-1l}-acetamid; 80) N-{5-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-1l }-acetamide;

81) N-{5-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilsulfamoil]-4-metil-tiazol-2-1l}-acetamid; 81) N-{5-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-1l }-acetamide;

82) 1,2-dimetil-1H-imidazol-4-sulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 82) 1,2-dimethyl-1H-imidazole-4-sulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide ;

83) 1,2-dimetil-1H-imidazol-4-sulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 83) 1,2-dimethyl-1H-imidazol-4-sulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide;

84) 5-klor-1,3-dimetil-1H-pirazol-4-sulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 84) 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)- phenyl]-amide;

85) 5-klor-1,3-dimetil-1H-pirazol-4-sulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 85) 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)- phenyl]-amide;

86) 5-brom-tiofen-2-sulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 86) 5-bromo-thiophene-2-sulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

87) 5-brom-tiofen-2-sulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 87) 5-bromo-thiophene-2-sulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

88) N-{4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluormetansulfonamid; 88) N-{4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide;

89) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluor-metansulfonamid; 89) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide;

90) 2,2,2-trifluor-etansulfonska kiselina-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 90) 2,2,2-trifluoroethanesulfonic acid-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

91) 2,2,2-trifluor-etansulfonska kiselina-3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 91) 2,2,2-trifluoroethanesulfonic acid-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

92) N-etil-N'-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonil-urea; 92) N-ethyl-N'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonyl-urea;

93) 2-klor-5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonamid; 93) 2-chloro-5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;

94) 2-metil-4-fenil-6,8-bis-trifluormetil-1,2,3,4-tetrahidroizokinolin; 94) 2-methyl-4-phenyl-6,8-bis-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline;

95) 2-amino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 95) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;

96) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-metilamino-acetamid; 96) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-methylamino-acetamide;

97) N-[6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetitamino-acetamid; 97) N-[6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;

98) 2-amino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-propionamid; 98) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;

99) 2-amino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-butiramid; 99) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;

100) 2,6-diamino-heksanska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 100) 2,6-diamino-hexanoic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

101) pirolidin-2-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 101) pyrrolidine-2-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

102) N-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izonikotinamid; 102) N-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isonicotinamide;

103) 1H-pirol-3-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin4-il)-fenil]-amid; 103) 1H-pyrrole-3-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin4-yl)-phenyl]-amide;

104) 1H-pirol-2-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 104) 1H-pyrrole-2-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

105) 1-metil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 105) 1-methyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

106) 1,4-dimetil-1H-pirol-2-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 106) 1,4-dimethyl-1H-pyrrole-2-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide;

107) 4-nitro-1H-pirol-2-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 107) 4-nitro-1H-pyrrole-2-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide;

108) 2,5-dimetil-1H-pirol-3-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 108) 2,5-dimethyl-1H-pyrrole-3-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide;

109) 1H-imidazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 109) 1H-imidazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide;

110) 1-metansulfonil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il-fenil]-amid; 110) 1-methanesulfonyl-piperidin-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl-phenyl]-amide;

111) 3,5-dimetil-1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 111) 3,5-dimethyl-1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide ;

112) 1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 112) 1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

113) 3-trifluormetil-1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 113) 3-trifluoromethyl-1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

114) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-metilamino-acetamid; 114) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-methylamino-acetamide;

115) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-acetamid; 115) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;

116) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-propionamid; 116) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;

117) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-butiramid; 117) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;

118) 2,6-diamino-heksanska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 118) 2,6-diamino-hexanoic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

119) pirolidin-2-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-1i)-fenil]-amid; 119) pyrrolidine-2-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-1i)-phenyl]-amide;

120) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izonikotinamid; 120) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isonicotinamide;

121) 1H-pirol-3-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 121) 1H-pyrrole-3-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

122) 1H-pirol-2-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 122) 1H-pyrrole-2-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

123) 1-metil-piperidin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 123) 1-methyl-piperidine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide;

124) 1,4-dimetil-1H-pirol-2-karbonska-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 124) 1,4-dimethyl-1H-pyrrole-2-carbono-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide;

125) 4-nitro-1H-pirol-2-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 125) 4-nitro-1H-pyrrole-2-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide;

126) 2,5-dimetil-1H-pirol-3-karbonska kiselina-[3-(6,8-di-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 126) 2,5-dimethyl-1H-pyrrole-3-carboxylic acid-[3-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-amide;

127) 1H-imidazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 127) 1H-imidazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

128) 1-metansulfonil-piperidin-4-karbonska kiselina-[3-6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil-amid; 128) 1-methanesulfonyl-piperidine-4-carboxylic acid-[3-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl-amide;

129) 3,5-dimetil-1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 129) 3,5-dimethyl-1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide ;

130) 1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 130) 1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide;

131) 3-trifluormetil-1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 131) 3-trifluoromethyl-1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide ;

132) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-tiourea; 132) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;

133) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-tiourea; 133) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;

134) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-tiourea; 134) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;

135) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dimetil-urea; 135) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;

136) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 136) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide;

137) piperidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 137) piperidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

138) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin4-il)-fenil]-amid; 138) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin4-yl)-phenyl]-amide;

139) pirolidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 139) pyrrolidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

140) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 140) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;

141) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 141) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea;

142) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 142) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;

143) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-furan-3-il)-urea; 143) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-furan-3-yl)-urea;

144) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-piran-4-il)-urea; 144) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-pyran-4-yl)-urea;

145) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-metil-1-(l-tetrahidroizokinolin-4-il)-urea; 145) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-methyl-1-(1-tetrahydroisoquinolin-4-yl) )-urea;

146) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenilj-1-(3-dimetilamino-propil)-1-metil-urea; 146) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-(3-dimethylamino-propyl)-1-methyl-urea ;

147) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-(2-dimetilamino-etil)-1-metil-urea; 147) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-(2-dimethylamino-ethyl)-1-methyl- urea;

148) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(3-dimetilamino-propil)-urea; 148) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(3-dimethylamino-propyl)-urea;

149) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-metoksi-etil)-urea; 149) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea;

150) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-piridin-3-il-urea; 150) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-pyridin-3-yl-urea;

151) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-piridin-4-il-urea; 151) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-pyridin-4-yl-urea;

152) 4-metil-piperazin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 152) 4-methyl-piperazine-1-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide;

153) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 153) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea;

154) 3-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dimetil-urea; 154) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;

155) 3-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 155) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;

156) piperidin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 156) piperidine-1-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

157) morfolin-4-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 157) morpholine-4-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

158) pirolidin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 158) pyrrolidine-1-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

159) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 159) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;

160) 4-metil-piperazin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 160) 4-methyl-piperazine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide;

161) pirolidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 161) pyrrolidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

162) 1-[4-(6,-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-metil-urea; 162) 1-[4-(6,-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea;

163) 3-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil[-1,1-dimetil-urea; 163) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl[-1,1-dimethyl-urea;

164) 3-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 164) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;

165) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 165) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;

166) piperidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 166) piperidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

167) morfolin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 167) morpholine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

168) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-formamid; 168) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-formamide;

169) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metil-amin; 169) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methyl-amine;

170) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3-dimetil-urea; 170) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;

171) 4-metil-piperazin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 171) 4-methyl-piperazine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide ;

172) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-l,3,3-trimetil-urea; 172) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;

173) piperidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 173) piperidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide;

174) morfolin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metil-amid; 174) morpholine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methyl-amide;

175) pirolidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 175) pyrrolidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide;

176) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-1-metil-urea; 176) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl- urea;

177) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3,3-dietil-1-metil-urea; 177) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3,3-diethyl-1-methyl-urea;

178) N-{3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil}-formamid; 178) N-{3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl}-formamide;

179) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amin; 179) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;

180) pirolidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 180) pyrrolidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide;

181) piperidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il-fenil]-metil-amid; 181) Piperidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl-phenyl]-methyl-amide;

182) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3,3-trimetil-urea; 182) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;

183) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3-dimetil-urea; 183) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;

184) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 184) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide;

185) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metil-amid; 185) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methyl-amide;

186) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-1-metil-urea; 186) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl- urea;

187) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3,3-dietil-1-metil-urea; 187) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3,3-diethyl-1-methyl-urea;

188) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina-2-dimetilamino-etil ester; 188) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid-2-dimethylamino-ethyl ester;

189) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina-2-dimetilamino-etil ester; 189) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid-2-dimethylamino-ethyl ester;

190) [2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina-2-dimetilamino-etil ester; 190) [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid-2-dimethylamino-ethyl ester;

191) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina metil ester; 191) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid methyl ester;

192) [3-(6,8-diklor-2-meti)-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina etil ester; 192) [3-(6,8-dichloro-2-methyl)-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid ethyl ester;

193) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina izopropil ester; 193) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid isopropyl ester;

194) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina 2,2-dimetil-propil ester; 194) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid 2,2-dimethyl-propyl ester;

195) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenill-karbaminska kiselina metil ester; 195) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl-carbamic acid methyl ester;

196) [4-(6,δ-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina izopropil ester; 196) [4-(6,δ-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid isopropyl ester;

197) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina 2,2-dimetil-propil ester; 197) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid 2,2-dimethyl-propyl ester;

198) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina etil ester; 198) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid ethyl ester;

199) (R)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamid; 199) (R)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;

200) (S)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamid; 200) (S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;

201) (R)-1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea; 201) (R)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;

202) (S)-1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea; 202) (S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;

203) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 203) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide;

204) 4-(3-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin; 204) 4-(3-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline;

205) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-hidroksi-etil)-urea; 205) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea;

206) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina etil ester; 206) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid ethyl ester;

207) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina, 207) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid,

kao i njihovim farmaceutski podnošljivim solima. as well as their pharmaceutically acceptable salts.

Izvanrednu i sasvim posebnu prednost imaju spojevi iz skupine koju čine: Compounds from the group consisting of:

1) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 1) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide;

2) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonamid; 2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;

3) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonamid; 3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;

4) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-metil-tiourea; 4) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea;

5) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 5) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea;

6) N-[4-(6-brom-8-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 6) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;

7) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 7) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide;

8) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 8) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide;

9) 1-acetil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 9) 1-acetyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

10) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 10) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide;

11) etansulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 11) ethanesulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

12) N',N'-dimetilamino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 12) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;

13) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 13) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide;

14) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-butiramid; 14) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-butyramide;

15) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 15) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide;

16) ciklopropankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 16) cyclopropanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

17) ciklobutankarbonska kiselina-[3-(6,8-diklor-2-metil-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 17) cyclobutanecarboxylic acid-[3-(6,8-dichloro-2-methyl-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide;

18) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2,2-trifluor-acetamid; 18) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2,2-trifluoroacetamide;

19) 1-acetil-piperidin-4-karbonska kiselina-[3-(6,8-di-klor-2-metil-1,2,3,4-tetrahidro-izokinoain-4-1l}-fenil]-amid; 19) 1-acetyl-piperidine-4-carboxylic acid-[3-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinoain-4-1l}-phenyl]-amide ;

20) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin 4-il)-fenil]-nikotinamid; 20) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline 4-yl)-phenyl]-nicotinamide;

21) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 21) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide;

22) etansulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 22) ethanesulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

23) N',N'-dimetilamino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 23) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;

24) ciklopropankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 24) cyclopropanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

25) 1-acetil-piperidin-4-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 25) 1-acetyl-piperidine-4-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

26) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 26) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea;

27) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 27) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea;

28) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 28) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea;

29) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 29) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea;

30) N-{5-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilsulfamoil]-4-metil-tiazol-2-1l}-acetamid; 30) N-{5-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-1l }-acetamide;

31) 1,2-dimetil-1H-imidazol-4-sulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 31) 1,2-dimethyl-1H-imidazol-4-sulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide;

32) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluor-metansulfonamid; 32) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide;

33) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluor-metansulfonamid; 33) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide;

34) N-etil-N'-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonil-urea; 34) N-ethyl-N'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonyl-urea;

35) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-acetamid; 35) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;

36) 2,6-diamino-heksanska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 36) 2,6-diamino-hexanoic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

37) 1H-pirol-3-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 37) 1H-pyrrole-3-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

38) 1-metil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 38) 1-methyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide;

39) 1-metansulfonil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 39) 1-methanesulfonyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

40) 1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 40) 1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide;

41) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-metilamino-acetamid; 41) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-methylamino-acetamide;

42) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-acetamid; 42) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;

43) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-propionamid; 43) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;

44) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-butiramid; 44) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;

45) 2,6-diamino-heksanska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 45) 2,6-diamino-hexanoic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

46) 1-metil-piperidin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 46) 1-methyl-piperidine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide;

47) 1H-imidazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 47) 1H-imidazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

48) 1-metansulfonil-piperidin-4-karbonska kiselina-[3-6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 48) 1-methanesulfonyl-piperidine-4-carboxylic acid-[3-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

49) 3,5-dimetil-1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 49) 3,5-dimethyl-1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide;

50) 1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 50) 1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

51) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dimetil-urea; 51) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;

52) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroi.zokinolin-4-il)-fenil] amid; 52) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl] amide;

53) piperidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 53) piperidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

54) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 54) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

55) pirolidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 55) pyrrolidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

56) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 56) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;

57) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 57) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea;

58) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 58) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;

59) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-furan-3-il)-urea; 59) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-furan-3-yl)-urea;

60) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-piran-4-il)-urea; 60) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-pyran-4-yl)-urea;

61) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-metil-1-(1-metil-piperidin-4-il)-urea; 61) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-methyl-1-(1-methyl-piperidine-4 -yl)-urea;

62) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-(3-dimetilaraino-propil)-1-metil-urea; 62) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-(3-dimethylaraino-propyl)-1-methyl- urea;

63) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-etil)-1-metil-urea; 63) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-ethyl)-1-methyl-urea;

64) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(3-dimetilamino-propil)-urea; 64) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(3-dimethylamino-propyl)-urea;

65) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-metoksi-etil)-urea; 65) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea;

66) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-piridin-3-il-urea; 66) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-pyridin-3-yl-urea;

67) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-piridin-4-il-urea; 67) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-pyridin-4-yl-urea;

68) 4-metil-piperazin-1-il-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 68) 4-methyl-piperazin-1-yl-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide;

69) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 69) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea;

70) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilarαino-etil)-urea; 70) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylaraino-ethyl)-urea;

71) 4-metil-piperazin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-1i)-fenil]amid; 71) 4-methyl-piperazine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-1i)-phenyl]amide;

72) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 72) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea;

73) 3-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dimetil-urea; 73) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;

74) 3-[4-{6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 74) 3-[4-{6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;

75) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahiroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 75) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrachiroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;

76) morfolin-4-karbonska-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 76) morpholine-4-carbon-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

77) N-[4-(6,e-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-formamid; 77) N-[4-(6,ε-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-formamide;

78) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-formamid; 78) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-formamide;

79) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3,3-trimetil-urea; 79) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;

80) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3-dimetil-urea; 80) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;

81) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 81) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide;

82) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 82) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide ;

83) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-1-metil-urea; 83) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl- urea;

84) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]karbaminska kiselina 2-dimetilamino-etil ester; 84) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]carbamic acid 2-dimethylamino-ethyl ester;

85) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 85) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester;

86) [2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 86) [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester;

87) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina metil ester; 87) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid methyl ester;

88) (R ili S)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamid; 88) (R or S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;

89) (R ili S)-1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea; 89) (R or S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;

90) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-hidroksi-etil)-urea; 90) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea;

kao i njihove farmaceutski podnošljive soli. as well as their pharmaceutically acceptable salts.

Izum, nadalje, obuhvaća upotrebu spojeva formule I za proizvodnju lijeka za liječenje bolesti na koje se može utjecati inhibicijom podtipa III izmjenjivača natrij-protona (NHE3), pri čemu u formuli I simboli imaju slijedeća značenja: The invention further encompasses the use of compounds of formula I for the manufacture of a medicament for the treatment of diseases which can be affected by inhibition of sodium-proton exchanger subtype III (NHE3), wherein in formula I the symbols have the following meanings:

R1, R2, R3 i R4 međusobno neovisno predstavljaju H, F, Cl, Br, J, CN, NO2, OH, NH2, CaH2a+1, CggH2qq-1, OCbH2b+1, COOR10, OCOR10, COR10 ili Ox-(CH2)y-fenil; R1, R2, R3 and R4 independently represent H, F, Cl, Br, J, CN, NO2, OH, NH2, CaH2a+1, CggH2qq-1, OCbH2b+1, COOR10, OCOR10, COR10 or Ox-(CH2 )y-phenyl;

a i b u skupinama CaH2a+1 i OCbH2b+1 su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; a and b in the groups CaH2a+1 and OCbH2b+1 are independently 1, 2, 3, 4, 5, 6, 7 or 8, whereby one or more H atoms can be replaced by F atoms;

qq je 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; qq is 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms;

R10 je H ili CcH2c+1; R10 is H or CcH2c+1;

c je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; c is 1, 2, 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms;

x je nula ili 1; x is zero or 1;

y je nula, 1, 2, 3 ili 4; y is zero, 1, 2, 3 or 4;

pri čemu fenilni prsten u skupini Ox-(CH2)y-fenil nije supstituiran ili je supstituiran s 1-3 supstituenta odabrana iz skupine koju čine F, Cl, Br, CN, NO2, OH, NH2 ili CdH2d+1; wherein the phenyl ring in the Ox-(CH2)y-phenyl group is not substituted or is substituted with 1-3 substituents selected from the group consisting of F, Cl, Br, CN, NO2, OH, NH2 or CdH2d+1;

d je 1, 2, 3, ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili d is 1, 2, 3, or 4, wherein one or more H atoms may be replaced by F atoms; or

R1, R2, R3 i R4 međusobno neovisno predstavljaju heteroaril, pri čemu u prstenu može biti nula, 1, 2, 3 ili 4 N atoma, nula ili 1 atom kisika ili nula ili l S atom; ili R 1 , R 2 , R 3 and R 4 independently represent heteroaryl, whereby the ring may contain zero, 1, 2, 3 or 4 N atoms, zero or 1 oxygen atom or zero or 1 S atom; or

R1, R2, R3 i R4 međusobno neovisno predstavljaju CONR11R12 ili NR11R12; R 1 , R 2 , R 3 and R 4 independently represent CONR 11 R 12 or NR 11 R 12 ;

R11 i R12 međusobno neovisno predstavljaju H, CeH2e+1 i CrrH2rr-1; R11 and R12 independently represent H, CeH2e+1 and CrrH2rr-1;

e je 1, 2, 3, 4, 5, 6, 7 ili 8, e is 1, 2, 3, 4, 5, 6, 7 or 8,

rr je 3, 4, 5, 6, 7, ili 8, rr is 3, 4, 5, 6, 7, or 8,

pri čemu u skupinama CeH2e+1 i CrrH2rr-1 jedan ili više H atoma smije biti zamijenjeno F atomima i jedna ili više CH2 skupina može biti zamijenjeno s F atomima O ili s NR13; whereby in the groups CeH2e+1 and CrrH2rr-1 one or more H atoms may be replaced by F atoms and one or more CH2 groups may be replaced by F atoms O or by NR13;

R13 je H ili CfH2f+1; R13 is H or CfH2f+1;

f je 1, 2, 3, ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili f is 1, 2, 3, or 4, wherein one or more H atoms may be replaced by F atoms; or

R13 i jedna CH2 skupina iz R11 ili R12 zajedno s N atomom, na koji su one povezane, tvore 5- ili 6-člani prsten; ili R13 and one CH2 group from R11 or R12 together with the N atom, to which they are attached, form a 5- or 6-membered ring; or

R11 i R12 zajedno s N atomom na koji su one povezane tvore 5-, 6- ili 7-člani prsten; ili R11 and R12 together with the N atom to which they are attached form a 5-, 6- or 7-membered ring; or

R11 i R12 međusobno neovisno predstavljaju COR14, CSR14 ili SO2R14; R 11 and R 12 independently represent COR 14 , CSR 14 or SO 2 R 14 ;

R14 je CgH2g+1; R14 is CgH2g+1;

g je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s F atomima O ili s NR13; ili g is 1, 2, 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms and one or more CH 2 groups may be replaced by F atoms O or by NR 13 ; or

R1, R2, R3 i R4 su međusobno neovisno -Oh-SOjR15, pri čemu R 1 , R 2 , R 3 and R 4 are mutually independently -OH-SO 1 R 15 , wherein

h je nula ili 1, h is zero or 1,

j je nula, 1 ili 2; j is zero, 1 or 2;

R15 je CkH2k+1, OH, OClH21+1 ili NR17R18; R15 is CkH2k+1, OH, OClH21+1 or NR17R18;

k je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; k is 1, 2, 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms;

l je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; l is 1, 2, 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms;

R17 i R18 međusobno neovisno predstavljaju H ili CmH2m+1; R17 and R18 independently represent H or CmH2m+1;

m je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu u skupini jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s O, CO, CS ili NR19; m is 1, 2, 3, 4, 5, 6, 7 or 8, wherein in the group one or more H atoms can be replaced by F atoms and one or more CH2 groups can be replaced by O, CO, CS or NR19 ;

R19 je H ili CnH2n+1; R19 is H or CnH2n+1;

n je 1, 2, 3 ili 4; n is 1, 2, 3 or 4;

pri čemu u skupini CnH2n+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili whereby in the group CnH2n+1 one or more H atoms can be replaced by F atoms; or

R17 i R18 zajedno s N atomom na koji su one povezane tvore 5-, 6- ili 7-člani prsten; ili R17 and R18 together with the N atom to which they are attached form a 5-, 6- or 7-membered ring; or

R19 i jedna CH2 skupina iz R17 ili R18 zajedno s N atomom na koji su one povezane tvore 5- ili 6-člani prsten; R19 and one CH2 group from R17 or R18 together with the N atom to which they are attached form a 5- or 6-membered ring;

R5 je H, CpH2p+1, CssH2ss-1, COR20 ili SO2R20; R5 is H, CpH2p+1, CssH2ss-1, COR20 or SO2R20;

p je 1, 2, 3, 4, 5, 6, 7 ili 8, p is 1, 2, 3, 4, 5, 6, 7 or 8,

ss je 4, 5, 6, 7 ili 8, ss is 4, 5, 6, 7 or 8,

R20 je CqH2q+1; R20 is CqH2q+1;

q je 1, 2, 3, 4, 5, 6, 7 ili 8, q is 1, 2, 3, 4, 5, 6, 7 or 8,

pri čemu u skupinama CpH2p+1, CssH2ss-1 i CqH2q+1 jedan ili više H atoma može biti zamijenjeno s F atomima, i jedna ili više CH2 skupina može biti zamijenjeno s O ili NR21; wherein in the groups CpH2p+1, CssH2ss-1 and CqH2q+1 one or more H atoms can be replaced by F atoms, and one or more CH2 groups can be replaced by O or NR21;

R21 je H ili CrH2r+1; R21 is H or CrH2r+1;

r je 1, 2, 3 ili 4; r is 1, 2, 3 or 4;

pri čemu u skupini CrH2r+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in the group CrH2r+1 one or more H atoms can be replaced by F atoms;

R6 je H, F, Cl, Br, I, CsH2s+1, CddH2dd-1, OH, OCtH2t+1 ili OCOR22; R6 is H, F, Cl, Br, I, CsH2s+1, CddH2dd-1, OH, OCtH2t+1 or OCOR22;

s i t su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8; s and t are independently 1, 2, 3, 4, 5, 6, 7 or 8;

dd je 3, 4, 5, 6, 7 ili 8, pri čemu u skupinama CsH2s+1, CddH2dd-1 i OCtH2t+1 jedan ili više H atoma može biti zamijenjeno s F atomima; dd is 3, 4, 5, 6, 7 or 8, whereby in the groups CsH2s+1, CddH2dd-1 and OCtH2t+1 one or more H atoms can be replaced by F atoms;

R22 je CuH2u+1; R22 is CuH2u+1;

u je 1, 2, 3 ili 4; u is 1, 2, 3 or 4;

pri čemu u skupini CuH2u+1 jedan ili više H atoma može biti zamijenjeno s F atomima: where in the group CuH2u+1 one or more H atoms can be replaced by F atoms:

R7, R8 i R9 su međusobno neovisno –Ov-SOw-R23; R7, R8 and R9 are independently of each other -Ov-SOw-R23;

v je nula ili 1; v is zero or 1;

w je nula, 1 ili 2; w is zero, 1 or 2;

R23 je CnnH2nn+1, CmmH2mm-1, OH, OCppH2pp+1 ili NR25R26; R23 is CnnH2nn+1, CmmH2mm-1, OH, OCppH2pp+1 or NR25R26;

nn i pp su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8, nn and pp are independently 1, 2, 3, 4, 5, 6, 7 or 8,

mm je 3, 4, 5, 6, 7 ili 8, mm is 3, 4, 5, 6, 7 or 8,

pri čemu u skupinama CnnH2nn+1, CmmH2mm-1 i OCppH2pp+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in the groups CnnH2nn+1, CmmH2mm-1 and OCppH2pp+1 one or more H atoms can be replaced by F atoms;

R25 i R26 su međusobno neovisno H, CN ili CzH2z+1, CzzH2zz-1; R25 and R26 are mutually independently H, CN or CzH2z+1, CzzH2zz-1;

z je 1, 2, 3, 4, 5, 6, 7 ili 8; z is 1, 2, 3, 4, 5, 6, 7 or 8;

zz je 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; i zz is 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms; and

u skupini CzH2z+1 jedan ili više H atoma može biti zamijenjeno s F atomima; i jedna ili više CH2 skupina može biti zamijenjeno s O, CO, CS ili s NR27; in the group CzH2z+1 one or more H atoms can be replaced by F atoms; and one or more CH 2 groups may be replaced by O, CO, CS or by NR 27 ;

R27 je H ili CaaH2aa+1; R27 is H or CaaH2aa+1;

aa je 1, 2, 3 ili 4; aa is 1, 2, 3 or 4;

pri čemu u skupini CaaH2aa+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili whereby in the group CaaH2aa+1 one or more H atoms can be replaced by F atoms; or

R25 i R26 zajedno s N atomom na koji su oni povezani tvore 5-, 6- ili 7-člani prsten, ili R25 and R26 together with the N atom to which they are attached form a 5-, 6- or 7-membered ring, or

R27 i jedna CH2 skupina iz R25 ili R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; ili R27 and one CH2 group from R25 or R26 together with the N atom to which they are attached form a 5- or 6-membered ring; or

R7, R8 i R9 su međusobno neovisno NR32COR30, NR32CSR30 ili NR32SObbR30; R7, R8 and R9 are independently NR32COR30, NR32CSR30 or NR32SObbR30;

R30 je H, CccH2cc+1, CyyH2yy-1, pirolidinil ili piperidinil, u kojim prstenovima jedna CH2 skupina može biti zamijenjena s O ili s NR33; R30 is H, CccH2cc+1, CyyH2yy-1, pyrrolidinyl or piperidinyl, in which rings one CH2 group can be replaced by O or by NR33;

R32 i R33 su međusobno neovisno H ili ChH2h+1; R32 and R33 are mutually independently H or ChH2h+1;

bb je 2 ili 3; bb is 2 or 3;

cc je 1, 2, 3, 4, 5, 6, 7 ili 8; cc is 1, 2, 3, 4, 5, 6, 7 or 8;

yy je 3, 4, 5, 6, 7 ili 8; yy is 3, 4, 5, 6, 7 or 8;

h je 1, 2, 3, 4, 5, 6, 7 ili 8, h is 1, 2, 3, 4, 5, 6, 7 or 8,

pri čemu u skupini ChH2h+1 jedan ili više H atoma smije biti zamijenjeno s F atomima, a u skupinama CccH2cc+1 i CyyH2yy-1 jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s NR31 i jedna CH2 skupina može biti zamijenjena s O; where in the group ChH2h+1 one or more H atoms can be replaced by F atoms, and in the groups CccH2cc+1 and CyyH2yy-1 one or more H atoms can be replaced by F atoms and one or more CH2 groups can be replaced by NR31 and one CH2 group can be replaced by O;

R31 je H, CkkCH2kk+1, COR65 ili SO2R65; R31 is H, CkkCH2kk+1, COR65 or SO2R65;

kk je 1, 2, 3, ili 4; kk is 1, 2, 3, or 4;

pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; wherein one or more H atoms may be replaced by F atoms;

R65 je H, CxxH2xx+1; R65 is H, CxxH2xx+1;

xx je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili xx is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or

R31 zajedno s jednom CH2 skupinom iz R30 tvori 5-, 6-ili 7-člani prsten; ili R31 together with one CH2 group from R30 forms a 5-, 6- or 7-membered ring; or

R30 je 5- ili 6-člani heteroaril s 1, 2, 3 ili 4 N atoma, s nula ili 1 S atomom i nula ili 1 O atomom, koji nije supstituiran ili je supstituiran s do tri supstituenta odabrana iz skupine koju čine F, Cl Br, I, CooH2oo+1, NR70R71; R30 is a 5- or 6-membered heteroaryl with 1, 2, 3 or 4 N atoms, with zero or 1 S atom and zero or 1 O atom, which is unsubstituted or substituted with up to three substituents selected from the group consisting of F, Cl Br, I, CooH2oo+1, NR70R71;

R70 i R71 su međusobno neovisno H, CuuH2uu+1 COR72; R70 and R71 are independently H, CuuH2uu+1 COR72;

R72 je H, CvvH2vv-1; R72 is H, CvvH2vv-1;

oo, uu i vv su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8; oo, uu and vv are independently 1, 2, 3, 4, 5, 6, 7 or 8;

pri čemu u skupinama CooH2oo+1, CuuH2uu+1 i CvvH2vv+1 i jedan ili više H atoma smije biti zamijenjeno s F atomima; ili where in the groups CooH2oo+1, CuuH2uu+1 and CvvH2vv+1 and one or more H atoms may be replaced by F atoms; or

R7, R8 i R9 su međusobno neovisno H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+l, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 ili OCOR42, R7, R8 and R9 are independently H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+l, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42,

ee i ff su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8; ee and ff are independently 1, 2, 3, 4, 5, 6, 7 or 8;

ww je 3, 4, 5, 6, 7 ili 8; ww is 3, 4, 5, 6, 7 or 8;

pri čemu u skupinama CeeH2ee+1, CwwH2ww-1 i OCffH2ff+1 jedan ili više H atoma može biti zamijenjeno s F atomima where in the groups CeeH2ee+1, CwwH2ww-1 and OCffH2ff+1 one or more H atoms can be replaced by F atoms

R40 i R41 su H, CttH2tt+1 ili C(NH)NH2; R40 and R41 are H, CttH2tt+1 or C(NH)NH2;

tt je 1, 2, 3, 3, 4, 5, 6, 7 ili 8; tt is 1, 2, 3, 3, 4, 5, 6, 7 or 8;

pri čemu u skupini CttH2tt+1 jedan ili više H atoma smije biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s O ili NR44; wherein in the group CttH2tt+1 one or more H atoms may be replaced by F atoms and one or more CH2 groups may be replaced by O or NR44;

R44 je H ili CggH2+1; R44 is H or CggH2+1;

gg je 1, 2, 3, 4, 5, 6, 7 ili 8; gg is 1, 2, 3, 4, 5, 6, 7 or 8;

pri čemu u skupini CggH2gg+1 jedan ili više H atoma može biti zamijenjeno s F atomima, ili where in the group CggH2gg+1 one or more H atoms can be replaced by F atoms, or

R40 i R41 s N atomom na koji su oni povezani tvore 5-ili 6-člani prsten; R40 and R41 with the N atom to which they are attached form a 5- or 6-membered ring;

R42 je H ili ChhH2hh+1; R42 is H or ChhH2hh+1;

hh je 1, 2, 3, 4, 5, 6, 7 ili 8; hh is 1, 2, 3, 4, 5, 6, 7 or 8;

pri čemu u skupini ChhH2hh+1 jedan ili više H atoma može biti zamijenjeno s F atomima, kao i njihovih farmaceutski podnošljivih soli. whereby in the group ChhH2hh+1 one or more H atoms can be replaced by F atoms, as well as their pharmaceutically acceptable salts.

Prednost se daje upotrebi spojeva formule I, u kojoj Preference is given to the use of compounds of formula I, in which

R1, R2, R3 i R4 međusobno neovisno predstavljaju H, F, Cl, Br, I, CN, NO2, OH, NH2, CaH2a+1, cikloalkil s 3, 4, 5 ili 6 C atoma, OCbH2b+1, COOR10; R1, R2, R3 and R4 independently represent H, F, Cl, Br, I, CN, NO2, OH, NH2, CaH2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms, OCbH2b+1, COOR10;

a i b su međusobno neovisno 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; a and b are independently 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms;

R10 je H ili CCH2C+1; R10 is H or CCH2C+1;

c je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili c is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or

R1, R2, R3 i R4 su međusobno neovisno 5- ili 6-člani heteroaril odabran iz skupine koju čine piridil, imidazolil, pirazolil, pirolil, triazolil, tetrazolil, tiazolil i oksazolil; ili R 1 , R 2 , R 3 and R 4 are independently 5- or 6-membered heteroaryl selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl and oxazolyl; or

R1, R2, R3 i R4 su međusobno neovisno CONR1R12 ili NR11R12; R 1 , R 2 , R 3 and R 4 are mutually independently CONR 1 R 12 or NR 11 R 12 ;

R11 i R12 su međusobno neovisno H, CeH2e+1, CrrH2rr-1; R11 and R12 are mutually independently H, CeH2e+1, CrrH2rr-1;

e je 1, 2, 3 ili 4, e is 1, 2, 3 or 4,

rr je 3, 4, 5 ili 6, rr is 3, 4, 5 or 6,

pri čemu u skupinama CeH2e+1 i CrrH2rr-1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili whereby in the groups CeH2e+1 and CrrH2rr-1 one or more H atoms may be replaced by F atoms; or

R11 i R12 su međusobno neovisno hidroksietil, N,N-di-metilaminoetil, N,N-dietilaminoetil, pirolidinoetil, N-metilpiperazinoetil, piperazinoetil, morfolinoetil ili piperidinoetil; ili R11 and R12 are mutually independently hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or

R11 i R12 zajedno s N atomom na koji su oni povezani tvore pirolidinski, piperidinski, N-metilpiperazinski, piperazinski ili morfolinski prsten; ili R11 and R12 together with the N atom to which they are attached form a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring; or

R11 i R12 su međusobno neovisno COR14, CSR14, CONHR14, CSNHR14 ili SO2R14; R 11 and R 12 are independently COR 14 , CSR 14 , CONHR 14 , CSNHR 14 or SO 2 R 14 ;

R14 je CgH2g+1; R14 is CgH2g+1;

g je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili g is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or

R1, R2, R3 i R4 su međusobno neovisno OSO3H, SO3H, SO2R15, pri čemu R1, R2, R3 and R4 are mutually independently OSO3H, SO3H, SO2R15, wherein

R15 je CkH2k+1, OC1H21+1 ili NR17R18; R15 is CkH2k+1, OC1H21+1 or NR17R18;

k je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; k is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms;

l je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; l is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms;

R17 i R18 su međusobno neovisno H, CmH2m+1, u kojem prva CH2 skupina povezana na dušik može biti zamijenjena sa CO, a druga CH2 skupina povezana na dušik može biti zamijenjena s NR19; R17 and R18 are independently H, CmH2m+1, wherein the first CH2 group attached to the nitrogen can be replaced by CO and the second CH2 group attached to the nitrogen can be replaced by NR19;

m je l, 2, 3, 4 ili 5, pri čemu u skupini CmH2m+1 jedan ili više H atoma može biti zamijenjeno s F atomima; m is 1, 2, 3, 4 or 5, whereby in the group CmH2m+1 one or more H atoms can be replaced by F atoms;

R19 je H ili CnHn+1; R 19 is H or CnHn+1;

n je 1, 2, 3 ili 4; n is 1, 2, 3 or 4;

pri čemu u skupini CnH2n+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili whereby in the group CnH2n+1 one or more H atoms can be replaced by F atoms; or

R17 i R18 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; R17 and R18 together with the N atom to which they are attached form a 5- or 6-membered ring;

R5 je H, CpH2p+1; C33H2ss-1; R5 is H, CpH2p+1; C33H2ss-1;

p je 1, 2, 3 ili 4; p is 1, 2, 3 or 4;

ss je 3, 4, 5 ili 6, pri čemu u CpH2p+1 i CssH2ss-1 jedan ili više H atoma može biti zamijenjeno s F atomima; ss is 3, 4, 5 or 6, whereby in CpH2p+1 and CssH2ss-1 one or more H atoms can be replaced by F atoms;

R6 je H, CsH2s+1, OCtH2t+1 ili OCOR22; R6 is H, CsH2s+1, OCtH2t+1 or OCOR22;

s i t su međusobno neovisno 1, 2, 3 ili 4; s and t are independently 1, 2, 3 or 4;

pri čemu u CsH2s+1 i OCtH2t+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in CsH2s+1 and OCtH2t+1 one or more H atoms can be replaced by F atoms;

R22 je CuH2u+1; R22 is CuH2u+1;

u je 1, 2, 3 ili 4; u is 1, 2, 3 or 4;

pri čemu u CuH2u+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in CuH2u+1 one or more H atoms can be replaced by F atoms;

R7, R8 i R9 su međusobno neovisno OSO3H, SO3H ili SO2R23; R 7 , R 8 and R 9 are mutually independently OSO 3 H, SO 3 H or SO 2 R 23 ;

R23 je CnnH2nn+1, CmmH2mm-1, OCppH2pp+1 ili NR25R26; R23 is CnnH2nn+1, CmmH2mm-1, OCppH2pp+1 or NR25R26;

nn i pp su međusobno neovisno 1, 2, 3, 4 ili 5, nn and pp are independently 1, 2, 3, 4 or 5,

mm je 3, 4, 5 ili 6, mm is 3, 4, 5 or 6,

pri čemu u CnnH2nn+1, CmmH2mm-1 i OCppH2pp+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in CnnH2nn+1, CmmH2mm-1 and OCppH2pp+1 one or more H atoms can be replaced by F atoms;

R25 i R26 su međusobno neovisno H, CN ili CzH2z+1, u kojem prva CH2 skupina povezana na dušik može biti zamijenjena sa CO ili CS, a druga CH2 skupina povezana na dušik može biti zamijenjena s NR27; R25 and R26 are independently H, CN or CzH2z+1, wherein the first CH2 group attached to the nitrogen can be replaced by CO or CS and the second CH2 group attached to the nitrogen can be replaced by NR27;

z je 1, 2, 3, 4, 5 ili 6; z is 1, 2, 3, 4, 5 or 6;

pri čemu u CzH2z+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in CzH2z+1 one or more H atoms can be replaced by F atoms;

R27 je H ili CaaH2aa+1; R27 is H or CaaH2aa+1;

aa je 1, 2, 3 ili 4; aa is 1, 2, 3 or 4;

pri čemu u CaaH2aa+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili where in CaaH2aa+1 one or more H atoms can be replaced by F atoms; or

R25 i R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten, ili R25 and R26 together with the N atom to which they are attached form a 5- or 6-membered ring, or

R27 i jedna CH2 skupina iz R25 ili R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; ili R27 and one CH2 group from R25 or R26 together with the N atom to which they are attached form a 5- or 6-membered ring; or

R7, R8 i R9 su međusobno neovisno NR32COR30, NR32CSR30 ili NR32SO2R30; R7, R8 and R9 are independently NR32COR30, NR32CSR30 or NR32SO2R30;

R30 je H, OH, CccH2cc+1 CyyH2yy-1; pirolidinil ili piperidinil, u kojim prstenovima jedna CH2 skupina može biti zamijenjena s O ili NR33; R30 is H, OH, CccH2cc+1 CyyH2yy-1; pyrrolidinyl or piperidinyl, in which rings one CH2 group may be replaced by O or NR33;

R32 i R33 su međusobno neovisno H ili ChH2h+1; R32 and R33 are mutually independently H or ChH2h+1;

cc je 1, 2, 3, 4, 5, 6, 7 ili 8; cc is 1, 2, 3, 4, 5, 6, 7 or 8;

yy je 3, 4, 5, 6; yy is 3, 4, 5, 6;

h je 1, 2, 3 ili 4; h is 1, 2, 3 or 4;

pri čemu u ChH2h+1 jedan ili više H atoma smije biti zamijenjeno s F atomima, a u skupinama CccH2cc+1 i CyyH2yy-1 jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s NR31, i jedna CH2 skupina može biti zamijenjena s O; whereby in ChH2h+1 one or more H atoms may be replaced by F atoms, and in the groups CccH2cc+1 and CyyH2yy-1 one or more H atoms may be replaced by F atoms and one or more CH2 groups may be replaced by NR31, and one CH2 group can be replaced by O;

R31 je H, CkkH2kk+1, COR65 ili SO2R65; R31 is H, CkkH2kk+1, COR65 or SO2R65;

kk je 1, 2, 3, ili 4; kk is 1, 2, 3, or 4;

pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; wherein one or more H atoms may be replaced by F atoms;

R65 je H, CxxH2xx+1; R65 is H, CxxH2xx+1;

xx je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili xx is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or

R31 zajedno s jednom CH2 skupinom iz R30 i N atomom na koji su oni zajedno povezani tvore 5- ili 6-člani prsten; ili R31 together with one CH2 group from R30 and the N atom to which they are connected form a 5- or 6-membered ring; or

R30 je 5- ili 6-člani heteroaromat odabran iz skupine koju čine piridil, imidazolil, pirazolil, pirolil, triazolil, tetrazolil, tienil, tiazolil i oksazolil, R30 is a 5- or 6-membered heteroaromatic selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thienyl, thiazolyl and oxazolyl,

koji nisu supstituirani ili su supstituirani s do tri supstituenta odabrana iz skupine koju čine F, Cl, Br, I, CooH2oo+l, NR70R71, which are unsubstituted or substituted with up to three substituents selected from the group consisting of F, Cl, Br, I, CooH2oo+l, NR70R71,

R70 i R71 su međusobno neovisno H, CuuH2uu+1 ili COR72; R70 and R71 are mutually independently H, CuuH2uu+1 or COR72;

R72 je H, CvvH2vv+1; R72 is H, CvvH2vv+1;

oo, uu i vv su međusobno neovisno 1, 2, 3 ili 4; oo, uu and vv are independently 1, 2, 3 or 4;

pri čemu u skupinama CooH2oo+1, CuuH2uu+1 i CvvH2vv+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili whereby in the groups CooH2oo+1, CuuH2uu+1 and CvvH2vv+1 one or more H atoms may be replaced by F atoms; or

R7, R8 i R9 su međusobno neovisno H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 ili OCOR42; R7, R8 and R9 are independently H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42;

ee i ff su međusobno neovisno 1, 2, 3 ili 4; ee and ff are independently 1, 2, 3 or 4;

ww je 3, 4, 5 ili 6, ww is 3, 4, 5 or 6,

pri čemu u skupinama CeeH2ee+1, CwwH2ww-1 i OCffH2ff+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in the groups CeeH2ee+1, CwwH2ww-1 and OCffH2ff+1 one or more H atoms can be replaced by F atoms;

R40 i R41 su H, CttH2tt+1 ili C(NH)NH2; R40 and R41 are H, CttH2tt+1 or C(NH)NH2;

tt je 1, 2, 3, 4, 5, 6, 7 ili 8; tt is 1, 2, 3, 4, 5, 6, 7 or 8;

pri čemu u skupinama CttH2tt+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili whereby in the groups CttH2tt+1 one or more H atoms may be replaced by F atoms; or

R40 i R41 su međusobno neovisno odabrani iz niza koji čine hidroksietil, N,N-dimetilaminoetil, N,N-dietilamino-etil, pirolidinoetil, N-metilpiperazinoetil, piperazino-etil, morfolinoetil ili piperidinoetil; ili R40 and R41 are mutually independently selected from the group consisting of hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or

R40 i R41 zajedno s N atomom na koji su oni povezani tvore prsten odabran iz skupine koju čine pirolidin, piperidin, N-metilpiperazin, piperazin i morfolin; R40 and R41 together with the N atom to which they are attached form a ring selected from the group consisting of pyrrolidine, piperidine, N-methylpiperazine, piperazine and morpholine;

R42 je H ili ChhH2hh+1; R42 is H or ChhH2hh+1;

hh je 1, 2, 3 ili 4; hh is 1, 2, 3 or 4;

pri čemu u skupini ChhH2hh+1 jedan ili više H atoma može biti zamijenjeno s F atomima; kao i njihovim farmaceutski podnošljivim solima. whereby in the group ChhH2hh+1 one or more H atoms can be replaced by F atoms; as well as their pharmaceutically acceptable salts.

Posebnu prednost ima upotreba spojeva formule I, u kojoj A particular advantage is the use of compounds of formula I, in which

R1, R2, R3 i R4 su međusobno neovisno H, F, Cl, Br, OH, NH2, CaH2a+1 cikloalkil s 3, 4, 5 ili 6 C atoma, OCbH2b+1; R1, R2, R3 and R4 are independently H, F, Cl, Br, OH, NH2, CaH2a+1 cycloalkyl with 3, 4, 5 or 6 C atoms, OCbH2b+1;

a i b u skupinama CaH2a+1 i OCbH2b+1 su međusobno neovisno 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili a and b in the groups CaH2a+1 and OCbH2b+1 are independently 1, 2, 3 or 4, whereby one or more H atoms can be replaced by F atoms; or

R1, R2, R3 i R4 su međusobno neovisno NR11R12; R 1 , R 2 , R 3 and R 4 are independently NR 11 R 12 ;

R11 i R12 su međusobno neovisno H, CeH2e+1, CrrH2rr-1;' R11 and R12 are mutually independently H, CeH2e+1, CrrH2rr-1;'

e je 1, 2, 3 ili 4, e is 1, 2, 3 or 4,

rr je 3, 4, 5 ili 6, rr is 3, 4, 5 or 6,

pri čemu u skupinama CeH2e+1 i CrrH2rr-1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili whereby in the groups CeH2e+1 and CrrH2rr-1 one or more H atoms may be replaced by F atoms; or

R11 i R12 zajedno s N atomima na koje su oni povezani tvore prsten odabran iz skupine koju čine pirolidin, piperidin, N-metilpiperazin, piperazin i morfolin; ili R11 and R12 together with the N atoms to which they are attached form a ring selected from the group consisting of pyrrolidine, piperidine, N-methylpiperazine, piperazine and morpholine; or

R11 i R12 su međusobno neovisno CORI4, CSR14, CONHR14, CSNHR14 ili SO2R14; R11 and R12 are mutually independently CORI4, CSR14, CONHR14, CSNHR14 or SO2R14;

R14 je CgH2g+1; R14 is CgH2g+1;

g je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili g is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or

R1, R2, R3 i R4 su međusobno neovisno OSO3H, SO3H, SO2R15; R1, R2, R3 and R4 are mutually independently OSO3H, SO3H, SO2R15;

R15 je CkH2k+l ili NR17R18; R15 is CkH2k+1 or NR17R18;

k je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; k is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms;

R17 i R18 su međusobno neovisno H ili CmH2m+1, R17 and R18 are independently H or CmH2m+1,

m je 1, 2, 3, 4 ili 5, pri čemu u skupini CmH2m+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili m is 1, 2, 3, 4 or 5, whereby in the group CmH2m+1 one or more H atoms can be replaced by F atoms; or

R17 i R18 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; R17 and R18 together with the N atom to which they are attached form a 5- or 6-membered ring;

R5 je H, CpH2p+1, CssH2ss-1, R5 is H, CpH2p+1, CssH2ss-1,

p je 1, 2, 3 ili 4; p is 1, 2, 3 or 4;

ss je 3, 4, 5 ili 6, pri čemu u CpH2p+1 i CssH2ss-1 jedan ili više H atoma može biti zamijenjeno s F atomima; ss is 3, 4, 5 or 6, whereby in CpH2p+1 and CssH2ss-1 one or more H atoms can be replaced by F atoms;

R6 je H, CH3; R 6 is H, CH 3 ;

R7, R8 i R9 su međusobno neovisno OSO3H, SO3H ili SO2R23; R 7 , R 8 and R 9 are mutually independently OSO 3 H, SO 3 H or SO 2 R 23 ;

R23 je CnnH2nn+1 ili NR25R26; R23 is CnnH2nn+1 or NR25R26;

nn je 1, 2, 3, 4 ili 5, nn is 1, 2, 3, 4 or 5,

pri čemu u CnnH2nn+1 jedan ili više H atoma može biti zamijenjeno s F atomima; where in CnnH2nn+1 one or more H atoms can be replaced by F atoms;

R25 i R26 su međusobno neovisno H, CN ili CzH2z+1, u kojem prva CH2 skupina povezana na dušik može biti zamijenjena sa CO ili CS, a druga CH2 skupina povezana na dušik može biti zamijenjena s NR27; R25 and R26 are independently H, CN or CzH2z+1, wherein the first CH2 group attached to the nitrogen may be replaced by CO or CS and the second CH2 group attached to the nitrogen may be replaced by NR27;

z je 1, 2, 3, 4, 5 ili 6; z is 1, 2, 3, 4, 5 or 6;

pri čemu u CzH2z+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in CzH2z+1 one or more H atoms can be replaced by F atoms;

R27 je H ili CaaH2aa+1; R27 is H or CaaH2aa+1;

aa je 1, 2, 3 ili 4; aa is 1, 2, 3 or 4;

pri čemu u CaaH2aa+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili where in CaaH2aa+1 one or more H atoms can be replaced by F atoms; or

R25 i R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten, ili R25 and R26 together with the N atom to which they are attached form a 5- or 6-membered ring, or

R27 i jedna CH2 skupina iz R25 ili R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; ili R27 and one CH2 group from R25 or R26 together with the N atom to which they are attached form a 5- or 6-membered ring; or

R7, R8 i R9 su međusobno neovisno NR32COR30, NR32CSR30 ili NR32SO2R30; R7, R8 and R9 are independently NR32COR30, NR32CSR30 or NR32SO2R30;

R30 je H, OH, CccH2cc+1, CyyH2yy-1, pirolidinil ili piperidinil, u kojim prstenovima jedna CH2 skupina može biti zamijenjena s O ili NR33; R30 is H, OH, CccH2cc+1, CyyH2yy-1, pyrrolidinyl or piperidinyl, in which rings one CH2 group may be replaced by O or NR33;

R32 i R33 su H, metil ili CF3; R32 and R33 are H, methyl or CF3;

cc je 1, 2, 3, 4, 5 ili 6; cc is 1, 2, 3, 4, 5 or 6;

yy je 3, 4, 5 ili 6; yy is 3, 4, 5 or 6;

pri čemu u skupinama CccH2cc+1 i CyyH2yy-1 jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s NR31, i jedna CH2 skupina može biti zamijenjena s O; wherein in the groups CccH2cc+1 and CyyH2yy-1 one or more H atoms can be replaced by F atoms and one or more CH2 groups can be replaced by NR31, and one CH2 group can be replaced by O;

R31 je H, metil, etil, CF3, CH2CF3, acetil, propionil, metansulfonil ili etansulfonil; ili R31 is H, methyl, ethyl, CF3, CH2CF3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl; or

R31 zajedno s jednom CH2 skupinom iz R30 i N atomom na koji su one zajedno povezane tvore 5- ili 6-člani prsten; ili R31 together with one CH2 group from R30 and the N atom to which they are connected form a 5- or 6-membered ring; or

R30 je piridil, imidazolil, pirazolil, pirolil, triazolil, tetrazolil, tiazolil ili oksazolil, koji nisu supstituirani ili su supstituirani s najviše 3 supstituenta odabrana iz skupine koju čine F, Cl, metil, etil, trifluor-metil, NH2, NH-acetil; ili R30 is pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl, which are unsubstituted or substituted with at most 3 substituents selected from the group consisting of F, Cl, methyl, ethyl, trifluoromethyl, NH2, NH-acetyl ; or

R7, R8 i R9 su međusobno neovisno H, F, Cl, OH, NH2, CeeH2ee+1, CwwH2ww-l, OCffH2ff+1, NR40R41, CONR40R41, COOR42 ili OCOR42, R7, R8 and R9 are independently H, F, Cl, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42 or OCOR42,

ee i ff su međusobno neovisno 1, 2, 3 ili 4; ee and ff are independently 1, 2, 3 or 4;

ww je 3, 4, 5 ili 6, ww is 3, 4, 5 or 6,

pri čemu u skupinama CeeH2ee+1, CwwH2ww-1 i OCffH2ff+1 jedan ili više H atoma može biti zamijenjeno s F atomima; whereby in the groups CeeH2ee+1, CwwH2ww-1 and OCffH2ff+1 one or more H atoms can be replaced by F atoms;

R40 i R41 su H, CttH2tt+1 ili C(NH)NH2; R40 and R41 are H, CttH2tt+1 or C(NH)NH2;

tt je 1, 2, 3 ili 4; tt is 1, 2, 3 or 4;

pri čemu u skupini CttH2tt+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili whereby in the group CttH2tt+1 one or more H atoms may be replaced by F atoms; or

R40 i R41 su međusobno neovisno hidroksietil, N,N-dimetilaminoetil, N,N-dietilaminoetil, pirolidinoetil, N-metilpiperazinoetil, piperazinoetil, morfolinoetil ili piperidinoetil; ili R40 and R41 are mutually independently hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or

R40 i R41 zajedno s N atomom na koji su oni povezani tvore pirolidinski, piperidinski, N-metilpiperazinski, piperazinski ili morfolinski prsten; R40 and R41 together with the N atom to which they are attached form a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring;

R42 je H ili ChhH2hh+1; R42 is H or ChhH2hh+1;

hh je 1, 2, 3 ili 4; hh is 1, 2, 3 or 4;

pri čemu u skupini ChhH2hh+1 jedan ili više H atoma može biti zamijenjeno s F atomima, kao i njihovih farmaceutski upotrebljivih soli. whereby in the group ChhH2hh+1 one or more H atoms can be replaced by F atoms, as well as their pharmaceutically usable salts.

Posve posebnu prednost daje se upotrebi spojeva koji su odabrani iz skupine koju čine: A very special preference is given to the use of compounds that are selected from the group consisting of:

1) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 1) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide;

2) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-benzolsulfonamid; 2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-benzenesulfonamide;

3) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-benzolsulfonamid; 3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-benzenesulfonamide;

4) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N,N-dimetil-benzol-sulfonamid; 4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N,N-dimethyl-benzene-sulfonamide;

5) 4-(4-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin; 5) 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline;

6) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina; 6) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid;

7) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidrosiokinolin-4-il)-N-etil-benzamid; 7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydrosioquinolin-4-yl)-N-ethyl-benzamide;

8) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-propil-benzamid; 8) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-propyl-benzamide;

9) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-N-(2-dimetilamino-etil)-benzamid; 9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-benzamide;

10) 6,8-diklor-2-metil-4-(4-morfolin-4-il-fenil)-1,2,3,4-tetrahidroizokinolin; 10) 6,8-dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;

11) [4-(6,8-diklor-2-metil-l,2/3, 4-tetrahidroizokinolin-4-il)-fenil]-dietil-amin; 11) [4-(6,8-dichloro-2-methyl-1,2/3,4-tetrahydroisoquinolin-4-yl)-phenyl]-diethylamine;

12) 6,8-diklor-2-metil-4-(4-piperidin-1-il-fenil)-1,2,3,4-tetrahidroizokinolin; 12) 6,8-dichloro-2-methyl-4-(4-piperidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;

13) 6,8-diklor-2-metil-4-(4-pirolidin-1-il-fenil)-1,2,3,4-tetrahidroizokinolin; 13) 6,8-dichloro-2-methyl-4-(4-pyrrolidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;

14) 6,8-diklor-2-metil-4-[4-(4-metil-piperazin-1-il)-fenil]-1,2,3,4-tetrahidro-izokinolin; 14) 6,8-dichloro-2-methyl-4-[4-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-isoquinoline;

15) 6,8-diklor-2-ciklopropil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 15) 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

16) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin; 16) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;

17) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-propil-urea; 17) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-propyl-urea;

18) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 18) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea;

19) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 19) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea;

20) N-[4-(6-metansulfonil-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 20) N-[4-(6-methanesulfonyl-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;

21) N-[4-(2,6,8-trimetil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 21) N-[4-(2,6,8-trimethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;

22) N-[4-(6-brom-8-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 22) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;

23) N-[4-(8-klor-2-metil-6-pirolidin-1-il-1,2,3,4-tetra-hidro-izokinolin-4-il)-fenil]-acetamid; 23) N-[4-(8-chloro-2-methyl-6-pyrrolidin-1-yl-1,2,3,4-tetra-hydro-isoquinolin-4-yl)-phenyl]-acetamide;

24) N-[4-(8-klor-2-metil-6-morfolin-4-il-1,2,3,4-tetra-hidro-izokinolin-4-il)-fenil]-acetamid; 24) N-[4-(8-chloro-2-methyl-6-morpholin-4-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;

25) N-{4-[8-klor-2-metil-6-(4-metil-piperazin-1-il)-l,2,3,4-tetrahidro-izokinolin-4-il]-fenil}-acetamid; 25) N-{4-[8-chloro-2-methyl-6-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}- acetamide;

26) N-{4-[8-klor-6-(ciklopropilmetil-amino)-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il]-fenil}-acetamid; 26) N-{4-[8-chloro-6-(cyclopropylmethyl-amino)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}-acetamide;

27) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-benzojeva kiselina; 27) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid;

28) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-N-metil-benzamid; 28) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-N-methyl-benzamide;

29) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-N-etil-2-hidroksi-benzamid; 29) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-ethyl-2-hydroxy-benzamide;

30) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-N-(2-dimetilamino)-etil)-2-hidroksi-benzamid; 30) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino)-ethyl)-2-hydroxy-benzamide;

31) N-[5-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-2-hidroksi-benzoil]-gvanidin; 31) N-[5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxy-benzoyl]-guanidine;

32) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 32) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide;

33) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin; 33) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;

34) 2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin; 34) 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;

35) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 35) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide;

36) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-butiramid; 36) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-butyramide;

37) pentanska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 37) pentanoic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

38) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 38) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide;

39) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2-dimetil-propionamid; 39) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;

40) ciklopropan-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 40) cyclopropane-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

41) ciklobutan-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 41) cyclobutane-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

42) ciklopentan-karbonska kiselina-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 42) cyclopentane-carboxylic acid-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

43) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2,2-trifluor-acetamid; 43) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2,2-trifluoroacetamide;

44) l-acetil-piperidin-4-karbonska kiselina-[4-(6,8-di-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 44) 1-acetyl-piperidine-4-carboxylic acid-[4-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide ;

45) N-(4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-nikotinamid; 45) N-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-nicotinamide;

46) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 46) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide;

47) etansulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 47) ethanesulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

48) N',N'-dimetilamino-N-[4-(6,8-diklor-2-netil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 48) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-netyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;

49) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 49) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide;

50) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-butiramid; 50) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-butyramide;

51) pentanska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 51) pentanoic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

52) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 52) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide;

53) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2-dimetil-propionamid; 53) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;

54) ciklopropankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 54) cyclopropanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

55) ciklobutankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-y))-fenil]-amid; 55) cyclobutanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl))-phenyl]-amide;

56) ciklopentankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 56) cyclopentanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

57) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2,2-trifluor-acetamid; 57) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2,2-trifluoroacetamide;

58) l-acetil-piperidin-4-karbonska kiselna-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 58) 1-acetyl-piperidin-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

59) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-nikotinamid; 59) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-nicotinamide;

60) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 60) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide;

61) etansulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 61) ethanesulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

62) N',N'-dimetilamino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 62) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;

63) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 63) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide;

64) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-butiramid; 64) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-butyramide;

65) pentanska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 65) pentanoic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

66) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 66) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide;

67) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2-dimetil-propionamid; 67) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide;

68) ciklopropankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 68) cyclopropanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

69) ciklobutankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-1zoehinoiin-4-il)-fenil]-amid; 69) cyclobutanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-1zoequinoin-4-yl)-phenyl]-amide;

70) ciklopentankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 70) cyclopentanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

71) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2,2-trifluor-acetamid; 71) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2,2-trifluoroacetamide;

72) 1-acetil-piperidin-4-karbonska kiselina-[2-(6,8-di-klor-2-metil-l,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 72) 1-acetyl-piperidine-4-carboxylic acid-[2-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide;

73) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 73) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide;

74) etan-sulfonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 74) ethane-sulfonic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

75) N',N'-dimetilamino-N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 75) N',N'-dimethylamino-N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;

76) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 76) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea;

77) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 77) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea;

78) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 78) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea;

79) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 79) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea;

80) N-{5-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilsulfamoil]-4-metil-tiazol-2-il}-acetamid; 80) N-{5-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl }-acetamide;

81) N-{5-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilsulfamoil]-4-metil-tiazol-2-il}-acetamid; 81) N-{5-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl }-acetamide;

82) l,2-dimetil-1H-imidazol-4-sulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 82) 1,2-dimethyl-1H-imidazole-4-sulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide;

83) 1,2-dimetil-1H-imidazol-4-sulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 83) 1,2-dimethyl-1H-imidazol-4-sulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide;

84) 5-klor-1,3-dimetil-1H-pirazol-4-sulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 84) 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl )-phenyl]-amide;

85) 5-klor-1,3-dimetil-1H-pirazol-4-sulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 85) 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl )-phenyl]-amide;

86) 5-brom-tiofen-2-sulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 86) 5-bromo-thiophene-2-sulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

87) 5-brom-tiofen-2-sulfonska kiselina-[3-(6,8-diklor-2-1αetil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 87) 5-bromo-thiophene-2-sulfonic acid-[3-(6,8-dichloro-2-1αethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

88) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluor-metansulfonamid; 88) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide;

89) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluor-metansulfonamid; 89) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide;

90) 2,2,2-trifluor-etansulfonska kiselina-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 90) 2,2,2-trifluoroethanesulfonic acid-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

91) 2,2,2-trifluor-etansulfonska kiselina-3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 91) 2,2,2-trifluoroethanesulfonic acid-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

92) N-etil-N'-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonil-urea; 92) N-ethyl-N'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonyl-urea;

93) 2-klor-5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonamid; 93) 2-chloro-5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;

94) 2-metil-4-fenil-1,2,3,4-tetrahidroizokinolin-8-ilamin; 94) 2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine;

95) 6,8-diklor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 95) 6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

96) 4-(8-amino-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenol; 96) 4-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenol;

97) 8-metoksi-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 97) 8-methoxy-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

98) 2-(8-amino-2-etil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenol; 98) 2-(8-amino-2-ethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenol;

99) 2-(8-amino-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenol; 99) 2-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenol;

100) 5-(8-amino-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-metoksi-fenol; 100) 5-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-methoxy-phenol;

101) 2-metil-8-nitro-4-fenil-1,2,3,4-tetrahidro-izokinolin; 101) 2-methyl-8-nitro-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

102) 4-(8-amino-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzol-1,2-diol; 102) 4-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-1,2-diol;

103) 2,8-dimetil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 103) 2,8-dimethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

104) 4-(3,4-diklor-fenil)-2-metil-1,2,3,4-tetrahidro-izokinolin; 104) 4-(3,4-dichloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinoline;

105) 4-(3,4-diklor-fenil)-2-metil-1,2,3,4-tetrahidro-izokinolin- 8-ilamin; 105) 4-(3,4-dichloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine;

106) 4-(2,4-diklor-fenil)-2-metil-1,2,3,4-tetrahidro-izokinolin-8-ilamin; 106) 4-(2,4-dichloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine;

107) 4-(3-klor-fenil)-2-metil-1,2,3,4-tetrahidroizokinolin-8-ilamin; 107) 4-(3-chloro-phenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine;

108) 2,4-dimetil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 108) 2,4-dimethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

109) 2-butil-4-fenil-1,2,3,4-tetrahidroizokinolin-8-ilamin; 109) 2-butyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine;

110 N-(2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin-8-il)-acetamid; 110 N-(2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-acetamide;

111) 7-klor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 111) 7-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

112) 8-klor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 112) 8-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

113) 2,6-dimetil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 113) 2,6-dimethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

114) 6-klor-2-metil-4-fenil-l,2f3,4-tetrahidro-izokinolin; 114) 6-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

115) 6-metoksi-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 115) 6-methoxy-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

116) 2-etil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 116) 2-ethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

117) 2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 117) 2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

118) 6,8-diklor-2-etil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 118) 6,8-dichloro-2-ethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

119) 4-(4-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin; 119) 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline;

120) 2-metil-4-fenil-6,8-bis-trifluormetil-1,2,3,4-tetrahidro-izokinolin; 120) 2-methyl-4-phenyl-6,8-bis-trifluoromethyl-1,2,3,4-tetrahydro-isoquinoline;

121) 6,8-diklor-2-1zopropil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 121) 6,8-dichloro-2-1isopropyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

122) 5,8-diklor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 122) 5,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

123) 6,8-diklor-4-(4-fluor-fenil)-2-metil-1,2,3,4-tetrahidro-izokinolin; 123) 6,8-dichloro-4-(4-fluoro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinoline;

124) 6,8-diklor-2-metil-4-p-tolil-1,2,3,4-tetrahidro-izokinolin; 124) 6,8-dichloro-2-methyl-4-p-tolyl-1,2,3,4-tetrahydro-isoquinoline;

125) 5,6-diklor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 125) 5,6-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

126) 6,7-diklor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 126) 6,7-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

127) 8-brom-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 127) 8-bromo-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

128) 6,8-diklor-4-(4-klor-fenil)-2-metil-1,2,3,4-tetrahidro-izokinolin; 128) 6,8-dichloro-4-(4-chloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinoline;

129) 6,8-diklor-2-ciklopropil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 129) 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline;

130) 2-amino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 130) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;

131) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-metilamino-acetamid; 131) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-methylamino-acetamide;

132) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-acetamid; 132) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;

133) 2-amino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-propionamid; 133) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;

134) 2-amino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-butiramid; 134) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;

135) 2,6-diamino-heksanska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin; 135) 2,6-diamino-hexanoic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline;

136) pirolidin-2-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 136) pyrrolidine-2-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

137) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izonikotinamid; 137) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isonicotinamide;

138) 1H-pirol-3-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 138) 1H-pyrrole-3-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

139) 1H-pirol-2-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 139) 1H-pyrrole-2-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

140) 1-metil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 140) 1-methyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide;

141) 1,4-dimetil-1H-pirol-2-karbonska kiselina-[4-(6,8-di-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 141) 1,4-dimethyl-1H-pyrrole-2-carboxylic acid-[4-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-amide;

142) 4-nitro-1H-pirol-2-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 142) 4-nitro-1H-pyrrole-2-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide;

143) 2,5-dimetil-1H-pirol-3-karbonska kiselina-[4-(6,8-di-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 143) 2,5-dimethyl-1H-pyrrole-3-carboxylic acid-[4-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-amide;

144) 1H-imidazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 144) 1H-imidazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

145) 1-metansulfonil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 145) 1-methanesulfonyl-piperidin-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

146) 3,5-dimetil-1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 146) 3,5-dimethyl-1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide;

147) 1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 147) 1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

148) 3-trifluormetil-1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 148) 3-trifluoromethyl-1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide ;

149) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-metilamino-acetamid; 149) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-methylamino-acetamide;

150) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-acetamid; 150) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;

151) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-propionamid; 151) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;

152) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-butiramid; 152) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;

153) 2,6-diamino-heksanska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 153) 2,6-diamino-hexanoic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

154) pirolidin-2-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 154) pyrrolidine-2-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

155) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izonikotinamid; 155) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isonicotinamide;

156) 1H-pirol-3-karbonska kiselina-3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 156) 1H-pyrrole-3-carboxylic acid-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

157) 1H-pirol-2-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 157) 1H-pyrrole-2-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

158) 1-metil-piperidin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 158) 1-methyl-piperidine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide;

159) 1,4-dimetil-1H-pirol-2-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 159) 1,4-dimethyl-1H-pyrrole-2-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide;

160) 4-nitro-1H-pirol-2-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 160) 4-nitro-1H-pyrrole-2-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide;

161) 2,5-dimetil-1H-pirol-3-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 161) 2,5-dimethyl-1H-pyrrole-3-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide;

162) 1H-imidazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 162) 1H-imidazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

163) 1-metansulfonil-piperidin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 163) 1-methanesulfonyl-piperidin-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

164) 3,5-dimetil-1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 164) 3,5-dimethyl-1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide;

165) 1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 165) 1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

166) 3-trifluormetil-1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 166) 3-trifluoromethyl-1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide ;

167) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-tiourea; 167) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;

168) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-tiourea; 168) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;

169) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-tiourea; 169) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-thiourea;

170) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dimetil-urea; 170) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;

171) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 171) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide;

172) piperidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 172) piperidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

173) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 173) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

174) pirolidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 174) pyrrolidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

175) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 175) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;

176) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 176) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea;

177) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 177) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;

178) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-furan-3-il)-urea; 178) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-furan-3-yl)-urea;

179) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-piran-4-il)-urea; 179) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-pyran-4-yl)-urea;

180) 3-t3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-metil-1-(l-metil-piperidin-4-il)-urea; 180) 3-t3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-methyl-1-(1-methyl-piperidine-4- il)-urea;

181) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-(3-dimetilamino-propil)-1-metil-urea; 181) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-(3-dimethylamino-propyl)-1-methyl- urea;

182) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-(2-dimetilamino-etil)-1-metil-urea; 182) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-(2-dimethylamino-ethyl)-1-methyl- urea;

183) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(3-dimetilamino-propil)-urea; 183) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(3-dimethylamino-propyl)-urea;

184) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-metoksi-etil)-urea; 184) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea;

185) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil)-3-piridin-3-il-urea; 185) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl)-3-pyridin-3-yl-urea;

186) l-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-piridin-4-il-urea; 186) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-pyridin-4-yl-urea;

187) 4-metil-piperazin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 187) 4-methyl-piperazine-1-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide;

188) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 188) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea;

189) 3-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-il-dimetil-urea; 189) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-yl-dimethyl-urea;

190) 3-[2-(6,8-diklor-2-metil-l,2,3,4-tetrahidroizokinolin-4-1l}-fenil]-1,1-dietil-urea; 190) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-11}-phenyl]-1,1-diethyl-urea;

191) piperidin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 191) piperidine-1-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

192) morfolin-4-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 192) morpholine-4-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

193) pirolidin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 193) pyrrolidine-1-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

194) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 194) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;

195) 4-metil-piperazin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 195) 4-methyl-piperazine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide;

196) pirolidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 196) pyrrolidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

197) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 197) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea;

198) 3-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin4-il)-fenil]-1,1-dimetil-urea; 198) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin4-yl)-phenyl]-1,1-dimethyl-urea;

199) 3-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 199) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;

200) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 200) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;

201) piperidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 201) piperidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

202) morfolin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 202) morpholine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

203) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-formamid; 203) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-formamide;

204) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amin; 204) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;

205) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3-dimetil-urea; 205) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;

206) 4-metil-piperazin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 206) 4-methyl-piperazine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide ;

207) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3,3-trimetil-urea; 207) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;

208) piperidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 208) piperidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide;

209) morfolin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 209) morpholine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide;

210) pirolidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 210) pyrrolidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide;

211) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-1-metil-urea; 211) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl- urea;

212) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3,3-dietil-1-metil-urea; 212) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3,3-diethyl-1-methyl-urea;

213) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-formamid; 213) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-formamide;

214) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amin; 214) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;

215) pirolidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 215) pyrrolidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide;

216) piperidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 216) piperidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide;

217) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-l,3,3-trimetil-urea; 217) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;

218) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3-dimetil-urea; 218) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;

219) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 219) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide;

220) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 220) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide ;

221) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-1-metil-urea; 221) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl- urea;

222) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3,3-dietil-1-metil-urea; 222) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3,3-diethyl-1-methyl-urea;

223) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 223) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester;

224) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 224) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester;

225) [2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 225) [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester;

226) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina metil ester; 226) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid methyl ester;

227) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina etil ester; 227) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid ethyl ester;

228) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina izopropil ester; 228) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid isopropyl ester;

229) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina 2,2-dimetil-propil ester; 229) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid 2,2-dimethyl-propyl ester;

230) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina metil ester; 230) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid methyl ester;

231) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina izopropil ester; 231) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid isopropyl ester;

232) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina 2,2-dimetil-propil ester; 232) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid 2,2-dimethyl-propyl ester;

233) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina etil ester; 233) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid ethyl ester;

234) (R)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamid; 234) (R)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;

235) (S)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamid; 235) (S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;

236) (R)-1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-eti1-urea; 236) (R)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;

237) (S)-1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea; 237) (S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;

238) N-[3-(6,8-difluor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 238) N-[3-(6,8-difluoro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;

239) 4-(3-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin; 239) 4-(3-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline;

240) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-hidroksi-etil)-urea; 240) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea;

241) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina etil ester; 241) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid ethyl ester;

242) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina, kao i njihovim farmacetski podnošljivim solima. 242) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid, as well as their pharmaceutically acceptable salts.

Izvanrednu i sasvim posebnu prednost daje se upotrebi spojeva koji su odabrani iz skupine koju čine: An extraordinary and very special advantage is given to the use of compounds that are selected from the group consisting of:

1) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 1) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide;

2) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonamid; 2) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide;

3) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokirtolin-4-il)-benzolsulfonamid; 3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isokirtolin-4-yl)-benzenesulfonamide;

4) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina; 4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid;

5) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-etil-benzamid; 5) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-ethyl-benzamide;

6) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-propil-benzamid; 6) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-propyl-benzamide;

7) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-N-(2-dimetilamino-etil)-benzamid; 7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-benzamide;

8) 6,8-diklor-2-metil-4-(4-morfolin-4-il-fenil)-1,2,3,4-tetrahidroizokinolin; 8) 6,8-dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline;

9) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin; 9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;

10) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 10) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea;

11) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 11) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea;

12) N-[4-(6-brom-8-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 12) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;

13) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-benzojeva kiselina; 13) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid;

14) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-N-(2-dimetilamino-etil)-2-hidroksi-benzamid; 14) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-2-hydroxy-benzamide;

15) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 15) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide;

16) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin; 16) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;

17) 2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin; 17) 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine;

18) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 18) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide;

19) l-acetil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 19) 1-acetyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

20) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 20) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide;

21) etansuifonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 21) ethanesulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

22) N',N'-dimetilamino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 22) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;

23) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 23) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide;

24) N-[3-(6,e-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-butiramid; 24) N-[3-(6,ε-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-butyramide;

25) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 25) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide;

26) ciklopropankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 26) cyclopropanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

27) ciklobutankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 27) cyclobutanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

28) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenill-2,2,2-trifluor-acetamid; 28) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl-2,2,2-trifluoroacetamide;

29) l-acetil-piperidin-4-karbonska kiselina-[3-(6,8-di-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 29) 1-acetyl-piperidine-4-carboxylic acid-[3-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide ;

30) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-nikotinamid; 30) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-nicotinamide;

31) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 31) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide;

32) etansulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 32) ethanesulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

33) N',N'-dimetilamino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 33) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide;

34) ciklopropankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 34) cyclopropanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

35) l-acetil-piperidin-4-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 35) 1-acetyl-piperidine-4-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

36) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 36) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea;

37) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 37) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea;

38) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 38) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea;

39) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 39) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea;

40) N-{5-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilsulfamoil]-4-metil-tiazol-2-il}-acetamid; 40) N-{5-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl }-acetamide;

41) l,2-dimetil-1H-imidazol-4-sulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 41) 1,2-dimethyl-1H-imidazole-4-sulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide;

42) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluor-metansulfonamid; 42) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide;

43) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluor-metansulfonamid; 43) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide;

44) N-etil-N'-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonil-urea; 44) N-ethyl-N'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonyl-urea;

45) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-acetamid; 45) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;

46) 2,6-diamino-heksanska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 46) 2,6-diamino-hexanoic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

47) 1H-pirol-3-karbonska kiselina-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 47) 1H-pyrrole-3-carboxylic acid-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

48) l-metil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 48) 1-methyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide;

49) l-metansulfonil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 49) 1-methanesulfonyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

50) 1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 50) 1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

51) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-metilamino-acetamid; 51) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-methylamino-acetamide;

52) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-acetamid; 52) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide;

53) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-propionamid; 53) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide;

54) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-butiramid; 54) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide;

55) 2,6-diamino-heksanska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 55) 2,6-diamino-hexanoic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

56) l-metil-piperidin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 56) 1-methyl-piperidine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide;

57) 1H-imidazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 57) 1H-imidazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

58) l-metansulfonil-piperidin-4-karbonska kiselina-[3-6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 58) 1-methanesulfonyl-piperidine-4-carboxylic acid-[3-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

59) 3,5-dimetil-1H-pirazoi-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 59) 3,5-dimethyl-1H-pyrazol-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide;

60) 1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 60) 1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

61) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dimetil-urea; 61) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;

62) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinoln-4-il)-fenil]-amid; 62) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinol-4-yl)-phenyl]-amide;

63) piperidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 63) piperidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

64) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 64) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

65) pirolidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 65) pyrrolidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

66) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 66) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;

67) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil-3-metil-urea; 67) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl-3-methyl-urea;

68) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil-3-(2-dimetilamino-etil)-urea; 68) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl-3-(2-dimethylamino-ethyl)-urea;

69) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-furan-3-il)-urea; 69) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-furan-3-yl)-urea;

70) l-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-piran-4-il)-urea; 70) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-pyran-4-yl)-urea;

71) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-metil-1-(l-metil-piperidin-4-il)-urea; 71) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-methyl-1-(1-methyl-piperidine-4 -yl)-urea;

72) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-(3-dimetiiamino-propil)-1-metil-urea; 72) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-(3-dimethylamino-propyl)-1-methyl- urea;

73) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-(2-dimetilamino-etil)-1-metil-urea; 73) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-(2-dimethylamino-ethyl)-1-methyl- urea;

74) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(3-dimetilamino-propil)-urea; 74) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(3-dimethylamino-propyl)-urea;

75) l-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-metoksi-etil)-urea; 75) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea;

76) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-piridin-3-il-urea; 76) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-pyridin-3-yl-urea;

77) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-piridin-4-il-urea; 77) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-pyridin-4-yl-urea;

78) 4-metil-piperazin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 78) 4-methyl-piperazine-1-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide;

79) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-metil-urea: 79) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea:

80) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 80) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;

81) 4-metil-piperazin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinoiin-4-il)-fenil]amid; 81) 4-methyl-piperazine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoin-4-yl)-phenyl]amide;

82) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 82) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea;

83) 3-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dimetil-urea; 83) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea;

84) 3-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 84) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea;

85) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 85) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea;

86) morfolin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinoiin-4-il)-fenil]-amid; 86) morpholine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoin-4-yl)-phenyl]-amide;

87) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-formamid; 87) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-formamide;

88) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amin; 88) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;

89) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-formamid; 89) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-formamide;

90) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amin; 90) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine;

91) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-l,3,3-trimetil-urea; 91) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea;

92) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3-dimetil-urea; 92) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea;

93) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2, 3, 4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 93) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide;

94) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 94) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide ;

95) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-1-metil-urea; 95) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl- urea;

96) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 96) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester;

97) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 97) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester;

98) [2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 98) [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester;

99) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina metil ester; 99) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid methyl ester;

100) (R ili S)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamid; 100) (R or S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide;

101) (R ili S)-1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea; 101) (R or S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea;

102) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-hidroksi-etil)-urea; 102) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea;

103) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina etil ester; 103) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid ethyl ester;

104 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina, kao i njihovim farmacetski podnošljivim solima. 104 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid, as well as their pharmaceutically acceptable salts.

Ako spojevi formule I imaju jedno ili više središta asimetrije, tada oni mogu imati kako S, tako također i R konfiguraciju. Spojevi mogu postojati kao optički izomeri, kao diastereomeri, kao racemati ili kao njihove smjese. If the compounds of formula I have one or more centers of asymmetry, then they can have both S and R configurations. The compounds may exist as optical isomers, as diastereomers, as racemates or as mixtures thereof.

Označeni alkilni ostaci, odnosno djelomično ili potpuno fluorirani alkil ostaci mogu imati ravan lanac ili oni mogu također biti razgranati. Skupine CaH2a-1, odnosno njihovi analozi do CyyH2yy-1 znače odgovarajuće alkenile, cikloalkile, cikloalkil-alkile ili alkil-cikloalkile. The labeled alkyl residues, i.e. partially or fully fluorinated alkyl residues, can have a straight chain or they can also be branched. The groups CaH2a-1, i.e. their analogues up to CyyH2yy-1 mean the corresponding alkenyl, cycloalkyl, cycloalkyl-alkyl or alkyl-cycloalkyl.

Kao heteroarili u obzir posebno dolaze 2- ili 3-tienil, 2- ili 3-furil, 1-, 2- ili 3-pirolil, l-, 2-, 4-ili 5-imidazolil, 1-, 3-, 4- ili 5-pirazolil, 1,2,3-tri-azol-1-, -4- ili 5-il, l,2,4-triazol-1-, -3- ili -5-il, 1-ili 5-tetrazolil, 2-, 4- ili 5-oksazolil, 3-, 4- ili 5-1zoksazolil, 1,2,3-oksadiazol-4- ili 5-il, l,2,4-oksa-di-azol-3- ili 5-il, 1,3,4-oksadiazol-2-il ili 5-il, 2-, 4-ili 5-tiazolil, 3-, 4- ili 5-izotiazolil, l, 3, 4-tiadiazol-2- ili -5-il, l,2,4-tiadiazol-3- ili 5-il, 1,2,3-tiadiazol-4- ili 5-il, 2-, 3- ili 4-piridil, 2-, 4-, 5- ili 6-pirimidinil, 3- ili 4-piridazinil, pirazinil, 1-, 2-, 3-, 4-, 5-, 6- ili 7-1ndolil, l-, 2-, 4- ili 5-benzimidazolil, 1-, 3-, 4-, 5-, 6- ili 7-indazolil, 2-, 3-, 4-, 5-, 6-, 7-ili 8-kinolil, l-, 3-, 4-, 5-, 6-, 7- ili 8-izokinolinil, 2-, 4-, 5-, 6-, 7- ili 8-kinazolinil, 3-, 4-, 5-, 6-, 7-ili 8-kinolinil, 2-, 3-, 5-, 6-, 7- ili 8-kinoksalinil, 1-, 4-, 5-, 6-, 7- ili 8-ftalazinil. Obuhvaćeni su, nadalje, odgovarajući N oksidi ovih spojeva, dakle npr. l-oksi-2-, 3- ili 4-piridil. As heteroaryls, 2- or 3-thienyl, 2- or 3-furyl, 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imidazolyl, 1-, 3-, 4 - or 5-pyrazolyl, 1,2,3-tri-azol-1-, -4- or 5-yl, 1,2,4-triazol-1-, -3- or -5-yl, 1-or 5-tetrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-1oxazolyl, 1,2,3-oxadiazol-4- or 5-yl, 1,2,4-oxa-diazole -3- or 5-yl, 1,3,4-oxadiazol-2-yl or 5-yl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 1, 3, 4- thiadiazol-2- or -5-yl, 1,2,4-thiadiazol-3- or 5-yl, 1,2,3-thiadiazol-4- or 5-yl, 2-, 3- or 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, 3- or 4-pyridazinyl, pyrazinyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl, 1-, 2-, 4- or 5-benzimidazolyl, 1-, 3-, 4-, 5-, 6- or 7-indazolyl, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl, 1- , 3-, 4-, 5-, 6-, 7- or 8-isoquinolinyl, 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl, 3-, 4-, 5-, 6- , 7-or 8-quinolinyl, 2-, 3-, 5-, 6-, 7- or 8-quinoxalinyl, 1-, 4-, 5-, 6-, 7- or 8-phthalazinyl. Furthermore, the corresponding N oxides of these compounds are covered, so for example 1-oxy-2-, 3- or 4-pyridyl.

Pri tome, prednost se daje petero- ili šesteročlanim heterociklima. Here, preference is given to five- or six-membered heterocycles.

Posebnu prednost imaju heterocikli imidazolil, pirazolil, pirolil, triazolil, tetrazolil, tiazolil i oksazolil. Particular preference is given to the heterocycles imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl and oxazolyl.

Kao CH2 skupine smatraju se također i terminalne skupine i one se tada gledaju kao CH2-H skupine. Terminal groups are also considered as CH2 groups and they are then viewed as CH2-H groups.

Opisat će se također i postupci za proizvodnju upotrijebljenih spojeva. The procedures for the production of the compounds used will also be described.

Tako se ovdje opisane tvari mogu proizvesti počevši od benzilamiskih predkurzora IV. Oni se, sa svoje strane, ako nisu komercijalno raspoloživi, mogu sintetizirati standardnim postupcima iz odgovarajućih benzil klorida ili bromida. Thus, the substances described here can be produced starting from the benzylic precursors IV. They, for their part, if they are not commercially available, can be synthesized by standard procedures from the corresponding benzyl chlorides or bromides.

[image] [image]

Tako dobivene benzilamine IV alkilira se s odgovarajuće supstituiranim alfa-bromacetofenonskim spojem V na način koji je stručnjaku poznat. The thus obtained benzylamine IV is alkylated with a suitably substituted alpha-bromoacetophenone compound V in a manner known to the expert.

[image] [image]

alfa-bromacetofenonski spojevi V mogu se dobiti iz odgovarajućih acetofenonskih predkurzora postupcima bromiranja koji su poznati iz literature. Redukcijom karbonilne skupine u VI i zatim ciklizacijom odgovarajućeg alkohola VII s kiselim katalizatorom (usp. Tetrahedron Lett.; 1989, 30, 5837; Org. Prep. Proced. Int.; 1995, 27, 513) poznatim se postupkom može dobiti željeni tetrahidro-izokinolin I. alpha-bromoacetophenone compounds V can be obtained from the corresponding acetophenone precursors by bromination procedures known from the literature. By reducing the carbonyl group in VI and then cyclizing the corresponding alcohol VII with an acid catalyst (cf. Tetrahedron Lett.; 1989, 30, 5837; Org. Prep. Proced. Int.; 1995, 27, 513) the desired tetrahydro- isoquinoline I.

[image] [image]

U slučaju kad je R6 različit od H, željeni spojevi formule I mogu se proizvesti npr. iz jodida VIII zamjenom halogenog s metalom i zatim nukleofilnim povezivanjem intermedijarnog litijevog organskog spoja na karbonilnu skupinu (usp. Chem. Pharm. Buli.; 1995, 43, 1543). In the case where R6 is different from H, the desired compounds of formula I can be produced, for example, from iodide VIII by replacing the halogen with a metal and then by nucleophilic coupling of the intermediate organolithium compound to the carbonyl group (cf. Chem. Pharm. Buli.; 1995, 43, 1543).

[image] [image]

Tercijarni alkoholi, koji pri tome nastaju, mogu se poznatim metodama prevesti u daljnje derivate. Tertiary alcohols, which are formed in the process, can be converted into further derivatives using known methods.

Za proizvodnju alkilno razgranatih analoga (I) odgovarajući ester difeniloctene kiseline X se alkilira u alfa položaju poznatim metodama. Željeni proizvodi XI mogu se standardnim postupcima prevesti u odgovarajuće amide XII, koji se analogno Pictet-Spenglerovoj reakciji prevedu u željene tetrahidroizokinoline I (usp. Tetrahedron; 1987, 43, 439; Chem. Pharm. Buli.; 1985, 33, 340). For the production of alkyl branched analogs (I), the corresponding diphenylacetic acid ester X is alkylated in the alpha position by known methods. The desired products XI can be converted by standard procedures into the corresponding amides XII, which are converted analogously to the Pictet-Spengler reaction into the desired tetrahydroisoquinolines I (cf. Tetrahedron; 1987, 43, 439; Chem. Pharm. Buli.; 1985, 33, 340).

[image] [image]

U objavljenim dokumentima WO 01 32 624 i W0 01 32 625 opisani su spojevi tipa I kao inhibitori ponovnog vezanja (e. reuptake) norepinefrina, dopamina i serotonina. U svakom slučaju, u tim patentnim prijavama su zaštićeni spojevi u kojima R1 i R2 smiju biti isključivo H. Kod spojeva prema izumu se je prije sve pokazalo da barem za R2 mora vrijediti uvjet da je on različit od H. Nadalje, pomoću jednog primjera spoja prema izumu moglo se je pokazati da se za ove spojeve ne mogu dokazati nikakva inhibitorska svojstva na spomenutim receptorima, tako da se opisani spojevi kako strukturno, tako također i po njihovim farmakološkim svojstvima razlikuju od spojeva opisanih u spomenutim patentnim prijavama. In the published documents WO 01 32 624 and WO 01 32 625, compounds of type I are described as reuptake inhibitors of norepinephrine, dopamine and serotonin. In any case, compounds in which R1 and R2 may be exclusively H are protected in these patent applications. In the compounds according to the invention, it was first of all shown that at least R2 must be different from H. Furthermore, using one example of a compound according to the invention, it was possible to show that no inhibitory properties can be demonstrated for these compounds on the mentioned receptors, so that the described compounds differ both structurally and also in terms of their pharmacological properties from the compounds described in the mentioned patent applications.

Spojevi tipa I opisani su, nadalje, u objavljenom spisu EP 11 13 007 kao agonisti i antagonisti estrogena. Moglo se je pokazati da spojevi prema izumu nemaju nikakvo djelovanje na navedenim receptorima, tako da i ovdje također strukturne razlike spojeva prema izumu imaju za posljedicu jasno drugačija farmakološka svojstvima. Compounds of type I are further described in the published document EP 11 13 007 as estrogen agonists and antagonists. It could be shown that the compounds according to the invention have no effect on the mentioned receptors, so that here too the structural differences of the compounds according to the invention result in clearly different pharmacological properties.

Moglo se je pokazati da spojevi formule I predstavljaju istaknute inhibitore izmjenjivača natrij -vodika (NHE), posebno podtipa 3 izmjenjivača natri-vodika (NHE3). The compounds of formula I have been shown to be prominent inhibitors of the sodium-hydrogen exchanger (NHE), especially the sodium-hydrogen exchanger subtype 3 (NHE3).

Zbog tih svojstava ovi su spojevi prikladni za liječenje bolesti koje su uzrokovane s manjkom kisika. Zbog svojih farmakoloških svojstava ovi spojevi su izvanredno prikladni kao antiaritmijski lijekovi s kardioprotektivnom komponentom za profilaksu infarkta i za liječenje infarkta, kao i za liječenje angine pektoris, pri čemu oni također preventivno inhibiraju ili jako umanjuju patofiziološke procese kod nastanka ishemijski uzrokovanih ozljeda, posebno kod ishemijski uzrokovanih srčanih arhitmija. Zbog njihovih zaštitnih učinaka protiv patoloških hipoksičnih i ishemijskih stanja, zbog inhibicije mehanizma stanične izmjene Na+/H+, spojevi formule I prema izumu mogu se upotrijebiti za liječenje svih akutnih ili kroničnih ozljeda uzrokovanih s ishemijom ili time primarno ili sekundarno uzrokovanih bolesti. To se odnosi na njihovu upotreba kao lijekova za operativne zahvate, npr. kod transplantacija organa, pri čemu se ovi spojevi mogu upotrijebiti kako za zaštitu organa u darovatelju prije i tijekom uzimanja organa, za zaštitu organa, na primjer, pri obradi s fiziološkim tekućinama ili tijekom njihovog odlaganja u fiziološke otopine, kao također i kod prenošenja u organizam primatelja. Ovi spojevi su također dragocjeni lijekovi protektivnog djelovanja kod provedbe angioplastičnih operativnih zahvata, na primjer, na srcu, kao također i na perifernim krvnim žilama. U skladu s njihovim protektivnim djelovanjem protiv ischemijski uzrokovanih ozljeda, ovi su spojevi također prikladni kao lijekovi za liječenje ishemija živčanog sistema, posebno CNS-a, pri čemu su oni prikladni, npr. za liječenje udara kapi ili moždanog edema. Nadalje, spojevi formule I prema izumu mogu se također upotrijebiti za liječenje nekih oblika šoka, kao što su na primjer alergijski, kardiogeni, hipovolemijski i bakterijski šokovi. Because of these properties, these compounds are suitable for the treatment of diseases caused by a lack of oxygen. Due to their pharmacological properties, these compounds are extremely suitable as antiarrhythmic drugs with a cardioprotective component for the prophylaxis of heart attacks and for the treatment of heart attacks, as well as for the treatment of angina pectoris, whereby they also prevent or greatly reduce pathophysiological processes in the occurrence of ischemic injuries, especially in ischemic caused by cardiac arrhythmias. Due to their protective effects against pathological hypoxic and ischemic conditions, due to the inhibition of the cellular Na+/H+ exchange mechanism, the compounds of formula I according to the invention can be used for the treatment of all acute or chronic injuries caused by ischemia or diseases caused by it primarily or secondarily. This refers to their use as drugs for surgical procedures, e.g. in organ transplants, where these compounds can be used both to protect organs in the donor before and during organ retrieval, to protect organs, for example, during treatment with physiological fluids or during their disposal in physiological solutions, as well as during their transfer to the recipient's body. These compounds are also valuable drugs with a protective effect in the implementation of angioplasty operations, for example, on the heart, as well as on peripheral blood vessels. In accordance with their protective action against ischemia-induced injuries, these compounds are also suitable as drugs for the treatment of ischemia of the nervous system, especially of the CNS, where they are suitable, for example, for the treatment of stroke or cerebral edema. Furthermore, the compounds of formula I according to the invention can also be used to treat some forms of shock, such as, for example, allergic, cardiogenic, hypovolemic and bacterial shocks.

Nadalje, ovi spojevi uzrokuju poboljšanje funkcije disanja i zbog toga se oni mogu upotrijebiti za liječenje stanja disanja u slijedećim kliničkim stanjima i bolestima: poremećena središnja funkcija disanja (npr. središnje apnoje spavanja, iznenadna smrt djeteta, postoperativna hipoksija), muskularno uvjetovani poremećaji disana, poremećaji disanja nakon dugotrajnog umjetnog disanja, poremećaji disanja kod prilagodbe u visinskim područjima, opstrukcijski i miješani oblik apnoje spavanja, akutne i kronične bolesti pluća s hipoksijom i hiperkapnijom. Furthermore, these compounds cause an improvement of the respiratory function and therefore they can be used to treat respiratory conditions in the following clinical conditions and diseases: impaired central respiratory function (eg central sleep apnea, sudden infant death, postoperative hypoxia), muscular respiratory disorders, breathing disorders after long-term artificial respiration, breathing disorders during adaptation in high altitude areas, obstructive and mixed form of sleep apnea, acute and chronic lung diseases with hypoxia and hypercapnia.

Dodatno, ovi spojevi povisuju tonus mišića gornjih dišnih puteva, tako da se može potisnuti hrkanje. In addition, these compounds increase the tone of the muscles of the upper respiratory tract, so that snoring can be suppressed.

Kombinacija NHE inhibitora s inhibitorom ugljiko-anhidraze (npr. acetazolamid), pri čemu potonji doprinosi metaboličkoj acidozi i time već povisuje sposobnost disanja, pokazala se je korisnom zbog pojačanog učinka i smanjene upotrebe aktivne tvari. The combination of an NHE inhibitor with a carbonic anhydrase inhibitor (e.g. acetazolamide), whereby the latter contributes to metabolic acidosis and thus already increases the ability to breathe, has been shown to be beneficial due to enhanced effect and reduced use of the active substance.

Pokazalo se je da upotrijebljeni spojevi prema izumu imaju blagi učinak čišćenja i stoga se mogu korisno upotrijebiti kao sredstva za čišćenje ili kod opasnog začepljenja crijeva, pri čemu je posebno povoljno sprečavanje ishemijskih ozljeda koje se pojavljuju sa začepljenjima u području crijeva. It has been shown that the compounds used according to the invention have a mild cleaning effect and can therefore be usefully used as cleaning agents or in case of dangerous intestinal obstruction, where it is particularly advantageous to prevent ischemic injuries that occur with obstructions in the intestinal area.

Nadalje, postoji mogućnost sprečavanja stvaranja žučnog kamenca. Furthermore, there is a possibility of preventing the formation of gallstones.

Spojevi formule I upotrijebljeni prema izumu odlikuju se, nadalje, s jakim inhibicijskim učinkom na proliferaciju stanica, na primjer na proliferaciju fibroblasta i na proliferaciju glatkih mišićnih stanica krvnih žila. Zbog toga spojevi formule I dolaze u obzir kao dragocjena terapeutska sredstva za bolesti kod kojih primarni ili sekundarni uzrok predstavlja proliferacija stanica, i oni se stoga mogu upotrijebiti kao antiaterosklerotici, sredstva protiv dijabetičkih kasnih komplikacija, bolesti raka, fibroznih oboljenja kao što je plućna fibroza, jetrena fibroza ili bubrežna fibroza, hipertrofije i hiperplazije organa, posebno kod hiperplazije, odnosno hipertrofije prostate. The compounds of formula I used according to the invention are furthermore characterized by a strong inhibitory effect on cell proliferation, for example on the proliferation of fibroblasts and on the proliferation of smooth muscle cells of blood vessels. Therefore, the compounds of formula I come into consideration as valuable therapeutic agents for diseases in which the primary or secondary cause is cell proliferation, and they can therefore be used as antiatherosclerotics, agents against diabetic late complications, cancer diseases, fibrotic diseases such as pulmonary fibrosis, liver fibrosis or renal fibrosis, organ hypertrophy and hyperplasia, especially hyperplasia or hypertrophy of the prostate.

Spojevi upotrijebljeni prema izumu su učinkoviti inhibitori staničnih antiportera natrij-protona {Na/H-1zmjenjivači) koji su kod brojnih oboljenja (esencijalna hipertonije, ateroskleroze, dijabetesa itd.) također povišeni i u takovim stanicama koje su lako dostupne za mjerenja, kao na primjer u eritrocitima, trombocitima ili u leukocitima. Spojevi upotrijebljeni prema izumu prikladni su stoga kao istaknuto i jednostavno znanstveno sredstvo, na primjer, za upotrebu kao dijagnostici za utvrđivanje i razlikovanje određenih oblika hipertonije, ali također i ateroskleroze, dijabetesa, proliferativnih oboljenja, itd. Nadalje, spojevi formule I prikladni su za preventivnu terapiju za sprečavanje geneze visokog krvnog tlaka, na primjer esencijalne hipertonije. The compounds used according to the invention are effective inhibitors of cellular sodium-proton antiporters (Na/H-1 exchangers) which, in numerous diseases (essential hypertension, atherosclerosis, diabetes, etc.) are also elevated in such cells that are easily accessible for measurements, such as for example in erythrocytes, platelets or in leukocytes. The compounds used according to the invention are therefore suitable as a distinguished and simple scientific tool, for example, for use as a diagnostic to determine and differentiate certain forms of hypertension, but also atherosclerosis, diabetes, proliferative diseases, etc. Furthermore, the compounds of formula I are suitable for preventive therapy to prevent the genesis of high blood pressure, for example essential hypertension.

Osim toga, pronađeno je da NHE inhibitori pokazuju povoljan utjecaj na serumske lipoproteine. Općenito je priznato da za nastajanje arteriosklerotičnih promjena krvnih žila, posebno koronarnih srčanih bolesti, bitan faktor rizika predstavlja previsoka vrijednost masnoće u krvi, takozvana hiperlipoproteinemija. Zbog toga za profilaksu i regresiju aterosklerotičnih promjena smanjenje povišenih lipoproteina u serumu ima izvanredan značaj. Spojevi upotrijebljeni prema izumu mogu se stoga upotrijebiti za profilaksu i za regresiju aterosklerotičnih promjena, pri čemu oni isključuju kauzalni faktor rizika. S tom zaštitom krvnih žila od sindroma endotelne disfunkcije, spojevi formule I su dragocjeni lijek za prevenciju i za liječenje koronarnih spasmi krvnih žila, aterogeneze i ateroskleroze, hipertrofije lijeve pretklijetke i dilatirajuće kardiomiopatije, i tromboznih oboljenja. In addition, NHE inhibitors have been found to have a beneficial effect on serum lipoproteins. It is generally recognized that an important risk factor for the development of arteriosclerotic changes in blood vessels, especially coronary heart disease, is an excessively high value of fat in the blood, so-called hyperlipoproteinemia. Therefore, for the prophylaxis and regression of atherosclerotic changes, the reduction of elevated lipoproteins in the serum is of extraordinary importance. The compounds used according to the invention can therefore be used for prophylaxis and for the regression of atherosclerotic changes, whereby they exclude the causal risk factor. With this protection of blood vessels from endothelial dysfunction syndrome, the compounds of formula I are a valuable drug for the prevention and treatment of coronary spasms of blood vessels, atherogenesis and atherosclerosis, left atrial hypertrophy and dilated cardiomyopathy, and thrombotic diseases.

Zbog toga se navedeni spojevi korisno upotrebljavaju za proizvodnju lijeka za prevenciju i liječenje apnoja spavanja i poremećaja disanja uzrokovanih s mišićima; za proizvodnju lijeka za prevenciju i liječenje hrkanja; za proizvodnju lijeka za smanjenje krvnog tlaka; za proizvodnju lijeka za prevenciju i liječenje oboljenja uzrokovanih s ishemijom i reperfuzijom središenjih i perifernih organa kao što je akutno otkazivanje bubrega, udar kapi, endogena stanja šoka, crijevne bolesti, itd.; za proizvodnju lijeka za liječenje diabetičkih kasnih ozljeda i kroničnih bolesti bubrega, posebno svih upala bubrega (nefritide), koje su povezane s povećanim izlučivanje proteina/albumina; za proizvodnju lijeka za liječenje napada ektoparazita u humanoj medicini i veterini; za proizvodnju lijeka za liječenje navedenih tegoba u kombinaciji s tvarima koje snizuju krvni tlak, ponajprije s inhibitorima enzima koji pretvara angiotenzin (e. Angiotensin Converting Enzime (AGE) inhibitori) s diureticima i salureticima kao što su furosemid, hidroklortiazid, pseudoaldosteron antagonisti i aldosteron-antagonisti; s modulatorima adenozin receptora, posebno s aktivatorima adenozin receptora (A2 agonisti); i s angiotenzin receptor antagonistima. For this reason, the mentioned compounds are usefully used for the production of medicine for the prevention and treatment of sleep apnea and breathing disorders caused by muscles; for the production of medicine for the prevention and treatment of snoring; for the production of blood pressure lowering medicine; for the production of medicine for the prevention and treatment of diseases caused by ischemia and reperfusion of central and peripheral organs, such as acute kidney failure, stroke, endogenous shock conditions, intestinal diseases, etc.; for the production of a drug for the treatment of diabetic late injuries and chronic kidney diseases, especially all inflammation of the kidneys (nephritis), which are associated with increased excretion of protein/albumin; for the production of a drug for the treatment of ectoparasite attacks in human medicine and veterinary medicine; for the production of a drug for the treatment of the mentioned complaints in combination with substances that lower blood pressure, primarily with inhibitors of the enzyme that converts angiotensin (e. Angiotensin Converting Enzyme (AGE) inhibitors) with diuretics and saluretics such as furosemide, hydrochlorothiazide, pseudoaldosterone antagonists and aldosterone- antagonists; with adenosine receptor modulators, especially adenosine receptor activators (A2 agonists); and with angiotensin receptor antagonists.

Zahtjeva se davanje inhibitora izmjene natrij-protona formule I kao novih lijekova za smanjenje povišene masnoće u krvi, kao također i kombinacije inhibitora izmjene natrij-protona s lijekovima koji imaju djelovanje u smislu sniženja krvnog tlaka i/ili lijekova koji djeluju hipolipidemijski. The administration of sodium-proton exchange inhibitors of formula I as new drugs for reducing elevated blood fat is requested, as well as combinations of sodium-proton exchange inhibitors with blood pressure-lowering drugs and/or hypolipidemic drugs.

Pri tome, lijekovi koji sadrže spoj I mogu se aplicirati oralno, parenteralno, intravenski, rektalno, transdermalno ili inhalacijom, pri čemu aplikacija kojoj se daje prednost ovisi o pojavnoj slici bolesti. Pri tome, spojevi I se mogu u primjeni dati sami ili zajedno s galenskim pomoćnim tvarima, i to kako u veterini, tako također i u humanoj medicini. In this case, drugs containing compound I can be administered orally, parenterally, intravenously, rectally, transdermally or by inhalation, the application being preferred depending on the appearance of the disease. In addition, compounds I can be administered alone or together with galenic excipients, both in veterinary medicine and in human medicine.

Stručnjaku su na osnovi njegovog stručnog znanja poznate pomoćne tvari prikladne za željenu formulaciju lijeka. Osim otapala, sredstava za tvorbu gela, podloga za čepiće, pomoćnih tvari za tablete i drugih nosača aktivnih tvari, mogu se upotrijebiti, na primjer, i antioksidanti, sredstva za dispergiranje, emulgatori, sredstva protiv pjene, sredstva za korekciju okusa, konzervansi, sredstva za pospješivanje otapanja ili bojila. Excipients suitable for the desired drug formulation are known to the expert based on his professional knowledge. In addition to solvents, gel formers, suppository bases, tablet excipients and other carriers of active substances, for example, antioxidants, dispersing agents, emulsifiers, antifoam agents, flavor correctors, preservatives, to promote dissolution or dyes.

Za oralne oblike primjene aktivni spojevi se pomiješaju s dodatnim tvarima koje su prikladne za tu svrhu, kao što su nosači, stabilizatori ili inertna sredstva za razrjeđivanje i uobičajenim postupcima se dovedu u oblik koji je prikladan za aplikaciju, kao što su tablete, dražeje, kapsule, vodene, alkoholne ili uljne otopine. Kao inertni nosači mogu se upotrijebiti npr. guma arabika, magnezijev oksid, magnezijev karbonat, kalijev fosfat, mliječni šećer, glukoza ili škrob, posebno kukuruzni škrob. Pri tome, pripravak se može izraditi suhim ili također mokrim postupkom granuliranja. Kao uljni nosači ili kao otapala u obzir dolaze, na primjer, biljna ili životinjska ulja, kao što je suncokretovo ulje ili riblje jetreno ulje. For oral forms of administration, the active compounds are mixed with additional substances that are suitable for this purpose, such as carriers, stabilizers or inert diluents, and are brought into a form that is suitable for application, such as tablets, dragees, capsules, by usual procedures. , aqueous, alcoholic or oily solutions. Gum arabic, magnesium oxide, magnesium carbonate, potassium phosphate, milk sugar, glucose or starch, especially corn starch, can be used as inert carriers. At the same time, the preparation can be made by a dry or also a wet granulation process. Suitable oil carriers or solvents are, for example, vegetable or animal oils, such as sunflower oil or fish liver oil.

Aktivni spojevi koji se upotrebljavaju za supkutanu ili intravensku aplikaciju mogu se dovesti u otopine, suspenzije ili emulzije, po želji, s uobičajenim tvarima kao što su sredstva za pospješivanje otapanja, emulgatori ili druge pomoćne tvari. Kao otapala u obzir dolaze npr. : voda, fiziološka otopine kuhinjske soli ili alkoholi, npr. etanol, propanol, glicerin, a osim toga također i otopine šećera kao otopine glukoze ili manita, ili također mješavine različitih navedenih otapala Active compounds used for subcutaneous or intravenous administration can be brought into solutions, suspensions or emulsions, if desired, with the usual substances such as solubilizers, emulsifiers or other auxiliary substances. Suitable solvents include, for example: water, physiological solutions of table salt or alcohols, e.g. ethanol, propanol, glycerine, and in addition also sugar solutions such as glucose or mannitol solutions, or also mixtures of the various mentioned solvents

Kao farmaceutske formulacije za davanje u obliku aerosola ili spreja prikladne su otopine, suspenzije ili emulzije aktivne tvari formule I u farmaceutski nedvojbenom otapalu, kao što je to posebno etanol ili voda, ili mješavina takovih otapala. Solutions, suspensions or emulsions of the active substance of formula I in a pharmaceutically acceptable solvent, such as in particular ethanol or water, or a mixture of such solvents, are suitable as pharmaceutical formulations for administration in the form of an aerosol or spray.

Formulacija prema potrebi može također sadržavati i druge farmaceutske pomoćne tvari, kao što su to tenzidi, emulgatori i stabilizatori, kao i potisni plin. Takav pripravak sadrži aktivnu tvar obično koncentracijom od približno 0,1 do 10, naročito od pribl. 0,3 do 3 mas. %. If necessary, the formulation may also contain other pharmaceutical excipients, such as surfactants, emulsifiers and stabilizers, as well as propellant gas. Such a preparation contains an active substance usually in a concentration of approximately 0.1 to 10, especially from approx. 0.3 to 3 wt. %.

Doziranje i učestalost davanje aktivne tvari formule I, koju se želi aplicirati, ovisi o jačini i trajanju djelovanja upotrijebljenog spoja; osim toga, to također ovisi i o vrsti i jačini bolesti koju se želi liječiti, kao i o spolu, starosti, težini i pojedinačnoj reakciji liječenog sisavca. The dosage and frequency of administration of the active substance of formula I, which is intended to be applied, depends on the strength and duration of action of the compound used; in addition, it also depends on the type and severity of the disease to be treated, as well as on the sex, age, weight and individual reaction of the treated mammal.

U prosjeku, dnevna doza spoja formule I za pacijenta teškog pribl. 75 kg iznosi najmanje 0,001 mg/kg, ponajprije 0,01 mg/kg, do najviše 10 mg/kg, ponajprije 1 mg/kg tjelesne težine. Kod akutnog izbijanja bolesti, eventualno neposredno nakon preživjelog srčanog infarkta, mogu biti također potrebne još viša, a prije svega učestalija doziranja, npr. do 4 pojedinačne doze dnevno. Posebno kod i. v. aplikacije, eventualno kod pacijenta s infarktom na intenzivnoj njezi, može biti potrebno i do 200 mg dnevno. On average, the daily dose of the compound of formula I for a patient with severe approx. 75 kg is at least 0.001 mg/kg, preferably 0.01 mg/kg, up to a maximum of 10 mg/kg, preferably 1 mg/kg of body weight. In the case of an acute outbreak of the disease, possibly immediately after surviving a heart attack, even higher and above all more frequent dosages may be necessary, for example up to 4 individual doses per day. Especially with i.v. application, possibly in a patient with a heart attack in intensive care, up to 200 mg per day may be necessary.

Opis pokusa i primjeri Description of experiments and examples

Popis upotrijebljenih kratica List of abbreviations used

Rt vrijeme retencije, Rt retention time,

TFA trifluoroctena kiselina, TFA trifluoroacetic acid,

HPLC (e. High Performance Liguid Chromatography) visokoučinska tekućinska kromatografija, HPLC (e. High Performance Liquid Chromatography) high performance liquid chromatography,

eq ekvivalent, eq equivalent,

LCMS (e. Liguid Chromatografy Mass Spectroscopy), masena spektroskopija tekućinske kromatografije, LCMS (e. Liguid Chromatografy Mass Spectroscopy), liquid chromatography mass spectroscopy,

MS (e. Mass Spectroscopy), masena spektroskopija, MS (e. Mass Spectroscopy), mass spectroscopy,

CI kemijska ionizacija, CI chemical ionization,

RT sobna temperatura, RT room temperature,

THF tetrahidrofuran, THF tetrahydrofuran,

TOTU O-[(etoksikarbonil}-cijanometilenamino]-N,N,N',N'-tetrametiluronijev tetrafluorborat, TOTU O-[(ethoxycarbonyl}-cyanomethyleneamino]-N,N,N',N'-tetramethyluronium tetrafluoroborate,

DMSO dimetilsulfoksid, abs. apsolutno, Zers. raspadanje, DMSO dimethylsulfoxide, abs. absolutely, Zers. decomposition,

DMF dimetilformamid. DMF dimethylformamide.

Općenito In general

Vremena retencije (Rt) koja se navode u nastavku odnose se na LCMS mjerenja sa slijedećim parametrima: The retention times (Rt) listed below refer to LCMS measurements with the following parameters:

Metoda A: Method A:

stacionarna faza: Merck Purospher 3μ 2 x 55 mm, stationary phase: Merck Purospher 3μ 2 x 55 mm,

mobilna faza: 95% H2O (0,05% TFA) → 95% acetonitril; mobile phase: 95% H2O (0.05% TFA) → 95% acetonitrile;

4 min; 95% acetonitril; 1,5 min → 5% acetonitril; l min; 0,5 ml/min, 30°C. 4 minutes; 95% acetonitrile; 1.5 min → 5% acetonitrile; l min; 0.5 ml/min, 30°C.

Metoda B: Method B:

stacionarna faza: Merck Purospher 3μ 2 x 55 mm, stationary phase: Merck Purospher 3μ 2 x 55 mm,

mobilna faza: O min 90% H2O (0,05% TFA) 2,5 min 95% acetonitril; 95% acetonitril do 3,3 min; 10% acetonitril 3,4 min; l ml/min. mobile phase: O min 90% H2O (0.05% TFA) 2.5 min 95% acetonitrile; 95% acetonitrile up to 3.3 min; 10% acetonitrile 3.4 min; l ml/min.

Metode B1: Methods B1:

stacionarna faza: YMC, J'sphere ODS H80 4μ 2 x 20 mm, stationary phase: YMC, J'sphere ODS H80 4μ 2 x 20 mm,

mobilna faza: 0 min 90% H2O (0,05% TFA) 1,9 min 95% acetonitril; 95% acetonitril do 2,4 min; 10% acetonitril 2,45 min; l ml/min. mobile phase: 0 min 90% H2O (0.05% TFA) 1.9 min 95% acetonitrile; 95% acetonitrile up to 2.4 min; 10% acetonitrile 2.45 min; l ml/min.

Metode C: Methods C:

štationarna faza: Merck LiChroCart 55-2 Purospher STAR RP 18e stationary phase: Merck LiChroCart 55-2 Purospher STAR RP 18e

otapalo: solvent:

otapalo A: acetonitril/voda 90:10 + 0,5% HCOOH solvent A: acetonitrile/water 90:10 + 0.5% HCOOH

otapalo B: acetonitril/voda 10:90 + 0,5% HCOOH solvent B: acetonitrile/water 10:90 + 0.5% HCOOH

protok: 0,75 ml/min flow rate: 0.75 ml/min

[image] vrijeme zaustavljanja: 6,20 min [image] stopping time: 6.20 min

temperatura: 40CC temperature: 40C

Metode D: Methods D:

stacionarna faza: Merck RP18 Purospher Star, 55 x 2 mm, veličina zrna 3μ stationary phase: Merck RP18 Purospher Star, 55 x 2 mm, grain size 3μ

otapalo: solvent:

otapalo A: acetonitril + 0,08% HCOOH solvent A: acetonitrile + 0.08% HCOOH

otapalo B: voda + 0,1% HCOOH solvent B: water + 0.1% HCOOH

protok: 0,45 ml/min flow rate: 0.45 ml/min

[image] temperatura: sobna temperatura. [image] temperature: room temperature.

Primjer 1 Example 1

N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]acetamid N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]acetamide

[image] [image]

Intermedijat 1 Intermediate 1

2,4-diklorbenzil-metil-amin je proizveden postupkom koji je poznat iz literature (J. Med. Chem.; 1984, 27, 1111). 2,4-dichlorobenzyl-methyl-amine was produced by a process known from the literature (J. Med. Chem.; 1984, 27, 1111).

Intermedijat 2 Intermediate 2

N-[4-(2-brom-acetil)-fenil]-acetamid se sintetizira bromiranjem N-(4-acetil-fenil)acetamida na način koji je stručnjaku poznat. N-[4-(2-bromo-acetyl)-phenyl]-acetamide is synthesized by brominating N-(4-acetyl-phenyl)acetamide in a manner known to a person skilled in the art.

Polazni spoj (0,256 mol) se stavi u 300 ml octene kiseline i pri 60°C se dokaplje otopinu od 39,9 g broma (1,0 ekv.) u 60 ml octene kiseline. Nakon 1,5 h se pusti ohladiti na sobnu temperaturu i reakcijsku smjesu se doda na l l ledene vode. Talog se odsisa, ispere s vodom i osuši, pri čemu se izolira 60 g naslovnog spoja (tal.: 192°C). The starting compound (0.256 mol) is placed in 300 ml of acetic acid and a solution of 39.9 g of bromine (1.0 equiv.) in 60 ml of acetic acid is added dropwise at 60°C. After 1.5 h, it is allowed to cool to room temperature and the reaction mixture is added to 1 l of ice water. The precipitate is filtered off with suction, washed with water and dried, whereby 60 g of the title compound is isolated (melting point: 192°C).

Intermedijat 3 Intermediate 3

N-{4-[2-(2,4-diklor-benzilamino)-acetil]-fenil}-acetamid N-{4-[2-(2,4-Dichloro-benzylamino)-acetyl]-phenyl}-acetamide

37,1 g (0,195 mol) intermedijata l stavi se u 400 ml dioksana i pomiješa se s otopinom od 60 g (0,234 mola) intermedijata 2 u 600 ml dioksana. Doda se 134 ml trietil-amina i miješa se 4 h pri sobnoj temperaturi. Nakon stajanja preko noći, talog se odfiltrira i filtrat se koncentrira u vakuumu. Ostatak se preuzme u octeni ester, ispere se s NaHCO3 i H20, osuši s MgSO4 i koncentrira. Pri tome se dobije uljasti ostatak koji se protrlja s mješavinom octenog estera i etera, pri čemu se izluči 36 g intermedijata 3 u obliku kristalinične krute tvari (tal.: 115-117°C). 37.1 g (0.195 mol) of intermediate 1 was placed in 400 ml of dioxane and mixed with a solution of 60 g (0.234 mol) of intermediate 2 in 600 ml 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 was taken up in ethyl acetate, washed with NaHCO 3 and H 2 O, dried with MgSO 4 and concentrated. This gives an oily residue, which is rubbed with a mixture of acetic ester and ether, whereby 36 g of intermediate 3 is excreted in the form of a crystalline solid (melting point: 115-117°C).

Intermedijat 4 Intermediate 4

N-{4-[2-(2,4-diklor-benzilamino)-1-hidroksi-etil]-fenil}-acetamid N-{4-[2-(2,4-dichloro-benzylamino)-1-hydroxy-ethyl]-phenyl}-acetamide

36 g (0,099 mola) intermedijata 3 otopi se u 500 ral metanola i pri 0°C se pomiješa sa 7,8 g (2 ekv. ) natrijevog borhidrida. Miješa se još 30 min pri 0°C i još jedan sat pri sobnoj temperaturi. Za obradu, reakcijsku smjesu se koncentrira i ostatak se podijeli između l N HCl i octenog estera. Vodenu fazu se odvoji, namjesti se na pH 9 i ekstrahira se dva puta s octenim esterom. Sjedinjene organske faze se osuše s MgSO4 i koncentriraju. Tako dobiven sirov proizvod se može dalje pretvarati bez daljnjeg čišćenja. 36 g (0.099 mol) of intermediate 3 were dissolved in 500 ral of methanol and mixed with 7.8 g (2 eq.) of sodium borohydride at 0°C. It is stirred for another 30 minutes at 0°C and another hour at room temperature. For workup, the reaction mixture is concentrated and the residue is partitioned between 1 N HCl and ethyl acetate. The aqueous phase is separated, adjusted to pH 9 and extracted twice with ethyl acetate. The combined organic phases are dried with MgSO4 and concentrated. The crude product thus obtained can be further processed without further purification.

N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide

20 g (0/054 mola) intermedijarnog spoja 4 se otopi u 250 ml diklormetana i pri 0°C pomiješa se, kap po kap, s 250 ml konc. H2SO4. Miješa se 2 h pri 0°C i l h pri sobnoj temperaturi. Za obradu, reakcijsku smjesu se doda k ledenoj vodi i talog se odsisa. Talog se preuzme u 300 ml l N NaOH i tri puta se ekstrahira s octenim esterom. Sušenjem organskih faza i koncentriranjem dobije se sirov proizvod, koji se protrlja s diizopropil eterom, pri čemu se izolira 11,7 g spoja iz ovog primjera kao kristaliničnu krutu tvar (tal.: 205-206°C). 20 g (0/054 mol) of intermediate compound 4 is dissolved in 250 ml of dichloromethane and mixed at 0°C, drop by drop, with 250 ml of conc. H2SO4. It is mixed for 2 hours at 0°C and 1 hour at room temperature. For processing, the reaction mixture is added to ice water and the precipitate is suctioned off. The precipitate is taken up in 300 ml of 1 N NaOH and extracted three times with ethyl acetate. Drying of the organic phases and concentration gives a crude product, which is triturated with diisopropyl ether, whereby 11.7 g of the compound from this example is isolated as a crystalline solid (melting point: 205-206°C).

1a: N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid hidroklorid 1a: N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide hydrochloride

[image] [image]

Analitički uzorak (100 mg) naslovnog spoja iz primjera l suspendira se u 10 ml 2 N HCl i pomiješa se s toliko THF-a da se dobije bistru otopinu. Koncentrira se u vakuumu, ostatak se protrlja s eterom i odsisa, nakon čega se dobije naslovni spoj kao kristalinična kruta tvar (Rt = 3,807 min; metoda A), tal.: 125:C uu raspadanje. An analytical sample (100 mg) of the title compound from Example 1 was suspended in 10 ml of 2 N HCl and mixed with enough THF to give a clear solution. It is concentrated in vacuo, the residue is triturated with ether and suction, after which the title compound is obtained as a crystalline solid (Rt = 3.807 min; method A), m.p.: 125:C uu decomposition.

Primjer 2 Example 2

2a: (+)-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzol-sulfonamid hidroklorid; 2a: (+)-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide hydrochloride;

2b: (+)-3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzol-sulfonamid hidroklorid; 2b: (+)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide hydrochloride;

2c: (-)-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzol-sulfonamid acetat; 2c: (-)-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide acetate;

2d: (-)-3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzol-sulfonamid acetat. 2d: (-)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide acetate.

[image] [image]

Intermedijat 1 Intermediate 1

2,4-diklorbenzil-metil-amin je proizveden postupkom koji je poznat iz literature (J. Med. Chem.; 1984, 27, 1111). 2,4-dichlorobenzyl-methyl-amine was produced by a procedure known from the literature (J. Med. Chem.; 1984, 27, 1111).

Intermedijat 2 Intermediate 2

2-[(2,4-diklor-benzil)-metil-amino]-1-fenil-etanon 2-[(2,4-dichloro-benzyl)-methyl-amino]-1-phenyl-ethanone

Intermedijat 1 reagira s 2-brom-1-fenil-etanonom na način opisan u primjeru l za intermedijat 3. Analognom obradom i čišćenjem na silika gelu dobije se željeni proizvod alkiliranja s dobrim iskorištenjem kao žućkasto ulje (Rt = 4,188 min, metoda A); MS (CI + )- 308,2/310,2). Intermediate 1 reacts with 2-bromo-1-phenyl-ethanone in the manner described in example 1 for intermediate 3. Analogous treatment and purification on silica gel gives the desired alkylation product with good recovery as a yellowish oil (Rt = 4.188 min, method A) ; MS (CI + )- 308.2/310.2).

Intermedijat 3 Intermediate 3

2-[(2,4-diklor-benzil)-metil-amino]-1-fenil-etanol 2-[(2,4-dichloro-benzyl)-methyl-amino]-1-phenyl-ethanol

Intermedijat 2 se reducira s natrijevim borhidridom, postupkom koji je opisan u primjeru l za intermedijat 4. Kad se kontrolom reakcije utvrdi potpunu pretvorbu, koncentrira se i ostatak se preuzme u octeni ester. Ispere se dva puta s vodom, osuši s MgSO4 i oslobodi od otapala. Sirov proizvod dobiven u kvantitativnom iskorištenju može se dalje pretvarati bez daljenjeg čišćenja (Rt = 4,149 min (metoda A); MS (CI+)- 310,2/312,2). Intermediate 2 is reduced with sodium borohydride, using the procedure described in example 1 for intermediate 4. When complete conversion is determined by reaction control, it is concentrated and the residue is taken up in the acetic ester. It is washed twice with water, dried with MgSO4 and freed from the solvent. The crude product obtained in quantitative recovery can be further converted without further purification (Rt = 4.149 min (method A); MS (CI+)- 310.2/312.2).

Intermedijat 4 Intermediate 4

6,8-diklor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin 6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline

20 g (64,5 mmola) intermedijata 3 otopi se u 55 ml diklormetana i ohladi se na 0"C. Tu otopinu se dokaplje u 55 ml prethodno ohlađene konc. H2SO4 i zatim se miješa dva sata pri sobnoj temperaturi. Za obradu se doda na led i sa 6 N NaOH se namjesti na jako lužnato. Ekstrahira se tri puta s diklormetanom. Sjedinjene organske faze se osuše s MgSO4 i koncentriraju. Uljasti sirov proizvod se očisti na silika gelu, pri čemu se dobije intermedijat 4 s 53%-tnim iskorištenjem (Rt = 4,444 min (metoda A); MS (CI+) 292,2/294,2). 20 g (64.5 mmol) of intermediate 3 are dissolved in 55 ml of dichloromethane and cooled to 0"C. This solution is added dropwise to 55 ml of pre-cooled conc. H2SO4 and then stirred for two hours at room temperature. For processing, add on ice and made strongly alkaline with 6 N NaOH. Extracted three times with dichloromethane. The combined organic phases were dried over MgSO4 and concentrated. The oily crude product was purified on silica gel to give intermediate 4 with 53% recovery (Rt = 4.444 min (method A); MS (CI+) 292.2/294.2).

4a: (-)-6,8-diklor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin-trifluoracetat; 4a: (-)-6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline-trifluoroacetate;

4b: (+)-6,8-diklor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin-trifluoracetat 4b: (+)-6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline-trifluoroacetate

Intermedijat 4 se rastavi na dva enantiomera na kiralnoj fazi pomoću HPLC. Intermediate 4 was resolved into two enantiomers on the chiral phase by HPLC.

Kiralni stupac: Chiralpak OD 250 x 4,6 cm; Chiral column: Chiralpak OD 250 x 4.6 cm;

Otapalo: n-heptan/izo-propanol 7:3 + 0,1% TFA; Solvent: n-heptane/iso-propanol 7:3 + 0.1% TFA;

Brzina protoka: l ml/min; Flow rate: l ml/min;

Rt ((-)-enantiomer/4a) = 9,340 min; Rt ((-)-enantiomer/4a) = 9.340 min;

Rt ((+)-enantiomer/4b) = 20,327 min. Rt ((+)-enantiomer/4b) = 20.327 min.

2a: (+)-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzol-sulfonamid hidroklorid; 2a: (+)-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide hydrochloride;

2b: (+)-3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzol-sulfonamid hidroklorid 2b: (+)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide hydrochloride

Suspenziju od 500 mg (1,7 mmola) intermedijata 4a u 10 ml diklormetana stavi se pri 0°C u 1,2 ml klorsulfonske kiseline. Miješa se jedan sat pri 0CC i još jedan sat pri sobnoj temperaturi. Doda se još 5 ml klorsulfonske kiseline i miješa se još jedan sat pri sobnoj temperaturi. Za obradu, sve se doda na led i namjesti se s NaHCO3 na pH vrijednost 8. Ekstrahira se tri puta s octenim esterom. Sjedinjene organske faze se osuše s Na2SO4 i oslobode od otapala. Tako dobiven sirov proizvod u 20 ml konc. otopine NH3 grije se tri sata pri 90:C. Nakon potpune pretvorbe, reakcijsku otopinu se koncentrira i ostatak se podijeli između vode i octenog estera. Organsku fazu se odvoji, a vodenu fazu se još jednom ekstrahira s octenim esterom. Sjedinjene organske faze se osuše s Na2SO4 i otapalo se odstrani u vakuumu. Zatim se kromatografira na silika gelu, čime se dobije 335 mg smjese iz primjera 2a i 2b u obliku žute amorfne krute tvari. Daljnjim čišćenjem na preparativnoj HPLC dobije se 212 mg para supstituiranog naslovnog spoja 2a, kao i 58 mg meta izomera 2b. A suspension of 500 mg (1.7 mmol) of intermediate 4a in 10 ml of dichloromethane was placed at 0°C in 1.2 ml of chlorosulfonic acid. It is stirred for one hour at 0°C and another hour at room temperature. Add another 5 ml of chlorosulfonic acid and stir for another hour at room temperature. For processing, everything is added to ice and adjusted with NaHCO3 to a pH value of 8. Extracted three times with ethyl acetate. The combined organic phases are dried with Na2SO4 and freed from the solvent. Thus obtained raw product in 20 ml conc. of NH3 solution is heated for three hours at 90:C. After complete conversion, the reaction solution was concentrated and the residue was partitioned between water and ethyl acetate. The organic phase is separated, and the aqueous phase is extracted once more with ethyl acetate. The combined organic phases were dried with Na2SO4 and the solvent was removed in vacuo. It is then chromatographed on silica gel, which gives 335 mg of the mixture from examples 2a and 2b in the form of a yellow amorphous solid. Further purification on preparative HPLC afforded 212 mg of the para substituted title compound 2a, as well as 58 mg of the meta isomer 2b.

Uvjeti preparativne HPLC Preparative HPLC conditions

kiralni stupac: Chiralpak AS 250 x 4,6 mm; chiral column: Chiralpak AS 250 x 4.6 mm;

otapalo: n-heptan/etanol/metanol/acetonitril 20:1,5:0,5:0,5 solvent: n-heptane/ethanol/methanol/acetonitrile 20:1.5:0.5:0.5

brzina protoka: l ml/min; flow rate: l ml/min;

Rt (glavna frakcija) = 14,145 min (→ 2a) ; Rt (main fraction) = 14.145 min (→ 2a) ;

Rt (sporedna frakcija) = 11,623 min (→ 2b). Rt (minor fraction) = 11.623 min (→ 2b).

Obje frakcije se otope u mješavini metanola i 2 N HCl i osuše smrzavanjem, pri čemu se naslovni spojevi 2a i 2b mogu dobiti u obliku kristalinične krute tvari. Both fractions were dissolved in a mixture of methanol and 2N HCl and freeze-dried, whereby the title compounds 2a and 2b could be obtained as crystalline solids.

Rt (2a) = 3,630 min (metoda A); Rt (2a) = 3.630 min (method A);

MS (2a), (ES+)-371,3/373,3 (M++H)/412,3/414,3 (M++CH3CN); MS (2a), (ES+)-371.3/373.3 (M++H)/412.3/414.3 (M++CH3CN);

Rt (2b) = 3,668 min (metoda A); Rt (2b) = 3.668 min (method A);

MS (2b), (ES+) = 371,3/373,3 (M++H)/412,3/414,3 (M++CH3CN). MS (2b), (ES + ) = 371.3/373.3 (M++H)/412.3/414.3 (M++CH 3 CN).

2c: (-)-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzol-sulfonamid acetat; 2c: (-)-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide acetate;

2d: (-)-3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzol-sulfonamid acetat 2d: (-)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide acetate

Sinteza naslovnog spoja vrši se postupkom opisanim pod 2a/2b, pri čemu se kao polazni spoj upotrebljava intermedijat 4b. Čišćenje i rastavljanje od očekivanog meta izomera vrši se pod slijedećim uvjetima: kiralni stupac: Chiralpak AS 250 x 4,6/12 mm, The synthesis of the title compound is carried out by the procedure described under 2a/2b, whereby intermediate 4b is used as the starting compound. Cleaning and separation from the expected meta isomer is performed under the following conditions: chiral column: Chiralpak AS 250 x 4.6/12 mm,

otapalo: acetonitril, solvent: acetonitrile,

brzina protoka: l ml/min, flow rate: l ml/min,

Rt (glavna frakcija) = 4,394 min (→ 2c) ; Rt (main fraction) = 4.394 min (→ 2c) ;

Rt (sporedna frakcija) = 4,130 min (→ 2d). Rt (minor fraction) = 4.130 min (→ 2d).

Očišćeni proizvodi se preuzmu u svakom slučaju u 10%-tnu otopinu octene kiseline i osuše se smrzavanjem, pri čemu se željeni acetat dobije kao blago žućkasta kruta tvar. In any case, the cleaned products are taken up in a 10% solution of acetic acid and freeze-dried, whereby the desired acetate is obtained as a slightly yellowish solid.

Rt (2c) = 3,656 min (metoda A); Rt (2c) = 3.656 min (method A);

MS (ES+)- 371,1/373,1 (M++H)/412,1/414,l (M++CH3CN)); MS (ES+) - 371.1/373.1 (M++H)/412.1/414.1 (M++CH3CN));

Rt (2d) = 1,562 min (metoda B); Rt (2d) = 1.562 min (method B);

MS (ES+) = 371,1/373,1 (M++H)/412, 1/414,l (M++CH3CN)). MS (ES+) = 371.1/373.1 (M++H)/412.1/414.1 (M++CH3CN)).

Primjer 3 Example 3

4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)- 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-

N,N-dimetil-benzolsulfonamid hidroklorid N,N-dimethyl-benzenesulfonamide hydrochloride

[image] [image]

Stavi se klorsulfonsku kiselinu (6,6 ml) i u obrocima se doda 6,8-diklor-2-metil-4-fenil-1,2,3,4-tetrahidro-1zo-kinolin (intermedijat 4, primjer 2). Zatim se miješa jedan sat pri 40°C. Zatim se reakcijsku smjesu ohladi na sobnu temperaturu i pomiješa s mješavinom leda i vode. Talog, koji se pri tome izluči, se odsisa i preuzme se u octeni ester, i nakon ispiranja sa zasićenom otopinom NaCl, osuši se preko magnezijevog sulfata. Zatim se koncentrira, čime se dobije A-( 6,8-diklor-2-metil-1,2,3,4-tetrahidro-1zo-kinolin-4-il)-benzolsulfonil-klorid kao kruti sirov proizvod, od čega se dio (150 mg) izravno doda u obrocima u otopinu dimetilamina (5 ml, pribl. 40% u vodi) ohlađenu na 10°C. Nastalu suspenziju se zatim miješa pri toj temperaturi 1,5 h. Zatim se pomiješa s ledenom vodom, ekstrahira se tri puta s octenim esterom, sjedinjene faze u octenom esteru se isperu sa zasićenom otopinom NaCl i osuše se preko magnezijevog sulfata. Ostatak se preuzme u vodu, pomiješa se s 2 N HCl i osuši se smrzavanjem. Tako dobiven sirov proizvod se zatim očisti pomoću preparativne HPLC. Chlorosulfonic acid (6.6 ml) was added and 6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-1zo-quinoline (intermediate 4, example 2) was added portionwise. It is then stirred for one hour at 40°C. The reaction mixture was then cooled to room temperature and mixed with a mixture of ice and water. The precipitate, which is secreted in the process, is sucked off and taken up in acetic ester, and after washing with a saturated NaCl solution, it is dried over magnesium sulfate. It is then concentrated to give A-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-1zo-quinolin-4-yl)-benzenesulfonyl chloride as a solid crude product, from which portion (150 mg) was added directly in portions to a solution of dimethylamine (5 ml, approx. 40% in water) cooled to 10°C. The resulting suspension is then stirred at this temperature for 1.5 h. It is then mixed with ice water, extracted three times with ethyl acetate, the combined phases in ethyl acetate are washed with saturated NaCl solution and dried over magnesium sulfate. The residue was taken up in water, mixed with 2N HCl and freeze-dried. The crude product thus obtained is then purified by preparative HPLC.

Uvjeti: Conditions:

stacionarna faza: Merck Purosfer RP18 (10 μM) 250 x 25 mm mobilna faza: 90% H; O (0,05% TFA) → 90% acetonitril; 40 min; protok: 25 ml/min. stationary phase: Merck Purosfer RP18 (10 μM) 250 x 25 mm mobile phase: 90% H; O (0.05% TFA) → 90% acetonitrile; 40 minutes; flow rate: 25 ml/min.

Dobivene frakcije proizvoda se sjedine, acetonitril se izvuče na rotacijskom aparatu za isparavanje, vodenu fazu se ispere sa zasićenom otopinom kalijevog karbonata i zatim se ekstrahira tri puta s octenim esterom. Sjedinjene faze u octenom esteru se isperu sa zasićenom otopinom NaCl, osuše preko magnezijevog sulfata i koncentriraju. Ostatak se preuzme u vodu, pomiješa se s 2 N HCl i osuši se smrzavanjem. Dobije se 80 mg svjetle krute tvari. Ona se sastoji iz pribl. 80% željenog spoja i pribl. 20% regio izomera (Rt = 4,000 min (metoda A); MS (CI+) = 399,1). The resulting product fractions are combined, the acetonitrile is removed on a rotary evaporator, the aqueous phase is washed with saturated potassium carbonate solution and then extracted three times with ethyl acetate. The combined phases in acetic ester are washed with saturated NaCl solution, dried over magnesium sulfate and concentrated. The residue was taken up in water, mixed with 2N HCl and freeze-dried. 80 mg of light solid is obtained. It consists of approx. 80% of the desired compound and approx. 20% regioisomer (Rt = 4,000 min (method A); MS (CI+) = 399.1).

Primjer 4 Example 4

4a: 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzol-sulfonamid hidroklorid 4a: 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide hydrochloride

[image] [image]

Intermedijat 1 Intermediate 1

4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-benzolsulfonil klorid 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-benzenesulfonyl chloride

Pri 0°C stavi se 1 mmol 6,8-diklor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolina (intermedijat 4, primjer 2) u l ml klorsulfonske kiseline i miješa se 3 sata pri sobnoj temperaturi. Za obradu se reakcijsku smjesu doda na led, s l N NaOH se namjesti na pH 7 do 8 i ekstrahira se dva puta s octenim esterom. Sjedinjene faze u octenom esteru se osuše s Na2SO4 i izrotiraju. Tako dobiven sirov proizvod se dalje pretvara bez daljnjeg čišćenja. At 0°C, 1 mmol of 6,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline (intermediate 4, example 2) is placed in 1 ml of chlorosulfonic acid and stirred for 3 hours at room temperature. For treatment, the reaction mixture is added to ice, adjusted to pH 7 to 8 with 1 N NaOH and extracted twice with ethyl acetate. The combined phases in ethyl acetate are dried with Na2SO4 and centrifuged. The crude product thus obtained is further converted without further purification.

Intermedijat 2 Intermediate 2

4-(6,8-diklor-2-1netil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzol-sulfonamid 4-(6,8-dichloro-2-1-ethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide

319 mg intermedijata l suspendira se u 6 ml 25%-tnog amonijaka i grije se pri 90°C. Nakon 3 h razrjedi se s vodom i ekstrahira s octenim esterom. Organsku fazu se odvoji i osuši s Na2SO4, pri čemu se dobije 165 mg naslovnog spoja. 319 mg of intermediate l is suspended in 6 ml of 25% ammonia and heated at 90°C. After 3 hours, it is diluted with water and extracted with acetic ester. The organic phase was separated and dried with Na2SO4, yielding 165 mg of the title compound.

4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzol-sulfonamid hidroklorid 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide hydrochloride

145 mg intermedijata 2 suspendira se u 15 ml dietil etera i pomiješa se s l ml eterske HCl. Nakon 30 minuta miješanja pri sobnoj temperaturi, talog se odsisa i osuši, pri čemu se dobije 136 mg hidroklorida u obliku žućkaste krute tvari. 145 mg of intermediate 2 is suspended in 15 ml of diethyl ether and mixed with 1 ml of ethereal HCl. After stirring at room temperature for 30 minutes, the precipitate was filtered off with suction and dried to give 136 mg of the hydrochloride as a yellowish solid.

4b: 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzol-sulfonamid acetat 4b: 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-sulfonamide acetate

[image] [image]

255 mg intermedijata 2 iz primjera 8 pomiješa se s 5 ml ledene octene kiseline i doda se 50 ml vode. Ostatak nakon filtracije teško topivih sastojaka se osuši smrzavanjem, pri čemu se dobije 250 mg naslovnog spoja. 255 mg of intermediate 2 from example 8 are mixed with 5 ml of glacial acetic acid and 50 ml of water are added. The residue after filtration of poorly soluble ingredients is freeze-dried, whereby 250 mg of the title compound is obtained.

Primjer 5 Example 5

4-(4-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin hidroklorid 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline hydrochloride

[image] [image]

Intermedijat 1 Intermediate 1

1-(4-brom-fenil)-2-[(2,4-diklor-benzil)-metil-amino]etanon 1-(4-bromo-phenyl)-2-[(2,4-dichloro-benzyl)-methyl-amino]ethanone

(2,4-diklor-benzil)-metil-amin (vidi primjer 1, intermedijat 1) i 2-brom-1-(4-brom-fenil)-etanon se dovedu u reakciju analogno postupku opisanom u primjeru l za intermedijat 3. Nakon analogne obrade i kromatografije na silika gelu može se izolirati proizvod alkiliranja sa 69%-tnim iskorištenjem. (2,4-dichloro-benzyl)-methyl-amine (see example 1, intermediate 1) and 2-bromo-1-(4-bromo-phenyl)-ethanone are reacted analogously to the procedure described in example 1 for intermediate 3 After analogous treatment and chromatography on silica gel, the alkylation product can be isolated with a 69% yield.

Intermedijat 2 Intermediate 2

l-(4-brom-fenil)-2-[(2,4-diklor-benzil)-metil-amino]etanol 1-(4-bromo-phenyl)-2-[(2,4-dichloro-benzyl)-methyl-amino]ethanol

Intermedijat 1 se reducira u odgovarajući alkohol s 2 ekvivalenta NaBH4, analogno postupku opisanom u primjeru l za intermedijat 4, koji se može izolirati s iskorištenjem od 86%. Intermediate 1 is reduced to the corresponding alcohol with 2 equivalents of NaBH4, analogously to the procedure described in example 1 for intermediate 4, which can be isolated with a yield of 86%.

Intermedijat 3 Intermediate 3

4-(4-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline

5,45 g (14,0 mmolova) l-(4-brom-fenil)-2-[(2,4-diklor-benzil)-metil-amino]-etanola stavi se u 15 ml diklormetana 1 pri CTC se pomiješa s 15 ml konc. H2SO4. Nakon miješanja 2 sata pri sobnoj temperaturi, reakcijsku smjesu se doda na led i sa 6 N NaOH se namjesti na alkalno. Ekstrahira se tri puta s diklormetanom. Sjedinjene organske faze se osuše s MgSO4 i koncentriraju. Za daljnje čišćenje ostatak se kromatografira na silika gelu, pri čemu se dobije 2,6 g naslovnog spoja kao žućkasto ulje. 5.45 g (14.0 mmol) of 1-(4-bromo-phenyl)-2-[(2,4-dichloro-benzyl)-methyl-amino]-ethanol are placed in 15 ml of dichloromethane 1 at RT and mixed with 15 ml conc. H2SO4. After stirring for 2 hours at room temperature, the reaction mixture was added to ice and made alkaline with 6 N NaOH. It is extracted three times with dichloromethane. The combined organic phases are dried with MgSO4 and concentrated. For further purification, the residue is chromatographed on silica gel, whereby 2.6 g of the title compound is obtained as a yellowish oil.

4-(4-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin hidroklorid 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline hydrochloride

[image] [image]

300 mg 4-(4-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolina se miješa u 2 N HCl pri sobnoj temperaturi. Nastali talog se odsisa i osuši. 300 mg of 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline was stirred in 2 N HCl at room temperature. The resulting precipitate is sucked off and dried.

Primjer 6 Example 6

4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid

[image] [image]

4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid

5,57 g (15 mmolova) 4-(4-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolina (primjer 5, intermedijat 3) otopi se u 150 ml aps. DMF/benzola (1:1). Nakon otplinjavanja otopine, pod argonom se doda 1,18 g (4,5 mmola) trifenilfosfina i 1,17 g (9 mmolova) Ca(HCO2)2. Nakon ponovnog prupuhivanja s argonom u otopinu se doda 867 mg (0,75 mmola) Pd(PF3)4 i ugljikov monoksid. Miješa se pri 120°C. Nakon šest sati pri 120°C i stajanja preko noći pod argonom, još jednom se doda 867 mg (0,75 mmola) Pd(PF3)4 i miješa se daljnjih osam sati pri 120°C, pri čemu se u otopinu uvodi ugljikov monoksid. Nakon ponovnog stajanja preko noći, doda se 135 mg PdCl2 i pusti se reagirati pod istim uvjetima. Za obradu se otapalo odstrani u vakuumu i ostatak se preuzme u octeni ester. Ekstrahira se tri puta s 2 N NaOH. Sjedinjene vodene faze se namjeste na pH vrijednost 6 sa 6 N HCl i ekstrahiraju se tri puta s octenim esterom. Organske faze se osuše s MgSO4 i oslobode se od otapala. Ostatak se očisti na silika gelu s mješavinom diklormetan/metanola, pri čemu se dobije 420 mg naslovnog spoja (Rt = 4,025 min (metoda A); MS (CI+) = 336,1/338,1). 5.57 g (15 mmol) of 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (Example 5, intermediate 3) were dissolved in 150 ml abs . DMF/benzene (1:1). After degassing the solution, 1.18 g (4.5 mmol) of triphenylphosphine and 1.17 g (9 mmol) of Ca(HCO2)2 are added under argon. After repurposing with argon, 867 mg (0.75 mmol) of Pd(PF3)4 and carbon monoxide are added to the solution. It is mixed at 120°C. After six hours at 120°C and standing overnight under argon, 867 mg (0.75 mmol) of Pd(PF3)4 is added once more and stirred for a further eight hours at 120°C, during which carbon monoxide is introduced into the solution . After standing again overnight, 135 mg of PdCl2 was added and allowed to react under the same conditions. For processing, the solvent is removed under vacuum and the residue is taken up in acetic ester. It is extracted three times with 2 N NaOH. The combined aqueous phases are adjusted to pH 6 with 6 N HCl and extracted three times with ethyl acetate. The organic phases are dried with MgSO4 and freed from the solvent. The residue was purified on silica gel with dichloromethane/methanol to give 420 mg of the title compound (Rt = 4.025 min (method A); MS (Cl+) = 336.1/338.1).

Primjer 7 Example 7

4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-etil-benzamid trifluoracetat 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-ethyl-benzamide trifluoroacetate

[image] [image]

146 mg (0,43 mmola) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeve kiseline (vidi primjer 6) otopi se u 5 ml DMF-a i pomiješa se s 1,0 ekvivalenta trietilamina. Pri 0°C se doda otopinu od 141 mg (0,43 mmol) TOTU-a u 3 ml DMF-a. Miješa se 30 min pri 0°C, kao i 30 min pri sobnoj temperaturi. Zatim se tu otopinu pri 0°C doda k otopini od 0,28 ml 2 M otopini etilamina i 0,06 ml (0,043 mmola) trietilamina u 5 ml DMF-a i reakcijsku smjesu se miješa tri sata pri sobnoj temperaturi. Za obradu se otapalo izdestilira u vakuumu, ostatak se preuzme u octeni ester i ispere se dva puta s l N KOH, kao i jednom s vodom. Organsku fazu se osuši s Na2SO4 i koncentrira. Za daljnje čišćenje kromatografira se na silika gelu (diklormetan/metanol 95:5). Daljnjim čišćenjem na prep. HPLC (acetonitrii/voda/trifluoroctena kiselina) dobije se željeni amid karbonske kiseline kao trifluoracetat. (Rt = 4,169 min (metoda A); MS (CI + )- 363,3/365,3). 146 mg (0.43 mmol) of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid (see example 6) is dissolved in 5 ml of DMF and mixed with 1.0 equivalents of triethylamine. A solution of 141 mg (0.43 mmol) of TOTU in 3 ml of DMF was added at 0°C. It is mixed for 30 min at 0°C, as well as 30 min at room temperature. This solution was then added at 0°C to a solution of 0.28 ml of a 2 M solution of ethylamine and 0.06 ml (0.043 mmol) of triethylamine in 5 ml of DMF and the reaction mixture was stirred for three hours at room temperature. For treatment, the solvent is distilled off in a vacuum, the residue is taken up in acetic ester and washed twice with 1 N KOH, as well as once with water. The organic phase is dried with Na2SO4 and concentrated. For further purification, it is chromatographed on silica gel (dichloromethane/methanol 95:5). Further cleaning on prep. HPLC (acetonitrile/water/trifluoroacetic acid) gives the desired carboxylic acid amide as trifluoroacetate. (Rt = 4.169 min (method A); MS (Cl + )- 363.3/365.3).

Primjer 8 Example 8

4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-propil-benzamid trifluoracetat 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-propyl-benzamide trifluoroacetate

[image] [image]

Počevši od n-propilamina i 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeve kiseline (vidi primjer 6) naslovni spoj se može proizvesti postupkom opisanim u primjeru 7. (Rt = 1,881 min (metoda B) ; MS (CI+) = 377,3/379,3). Starting from n-propylamine and 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid (see Example 6) the title compound can be prepared by the procedure described in example 7 (Rt = 1.881 min (method B) ; MS (CI+) = 377.3/379.3).

Primjer 9 Example 9

4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-N-(2-dimetilamino-etil)-benzamid trifluoracetat 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-benzamide trifluoroacetate

[image] [image]

proizveden je analogno primjeru 7 počevši od spoja iz primjera 6 i N1,N1-dimetiletan-1,2-diamina reakcijom povezivanja posredstvom TOTU-a (Rt - 1,449 min (metoda B); MS (CI+) = 406,3/408, 3). was produced analogously to example 7 starting from the compound from example 6 and N1,N1-dimethylethane-1,2-diamine by coupling reaction by means of TOTU (Rt - 1.449 min (method B); MS (CI+) = 406.3/408, 3).

Primjer 10 Example 10

6,8-diklor-2-metil-4-(4-morfolin-4-il-fenil)-1,2,3,4-tetrahidroizokinolin trifluoracetat 6,8-dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline trifluoroacetate

[image] [image]

456 mg (1,4 mmola) Cs2CO3, 6,75 mg (0,03 mmola) paladijevog acetata, te 28 mg (0,045 mmola) 2,2-bis-(di-fenilfosfino)-1,1-binaftila stavi se u 5 ml aps. toluola. Pod argonom se doda otopinu 0,104 ml (1,2 mmola) morfolina u 2,5 ml aps. DMF-a, kao i otopinu iz 371 mg (1,0 mmola) 4-(4-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidro-1zo-kinolina u 2,5 ml aps. toluola i miješa se ukupno 9 sati pri 100°C. Za obradu se otapalo odstrani, ostatak se preuzme u diklormetan i odfiltrira se od netopivih sastojaka. Ostatak nakon koncentriranja filtrata se kromatografira na silika gelu (CH2Cl2/metanol 95:5), pri čemu se dobije 350 mg željenog morfolinskog derivata. Nakon daljnjeg čišćenja na prep. HPLC može se izolirati 160 mg odgovarajućeg trifluoracetata u obliku bezbojne krute tvari. 456 mg (1.4 mmol) of Cs2CO3, 6.75 mg (0.03 mmol) of palladium acetate, and 28 mg (0.045 mmol) of 2,2-bis-(di-phenylphosphino)-1,1-binaphthyl were placed in 5 ml abs. toluene. Under argon, a solution of 0.104 ml (1.2 mmol) of morpholine in 2.5 ml of abs. of DMF, as well as a solution of 371 mg (1.0 mmol) of 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-1iso-quinoline in 2.5 ml abs. toluene and mixed for a total of 9 hours at 100°C. For processing, the solvent is removed, the residue is taken up in dichloromethane and filtered from insoluble ingredients. After concentrating the filtrate, the residue is chromatographed on silica gel (CH2Cl2/methanol 95:5), whereby 350 mg of the desired morpholine derivative is obtained. After further cleaning on prep. 160 mg of the corresponding trifluoroacetate can be isolated by HPLC as a colorless solid.

Primjer 11 Example 11

[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-dietil-amin trifluoracetat [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-diethyl-amine trifluoroacetate

[image] [image]

Počevši od dietilamina i 4-(4-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolina (primjer 5, intermedijat 3), analogno postupku opisanom u primjeru 10. Trajanje reakcije: 2 dana pri 100°C; trostruka količina Pd katalizatora i fosfinskog liganda. Nakon prep. HPLC može se izolirati željeni trifluoracetat kao bezbojna kruta tvar. Starting from diethylamine and 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (example 5, intermediate 3), analogously to the procedure described in example 10. Duration of reaction : 2 days at 100°C; triple amount of Pd catalyst and phosphine ligand. After Rev. HPLC can isolate the desired trifluoroacetate as a colorless solid.

Primjer 12 Example 12

6,8-diklor-2-metil-4-(4-piperidin-1-il-fenil)-1,2,3,4-tetrahidroizokinolin trifluoracetat 6,8-dichloro-2-methyl-4-(4-piperidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline trifluoroacetate

[image] [image]

Analogno postupku koji je opisan u primjeru 10 može se dobiti željeni piperidinski derivat počevši od piperidina i 4-(4-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidro-1zo-kinolin (primjer 5, intermedijat 3). Analogous to the procedure described in example 10, the desired piperidine derivative can be obtained starting from piperidine and 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-1zo- quinoline (example 5, intermediate 3).

Primjer 13 Example 13

6,8-diklor-2-metil-4-(4-pirolidin-1-il-fenil)-1,2,3,4-tetrahidroizokinolin hidroklorid 6,8-dichloro-2-methyl-4-(4-pyrrolidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride

[image] [image]

Reakcija se odvija analogno postupku opisanim u primjeru 10, počevši od pirolidina i 4-(4-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolina (primjer 5, intermedijat 3). Nakon kromatografskog čišćenja, dobiveni proizvod se preuzme u mješavinu DMSO/acetonitrila, pri čemu se izluči talog. On se odfiltrirta i otopi se u 2 N HCl i osuši smrzavanjem, pri čemu se dobije naslovni spoj kao bezbojna kruta tvar. The reaction proceeds analogously to the procedure described in example 10, starting from pyrrolidine and 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (example 5, intermediate 3) . After chromatographic purification, the obtained product is taken up in a mixture of DMSO/acetonitrile, whereby the precipitate is separated. It was filtered off and dissolved in 2N HCl and freeze-dried to give the title compound as a colorless solid.

Primjer 14 Example 14

6,8-diklor-2-metil-4-[4-(4-metil-piperazin-1-il)-fenil]-1,2,3,4-tetrahidro-izokinolin trifluoracetat 6,8-dichloro-2-methyl-4-[4-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-isoquinoline trifluoroacetate

[image] [image]

Pretvorbom N-metil-piperazina i 4-(4-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolina (primjer 5, intermedijat 3) postupkom opisanim u primjeru 10 dobije se naslovni spoj u obliku bezbojne krute tvari. The conversion of N-methyl-piperazine and 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (example 5, intermediate 3) by the procedure described in example 10 gives the title compound as a colorless solid.

Primjer 15 Example 15

6,8-diklor-2-ciklopropil-4-fenil-1,2,3,4-tetrahidro-izokinolin trifluoracetat 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline trifluoroacetate

[image] [image]

Intermedijat 1 Intermediate 1

Ciklopropil-(2,4-diklor-benzil)-amin Cyclopropyl-(2,4-dichloro-benzyl)-amine

5,25 g (30 mmolova) 2,4-diklorbenzaldehida se stavi u 140 ml metanola i pri sobnoj temperaturi se doda otopinu od 1,71 g (30 mmolova) ciklopropilamina. Miješa se 40 min pri sobnoj temperaturi i zatim se u obrocima pomiješa s 1,42 g (37,5 mmolova) NaBH4. Nakon stajanja preko noći otapalo se odstrani i ostatak se preuzme u 2 N HCl. Ekstrahira se dva puta s octenim esterom. Vodenu fazu se namjesti lužnatom s NaOH i ponovno se ekstrahira dva puta s octenim esterom. Organsku fazu se osuši s MgSO4 i koncentrira. Tako dobiven sirov proizvod u obliku blago žućkastog ulja može se dalje pretvarati bez daljnjeg čišćenja. 5.25 g (30 mmol) of 2,4-dichlorobenzaldehyde is placed in 140 ml of methanol and added to a solution of 1.71 g (30 mmol) of cyclopropylamine at room temperature. It is stirred for 40 min at room temperature and then mixed with 1.42 g (37.5 mmol) of NaBH4 in portions. After standing overnight, the solvent was removed and the residue was taken up in 2 N HCl. It is extracted twice with acetic ester. The aqueous phase is made alkaline with NaOH and extracted again twice with ethyl acetate. The organic phase is dried with MgSO4 and concentrated. The thus obtained crude product in the form of a slightly yellowish oil can be further converted without further purification.

Intermedijat 2 Intermediate 2

2-[ciklopropil-(2,4-diklor-benzil}-amino]-1-fenil-etanon Intermedijat 1 se dovede u reakciju s alfa-brom-acetofenonom u prisutnosti trietilamina u dioksanu, postupkom koji je opisan u primjeru l za intermedijat 3. Za obradu se otapalo izdestilira i ostatak se preuzme u octeni ester. Ispere se dva puta s vodom i s 2 N HCl, osuši se s MgSO4 i koncentrira. Tako dobiven sirov proizvod može se dalje pretvarati bez daljnjeg čišćenja. 2-[cyclopropyl-(2,4-dichloro-benzyl}-amino]-1-phenyl-ethanone Intermediate 1 is reacted with alpha-bromo-acetophenone in the presence of triethylamine in dioxane, following the procedure described in example 1 for intermediate 3. For workup, the solvent is distilled off and the residue is taken up in the acetic ester. It is washed twice with water and with 2 N HCl, dried over MgSO4 and concentrated. The crude product thus obtained can be further converted without further purification.

Intermedijat 3 Intermediate 3

2-[ciklopropil-(2,4-diklor-benzil)-amino]-1-fenil-etanol 2-[cyclopropyl-(2,4-dichloro-benzyl)-amino]-1-phenyl-ethanol

Intermedijat 2 se reducira analogno postupku opisanom u primjeru l za intermedijat 4 s NaBH4. Za obradu se koncentrira i ostatak se podijeli između l N HCl i octenog estera. Vodenu fazu se odvoji i još jednom se ekstrahira s octenim esterom. Sjedinjene organske faze se osuše s MgSO4 i otapalo se odstrani u vakuumu. Intermediate 2 is reduced analogously to the procedure described in example 1 for intermediate 4 with NaBH4. For workup, it is concentrated and the residue is partitioned between 1N HCl and ethyl acetate. The aqueous phase is separated and extracted once more with ethyl acetate. The combined organic phases were dried over MgSO4 and the solvent was removed in vacuo.

6,8-diklor-2-ciklopropil-4-fenil-1,2,3,4-tetrahidro-izokinolin trifluoracetat 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline trifluoroacetate

Intermedijat 3 (1,9 g) se bez daljnjeg čišćenja otopi u 10 ml diklormetana i ciklizira se postupkom koji je opisan u primjeru l s konc. H2SO4. Za obradu se reakcijsku smjesu doda na led. Organsku fazu se odvoji i vodenu fazu se još jednom ekstrahira s diklormetanom. Sjedinjene organske faze se osuše s MgSO4 i oslobode od otapala. Kromatografijom na silika gelu (n-heptan/octeni ester 5:1 → 3:1) dobije se 200 mg žućkastog ulja koje se podvrgava daljnjem čišćenju na prep. HPLC. Pri tome se dobije 184 mg naslovnog spoja kao trifluoracetata. Intermediate 3 (1.9 g) was dissolved without further purification in 10 ml of dichloromethane and cyclized by the procedure described in example 1 with conc. H2SO4. For processing, the reaction mixture is added to ice. The organic phase is separated and the aqueous phase is extracted once more with dichloromethane. The combined organic phases are dried with MgSO4 and freed from the solvent. Chromatography on silica gel (n-heptane/acetic ester 5:1 → 3:1) yields 200 mg of a yellowish oil, which undergoes further purification on prep. HPLC. This gives 184 mg of the title compound as trifluoroacetate.

Primjer 16 Example 16

16a: (-)-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 16a: (-)-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide;

16b: (+)-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid 16b: (+)-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide

[image] [image]

500 mg naslovnog spoja iz primjera l se rastavi na kiralnoj fazi, pri čemu se dobije pribl. 250 mg obaju enantiomera acetamida, 16a i 16b. 500 mg of the title compound from example 1 is resolved on the chiral phase, yielding approx. 250 mg of both enantiomers of acetamide, 16a and 16b.

Kiralni stupac: Chiralpak OD 250 x 4,6 mm; Chiral column: Chiralpak OD 250 x 4.6 mm;

otapalo: acetonitril; solvent: acetonitrile;

brzina protoka: l ml/min; flow rate: l ml/min;

Rt ((-)-enantiomer/16a) = 5,856 min; Rt ((-)-enantiomer/16a) = 5.856 min;

Rt ((+)-enantiomer/16b) = 8,613 min. Rt ((+)-enantiomer/16b) = 8.613 min.

Primjer 17 Example 17

4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin hidroklorid 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine hydrochloride

[image] [image]

Intermedijat 1 Intermediate 1

4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine

3,0 g (8,6 mmolova) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamida (primjer 1) otopi se u 100 ml 20%-tne otopine natrijevog metanolata i grije se 4 sata pod refluksom. Doda se još 2,0 g (29,4 mmolova} krutog natrijevog metanolata i grije se još tri sata pod refluksom. Za obradu se otapalo odstrani, ostatak se preuzme u 200 ml vode i ekstrahira se dva puta s diklormetanom. Sjedinjene organske faze se osuše s MgSO4 i koncentriraju. Za daljnje čišćenje vrši se kromatografiju na silika gelu (octeni ester/heptan 1:1), pri čemu se dobije anilin u kvantitativnom iskorištenjem kao žućkasto ulje. 3.0 g (8.6 mmol) of N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide (example 1 ) is dissolved in 100 ml of 20% sodium methanolate solution and heated for 4 hours under reflux. Another 2.0 g (29.4 mmol) of solid sodium methanolate is added and heated for another three hours under reflux. For processing, the solvent is removed, the residue is taken up in 200 ml of water and extracted twice with dichloromethane. The combined organic phases are dried with MgSO4 and concentrated.For further purification, chromatography on silica gel (acetic ester/heptane 1:1) is performed, whereby aniline is obtained in quantitative recovery as a yellowish oil.

4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin hidroklorid 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine hydrochloride

200 mg (0,65 mmola) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamina otopi se u 30 ml etanolne HCl. Bistru otopinu se koncentrira u vakuumu. Ostatak se protrlja s eterom, odsisa i osuši, pri čemu se može izolirati 208 mg željenog hidroklorida. 200 mg (0.65 mmol) of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine was dissolved in 30 ml of ethanolic HCl. The clear solution is concentrated in vacuo. The residue is triturated with ether, suction filtered and dried, whereby 208 mg of the desired hydrochloride can be isolated.

Primjer 18 Example 18

N-etil-N'-4-(6,B-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonil-urea hidroklorid N-ethyl-N'-4-(6,B-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonyl-urea hydrochloride

[image] [image]

1,0 mmol 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzol-sulfonamida (primjer 4, intermedijat 2) u 15 ml suhog acetona pomiješa se s 350 mg (2,5 ekv.) K2CO3 i miješa se 1,5 sati pri sobnoj temperaturi. Pri sobnoj temperaturi se dokaplje otopinu od 2,5 ekv. etilizocijanata u acetonu i otopinu se grije pod refluksom. Za obradu se koncentrira u vakuumu, ostatak se preuzme u vodu i ekstrahira se dva puta s octenim esterom. Vodenu fazu se zakiseli sa 6 N HCl i nastali talog se odsisa. Ispere se s octenim esterom i osuši u vakuumu, čime se dobije naslovni spoj u dobrom iskorištenju. 1.0 mmol of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide (example 4, intermediate 2) in 15 ml of dry acetone is mixed with 350 mg (2.5 eq.) of K2CO3 and stirred for 1.5 hours at room temperature. A solution of 2.5 equiv is added dropwise at room temperature. of ethyl isocyanate in acetone and the solution is heated under reflux. For processing, it is concentrated in vacuo, the residue is taken up in water and extracted twice with ethyl acetate. The aqueous phase is acidified with 6 N HCl and the resulting precipitate is filtered off with suction. It is washed with ethyl acetate and dried in vacuo to give the title compound in good yield.

Primjer 19 Example 19

1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-propil-urea 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-propyl-urea

[image] [image]

U otopinu od 500 mg (1,63 mmola) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamina (vidi primjer 17) u 15 ml toluola uz miješanje se dokaplje otopinu od 0,17 g (2,0 mmola) n-propilizocijanata u toluolu. Nakon jednog sata pri 40°C doda se još 0,17 g n-propilizocijanata i miješa se jedan sat pri 80°C. Za obradu se otapalo odstrani i ostatak se protrlja s vodom i eterom. Nakon sušenja se dobije 503 mg željene n-propil-uree. In a solution of 500 mg (1.63 mmol) of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (see example 17) in 15 ml of toluene is added dropwise to a solution of 0.17 g (2.0 mmol) of n-propylisocyanate in toluene. After one hour at 40°C, another 0.17 g of n-propylisocyanate is added and stirred for one hour at 80°C. For processing, the solvent is removed and the residue is triturated with water and ether. After drying, 503 mg of the desired n-propyl urea is obtained.

19a: 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-propil-urea hidroklorid 19a: 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-propyl-urea hydrochloride

[image] [image]

450 mg 1-[4-( 6,8-diklor-2-metil-l,2,374-tetrahidro-izokinolin-4-il)-fenil]-3-propil-uree se otopi u mješavini od 2 N HCl i THF-a. Bistru otopinu se koncentrira u vakuumu i ostatak se protrlja s eterom i odsisa. Sušenjem se dobije 473 mg željenog hidroklorida. 450 mg of 1-[4-(6,8-dichloro-2-methyl-1,2,374-tetrahydro-isoquinolin-4-yl)-phenyl]-3-propyl-urea are dissolved in a mixture of 2 N HCl and THF- And. The clear solution is concentrated in vacuo and the residue triturated with ether and suction. Drying gives 473 mg of the desired hydrochloride.

Primjer 20 Example 20

1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-metil-tiourea 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea

[image] [image]

Počevši od 500 mg (1,63 mmola) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenilamina (vidi primjer 17) i 220 mg (3,0 mmola) metilizotiocijanata analogno postupku opisanom u primjeru 19, može se izolirati 245 mg željene tiouree. Starting with 500 mg (1.63 mmol) of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenylamine (see Example 17) and 220 mg (3, 0 mmol) of methylisothiocyanate analogously to the procedure described in example 19, 245 mg of the desired thiourea can be isolated.

Primjer 21 Example 21

1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea

[image] [image]

Priprava se odvija analogno postupku opisanom u primjeru počevši od 4-(6,8-diklor-2-metil-1,2,3,4-tetra-hidro-izokinolin-4-il)-fenilamina (500 mg; 1,63 nunola) i etilizocijanata (284 mg/4 mmola). The preparation is carried out analogously to the procedure described in the example starting from 4-(6,8-dichloro-2-methyl-1,2,3,4-tetra-hydro-isoquinolin-4-yl)-phenylamine (500 mg; 1.63 nunol) and ethyl isocyanate (284 mg/4 mmol).

21a: 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etilurea hidroklorid 21a: 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethylurea hydrochloride

[image] [image]

Prevođenje u odgovarajući hidroklorid vrši se analogno postupku koji je opisan u primjeru 19a. Conversion to the corresponding hydrochloride is carried out analogously to the procedure described in example 19a.

Primjer 22 Example 22

N-[4-(6-metanesulfonil-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid N-[4-(6-methanesulfonyl-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide

[image] [image]

Intermedijat 1 Intermediate 1

(4-metansulfonil-benzil)-metil-amin se sintetizira počevši od l-brom-metil-4-raetansulfonil-benzola i metil-amina na način koji je stručnjaku poznat. (4-methanesulfonyl-benzyl)-methyl-amine is synthesized starting from 1-bromo-methyl-4-ethanesulfonyl-benzene and methyl-amine in a manner known to the expert.

Priprava naslovnog spoja odvija se analogno postupku sinteze koji je opisan u primjeru počevši od (4-metan-sulfonil-benzil)-metil-amina (intermedijat 1) i N-[4-(2-brom-acetil)-fenil]-acetamida (primjer l, intermedijat 2). The preparation of the title compound proceeds analogously to the synthesis procedure described in the example starting from (4-methane-sulfonyl-benzyl)-methyl-amine (intermediate 1) and N-[4-(2-bromo-acetyl)-phenyl]-acetamide (example 1, intermediate 2).

Primjer 23 Example 23

N-[4-(2,6,8-trimetil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid N-[4-(2,6,8-trimethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide

[image] [image]

Počevši od (2,4-dimetil-benzil)-metil-amina, koji je proizveden iz l-brom-metil-2,4-dimetil-benzola i metilamina na način koji je stručnjaku poznat, i N-[4-(2-brom-acetil)-fenil]-acetamida (primjer l, intermedijat 2) dobije se postupkom opisanim u primjeru 1. Starting with (2,4-dimethyl-benzyl)-methyl-amine, which is prepared from l-bromo-methyl-2,4-dimethyl-benzene and methylamine in a manner known to the person skilled in the art, and N-[4-(2 -bromo-acetyl)-phenyl]-acetamide (example 1, intermediate 2) is obtained by the procedure described in example 1.

Primjer 24 Example 24

N-[4-(6-brom-8-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide

[image] [image]

Počevši od (4-brom-2-klor-benzil)-metil-amina/ koji se može proizvesti iz 4-brom-1-brommetil-2-klor-benzola i metilamina, na način koji je stručnjaku poznat, i N-[4-(2-brom-acetil)-fenil]-acetamida (primjer l, intermedijat 2} dobije se postupkom opisanim u primjeru 1. Starting from (4-bromo-2-chloro-benzyl)-methyl-amine/ which can be prepared from 4-bromo-1-bromomethyl-2-chloro-benzene and methylamine, in a manner known to the skilled person, and N-[ 4-(2-bromo-acetyl)-phenyl]-acetamide (example 1, intermediate 2} is obtained by the procedure described in example 1.

Primjer 25 Example 25

N-[4-(8-klor-2-metil-6-pirolidin-1-il-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid N-[4-(8-chloro-2-methyl-6-pyrrolidin-1-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide

[image] [image]

1,02 g (3,12 mmola) Cs2CO3, 8,8 mg (0,04 mmola) paladijevog acetata, kao i 36,1 mg (0,06 mmola) 2,2-bis-difenilfosfino-1,1-binaftila stavi se pod argonom u 6,5 ml aps. toluola. Pri sobnoj temperaturi se doda otopinu od 512 mg (1,3 mmola) N-[4-(6-brom-8-klor-2-metil-1,2,3,4-tetra-hidroizokinolin-4-il)-fenil]-acetamida (primjer 24) u 4 ml aps. DMF-a, kao i otopinu iz 111 mg (1,56 mmola) pirolidina u 4 ml DMF-a i grije se 7 sati pri 100°C. Za obradu se otapalo odstrani u vakuumu i ostatak se preuzme u diklor-metan. Netopivi sastojci se odfiltriraju i filtrat se koncentrira. Ostatak se kromatografira na silika gelu s mješavinom diklormetana i metanola, pri čemu se može izolirati 360 mg spoja iz ovog primjera. 1.02 g (3.12 mmol) of Cs2CO3, 8.8 mg (0.04 mmol) of palladium acetate, as well as 36.1 mg (0.06 mmol) of 2,2-bis-diphenylphosphino-1,1-binaphthyl placed under argon in 6.5 ml abs. toluene. At room temperature, a solution of 512 mg (1.3 mmol) of N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)- of phenyl]-acetamide (example 24) in 4 ml abs. of DMF, as well as a solution of 111 mg (1.56 mmol) of pyrrolidine in 4 ml of DMF and heated for 7 hours at 100°C. For processing, the solvent is removed in vacuo and the residue is taken up in dichloromethane. The insoluble ingredients are filtered off and the filtrate is concentrated. The residue is chromatographed on silica gel with a mixture of dichloromethane and methanol, whereby 360 mg of the compound from this example can be isolated.

25a: N-[4-(8-klor-2-metil-6-pirolidin-1-il-1,2,3,4-tetra-hidro-izokinolin-4-il)-fenil]-acetamid hidroklorid 25a: N-[4-(8-chloro-2-methyl-6-pyrrolidin-1-yl-1,2,3,4-tetra-hydro-isoquinolin-4-yl)-phenyl]-acetamide hydrochloride

[image] [image]

320 mg N-[4-(8-klor-2-metil-6-pirolidin-1-il-1,2,3,4-tetrahidro-izokinolin-4-il)- fenil]-acetamida se otopi u 20 ml etanolne HCl, miješa se 30 min pri sobnoj temperaturi i koncentrira se. Ostatak se preuzme u vodu i osuši se smrzavanjem. 320 mg of N-[4-(8-chloro-2-methyl-6-pyrrolidin-1-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide is dissolved in 20 ml ethanolic HCl, stirred for 30 min at room temperature and concentrated. The residue is taken up in water and freeze-dried.

Primjer 26 Example 26

N-[4-(8-klor-2-metil-6-morfolin-4-il-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid trifluoracetat N-[4-(8-chloro-2-methyl-6-morpholin-4-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide trifluoroacetate

[image] [image]

Priprava se odvija analogno postupku opisanom u primjeru 25 počevši od N-[4-(6-brom-8-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamida (primjer 24) i morfolina. Nakon kromatografskog rastavijanja na silika gelu nastavlja se daljnje čišćenje na prep. HPLC. The preparation is carried out analogously to the procedure described in example 25 starting from N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide (example 24) and morpholine. After chromatographic separation on silica gel, further purification continues on prep. HPLC.

Primjer 27 Example 27

N-{4-[8-klor-2-metil-6-(4-metil-piperazin-1-il)-1,2,3,4-tetrahidro-izokinolin-4-il]-fenil}-acetamid N-{4-[8-chloro-2-methyl-6-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}-acetamide

[image] [image]

Proizvodnja se vrši analogno postupku opisanom u primjeru 25 počevši od N-[4-(6-brom-8-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamida (primjer 24) i N-metil-piperazina. Production is carried out analogously to the procedure described in example 25 starting from N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide (example 24) and N-methyl-piperazine.

27a: N-4-[8-klor-2-metil-6-(4-metil-piperazin-1-il)-l,2,3,4-tetrahidro-izokinolin-4-il]-fenilj-acetamid hidroklorid 27a: N-4-[8-chloro-2-methyl-6-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl-acetamide hydrochloride

[image] [image]

220 mg N-{4-[8-klor-2-metil-6-(4-metil-piperazin-1-il)-1,2,3,4-tetrahidro-izokinolin-4-il]-fenil}-acetamida otopi se u malo metanola, razrijedi se s 2 N HCl i osuši se smrzavanjem, pri čemu se dobije 226 mg željenog hidro-klorida. 220 mg N-{4-[8-chloro-2-methyl-6-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}- of acetamide is dissolved in a little methanol, diluted with 2 N HCl and freeze-dried to give 226 mg of the desired hydrochloride.

Primjer 28 Example 28

N-{4-[8-klor-6-(ciklopropilmetil-amino)-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il]-fenil}-acetamid hidroklorid N-{4-[8-chloro-6-(cyclopropylmethyl-amino)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}-acetamide hydrochloride

[image] [image]

Proizvodnja se vrši analogno postupku opisanom u primjeru 25 počevši od N-[4-(6-brom-8-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamida (primjer 24) i C-ciklopropil-metilamina. Na kromatografsko rastavljanje na silika gelu nastavlja se daljnje čišćenje na prep. HPLC. Očišćen spoj se otopi u l N HCl, razrijedi se s vodom i osuši smrzavanjem. Production is carried out analogously to the procedure described in example 25 starting from N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide (example 24) and C-cyclopropyl-methylamine. Chromatographic separation on silica gel is followed by further purification on prep. HPLC. The purified compound was dissolved in 1 N HCl, diluted with water and freeze-dried.

Primjer 29 Example 29

5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-benzojeva kiselina 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid

[image] [image]

Intermedijat 1 Intermediate 1

Etil ester 5-acetil-2-hidroksi-benzojeve kiseline dobije se na način koji je stručnjaku poznat iz 5-acetil-2-hidroksi-benzojeve kiseline esterifikacijom s kiselim katalizatotom. Ethyl ester of 5-acetyl-2-hydroxy-benzoic acid is obtained in a manner known to the expert from 5-acetyl-2-hydroxy-benzoic acid by esterification with an acid catalyst.

Intermedijat 2 Intermediate 2

Etil ester 5-(2-brom-acetil)-2-hidroksi-benzojeve kiseline dobije se poznatim postupkom iz etil estera 5-acetil-2-hidroksi-benzojeve kiseline analogno postupkuopisanom u primjeru l za intermedijat 2. Ethyl ester of 5-(2-bromo-acetyl)-2-hydroxy-benzoic acid is obtained by a known process from ethyl ester of 5-acetyl-2-hydroxy-benzoic acid analogously to the procedure described in example 1 for intermediate 2.

Intermedijat 3 Intermediate 3

Etil ester 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-benzojeve kiseline 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid ethyl ester

Počevši od etil estera 5-(2-brom-acetil)-2-hidroksi-benzojeve kiseline i 2,4-diklorbenzil-metil-amina (vidi primjer l, intermedijat 1), naslovni spoj se sintetizira postupkom opisanim u primjeru 1. Starting from the ethyl ester of 5-(2-bromo-acetyl)-2-hydroxy-benzoic acid and 2,4-dichlorobenzyl-methyl-amine (see example 1, intermediate 1), the title compound is synthesized by the procedure described in example 1.

5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-benzojeva kiselina 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid

6,8 g (18 mmolova) etil estera 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2hidroksi-benzojeve kiseline saponificira se na način koji je stručnjaku poznat u mješavini etanola i 2N KOH, pri čemu se dobije 5,4 g slobodne kiseline. 6.8 g (18 mmol) of ethyl ester of 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid is saponified in the manner known to the expert in a mixture of ethanol and 2N KOH, whereby 5.4 g of the free acid is obtained.

29a: 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-benzojeva kiselina, natrijeva sol | 29a: 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid, sodium salt |

[image] [image]

352 mg (1 mmol) slobodne kiseline 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-2-hidroksi-benzojeve kiseline otopi se u 10 ml 0,1 M NaOH, razrijedi se s vodom i osuši se smrzavanjem, pri čemu se dobije 375 mg naslovnog spoja. 352 mg (1 mmol) of free acid 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxy-benzoic acid is dissolved in 10 ml of 0.1 M NaOH, diluted with water and freeze-dried to give 375 mg of the title compound.

Primjer 30 Example 30

5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-N-metil-benzamid trifluoracetat 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-N-methyl-benzamide trifluoroacetate

[image] [image]

Počevši od 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-benzojeve kiseline naslovni spoj se može proizvesti reakcijom s metilaminoiα posredstvom TOTU-a analogno postupku opisanom u primjeru 7. Starting from 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid the title compound can be produced by reaction with methylaminoiα via TOTU analogous to the procedure described in example 7.

Primjer 31 Example 31

5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-N-etil-2-hidroksi-benzamid trifluoracetat 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-ethyl-2-hydroxy-benzamide trifluoroacetate

[image] [image]

Počevši od 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-benzojeve kiseline naslovni spoj se može proizvesti reakcijom s etilaminom posredstvom TOTU-a analogno postupku opisanom u primjeru 7. Starting from 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid the title compound can be produced by reaction with ethylamine via TOTU analogous to the procedure described in example 7.

Primjer 32 Example 32

5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-N-(2-dimetilamino-etil)-2-hidroksi-benzamid trifluoracetat 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-2-hydroxy-benzamide trifluoroacetate

[image] [image]

Počevši od 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-benzojeve kiseline naslovni spoj može proizvesti reakcijom s NI,Nl-dimetil-etan-1,2-diaminom posredstvom TOTU-a analogno postupku opisanom u primjeru 7. Starting from 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid the title compound can be produced by reaction with N1,N1-dimethyl- with ethane-1,2-diamine by means of TOTU analogously to the procedure described in example 7.

Primjer 33 Example 33

N-[5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-benzoil]-gvanidin N-[5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoyl]-guanidine

[image] [image]

K otopini od 2,39 g (25 mmolova) gvanidin hidroklorida u 15 ml aps, DMF-a doda se 2,52 g kalijevog terc-butilata i miješa se 45 min pri sobnoj temperaturi. Doda se otopinu od 950 mg (2,5 mmola) etil estera 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-benzojeve kiseline (primjer 29, intermedijat 3) u 10 ml aps. DMF-a i miješa se četiri sata pri sobnoj temperaturi. Kad se više ne može utvrditi nikakvu daljnju reakciju, talog se odsisa i otapalo se odstrani u vakuumu. Ostatak se preuzme u 2 N HCl i ekstrahira se dva puta s diklormetanom. Vodenu fazu se namjesti na pH pribl. 10 s KOH, pri čemu se željeni acil-gvanidin izluči kao bezbojni talog. Odsisavanjem i sušenjem se dobije 793 mg naslovnog spoja. To a solution of 2.39 g (25 mmol) of guanidine hydrochloride in 15 ml of aps, DMF, 2.52 g of potassium tert-butylate was added and stirred for 45 min at room temperature. Add to a solution of 950 mg (2.5 mmol) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid ethyl ester (example 29, intermediate 3) in 10 ml abs. of DMF and stirred for four hours at room temperature. When no further reaction can be detected, the precipitate is filtered off with suction and the solvent is removed in vacuo. The residue is taken up in 2 N HCl and extracted twice with dichloromethane. Adjust the aqueous phase to a pH of approx. 10 with KOH, whereby the desired acyl-guanidine is precipitated as a colorless precipitate. Suction and drying yielded 793 mg of the title compound.

Primjer 34 Example 34

N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide

[image] [image]

N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide

Priprava željenog meta acetanilida vrši se analogno postupku sinteze koji je opisan za primjer l, počevši od N-(3-acetil-fenil)-acetamida i 2, 4-diklorbenzil-metil-amina (primjer l, intermedijat 1) u četiri analogna stupnja. The preparation of the desired target acetanilide is carried out analogously to the synthesis procedure described for example 1, starting from N-(3-acetyl-phenyl)-acetamide and 2, 4-dichlorobenzyl-methyl-amine (example 1, intermediate 1) in four analogous stages .

Primjer 35 Example 35

3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine

[image] [image]

Odcjepljivanje acetila iz N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4il)-fenil]-acetamida (primjer 34) vrši se postupkom opisanim u primjeru 17 za intermedijat 1 u prisutnosti natrijevog metanolata. Acetyl separation from N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4yl)-phenyl]-acetamide (example 34) is carried out by the procedure described in example 17 for intermediate 1 in the presence of sodium methanolate.

Primjer 36 Example 36

2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine

[image] [image]

Intermedijat 1 Intermediate 1

N-[2-(2-brom-acetil)-fenil]-acetamid N-[2-(2-bromo-acetyl)-phenyl]-acetamide

31 g (0,175 mol} N-(2-acetilfenil)-acetamida (proizveden aciliranjem 2-aminoacetofenona s acetil kloridom prema Fuerstner, Alois; Jumbam, Denis N. : Tetrahedron; 48; 29; 5991-6010, (1992)) se otopi u 200 ml ledene octene kiseline. U ledenu octenu kiselinu se doda 127 ml 33%-tne HBr i zatim se pusti da pri sobnoj temperaturi doteče 8,75 ml (0,175 mola) broma. Reakcijsku smjesu se miješa preko noći pri sobnoj temperaturi. Zatim se reakcijsku smjesu umiješa u 1,5 l ledene vode, iztaloženi proizvod se odsisa, dobro se ispere s ledenom vodom i osuši u vakuumu. Prema HPLC i NMR sirov proizvod sadrži nešto edukta i dvostruko bromiranog proizvoda, ali je on dovoljno čist za daljnju pretvorbu (pribl. 85%-tni). Iskorištenje: 43 g 31 g (0.175 mol} of N-(2-acetylphenyl)-acetamide (produced by acylation of 2-aminoacetophenone with acetyl chloride according to Fuerstner, Alois; Jumbam, Denis N. : Tetrahedron; 48; 29; 5991-6010, (1992)) were dissolve in 200 ml of glacial acetic acid. 127 ml of 33% HBr is added to the glacial acetic acid and then 8.75 ml (0.175 mol) of bromine is allowed to flow in at room temperature. The reaction mixture is stirred overnight at room temperature. Then the reaction mixture is mixed in 1.5 l of ice water, the precipitated product is filtered off with suction, washed well with ice water and dried in vacuum.According to HPLC and NMR, the crude product contains some educt and doubly brominated product, but it is pure enough for further conversion (approx. 85%) Yield: 43 g

Intermedijat 2 Intermediate 2

N-(2-{2-[(2,4-diklor-benzil)-metil-amino]-acetil}-fenil}-acetamid N-(2-{2-[(2,4-dichloro-benzyl)-methyl-amino]-acetyl}-phenyl}-acetamide

12,4 g (65,24 mmola) 2,4-diklor-N-metilbenzilamina (primjer l, intermedijat 1) se otopi u 200 ml dioksana. K tome se doda 19,96 g sirovog proizvoda iz prethodnog bromiranja, također otopljenog u 200 ml dioksana i 45 ml trietilamina. Reakcijsku smjesu se miješa preko noći pri sobnoj temperaturi i zatim se profiltrira. Filtrat se ispari, ostatak se preuzme u octeni ester i ispere se sa zasićenom otopinom natrijevog hidrogenkarbonata i sa zas. otopinom NaCl, osuši se preko natrijevog sulfata i izrotira. Sirov proizvod (20,4 g) je prema NMR dovoljno čist za daljnju pretvorbu. 12.4 g (65.24 mmol) of 2,4-dichloro-N-methylbenzylamine (Example 1, intermediate 1) were dissolved in 200 ml of dioxane. To this is added 19.96 g of the crude product from the previous bromination, also dissolved in 200 ml of dioxane and 45 ml of triethylamine. The reaction mixture was stirred overnight at room temperature and then filtered. The filtrate is evaporated, the residue is taken up in acetic ester and washed with a saturated solution of sodium bicarbonate and with sat. NaCl solution, dried over sodium sulfate and spun. The crude product (20.4 g) is sufficiently pure for further conversion according to NMR.

Intermedijat 3 Intermediate 3

N-(2-{2-[(2,4-diklor-benzil)-metil-amino]-1-hidroksi-etil}-fenil)-acetamid N-(2-{2-[(2,4-dichloro-benzyl)-methyl-amino]-1-hydroxy-ethyl}-phenyl)-acetamide

20 g sirovog proizvoda iz prethodnog stupnja (pribl. 50 mmolova) otopi u 200 ml metanola i u ledenoj kupelji se ohladi na <5°C. K tome se, uz dobro miješanje, doda u obrocima 4,3 g (109 mmolova) natrijevog borhidrida, tako da unutarnja temperatura ne prijeđe 10CC. Zatim se miješa još 30 min na ledenoj kupelji i l h pri sobnoj temperaturi. Nakon stajanja preko noći, reakcijsku smjesu se ispari, ostatak se preuzme u octeni ester, ispere se 3 puta s vodom i jednom s otopinom NaCl, osuši se preko natrijevog sulfata i izrotira. Sirov proizvod (19,4 g) se pretvara dalje bez čišćenja. Dissolve 20 g of the crude product from the previous step (approx. 50 mmol) in 200 ml of methanol and cool it to <5°C in an ice bath. To this, with good mixing, 4.3 g (109 mmol) of sodium borohydride are added in portions, so that the internal temperature does not exceed 10°C. Then it is stirred for another 30 min in an ice bath and 1 h at room temperature. After standing overnight, the reaction mixture is evaporated, the residue is taken up in acetic ester, washed 3 times with water and once with NaCl solution, dried over sodium sulfate and spun. The crude product (19.4 g) is converted further without purification.

Intermedijat 4 Intermediate 4

l-(2-amino-fenil)-2-[(2,4-diklor-benzil)-metil-amino]etanol 10 g sirovog proizvoda iz prethodnog stupnja se otopi u 300 ml metanola. Doda se 200 ml konc. solne kiseline i miješa se 10 h pri 50 C. Pusti se ohladiti, reakcijsku smjesu se prelije u vodu i pH vrijednost se namjesti na 10-12 s 20%-tnom NaOH. Proizvod se ekstrahira s octenim esterom, sjedinjeni ekstrakti se isperu s otopinom NaCl, osuše se preko natrijevog sulfata i ispare. Sirov proizvod (9,9 g) sadrži nešto NaCl, koji međutim ne smeta daljnjoj pretvorbi. 1-(2-amino-phenyl)-2-[(2,4-dichloro-benzyl)-methyl-amino]ethanol 10 g of the crude product from the previous step is dissolved in 300 ml of methanol. Add 200 ml conc. of hydrochloric acid and stirred for 10 h at 50 C. Allow to cool, pour the reaction mixture into water and adjust the pH to 10-12 with 20% NaOH. The product is extracted with acetic ester, the combined extracts are washed with NaCl solution, dried over sodium sulfate and evaporated. The crude product (9.9 g) contains some NaCl, which, however, does not interfere with further conversion.

2-(6,8-diklor-2-metil-l/ 2, 3,4-tetrahidro-izokinolin-4-il)-fenilamin 2-(6,8-dichloro-2-methyl-1/2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine

9, 9 g sirovog proizvoda iz prethodnog stupnja se otopi u 350 ml klorforma. Uz hlađenje na ledenoj kupelji dokaplje se 123 ml konc. sumporne kiseline. Miješa se 2 h na ledenoj kupelji, zatim se pusti da polako dođe na sobnu temperaturu i zatim se grije preko noći pri 50°C. Ohlađenu reakcijsku smjesu se prelije na led i s natrijevom lužinom se namjesti alkalno (pH > 10). Organsku fazu se odvoji, a vodenu fazu se ekstrahira dva puta s metilen kloridom, sjedinjene organske faze se isperu s vodom i s NaCl, osuše se preko natrijevog sulfata i ispare. 9.9 g of the crude product from the previous step is dissolved in 350 ml of chloroform. After cooling in an ice bath, 123 ml conc. sulfuric acid. It is stirred for 2 h in an ice bath, then allowed to slowly come to room temperature and then heated overnight at 50°C. The cooled reaction mixture is poured over ice and made alkaline (pH > 10) with sodium hydroxide solution. The organic phase is separated, and the aqueous phase is extracted twice with methylene chloride, the combined organic phases are washed with water and NaCl, dried over sodium sulfate and evaporated.

Opći propis za proizvodnju spojeva iz primjera 37 do 77: General regulation for the production of compounds from examples 37 to 77:

154 mg (0,5 mmola) naslovnog spoja iz primjera 35, primjera 36 ili primjera 17 i intermedijat 1 se stavi u 5 ml diklormetana i pomiješa se s 0,076 ml (0,55 mmola) trietilamina. Pri 0°C se doda otopinu od 1,1 ekvivalenta (0,55 mmola) kiselinskog klorida u 5 ml diklormetana i potopljeno se miješa preko noći. Za obradu se profiltrira i oslobodi od otapala. Ostatak se otopi u 20 ml octenog estera i jednom se ispere s 5%-tnom otopinom NaHCO3 i jednom s 5%-tnom otopinom NaCl i osuši se. Nakon koncentriranja otapala slijedi krajnje čišćenje na prep. HPLC. 154 mg (0.5 mmol) of the title compound from Example 35, Example 36 or Example 17 and intermediate 1 were placed in 5 ml of dichloromethane and mixed with 0.076 ml (0.55 mmol) of triethylamine. At 0°C, a solution of 1.1 equivalents (0.55 mmol) of acid chloride in 5 ml of dichloromethane was added and stirred under immersion overnight. For processing, it is filtered and freed from the solvent. The residue is dissolved in 20 ml of ethyl acetate and washed once with a 5% NaHCO3 solution and once with a 5% NaCl solution and dried. After the concentration of the solvent, the final cleaning on prep. HPLC.

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

*) Proizvod se izluči iz reakcijske otopine i nije mu potrebno nikakvo daljnje čišćenje. ;Primjer 78 ;1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea trifluoracetat ;[image] ;0,355 nunola spoja iz primjera 35 otopi se u 5 ml suhog acetonitrila i pomiješa se s 0,39 mmola etil izocijanata. Nakon stajanja preko noći uz isključenje vlage, otapalo se odstrani i sirov proizvod se očisti na preparativnoj HPLC, pri čemu se dobije naslovni spoj kao bezbojna kruta tvar. ;Primjer 79 ;1-[3-(6,8-diklor-2-metil-l/2/3, 4-tetrahidro-izokinolin-4-il)-fenil]-3-metil-tiourea trifluoracetat ;[image] ;Počevši od spoja iz primjera 35 i metil izotiocijanata naslovni spoj se sintetizira postupkom opisanim u primjeru 78. ;Primjer 80 ;1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea ;[image] ;Počevši od spoja iz primjera 36 i etil izocianata analogno postupku iz primjera 78. Za obradu se nastali talog odsisa i ispere s acetonitrilom, pri čemu se dobije željenu etilureu kao bezbojnu krutu tvar. ;Primjer 81 ;1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-metil-tiourea trifluoracetat ;[image] ;Spoj iz primjera 36 i metil izotiocianat reagiraju analogno postupku opisanom u primjeru 78. ;Primjer 82 ;Etansulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid hidroklorid ;[image] ;307,1 mg (1 mmol) spoja iz primjera 35 otopi se u 10 ml piridina i pri 0°C se pomiješa s 0,19 g (1,5 mmola) etansulfonil klorida, kao i s katalitičkom količinom DMAP-a. Miješa se pri sobnoj temperaturi. Za obradu se otapalo odstrani u vakuumu, ostatak se preuzme u octeni ester i ispere s vodom. Organsku fazu se osuši s MgSO4 i koncentrira. Sirov proizvod se kromatografira na silika gelu. Tako dobiven sulfonamid se otopi u mješavini THF/2N HCl i ponovno se koncentrira u vakuumu, pri čemu se dobije 208 mg željenog hidroklorida. ;Primjer 83 ;N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamid hidroklorid ;[image] ;Počevši od spoja iz primjera 35 i metansulfonil klorida analogno postupku opisanom u primjeru 82. ;Primjer 84 ;Etansulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid hidroklorid ;[image] ;Počevši od spoja iz primjera 17, intermedijata l i etansulfonil klorida analogno postupku opisanom u primjeru 82. ;Primjer 85 ;N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]metansulfonamid hidroklorid ;[image] ;Počevši od spoja iz primjera 17, intermedijata l i metansulfonil klorida analogno postupku opisanom u primjeru 82. ;Primjer 86 ;86a: (-)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; ;86b: (+)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid ;[image] ;2,0 g naslovnog spoja iz primjera 34 rastavi se na kiralnoj fazi, pri čemu se dobije pribl. 1,0 g dvaju enantiomernih acetamida 86a i 86b. Kiralni stupac: Chiralpak ADH/31 250 x 4,6 mm; otapalo: acetonitril; brzina protoka: l ml/min; Rt ((-)-enantiomer/86a)= 5,541 min; Rt ((+)-Enantioraer/86b) = 7,033 min. ;Opći propis za pripravu spojeva iz primjera 87 do 98 ;1,0 mmol 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamina (primjer 17, intermedijat 1), odnosno 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-1zo-kinolin-4-il)-fenilamina (primjer 35) se stavi u 10 ml piridina i pri O'C se dokaplje otopinu od 1,2 ekvivalenta odgovarajućeg klorida sulfonske kiseline (vidi tablicu 2) u 5 ml diklormetana. Miješa se pri sobnoj temperaturi. Ovisno o napredovanju reakcije, doda se katalitičku količinu DMAP-a i prema potrebi reakcijsku temperaturu se povisi na 50°C sve dok se više ne može utvrditi nikakvu daljnju pretvorbu. Za obradu se koncentrira i ostatak se podijeli između octenog estera i zas. otopinom NaHCO3. Organsku fazu se odvoji i još jednom se ispere sa zas. otopinom NaHCO3 i H2O, osuši se s Na2SO4 i koncentrira. Za daljnje čišćenje se tako dobiven sirov proizvod kromatografira na silika gelu. Za prevođenje tako dobivenog proizvoda u odgovarajući hidroklorid, tvari se otope u 2 N HCl ili etanolnoj HCl i oslobode se otapala, pri čemu se dobiju željene HCl soli. ;Čišćenjem na uređaju za preparativnu HPLC dobiju se odgovarajući proizvodi kao trifluoracetati. ;Tablica 2: ;[image] ;[image] ;[image] ;[image] ;[image] ;Opći radni propis za sintezu spojeva iz primjera 99 do 110 ;Priprava aminske komponente ;4,0 mmola aromatskog aldehida (vidi tablicu 3) miješa se 2 sata pri sobnoj temperaturi s 8,0 mmolova alifatskog amina (vidi tablicu 3) u metanolu i zatim se, ovisno o napredovanju reakcije, pomiješa u obrocima s 0,67 do 2,0 ekv. NaBH4. Nakon stajanja preko noći pri sobnoj temperaturi, otapalo se odstrani i ostatak se preuzme u l N HCl. Ekstrahira se s diklormetanom. Vodenu fazu se namjesti na pH vrijednost 11 do 12 s NaOH i ponovno se ekstrahira se s diklormetanom. Organske faze se osuše s MgSO4 i izrotiraju. Daljnje čišćenje se vrši kromatografijom na silika gelu ili na prep. HPLC. ;Priprava bromketonske komponente ;Komponentu bromketona sintetizira se postupcima koji su poznati iz literature počevši od komercijalno dostupnih acetofenona, obradom s bromom u ledenoj octenoj kiselini analogno primjeru I, intermedijat 2. ;Počevši od aminskih i bromketonskih komponenata navedenih u tablici 3 mogu se proizvesti spojevi iz primjera 100 do 111 analogno putu sinteze koji je prikazan u primjeru l (alkiliranje aminske komponente s brom-ketonskom komponentom, zatim redukcija s NaBH4 i na kraju ciklizacija posredstvom H2SO4). ;Dobiveni tetrahidroizokinolini mogu se prevesti u odgovarajuće soli na način koji je stručnjaku poznat. ;Tablica 3 ;[image] ;[image] ;*) Sinteza je opisana u Lang et al., DOS 24 36 263. *) The product is excreted from the reaction solution and does not need any further purification. Example 78 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea trifluoroacetate ;[image] 0.355 mol of the compound from Example 35 was dissolved in 5 ml of dry acetonitrile and mixed with 0.39 mmol of ethyl isocyanate. After standing overnight with exclusion of moisture, the solvent was removed and the crude product was purified by preparative HPLC to give the title compound as a colorless solid. Example 79 1-[3-(6,8-dichloro-2-methyl-1/2/3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea trifluoroacetate ;[image] ;Starting with the compound from example 35 and methyl isothiocyanate, the title compound is synthesized by the procedure described in example 78. ;Example 80 ;1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro- isoquinolin-4-yl)-phenyl]-3-ethyl-urea ;[image] ;Starting with the compound from example 36 and ethyl isocyanate analogously to the procedure from example 78. For processing, the resulting precipitate is suctioned off and washed with acetonitrile, which gives the desired ethylurea as a colorless solid. Example 81 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea trifluoroacetate ;[image] ;The compound from example 36 and methyl isothiocyanate react analogously to the procedure described in example 78. ;Example 82 ;Ethanesulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline-4 -yl)-phenyl]-amide hydrochloride ; [image] ; 307.1 mg (1 mmol) of the compound from example 35 is dissolved in 10 ml of pyridine and mixed with 0.19 g (1.5 mmol) at 0°C of ethanesulfonyl chloride, as well as with a catalytic amount of DMAP. Mix at room temperature. For processing, the solvent is removed under vacuum, the residue is taken up in acetic ester and washed with water. The organic phase is dried with MgSO4 and concentrated. The crude product is chromatographed on silica gel. The sulfonamide thus obtained is dissolved in a THF/2N HCl mixture and concentrated again in vacuo to give 208 mg of the desired hydrochloride. ;Example 83 ;N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide hydrochloride ;[image] ;Starting from the compound from example 35 and methanesulfonyl chloride analogously to the procedure described in example 82. ; Example 84 ; Ethansulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl) -phenyl]-amide hydrochloride ;[image] ;Starting with the compound from example 17, intermediate 1 and ethanesulfonyl chloride analogously to the procedure described in example 82. ;Example 85 ;N-[4-(6,8-dichloro-2-methyl-1 ,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]methanesulfonamide hydrochloride ;[image] ;Starting with the compound from example 17, intermediate 1 and methanesulfonyl chloride analogously to the procedure described in example 82. ;Example 86 ;86a: ( -)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide; ;86b: (+)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide ;[image] ;2 .0 g of the title compound from example 34 is separated on the chiral phase, whereby approx. 1.0 g of two enantiomeric acetamides 86a and 86b. Chiral column: Chiralpak ADH/31 250 x 4.6 mm; solvent: acetonitrile; flow rate: l ml/min; Rt ((-)-enantiomer/86a)= 5.541 min; Rt ((+)-Enantiomer/86b) = 7.033 min. ; General recipe for the preparation of compounds from examples 87 to 98 ; 1.0 mmol of 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (example 17 , intermediate 1), or 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-1zo-quinolin-4-yl)-phenylamine (example 35) is placed in 10 ml of pyridine and at 0'C, a solution of 1.2 equivalents of the corresponding sulfonic acid chloride (see Table 2) in 5 ml of dichloromethane is added dropwise. Mix at room temperature. Depending on the progress of the reaction, a catalytic amount of DMAP is added and, if necessary, the reaction temperature is raised to 50°C until no further conversion can be detected. For processing, it is concentrated and the residue is divided between acetic ester and sat. NaHCO3 solution. The organic phase is separated and washed once more with sat. NaHCO3 and H2O solution, dried with Na2SO4 and concentrated. For further purification, the thus obtained crude product is chromatographed on silica gel. To convert the thus obtained product into the corresponding hydrochloride, the substances are dissolved in 2 N HCl or ethanolic HCl and freed from the solvent, whereby the desired HCl salts are obtained. Purification on a preparative HPLC device gives the corresponding products as trifluoroacetates. ;Table 2: ;[image] ;[image] ;[image] ;[image] ;[image] ;General working regulation for the synthesis of compounds from examples 99 to 110 ;Preparation of the amine component ;4.0 mmol of aromatic aldehyde (see table 3) it is mixed for 2 hours at room temperature with 8.0 mmol of aliphatic amine (see table 3) in methanol and then, depending on the progress of the reaction, it is mixed in portions with 0.67 to 2.0 equiv. NaBH4. After standing overnight at room temperature, the solvent was removed and the residue was taken up in 1 N HCl. It is extracted with dichloromethane. The aqueous phase is adjusted to pH 11 to 12 with NaOH and extracted again with dichloromethane. The organic phases are dried with MgSO4 and centrifuged. Further purification is performed by chromatography on silica gel or on prep. HPLC. ;Preparation of the bromoketone component ;The bromoketone component is synthesized by methods known from the literature starting from commercially available acetophenones, by treatment with bromine in glacial acetic acid analogous to example I, intermediate 2. ;Starting from the amine and bromoketone components listed in Table 3, compounds can be produced from examples 100 to 111 analogously to the synthesis route shown in example 1 (alkylation of the amine component with the bromo-ketone component, then reduction with NaBH4 and finally cyclization by means of H2SO4). The obtained tetrahydroisoquinolines can be converted into the corresponding salts in a manner known to the expert. ;Table 3 ;[image] ;[image] ;*) The synthesis is described in Lang et al., DOS 24 36 263.

Opći radni propis za pripravu spojeva iz primjera 111 do 124 General working regulations for the preparation of compounds from examples 111 to 124

0,358 mmola kiseline navedene u tablici 4 otopi se u l ml DMF-a i doda se 0,221 ml (1,30 mmola) diizopropiletil-amina. Pri 0°C dokaplje se otopinu od 128 mg (0,390 mmola) TOTU-a u l ml DMF-a. Kad se otopinu od 100 mg (0,325 mmola) aminske komponente, navedene u tablici 4, pomiješa u 2 ml DMF-a, miješa se preko noći pri sobnoj temperaturi. Za obradu se neotopljeni sastojci odfiltriraju i isperu s 20 ml octenog estera. Filtrat se ispere dva puta sa zas. otopinom NaHCO3, kao i jednom s 5%-tnom otopinom NaCl, osuši se i koncentrira. 0.358 mmol of the acid listed in Table 4 was dissolved in 1 ml of DMF and 0.221 ml (1.30 mmol) of diisopropylethylamine was added. At 0°C, a solution of 128 mg (0.390 mmol) of TOTU in 1 ml of DMF was added dropwise. When a solution of 100 mg (0.325 mmol) of the amine component listed in Table 4 was mixed in 2 ml of DMF, it was stirred overnight at room temperature. For processing, undissolved ingredients are filtered off and washed with 20 ml of acetic ester. The filtrate is washed twice with sat. with a NaHCO3 solution, as well as once with a 5% NaCl solution, dried and concentrated.

Bilo koji sirov proizvod koji još sadrži Boe zaštitne skupine deprotektira se bez daljnjeg čišćenja (vidi dolje opći radni propis za odcjepljenje Boe zaštitnih skupina). Komponente koje nisu zaštićene sa Boe zaštitnim skupinama će nakon obrade, zbog čišćenja na preparativnoj HPLC, dati željene spojeve u obliku trifluoracetata. Any crude product that still contains Boe protecting groups is deprotected without further purification (see below general operating procedure for removal of Boe protecting groups). Components that are not protected with Boe protecting groups will after processing, due to cleaning on preparative HPLC, give the desired compounds in the form of trifluoroacetate.

Opći radni propis za pripravu spojeva iz primjera 124 do 147 General working regulations for the preparation of compounds from examples 124 to 147

0,358 mmola kiseline navedene u tablici 4 otopi se u l ml DMF-a i doda se 0,221 ml (1,30 mmola) diizopropiletil-amina. Pri 0°C se pomiješa sa 151 mg (0,975 mmola) dietil-karbodiimida, s otopinom od 132 mg (0,975 mmola) HOBt-a u l ml DMF-a, kao i s 20 mg (0,162 mmola) DMAP-a. Kad se dokaplje otopinu aminske komponente u 2 ml DMF-a, navedene u tablici 4, miješa se preko noći pri sobnoj temtperaturi. Za obradu se neotopljeni sastojci odfiltriraju i isperu s 20 ml octenog estera. Filtrat se ispere dva puta sa zas. otopinom NaHCO3, kao i jednom s 5%-tnom otopinom NaCl, osuši se i koncentrira. 0.358 mmol of the acid listed in Table 4 was dissolved in 1 ml of DMF and 0.221 ml (1.30 mmol) of diisopropylethylamine was added. At 0°C, it is mixed with 151 mg (0.975 mmol) of diethylcarbodiimide, with a solution of 132 mg (0.975 mmol) of HOBt in 1 ml of DMF, as well as with 20 mg (0.162 mmol) of DMAP. When the solution of the amine component in 2 ml of DMF, listed in table 4, is added dropwise, it is stirred overnight at room temperature. For processing, undissolved ingredients are filtered off and washed with 20 ml of acetic ester. The filtrate is washed twice with sat. with a NaHCO3 solution, as well as once with a 5% NaCl solution, dried and concentrated.

Bilo koji sirov proizvod koji još sadrži Boe zaštitne skupine deprotektira se bez daljnjeg čišćenja (vidi dolje opći radni propis za odcjepljenje Boe zaštitnih skupina). Komponente koje nisu zaštićene sa Boc zaštitnim skupinama će nakon obrade, zbog čišćenja na preparativnoj HPLC, dati željene spojeve u obliku trifluoracetata. Any crude product that still contains Boe protecting groups is deprotected without further purification (see below general operating procedure for removal of Boe protecting groups). Components that are not protected with Boc protecting groups will after processing, due to cleaning on preparative HPLC, give the desired compounds in the form of trifluoroacetate.

Opći radni propis za odcjepljenje Boc zaštinih skupina General working regulation for the separation of Boc protection groups

Dobiven sirov proizvod se miješa jedan sat u 5 ml 10%-tne otopine trifluoroctene kiseline u diklormetanu pri sobnoj temperaturi. Zatim se koncentrira u vakuumu i ostatak se očisti na preparativnoj HPLC, pri čemu se dobije željeni spoj kao trifluoracetat. The obtained crude product is stirred for one hour in 5 ml of a 10% solution of trifluoroacetic acid in dichloromethane at room temperature. It is then concentrated in vacuo and the residue is purified by preparative HPLC to give the desired compound as trifluoroacetate.

Tablica 4 Table 4

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

Primjer 148 Example 148

1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-tiourea hidroklorid 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea hydrochloride

[image] [image]

2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin (95 mg, spoj iz primjera 36) se stavi u 4 ml acetonitrila i uz miješanje se doda 27 mg etil izotio-cijanata. Nakon stajanja 15 sati pri sobnoj temperaturi, otapalo se odstrani u vakuumu i ostatak se očisti na prep. HPLC. 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (95 mg, compound from Example 36) was placed in 4 ml of acetonitrile and, with stirring, add 27 mg of ethyl isothiocyanate. After standing for 15 hours at room temperature, the solvent is removed under vacuum and the residue is purified on prep. HPLC.

Tako dobiven trifluoracetat se preuzme u vodu i s K2CO3 se namjesti alkalno. Vodenu fazu se ekstrahira s octenim esterom. Organsku fazu se odvoji, osuši se s MgSO4 i koncentrira. Ostatak se preuzme u razrijeđenu HCl i osuši smrzavanjem, pri čemu se dobije 36 mg naslovnog spoja. The thus obtained trifluoroacetate is taken up in water and made alkaline with K2CO3. The aqueous phase is extracted with ethyl acetate. The organic phase is separated, dried with MgSO4 and concentrated. The residue was taken up in dilute HCl and freeze-dried to give 36 mg of the title compound.

Primjer 149 Example 149

1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3etil-tiourea hidroklorid 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea hydrochloride

[image] [image]

4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin (50 mg, spoj iz primjera 17, intermedijat 1) se stavi u 4 ml THF-a i pomiješa se s etilizotiocijanatom (14 mg). Nakon grijanja 2 sata pod refluksom, reakcijsku otopinu se koncentrira i grije se 2 sata pri 85°C. Tako dobiven sirov proizvod se očisti na prep. HPLC. Daljnjom obradom tako dobivenog trifluoracetata, kako je opisano u primjeru 148, i nakon sušenja smrzavanjem dobije se 33 mg željenog hidroklorida. 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (50 mg, compound from Example 17, intermediate 1) was placed in 4 ml of THF- and mixed with ethyl isothiocyanate (14 mg). After heating for 2 hours under reflux, the reaction solution is concentrated and heated for 2 hours at 85°C. The raw product obtained in this way is purified on prep. HPLC. Further processing of the thus obtained trifluoroacetate, as described in example 148, and after freeze-drying, yielded 33 mg of the desired hydrochloride.

Primjer 150 Example 150

1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-tioure trifluoracetat 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-thiourea trifluoroacetate

[image] [image]

3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin (50 mg, spoj iz primjera 35) se otopi u 3 ml THF-a i uz miješanje se pomiješa sa 14 mg etilizotio-cijanata. Nakon grijanja 2 sata pod refluksom, reakcijsku otopinu se koncentrira i grije se 2 sata pri 85°C. Tako dobiven sirov proizvod se očisti na prep. HPLC, pri čemu se dobije 66 mg naslovnog spoja. 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (50 mg, compound from Example 35) was dissolved in 3 ml of THF and with the mixture is mixed with 14 mg of ethyl isothiocyanate. After heating for 2 hours under reflux, the reaction solution is concentrated and heated for 2 hours at 85°C. The raw product obtained in this way is purified on prep. HPLC, yielding 66 mg of the title compound.

Primjer 151 Example 151

3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-1,1-dimetil-urea hidroklorid 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea hydrochloride

[image] [image]

Intermedijat 1 Intermediate 1

[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilj-karbaminska kiselina-4-nitro-fenil ester hidroklorid 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin (350 mg, spoj iz primjera 35) se otopi u 17,5 ml diklormetana i uz miješanje se pomiješa s 230 mg 4-nitrofenil estera klor-mravlje kiseline. Nakon 4,5 sata doda se još 0,1 ekvivalenta (23 mg) 4-nitrofenil estera klor-mravlje kiseline i otopinu se miješa preko noći. Za obradu se nastali talog odfiltrira i ispere se s diklor-metanom. Tako dobiven naslovni spoj može se dalje pretvarati bez daljnjeg čišćenja. [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylj-carbamic acid-4-nitro-phenyl ester hydrochloride 3-(6,8- Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (350 mg, compound from Example 35) was dissolved in 17.5 ml of dichloromethane and mixed with 230 mg of 4 -nitrophenyl ester of chloroformic acid. After 4.5 hours, another 0.1 equivalent (23 mg) of chloroformic acid 4-nitrophenyl ester was added and the solution was stirred overnight. For processing, the resulting precipitate is filtered off and washed with dichloromethane. The title compound thus obtained can be further converted without further purification.

3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-1,1-dimetil-urea hidroklorid 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea hydrochloride

35 mg [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-1zo-kinolin-4-il)-fenil]-karbaminska kiselina-4-nitro-fenil-ester hidroklorida (intermedijat 1) suspendira se u 3,5 ml diklormetana i uz miješanje se dokaplje otopinu od 3,7 mg dimetilamina u l ml diklormetana. Nakon l sata razrijedi se s diklormetanom i ispere se s vodenom otopinom K2CO3. Organsku fazu se odvoji i ispere se dva puta sa zas. otopinom K2CO3, osuši se s MgSO4 i koncentrira. Ostatak se preuzme u razlijedenu HCl i osuši smrzavanjem, pri čemu se dobije 29 mg naslovnog spoja. 35 mg [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-1zo-quinolin-4-yl)-phenyl]-carbamic acid-4-nitro-phenyl-ester hydrochloride ( intermediate 1) is suspended in 3.5 ml of dichloromethane and a solution of 3.7 mg of dimethylamine in 1 ml of dichloromethane is added dropwise while stirring. After 1 hour, it is diluted with dichloromethane and washed with an aqueous solution of K2CO3. The organic phase is separated and washed twice with sat. K2CO3 solution, dried with MgSO4 and concentrated. The residue was taken up in dilute HCl and freeze-dried to give 29 mg of the title compound.

Slijedeći primjeri su proizvedeni analogno postupku opisanom u primjeru 151 počevši od intermedijata l i odgovarajućih aminskih komponenata. The following examples were produced analogously to the procedure described in example 151 starting from intermediate 1 and the corresponding amine components.

Tablica 5 Table 5

[image] [image]

[image] [image]

Slijedeći primjeri su proizvedeni analogno postupku opisanom u primjeru 151. Kao otapalo je poslužio THF, a reakcija je provedena u zatvorenoj reakcijskoj posudi. Kod primjera 159 do 166 bile su potrebne reakcijske temperature od 85°C. Primjer 167 je očišćen pomoću prep. HPLC. The following examples were produced analogously to the procedure described in example 151. The solvent was THF, and the reaction was carried out in a closed reaction vessel. Examples 159 to 166 required reaction temperatures of 85°C. Example 167 was cleaned using prep. HPLC.

Tablica 6: Table 6:

[image] [image]

[image] [image]

Primjer 168 Example 168

4-metil-piperazin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid hidroklorid 4-methyl-piperazine-1-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide hydrochloride

[image] [image]

Intermedijat 1 Intermediate 1

[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina-4-nitro-fenil-ester hidroklorid 2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin (200 mg, spoj iz primjera 36) se otopi u 10 ml diklormetana i uz miješanje se pomiješa sa 131 mg klor-mravlja kiselina-4-nitrofenil estera. Nakon 3,5 sata nastali talog se odsisa i ispere s diklormetanom. Tako dobiven sirov proizvod se prekristalizira iz diklormetana, pri čemu se dobije 159 mg naslovnog spoja. [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid-4-nitro-phenyl-ester hydrochloride 2-(6, 8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (200 mg, compound from Example 36) was dissolved in 10 ml of dichloromethane and mixed with 131 mg of chlorine -formic acid-4-nitrophenyl ester. After 3.5 hours, the resulting precipitate is suctioned off and washed with dichloromethane. The crude product thus obtained is recrystallized from dichloromethane, whereby 159 mg of the title compound is obtained.

4-metil-piperazin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2, 3,4-tetrahidro-izokinolin-4-il)-fenil]-amid hidroklorid 4-Methyl-piperazine-1-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide hydrochloride

15 mg [2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-1zo-kinolin-4-il)-fenil]-karbaminska kiselina-4-nitro-fenil-ester hidroklorida se suspendira u 2 ml diklormetana i pomiješa se s otopinom od 3,2 mg 1-metil-piperazina u l ml diklormetana. Nakon l sata se razrijedi s diklormetanom i ispere se s vodenom otopinom K2CO3. Organsku fazu se odvoji i ispere dva puta sa zas. otopinom K2CO3, osuši se preko MgSO4 i koncentrira. Ostatak se preuzme u razrijeđenu HCl i osuši smrzavanjem, pri čemu se dobije 13 mg naslovnog spoja. 15 mg of [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-1zo-quinolin-4-yl)-phenyl]-carbamic acid-4-nitro-phenyl-ester hydrochloride se suspended in 2 ml of dichloromethane and mixed with a solution of 3.2 mg of 1-methyl-piperazine in 1 ml of dichloromethane. After 1 hour, it is diluted with dichloromethane and washed with an aqueous solution of K2CO3. The organic phase is separated and washed twice with sat. K2CO3 solution, dried over MgSO4 and concentrated. The residue was taken up in dilute HCl and freeze-dried to give 13 mg of the title compound.

Slijedeći primjeri su proizvedeni analogno postupku opisanom u primjeru 168. The following examples were produced analogously to the procedure described in example 168.

Tablica 7 Table 7

[image] [image]

Primjer 176 Example 176

4-metil-piperazin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid hidroklorid 4-methyl-piperazine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide hydrochloride

[image] [image]

Intermedijat 1 Intermediate 1

[4-(6,8-diklor-2-metil-l,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina-4-nitro-fenil-ester hidroklorid [4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid-4-nitro-phenyl-ester hydrochloride

4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin (200 mg, spoj iz primjera 17, intermedijat 1) se otopi u 10 ml diklormetana i uz miješanje se pomiješa sa 131 mg klormravlja kiselina-4-nitrofenil estera. Nakon 4,5 sata nastali talog se odsisa i ispere s diklormetanom. Tako dobiven sirov proizvod se dva puta kristalizira iz diklormetana, pri čemu se dobije 254 mg naslovnog spoja. 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (200 mg, compound from Example 17, intermediate 1) was dissolved in 10 ml of dichloromethane and with stirring, it is mixed with 131 mg of chloroformic acid-4-nitrophenyl ester. After 4.5 hours, the resulting precipitate is suctioned off and washed with dichloromethane. The crude product thus obtained is crystallized twice from dichloromethane, whereby 254 mg of the title compound is obtained.

4-metil-piperazin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid hidroklorid 15 mg [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-1zo-kinolin-4-il)-fenil]-karbaminska kiselina-4-nitro-fenil-ester hidroklorida se suspendira u 2 ml diklormetana i pomiješa se s otopinom od 3,2 mg 1-metil-piperazina u l ml diklormetana. Nakon 5 sati miješanja i stajanja preko noći, razrijedi se s diklormetanom i ispere s vodenom otopinom K2CO3. Organsku fazu se odvoji i ispere se dva puta sa zas. K2CO3, osuši se s MgSO4 i koncentrira. Ostatak se preuzme u razrijeđenu HCl i osuši smrzavanjem, pri čemu se dobije 13 mg naslovnog spoja. 4-methyl-piperazine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide hydrochloride 15 mg [ 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydro-1zo-quinolin-4-yl)-phenyl]-carbamic acid-4-nitro-phenyl-ester hydrochloride is suspended in 2 ml of dichloromethane and mixed with a solution of 3.2 mg of 1-methyl-piperazine in 1 ml of dichloromethane. After stirring for 5 hours and standing overnight, it is diluted with dichloromethane and washed with an aqueous solution of K2CO3. The organic phase is separated and washed twice with sat. K2CO3, dried with MgSO4 and concentrated. The residue was taken up in dilute HCl and freeze-dried to give 13 mg of the title compound.

Slijedeći primjeri proizvedeni su analogno postupku opisanom u primjeru 176. The following examples were produced analogously to the procedure described in example 176.

Tablica 8 Table 8

[image] [image]

[image] [image]

Primjer 184 Example 184

N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]formamid hidroklorid N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]formamide hydrochloride

[image] [image]

4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin (200 mg, spoj iz primjera 17, intermedijat 1) otopi se u l ml mravlje kiseline i grije se 15 min pod refluksom. Nakon stajanja preko noći reakcijsku smjesu se doda u mješavinu leda i vode i ekstrahira se dva puta s octenim esterom. Sjedinjene organske faze se osuše preko MgSO4 i koncentriraju. Ostatak se preuzme u diklormetan i ispere sa zas. otopinom NaHCO3. Faze se odvoje i vodenu fazu se ekstrahira još tri puta s diklormetanom. Sušenjem organske faze (MgSO4) i odstranjivanjem otapala destilacijom dobije se 167 mg sirovog proizvoda. 10 mg se otopi u razrijeđenoj HCl i osuši smrzavanjem, pri čemu se dobije 11 mg naslovnog spoja. 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (200 mg, compound from Example 17, intermediate 1) was dissolved in 1 ml of formic acid and it is heated for 15 min under reflux. After standing overnight, the reaction mixture was added to a mixture of ice and water and extracted twice with ethyl acetate. The combined organic phases are dried over MgSO4 and concentrated. The residue is taken up in dichloromethane and washed with sat. NaHCO3 solution. The phases are separated and the aqueous phase is extracted three more times with dichloromethane. By drying the organic phase (MgSO4) and removing the solvent by distillation, 167 mg of crude product is obtained. 10 mg was dissolved in dilute HCl and freeze-dried to give 11 mg of the title compound.

Primjer 185 Example 185

[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]metil-amin hidroklorid [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]methyl-amine hydrochloride

[image] [image]

N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil] formamid (150 mg, spoj iz primjera 184) otopi se u 2,5 ml THF-a i pri 50°C pod argonom se dokaplje u otopinu od 0,45 ml l M otopine litij-aluminijevog hidrid, THF-a u 2,5 ml THF-a. Grije se l sat pod refluksom. Nakon stajanja preko noći pri 50°C doda se još 0,22 ml l M otopine litij-aluminijevog hidrida i grije se još jedan sat pod refluksom. Za obradu se otapalo odstrani i ostatak se podijeli između diklormetana i vodene HCl. Faze se rastave i vodenu fazu se ekstrahira tri puta s diklormetanom. Sjedinjene organske faze se osuše na MgSO4 i koncentriraju. Daljnje čišćenje se vrši na prep. HPLC. Tako dobiven proizvod se preuzme u otopinu NaHCO3 i ekstrahira se s diklormetanom. Sušenjem organske faze s MgSO4 dobije se 80 mg slobodne baze. 10 mg se preuzme u razrijeđenu HCl i osuši smrzavanjem, pri čemu se dobije 10 mg naslovnog spoja. N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl] formamide (150 mg, compound from Example 184) was dissolved in 2.5 ml of THF and at 50°C under argon is added dropwise to a solution of 0.45 ml of a 1 M solution of lithium aluminum hydride, THF in 2.5 ml of THF. It is heated under reflux for 1 hour. After standing overnight at 50°C, another 0.22 ml of 1 M lithium-aluminum hydride solution is added and heated for another hour under reflux. For workup, the solvent was removed and the residue was partitioned between dichloromethane and aqueous HCl. The phases are separated and the aqueous phase is extracted three times with dichloromethane. The combined organic phases are dried over MgSO4 and concentrated. Further cleaning is done on prep. HPLC. The product thus obtained is taken up in NaHCO3 solution and extracted with dichloromethane. By drying the organic phase with MgSO4, 80 mg of the free base is obtained. 10 mg was taken up in dilute HCl and freeze-dried to give 10 mg of the title compound.

Primjer 186 Example 186

1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-1,3-dimetil-urea hidroklorid 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea hydrochloride

[image] [image]

Naslovni spoj je proizveden postupkom opisanim u primjeru 151 počevši od [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amina (primjer 185), 4-nitrofenilklorformata i metilaraina (20 ul, 2 M u THF-u), pri čemu se dobije 9 mg željenog hidroklorida. The title compound was prepared by the procedure described in Example 151 starting from [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine (Example 185), 4-nitrophenylchloroformate and methylaraine (20 µl, 2 M in THF), to give 9 mg of the desired hydrochloride.

Analogno primjeru 186 dobiveni su slijedeći spojevi počevši od [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-1zo-kinolin-4-il)-fenil]-metil-amina (primjer 185), 4-nitrofenilklorformata i odgovarajućih aminskih komponenata: Analogous to example 186, the following compounds were obtained starting from [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-1zo-quinolin-4-yl)-phenyl]-methyl-amine (example 185), 4-nitrophenylchloroformate and corresponding amine components:

[image] [image]

[image] [image]

Primjer 194 Example 194

N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-formamid N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-formamide

[image] [image]

3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin (600 mg, spoj iz primjera 35) otopi se u 2,4 ml mravlje kiseline i grije se 15 min pod refluksom. Nakon stajanja preko noći, reakcijsku smjesu se doda na mješavinu leda i vode i zas. otopine NaHCO3 i ekstrahira se tri puta s diklormetanom. Sjedinjene organske faze se osuše s MgSO4 i koncentriraju, pri čemu se dobije 588 mg naslovnog spoja. 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine (600 mg, compound from Example 35) was dissolved in 2.4 ml of formic acid and it is heated for 15 min under reflux. After standing overnight, the reaction mixture is added to a mixture of ice and water and sat. NaHCO3 solution and extracted three times with dichloromethane. The combined organic phases were dried over MgSO4 and concentrated to give 588 mg of the title compound.

Primjer 195 Example 195

[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amin hidroklorid [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine hydrochloride

[image] [image]

N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil] formamid (588 mg, spoj iz primjera 194) se otopi u 10 ml THF-a i pri 50°C i pod argonom doda se k otopini od 1,8 ml l M otopine litij-aluminijevog hidrida u THF-u. Grije se l sat pod refluksom. Nakon stajanja preko noći pri 50°C doda se još 2 ml l M otopine litij-aluminijevog hidrida i grije se još 30 min pod refluksom. Za obradu se pomiješa s ledom i vodenu fazu se četiri puta ekstrahira s octenim esterom. Sjedinjene organske faze se osuše s MgSO4 i koncentriraju. Daljnje čišćenje se vrši na prep. HPLC. Tako dobiven proizvod se preuzme u otopinu NaHCO3 i ekstrahira se s octenim esterom. Sušenjem organske faze s MgSO4 dobije se 270 mg slobodne baze. 45 mg se preuzme u razrijeđenu HCl i osuši smrzavanjem, pri čemu se dobije 45 mg naslovnog spoja. N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl] formamide (588 mg, compound from Example 194) was dissolved in 10 ml of THF- and at 50°C and under argon, it is added to a solution of 1.8 ml of a 1 M solution of lithium aluminum hydride in THF. It is heated under reflux for 1 hour. After standing overnight at 50°C, another 2 ml of 1 M lithium-aluminum hydride solution is added and heated for another 30 min under reflux. For processing, it is mixed with ice and the aqueous phase is extracted four times with ethyl acetate. The combined organic phases are dried with MgSO4 and concentrated. Further cleaning is done on prep. HPLC. The product thus obtained is taken up in NaHCO3 solution and extracted with acetic ester. By drying the organic phase with MgSO4, 270 mg of the free base is obtained. 45 mg was taken up in dilute HCl and freeze-dried to give 45 mg of the title compound.

Postupkom opisanim u primjeru 151 mogu se proizvesti spojevi slijedećih primjera, počevši od [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amina (primjer 195), 4-nitroklorformata i odgovarajućih aminskih komponenata. The process described in example 151 can produce compounds of the following examples, starting from [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl- amine (example 195), 4-nitrochloroformate and corresponding amine compds.

Tablica 10: Table 10:

[image] [image]

[image] [image]

[image] [image]

Primjer 204 Example 204

[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina-2-dimetilamino-etil-ester hidroklorid [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid-2-dimethylamino-ethyl-ester hydrochloride

[image] [image]

Uz miješanje i u atmosferi argona 15 mg [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina-4-nitro-fenil ester hidroklorida (vidi primjer 151, intermedijat 1) suspendira se u 1,5 ml diklor-metana i pomiješa se s otopinom od 3 mg 2-dimetil-amino-etanola u 0,5 ml diklormetana i miješa se 6 sati. Nakon stajanja preko noći doda se vodu, diklormetan i zas. otopinu NaHCO3 i organsku fazu se odvoji. Fazu u diklor-metanu se ispere tri puta sa zas. otopinom NaHCO3, osuši se s MgSO4 osuši i otapalo se odstrani u vakuumu. Tako dobiven sirov proizvod se očisti na prep. HPLC. Frakcije s proizvodom se koncentriraju i podijele između octenog estera i zas. otopine NaHCO3. Organsku fazu se odovji, osuši s MgSO4 i koncentrira. Ostatak se preuzme u razr. HCl i osuši smrzavanjem, pri čemu se dobije 5 mg naslovnog spoja. With stirring and in an argon atmosphere 15 mg [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid-4-nitro-phenyl ester of the hydrochloride (see example 151, intermediate 1) is suspended in 1.5 ml of dichloromethane and mixed with a solution of 3 mg of 2-dimethylaminoethanol in 0.5 ml of dichloromethane and stirred for 6 hours. After standing overnight, add water, dichloromethane and sat. NaHCO3 solution and the organic phase is separated. The phase in dichloromethane is washed three times with sat. NaHCO3 solution, dried with MgSO4 and the solvent was removed in vacuo. The raw product obtained in this way is purified on prep. HPLC. Fractions with the product are concentrated and divided between acetic ester and sat. of NaHCO3 solution. The organic phase is removed, dried with MgSO4 and concentrated. The rest is taken over in div. HCl and freeze-dried to give 5 mg of the title compound.

Analognim postupkom proizvedeni su odgovarajući izomere [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-1zo-kinolin-4-il)-fenil]-karbaminska kiselina-2-dimetil-amino-etil ester hidroklorida i [2-(6, S-diklor-2-1αetil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina-2-dimetilamino-etil ester hidroklorida počevši od [4-(6,8-di-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina-4-nitro-fenil-ester hidro-klorida i [2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina-4-nitro-fenil-ester hidroklorida. The corresponding isomers [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-1zo-quinolin-4-yl)-phenyl]-carbamic acid-2-dimethyl-amino -ethyl ester hydrochloride and [2-(6,S-dichloro-2-1αethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid-2-dimethylamino-ethyl ester hydrochloride starting of [4-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid-4-nitro-phenyl-ester hydrochloride and [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid-4-nitro-phenyl-ester hydrochloride.

Tablica 11 Table 11

[image] [image]

Primjer 207 Example 207

[3-(6,8-diklor-2metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina-metil ester hidroklorid [3-(6,8-dichloro-2methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid methyl ester hydrochloride

[image] [image]

Pod atmosferom argona i uz miješanje 15 mg 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil-amina (primjer 35) se stavi u 1,5 ml diklormetana i pomiješa se s otopinom od 4,6 mg metilklorformata u 0,5 ml diklormetana. Nakon 6 sati miješanja i stajanja preko noći doda se daljnjih 2,3 mg metilklorformata i miješa se još 5 sati. Za obradu se otapalo odstrani, ostatak se preuzme u razrijeđenu HCl i osuši smrzavanjem, pri čemu se dobije 20 mg naslovnog spoja. Under an atmosphere of argon and with stirring, 15 mg of 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl-amine (example 35) is placed in 1, 5 ml of dichloromethane and mixed with a solution of 4.6 mg of methylchloroformate in 0.5 ml of dichloromethane. After stirring for 6 hours and standing overnight, a further 2.3 mg of methylchloroformate was added and stirred for another 5 hours. For workup, the solvent was removed, the residue was taken up in dilute HCl and freeze-dried, whereby 20 mg of the title compound was obtained.

Analognim postupkom mogu se proizvesti slijedeći karbamati počevši od odgovarajućih anilina 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamina, odnosno 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-1zo-kinolin-4-il)-fenilamina. The following carbamates can be produced by an analogous process starting from the corresponding anilines 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine, i.e. 4-(6,8 -dichloro-2-methyl-1,2,3,4-tetrahydro-1zo-quinolin-4-yl)-phenylamine.

Tablica 11 Table 11

[image] [image]

[image] [image]

Primjer 215 Example 215

215a: (+)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamid hidroklorid; 215a: (+)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide hydrochloride;

215b: (-)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamid hidroklorid 215b: (-)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide hydrochloride

[image] [image]

96 mg racemične smjese N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamida (vidi primjer 83) rastavi se na enantiomere na kiralnoj prep. HPLC. 96 mg of the racemic mixture of N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide (see example 83) was separated into enantiomers on chiral prep. HPLC.

Kiralni stupac: Chiralpak AD 250 x 50 mm, 20 μ; Chiral column: Chiralpak AD 250 x 50 mm, 20 μ;

otapalo: heptan:etanol:metanol = 10:1:1; solvent: heptane:ethanol:methanol = 10:1:1;

brzina protoka: 50 ml/min. flow rate: 50 ml/min.

Dobiveni enantiomeri se otope u razrijeđenoj HCl i osuše smrzavanjem, pri čemu se u svakom slučaju dobije 37 mg naslovnog spoja 215a, odnosno 215b. Enantiomerna čistoća utvrđena je na kiralnoj HPLC. The obtained enantiomers were dissolved in dilute HCl and freeze-dried, whereby in each case 37 mg of the title compound 215a and 215b were obtained. Enantiomeric purity was determined by chiral HPLC.

Kiralni stupac: Chiralpak AD-H/31 250 x 4,6 mm; Chiral column: Chiralpak AD-H/31 250 x 4.6 mm;

otapalo: heptan:etanol:metanol = 10:1:1; solvent: heptane:ethanol:methanol = 10:1:1;

brzina protoka: l ml/min. flow rate: l ml/min.

Rt (prvi isprani enantiomer) = 6,84 min, 100% ee; Rt (first eluted enantiomer) = 6.84 min, 100% ee;

Rt (drugi isprani enantiomer) = 8,02 min, 100% ee. Rt (second eluted enantiomer) = 8.02 min, 100% ee.

Primjer 216 Example 216

216a: (+)-1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea hidroklorid; 216a: (+)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea hydrochloride;

216b: (-)-1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea hidroklorid 216b: (-)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea hydrochloride

[image] [image]

316 mg racemične smjese l-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-uree (spoj iz primjera 80) se rastavi na enantiomere na kiralnoj prep. HPLC. 316 mg of a racemic mixture of 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea (compound from example 80 ) is separated into enantiomers on chiral prep. HPLC.

Kiralni stupac: Chiralpak OD 250 x 50 mm, 20μ; Chiral column: Chiralpak OD 250 x 50 mm, 20μ;

otapalo: heptanretanol:izo-propanol = 50:2:1:0,3% dietil- solvent: heptanerethanol:iso-propanol = 50:2:1:0.3% diethyl-

ammin; brzina protoka: 50 ml/min. amen flow rate: 50 ml/min.

Enantiomeri se odvojeno podvrgavaju daljnjem čišćenju na prep. HPLC. Dobiveni proizvod se podijeli između zas. otopine NaHCO3 i octenog estera, organsku fazu se odvoji, osuši s MgSO4 i oslobodi od otapala. Ostatak se otopi u razrijeđenoj HCl i osuši smrzavanjem, čime se dobije 37 mg prvog ispranog enantiomera i 58 mg drugog ispranog enantiomera. Enantiomrna čistoća utvrđena je pomoću analitičke HPLC. Enantiomers are separately subjected to further purification on prep. HPLC. The obtained product is divided between the solution of NaHCO3 and acetic ester, the organic phase is separated, dried with MgSO4 and freed from the solvent. The residue was dissolved in dilute HCl and freeze-dried to give 37 mg of the first washed enantiomer and 58 mg of the second washed enantiomer. Enantiomeric purity was determined by analytical HPLC.

Kiralni stupac: Chiralpak OD-20, 250 x 4, 6 mm; Chiral column: Chiralpak OD-20, 250 x 4.6 mm;

otapalo: heptan:etanol:izopropanol = 50:2:1 (0,3% dietil-amina); solvent: heptane:ethanol:isopropanol = 50:2:1 (0.3% diethylamine);

brzina protoka: l ml/min; flow rate: l ml/min;

Rt (prvi isprani enantiomer) = 9,22 min, 100% ee; Rt (first eluted enantiomer) = 9.22 min, 100% ee;

Rt (drugi isprani enantiomer) = 9,96 min, 98% ee. Rt (second eluting enantiomer) = 9.96 min, 98% ee.

Primjer 217 Example 217

N-[3-(6,8-difluoro-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid hidroklorid N-[3-(6,8-difluoro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide hydrochloride

[image] [image]

Intermedijat 1 Intermediate 1

2,4-difluorbenzil-metil-arain 2,4-difluorobenzyl-methyl-araine

Počevši od 2,4-difluorbenzaldehida može se proizvesti 2,4-difluorbenzil-metil-amin na način koji je stručnjaku poznat (usporedi primjer l, intermedijat 1). Starting from 2,4-difluorobenzaldehyde, 2,4-difluorobenzyl-methyl-amine can be produced in a manner known to the person skilled in the art (compare example 1, intermediate 1).

N-[3-(6,8-difluoro-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid hidroklorid N-[3-(6,8-difluoro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide hydrochloride

Naslovni spoj se može proizvesti počevši od N-(3-acetil-fenil)-acetaraida i 2,4-difluor-benzil-metil-amina (intermedijat 1) postupkom sinteze koji je opisan u primjeru 1. The title compound can be prepared starting from N-(3-acetyl-phenyl)-acetaraide and 2,4-difluoro-benzyl-methyl-amine (intermediate 1) by the synthetic procedure described in Example 1.

Primjer 218 Example 218

4-(3-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin hidroklorid 4-(3-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline hydrochloride

[image] [image]

Naslovni spoj se može proizvesti počevši od 2,4-diklorbenzil-metil-arnina (vidi primjer 1} i 2-brom-1-(3-brom-fenil)-etanona kao sredstva za alkiliranje postupkom sinteze koji je opisan u primjeru 1. The title compound can be prepared starting from 2,4-dichlorobenzyl-methyl-arnine (see Example 1} and 2-bromo-1-(3-bromo-phenyl)-ethanone as an alkylating agent by the synthetic procedure described in Example 1.

Primjer 219 Example 219

l-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il}-fenil]-3-(2-hidroksi-etil)-urea 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl}-phenyl]-3-(2-hydroxy-ethyl)-urea

[image] [image]

509 mg (1 mmol) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina-4-nitro-fenil ester hidroklorida (spoj iz primjera 151, intermedijat 1) otopi se u 15 ml aps. DMF-a i pri 0°C se pomiješa s otopinom od 67,2 mg (1,1 mmola) 2-aminoetanola u 10 ml DMF-a. Miješa se tri sata pri sobnoj temperaturi i zatim se otapalo odstrani u vakuumu. Ostatak se podijeli između octenog estera i zas. otopine NaHCO3. Organsku fazu se odvoji i vodenu fazu se ekstrahira još dva puta s octenim esterom. Sjedinjene organske faze se isperu sa zas. otopinom NaCl, osuše se s MgSO4 i koncentriraju. Kromatografijom na silika gelu (diklormetan/metanol) dobije se 265 mg naslovnog spoja. 509 mg (1 mmol) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid-4-nitro-phenyl ester hydrochloride (compound from example 151, intermediate 1) is dissolved in 15 ml abs. of DMF and at 0°C was mixed with a solution of 67.2 mg (1.1 mmol) of 2-aminoethanol in 10 ml of DMF. It was stirred for three hours at room temperature and then the solvent was removed in vacuo. The residue is divided between acetic ester and sat. of NaHCO3 solution. The organic phase is separated and the aqueous phase is extracted two more times with ethyl acetate. The combined organic phases are washed with sat. NaCl solution, dried with MgSO4 and concentrated. Chromatography on silica gel (dichloromethane/methanol) gives 265 mg of the title compound.

Primjer 220 Example 220

3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina etil ester 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid ethyl ester

[image] [image]

Intermedijat 1 Intermediate 1

3-acetil-benzojeva kiselina je dobivena na način koji je stručnjaku poznat iz 3-acetilbenzonitrila saponifikacijom nitrilne skupine. 3-acetyl-benzoic acid was obtained in a manner known to the expert from 3-acetylbenzonitrile by saponification of the nitrile group.

Intermedijat 2 Intermediate 2

3-acetil-benzojeva kiselina-etil ester dobije se iz intermedijata l na način koji je stručnjaku poznat. Intermedijat 3 3-Acetyl-benzoic acid-ethyl ester is obtained from intermediate 1 in a manner known to the expert. Intermediate 3

3-(2-brom-acetil)-benzojeva kiselina-etil ester sintetizira se analogno postupku opisanom u primjeru l, intermedijat 2 iz 3-acetil-benzojeva kiselina-etil estera (intermedijat 2). 3-(2-bromo-acetyl)-benzoic acid-ethyl ester is synthesized analogously to the procedure described in example 1, intermediate 2 from 3-acetyl-benzoic acid-ethyl ester (intermediate 2).

3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina-etil ester 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid-ethyl ester

Analogno postupku sinteze koji je opisan u primjeru l, počevši od 3-(2-brom-acetil)-benzojeva kiselina-etil estera (intermedijat 3) i 2,4-diklorbenzilmetil-amina (primjer l, interraedijat 1) i daljnjim postupkom, nakon reakcije alkiliranja, redukcije i reakcije zatvaranja prstena dobije se 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina-etil ester. Analogously to the synthesis procedure described in example 1, starting from 3-(2-bromo-acetyl)-benzoic acid-ethyl ester (intermediate 3) and 2,4-dichlorobenzylmethyl-amine (example 1, intermediate 1) and with a further procedure, after alkylation reaction, reduction and ring closing reaction, 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid ethyl ester is obtained.

Primjer 221 Example 221

3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid

[image] [image]

500 mg 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina-etil estera (spoj iz primjera 220) otopi se u 15 ml metanola i pomiješa se s 10 ml 2 N KOH. Nakon jednog sata pri 50°C, koncentrira se u vakuumu i ostatak se podijeli između vode i etera. Vodenu fazu se s 2 N HCl namjesti na pH vrijednost od pribl. 6 i nastali talog se odsisa. Sušenjem se dobije 304 mg naslovnog spoja kao bezbojna kruta tvar. 500 mg of 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid-ethyl ester (compound from example 220) is dissolved in 15 ml of methanol and mixed with 10 ml of 2 N KOH. After one hour at 50°C, it was concentrated in vacuo and the residue was partitioned between water and ether. Adjust the aqueous phase with 2 N HCl to a pH value of approx. 6 and the formed precipitate is sucked off. Drying gave 304 mg of the title compound as a colorless solid.

Analitički podaci za spojeve iz primjera 1 do 221: Analytical data for compounds from examples 1 to 221:

Tablica 13: Table 13:

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

[image] [image]

Farmakološki podaci Pharmacological data

Opis ispitivanja Test description

U ovom ispitivanju utvrđeno je popravljanje intracelularnog pHs (pHi) nakon zakiseljavanja, koji se kod funkcionalno sposobnog NHE upotrebljava također i pod uvjetima bez bikarbonata. U tu svrhu utvrđeni su pHi s fluorescentnim bojilom BCECF (Calbiochem, upotrebljava se predkurzor BCECF-AM) koje je osjetljivo na pH. Stanice su najprije obojene s BCECF. BCECF fluorescencija je utvrđena u "Ratio Fluorescence Spectrometer-u" (Foton Technologγ International, South Brunswick, N. J., USA) pri pobudnim valnim duljinama od 505 i 440 nm i emisijskoj valnoj duljini od 535 nm i pomoću baždarnih kruvilja je preračunata u pHi. Stanice obojene s BCECF su inkubirane u puferu NH4Cl (pH 7,4) (NH4C1 pufer: 115 mM NaCl, 20 mM NH4C1, 5 mM KCl, l mM CaCl2, l mM MgSO4, 20 mM Hepes-a, 5 mM glukoze, Img/ml BSA; s l M NaOH je namješten pH od 7,4). Intracelarno zakiseljavanje uzrokovano je dodatkom 975 μl pufera bez NH4C1 (vidi dolje) k stanicama inkubiranim u alikvotima od 25 μl pufera NH4Cl. Zatim je brzina povišenja pH registrirana pri NHE1 nakon dvije minute, pri NHE2 nakon pet minuta i pri NHE3 nakon tri minute. Za izračunavanje jačine inhibicije ispitnih tvari stanice su najprije ispitane u puferima, u kojima nije dolazilo do potpunog, odnosno do nikakvog oporavka pH. Za potpuni oporavak pH (100%) stanice su inkubirane u puferu koji je sadržavao Na+ (133,8 mM NaCl, 4,7 mM KCl, 1,25 mM CaCl2, 1,25 mM MgCl2, 0,97 mM Na2HPO4, 0,23 mM NaH2PO4, 5 mM Hepes-a, 5 mM glukoze, s l M NaOH je namješten pH od 7,0). Za određivanje 0%-tne vrijednosti stanice su inkubirane u puferu bez Na+ (133,8 mM holin klorid, 4,7 mM KĆI, 1,25 mM CaCl2, 1,25 mM MgCl2, 0,97 mM K2HPO4, 0,23 mM KH2PO4, 5 mM Hepes-a, 5 mM glukoze, s l M NaOH je namješten pH od 7,0). Ispitne tvari su stavljene u pufer koji je sadržavao Na+. Povišenje intracelularnih pH vrijednosti kod svake ispitane koncentracije tvari izraženo je kao postotak od maksimalnog povišenje. Iz postotnih vrijednosti povišenje pH pomoću programa Sigma-Plot je izračunata vrijednost IC50 dotične tvari za pojedinačne podtipove NHE. In this study, the correction of intracellular pHs (pHi) after acidification was determined, which is used in functionally capable NHE also under bicarbonate-free conditions. For this purpose, pHi were determined with the fluorescent dye BCECF (Calbiochem, the precursor BCECF-AM is used), which is sensitive to pH. Cells were first stained with BCECF. BCECF fluorescence was determined in a "Ratio Fluorescence Spectrometer" (Foton Technologγ International, South Brunswick, N.J., USA) at excitation wavelengths of 505 and 440 nm and emission wavelength of 535 nm and was converted to pHi using standard curves. BCECF-stained cells were incubated in NH4Cl buffer (pH 7.4) (NH4Cl buffer: 115 mM NaCl, 20 mM NH4Cl, 5 mM KCl, l mM CaCl2, l mM MgSO4, 20 mM Hepes, 5 mM glucose, Img /ml BSA; the pH was adjusted to 7.4 with 1 M NaOH). Intracellular acidification was induced by the addition of 975 μl buffer without NH4Cl (see below) to cells incubated in 25 μl aliquots of NH4Cl buffer. Then, the rate of pH increase was registered at NHE1 after two minutes, at NHE2 after five minutes and at NHE3 after three minutes. To calculate the inhibition strength of the test substances, the cells were first tested in buffers, in which there was no complete or no pH recovery. For complete pH recovery (100%), cells were incubated in a buffer containing Na+ (133.8 mM NaCl, 4.7 mM KCl, 1.25 mM CaCl2, 1.25 mM MgCl2, 0.97 mM Na2HPO4, 0, 23 mM NaH2PO4, 5 mM Hepes, 5 mM glucose, with 1 M NaOH adjusted to pH 7.0). To determine the 0% value, cells were incubated in buffer without Na+ (133.8 mM choline chloride, 4.7 mM KCl, 1.25 mM CaCl2, 1.25 mM MgCl2, 0.97 mM K2HPO4, 0.23 mM KH2PO4, 5 mM Hepes, 5 mM glucose, with 1 M NaOH adjusted to pH 7.0). The test substances were placed in a buffer containing Na+. The increase in intracellular pH values at each tested substance concentration was expressed as a percentage of the maximum increase. The IC50 value of the respective substance for individual NHE subtypes was calculated from the percentage values of the pH increase using the Sigma-Plot program.

Rezultati the results

Tablica 14 Table 14

[image] [image]

Claims (26)

1. 4-feniltetrahidroizokinolin formule I [image] naznačen time, da R1, R2, R3 i R4 međusobno neovisno predstavljaju H, F, Cl, Br, J, CN, NO2, OH, NH2, CaH2a+1, CqqH2qq-1, OCbH2b+1, COOR10, OCOR10, COR10 ili Ox-(CH2)y-fenil; a i b u skupinama CaH2a+1 i OCbH2b+1 su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; qq je 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; R10 je H ili CCH2c+1; c je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma smije biti zamijene s F atomima; x je nula ili 1; y je nula, 1, 2, 3 ili 4; pri čemu fenilni prsten u skupini Ox-(CH2)y-fenil nije supstituiran ili je supstituiran s 1-3 supstituenta odabrana iz skupine koju čine F, Cl, Br, CN, NO2, OH, NH2 ili CdH2d+1, d je 1, 2, 3, ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R1, R2, R3 i R4 međusobno neovisno predstavljaju heteroaril, pri čemu u prstenu može biti nula, 1, 2, 3 ili 4 N atoma, nula ili 1 atom kisika ili nula ili 1 S atom; ili R1, R2, R3 i R4 međusobno neovisno predstavljaju CONR11R12 ili NR11R12; R11 i R12 međusobno neovisno predstavljaju H, CeH2e+1, CrrHrr-1; e je 1, 2, 3, 4, 5, 6, 7 ili 8, rr je 3, 4, 5, 6, 7, ili 8, pri čemu u skupinama CeH2e+1 i CrrH2rr-1 jedan ili više H atoma smije biti zamijenjeno F atomima i jedna ili više CH2 skupina može biti zamijenjeno s F atomima O ili s NR13; R13 je H ili CfH2f+1; F je 1, 2, 3, ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R13 i jedna CH2 skupina iz R11 ili R12 zajedno s N atomom, na koji su one povezane, tvore 5- ili 6-člani prsten; ili R11 i R12 zajedno s N atomom na koji su one povezane tvore 5-, 6- ili 7-člani prsten; ili R11 i R12 međusobno neovisno predstavljaju COR14, CSR14 ili SO2R14; R14 je CgH2g+1; g je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s F atomima O ili s NR13; ili R1, R2, R3 i R4 su međusobno neovisno –Oh-SOjR15, pri čemu h je nula ili 1, j je nula, 1 ili 2; R15 je CkH2k+1, OH, OClH2l+1 ili NR17R18; k je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; l je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; R17 i R18 međusobno neovisno predstavljaju H ili CmH2m+1; m je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu u skupini CmH2m+1 jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s O, CO, CS ili NR19; R19 je H ili CnH2n+1; n je 1, 2, 3 ili 4; pri čemu u skupini CnH2n+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili R17 i R18 zajedno s N atomom na koji su one povezane tvore 5-, 6- ili 7-člani prsten; ili R19 i jedna CH2 skupina iz R17 ili R18 zajedno s N atomom na koji su one povezane tvore 5- ili 6-člani prsten; pri čemu, međutim, R2 mora uvijek biti različit od H, R5 je H, CpH2p+1, CssH2ss-1, COR20 ili SO2R20; p je 1, 2, 3, 4, 5, 6, 7 ili 8, ss je 4, 5, 6, 7 ili 8, R20 je CqH2q+1; q je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu u skupinama CpH2p+1, CssH2ss-1 i CqH2q+1 jedan ili više H atoma može biti zamijenjeno s F atomima, i jedna ili više CH2 skupina može biti zamijenjeno s O ili NR21; R21 je H ili CrH2r+1; r je 1, 2, 3 ili 4; pri čemu u skupini CrH2r+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R6 je H, F, Cl, Br, I, CsH2s+1, CddH2dd-1, OH, OCtH2t+1 ili OCOR22; s i t su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8; dd je 3, 4, 5, 6, 7 ili 8, pri čemu u skupinama CsH2s+1, CddH2dd-1 i OCtH2t+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R22 je CuH2u+1; u je 1, 2, 3 ili 4; pri čemu u skupini CuH2u+1 jedan ili više H atoma može biti zamijenjeno s F atomima: R7, R8 i R9 su međusobno neovisno -Ov-SOw-R23; v je nula ili 1; w je nula, 1 ili 2; R23 je CnnH2nn+1, CmmH2mm-1, OH, OCppH2pp+1 ili NR25R26; nn i pp su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8, mm je 3, 4, 5, 6, 7 ili 8, pri čemu u skupinama CnnH2nn+1, CmmH2mm-1 i OCppH2pp+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R25 i R26 su međusobno neovisno H, CN ili CzH2z+1, CzzH2zz-1; z je 1, 2, 3, 4, 5, 6, 7 ili 8; zz je 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; i u skupini CzH2z+1 jedan ili više H atoma može biti zamijenjeno s F atomima; i jedna ili više CH2 skupina može biti zamijenjeno s O, CO, CS ili s NR27; R27 je H ili CaaH2aa+1; aa je 1, 2, 3 ili 4; pri čemu u skupini CaaH2aa+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili R25 i R26 zajedno s N atomom na koji su oni povezani tvore 5-, 6- ili 7-člani prsten, ili R27 i jedna CH2 skupina iz R25 ili R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; ili R7, R8 i R9 su međusobno neovisno NR32COR30, NR32CSR30 ili NR32SObbR30; R30 je H, CccH2cc+1, CyyH2yy-1, pirolidinil ili piperidinil, u kojim prstenovima jedna CH2 skupina može biti zamijenjena s O ili s NR33; R32 i R33 su međusobno neovisno H ili ChH2h+1; bb je 2 ili 3; cc je 1, 2, 3, 4, 5, 6, 7 ili 8; yy je 3, 4, 5, 6, 7 ili 8; h je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu u skupini ChH2h+1 jedan ili više H atoma smije biti zamijenjeno s F atomima, a u skupinama CccH2cc+1 i CyyH2yy-1 jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s NR31 i jedna CH2 skupina može biti zamijenjena s O; R31 je H, C,ckH2kk+1, COR65 ili SO2R65; kk je 1, 2, 3, ili 4; pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; R65 je H, CxxH2xx+1; xx je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R31 zajedno s jednom CH2 skupinom iz R30 tvori 5-, 6-ili 7-člani prsten; ili R30 je 5- ili 6-člani heteroaril s 1, 2, 3 ili 4 N atoma, s nula ili 1 S atomom i nula ili 1 O atomom, koji nije supstituiran ili je supstituiran s do tri supstituenta odabrana iz skupine koju čine F, Cl Br, I, CooH2oo+1, NR70R71; R70 i R71 su međusobno neovisno H, CuuH2uu+1 i COR72; R72 je H, CwH2w+1; oo, uu i vv su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8; pri čemu u skupinama CooH2oo+1, CuuH2uu+1 i CwH2w+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R7, R8 i R9 su međusobno neovisno H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 ili OCOR42, ee i ff su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8; ww je 3, 4, 5, 6, 7 ili 8; pri čemu u skupinama CeeH2ee+1, CwwH2ww-1 i OCffH2ff+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R40 i R41 su H, CttH2tt+1 ili C(NH)NH2; tt je 1, 2, 3, 3, 4, 5, 6, 7 ili 8; pri čemu u skupini CttH2tt+1 jedan ili više H atoma smije biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s O ili NR44; R44 je H ili CggH2gg+1; gg je 1, 2, 3, 4, 5, 6, 7 ili 8; pri čemu u skupini CggH2gg+1 jedan ili više H atoma može biti zamijenjeno s F atomima i R44 zajedno s jednom (CH2) skupinom iz R40 ili R41 i N atomom na koji su one zajedno povezane mogu tvoriti 5 ili 6-člani prsten; ili R40 i R41 s N atomom na koji su oni povezani tvore 5-ili 6-člani prsten; R42 je H ili ChhH2hh+1; hh je 1, 2, 3, 4, 5, 6, 7 ili 8; pri čemu u skupini ChhH2hh+1 jedan ili više H atoma može biti zamijenjeno s F atomima; pri čemu, međutim, dva supstituenta iz skupina R7, R8 i R9 ne smiju biti istovremeno OH ili OCH3, i pri čemu najmanje jedan od ostataka R7, R8 ili R9 mora biti odabran iz skupine koju čine CONR40R41, -OvSOwR23, NR32COR30, NR32CSR30 i NR32SObbR30; kao i njihove farmacetski podnošljive soli i trifluor-acetate.1. 4-phenyltetrahydroisoquinoline of formula I [image] indicated by that R1, R2, R3 and R4 independently represent H, F, Cl, Br, J, CN, NO2, OH, NH2, CaH2a+1, CqqH2qq-1, OCbH2b+1, COOR10, OCOR10, COR10 or Ox-(CH2 )y-phenyl; a and b in the groups CaH2a+1 and OCbH2b+1 are independently 1, 2, 3, 4, 5, 6, 7 or 8, whereby one or more H atoms can be replaced by F atoms; qq is 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms; R10 is H or CCH2c+1; c is 1, 2, 3, 4, 5, 6, 7 or 8, whereby one or more H atoms may be replaced by F atoms; x is zero or 1; y is zero, 1, 2, 3 or 4; wherein the phenyl ring in the Ox-(CH2)y-phenyl group is not substituted or is substituted with 1-3 substituents selected from the group consisting of F, Cl, Br, CN, NO2, OH, NH2 or CdH2d+1, d is 1, 2, 3, or 4, wherein one or more H atoms may be replaced by F atoms; or R 1 , R 2 , R 3 and R 4 independently represent heteroaryl, whereby the ring may contain zero, 1, 2, 3 or 4 N atoms, zero or 1 oxygen atom or zero or 1 S atom; or R 1 , R 2 , R 3 and R 4 independently represent CONR 11 R 12 or NR 11 R 12 ; R11 and R12 independently represent H, CeH2e+1, CrrHrr-1; e is 1, 2, 3, 4, 5, 6, 7 or 8, rr is 3, 4, 5, 6, 7, or 8, whereby in the groups CeH2e+1 and CrrH2rr-1 one or more H atoms may be replaced by F atoms and one or more CH2 groups may be replaced by F atoms O or by NR13; R13 is H or CfH2f+1; F is 1, 2, 3, or 4, wherein one or more H atoms may be replaced by F atoms; or R13 and one CH2 group from R11 or R12 together with the N atom, to which they are attached, form a 5- or 6-membered ring; or R11 and R12 together with the N atom to which they are attached form a 5-, 6- or 7-membered ring; or R 11 and R 12 independently represent COR 14 , CSR 14 or SO 2 R 14 ; R14 is CgH2g+1; g is 1, 2, 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms and one or more CH 2 groups may be replaced by F atoms O or by NR 13 ; or R1, R2, R3 and R4 are mutually independently -OH-SOjR15, wherein h is zero or 1, j is zero, 1 or 2; R15 is CkH2k+1, OH, OClH21+1 or NR17R18; k is 1, 2, 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms; l is 1, 2, 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms; R17 and R18 independently represent H or CmH2m+1; m is 1, 2, 3, 4, 5, 6, 7 or 8, whereby in the group CmH2m+1 one or more H atoms can be replaced by F atoms and one or more CH2 groups can be replaced by O, CO, CS or NR19; R19 is H or CnH2n+1; n is 1, 2, 3 or 4; whereby in the group CnH2n+1 one or more H atoms can be replaced by F atoms; or R17 and R18 together with the N atom to which they are attached form a 5-, 6- or 7-membered ring; or R19 and one CH2 group from R17 or R18 together with the N atom to which they are attached form a 5- or 6-membered ring; where, however, R2 must always be different from H, R5 is H, CpH2p+1, CssH2ss-1, COR20 or SO2R20; p is 1, 2, 3, 4, 5, 6, 7 or 8, ss is 4, 5, 6, 7 or 8, R20 is CqH2q+1; q is 1, 2, 3, 4, 5, 6, 7 or 8, wherein in the groups CpH2p+1, CssH2ss-1 and CqH2q+1 one or more H atoms can be replaced by F atoms, and one or more CH2 groups can be replaced by O or NR21; R21 is H or CrH2r+1; r is 1, 2, 3 or 4; whereby in the group CrH2r+1 one or more H atoms can be replaced by F atoms; R6 is H, F, Cl, Br, I, CsH2s+1, CddH2dd-1, OH, OCtH2t+1 or OCOR22; s and t are independently 1, 2, 3, 4, 5, 6, 7 or 8; dd is 3, 4, 5, 6, 7 or 8, whereby in the groups CsH2s+1, CddH2dd-1 and OCtH2t+1 one or more H atoms can be replaced by F atoms; R22 is CuH2u+1; u is 1, 2, 3 or 4; where in the group CuH2u+1 one or more H atoms can be replaced by F atoms: R7, R8 and R9 are mutually independently -Ov-SOw-R23; v is zero or 1; w is zero, 1 or 2; R23 is CnnH2nn+1, CmmH2mm-1, OH, OCppH2pp+1 or NR25R26; nn and pp are independently 1, 2, 3, 4, 5, 6, 7 or 8, mm is 3, 4, 5, 6, 7 or 8, whereby in the groups CnnH2nn+1, CmmH2mm-1 and OCppH2pp+1 one or more H atoms can be replaced by F atoms; R25 and R26 are mutually independently H, CN or CzH2z+1, CzzH2zz-1; z is 1, 2, 3, 4, 5, 6, 7 or 8; zz is 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms; and in the group CzH2z+1 one or more H atoms can be replaced by F atoms; and one or more CH 2 groups may be replaced by O, CO, CS or by NR 27 ; R27 is H or CaaH2aa+1; aa is 1, 2, 3 or 4; whereby in the group CaaH2aa+1 one or more H atoms can be replaced by F atoms; or R25 and R26 together with the N atom to which they are attached form a 5-, 6- or 7-membered ring, or R27 and one CH2 group from R25 or R26 together with the N atom to which they are attached form a 5- or 6-membered ring; or R7, R8 and R9 are independently NR32COR30, NR32CSR30 or NR32SObbR30; R30 is H, CccH2cc+1, CyyH2yy-1, pyrrolidinyl or piperidinyl, in which rings one CH2 group can be replaced by O or by NR33; R32 and R33 are mutually independently H or ChH2h+1; bb is 2 or 3; cc is 1, 2, 3, 4, 5, 6, 7 or 8; yy is 3, 4, 5, 6, 7 or 8; h is 1, 2, 3, 4, 5, 6, 7 or 8, where in the group ChH2h+1 one or more H atoms may be replaced by F atoms, and in the groups CccH2cc+1 and CyyH2yy-1 one or more H atoms may be replaced by F atoms and one or more CH2 groups may be replaced by NR31 and one CH2 group can be replaced by O; R31 is H, C,ckH2kk+1, COR65 or SO2R65; kk is 1, 2, 3, or 4; wherein one or more H atoms may be replaced by F atoms; R65 is H, CxxH2xx+1; xx is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or R31 together with one CH2 group from R30 forms a 5-, 6- or 7-membered ring; or R30 is a 5- or 6-membered heteroaryl with 1, 2, 3 or 4 N atoms, with zero or 1 S atom and zero or 1 O atom, which is unsubstituted or substituted with up to three substituents selected from the group consisting of F, Cl Br, I, CooH2oo+1, NR70R71; R70 and R71 are independently H, CuuH2uu+1 and COR72; R72 is H, CwH2w+1; oo, uu and vv are independently 1, 2, 3, 4, 5, 6, 7 or 8; whereby in the groups CooH2oo+1, CuuH2uu+1 and CwH2w+1 one or more H atoms may be replaced by F atoms; or R7, R8 and R9 are independently H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42, ee and ff are independently 1, 2, 3, 4, 5, 6, 7 or 8; ww is 3, 4, 5, 6, 7 or 8; whereby in the groups CeeH2ee+1, CwwH2ww-1 and OCffH2ff+1 one or more H atoms can be replaced by F atoms; R40 and R41 are H, CttH2tt+1 or C(NH)NH2; tt is 1, 2, 3, 3, 4, 5, 6, 7 or 8; wherein in the group CttH2tt+1 one or more H atoms may be replaced by F atoms and one or more CH2 groups may be replaced by O or NR44; R44 is H or CggH2gg+1; gg is 1, 2, 3, 4, 5, 6, 7 or 8; wherein in the group CggH2gg+1 one or more H atoms can be replaced by F atoms and R44 together with one (CH2) group from R40 or R41 and the N atom to which they are connected together can form a 5- or 6-membered ring; or R40 and R41 with the N atom to which they are attached form a 5- or 6-membered ring; R42 is H or ChhH2hh+1; hh is 1, 2, 3, 4, 5, 6, 7 or 8; whereby in the group ChhH2hh+1 one or more H atoms can be replaced by F atoms; whereby, however, two substituents from groups R7, R8 and R9 must not be simultaneously OH or OCH3, and wherein at least one of the residues R7, R8 or R9 must be selected from the group consisting of CONR40R41, -OvSOwR23, NR32COR30, NR32CSR30 and NR32SObbR30; as well as their pharmaceutically acceptable salts and trifluoroacetates. 2. Spojevi formule I prema zahtjevu 1, naznačeni time, da R1, R2, R3 i R4 međusobno neovisno predstavljaju H, F, Cl, Br, I, CN, NO2, OH, NH2, CaH2a+1, cikloalkil s 3, 4, 5 ili 6 C atoma, OCbH2b+1, COOR10; a i b su međusobno neovisno 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; R10 je H ili CcH2c+1; c je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R1, R2, R3 i R4 su međusobno neovisno 5- ili 6-člani heteroaril odabran iz skupine koju čine piridil, imidazolil, pirazolil, pirolil, triazolil, tetrazolil, tiazolil i oksazolil; ili R1, R2, R3 i R4 su međusobno neovisno CONR1R12 ili NR11R12; R11 i R12 su međusobno neovisno H, CeH2e+1, CrrH2rr-1; e je 1, 2, 3 ili 4, rr je 3, 4, 5 ili 6, pri čemu u skupinama CeH2e+1 i CrrH2rr-1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R11 i R12 su međusobno neovisno hidroksietil, N,N-di-metilaminoetil, N,N-dietilaminoetil, pirolidinoetil, N-metilpiperazinoetil, piperazinoetil, morfolinoetil ili piperidinoetil; ili R11 i R12 zajedno s N atomom na koji su oni povezani tvore pirolidinski, piperidinski, N-metilpiperazinski, piperazinski ili morfolinski prsten; ili R11 i R12 su međusobno neovisno COR14, CSR14, CONHR14, CSNHR14 ili SO2R14; R14 je CgH2g+1; g je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili R1, R2, R3 i R4 su međusobno neovisno OSO3H, SO3H, SO2R15, pri čemu R15 je CkH2k+1, OClH2l+1 ili NR17R18; k je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; l je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; R17 i R18 su međusobno neovisno H, CmH2m+1, u kojem prva CH2 skupina povezana na dušik može biti zamijenjena sa CO, a druga CH2 skupina povezana na dušik može biti zamijenjena s NR19; m je 1, 2, 3, 4 ili 5, pri čemu u skupini CmH2m+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R19 je H ili CnHn+1; n je 1, 2, 3 ili 4; pri čemu u skupini CnH2n+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili R17 i R18 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; pri čemu, međutim, R2 mora uvijek biti različit od H, R5 je H, CpH2p+1; p je 1, 2, 3 ili 4; pri čemu u CpH2p+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R6 je H, CsH2s+1, OCtH2t+1 ili OCOR22; s i t su međusobno neovisno 1, 2, 3 ili 4; pri čemu u CsH2s+1 i OCtH2t+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R22 je CuH2u+1; u je 1, 2, 3 ili 4; pri čemu u CuH2u+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R7, R8 i R9 su međusobno neovisno OSO3H, SO3H ili SO2R23; R23 je CnnH2nn+1, CmmH2mm-1, OCppH2pp+1 ili NR25R26; nn i pp su međusobno neovisno 1, 2, 3, 4 ili 5, mm je 3, 4, 5 ili 6, pri čemu u CnnH2nn+1, CmmH2mm-1 i OCppH2pp+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R25 i R26 su međusobno neovisno H, CN ili CzH2z+1, u kojem prva CH2 skupina povezana na dušik može biti zamijenjena sa CO ili CS, a druga CH2 skupina povezana na dušik može biti zamijenjena s NR27; z je 1, 2, 3, 4, 5 ili 6; pri čemu u CzH2z+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R27 je H ili CaaH2aa+1; aa je 1, 2, 3 ili 4; pri čemu u CaaH2aa+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili R25 i R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten, ili R27 i jedna CH2 skupina iz R25 ili R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; ili R7, R8 i R9 su međusobno neovisno NR32COR30, NR32CSR30 ili NR32SO2R30; R30 je H, OH, CccH2cc+1, CyyH2yy-1; pirolidinil ili piperidinil, u kojim prstenovima jedna CH2 skupina može biti zamijenjena s O ili NR33; R32 i R33 su međusobno neovisno H ili ChH2h+1; cc je 1, 2, 3, 4, 5, 6, 7 ili 8; yy je 3, 4, 5, 6; h je 1, 2, 3 ili 4; pri čemu u ChH2h+1 jedan ili više H atoma smije biti zamijenjeno s F atomima, a u skupinama CccH2cc+1 i CyyH2yy-1 jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s NR31, i jedna CH2 skupina može biti zamijenjena s O; R31 je H, CkkH2kk+1, COR65 ili SO2R65; kk je 1, 2, 3, ili 4; pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; R65 je H, CxxH2xx+1; xx je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R31 zajedno s jednom CH2 skupinom iz R30 i N atomom na koji su oni zajedno povezani tvore 5- ili 6-člani prsten; ili R30 je 5- ili 6-člani heteroaromat odabran iz skupine koju čine piridil, imidazolil, pirazolil, pirolil, triazolil, tetrazolil, tienil, tiazolil i oksazolil, koji nisu supstituirani ili su supstituirani s do tri supstituenta odabrana iz skupine koju čine F, Cl, Br, I, CooH2oo+1, NR70R71, R70 i R71 su međusobno neovisno H, CuuH2uu+1 ili COR72; R72 je H, CwH2w+1; oo, uu i vv su međusobno neovisno 1, 2, 3 ili 4; pri čemu u skupinama CooH2oo+1, CuuH2uu+1 i CwH2w+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R7, R8 i R9 su međusobno neovisno H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 ili OCOR42; ee i ff su međusobno neovisno 1, 2, 3 ili 4; ww je 3, 4, 5 ili 6, pri čemu u skupinama CeeH2ee+1, CwwH2ww-1 i OCffH2ff+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R40 i R41 su H, CttH2tt+1 ili C(NH)NH2; tt je 1, 2, 3, 4, 5, 6, 7 ili 8; pri čemu u skupinama CttH2tt+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R40 i R41 su međusobno neovisno odabrani iz niza koji čine hidroksietil, N,N-dimetilaminoetil, N,N-dietilamino-etil, pirolidinoetil, N-metilpiperazinoetil, piperazino-etil, morfolinoetil ili piperidinoetil; ili R40 i R41 zajedno s N atomom na koji su oni povezani tvore prsten odabran iz skupine koju čine pirolidin, piperidin, N-metilpiperazin, piperazin i morfolin; R42 je H ili ChhH2hh+1; hh je 1, 2, 3 ili 4; pri čemu u skupini ChhH2hh+1 jedan ili više H atoma može biti zamijenjeno s F atomima; pri čemu, međutim, dva supstituenta iz skupina R7, R8 i R9 ne smiju biti istovremeno OH ili OCH3, i pri čemu najmanje jedan od ostataka R7, R8 ili R9 mora biti odabran iz skupine koju čine CONR40R41, -OvSOwR23, NR32COR30, NR32CSR30 i NR32SObbR30; kao i njihovim farmaceutski podnošljivim solima i trifluor-acetatima.2. Compounds of formula I according to claim 1, characterized in that R1, R2, R3 and R4 independently represent H, F, Cl, Br, I, CN, NO2, OH, NH2, CaH2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms, OCbH2b+1, COOR10; a and b are independently 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; R10 is H or CcH2c+1; c is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or R 1 , R 2 , R 3 and R 4 are independently 5- or 6-membered heteroaryl selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl and oxazolyl; or R 1 , R 2 , R 3 and R 4 are mutually independently CONR 1 R 12 or NR 11 R 12 ; R11 and R12 are mutually independently H, CeH2e+1, CrrH2rr-1; e is 1, 2, 3 or 4, rr is 3, 4, 5 or 6, whereby in the groups CeH2e+1 and CrrH2rr-1 one or more H atoms may be replaced by F atoms; or R11 and R12 are mutually independently hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or R11 and R12 together with the N atom to which they are attached form a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring; or R 11 and R 12 are independently COR 14 , CSR 14 , CONHR 14 , CSNHR 14 or SO 2 R 14 ; R14 is CgH2g+1; g is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or R1, R2, R3 and R4 are mutually independently OSO3H, SO3H, SO2R15, wherein R15 is CkH2k+1, OClH21+1 or NR17R18; k is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; l is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; R17 and R18 are independently H, CmH2m+1, wherein the first CH2 group attached to the nitrogen can be replaced by CO and the second CH2 group attached to the nitrogen can be replaced by NR19; m is 1, 2, 3, 4 or 5, whereby in the group CmH2m+1 one or more H atoms can be replaced by F atoms; R 19 is H or CnHn+1; n is 1, 2, 3 or 4; whereby in the group CnH2n+1 one or more H atoms can be replaced by F atoms; or R17 and R18 together with the N atom to which they are attached form a 5- or 6-membered ring; where, however, R2 must always be different from H, R5 is H, CpH2p+1; p is 1, 2, 3 or 4; whereby in CpH2p+1 one or more H atoms can be replaced by F atoms; R6 is H, CsH2s+1, OCtH2t+1 or OCOR22; s and t are independently 1, 2, 3 or 4; whereby in CsH2s+1 and OCtH2t+1 one or more H atoms can be replaced by F atoms; R22 is CuH2u+1; u is 1, 2, 3 or 4; whereby in CuH2u+1 one or more H atoms can be replaced by F atoms; R 7 , R 8 and R 9 are mutually independently OSO 3 H, SO 3 H or SO 2 R 23 ; R23 is CnnH2nn+1, CmmH2mm-1, OCppH2pp+1 or NR25R26; nn and pp are independently 1, 2, 3, 4 or 5, mm is 3, 4, 5 or 6, whereby in CnnH2nn+1, CmmH2mm-1 and OCppH2pp+1 one or more H atoms can be replaced by F atoms; R25 and R26 are independently H, CN or CzH2z+1, wherein the first CH2 group attached to the nitrogen may be replaced by CO or CS and the second CH2 group attached to the nitrogen may be replaced by NR27; z is 1, 2, 3, 4, 5 or 6; whereby in CzH2z+1 one or more H atoms can be replaced by F atoms; R27 is H or CaaH2aa+1; aa is 1, 2, 3 or 4; where in CaaH2aa+1 one or more H atoms can be replaced by F atoms; or R25 and R26 together with the N atom to which they are attached form a 5- or 6-membered ring, or R27 and one CH2 group from R25 or R26 together with the N atom to which they are attached form a 5- or 6-membered ring; or R7, R8 and R9 are independently NR32COR30, NR32CSR30 or NR32SO2R30; R30 is H, OH, CccH2cc+1, CyyH2yy-1; pyrrolidinyl or piperidinyl, in which rings one CH2 group may be replaced by O or NR33; R32 and R33 are mutually independently H or ChH2h+1; cc is 1, 2, 3, 4, 5, 6, 7 or 8; yy is 3, 4, 5, 6; h is 1, 2, 3 or 4; whereby in ChH2h+1 one or more H atoms may be replaced by F atoms, and in the groups CccH2cc+1 and CyyH2yy-1 one or more H atoms may be replaced by F atoms and one or more CH2 groups may be replaced by NR31, and one CH2 group can be replaced by O; R31 is H, CkkH2kk+1, COR65 or SO2R65; kk is 1, 2, 3, or 4; wherein one or more H atoms may be replaced by F atoms; R65 is H, CxxH2xx+1; xx is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or R31 together with one CH2 group from R30 and the N atom to which they are connected form a 5- or 6-membered ring; or R30 is a 5- or 6-membered heteroaromatic selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thienyl, thiazolyl and oxazolyl, which are unsubstituted or substituted with up to three substituents selected from the group consisting of F, Cl , Br, I, CooH2oo+1, NR70R71, R70 and R71 are mutually independently H, CuuH2uu+1 or COR72; R72 is H, CwH2w+1; oo, uu and vv are independently 1, 2, 3 or 4; whereby in the groups CooH2oo+1, CuuH2uu+1 and CwH2w+1 one or more H atoms may be replaced by F atoms; or R7, R8 and R9 are independently H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42; ee and ff are independently 1, 2, 3 or 4; ww is 3, 4, 5 or 6, whereby in the groups CeeH2ee+1, CwwH2ww-1 and OCffH2ff+1 one or more H atoms can be replaced by F atoms; R40 and R41 are H, CttH2tt+1 or C(NH)NH2; tt is 1, 2, 3, 4, 5, 6, 7 or 8; whereby in the groups CttH2tt+1 one or more H atoms may be replaced by F atoms; or R40 and R41 are mutually independently selected from the group consisting of hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or R40 and R41 together with the N atom to which they are attached form a ring selected from the group consisting of pyrrolidine, piperidine, N-methylpiperazine, piperazine and morpholine; R42 is H or ChhH2hh+1; hh is 1, 2, 3 or 4; whereby in the group ChhH2hh+1 one or more H atoms can be replaced by F atoms; whereby, however, two substituents from groups R7, R8 and R9 must not be simultaneously OH or OCH3, and wherein at least one of the residues R7, R8 or R9 must be selected from the group consisting of CONR40R41, -OvSOwR23, NR32COR30, NR32CSR30 and NR32SObbR30; as well as their pharmaceutically acceptable salts and trifluoroacetates. 3. Spojevi formule I prema zahtjevu 1 ili 2, naznačeni time, da R1, R2, R3 i R4 su međusobno neovisno H, F, Cl, Br, OH, NH2, CaH2a+1, cikloalkil s 3, 4, 5 ili 6 C atoma, OCbH2b+1; a i b u skupinama CaH2a+1 i OCbH2b+1 su međusobno neovisno 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili R1, R2, R3 i R4 su međusobno neovisno NR11R12; R11 i R12 su međusobno neovisno H, CeH2e+1, CrrH2rr-1; e je 1, 2, 3 ili 4, rr je 3, 4, 5 ili 6, pri čemu u skupinama CeH2e+1 i CrrH2rr-1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R11 i R12 zajedno s N atomima na koje su oni povezani tvore prsten odabran iz skupine koju čine pirolidin, piperidin, N-metilpiperazin, piperazin i morfolin; ili R11 i R12 su međusobno neovisno COR14, CSR14, CONHR14, CSNHR14 ili SO2R14; R14 je CgH2g+1; g je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili R1, R2, R3 i R4 su međusobno neovisno OSO3H, SO3H, SO2R15; R15 je ChH2k, CkH2k+1 ili NR17R18; k je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; R17 i R18 su međusobno neovisno H ili CmH2m+1; m je 1, 2, 3, 4 ili 5, pri čemu u skupini CmH2m+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili R17 i R18 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; pri čemu, međutim, R2 mora uvijek biti različit od H; R5 je metil ili trifluoremetil; R6 je H; R7, R8 i R9 su međusobno neovisno OSO3H, SO3H ili SO2R23; R23 je CnnH2nn+1 ili NR25R26; nn je 1, 2, 3, 4 ili 5, pri čemu u CnnH2nn+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R25 i R26 su međusobno neovisno H, CN ili CzH2z+1, u kojem prva CH2 skupina povezana na dušik može biti zamijenjena sa CO ili CS, a druga CH2 skupina povezana na dušik može biti zamijenjena s NR27; z je 1, 2, 3, 4, 5 ili 6; pri čemu u CzH2z+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R27 je H ili CaaH2aa+1; aa je 1, 2, 3 ili 4; pri čemu u CaaH2aa+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili R25 i R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten, ili R27 i jedna CH2 skupina iz R25 ili R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; ili R7, R8 i R9 su međusobno neovisno NR32COR30, NR32CSR30 ili NR32SO2R30; R30 je H, OH, CccH2cc+1, CyyH2yy-1, pirolidinil ili piperidinil, u kojim prstenovima jedna CH2 skupina može biti zamijenjena s O ili NR33; R32 i R33 su H, metil ili CF3; cc je 1, 2, 3, 4, 5, 6, 7 ili 8; yy 3, 4, 5, 6; pri čemu u skupinama CccH2cc+1 i CyyH2yy-1 jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s NR31, i jedna CH2 skupina može biti zamijenjena s O; R31 je H, metil, etil, CF3, CH2CF3, acetil, propionil, metansulfonil ili etansulfonil; ili R31 zajedno s jednom CH2 skupinom iz R30 i N atomom na koji su one zajedno povezane tvore 5- ili 6-člani prsten; ili R30 je piridil, imidazolil, pirazolil, pirolil, triazolil, tetrazolil, tiazolil ili oksazolil, koji nisu supstituirani ili su supstituirani s najviše 3 supstituenta odabrana iz skupine koju čine F, Cl, metil, etil, trifluor-metll, NH2, NH-acetil; ili R7, R8 i R9 su međusobno neovisno H, F, Cl, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42 ili OCOR42, ee i ff su međusobno neovisno 1, 2, 3 ili 4; ww je 3, 4, 5 ili 6, pri čemu u skupinama CeeH2ee+1, CwwH2ww-1 i OCffH2ff+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R40 i R41 su H, CttH2tt+1 ili C(NH)NH2; tt je 1, 2, 3 ili 4; pri čemu u skupini CttH2tt+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R40 i R41 su međusobno neovisno hidroksietil, N,N-dimetilaminoetil, N,N-dietilaminoetil, pirolidinoetil, N-metilpiperazinoetil, piperazinoetil, morfolinoetil ili piperidinoetil; ili R40 i R41 zajedno s N atomom na koji su oni povezani tvore pirolidinski, piperidinski, N-metilpiperazinski, piperazinski ili morfolinski prsten; R42 je H ili ChhH2hh+1; hh je 1, 2, 3 ili 4; pri čemu u skupini ChhH2hh+1, jedan ili više H atoma može biti zamijenjeno s F atomima; pri čemu, međutim, dva supstituenta iz skupina R7, R8 i R9 ne smiju biti istovremeno OH ili OCH3, i pri čemu najmanje jedan od ostataka R7, R8 ili R9 mora biti odabran iz skupine koju čine CONR40R41, -OvSOwR23, NR32COR30, NR32CSR30 i NR32SObbR30; kao i njihovim farmaceutski podnošljivim solima i trifluor-acetatima.3. Compounds of formula I according to claim 1 or 2, characterized in that R1, R2, R3 and R4 are independently H, F, Cl, Br, OH, NH2, CaH2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms, OCbH2b+1; a and b in the groups CaH2a+1 and OCbH2b+1 are independently 1, 2, 3 or 4, whereby one or more H atoms can be replaced by F atoms; or R 1 , R 2 , R 3 and R 4 are independently NR 11 R 12 ; R11 and R12 are mutually independently H, CeH2e+1, CrrH2rr-1; e is 1, 2, 3 or 4, rr is 3, 4, 5 or 6, whereby in the groups CeH2e+1 and CrrH2rr-1 one or more H atoms may be replaced by F atoms; or R11 and R12 together with the N atoms to which they are attached form a ring selected from the group consisting of pyrrolidine, piperidine, N-methylpiperazine, piperazine and morpholine; or R 11 and R 12 are independently COR 14 , CSR 14 , CONHR 14 , CSNHR 14 or SO 2 R 14 ; R14 is CgH2g+1; g is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or R1, R2, R3 and R4 are mutually independently OSO3H, SO3H, SO2R15; R15 is ChH2k, CkH2k+1 or NR17R18; k is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; R17 and R18 are mutually independently H or CmH2m+1; m is 1, 2, 3, 4 or 5, whereby in the group CmH2m+1 one or more H atoms can be replaced by F atoms; or R17 and R18 together with the N atom to which they are attached form a 5- or 6-membered ring; wherein, however, R 2 must always be different from H; R 5 is methyl or trifluoromethyl; R 6 is H; R 7 , R 8 and R 9 are mutually independently OSO 3 H, SO 3 H or SO 2 R 23 ; R23 is CnnH2nn+1 or NR25R26; nn is 1, 2, 3, 4 or 5, where in CnnH2nn+1 one or more H atoms can be replaced by F atoms; R25 and R26 are independently H, CN or CzH2z+1, wherein the first CH2 group attached to the nitrogen may be replaced by CO or CS and the second CH2 group attached to the nitrogen may be replaced by NR27; z is 1, 2, 3, 4, 5 or 6; whereby in CzH2z+1 one or more H atoms can be replaced by F atoms; R27 is H or CaaH2aa+1; aa is 1, 2, 3 or 4; where in CaaH2aa+1 one or more H atoms can be replaced by F atoms; or R25 and R26 together with the N atom to which they are attached form a 5- or 6-membered ring, or R27 and one CH2 group from R25 or R26 together with the N atom to which they are attached form a 5- or 6-membered ring; or R7, R8 and R9 are independently NR32COR30, NR32CSR30 or NR32SO2R30; R30 is H, OH, CccH2cc+1, CyyH2yy-1, pyrrolidinyl or piperidinyl, in which rings one CH2 group may be replaced by O or NR33; R32 and R33 are H, methyl or CF3; cc is 1, 2, 3, 4, 5, 6, 7 or 8; yy 3, 4, 5, 6; wherein in the groups CccH2cc+1 and CyyH2yy-1 one or more H atoms can be replaced by F atoms and one or more CH2 groups can be replaced by NR31, and one CH2 group can be replaced by O; R31 is H, methyl, ethyl, CF3, CH2CF3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl; or R31 together with one CH2 group from R30 and the N atom to which they are connected form a 5- or 6-membered ring; or R30 is pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl, which are unsubstituted or substituted with at most 3 substituents selected from the group consisting of F, Cl, methyl, ethyl, trifluoromethyl, NH2, NH-acetyl ; or R7, R8 and R9 are independently H, F, Cl, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42 or OCOR42, ee and ff are independently 1, 2, 3 or 4; ww is 3, 4, 5 or 6, whereby in the groups CeeH2ee+1, CwwH2ww-1 and OCffH2ff+1 one or more H atoms can be replaced by F atoms; R40 and R41 are H, CttH2tt+1 or C(NH)NH2; tt is 1, 2, 3 or 4; whereby in the group CttH2tt+1 one or more H atoms may be replaced by F atoms; or R40 and R41 are mutually independently hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or R40 and R41 together with the N atom to which they are attached form a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring; R42 is H or ChhH2hh+1; hh is 1, 2, 3 or 4; wherein in the group ChhH2hh+1, one or more H atoms can be replaced by F atoms; whereby, however, two substituents from groups R7, R8 and R9 must not be simultaneously OH or OCH3, and wherein at least one of the residues R7, R8 or R9 must be selected from the group consisting of CONR40R41, -OvSOwR23, NR32COR30, NR32CSR30 and NR32SObbR30; as well as their pharmaceutically acceptable salts and trifluoroacetates. 4. Spojevi formule I prema zahtjevima 1-3, naznačeni time, da R1, R2, R3 i R4 su međusobno neovisno H, F, Cl, Br, OH, NH2, CaH2a+1, cikloalkil s 3, 4, 5 ili 6 C atoma, OCbH2b+1; a i b u skupinama CaH2a+1 i OCbH2b+1 su međusobno neovisno 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili R1, R2, R3 i R4 su međusobno neovisno NR11R12; R11 i R12 su međusobno neovisno H, CeH2e+1, CrrH2rr-1; e je 1, 2, 3 ili 4, rr je 3, 4, 5 ili 6, pri čemu u skupinama CeH2e+1 i CrrH2rr-1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R11 i R12 zajedno s N atomom na koji su oni povezani tvore prsten odabran iz skupine koju čine pirolidin, piperidin, N-metilpiperazin, piperazin i morfolin; ili R11 i R12 su međusobno neovisno COR14, CSR14, CONHR14, CSNHR14 ili SO2R14; R14 je CgH2g+1; g je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili R1, R2, R3 i R4 su međusobno neovisno OSO3H, SO3H, SO2R15; R15 je CkH2k+1 ili NR17R18; k je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; R17 i R18 su međusobno neovisno H ili CmH2m+1; m je 1, 2, 3, 4 ili 5, pri čemu u skupini CmH2m+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili R17 i R18 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; pri čemu, međutim, R2 mora uvijek biti različit od H; R5 je metil ili trifluoremetil; R6 je H; R7, R8 i R9 su međusobno neovisno OSO3H, SO3H ili SO2R23; R23 je CnnH2nn+1 ili NR25R26; nn je 1, 2, 3, 4 ili 5, pri čemu u CnnH2nn+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R25 i R26 su međusobno neovisno H, CN ili CzH2z+1, u. kojem prva CH2 skupina povezana na dušik može biti zamijenjena sa CO ili CS, a druga CH2 skupina povezana na dušik može biti zamijenjena NR27; z je 1, 2, 3, 4, 5 ili 6; pri čemu u CzH2z+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R27 je H ili CaaH2aa+1; aa je 1, 2, 3 ili 4; pri čemu u CaaH2aa+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili R25 i R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten, ili R27 i jedna CH2 skupina iz R25 ili R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; ili R7, R8 i R9 su međusobno neovisno NR32COR30, NR32CSR30 ili NR32SO2R30; R30 je H, OH, CccH2cc+1, CyyH2yy-1, pirolidinil ili piperidinil, u kojim prstenovima jedna CH2 skupina može biti zamijenjena O ili NR33; R32 i R33 su H, metil ili CF3; cc je 1, 2, 3, 4, 5, 6, 7 ili 8; yy je 3, 4, 5 ili 6; pri čemu u skupinama CccH2cc+1 i CyyH2yy-1 jedan više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s NR31, i jedna CH2 skupina može biti zamijenjena s O; R31 je H, metil, etil, CF3, CH3CF3, acetil, propionil, metansulfonil ili etansulfonil; ili R31 zajedno s jednom CH2 skupinom iz R30 i N atomom na koji su oni zajedno povezani tvore 5-ili 6-člani prsten; ili R30 je piridil, imidazolil, pirazolil, pirolil, triazolil, tetrazolil, tiazolil ili oksazolil, koji nisu supstituirani ili su supstituirani s najviše 3 supstituenta odabrana iz skupine koju čine F, Cl, metil, etil, trifluor-metil, NH2, NH-acetil; ili R7, R8 i R9 su međusobno neovisno H, F, Cl, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR4OR41, CONR40R41, COOR42 ili COR42, ee i ff su međusobno neovisno 1, 2, 3 ili 4; ww je 3, 4, 5 ili 6, pri čemu u skupinama C2eeH2ee+1, CwwH2ww-1 i OCffH2ff+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R40 i R41 su H, CttH2tt+1 ili C(NH)NH2; tt je 1, 2, 3 ili 4; pri čemu u skupini CttH2tt+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R40 i R41 su međusobno neovisno hidroksietil, N,N-dimetilaminoetil, N,N-dietilaminoetil, pirolidinoetil, N-metilpiperazinoetil, piperazinoetil, morfolinoetil ili piperidinoetil; ili R40 i R41 zajedno s N atomom na koji su oni povezani tvore pirolidinski, piperidinski, N-metilpiperazinski, piperazinski ili morfolinski prten; R42 je H ili ChhH2hh+1; hh je 1, 2, 3 ili 4; pri čemu u skupini ChhH2hh+1 jedan ili više H atoma može biti zamijenjeno s F atomima; pri čemu, međutim, dva supstituenta iz skupina R7, R8 i R9 ne smiju biti istovremeno OH ili OCH3, i pri čemu najmanje jedan od ostataka R7, R8 ili R9 mora biti odabran iz skupine koju čine -OvSOwR23, NR32COR30, NR32CSR30 i NR32SObbR30; kao i njihove farmaceutski podnošljive soli i trifluoracetati.4. Compounds of formula I according to claims 1-3, characterized in that R1, R2, R3 and R4 are independently H, F, Cl, Br, OH, NH2, CaH2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms, OCbH2b+1; a and b in the groups CaH2a+1 and OCbH2b+1 are independently 1, 2, 3 or 4, whereby one or more H atoms can be replaced by F atoms; or R 1 , R 2 , R 3 and R 4 are independently NR 11 R 12 ; R11 and R12 are mutually independently H, CeH2e+1, CrrH2rr-1; e is 1, 2, 3 or 4, rr is 3, 4, 5 or 6, whereby in the groups CeH2e+1 and CrrH2rr-1 one or more H atoms may be replaced by F atoms; or R11 and R12 together with the N atom to which they are attached form a ring selected from the group consisting of pyrrolidine, piperidine, N-methylpiperazine, piperazine and morpholine; or R 11 and R 12 are independently COR 14 , CSR 14 , CONHR 14 , CSNHR 14 or SO 2 R 14 ; R14 is CgH2g+1; g is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or R1, R2, R3 and R4 are mutually independently OSO3H, SO3H, SO2R15; R15 is CkH2k+1 or NR17R18; k is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; R17 and R18 are mutually independently H or CmH2m+1; m is 1, 2, 3, 4 or 5, whereby in the group CmH2m+1 one or more H atoms can be replaced by F atoms; or R17 and R18 together with the N atom to which they are attached form a 5- or 6-membered ring; wherein, however, R 2 must always be different from H; R 5 is methyl or trifluoromethyl; R 6 is H; R 7 , R 8 and R 9 are mutually independently OSO 3 H, SO 3 H or SO 2 R 23 ; R23 is CnnH2nn+1 or NR25R26; nn is 1, 2, 3, 4 or 5, where in CnnH2nn+1 one or more H atoms can be replaced by F atoms; R25 and R26 are independently H, CN or CzH2z+1, in which the first CH2 group attached to the nitrogen can be replaced by CO or CS, and the second CH2 group attached to the nitrogen can be replaced by NR27; z is 1, 2, 3, 4, 5 or 6; whereby in CzH2z+1 one or more H atoms can be replaced by F atoms; R27 is H or CaaH2aa+1; aa is 1, 2, 3 or 4; where in CaaH2aa+1 one or more H atoms can be replaced by F atoms; or R25 and R26 together with the N atom to which they are attached form a 5- or 6-membered ring, or R27 and one CH2 group from R25 or R26 together with the N atom to which they are attached form a 5- or 6-membered ring; or R7, R8 and R9 are independently NR32COR30, NR32CSR30 or NR32SO2R30; R30 is H, OH, CccH2cc+1, CyyH2yy-1, pyrrolidinyl or piperidinyl, in which rings one CH2 group may be replaced by O or NR33; R32 and R33 are H, methyl or CF3; cc is 1, 2, 3, 4, 5, 6, 7 or 8; yy is 3, 4, 5 or 6; wherein in the groups CccH2cc+1 and CyyH2yy-1 one or more H atoms can be replaced by F atoms and one or more CH2 groups can be replaced by NR31, and one CH2 group can be replaced by O; R31 is H, methyl, ethyl, CF3, CH3CF3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl; or R31 together with one CH2 group from R30 and the N atom to which they are connected form a 5- or 6-membered ring; or R30 is pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl, which are unsubstituted or substituted with at most 3 substituents selected from the group consisting of F, Cl, methyl, ethyl, trifluoromethyl, NH2, NH-acetyl ; or R7, R8 and R9 are independently H, F, Cl, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR4OR41, CONR40R41, COOR42 or COR42, ee and ff are independently 1, 2, 3 or 4; ww is 3, 4, 5 or 6, whereby in the groups C2eeH2ee+1, CwwH2ww-1 and OCffH2ff+1 one or more H atoms can be replaced by F atoms; R40 and R41 are H, CttH2tt+1 or C(NH)NH2; tt is 1, 2, 3 or 4; whereby in the group CttH2tt+1 one or more H atoms may be replaced by F atoms; or R40 and R41 are mutually independently hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or R40 and R41 together with the N atom to which they are attached form a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring; R42 is H or ChhH2hh+1; hh is 1, 2, 3 or 4; whereby in the group ChhH2hh+1 one or more H atoms can be replaced by F atoms; whereby, however, two substituents from groups R7, R8 and R9 must not be simultaneously OH or OCH3, and wherein at least one of the residues R7, R8 or R9 must be selected from the group consisting of -OvSOwR23, NR32COR30, NR32CSR30 and NR32SObbR30; as well as their pharmaceutically acceptable salts and trifluoroacetates. 5. Spoj formule I, naznačen time, da je on odabran iz skupine koju čine: 1) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 2) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-benzolsulfonamid; 3) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-benzolsulfonamid; 4) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N,N-dimetil-benzol-sulfonamid; 5) 4-(4-bromfenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin; 6) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-benzojeva kiselina; 7) 4-(6,8-diklor-2-metil)-1,2,3,4-tetrahidroizokinolin-4-il)-N-etil-benzamid; 8) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-propil-benzamid; 9) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-(2-dimetilaminoetil)-benzamid; 10) 6,8-diklor-2-metil-4-(4-morfolin-4-il-fenil)-1,2,3,4-tetrahidroizokinolin; 11) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-dietil-amin; 12) 6,8-diklor-2-metil-4-(4-piperidin-1-il-fenil)-1,2,3,4-tetahidroizokinolin; 13) 6,8-diklor-2-metil-4-(4-pirolidin-1-il-fenil)-1,2,3,4-tetrahidroizokinolin; 14) 6,8-diklor-2-metil-4-[4-(4-metil-piperazin-1-il)-fenil]-1,2,3,4-tetrahidroizokinolin; 15) 6,8-diklor-2-ciklopropil-4-fenil-1,2,3,4-tetrahidroizokinolin; 16) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin; 17) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-propil-urea; 18) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 19) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea; 20) N-[4-(6-metansulfonil-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 21) N-[4-(2,6,8-trimetil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 22) N-[4-(6-brom-8-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-1l}-fenil]-acetamid; 23) N-[4-{8-klor-2-metil-6-pirolidin-1-il-1,2,3,4-tetra-hidroizokinolin-4-il)-fenil]-acetamid; 24) N-[4-(8-klor-2-metil-6-morfolin-4-il-1,2,3,4-tetra-hidroizokinolin-4-il)-fenil]-acetamid; 25) N-{4-[8-klor-2-metil-6-(4-metil-piperazin-1-il)-1,2,3,4-tetrahidro-izokinolin-4-il]-fenil}-acetamid; 26) N-{4-[8-klor-6-(ciklopropilmetil-amino)-2-metil-1,2,3,4-tetrahidroizokinolin-4-il]-fenil}-acetamid; 27) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-2-hidroksi-benzojeva kiselina; 28) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-2-hidroksi-N-metil-benzamid; 29) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-etil-2-hidroksi-benzamid; 30) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-(2-dimetilamino-etil)-2-hidroksi-benzamid; 31) N-[5-(6, δ-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-2-hidroksibenzoil]-gvanidin; 32) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 33) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenilamin; 34) 2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenilamin; 35) N-[4-{6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 36) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-butiramid; 37) pentanska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 38) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 39) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2-dimetil-propionamid; 40) ciklopropankarbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 41) ciklobutankarbonska kiselina-[4-(6,diklor-2-metil-1,2,3, 4-tetrahidroizokinolin-4-il)-fenil]-amid; 42) ciklopentankarbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 43) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2,2-trifluoracetamid; 44) 1-acetil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 45) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-nikotinamid; 46) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metansulfonamid; 47) etansulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 48) N',N'-dimetilamino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 49) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 50) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-butiramid; 51) pentanska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 52) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 53) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2-dimetil-propionamid; 54) ciklopropankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 55) ciklobutankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 56) ciklopentankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil-amid; 57) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin 4-il)-fenil]-2,2,2-trifluoracetamid; 58) 1-acetil-piperidin-4-karbonska kiselina-[3-(6,8-di-klor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 59) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-nikotinamid; 60) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 61) etansulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 62) N',N'-dimetilamino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-sulfamid; 63) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 64) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenilj-butiramid; 65) pentanska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 66) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 67) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2-dimetil-propionamid; 68) ciklopropankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 69) ciklobutankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 70) ciklopentankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 71) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2,2-trifluoracetamid; 72) 1-acetil-piperidin-4-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 73) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 74) etansulfonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 75) N',N'-dimetilamino-N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-sulfamid; 76) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 77) 1-[3-(6,δ-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 78) 1-[2-(6,δ-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 79) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinotin-4-il)-feni ]-3-metil-tiourea; 80) N-{5-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilsulfamoil]-4-metil-tiazol-2-1l}-acetamid; 81) N-{5-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilsulfamoil]-4-metil-tiazol-2-1l}-acetamid; 82) 1,2-dimetil-1H-imidazol-4-sulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 83) 1,2-dimetil-1H-imidazol-4-sulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 84) 5-klor-1,3-dimetil-1H-pirazol-4-sulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 85) 5-klor-1,3-dimetil-1H-pirazol-4-sulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 86) 5-brom-tiofen-2-sulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 87) 5-brom-tiofen-2-sulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 88) N-{4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluormetansulfonamid; 89) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluor-metansulfonamid; 90) 2,2,2-trifluor-etansulfonska kiselina-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 91) 2,2,2-trifluor-etansulfonska kiselina-3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 92) N-etil-N'-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonil-urea; 93) 2-klor-5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonamid; 94) 2-metil-4-fenil-6,8-bis-trifluormetil-1,2,3,4-tetrahidroizokinolin; 95) 2-amino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 96) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-metilamino-acetamid; 97) N-[6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetitamino-acetamid; 98) 2-amino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-propionamid; 99) 2-amino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-butiramid; 100) 2,6-diamino-heksanska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 101) pirolidin-2-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 102) N-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izonikotinamid; 103) 1H-pirol-3-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin4-il)-fenil]-amid; 104) 1H-pirol-2-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 105) 1-metil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 106) 1,4-dimetil-1H-pirol-2-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 107) 4-nitro-1H-pirol-2-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 108) 2,5-dimetil-1H-pirol-3-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 109) 1H-imidazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 110) 1-metansulfonil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il-fenil]-amid; 111) 3,5-dimetil-1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 112) 1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 113) 3-trifluormetil-1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 114) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-metilamino-acetamid; 115) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-acetamid; 116) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-propionamid; 117) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-butiramid; 118) 2,6-diamino-heksanska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 119) pirolidin-2-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-1i)-fenil]-amid; 120) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izonikotinamid; 121) 1H-pirol-3-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 122) 1H-pirol-2-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 123) 1-metil-piperidin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 124) 1,4-dimetil-1H-pirol-2-karbonska-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 125) 4-nitro-1H-pirol-2-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 126) 2,5-dimetil-1H-pirol-3-karbonska kiselina-[3-(6,8-di-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 127) 1H-imidazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 128) 1-metansulfonil-piperidin-4-karbonska kiselina-[3-6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil-amid; 129) 3,5-dimetil-1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 130) 1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 131) 3-trifluormetil-1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 132) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-tiourea; 133) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-tiourea; 134) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-tiourea; 135) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dimetil-urea; 136) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 137) piperidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 138) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin4-il)-fenil]-amid; 139) pirolidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 140) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 141) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 142) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 143) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-furan-3-il)-urea; 144) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-piran-4-il)-urea; 145) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-metil-1-(l-tetrahidroizokinolin-4-il)-urea; 146) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenilj-1-(3-dimetilamino-propil)-1-metil-urea; 147) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-(2-dimetilamino-etil)-1-metil-urea; 148) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(3-dimetilamino-propil)-urea; 149) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-metoksi-etil)-urea; 150) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-piridin-3-il-urea; 151) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-piridin-4-il-urea; 152) 4-metil-piperazin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 153) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 154) 3-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dimetil-urea; 155) 3-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 156) piperidin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 157) morfolin-4-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 158) pirolidin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 159) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 160) 4-metil-piperazin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 161) pirolidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 162) 1-[4-(6,-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-metil-urea; 163) 3-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil[-1,1-dimetil-urea; 164) 3-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 165) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 166) piperidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 167) morfolin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 168) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-formamid; 169) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metil-amin; 170) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3-dimetil-urea; 171) 4-metil-piperazin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 172) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-l,3,3-trimetil-urea; 173) piperidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 174) morfolin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metil-amid; 175) pirolidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 176) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-1-metil-urea; 177) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3,3-dietil-1-metil-urea; 178) N-{3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil}-formamid; 179) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amin; 180) pirolidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 181) piperidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il-fenil]-metil-amid; 182) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3,3-trimetil-urea; 183) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3-dimetil-urea; 184) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 185) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metil-amid; 186) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-1-metil-urea; 187) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3,3-dietil-1-metil-urea; 188) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina-2-dimetilamino-etil ester; 189) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina-2-dimetilamino-etil ester; 190) [2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina-2-dimetilamino-etil ester; 191) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina metil ester; 192) [3-(6,8-diklor-2-meti)-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina etil ester; 193) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina izopropil ester; 194) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina 2,2-dimetil-propil ester; 195) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenill-karbaminska kiselina metil ester; 196) [4-(6,δ-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina izopropil ester; 197) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina 2,2-dimetil-propil ester; 198) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina etil ester; 199) (R)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamid; 200) (S)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamid; 201) (R)-1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea; 202) (S)-1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea; 203) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 204) 4-(3-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin; 205) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-hidroksi-etil)-urea; 206) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina etil ester; 207) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina, kao i njihove farmacetski podnošljive soli. 5. Compound of formula I, indicated by the fact that it is selected from the group consisting of: 1) N-[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) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N,N-dimethyl-benzene-sulfonamide; 5) 4-(4-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline; 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)-N-ethyl-benzamide; 8) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-propyl-benzamide; 9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-(2-dimethylaminoethyl)-benzamide; 10) 6,8-dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline; 11) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-diethyl-amine; 12) 6,8-dichloro-2-methyl-4-(4-piperidin-1-yl-phenyl)-1,2,3,4-tetahydroisoquinoline; 13) 6,8-dichloro-2-methyl-4-(4-pyrrolidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline; 14) 6,8-dichloro-2-methyl-4-[4-(4-methyl-piperazin-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-tetrahydro-isoquinolin-4-yl)-phenylamine; 17) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-propyl-urea; 18) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea; 19) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea; 20) N-[4-(6-methanesulfonyl-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide; 21) N-[4-(2,6,8-trimethyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide; 22) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-1l}-phenyl]-acetamide; 23) N-[4-{ 8-chloro-2-methyl-6-pyrrolidin-1-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide; 24) N-[4-(8-chloro-2-methyl-6-morpholin-4-yl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide; 25) N-{4-[8-chloro-2-methyl-6-(4-methyl-piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}- acetamide; 26) N-{4-[8-chloro-6-(cyclopropylmethyl-amino)-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-hydroxy-benzoic acid; 28) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxy-N-methyl-benzamide; 29) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-ethyl-2-hydroxy-benzamide; 30) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-2-hydroxy-benzamide; 31) N-[5-(6,δ-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxybenzoyl]-guanidine; 32) N-[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) N-[4-{6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide; 36) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide; 37) pentanoic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 38) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide; 39) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide; 40) cyclopropanecarboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 41) cyclobutanecarboxylic acid-[4-(6,dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 42) cyclopentanecarboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 43) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2,2-trifluoroacetamide; 44) 1-acetyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide; 45) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-nicotinamide; 46) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methanesulfonamide; 47) ethanesulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 48) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide; 49) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide; 50) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-butyramide; 51) pentanoic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 52) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide; 53) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide; 54) cyclopropanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 55) cyclobutanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 56) cyclopentanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl-amide; 57) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline 4-yl)-phenyl]-2,2,2-trifluoroacetamide; 58) 1-acetyl-piperidine-4-carboxylic acid-[3-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 59) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-nicotinamide; 60) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide; 61) ethanesulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 62) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-sulfamide; 63) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide; 64) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenylj-butyramide; 65) pentanoic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 66) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide; 67) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide; 68) cyclopropanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 69) cyclobutanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 70) cyclopentanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 71) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2,2-trifluoroacetamide; 72) 1-acetyl-piperidine-4-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 73) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide; 74) ethanesulfonic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 75) N',N'-dimethylamino-N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-sulfamide; 76) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea; 77) 1-[3-(6,δ-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea; 78) 1-[2-(6,δ-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea; 79) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinotin-4-yl)-phenyl]-3-methyl-thiourea; 80) N-{5-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-1l }-acetamide; 81) N-{5-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-1l }-acetamide; 82) 1,2-dimethyl-1H-imidazole-4-sulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide ; 83) 1,2-dimethyl-1H-imidazol-4-sulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide; 84) 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)- phenyl]-amide; 85) 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)- phenyl]-amide; 86) 5-bromo-thiophene-2-sulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 87) 5-bromo-thiophene-2-sulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 88) N-{4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide; 89) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide; 90) 2,2,2-trifluoroethanesulfonic acid-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 91) 2,2,2-trifluoroethanesulfonic acid-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 92) N-ethyl-N'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonyl-urea; 93) 2-chloro-5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide; 94) 2-methyl-4-phenyl-6,8-bis-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline; 95) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide; 96) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-methylamino-acetamide; 97) N-[6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide; 98) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide; 99) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide; 100) 2,6-diamino-hexanoic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 101) pyrrolidine-2-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 102) N-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isonicotinamide; 103) 1H-pyrrole-3-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin4-yl)-phenyl]-amide; 104) 1H-pyrrole-2-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 105) 1-methyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 106) 1,4-dimethyl-1H-pyrrole-2-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide; 107) 4-nitro-1H-pyrrole-2-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide; 108) 2,5-dimethyl-1H-pyrrole-3-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide; 109) 1H-imidazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide; 110) 1-methanesulfonyl-piperidin-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl-phenyl]-amide; 111) 3,5-dimethyl-1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 112) 1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 113) 3-trifluoromethyl-1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 114) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-methylamino-acetamide; 115) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide; 116) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide; 117) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide; 118) 2,6-diamino-hexanoic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 119) pyrrolidine-2-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-1i)-phenyl]-amide; 120) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isonicotinamide; 121) 1H-pyrrole-3-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 122) 1H-pyrrole-2-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 123) 1-methyl-piperidine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide; 124) 1,4-dimethyl-1H-pyrrole-2-carbono-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide; 125) 4-nitro-1H-pyrrole-2-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide; 126) 2,5-dimethyl-1H-pyrrole-3-carboxylic acid-[3-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-amide; 127) 1H-imidazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 128) 1-methanesulfonyl-piperidine-4-carboxylic acid-[3-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl-amide; 129) 3,5-dimethyl-1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide ; 130) 1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide; 131) 3-trifluoromethyl-1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide ; 132) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-thiourea; 133) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-thiourea; 134) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-thiourea; 135) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea; 136) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide; 137) piperidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 138) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin4-yl)-phenyl]-amide; 139) pyrrolidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 140) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea; 141) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea; 142) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea; 143) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-furan-3-yl)-urea; 144) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-pyran-4-yl)-urea; 145) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-methyl-1-(1-tetrahydroisoquinolin-4-yl) )-urea; 146) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-(3-dimethylamino-propyl)-1-methyl-urea ; 147) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-(2-dimethylamino-ethyl)-1-methyl- urea; 148) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(3-dimethylamino-propyl)-urea; 149) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea; 150) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-pyridin-3-yl-urea; 151) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-pyridin-4-yl-urea; 152) 4-methyl-piperazine-1-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide; 153) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea; 154) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea; 155) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea; 156) piperidine-1-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 157) morpholine-4-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 158) pyrrolidine-1-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 159) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea; 160) 4-methyl-piperazine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide; 161) pyrrolidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 162) 1-[4-(6,-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea; 163) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl[-1,1-dimethyl-urea; 164) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea; 165) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea; 166) piperidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 167) morpholine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 168) N-[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)-phenyl]-methyl-amine; 170) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea; 171) 4-methyl-piperazine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide ; 172) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea; 173) piperidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide; 174) morpholine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methyl-amide; 175) pyrrolidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide; 176) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl- urea; 177) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3,3-diethyl-1-methyl-urea; 178) N-{3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl}-formamide; 179) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine; 180) pyrrolidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide; 181) Piperidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl-phenyl]-methyl-amide; 182) 1- [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea; 183) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea; 184) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide; 185) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methyl-amide; 186) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl- urea; 187) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3,3-diethyl-1-methyl-urea; 188) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid-2-dimethylamino-ethyl ester; 189) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid-2-dimethylamino-ethyl ester; 190) [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid-2-dimethylamino-ethyl ester; 191) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid methyl ester; 192) [3-(6,8-dichloro-2-methyl)-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid ethyl ester; 193) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid isopropyl ester; 194) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid 2,2-dimethyl-propyl ester; 195) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl-carbamic acid methyl ester; 196) [4-(6,δ-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid isopropyl ester; 197) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid 2,2-dimethyl-propyl ester; 198) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid ethyl ester; 199) (R)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide; 200) (S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide; 201) (R)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea; 202) (S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea; 203) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide; 204) 4-(3-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline; 205) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea; 206) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid ethyl ester; 207) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid, as well as their pharmaceutically acceptable salts. 6. Spoj formule I prema zahtjevu 1, naznačen time, da je on odabran iz skupine koju čine: 1) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 2) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonamid; 3) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonamid; 4) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-metil-tiourea; 5) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 6) N-[4-(6-brom-8-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 7) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 8) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 9) 1-acetil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 10) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 11) etansulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 12) N',N'-dimetilamino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 13) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 14) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-butiramid; 15) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 16) ciklopropankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 17) ciklobutankarbonska kiselina-[3-(6,8-diklor-2-metil-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 18) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2,2-trifluor-acetamid; 19) 1-acetil-piperidin-4-karbonska kiselina-[3-(6,8-di-klor-2-metil-1,2,3,4-tetrahidro-izokinoain-4-1l}-fenil]-amid; 20) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin 4-il)-fenil]-nikotinamid; 21) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 22) etansulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 23) N',N'-dimetilamino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 24) ciklopropankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 25) 1-acetil-piperidin-4-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 26) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 27) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 28) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 29) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 30) N-{5-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilsulfamoil]-4-metil-tiazol-2-1l}-acetamid; 31) 1,2-dimetil-1H-imidazol-4-sulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 32) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluor-metansulfonamid; 33) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluor-metansulfonamid; 34) N-etil-N'-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonil-urea; 35) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-acetamid; 36) 2,6-diamino-heksanska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 37) 1H-pirol-3-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 38) 1-metil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 39) 1-metansulfonil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 40) 1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 41) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-metilamino-acetamid; 42) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-acetamid; 43) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-propionamid; 44) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-butiramid; 45) 2,6-diamino-heksanska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 46) 1-metil-piperidin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 47) 1H-imidazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 48) 1-metansulfonil-piperidin-4-karbonska kiselina-[3-6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 49) 3,5-dimetil-1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 50) 1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 51) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dimetil-urea; 52) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroi.zokinolin-4-il)-fenil] amid; 53) piperidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 54) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 55) pirolidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 56) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 57) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 58) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 59) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-furan-3-il)-urea; 60) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-piran-4-il)-urea; 61) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-metil-1-(1-metil-piperidin-4-il)-urea; 62) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-(3-dimetilaraino-propil)-1-metil-urea; 63) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-etil)-1-metil-urea; 64) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(3-dimetilamino-propil)-urea; 65) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-metoksi-etil)-urea; 66) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-piridin-3-il-urea; 67) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-piridin-4-il-urea; 68) 4-metil-piperazin-1-il-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-amid; 69) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 70) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilarαino-etil)-urea; 71) 4-metil-piperazin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-1i)-fenil]amid; 72) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 73) 3-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dimetil-urea; 74) 3-[4-{6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 75) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahiroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 76) morfolin-4-karbonska-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 77) N-[4-(6,e-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-formamid; 78) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-formamid; 79) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3,3-trimetil-urea; 80) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3-dimetil-urea; 81) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 82) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 83) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-1-metil-urea; 84) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]karbaminska kiselina 2-dimetilamino-etil ester; 85) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 86) [2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 87) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina metil ester; 88) (R ili S)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamid; 89) (R ili S)-1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea; 90) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-hidroksi-etil)-urea; kao i njihove farmacetski podnošljive soli.6. The compound of formula I according to claim 1, characterized in that it is selected from the group consisting of: 1) N-[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-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide; 3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide; 4) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-thiourea; 5) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea; 6) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide; 7) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-acetamide; 8) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide; 9) 1-acetyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 10) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide; 11) ethanesulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 12) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide; 13) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide; 14) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-butyramide; 15) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide; 16) cyclopropanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 17) cyclobutanecarboxylic acid-[3-(6,8-dichloro-2-methyl-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide; 18) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2,2-trifluoroacetamide; 19) 1-acetyl-piperidine-4-carboxylic acid-[3-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinoain-4-1l}-phenyl]-amide ; 20) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline 4-yl)-phenyl]-nicotinamide; 21) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide; 22) ethanesulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 23) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide; 24) cyclopropanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 25) 1-acetyl-piperidine-4-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 26) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea; 27) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea; 28) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea; 29) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea; 30) N-{5-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-1l }-acetamide; 31) 1,2-dimethyl-1H-imidazol-4-sulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide; 32) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide; 33) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide; 34) N-ethyl-N'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonyl-urea; 35) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide; 36) 2,6-diamino-hexanoic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 37) 1H-pyrrole-3-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 38) 1-methyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide; 39) 1-methanesulfonyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 40) 1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide; 41) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-methylamino-acetamide; 42) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide; 43) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide; 44) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide; 45) 2,6-diamino-hexanoic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 46) 1-methyl-piperidine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide; 47) 1H-imidazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 48) 1-methanesulfonyl-piperidine-4-carboxylic acid-[3-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 49) 3,5-dimethyl-1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide; 50) 1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 51) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea; 52) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl] amide; 53) piperidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 54) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 55) pyrrolidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 56) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea; 57) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea; 58) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea; 59) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-furan-3-yl)-urea; 60) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-pyran-4-yl)-urea; 61) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-methyl-1-(1-methyl-piperidine-4 -yl)-urea; 62) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-(3-dimethylaraino-propyl)-1-methyl- urea; 63) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-ethyl)-1-methyl-urea; 64) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(3-dimethylamino-propyl)-urea; 65) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea; 66) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-pyridin-3-yl-urea; 67) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-pyridin-4-yl-urea; 68) 4-methyl-piperazin-1-yl-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-amide; 69) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea; 70) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylaraino-ethyl)-urea; 71) 4-methyl-piperazine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-1i)-phenyl]amide; 72) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea; 73) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea; 74) 3-[4-{6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea; 75) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrachiroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea; 76) morpholine-4-carbon-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 77) N-[4-(6,ε-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-formamide; 78) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-formamide; 79) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea; 80) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea; 81) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide; 82) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide ; 83) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl- urea; 84) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]carbamic acid 2-dimethylamino-ethyl ester; 85) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester; 86) [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester; 87) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid methyl ester; 88) (R or S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide; 89) (R or S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea; 90) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea; as well as their pharmaceutically acceptable salts. 7. Upotreba spoja formule I kao i njegovih farmacetski podnošljivih soli, naznačena time, da se oni koriste za proizvodnju lijeka za liječenje bolesti na koje se može utjecati s inhibicijom podtipa III izmjenjivača natrij-protona (NHE3), pri čemu u formuli I simboli imaju slijedeća značenja: R1, R2, R3 i R4 međusobno neovisno predstavljaju H, F, Cl, Br, J, CN, NO2, OH, NH2, CaH2a+1, CggH2qq-1, OCbH2b+1, COOR10, OCOR10, COR10 ili Ox-(CH2)y-fenil; a i b u skupinama CaH2a+1 i OCbH2b+1 su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; qq 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; R10 je H ili CcH2c+1; c je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; x je nula ili 1; y je nula, 1, 2, 3 ili 4; pri čemu fenilni prsten u skupini Ox-(CH2)y-fenil nije supstituiran ili je supstituiran s 1-3 supstituenta odabrana iz skupine koju čine F, Cl, Br, CN, NO2, OH, NH2 ili CdH2d+1; d je 1, 2, 3, ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R1, R2, R3 i R4 međusobno neovisno predstavljaju heteroaril, pri čemu u prstenu može biti nula, 1, 2, 3 ili 4 N atoma, nula ili 1 atom kisika ili nula ili l S atom; ili R1, R2, R3 i R4 međusobno neovisno predstavljaju CONR11R12 ili NR11R12; R11 i R12 međusobno neovisno predstavljaju H, CeH2e+1 i CrrH2rr-1; e je 1, 2, 3, 4, 5, 6, 7 ili 8, rr je 3, 4, 5, 6, 7, ili 8, pri čemu u skupinama CeH2e+1 i CrrH2rr-1 jedan ili više H atoma smije biti zamijenjeno F atomima i jedna ili više CH2 skupina može biti zamijenjeno s F atomima O ili s NR13; R13 je H ili CfH2f+1; f je 1, 2, 3, ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R13 i jedna CH2 skupina iz R11 ili R12 zajedno s N atomom, na koji su one povezane, tvore 5- ili 6-člani prsten; ili R11 i R12 zajedno s N atomom na koji su one povezane tvore 5-, 6- ili 7-člani prsten; ili R11 i R12 međusobno neovisno predstavljaju COR14, CSR14 ili SO2R14; R14 je CgH2g+1; g je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s F atomima O ili s NR13; ili R1, R2, R3 i R4 su međusobno neovisno -Oh-SOjR15, pri čemu h je nula ili 1, j je nula, 1 ili 2; R15 je CkH2k+1, OH, OClH21+1 ili NR17R18; k je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; l je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; R17 i R18 međusobno neovisno predstavljaju H ili CmH2m+1; m je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu u skupini jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s O, CO, CS ili NR19; R19 je H ili CnH2n+1; n je 1, 2, 3 ili 4; pri čemu u skupini CnH2n+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili R17 i R18 zajedno s N atomom na koji su one povezane tvore 5-, 6- ili 7-člani prsten; ili R19 i jedna CH2 skupina iz R17 ili R18 zajedno s N atomom na koji su one povezane tvore 5- ili 6-člani prsten; R5 je H, CpH2p+1, CssH2ss-1, COR20 ili SO2R20; p je 1, 2, 3, 4, 5, 6, 7 ili 8, ss je 4, 5, 6, 7 ili 8, R20 je CqH2q+1; q je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu u skupinama CpH2p+1, CssH2ss-1 i CqH2q+1 jedan ili više H atoma može biti zamijenjeno s F atomima, i jedna ili više CH2 skupina može biti zamijenjeno s O ili NR21; R21 je H ili CrH2r+1; r je 1, 2, 3 ili 4; pri čemu u skupini CrH2r+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R6 je H, F, Cl, Br, I, CsH2s+1, CddH2dd-1, OH, OCtH2t+1 ili OCOR22; s i t su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8; d.d. je 3, 4, 5, 6, 7 ili 8, pri čemu u skupinama CsH2s+1, CddH2dd-1 i OCtH2t+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R22 je CuH2u+1; u je 1, 2, 3 ili 4; pri čemu u skupini CuH2u+1 jedan ili više H atoma može biti zamijenjeno s F atomima: R7, R8 i R9 su međusobno neovisno –Ov-SOw-R23; v je nula ili 1; w je nula, 1 ili 2; R23 je CnnH2nn+1, CmmH2mm-1, OH, OCppH2pp+1 ili NR25R26; nn i pp su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8, mm je 3, 4, 5, 6, 7 ili 8, pri čemu u skupinama CnnH2nn+1, CmmH2mm-1 i OCppH2pp+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R25 i R26 su međusobno neovisno H, CN ili CzH2z+1, CzzH2zz-1; z je 1, 2, 3, 4, 5, 6, 7 ili 8; zz je 3, 4, 5, 6, 7 ili 8, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; i u skupini CzH2z+1 jedan ili više H atoma može biti zamijenjeno s F atomima; i jedna ili više CH2 skupina može biti zamijenjeno s O, CO, CS ili s NR27; R27 je H ili CaaH2aa+1; aa je 1, 2, 3 ili 4; pri čemu u skupini CaaH2aa+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili R25 i R26 zajedno s N atomom na koji su oni povezani tvore 5-, 6- ili 7-člani prsten, ili R27 i jedna CH2 skupina iz R25 ili R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; ili R7, R8 i R9 su međusobno neovisno NR32COR30, NR32CSR30 ili NR32SObbR30; R30 je H, CccH2cc+1, CyyH2yy-1, pirolidinil ili piperidinil, u kojim prstenovima jedna CH2 skupina može biti zamijenjena s O ili s NR33; R32 i R33 su međusobno neovisno H ili ChH2h+1; bb je 2 ili 3; cc je 1, 2, 3, 4, 5, 6, 7 ili 8; yy je 3, 4, 5, 6, 7 ili 8; h je 1, 2, 3, 4, 5, 6, 7 ili 8, pri čemu u skupini ChH2h+1 jedan ili više H atoma smije biti zamijenjeno s F atomima, a u skupinama CccH2cc+1 i CyyH2yy-1 jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s NR31 i jedna CH2 skupina može biti zamijenjena s O; R31 je H, CkkCH2kk+1, COR65 ili SO2R65; kk je 1, 2, 3, ili 4; pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; R65 je H, CxxH2xx+1; xx je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R31 zajedno s jednom CH2 skupinom iz R30 tvori 5-, 6-ili 7-člani prsten; ili R30 je 5- ili 6-člani heteroaril s 1, 2, 3 ili 4 N atoma, s nula ili 1 S atomom i nula ili 1 O atomom, koji nije supstituiran ili je supstituiran s do tri supstituenta odabrana iz skupine koju čine F, Cl Br, I, CooH2oo+1, NR70R71; R70 i R71 su međusobno neovisno H, CuuH2uu+1 COR72; R72 je H, CvvH2vv-1; oo, uu i vv su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8; pri čemu u skupinama CooH2oo+1, CuuH2uu+1 i CvvH2vv+1 i jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R7, R8 i R9 su međusobno neovisno H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+l, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 ili OCOR42, ee i ff su međusobno neovisno 1, 2, 3, 4, 5, 6, 7 ili 8; ww je 3, 4, 5, 6, 7 ili 8; pri čemu u skupinama CeeH2ee+1, CwwH2ww-1 i OCffH2ff+1 jedan ili više H atoma može biti zamijenjeno s F atomima R40 i R41 su H, CttH2tt+1 ili C(NH)NH2; tt je 1, 2, 3, 3, 4, 5, 6, 7 ili 8; pri čemu u skupini CttH2tt+1 jedan ili više H atoma smije biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s O ili NR44; R44 je H ili CggH2+1; gg je 1, 2, 3, 4, 5, 6, 7 ili 8; pri čemu u skupini CggH2gg+1 jedan ili više H atoma može biti zamijenjeno s F atomima, ili R40 i R41 s N atomom na koji su oni povezani tvore 5-ili 6-člani prsten; R42 je H ili ChhH2hh+1; hh je 1, 2, 3, 4, 5, 6, 7 ili 8; pri čemu u skupini ChhH2hh+1 jedan ili više H atoma može biti zamijenjeno s F atomima.7. Use of a compound of formula I as well as a pharmaceutically acceptable salt thereof, characterized in that they are used for the manufacture of a medicament for the treatment of diseases which can be affected by inhibition of the sodium-proton exchanger subtype III (NHE3), wherein in formula I the symbols have the following meanings: R1, R2, R3 and R4 independently represent H, F, Cl, Br, J, CN, NO2, OH, NH2, CaH2a+1, CggH2qq-1, OCbH2b+1, COOR10, OCOR10, COR10 or Ox-(CH2 )y-phenyl; a and b in the groups CaH2a+1 and OCbH2b+1 are independently 1, 2, 3, 4, 5, 6, 7 or 8, whereby one or more H atoms can be replaced by F atoms; qq 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms; R10 is H or CcH2c+1; c is 1, 2, 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms; x is zero or 1; y is zero, 1, 2, 3 or 4; wherein the phenyl ring in the Ox-(CH2)y-phenyl group is not substituted or is substituted with 1-3 substituents selected from the group consisting of F, Cl, Br, CN, NO2, OH, NH2 or CdH2d+1; d is 1, 2, 3, or 4, wherein one or more H atoms may be replaced by F atoms; or R 1 , R 2 , R 3 and R 4 independently represent heteroaryl, whereby the ring may contain zero, 1, 2, 3 or 4 N atoms, zero or 1 oxygen atom or zero or 1 S atom; or R 1 , R 2 , R 3 and R 4 independently represent CONR 11 R 12 or NR 11 R 12 ; R11 and R12 independently represent H, CeH2e+1 and CrrH2rr-1; e is 1, 2, 3, 4, 5, 6, 7 or 8, rr is 3, 4, 5, 6, 7, or 8, whereby in the groups CeH2e+1 and CrrH2rr-1 one or more H atoms may be replaced by F atoms and one or more CH2 groups may be replaced by F atoms O or by NR13; R13 is H or CfH2f+1; f is 1, 2, 3, or 4, wherein one or more H atoms may be replaced by F atoms; or R13 and one CH2 group from R11 or R12 together with the N atom, to which they are attached, form a 5- or 6-membered ring; or R11 and R12 together with the N atom to which they are attached form a 5-, 6- or 7-membered ring; or R 11 and R 12 independently represent COR 14 , CSR 14 or SO 2 R 14 ; R14 is CgH2g+1; g is 1, 2, 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms and one or more CH 2 groups may be replaced by F atoms O or by NR 13 ; or R 1 , R 2 , R 3 and R 4 are mutually independently -OH-SO 1 R 15 , wherein h is zero or 1, j is zero, 1 or 2; R15 is CkH2k+1, OH, OClH21+1 or NR17R18; k is 1, 2, 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms; l is 1, 2, 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms; R17 and R18 independently represent H or CmH2m+1; m is 1, 2, 3, 4, 5, 6, 7 or 8, wherein in the group one or more H atoms can be replaced by F atoms and one or more CH2 groups can be replaced by O, CO, CS or NR19 ; R19 is H or CnH2n+1; n is 1, 2, 3 or 4; whereby in the group CnH2n+1 one or more H atoms can be replaced by F atoms; or R17 and R18 together with the N atom to which they are attached form a 5-, 6- or 7-membered ring; or R19 and one CH2 group from R17 or R18 together with the N atom to which they are attached form a 5- or 6-membered ring; R5 is H, CpH2p+1, CssH2ss-1, COR20 or SO2R20; p is 1, 2, 3, 4, 5, 6, 7 or 8, ss is 4, 5, 6, 7 or 8, R20 is CqH2q+1; q is 1, 2, 3, 4, 5, 6, 7 or 8, wherein in the groups CpH2p+1, CssH2ss-1 and CqH2q+1 one or more H atoms can be replaced by F atoms, and one or more CH2 groups can be replaced by O or NR21; R21 is H or CrH2r+1; r is 1, 2, 3 or 4; whereby in the group CrH2r+1 one or more H atoms can be replaced by F atoms; R6 is H, F, Cl, Br, I, CsH2s+1, CddH2dd-1, OH, OCtH2t+1 or OCOR22; s and t are independently 1, 2, 3, 4, 5, 6, 7 or 8; d.d. is 3, 4, 5, 6, 7 or 8, whereby in the groups CsH2s+1, CddH2dd-1 and OCtH2t+1 one or more H atoms can be replaced by F atoms; R22 is CuH2u+1; u is 1, 2, 3 or 4; where in the group CuH2u+1 one or more H atoms can be replaced by F atoms: R7, R8 and R9 are independently of each other -Ov-SOw-R23; v is zero or 1; w is zero, 1 or 2; R23 is CnnH2nn+1, CmmH2mm-1, OH, OCppH2pp+1 or NR25R26; nn and pp are independently 1, 2, 3, 4, 5, 6, 7 or 8, mm is 3, 4, 5, 6, 7 or 8, whereby in the groups CnnH2nn+1, CmmH2mm-1 and OCppH2pp+1 one or more H atoms can be replaced by F atoms; R25 and R26 are mutually independently H, CN or CzH2z+1, CzzH2zz-1; z is 1, 2, 3, 4, 5, 6, 7 or 8; zz is 3, 4, 5, 6, 7 or 8, wherein one or more H atoms may be replaced by F atoms; and in the group CzH2z+1 one or more H atoms can be replaced by F atoms; and one or more CH 2 groups may be replaced by O, CO, CS or by NR 27 ; R27 is H or CaaH2aa+1; aa is 1, 2, 3 or 4; whereby in the group CaaH2aa+1 one or more H atoms can be replaced by F atoms; or R25 and R26 together with the N atom to which they are attached form a 5-, 6- or 7-membered ring, or R27 and one CH2 group from R25 or R26 together with the N atom to which they are attached form a 5- or 6-membered ring; or R7, R8 and R9 are independently NR32COR30, NR32CSR30 or NR32SObbR30; R30 is H, CccH2cc+1, CyyH2yy-1, pyrrolidinyl or piperidinyl, in which rings one CH2 group can be replaced by O or by NR33; R32 and R33 are mutually independently H or ChH2h+1; bb is 2 or 3; cc is 1, 2, 3, 4, 5, 6, 7 or 8; yy is 3, 4, 5, 6, 7 or 8; h is 1, 2, 3, 4, 5, 6, 7 or 8, where in the group ChH2h+1 one or more H atoms may be replaced by F atoms, and in the groups CccH2cc+1 and CyyH2yy-1 one or more H atoms may be replaced by F atoms and one or more CH2 groups may be replaced by NR31 and one CH2 group can be replaced by O; R31 is H, CkkCH2kk+1, COR65 or SO2R65; kk is 1, 2, 3, or 4; wherein one or more H atoms may be replaced by F atoms; R65 is H, CxxH2xx+1; xx is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or R31 together with one CH2 group from R30 forms a 5-, 6- or 7-membered ring; or R30 is a 5- or 6-membered heteroaryl with 1, 2, 3 or 4 N atoms, with zero or 1 S atom and zero or 1 O atom, which is unsubstituted or substituted with up to three substituents selected from the group consisting of F, Cl Br, I, CooH2oo+1, NR70R71; R70 and R71 are independently H, CuuH2uu+1 COR72; R72 is H, CvvH2vv-1; oo, uu and vv are independently 1, 2, 3, 4, 5, 6, 7 or 8; whereby in the groups CooH2oo+1, CuuH2uu+1 and CvvH2vv+1 one or more H atoms may be replaced by F atoms; or R7, R8 and R9 are independently H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+l, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42, ee and ff are independently 1, 2, 3, 4, 5, 6, 7 or 8; ww is 3, 4, 5, 6, 7 or 8; where in the groups CeeH2ee+1, CwwH2ww-1 and OCffH2ff+1 one or more H atoms can be replaced by F atoms R40 and R41 are H, CttH2tt+1 or C(NH)NH2; tt is 1, 2, 3, 3, 4, 5, 6, 7 or 8; wherein in the group CttH2tt+1 one or more H atoms may be replaced by F atoms and one or more CH2 groups may be replaced by O or NR44; R44 is H or CggH2+1; gg is 1, 2, 3, 4, 5, 6, 7 or 8; where in the group CggH2gg+1 one or more H atoms can be replaced by F atoms, or R40 and R41 with the N atom to which they are attached form a 5- or 6-membered ring; R42 is H or ChhH2hh+1; hh is 1, 2, 3, 4, 5, 6, 7 or 8; whereby in the group ChhH2hh+1 one or more H atoms can be replaced by F atoms. 8. Upotreba prema zahtjevu 7, naznačena time, da se koriste spojevi formule I, u kojoj R1, R2, R3 i R4 međusobno neovisno predstavljaju H, F, Cl, Br, I, CN, NO2, OH, NH2, CaH2a+1, cikloalkil s 3, 4, 5 ili 6 C atoma, OCbH2b+1, COOR10; a i b su međusobno neovisno 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; R10 je H ili CCH2c+1; c je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R1, R2, R3 i R4 su međusobno neovisno 5- ili 6-člani heteroaril odabran iz skupine koju čine piridil, imidazolil, pirazolil, pirolil, triazolil, tetrazolil, tiazolil i oksazolil; ili R1, R2, R3 i R4 su međusobno neovisno CONR1R12 ili NR11R12; R11 i R12 su međusobno neovisno H, CeH2e+1, CrrH2rr-1; e je 1, 2, 3 ili 4, rr je 3, 4, 5 ili 6, pri čemu u skupinama CeH2e+1 i CrrH2rr-1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R11 i R12 su međusobno neovisno hidroksietil, N,N-di-metilaminoetil, N,N-dietilaminoetil, pirolidinoetil, N-metilpiperazinoetil, piperazinoetil, morfolinoetil ili piperidinoetil; ili R11 i R12 zajedno s N atomom na koji su oni povezani tvore pirolidinski, piperidinski, N-metilpiperazinski, piperazinski ili morfolinski prsten; ili R11 i R12 su međusobno neovisno COR14, CSR14, CONHR14, CSNHR14 ili SO2R14; R14 je CgH2g+1; g je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili R1, R2, R3 i R4 su međusobno neovisno OSO3H, SO3H, SO2R15, pri čemu R15 je CkH2k+1, OC1H21+1 ili NR17R18; k je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; l je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; R17 i R18 su međusobno neovisno H, CmH2m+1, u kojem prva CH2 skupina povezana na dušik može biti zamijenjena sa CO, a druga CH2 skupina povezana na dušik može biti zamijenjena s NR19; m je l, 2, 3, 4 ili 5, pri čemu u skupini CmH2m+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R19 je H ili CnHn+1; n je 1, 2, 3 ili 4; pri čemu u skupini CnH2n+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili R17 i R18 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; R5 je H, CpH2p+1; C33H2ss-1; p je 1, 2, 3 ili 4; ss je 3, 4, 5 ili 6, pri čemu u CpH2p+1 i CssH2ss-1 jedan ili više H atoma može biti zamijenjeno s F atomima; R6 je H, CsH2s+1, OCtH2t+1 ili OCOR22; s i t su međusobno neovisno 1, 2, 3 ili 4; pri čemu u CsH2s+1 i OCtH2t+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R22 je CuH2u+1; u je 1, 2, 3 ili 4; pri čemu u CuH2u+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R7, R8 i R9 su međusobno neovisno OSO3H, SO3H ili SO2R23; R23 je CnnH2nn+1, CmmH2mm-1, OCppH2pp+1 ili NR25R26; nn i pp su međusobno neovisno 1, 2, 3, 4 ili 5, mm je 3, 4, 5 ili 6, pri čemu u CnnH2nn+1, CmmH2mm-1 i OCppH2pp+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R25 i R26 su međusobno neovisno H, CN ili CzH2z+1, u kojem prva CH2 skupina povezana na dušik može biti zamijenjena sa CO ili CS, a druga CH2 skupina povezana na dušik može biti zamijenjena s NR27; z je 1, 2, 3, 4, 5 ili 6; pri čemu u CzH2z+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R27 je H ili CaaH2aa+1; aa je 1, 2, 3 ili 4; pri čemu u CaaH2aa+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili R25 i R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten, ili R27 i jedna CH2 skupina iz R25 ili R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; ili R7, R8 i R9 su međusobno neovisno NR32COR30, NR32CSR30 ili NR32SO2R30; R30 je H, OH, CccH2cc+1 CyyH2yy-1; pirolidinil ili piperidinil, u kojim prstenovima jedna CH2 skupina može biti zamijenjena s O ili NR33; R32 i R33 su međusobno neovisno H ili ChH2h+1; cc je 1, 2, 3, 4, 5, 6, 7 ili 8; yy je 3, 4, 5, 6; h je 1, 2, 3 ili 4; pri čemu u ChH2h+1 jedan ili više H atoma smije biti zamijenjeno s F atomima, a u skupinama CccH2cc+1 i CyyH2yy-1 jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s NR31, i jedna CH2 skupina može biti zamijenjena s O; R31 je H, CkkH2kk+1, COR65 ili SO2R65; kk je 1, 2, 3, ili 4; pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; R65 je H, CxxH2xx+1; xx je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R31 zajedno s jednom CH2 skupinom iz R30 i N atomom na koji su oni zajedno povezani tvore 5- ili 6-člani prsten; ili R30 je 5- ili 6-člani heteroaromat odabran iz skupine koju čine piridil, imidazolil, pirazolil, pirolil, triazolil, tetrazolil, tienil, tiazolil i oksazolil, koji nisu supstituirani ili su supstituirani s do tri supstituenta odabrana iz skupine koju čine F, Cl, Br, I, CooH2oo+l, NR70R71, R70 i R71 su međusobno neovisno H, CuuH2uu+1 ili COR72; R72 je H, CvvH2vv+1; oo, uu i vv su međusobno neovisno 1, 2, 3 ili 4; pri čemu u skupinama CooH2oo+1, CuuH2uu+1 i CvvH2vv+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R7, R8 i R9 su međusobno neovisno H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 ili OCOR42; ee i ff su međusobno neovisno 1, 2, 3 ili 4; ww je 3, 4, 5 ili 6, pri čemu u skupinama CeeH2ee+1, CwwH2ww-1 i OCffH2ff+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R40 i R41 su H, CttH2tt+1 ili C(NH)NH2; tt je 1, 2, 3, 4, 5, 6, 7 ili 8; pri čemu u skupinama CttH2tt+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R40 i R41 su međusobno neovisno odabrani iz niza koji čine hidroksietil, N,N-dimetilaminoetil, N,N-dietilamino-etil, pirolidinoetil, N-metilpiperazinoetil, piperazino-etil, morfolinoetil ili piperidinoetil; ili R40 i R41 zajedno s N atomom na koji su oni povezani tvore prsten odabran iz skupine koju čine pirolidin, piperidin, N-metilpiperazin, piperazin i morfolin; R42 je H ili ChhH2hh+1; hh je 1, 2, 3 ili 4; pri čemu u skupini ChhH2hh+1 jedan ili više H atoma može biti zamijenjeno s F atomima. 8. Use according to claim 7, characterized in that compounds of formula I are used, in which R1, R2, R3 and R4 independently represent H, F, Cl, Br, I, CN, NO2, OH, NH2, CaH2a+1, cycloalkyl with 3, 4, 5 or 6 C atoms, OCbH2b+1, COOR10; a and b are independently 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; R10 is H or CCH2c+1; c is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or R 1 , R 2 , R 3 and R 4 are independently 5- or 6-membered heteroaryl selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl and oxazolyl; or R 1 , R 2 , R 3 and R 4 are mutually independently CONR 1 R 12 or NR 11 R 12 ; R11 and R12 are mutually independently H, CeH2e+1, CrrH2rr-1; e is 1, 2, 3 or 4, rr is 3, 4, 5 or 6, whereby in the groups CeH2e+1 and CrrH2rr-1 one or more H atoms may be replaced by F atoms; or R11 and R12 are mutually independently hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or R11 and R12 together with the N atom to which they are attached form a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring; or R 11 and R 12 are independently COR 14 , CSR 14 , CONHR 14 , CSNHR 14 or SO 2 R 14 ; R14 is CgH2g+1; g is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or R1, R2, R3 and R4 are mutually independently OSO3H, SO3H, SO2R15, wherein R15 is CkH2k+1, OC1H21+1 or NR17R18; k is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; l is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; R17 and R18 are independently H, CmH2m+1, wherein the first CH2 group attached to the nitrogen can be replaced by CO and the second CH2 group attached to the nitrogen can be replaced by NR19; m is 1, 2, 3, 4 or 5, whereby in the group CmH2m+1 one or more H atoms can be replaced by F atoms; R 19 is H or CnHn+1; n is 1, 2, 3 or 4; whereby in the group CnH2n+1 one or more H atoms can be replaced by F atoms; or R17 and R18 together with the N atom to which they are attached form a 5- or 6-membered ring; R5 is H, CpH2p+1; C33H2ss-1; p is 1, 2, 3 or 4; ss is 3, 4, 5 or 6, whereby in CpH2p+1 and CssH2ss-1 one or more H atoms can be replaced by F atoms; R6 is H, CsH2s+1, OCtH2t+1 or OCOR22; s and t are independently 1, 2, 3 or 4; whereby in CsH2s+1 and OCtH2t+1 one or more H atoms can be replaced by F atoms; R22 is CuH2u+1; u is 1, 2, 3 or 4; whereby in CuH2u+1 one or more H atoms can be replaced by F atoms; R 7 , R 8 and R 9 are mutually independently OSO 3 H, SO 3 H or SO 2 R 23 ; R23 is CnnH2nn+1, CmmH2mm-1, OCppH2pp+1 or NR25R26; nn and pp are independently 1, 2, 3, 4 or 5, mm is 3, 4, 5 or 6, whereby in CnnH2nn+1, CmmH2mm-1 and OCppH2pp+1 one or more H atoms can be replaced by F atoms; R25 and R26 are independently H, CN or CzH2z+1, wherein the first CH2 group attached to the nitrogen may be replaced by CO or CS and the second CH2 group attached to the nitrogen may be replaced by NR27; z is 1, 2, 3, 4, 5 or 6; whereby in CzH2z+1 one or more H atoms can be replaced by F atoms; R27 is H or CaaH2aa+1; aa is 1, 2, 3 or 4; where in CaaH2aa+1 one or more H atoms can be replaced by F atoms; or R25 and R26 together with the N atom to which they are attached form a 5- or 6-membered ring, or R27 and one CH2 group from R25 or R26 together with the N atom to which they are attached form a 5- or 6-membered ring; or R7, R8 and R9 are independently NR32COR30, NR32CSR30 or NR32SO2R30; R30 is H, OH, CccH2cc+1 CyyH2yy-1; pyrrolidinyl or piperidinyl, in which rings one CH2 group may be replaced by O or NR33; R32 and R33 are mutually independently H or ChH2h+1; cc is 1, 2, 3, 4, 5, 6, 7 or 8; yy is 3, 4, 5, 6; h is 1, 2, 3 or 4; whereby in ChH2h+1 one or more H atoms may be replaced by F atoms, and in the groups CccH2cc+1 and CyyH2yy-1 one or more H atoms may be replaced by F atoms and one or more CH2 groups may be replaced by NR31, and one CH2 group can be replaced by O; R31 is H, CkkH2kk+1, COR65 or SO2R65; kk is 1, 2, 3, or 4; wherein one or more H atoms may be replaced by F atoms; R65 is H, CxxH2xx+1; xx is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or R31 together with one CH2 group from R30 and the N atom to which they are connected form a 5- or 6-membered ring; or R30 is a 5- or 6-membered heteroaromatic selected from the group consisting of pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thienyl, thiazolyl and oxazolyl, which are unsubstituted or substituted with up to three substituents selected from the group consisting of F, Cl, Br, I, CooH2oo+l, NR70R71, R70 and R71 are mutually independently H, CuuH2uu+1 or COR72; R72 is H, CvvH2vv+1; oo, uu and vv are independently 1, 2, 3 or 4; whereby in the groups CooH2oo+1, CuuH2uu+1 and CvvH2vv+1 one or more H atoms may be replaced by F atoms; or R7, R8 and R9 are independently H, F, Cl, Br, I, NO2, CN, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42, COR42 or OCOR42; ee and ff are independently 1, 2, 3 or 4; ww is 3, 4, 5 or 6, whereby in the groups CeeH2ee+1, CwwH2ww-1 and OCffH2ff+1 one or more H atoms can be replaced by F atoms; R40 and R41 are H, CttH2tt+1 or C(NH)NH2; tt is 1, 2, 3, 4, 5, 6, 7 or 8; whereby in the groups CttH2tt+1 one or more H atoms may be replaced by F atoms; or R40 and R41 are mutually independently selected from the group consisting of hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or R40 and R41 together with the N atom to which they are attached form a ring selected from the group consisting of pyrrolidine, piperidine, N-methylpiperazine, piperazine and morpholine; R42 is H or ChhH2hh+1; hh is 1, 2, 3 or 4; whereby in the group ChhH2hh+1 one or more H atoms can be replaced by F atoms. 9. Upotreba prema zahtjevu 7, naznačena time, da u formuli I: R1, R2, R3 i R4 su međusobno neovisno H, F, Cl, Br, OH, NH2, CaH2a+1 cikloalkil s 3, 4, 5 ili 6 C atoma, OCbH2b+1; a i b u skupinama CaH2a+1 i OCbH2b+1 su međusobno neovisno 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili R1, R2, R3 i R4 su međusobno neovisno NR11R12; R11 i R12 su međusobno neovisno H, CeH2e+1, CrrH2rr-1;' e je 1, 2, 3 ili 4, rr je 3, 4, 5 ili 6, pri čemu u skupinama CeH2e+1 i CrrH2rr-1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R11 i R12 zajedno s N atomima na koje su oni povezani tvore prsten odabran iz skupine koju čine pirolidin, piperidin, N-metilpiperazin, piperazin i morfolin; ili R11 i R12 su međusobno neovisno CORI4, CSR14, CONHR14, CSNHR14 ili SO2R14; R14 je CgH2g+1; g je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; ili R1, R2, R3 i R4 su međusobno neovisno OSO3H, SO3H, SO2R15; R15 je CkH2k+l ili NR17R18; k je 1, 2, 3 ili 4, pri čemu jedan ili više H atoma može biti zamijenjeno s F atomima; R17 i R18 su međusobno neovisno H ili CmH2m+1, m je 1, 2, 3, 4 ili 5, pri čemu u skupini CmH2m+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili R17 i R18 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; R5 je H, CpH2p+1, CssH2ss-1, p je 1, 2, 3 ili 4; ss je 3, 4, 5 ili 6, pri čemu u CpH2p+1 i CssH2ss-1 jedan ili više H atoma može biti zamijenjeno s F atomima; R6 je H, CH3; R7, R8 i R9 su međusobno neovisno OSO3H, SO3H ili SO2R23; R23 je CnnH2nn+1 ili NR25R26; nn je 1, 2, 3, 4 ili 5, pri čemu u CnnH2nn+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R25 i R26 su međusobno neovisno H, CN ili CzH2z+1, u kojem prva CH2 skupina povezana na dušik može biti zamijenjena sa CO ili CS, a druga CH2 skupina povezana na dušik može biti zamijenjena s NR27; z je 1, 2, 3, 4, 5 ili 6; pri čemu u CzH2z+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R27 je H ili CaaH2aa+1; aa je 1, 2, 3 ili 4; pri čemu u CaaH2aa+1 jedan ili više H atoma može biti zamijenjeno s F atomima; ili R25 i R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten, ili R27 i jedna CH2 skupina iz R25 ili R26 zajedno s N atomom na koji su oni povezani tvore 5- ili 6-člani prsten; ili R7, R8 i R9 su međusobno neovisno NR32COR30, NR32CSR30 ili NR32SO2R30; R30 je H, OH, CccH2cc+1, CyyH2yy-1, pirolidinil ili piperidinil, u kojim prstenovima jedna CH2 skupina može biti zamijenjena s O ili NR33; R32 i R33 su H, metil ili CF3; cc je 1, 2, 3, 4, 5 ili 6; yy je 3, 4, 5 ili 6; pri čemu u skupinama CccH2cc+1 i CyyH2yy-1 jedan ili više H atoma može biti zamijenjeno s F atomima i jedna ili više CH2 skupina može biti zamijenjeno s NR31, i jedna CH2 skupina može biti zamijenjena s O; R31 je H, metil, etil, CF3, CH2CF3, acetil, propionil, metansulfonil ili etansulfonil; ili R31 zajedno s jednom CH2 skupinom iz R30 i N atomom na koji su one zajedno povezane tvore 5- ili 6-člani prsten; ili R30 je piridil, imidazolil, pirazolil, pirolil, triazolil, tetrazolil, tiazolil ili oksazolil, koji nisu supstituirani ili su supstituirani s najviše 3 supstituenta odabrana iz skupine koju čine F, Cl, metil, etil, trifluor-metil, NH2, NH-acetil; ili R7, R8 i R9 su međusobno neovisno H, F, Cl, OH, NH2, CeeH2ee+1, CwwH2ww-l, OCffH2ff+1, NR40R41, CONR40R41, COOR42 ili OCOR42, ee i ff su međusobno neovisno 1, 2, 3 ili 4; ww je 3, 4, 5 ili 6, pri čemu u skupinama CeeH2ee+1, CwwH2ww-1 i OCffH2ff+1 jedan ili više H atoma može biti zamijenjeno s F atomima; R40 i R41 su H, CttH2tt+1 ili C(NH)NH2; tt je 1, 2, 3 ili 4; pri čemu u skupini CttH2tt+1 jedan ili više H atoma smije biti zamijenjeno s F atomima; ili R40 i R41 su međusobno neovisno hidroksietil, N,N-dimetilaminoetil, N,N-dietilaminoetil, pirolidinoetil, N-metilpiperazinoetil, piperazinoetil, morfolinoetil ili piperidinoetil; ili R40 i R41 zajedno s N atomom na koji su oni povezani tvore pirolidinski, piperidinski, N-metilpiperazinski, piperazinski ili morfolinski prsten; R42 je H ili ChhH2hh+1; hh je 1, 2, 3 ili 4; pri čemu u skupini ChhH2hh+1 jedan ili više H atoma može biti zamijenjeno s F atomima.9. Use according to claim 7, characterized in that in formula I: R1, R2, R3 and R4 are independently H, F, Cl, Br, OH, NH2, CaH2a+1 cycloalkyl with 3, 4, 5 or 6 C atoms, OCbH2b+1; a and b in the groups CaH2a+1 and OCbH2b+1 are independently 1, 2, 3 or 4, whereby one or more H atoms can be replaced by F atoms; or R 1 , R 2 , R 3 and R 4 are independently NR 11 R 12 ; R11 and R12 are mutually independently H, CeH2e+1, CrrH2rr-1;' e is 1, 2, 3 or 4, rr is 3, 4, 5 or 6, whereby in the groups CeH2e+1 and CrrH2rr-1 one or more H atoms may be replaced by F atoms; or R11 and R12 together with the N atoms to which they are attached form a ring selected from the group consisting of pyrrolidine, piperidine, N-methylpiperazine, piperazine and morpholine; or R11 and R12 are mutually independently CORI4, CSR14, CONHR14, CSNHR14 or SO2R14; R14 is CgH2g+1; g is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; or R1, R2, R3 and R4 are mutually independently OSO3H, SO3H, SO2R15; R15 is CkH2k+1 or NR17R18; k is 1, 2, 3 or 4, wherein one or more H atoms may be replaced by F atoms; R17 and R18 are independently H or CmH2m+1, m is 1, 2, 3, 4 or 5, whereby in the group CmH2m+1 one or more H atoms can be replaced by F atoms; or R17 and R18 together with the N atom to which they are attached form a 5- or 6-membered ring; R5 is H, CpH2p+1, CssH2ss-1, p is 1, 2, 3 or 4; ss is 3, 4, 5 or 6, whereby in CpH2p+1 and CssH2ss-1 one or more H atoms can be replaced by F atoms; R 6 is H, CH 3 ; R 7 , R 8 and R 9 are mutually independently OSO 3 H, SO 3 H or SO 2 R 23 ; R23 is CnnH2nn+1 or NR25R26; nn is 1, 2, 3, 4 or 5, where in CnnH2nn+1 one or more H atoms can be replaced by F atoms; R25 and R26 are independently H, CN or CzH2z+1, wherein the first CH2 group attached to the nitrogen may be replaced by CO or CS and the second CH2 group attached to the nitrogen may be replaced by NR27; z is 1, 2, 3, 4, 5 or 6; whereby in CzH2z+1 one or more H atoms can be replaced by F atoms; R27 is H or CaaH2aa+1; aa is 1, 2, 3 or 4; where in CaaH2aa+1 one or more H atoms can be replaced by F atoms; or R25 and R26 together with the N atom to which they are attached form a 5- or 6-membered ring, or R27 and one CH2 group from R25 or R26 together with the N atom to which they are attached form a 5- or 6-membered ring; or R7, R8 and R9 are independently NR32COR30, NR32CSR30 or NR32SO2R30; R30 is H, OH, CccH2cc+1, CyyH2yy-1, pyrrolidinyl or piperidinyl, in which rings one CH2 group may be replaced by O or NR33; R32 and R33 are H, methyl or CF3; cc is 1, 2, 3, 4, 5 or 6; yy is 3, 4, 5 or 6; wherein in the groups CccH2cc+1 and CyyH2yy-1 one or more H atoms can be replaced by F atoms and one or more CH2 groups can be replaced by NR31, and one CH2 group can be replaced by O; R31 is H, methyl, ethyl, CF3, CH2CF3, acetyl, propionyl, methanesulfonyl or ethanesulfonyl; or R31 together with one CH2 group from R30 and the N atom to which they are connected form a 5- or 6-membered ring; or R30 is pyridyl, imidazolyl, pyrazolyl, pyrrolyl, triazolyl, tetrazolyl, thiazolyl or oxazolyl, which are unsubstituted or substituted with at most 3 substituents selected from the group consisting of F, Cl, methyl, ethyl, trifluoromethyl, NH2, NH-acetyl ; or R7, R8 and R9 are independently H, F, Cl, OH, NH2, CeeH2ee+1, CwwH2ww-1, OCffH2ff+1, NR40R41, CONR40R41, COOR42 or OCOR42, ee and ff are independently 1, 2, 3 or 4; ww is 3, 4, 5 or 6, whereby in the groups CeeH2ee+1, CwwH2ww-1 and OCffH2ff+1 one or more H atoms can be replaced by F atoms; R40 and R41 are H, CttH2tt+1 or C(NH)NH2; tt is 1, 2, 3 or 4; whereby in the group CttH2tt+1 one or more H atoms may be replaced by F atoms; or R40 and R41 are mutually independently hydroxyethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, pyrrolidinoethyl, N-methylpiperazinoethyl, piperazinoethyl, morpholinoethyl or piperidinoethyl; or R40 and R41 together with the N atom to which they are attached form a pyrrolidine, piperidine, N-methylpiperazine, piperazine or morpholine ring; R42 is H or ChhH2hh+1; hh is 1, 2, 3 or 4; whereby in the group ChhH2hh+1 one or more H atoms can be replaced by F atoms. 10. Upotreba prema zahtjevu 7, naznačena time, da su spojevi formule I odabrani iz skupine koju čine: 1) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 2) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-benzolsulfonamid; 3) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-benzolsulfonamid; 4) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N,N-dimetil-benzol-sulfonamid; 5) 4-(4-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin; 6) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina; 7) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidrosiokinolin-4-il)-N-etil-benzamid; 8) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-propil-benzamid; 9) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-N-(2-dimetilamino-etil)-benzamid; 10) 6,8-diklor-2-metil-4-(4-morfolin-4-il-fenil)-1,2,3,4-tetrahidroizokinolin; 11) [4-(6,8-diklor-2-metil-l,2/3, 4-tetrahidroizokinolin-4-il)-fenil]-dietil-amin; 12) 6,8-diklor-2-metil-4-(4-piperidin-1-il-fenil)-1,2,3,4-tetrahidroizokinolin; 13) 6,8-diklor-2-metil-4-(4-pirolidin-1-il-fenil)-1,2,3,4-tetrahidroizokinolin; 14) 6,8-diklor-2-metil-4-[4-(4-metil-piperazin-1-il)-fenil]-1,2,3,4-tetrahidro-izokinolin; 15) 6,8-diklor-2-ciklopropil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 16) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin; 17) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-propil-urea; 18) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 19) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 20) N-[4-(6-metansulfonil-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 21) N-[4-(2,6,8-trimetil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 22) N-[4-(6-brom-8-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 23) N-[4-(8-klor-2-metil-6-pirolidin-1-il-1,2,3,4-tetra-hidro-izokinolin-4-il)-fenil]-acetamid; 24) N-[4-(8-klor-2-metil-6-morfolin-4-il-1,2,3,4-tetra-hidro-izokinolin-4-il)-fenil]-acetamid; 25) N-{4-[8-klor-6-(ciklopropilmetil-amino)-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il]-fenil}-acetamid; 27) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-benzojeva kiselina; 28) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-N-metil-benzamid; 29) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-N-etil-2-hidroksi-benzamid; 30) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-N-(2-dimetilamino)-etil)-2-hidroksi-benzamid; 31) N-[5-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-2-hidroksi-benzoil]-gvanidin; 32) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 33) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin; 34) 2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin; 35) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 36) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-butiramid; 37) pentanska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 38) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 39) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2-dimetil-propionamid; 40) ciklopropan-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 41) ciklobutan-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 42) ciklopentan-karbonska kiselina-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 43) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2,2-trifluor-acetamid; 44) l-acetil-piperidin-4-karbonska kiselina-[4-(6,8-di-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 45) N-(4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-nikotinamid; 46) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 47) etansulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 48) N',N'-dimetilamino-N-[4-(6,8-diklor-2-netil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 49) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 50) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-butiramid; 51) pentanska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 52) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 53) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2-dimetil-propionamid; 54) ciklopropankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 55) ciklobutankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-y))-fenil]-amid; 56) ciklopentankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 57) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2,2-trifluor-acetamid; 58) l-acetil-piperidin-4-karbonska kiselna-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 59) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-nikotinamid; 60) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 61) etansulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 62) N',N'-dimetilamino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 63) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 64) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-butiramid; 65) pentanska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 66) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 67) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2-dimetil-propionamid; 68) ciklopropankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 69) ciklobutankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-1zoehinoiin-4-il)-fenil]-amid; 70) ciklopentankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 71) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2,2,2-trifluor-acetamid; 72) 1-acetil-piperidin-4-karbonska kiselina-[2-(6,8-di-klor-2-metil-l,2,3,4-tetrahidroizokinolin-4-il)-fenil]amid; 73) N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 74) etan-sulfonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 75) N',N'-dimetilamino-N-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 76) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 77) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 78) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 79) 1-[2-(6,e-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 80) N-{5-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilsulfamoil]-4-metil-tiazol-2-il}-acetamid; 81) N-{5-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilsulfamoil]-4-metil-tiazol-2-il}-acetamid; 82) l,2-dimetil-1H-imidazol-4-sulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 83) 1,2-dimetil-1H-imidazol-4-sulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 84) 5-klor-1,3-dimetil-1H-pirazol-4-sulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 85) 5-klor-1,3-dimetil-1H-pirazol-4-sulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 86) 5-brom-tiofen-2-sulfonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 87) 5-brom-tiofen-2-sulfonska kiselina-[3-(6,8-diklor-2-1αetil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 88) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluor-metansulfonamid; 89) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluor-metansulfonamid; 90) 2,2,2-trifluor-etansulfonska kiselina-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 91) 2,2,2-trifluor-etansulfonska kiselina-3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 92) N-etil-N'-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonil-urea; 93) 2-klor-5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonamid; 94) 2-metil-4-fenil-1,2,3,4-tetrahidroizokinolin-8-ilamin; 95) 6,8-diklor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 96) 4-(8-amino-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenol; 97) 8-metoksi-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 98) 2-(8-amino-2-etil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenol; 99) 2-(8-amino-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenol; 100) 5-(8-amino-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-metoksi-fenol; 101) 2-metil-8-nitro-4-fenil-1,2,3,4-tetrahidro-izokinolin; 102) 4-(8-amino-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzol-1,2-diol; 103) 2,8-dimetil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 104) 4-(3,4-diklor-fenil)-2-metil-1,2,3,4-tetrahidro-izokinolin; 105) 4-(3,4-diklor-fenil)-2-metil-1,2,3,4-tetrahidro-izokinolin- 8-ilamin; 106) 4-(2,4-diklor-fenil)-2-metil-1,2,3,4-tetrahidro-izokinolin-8-ilamin; 107) 4-(3-klor-fenil)-2-metil-1,2,3,4-tetrahidroizokinolin-8-ilamin; 108) 2,4-dimetil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 109) 2-butil-4-fenil-1,2,3,4-tetrahidroizokinolin-8-ilamin; 110) N-(2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin-8-il)-acetamid; 111) 7-klor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 112) 8-klor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 113) 2,6-dimetil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 114) 6-klor-2-metil-4-fenil-l,2f3,4-tetrahidro-izokinolin; 115) 6-metoksi-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 116) 2-etil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 117) 2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 118) 6,8-diklor-2-etil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 119) 4-(4-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin; 120) 2-metil-4-fenil-6,8-bis-trifluormetil-1,2,3,4-tetrahidro-izokinolin; 121) 6,8-diklor-2-1zopropil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 122) 5,8-diklor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 123) 6,8-diklor-4-(4-fluor-fenil)-2-metil-1,2,3,4-tetrahidro-izokinolin; 124) 6,8-diklor-2-metil-4-p-tolil-1,2,3,4-tetrahidro-izokinolin; 125) 5,6-diklor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 126) 6,7-diklor-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 127) 8-brom-2-metil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 128) 6,8-diklor-4-(4-klor-fenil)-2-metil-1,2,3,4-tetrahidro-izokinolin; 129) 6,8-diklor-2-ciklopropil-4-fenil-1,2,3,4-tetrahidro-izokinolin; 130) 2-amino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 131) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-metilamino-acetamid; 132) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-acetamid; 133) 2-amino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-propionamid; 134) 2-amino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-butiramid; 135) 2,6-diamino-heksanska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin; 136) pirolidin-2-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 137) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izonikotinamid; 138) 1H-pirol-3-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 139) 1H-pirol-2-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 140) l-metil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 141) l,4-dimetil-1H-pirol-2-karbonska kiselina-[4-(6,8-di-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 142) 4-nitro-1H-pirol-2-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 143) 2,5-dimetil-1H-pirol-3-karbonska kiselina-[4-(6,8-di-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 144) 1H-imidazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 145) l-metansulfonil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 146) 3,5-dimetil-1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 147) 1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 148) 3-trifluormetil-1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 149) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-metilamino-acetamid; 150) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-acetamid; 151) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-propionamid; 152) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-butiramid; 153) 2,6-diamino-heksanska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 154) pirolidin-2-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 155) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izonikotinamid; 156) 1H-pirol-3-karbonska kiselina-3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 157) 1H-pirol-2-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 158) l-metil-piperidin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 159) l,4-dimetil-1H-pirol-2-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 160) 4-nitro-1H-pirol-2-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 161) 2,5-dimetil-1H-pirol-3-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 162) 1H-imidazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 163) l-metansulfonil-piperidin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 164) 3,5-dimetil-1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 165) 1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 166) 3-trifluormetil-1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 167) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-tiourea; 168) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-tiourea; 169) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-tiourea; 170) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dimetil-urea; 171) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 172) piperidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 173) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 174) pirolidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 175) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 176) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 177) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 178) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-furan-3-il)-urea; 179) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-piran-4-il)-urea; 180) 3-t3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-metil-1-(l-metil-piperidin-4-il)-urea; 181) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-(3-dimetilamino-propil)-1-metil-urea; 182) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-(2-dimetilamino-etil)-1-metil-urea; 183) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(3-dimetilamino-propil)-urea; 184) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-metoksi-etil)-urea; 185) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil)-3-piridin-3-il-urea; 186) l-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-piridin-4-il-urea; 187) 4-metil-piperazin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 188) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 189) 3-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-il-dimetil-urea; 190) 3-[2-(6,8-diklor-2-metil-l,2,3,4-tetrahidroizokinolin-4-1l}-fenil]-1,1-dietil-urea; 191) piperidin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 192) morfolin-4-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 193) pirolidin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 194) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 195) 4-metil-piperazin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 196) pirolidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 197) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 198) 3-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin4-il)-fenil]-1,1-dimetil-urea; 199) 3-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 200) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 201) piperidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 202) morfolin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 203) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-formamid; 204) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amin; 205) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3-dimetil-urea; 206) 4-metil-piperazin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 207) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3,3-trimetil-urea; 208) piperidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 209) morfolin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 210) pirolidin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 211) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-1-metil-urea; 212) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3,3-dietil-1-metil-urea; 213) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-formamid; 214) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amin; 215) pirolidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 216) piperidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 217) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-l,3,3-trimetil-urea; 218) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3-dimetil-urea; 219) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 220) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 221) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-1-metil-urea; 222) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3,3-dietil-1-metil-urea; 223) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 224) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 225) [2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 226) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina metil ester; 227) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina etil ester; 228) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina izopropil ester; 229) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina 2,2-dimetil-propil ester; 230) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina metil ester; 231) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina izopropil ester; 232) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina 2,2-dimetil-propil ester; 233) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina etil ester; 234) (R)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamid; 235) (S)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamid; 236) (R)-1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-eti1-urea; 237) (S)-1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea; 238) N-[3-(6,8-difluor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 239) 4-(3-brom-fenil)-6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin; 240) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-hidroksi-etil)-urea; 241) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina etil ester; 242) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina, kao i njihove farmacetski podnošljive soli. 10. Use according to claim 7, characterized in that the compounds of formula I are selected from the group consisting of: 1) N-[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) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N,N-dimethyl-benzene-sulfonamide; 5) 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline; 6) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid; 7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydrosioquinolin-4-yl)-N-ethyl-benzamide; 8) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-propyl-benzamide; 9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-benzamide; 10) 6,8-dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline; 11) [4-(6,8-dichloro-2-methyl-1,2/3,4-tetrahydroisoquinolin-4-yl)-phenyl]-diethylamine; 12) 6,8-dichloro-2-methyl-4-(4-piperidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline; 13) 6,8-dichloro-2-methyl-4-(4-pyrrolidin-1-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline; 14) 6,8-dichloro-2-methyl-4-[4-(4-methyl-piperazin-1-yl)-phenyl]-1,2,3,4-tetrahydro-isoquinoline; 15) 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 16) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine; 17) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-propyl-urea; 18) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea; 19) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea; 20) N-[4-(6-methanesulfonyl-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide; 21) N-[4-(2,6,8-trimethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide; 22) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide; 23) N-[4-(8-chloro-2-methyl-6-pyrrolidin-1-yl-1,2,3,4-tetra-hydro-isoquinolin-4-yl)-phenyl]-acetamide; 24) N-[4-(8-chloro-2-methyl-6-morpholin-4-yl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide; 25) N-{4-[8-chloro-6-(cyclopropylmethyl-amino)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl]-phenyl}-acetamide; 27) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid; 28) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-N-methyl-benzamide; 29) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-ethyl-2-hydroxy-benzamide; 30) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino)-ethyl)-2-hydroxy-benzamide; 31) N-[5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-2-hydroxy-benzoyl]-guanidine; 32) N-[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-tetrahydro-isoquinolin-4-yl)-phenylamine; 34) 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine; 35) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide; 36) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-butyramide; 37) pentanoic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 38) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide; 39) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide; 40) cyclopropane-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 41) cyclobutane-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 42) cyclopentane-carboxylic acid-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 43) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2,2-trifluoroacetamide; 44) 1-acetyl-piperidine-4-carboxylic acid-[4-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide ; 45) N-(4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-nicotinamide; 46) N-[4-(6,8- dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide; 47) ethanesulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 48) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-netyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide; 49) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide; 50) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-butyramide; 51) pentanoic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 52) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide; 53) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide; 54) cyclopropanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 55) cyclobutanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl))-phenyl]-amide; 56) cyclopentanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 57) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2,2-trifluoroacetamide; 58) 1-acetyl-piperidin-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 59) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-nicotinamide; 60) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide; 61) ethanesulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 62) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide; 63) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide; 64) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-butyramide; 65) pentanoic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 66) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide; 67) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2-dimethyl-propionamide; 68) cyclopropanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 69) cyclobutanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-1zoequinoin-4-yl)-phenyl]-amide; 70) cyclopentanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 71) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2,2,2-trifluoroacetamide; 72) 1-acetyl-piperidine-4-carboxylic acid-[2-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]amide; 73) N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide; 74) ethane-sulfonic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 75) N',N'-dimethylamino-N-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide; 76) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea; 77) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea; 78) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea; 79) 1-[2-(6,ε-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea; 80) N-{5-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl }-acetamide; 81) N-{5-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl }-acetamide; 82) 1,2-dimethyl-1H-imidazole-4-sulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide; 83) 1,2-dimethyl-1H-imidazol-4-sulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide; 84) 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl )-phenyl]-amide; 85) 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl )-phenyl]-amide; 86) 5-bromo-thiophene-2-sulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 87) 5-bromo-thiophene-2-sulfonic acid-[3-(6,8-dichloro-2-1αethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 88) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide; 89) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide; 90) 2,2,2-trifluoroethanesulfonic acid-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 91) 2,2,2-trifluoroethanesulfonic acid-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 92) N-ethyl-N'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonyl-urea; 93) 2-chloro-5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-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-tetrahydro-isoquinoline; 96) 4-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenol; 97) 8-methoxy-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 98) 2-(8-amino-2-ethyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenol; 99) 2-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenol; 100) 5-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-methoxy-phenol; 101) 2-methyl-8-nitro-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 102) 4-(8-amino-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzene-1,2-diol; 103) 2,8-dimethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 104) 4-(3,4-dichloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinoline; 105) 4-(3,4-dichloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine; 106) 4-(2,4-dichloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-ylamine; 107) 4-(3-chloro-phenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine; 108) 2,4-dimethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 109) 2-butyl-4-phenyl-1,2,3,4-tetrahydroisoquinolin-8-ylamine; 110) N-(2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-acetamide; 111) 7-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 112) 8-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 113) 2,6-dimethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 114) 6-chloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 115) 6-methoxy-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 116) 2-ethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 117) 2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 118) 6,8-dichloro-2-ethyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 119) 4-(4-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline; 120) 2-methyl-4-phenyl-6,8-bis-trifluoromethyl-1,2,3,4-tetrahydro-isoquinoline; 121) 6,8-dichloro-2-1isopropyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 122) 5,8-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 123) 6,8-dichloro-4-(4-fluoro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinoline; 124) 6,8-dichloro-2-methyl-4-p-tolyl-1,2,3,4-tetrahydro-isoquinoline; 125) 5,6-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 126) 6,7-dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 127) 8-bromo-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 128) 6,8-dichloro-4-(4-chloro-phenyl)-2-methyl-1,2,3,4-tetrahydro-isoquinoline; 129) 6,8-dichloro-2-cyclopropyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline; 130) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide; 131) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-methylamino-acetamide; 132) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide; 133) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide; 134) 2-amino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide; 135) 2,6-diamino-hexanoic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline; 136) pyrrolidine-2-carboxylic acid-[4-( 6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 137) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isonicotinamide; 138) 1H-pyrrole-3-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 139) 1H-pyrrole-2-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 140) 1-methyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide; 141) 1,4-dimethyl-1H-pyrrole-2-carboxylic acid-[4-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-amide; 142) 4-nitro-1H-pyrrole-2-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide; 143) 2,5-dimethyl-1H-pyrrole-3-carboxylic acid-[4-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)- phenyl]-amide; 144) 1H-imidazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 145) 1-methanesulfonyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 146) 3,5-dimethyl-1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide; 147) 1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 148) 3-trifluoromethyl-1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide ; 149) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-methylamino-acetamide; 150) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide; 151) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide; 152) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide; 153) 2,6-diamino-hexanoic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 154) pyrrolidine-2-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 155) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isonicotinamide; 156) 1H-pyrrole-3-carboxylic acid-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 157) 1H-pyrrole-2-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 158) 1-methyl-piperidine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide; 159) 1,4-dimethyl-1H-pyrrole-2-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide; 160) 4-nitro-1H-pyrrole-2-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide; 161) 2,5-dimethyl-1H-pyrrole-3-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide; 162) 1H-imidazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 163) 1-methanesulfonyl-piperidine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 164) 3,5-dimethyl-1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide; 165) 1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 166) 3-trifluoromethyl-1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide ; 167) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-thiourea; 168) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-thiourea; 169) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-thiourea; 170) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea; 171) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide; 172) piperidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 173) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 174) pyrrolidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 175) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea; 176) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea; 177) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea; 178) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-furan-3-yl)-urea; 179) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-pyran-4-yl)-urea; 180) 3-t3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-methyl-1-(1-methyl-piperidine-4- il)-urea; 181) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-(3-dimethylamino-propyl)-1-methyl- urea; 182) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-(2-dimethylamino-ethyl)-1-methyl- urea; 183) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(3-dimethylamino-propyl)-urea; 184) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea; 185) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl)-3-pyridin-3-yl-urea; 186) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-pyridin-4-yl-urea; 187) 4-methyl-piperazine-1-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide; 188) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea; 189) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-yl-dimethyl-urea; 190) 3-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-1l}-phenyl]-1,1-diethyl-urea; 191) piperidine-1- carboxylic acid [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 192) morpholine-4-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 193) pyrrolidine-1-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 194) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea; 195) 4-methyl-piperazine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide; 196) pyrrolidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 197) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea; 198) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin4-yl)-phenyl]-1,1-dimethyl-urea; 199) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea; 200) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea; 201) piperidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 202) morpholine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 203) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-formamide; 204) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine; 205) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea; 206) 4-methyl-piperazine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide ; 207) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea; 208) piperidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide; 209) morpholine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide; 210) pyrrolidine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide; 211) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl- urea; 212) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3,3-diethyl-1-methyl-urea; 213) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-formamide; 214) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine; 215) pyrrolidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide; 216) piperidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide; 217) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea; 218) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea; 219) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide; 220) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide ; 221) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl- urea; 222) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3,3-diethyl-1-methyl-urea; 223) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester; 224) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester; 225) [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester; 226) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid methyl ester; 227) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid ethyl ester; 228) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid isopropyl ester; 229) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid 2,2-dimethyl-propyl ester; 230) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid methyl ester; 231) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid isopropyl ester; 232) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid 2,2-dimethyl-propyl ester; 233) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid ethyl ester; 234) (R)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide; 235) (S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide; 236) (R)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea; 237) (S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea; 238) N-[3-(6,8-difluoro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide; 239) 4-(3-bromo-phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoline; 240) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea; 241) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid ethyl ester; 242) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid, as well as their pharmaceutically acceptable salts. 11. Upotreba prema zahtjevu 7, naznačena time, da su spojevi formule I odabrani iz skupine koju čine: 1) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 2) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonamid; 3) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokirtolin-4-il)-benzolsulfonamid; 4) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina; 5) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-etil-benzamid; 6) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-N-propil-benzamid; 7) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-N-(2-dimetilamino-etil)-benzamid; 8) 6,8-diklor-2-metil-4-(4-morfolin-4-il-fenil)-1,2,3,4-tetrahidroizokinolin; 9) 4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin; 10) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 11) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 12) N-[4-(6-brom-8-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-acetamid; 13) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-2-hidroksi-benzojeva kiselina; 14) 5-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-N-(2-dimetilamino-etil)-2-hidroksi-benzamid; 15) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-acetamid; 16) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin; 17) 2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilamin; 18) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 19) l-acetil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 20) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 21) etansuifonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 22) N',N'-dimetilamino-N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 23) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-propionamid; 24) N-[3-(6,e-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-butiramid; 25) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-izobutiramid; 26) ciklobutankarbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 28) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenill-2,2,2-trifluor-acetamid; 29) l-acetil-piperidin-4-karbonska kiselina-[3-(6,8-di-klor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 30) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-nikotinamid; 31) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-metan-sulfonamid; 32) etansulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 33) N',N'-dimetilamino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-sulfamid; 34) ciklopropankarbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 35) l-acetil-piperidin-4-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 36) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 37) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 38) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-etil-urea; 39) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-tiourea; 40) N-{5-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenilsulfamoil]-4-metil-tiazol-2-il}-acetamid; 41) l,2-dimetil-1H-imidazol-4-sulfonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 42) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluor-metansulfonamid; 43) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-C,C,C-trifluor-metansulfonamid; 44) N-etil-N'-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzolsulfonil-urea; 45) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-acetamid; 46) 2,6-diamino-heksanska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 47) 1H-pirol-3-karbonska kiselina-4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 48) l-metil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 49) l-metansulfonil-piperidin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 50) 1H-pirazol-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 51) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-metilamino-acetamid; 52) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-2-dimetilamino-acetamid; 53) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-propionamid; 54) 2-amino-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-butiramid; 55) 2,6-diamino-heksanska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 56) l-metil-piperidin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]amid; 57) 1H-imidazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 58) l-metansulfonil-piperidin-4-karbonska kiselina-[3-6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 59) 3,5-dimetil-1H-pirazoi-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 60) 1H-pirazol-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 61) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dimetil-urea; 62) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinoln-4-il)-fenil]-amid; 63) piperidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 64) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 65) pirolidin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 66) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 67) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil-3-metil-urea; 68) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil-3-(2-dimetilamino-etil)-urea; 69) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-furan-3-il)-urea; 70) l-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(tetrahidro-piran-4-il)-urea; 71) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-metil-1-(l-metil-piperidin-4-il)-urea; 72) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-(3-dimetiiamino-propil)-1-metil-urea; 73) 3-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1-(2-dimetilamino-etil)-1-metil-urea; 74) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(3-dimetilamino-propil)-urea; 75) l-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-metoksi-etil)-urea; 76) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-piridin-3-il-urea; 77) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-piridin-4-il-urea; 78) 4-metil-piperazin-1-karbonska kiselina-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-amid; 79) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-metil-urea: 80) 1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 81) 4-metil-piperazin-1-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinoiin-4-il)-fenil]amid; 82) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-metil-urea; 83) 3-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dimetil-urea; 84) 3-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,1-dietil-urea; 85) 1-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-urea; 86) morfolin-4-karbonska kiselina-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinoiin-4-il)-fenil]-amid; 87) N-[4-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-formamid; 88) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amin; 89) N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-formamid; 90) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amin; 91) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-l,3,3-trimetil-urea; 92) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-1,3-dimetil-urea; 93) morfolin-4-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2, 3, 4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 94) 4-metil-piperazin-1-karbonska kiselina-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metil-amid; 95) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-dimetilamino-etil)-1-metil-urea; 96) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 97) [4-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 98) [2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina 2-dimetilamino-etil ester; 99) [3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-karbaminska kiselina metil ester; 100) (R ili S)-N-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-metansulfonamid; 101) (R ili S)-1-[2-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-fenil]-3-etil-urea; 102) 1-[3-(6,8-diklor-2-metil-1,2,3,4-tetrahidroizokinolin-4-il)-fenil]-3-(2-hidroksi-etil)-urea; 103) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina etil ester; 104) 3-(6,8-diklor-2-metil-1,2,3,4-tetrahidro-izokinolin-4-il)-benzojeva kiselina, kao i njihove farmacetski podnošljive soli.11. Use according to claim 7, characterized in that the compounds of formula I are selected from the group consisting of: 1) N-[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-tetrahydro-isoquinolin-4-yl)-benzenesulfonamide; 3) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isokirtolin-4-yl)-benzenesulfonamide; 4) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid; 5) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-ethyl-benzamide; 6) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-propyl-benzamide; 7) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-benzamide; 8) 6,8-dichloro-2-methyl-4-(4-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydroisoquinoline; 9) 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine; 10) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea; 11) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea; 12) N-[4-(6-bromo-8-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-acetamide; 13) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-2-hydroxy-benzoic acid; 14) 5-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-N-(2-dimethylamino-ethyl)-2-hydroxy-benzamide; 15) N-[3-(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-tetrahydro-isoquinolin-4-yl)-phenylamine; 17) 2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylamine; 18) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide; 19) 1-acetyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 20) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide; 21) ethanesulfonic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 22) N',N'-dimethylamino-N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide; 23) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-propionamide; 24) N-[3-(6,ε-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-butyramide; 25) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-isobutyramide; 26) cyclobutanecarboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 28) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl-2,2,2-trifluoroacetamide; 29) 1-acetyl-piperidine-4-carboxylic acid-[3-(6,8-di-chloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide ; 30) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-nicotinamide; 31) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-methane-sulfonamide; 32) ethanesulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 33) N',N'-dimethylamino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-sulfamide; 34) cyclopropanecarboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 35) 1-acetyl-piperidine-4-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 36) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea; 37) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea; 38) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-ethyl-urea; 39) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-thiourea; 40) N-{5-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenylsulfamoyl]-4-methyl-thiazol-2-yl }-acetamide; 41) 1,2-dimethyl-1H-imidazole-4-sulfonic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide; 42) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide; 43) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-C,C,C-trifluoromethanesulfonamide; 44) N-ethyl-N'-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonyl-urea; 45) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide; 46) 2,6-diamino-hexanoic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 47) 1H-pyrrole-3-carboxylic acid-4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 48) 1-methyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide; 49) 1-methanesulfonyl-piperidine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 50) 1H-pyrazole-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 51) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-methylamino-acetamide; 52) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-2-dimethylamino-acetamide; 53) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-propionamide; 54) 2-amino-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-butyramide; 55) 2,6-diamino-hexanoic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 56) 1-methyl-piperidine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]amide; 57) 1H-imidazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 58) 1-methanesulfonyl-piperidine-4-carboxylic acid-[3-6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 59) 3,5-dimethyl-1H-pyrazol-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl] -amide; 60) 1H-pyrazole-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 61) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea; 62) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinol-4-yl)-phenyl]-amide; 63) piperidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 64) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 65) pyrrolidine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 66) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea; 67) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl-3-methyl-urea; 68) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl-3-(2-dimethylamino-ethyl)-urea; 69) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-furan-3-yl)-urea; 70) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(tetrahydro-pyran-4-yl)-urea; 71) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-methyl-1-(1-methyl-piperidine-4 -yl)-urea; 72) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-(3-dimethylamino-propyl)-1-methyl- urea; 73) 3-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1-(2-dimethylamino-ethyl)-1-methyl- urea; 74) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(3-dimethylamino-propyl)-urea; 75) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-methoxy-ethyl)-urea; 76) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-pyridin-3-yl-urea; 77) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-pyridin-4-yl-urea; 78) 4-methyl-piperazine-1-carboxylic acid-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-amide; 79) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-methyl-urea: 80) 1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea; 81) 4-methyl-piperazine-1-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoin-4-yl)-phenyl]amide; 82) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-methyl-urea; 83) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-dimethyl-urea; 84) 3-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,1-diethyl-urea; 85) 1-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-urea; 86) morpholine-4-carboxylic acid-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinoin-4-yl)-phenyl]-amide; 87) N-[4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-formamide; 88) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine; 89) N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-formamide; 90) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amine; 91) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3,3-trimethyl-urea; 92) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-1,3-dimethyl-urea; 93) morpholine-4-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide; 94) 4-methyl-piperazine-1-carboxylic acid-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methyl-amide ; 95) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-dimethylamino-ethyl)-1-methyl- urea; 96) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester; 97) [4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester; 98) [2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid 2-dimethylamino-ethyl ester; 99) [3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-carbamic acid methyl ester; 100) (R or S)-N-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-methanesulfonamide; 101) (R or S)-1-[2-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-phenyl]-3-ethyl-urea; 102) 1-[3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea; 103) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid ethyl ester; 104) 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzoic acid, as well as their pharmaceutically acceptable salts. 12. Upotreba spoja I prema zahtjevu 1, naznačena time, da se on koristi za proizvodnju lijeka za liječenje ili profilaksu poremećaja respiratorne funkcije.12. Use of compound I according to claim 1, characterized in that it is used for the production of a medicine for the treatment or prophylaxis of respiratory function disorders. 13. Upotreba spoja I prema zahtjevu 7, naznačena time, da se on koristi za proizvodnju lijeka za liječenje ili profilaksu poremećaja disanja, posebno poremećaja disanja uzrokovanih spavanjem kao što su apnoje spavanja.13. The use of compound I according to claim 7, characterized in that it is used for the production of a drug for the treatment or prophylaxis of breathing disorders, especially breathing disorders caused by sleep such as sleep apnea. 14. Upotreba spoja I prema zahtjevu 7, naznačena time, da se on koristi za proizvodnju lijeka za liječenje ili profilaksu hrkanja.14. Use of compound I according to claim 7, characterized in that it is used for the production of a medicine for the treatment or prophylaxis of snoring. 15. Upotreba spoja I prema zahtjevu 7, naznačena time, da se on koristi za proizvodnju lijeka za liječenje ili profilaksu akutnih i kroničnih bolesti bubrega, posebno akutnog otkazivanja bubrega i kroničnog otkazivanja bubrega.15. Use of compound I according to claim 7, characterized in that it is used for the production of a drug for the treatment or prophylaxis of acute and chronic kidney diseases, especially acute kidney failure and chronic kidney failure. 16. Upotreba spoja I prema zahtjevu 7, naznačena time, da se on koristi za proizvodnju lijeka za liječenje ili profilaksu poremećaja funkcije crijeva.16. Use of compound I according to claim 7, characterized in that it is used for the production of a medicine for the treatment or prophylaxis of bowel function disorders. 17. Upotreba spoja I prema zahtjevu 7, naznačena time, da se on koristi za proizvodnju lijeka za liječenje ili profilaksu poremećaja funkcije žuči.17. The use of compound I according to claim 7, characterized in that it is used for the production of a medicine for the treatment or prophylaxis of disorders of the bile function. 18. Upotreba spoja I prema zahtjevu 7, naznačena time, da se on koristi za proizvodnju lijeka za liječenje ili profilaksu ishemijskih stanja perifernog i središnjeg nervnog sistema i udara kapi.18. Use of compound I according to claim 7, characterized in that it is used for the production of a drug for the treatment or prophylaxis of ischemic conditions of the peripheral and central nervous system and stroke. 19. Upotreba spoja I prema zahtjevu 7, naznačena time, da se on koristi za proizvodnju lijeka za liječenje ili profilaksu ishemijskih stanja perifernih organa i udova.19. Use of compound I according to claim 7, characterized in that it is used for the production of a medicine for the treatment or prophylaxis of ischemic conditions of peripheral organs and limbs. 20. Upotreba spoja I prema zahtjevu 7, naznačena time, da se on koristi za proizvodnju lijeka za liječenje stanja šoka.20. Use of compound I according to claim 7, characterized in that it is used for the production of a medicine for the treatment of shock conditions. 21. Upotreba spoja I prema zahtjevu 7, naznačena time, da se on koristi za proizvodnju lijeka koji se upotrebljava kod kirurških operacija i transplantacija organa.21. Use of compound I according to claim 7, characterized in that it is used for the production of a medicine used in surgical operations and organ transplants. 22. Upotreba spoja I prema zahtjevu 7, naznačena time, da se on koristi za proizvodnju lijeka za konzerviranje i odlaganje transplantata za kirurške zahvate.22. Use of compound I according to claim 7, characterized in that it is used for the production of a medicine for preservation and disposal of grafts for surgical procedures. 23. Upotreba spoja I prema zahtjevu 7, naznačena time, da se on koristi za proizvodnju lijeka liječenje bolesti kod kojih primarni ili sekundarni uzrok predstavlja proliferacija stanica.23. The use of compound I according to claim 7, characterized in that it is used for the production of medicine for the treatment of diseases in which the primary or secondary cause is cell proliferation. 24. Upotreba spoja I prema zahtjevu 7, naznačena time, da se on koristi za proizvodnju lijeka za liječenje ili profilaksu poremećaja metabolizma masti.24. Use of compound I according to claim 7, characterized in that it is used for the production of a drug for the treatment or prophylaxis of fat metabolism disorders. 25. Upotreba spoja I prema zahtjevu 7, naznačena time, da se on koristi za proizvodnju lijeka za liječenje ili profilaksu napada ektoparazita.25. Use of compound I according to claim 7, characterized in that it is used for the production of a drug for the treatment or prophylaxis of ectoparasite attacks. 26. Lijek, naznačen time, da on sadrži učinkovitu količinu spoja prema zahtjevu 1.26. Medicine, characterized in that it contains an effective amount of the compound according to claim 1.
HR20040507A 2001-12-05 2004-06-04 Substituted 4-phenyltetrahydroisoquinoline methods HRP20040507A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10159714 2001-12-05
PCT/EP2002/012990 WO2003048129A1 (en) 2001-12-05 2002-11-20 Substituted 4-phenyltetrahydroisoquinolines, method for the production thereof, the use thereof as medicaments, in addition to a medicament containing same

Publications (1)

Publication Number Publication Date
HRP20040507A2 true HRP20040507A2 (en) 2005-08-31

Family

ID=7708117

Family Applications (1)

Application Number Title Priority Date Filing Date
HR20040507A HRP20040507A2 (en) 2001-12-05 2004-06-04 Substituted 4-phenyltetrahydroisoquinoline methods

Country Status (34)

Country Link
EP (1) EP1453810B1 (en)
JP (1) JP4510457B2 (en)
KR (1) KR20050044724A (en)
CN (1) CN100497314C (en)
AR (1) AR037620A1 (en)
AT (1) ATE425968T1 (en)
AU (1) AU2002356689B2 (en)
BR (1) BR0214753A (en)
CA (1) CA2469385A1 (en)
CO (1) CO5580748A2 (en)
DE (1) DE50213372D1 (en)
DK (1) DK1453810T3 (en)
EC (1) ECSP045138A (en)
ES (1) ES2324528T3 (en)
HK (1) HK1072597A1 (en)
HR (1) HRP20040507A2 (en)
HU (1) HUP0600854A2 (en)
IL (1) IL162316A0 (en)
MA (1) MA27147A1 (en)
MX (1) MXPA04005343A (en)
MY (1) MY157371A (en)
NO (1) NO326650B1 (en)
NZ (1) NZ533322A (en)
OA (1) OA12740A (en)
PE (1) PE20030726A1 (en)
PL (1) PL369313A1 (en)
PT (1) PT1453810E (en)
RS (1) RS48004A (en)
RU (1) RU2298003C2 (en)
TN (1) TNSN04100A1 (en)
TW (1) TWI281860B (en)
UA (1) UA77042C2 (en)
WO (1) WO2003048129A1 (en)
ZA (1) ZA200403711B (en)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10312963A1 (en) * 2003-03-24 2004-10-07 Aventis Pharma Deutschland Gmbh Substituted 4-phenyltetrahydroisoquinolines, process for their preparation, their use as medicament, and medicament containing them
TW200526626A (en) 2003-09-13 2005-08-16 Astrazeneca Ab Chemical compounds
DE102004046492A1 (en) * 2004-09-23 2006-03-30 Sanofi-Aventis Deutschland Gmbh Substituted 4-phenyltetrahydroisoquinolines, process for their preparation, their use as medicament, and medicament containing them
US20060111393A1 (en) * 2004-11-22 2006-05-25 Molino Bruce F 4-Phenyl substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine and serotonin
DE102005001411A1 (en) * 2005-01-12 2006-07-27 Sanofi-Aventis Deutschland Gmbh Substituted 4-phenyltetrahydroisoquinolines, process for their preparation, their use as medicament, and medicament containing them
UA94901C2 (en) 2005-02-18 2011-06-25 Астразенека Аб Antibacterial piperidine derivatives
CN101171247A (en) * 2005-03-04 2008-04-30 阿斯利康(瑞典)有限公司 Pyrrole derivatives as DNA gyrase and topoisomerase inhibitors
DE102005044817A1 (en) * 2005-09-20 2007-03-22 Sanofi-Aventis Deutschland Gmbh Substituted 4-phenyltetrahydroisoquinolines, process for their preparation, their use as medicament, and medicament containing them
DE102006012545A1 (en) 2006-03-18 2007-09-27 Sanofi-Aventis Substituted 2-amino-4-phenyl-dihydroquinolines, process for their preparation, their use as medicament, and medicament containing them
WO2018129556A1 (en) * 2017-01-09 2018-07-12 Ardelyx, Inc. Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders
US10543207B2 (en) 2008-12-31 2020-01-28 Ardelyx, Inc. Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders
MX345283B (en) 2008-12-31 2017-01-24 Ardelyx Inc Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders.
ES2446971T3 (en) 2009-05-12 2014-03-11 Albany Molecular Research, Inc. Tetrahydroisoquinolines substituted with aryl, heteroaryl, and heterocycle and their use
KR102138391B1 (en) * 2012-08-21 2020-07-27 알데릭스, 인코포레이티드 Compounds and methods for inhibiting nhe-mediaded antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders
JP6377132B2 (en) 2013-04-12 2018-08-22 アーデリクス，インコーポレーテッド NHE3-binding compounds and methods of inhibiting phosphate transport
CN103788084A (en) * 2014-03-02 2014-05-14 湖南华腾制药有限公司 Tetrahydroisoquinoline derivative and synthesis method thereof
BR112017000691B1 (en) 2014-07-25 2023-02-14 Taisho Pharmaceutical Co., Ltd PHENYLTETRAHYDROISOQUINOLINE REPLACED WITH HETEROARI-LA, ITS USE, DRUG, NHE3, SODIUM ABSORPTION AND PHOSPHORUS ABSORPTION INHIBITORS, INTESTINAL WATER SECRETION PROMOTER AND PROPHYLACTIC OR THERAPEUTIC DRUGS FOR CONSTIPATION
JP6903923B2 (en) * 2016-01-22 2021-07-14 大正製薬株式会社 A drug containing a phenyltetrahydroisoquinoline compound substituted with a heteroaryl as an active ingredient.
EA201991676A1 (en) 2017-01-09 2020-01-30 Арделикс, Инк. NHE-MEDIATED ANTI-PORT INHIBITORS
EP3565808A1 (en) 2017-01-09 2019-11-13 Ardelyx, Inc. Compounds useful for treating gastrointestinal tract disorders
CA3202573A1 (en) * 2020-12-18 2022-06-23 Shuchun GUO Benzoheterocycle substituted tetrahydroisoquinoline compound

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19951702A1 (en) * 1999-10-27 2001-05-03 Aventis Pharma Gmbh Use of 2-amino-3,4-dihydroquinazolines for the manufacture of a medicament for the treatment or prophylaxis of diseases caused by ischemic conditions
ES2304984T3 (en) * 1999-11-03 2008-11-01 Amr Technology, Inc. TETRA-HYDROISOQUINOLINAS OF ARILICA AND HETEROARILICA SUBSTITUTION AND ITS USE TO BLOCK THE RECOVERY OF NOREPINEFRINE, DOPAMINE AND SEROTONINE.
MXPA02004329A (en) * 1999-11-03 2005-08-26 Amr Technology Inc 4 phenyl substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine and serotonin.
EP1113007A1 (en) * 1999-12-24 2001-07-04 Pfizer Inc. Tetrahydroisoquinoline compounds as estrogen agonists/antagonists
DE10019062A1 (en) * 2000-04-18 2001-10-25 Merck Patent Gmbh Use of known and new 2-guanidino-4-aryl-quinazoline derivatives as NHE-3 inhibitors useful for the treatment of e.g. hypertension, thrombosis, cardiac ischemia, peripheral and CNS ischemia

Also Published As

Publication number Publication date
WO2003048129A1 (en) 2003-06-12
KR20050044724A (en) 2005-05-12
RU2004120295A (en) 2006-01-10
DK1453810T3 (en) 2009-07-20
HK1072597A1 (en) 2005-09-02
NO326650B1 (en) 2009-01-26
CN100497314C (en) 2009-06-10
OA12740A (en) 2006-06-30
AR037620A1 (en) 2004-11-17
IL162316A0 (en) 2005-11-20
PE20030726A1 (en) 2003-09-30
ES2324528T3 (en) 2009-08-10
PT1453810E (en) 2009-05-27
EP1453810B1 (en) 2009-03-18
CO5580748A2 (en) 2005-11-30
EP1453810A1 (en) 2004-09-08
JP4510457B2 (en) 2010-07-21
NZ533322A (en) 2006-02-24
AU2002356689B2 (en) 2008-05-15
TW200306190A (en) 2003-11-16
RU2298003C2 (en) 2007-04-27
TWI281860B (en) 2007-06-01
BR0214753A (en) 2004-12-14
ECSP045138A (en) 2004-08-27
UA77042C2 (en) 2006-10-16
MY157371A (en) 2016-06-15
TNSN04100A1 (en) 2006-06-01
MXPA04005343A (en) 2004-09-27
AU2002356689A1 (en) 2003-06-17
NO20042158L (en) 2004-08-27
CA2469385A1 (en) 2003-06-12
RS48004A (en) 2006-10-27
MA27147A1 (en) 2005-01-03
ATE425968T1 (en) 2009-04-15
JP2005515205A (en) 2005-05-26
DE50213372D1 (en) 2009-04-30
CN1617856A (en) 2005-05-18
ZA200403711B (en) 2005-06-09
PL369313A1 (en) 2005-04-18
HUP0600854A2 (en) 2007-02-28

Similar Documents

Publication Publication Date Title
HRP20040507A2 (en) Substituted 4-phenyltetrahydroisoquinoline methods
US6911453B2 (en) Substituted 4-phenyltetrahydroisoquinolinium, process for their preparation, their use as a medicament, and medicament containing them
EP1794128B1 (en) Substituted 4-phenyltetrahydroisoquinolines, method for the production thereof, their use as a medicament, and a medicament containing them
EP1838315B1 (en) Substituted 4-phenyltetrahydroisoquinolines, methods for producing them, their use as drug, and drug containing them
US6703405B2 (en) Substituted 4-phenyltetrahydroisoquinolinium salts, process for their preparation, their use as a medicament, and medicament containing them
EP1613600A1 (en) Substituted 4-phenyltetrahydroisoquinolines, method for the production thereof, the use of the same as medicaments, and medicament containing such compounds
EP1465870B1 (en) Substituted 4-phenyltetrahydroisoquinolinium salts, method for production and use thereof as a medicament and medicaments comprising the same
RU2315766C2 (en) Substituted thiopenes, their using as medicinal or diagnostic agent and medicinal agent comprising thereof
HRP980527A2 (en) Sulfonamid-substituted chromans, process for their preparation, their use as medicine, and pharmaceutical preparation containing them

Legal Events

Date Code Title Description
A1OB Publication of a patent application
PNAN Change of the applicant name, address/residence

Owner name: SANOFI-AVENTIS DEUTSCHLAND GMBH, DE

ARAI Request for the grant of a patent on the basis of the submitted results of a substantive examination of a patent application
ODRP Renewal fee for the maintenance of a patent

Payment date: 20081117

Year of fee payment: 7

OBST Application withdrawn