MXPA98006923A - Pharmaceutical combined preparation based on an inhibitor of the exchanger between sodium and hydrogen and of a medicine intended for the treatment of cardio-circulatory diseases - Google Patents
Pharmaceutical combined preparation based on an inhibitor of the exchanger between sodium and hydrogen and of a medicine intended for the treatment of cardio-circulatory diseasesInfo
- Publication number
- MXPA98006923A MXPA98006923A MXPA/A/1998/006923A MX9806923A MXPA98006923A MX PA98006923 A MXPA98006923 A MX PA98006923A MX 9806923 A MX9806923 A MX 9806923A MX PA98006923 A MXPA98006923 A MX PA98006923A
- Authority
- MX
- Mexico
- Prior art keywords
- alkyl
- group
- hydrogen
- substituted
- zero
- Prior art date
Links
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 30
- 239000003112 inhibitor Substances 0.000 title claims abstract description 29
- 201000010099 disease Diseases 0.000 title claims abstract description 8
- 230000002425 cardiocirculatory Effects 0.000 title claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 title claims description 573
- 239000001257 hydrogen Substances 0.000 title claims description 512
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 title claims description 305
- 239000011734 sodium Substances 0.000 title claims description 11
- 239000003814 drug Substances 0.000 title claims description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 title description 6
- 229910052708 sodium Inorganic materials 0.000 title description 6
- 210000002216 Heart Anatomy 0.000 claims abstract description 27
- 230000001681 protective Effects 0.000 claims abstract description 11
- 230000004087 circulation Effects 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 813
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 471
- 239000000460 chlorine Substances 0.000 claims description 432
- 229910052801 chlorine Inorganic materials 0.000 claims description 427
- 229910052731 fluorine Inorganic materials 0.000 claims description 427
- 125000001424 substituent group Chemical group 0.000 claims description 411
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 377
- 125000004432 carbon atoms Chemical group C* 0.000 claims description 364
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 312
- -1 chloro, methyl Chemical group 0.000 claims description 268
- 229910052760 oxygen Inorganic materials 0.000 claims description 254
- 239000001301 oxygen Substances 0.000 claims description 232
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 227
- MYMOFIZGZYHOMD-UHFFFAOYSA-N oxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 227
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 220
- 150000002431 hydrogen Chemical class 0.000 claims description 205
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 192
- 229910052717 sulfur Inorganic materials 0.000 claims description 148
- 229910052794 bromium Inorganic materials 0.000 claims description 127
- 229910052740 iodine Inorganic materials 0.000 claims description 114
- 125000003342 alkenyl group Chemical group 0.000 claims description 113
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 113
- 229910052799 carbon Inorganic materials 0.000 claims description 104
- 150000003839 salts Chemical class 0.000 claims description 85
- 239000011780 sodium chloride Substances 0.000 claims description 85
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 82
- 125000001624 naphthyl group Chemical group 0.000 claims description 80
- 229910052757 nitrogen Inorganic materials 0.000 claims description 59
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 55
- 125000001072 heteroaryl group Chemical group 0.000 claims description 55
- 125000003545 alkoxy group Chemical group 0.000 claims description 41
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 41
- NINIDFKCEFEMDL-UHFFFAOYSA-N sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 39
- 239000011593 sulfur Substances 0.000 claims description 39
- AJDQRQQNNLZLPM-UHFFFAOYSA-N N-(diaminomethylidene)benzamide Chemical class NC(N)=NC(=O)C1=CC=CC=C1 AJDQRQQNNLZLPM-UHFFFAOYSA-N 0.000 claims description 34
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 33
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 30
- 125000003118 aryl group Chemical group 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 20
- 150000002367 halogens Chemical group 0.000 claims description 19
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 125000002947 alkylene group Chemical group 0.000 claims description 16
- 125000001153 fluoro group Chemical group F* 0.000 claims description 16
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 16
- 125000001589 carboacyl group Chemical group 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 14
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 14
- 125000004433 nitrogen atoms Chemical group N* 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- 150000001409 amidines Chemical class 0.000 claims description 11
- 125000005842 heteroatoms Chemical group 0.000 claims description 11
- BAVYZALUXZFZLV-UHFFFAOYSA-N methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 11
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- ROSDSFDQCJNGOL-UHFFFAOYSA-N dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 10
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 9
- 125000005493 quinolyl group Chemical group 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
- 150000007513 acids Chemical class 0.000 claims description 7
- 239000011575 calcium Substances 0.000 claims description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 150000002829 nitrogen Chemical group 0.000 claims description 7
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 6
- 125000004430 oxygen atoms Chemical group O* 0.000 claims description 6
- 150000003254 radicals Chemical class 0.000 claims description 6
- 125000004434 sulfur atoms Chemical group 0.000 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- LPAGFVYQRIESJQ-UHFFFAOYSA-N 2,3-dihydro-1H-indole Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 240000003584 Ziziphus jujuba Species 0.000 claims description 4
- 150000001336 alkenes Chemical class 0.000 claims description 4
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
- 125000005605 benzo group Chemical group 0.000 claims description 4
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 239000000969 carrier Substances 0.000 claims description 4
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 3
- 210000004369 Blood Anatomy 0.000 claims description 3
- UWYZHKAOTLEWKK-UHFFFAOYSA-N Tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims description 3
- 125000005418 aryl aryl group Chemical group 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 229940079593 drugs Drugs 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 2
- 125000006313 (C5-C8) alkyl group Chemical group 0.000 claims description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 2
- 229940030606 DIURETICS Drugs 0.000 claims description 2
- 229940083094 Guanine derivatives acting on arteriolar smooth muscle Drugs 0.000 claims description 2
- 125000005741 alkyl alkenyl group Chemical group 0.000 claims description 2
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 2
- 125000005466 alkylenyl group Chemical group 0.000 claims description 2
- 230000001396 anti-anti-diuretic Effects 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 2
- 239000002934 diuretic Substances 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 150000002357 guanidines Chemical group 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 230000036651 mood Effects 0.000 claims description 2
- 229940083145 peripherally acting antiadrenergic agents Guanine derivatives Drugs 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 125000005413 thiopyridyl group Chemical group 0.000 claims description 2
- 125000004429 atoms Chemical group 0.000 claims 14
- 125000002883 imidazolyl group Chemical group 0.000 claims 8
- 125000002877 alkyl aryl group Chemical group 0.000 claims 6
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 6
- 206010020772 Hypertension Diseases 0.000 claims 5
- 125000000304 alkynyl group Chemical group 0.000 claims 4
- 125000003435 aroyl group Chemical group 0.000 claims 4
- 150000002926 oxygen Chemical compound 0.000 claims 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 3
- 206010007521 Cardiac arrhythmias Diseases 0.000 claims 3
- 206010007554 Cardiac failure Diseases 0.000 claims 3
- 206010019280 Heart failure Diseases 0.000 claims 3
- 125000001931 aliphatic group Chemical group 0.000 claims 3
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims 3
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims 3
- 125000003107 substituted aryl group Chemical compound 0.000 claims 3
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims 2
- 125000001989 1,3-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([H])C([*:2])=C1[H] 0.000 claims 2
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 claims 2
- IWXNYAIICFKCTM-UHFFFAOYSA-N Cariporide Chemical compound CC(C)C1=CC=C(C(=O)N=C(N)N)C=C1S(C)(=O)=O IWXNYAIICFKCTM-UHFFFAOYSA-N 0.000 claims 2
- 102100004109 HEY1 Human genes 0.000 claims 2
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N Phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 claims 2
- 241000687904 Soa Species 0.000 claims 2
- 125000002723 alicyclic group Chemical group 0.000 claims 2
- 239000003416 antiarrhythmic agent Substances 0.000 claims 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N benzohydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims 2
- 125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 2
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 claims 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 claims 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims 1
- 206010003119 Arrhythmia Diseases 0.000 claims 1
- 125000006374 C2-C10 alkenyl group Chemical compound 0.000 claims 1
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 1
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- 206010007559 Cardiac failure congestive Diseases 0.000 claims 1
- 229950008393 Cariporide Drugs 0.000 claims 1
- SDIXRDNYIMOKSG-UHFFFAOYSA-L Disodium methyl arsenate Chemical compound [Na+].[Na+].C[As]([O-])([O-])=O SDIXRDNYIMOKSG-UHFFFAOYSA-L 0.000 claims 1
- XEHVFKKSDRMODV-UHFFFAOYSA-N Ethynyl radical Chemical group C#[C] XEHVFKKSDRMODV-UHFFFAOYSA-N 0.000 claims 1
- QAKJXJZBXCVFLX-UHFFFAOYSA-N N-(diaminomethylidene)-1H-indole-2-carboxamide Chemical class C1=CC=C2NC(C(=O)N=C(N)N)=CC2=C1 QAKJXJZBXCVFLX-UHFFFAOYSA-N 0.000 claims 1
- 210000004940 Nucleus Anatomy 0.000 claims 1
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 claims 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 claims 1
- 102000018674 Sodium Channels Human genes 0.000 claims 1
- 108010052164 Sodium Channels Proteins 0.000 claims 1
- ORGHESHFQPYLAO-UHFFFAOYSA-N Vinyl radical Chemical group C=[CH] ORGHESHFQPYLAO-UHFFFAOYSA-N 0.000 claims 1
- 239000002170 aldosterone antagonist Substances 0.000 claims 1
- 125000005024 alkenyl aryl group Chemical compound 0.000 claims 1
- 125000005217 alkenylheteroaryl group Chemical compound 0.000 claims 1
- 150000003973 alkyl amines Chemical class 0.000 claims 1
- 125000005025 alkynylaryl group Chemical compound 0.000 claims 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 239000003160 antidiuretic agent Substances 0.000 claims 1
- 239000002220 antihypertensive agent Substances 0.000 claims 1
- 229940111121 antirheumatic drugs Quinolines Drugs 0.000 claims 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims 1
- 239000002876 beta blocker Substances 0.000 claims 1
- 239000000480 calcium channel blocker Substances 0.000 claims 1
- 229910000099 calcium monohydride Inorganic materials 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
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- 201000006233 congestive heart failure Diseases 0.000 claims 1
- 230000000875 corresponding Effects 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
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- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims 1
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- NHNBFGGVMKEFGY-UHFFFAOYSA-N nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims 1
- 230000003000 nontoxic Effects 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 230000003287 optical Effects 0.000 claims 1
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- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims 1
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- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 230000000069 prophylaxis Effects 0.000 claims 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 1
- 125000002098 pyridazinyl group Chemical group 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- QGKLPGKXAVVPOJ-UHFFFAOYSA-N pyrrolidin-3-one Chemical compound O=C1CCNC1 QGKLPGKXAVVPOJ-UHFFFAOYSA-N 0.000 claims 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims 1
- 125000005942 tetrahydropyridyl group Chemical group 0.000 claims 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 125000001425 triazolyl group Chemical group 0.000 claims 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 9
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- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 8
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- 230000000747 cardiac effect Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
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- 229910001415 sodium ion Inorganic materials 0.000 description 2
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 1
- 241001649081 Dina Species 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 206010022114 Injury Diseases 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001143 conditioned Effects 0.000 description 1
- 230000003247 decreasing Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 230000002349 favourable Effects 0.000 description 1
- 230000012105 intracellular pH reduction Effects 0.000 description 1
- 230000003902 lesions Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000001052 transient Effects 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
Abstract
In this case, such combinations of an NHE inhibitor may consist of one or more therapeutic components active in the circulation. The combination of the protective properties of the heart with known therapies of cardiocirculatory diseases leads on the one hand to an improvement in the quality of the treatment and on the other hand, in numerous combinations, to an additive or enhancer reinforcement of the effects on the heart and circulation of the individual components of effect, taken by sun
Description
Combined pharmaceutical preparation based on an inhibitor of the exchanger between sodium and hydrogen and a drug for the treatment of cardio-circulatory diseases
The invention relates to the combination of inhibitors of exchange between sodium and hydrogen with other active substances on the heart and circulation, for the treatment of cardio-circulatory diseases. The inhibitors of the exchanger between sodium and hydrogen (NHE, of Na tri um-Hydrogen-Exchanger) have been characterized in recent years in numerous preclinical studies as substances that are appropriate, in the case of decreased blood circulation of the heart, of a superior mode to protect the exposed cardiac tissue with respect to death. The protection of cardiac tissue by means of NHE inhibitors comprises all the manifestations of the lesions caused by the defective blood circulation, beginning with heart rhythm disorders, going through a hypercontraction of the cardiac muscle (myocardium) and a transient loss of functions until reaching to the death of heart tissue and the permanent injuries that are linked to it. The mechanism of the effect of the NHE inhibitors is that they decrease the increased inward current of sodium ions, which results in tissues traveled by the blood in a defective manner as a result of intracellular acidification and subsequent activation of the NHE. This further delays an overload with sodium of the tissue. Since the transport of sodium ions and calcium ions are coupled to the heart tissue, this prevents overload with calcium from heart cells, which is life-threatening. This unique mechanism of effect of the NHE inhibitors makes possible its advantageous combination with active substances that are used for the treatment of different cardio-circulatory diseases and its effect on the heart and circulation is based on different mechanisms of effect.
In such a case, these combinations of an NHE inhibitor may consist of one or several therapeutic components active on the heart. The combination of the protective properties of the heart with the known therapies for cardio-circulatory diseases leads, on the one hand, to an improvement in the quality of the treatment and, on the other hand, in numerous combinations to an additive or potentiator reinforcement of the Effects on the heart and circulation of individual components of effect. In such a case, the mechanistically conditioned avoidance of sodium overload of heart cells by NHE inhibitors has a particularly favorable effect on the success of treatment with the participant in the combination that is active on the heart and circulation. In the case of active substances known and identified as NHE inhibiting agents, these are guanidine derivatives, preferably acyl guanidines, among others, as described in the following publications and patent disclosures: Edward J. Cragoe, Jr. . , "DIURETICS, Chemi stry, Pharmacology and Medicine", J. WILEY & Sons (1983), 303-341, and in addition they are compounds of the following formulas:
I (HOE 89 / F 288 - US 5,292,755) a) Benzoylguanidines of Formula I
wherein they mean: R (l) or R (2) R (6) -S (O) or R (7) R (8) N-02S; and the respectively another substituent R (l) or R (2) H, F, Cl, Br, alkyl (C.-C4), alkoxy (C.-C or phenoxy, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of fluoro, chloro, methyl and methoxy, or the respectively another substituent R (l) or R (2) R (6) -S (0) p or R (7) R (8) N- n null, 1 or 2, R (6) (C1-C6) alkyl, (C5-C7) cycloalkyl, cyclopentylmethyl, cyclohexylmethyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of Fluoro, chloro, methyl and methoxy; R (7) and R (8) equal or different, H or alkyl (C * -C6); or R (7) phenyl- (CH2) m; m 1 - 4; or R (7) phenyl, which is unsubstituted or substituted with 1-2 substituents selected from the group consisting of fluoro, chloro, methyl and methoxy, - or R (7) and R (8) in common a chain (C4) -C7) linear or branched or, the chain being able to be interrupted additionally by O, S or NR (9); R (9) H or methyl; or R (7) and R (8) in common with the nitrogen atom, to which they are attached, a system of dihydroindole, tetrahydroquinoline or tetrahydroisoquinoline; R (3), R (4) and R (5) independently of each other, H or (C-C2) alkyl, R (3) and R (4) in common, an alkylene chain (C2-C4);
R (4) and R (5) in common, an alkylene chain (C4-C7); as well as its pharmaceutically compatible salts;
(IIOE 92 / F 34 - \ 7 5.371.924) b) Uenzoilguan dinas of Formula I
wherein they mean: R (l) R (4) -S0m OR R (5) R (6) N-S02-; m zero, 1 or 2, - R (4) and R (5) C, -C8 alkyl, C3-C6 alkenyl or CnH2n-R (7); n zero, 1, 2, 3 or 4; R (7) C5 ~ C7 cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9); R (8) and R (9) H or C 1 -C 4 alkyl;
R (5) H; R (6) H or C, -C 4, or R (5) alkyl and R (6) in common 4 or 5 methylene groups, of which a CH 2 group may be replaced by an O, S, NH, N- CH3 or N-benzyl; R (2) hydrogen, F, Cl, Br, alkyl (CrC4), 0- (CH2) mCpF2p + 1 or -X-R (IO); m zero or 1; P 1, 2 or 3; X 0, S or NR (l l); R (10) H, C -C6 alkyl, C5-C6 cycloalkyl, cyclohexylmethyl, cyclopentylmethyl or -CnH2n-R (12); n zero, 1, 2, 3 or 4; R (12) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9); R (8) and R (9) equal to H or C -C4 alkyl; R (ll) hydrogen or C-C3 alkyl or R (10) and R (ll) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by O, S, NH, N-CH3 or N-benzyl; R (3) as defined R (l), or C1-C6 alkyl, nitro, cyano, trifluoromethyl, F, Cl, Br, I or -X-R (IO); X 0, S or NR (ll); R (10) equal to H, C1-C6 alkyl, C5-C7 cycloalkyl, cyclohexylmethyl, cyclopentylmethyl or -CnH2n-R (12); n from zero to 4; R (12) phenyl, which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9); R (8) and R (9) H or C-C4 alkyl;
R (ll) alkyl C.-C3, or R (10) and R (ll) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by 0, S, NH, N-CH3 or N -benzyl; as well as their physiologically compatible salts;
(HOE 92 / F 035 - EP-OS 556,673) c) Ortho-substituted benzoylguanidines of Formula I
wherein they mean: R (l) F, Cl, Br, I, alkyl C.-C6 and -X-R (6); X 0, S, NR (7) or Y-Z0; And O or NR (7); Z C or SO; R (6) H, C 1 -C 6 alkyl, C 5 -C 7 cycloalkyl, cyclohexylmethyl, cyclopentylmethyl, -C n H 2n-R (8); m zero or 1; 1-3; n from zero to 4; R (8) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of the groups F, Cl, CF3, methyl, methoxy and NR (9) R (10);
R (9) and R (10) H or C-C4 alkyl; R (7) H or alkyl C ^ j, - or R (6) and R (7) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by O, S, NH, N-CH3 or N-benzyl; R (3) H or -X-R (6); X O, S, NR (7) or Y-ZO; R (7) H or C C3 alkyl; And O or NR (7); wherein Y is attached to the phenyl radical of Formula I, Z C or SO; R (6) H, C * -C6 alkyl, C-C6 cycloalkyl, cyclohexylmethyl, cyclopentylmethyl, _ (CH2) mCF2. O -CnH2n-R (8); m zero or 1; p 1 - 3; n from zero to 4, - R (8) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10); R (9) and R (10) H or C, -C4 alkyl; or R (6) and R (7) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by O, S, NH, N-CH3 or N-benzyl; R (2) and R (4) equal or different, R (ll) -SOa- or R (12) R (13) N-SOz-; q zero - 2; R (ll) C 1 -C 4 alkyl, which is unsubstituted or carries phenyl as a substituent, the phenyl being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3, methyl, methoxy and NR ( 9) R (10); R (9) and R (10) H or C-C4 alkyl; R (12) and R (13) as defined R (6) and R (7); or one of the two radicals R (2) or R (4) hydrogen or as defined R (l); R (5) H, methyl, F, Cl or methoxy, as well as their pharmaceutically compatible salts;
(HOE 92 / F 036 - US 5,364,868) d) Benzoylguanidines of Formula I
wherein they mean: R (l) or R (2) an ammo group -NR (3) R (4); R (3) and R (4) equal or different, H, C 1 -C 6 alkyl or C 3 -C 7 cycloalkyl; or R (3) phen? l- (CH, 2'P 'P zero, 1, 2, 3 or 4; or R (3) phenyl, the phenyl being in each case unsubstituted or carrying one to two substituents selected from the group consisting of fluoro, chloro, methyl and ethoxy, or R (3) and R. (4) can be in common a linear or branched C4-C7 ethylene chain, with a member -CH2- of the methylene chain is replaced by oxygen, S or NR (5), - R (5) H or lower alkyl; respectively another substituent R (1) or R (2) H, F, Cl, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, CF 3, Cm 2+ + 1 -CH 2 -, benzyl or phenoxy, the respective phenyl radical being replacing or carrying one to two substituents selected from the group consisting of methyl, methoxy, fluoro and chloro; m 1, 2 0 3; as well as its pharmaceutically compatible salts;
(92 / F 197 K - NZ 248.013) e) Benzoylguanidmas of Formula I
wherein they mean: R (l) R (4) -SOm or R (5) R (6) NM-S02-; m zero, 1 or 2; R (4) and R (5) C ^ Cg alkyl, C3-C6 alkenyl or -CnH2n-R (7); n zero, 1, 2, 3 or 4; R (7) C?-Calalkyl-C5-C7 or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8 -R ( 9); P. {8) and R (9) H or C-C4 alkyl; or R (>) II; R (6) H or C-C4 alkyl; or R (5) and R (6) in common 4 or 5 groups of filled me, of which a CH2 group can be replaced by an O, S, NH, N-CH3 or N-benzyl; R (2) hydrogen, straight or branched (C5-C8) alkyl, -CR (13) = CHR (12) or -C = CR (12); R (12) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (14) R (15); R (14) and R (15) H or alkyl (C.-C4); or R (12) heteroaryl (C.-C,), which is unsubstituted or substituted the same as phenyl; or R (12) (C1-C6) alkyl which is unsubstituted or substituted with 1-3 OH; or R (12) cycloalkyl (C3-C8); R (13) hydrogen or methyl, or R (12) cycloalkyl (C3-C8), cycloalkyl (C3-C8) -alkyl (C1-C4), phenyl, C6H5-alkyl (C1-C4), naphthyl, biphenyl 1, 1-d-phenol-alkyl (C 1 -C 4), cyclopentadienyl, pipdyl, pyrrolyl, furanyl, thienyl, thiazolyl, oxazolyl, mdenyl, quinolyl, ndolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, ylidazolyl , pyrazolyl, tpazolyl, tetrazolyl, isoxazolyl, isothiazolyl, pyrazinyl, pi imidinyl, pipdazinyl, indazolyl, isoquinolyl, phthalaziml, quinoxalmyl, quinazolyl or cinolmyl; R (3) as defined R (2), and the aromatic substituents R (2) or R (3) being unsubstituted or substituted with 1-3 substituents taken between the groups of F, Cl, CF3, alkyl (C) ^ - ^), alkoxy (C.-C, or NR (10) R (11) with R (10) and R (ll) in the meaning of H or alkyl (C-C), as well as their pharmaceutically compatible salts .
(HOE 92 / F 303 K - EP-OS 589,336, NZ 248,703) f) Benzoylguanid ace of Formula I
where they mean: R (l) or R (2) R (3) -S (0) n- o
R (N-02S pectively another substituent R (l) or R (2) H, OH, F, Cl, Br, I, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, benzyloxy or phenoxy, which is unsubstituted or one to three substituents selected from the group consisting of fluoro, chloro, methyl, methoxy, hydroxy or benzyloxy, R (3) -S (0) n, -NR (4) R (5) or 3, 4-dehydropipepdine R (3) C 1 -C 6 alkyl, C 5 -C 7 cycloalkyl, cyclopentylmethyl, cyclohexylmethyl or phenyl, which is unsubstituted or carries one to three substituents selected from the group consisting of fluoro, chloro, methyl and methoxy; R (4) and R (5) equal or different, H or C -C6 alkyl, or R (4) phenyl- (CH2) m-; m 1, 2, 3 or 4; or R (4) phenyl, which is unsubstituted or it carries from one to two substituents selected from the group consisting of fluoro, chloro, methyl and methoxy, or R (4) and R (5) in common a linear or branched C4-C7 chain, the chain being able to be further interrupted by O, S or NR (6), R (6) H or methyl, or R (4) and R (5) in common with the nitrogen atom, to which they are attached, a system of dihydroindole, tetrahydroquinoline or tetrahydroisoquinoline; n zero, 1 or 2;
as well as its pharmaceutically compatible salts,
(92 / F 304 - US 5,416,094) g) Isoqumolines of Formula I
wherein they mean: R (l) hydrogen, alkyl, cycloalkyl, arylalkyl, alkenyl, substituted aminoalkyl or a ring of hetero or heteroaryl, the rings being unsubstituted or substituted with 1-3 groups selected from the group consisting of halogen, nitro, animo, mono (lower alkyl) ammo, di (lower alkyl) amino, lower alkyl, lower alkoxy, benzyloxy, phenoxy, hydroxy, trifluoromethyl, R (2) hydrogen, halogen, alkyl or aplo; which is unsubstituted or substituted with 1-3 groups selected from the group consisting of halogen, nitro, ammo, mono (lower alkyl) amino, di (lower alkyl) amino, lower alkyl, lower alkoxy, benzyloxy, phenoxy, hydroxy,
X (2), X (3) and X (4) independently of one another, hydrogen, halogen, nitro, ammo, alkyl, sulfonamido, mono (lower alkyl) ammo, di (lower alkyl) amino, lower alkyl, benzyloxy, hydroxy; X (l) hydrogen, oxygen, sulfur or NR (7); R (7) hydrogen, alkyl, cycloalkyl, arylalkyl, alkenyl, substituted aminoalkyl or an aplo or heteroaryl ring; which rings are unsubstituted or substituted with 1-3 groups selected from the group consisting of halogen, nitro, amino, mono (lower alkyl) amino, di (lower alkyl) amino, lower alkyl, lower alkoxy, benzyloxy, phenoxy, hydroxy and trifluoromethyl; in which substituents each alkyl chain or alkenyl chain may be interrupted by oxygen, sulfur or NR (8); R (8) hydrogen, alkyl, cycloalkyl, aplakyl, alkenyl, substituted aminoalkyl or an aryl or heteroaryl ring, whose rings are unsubstituted or substituted with 1-3 groups selected from the group consisting of halogen, nitro, ammo, mono (lower alkyl) to ino, di (lower alkyl) amino, lower alkyl, lower alkoxy, benzyloxy, phenoxy, hydroxy and trifluoromethyl; and their pharmaceutically acceptable salts;
(92 / F 404 - EP 602,522, NZ 250,438) h) Compounds of Formula I O NH
where R (l) is hydrogen, F, Cl, Br, I, -N02-, -C = N, -CF, R (4) -SO. or
R (5) R (6) N-S02-; m zero, 1 or 2; R (4) and R (5) alkyl (C.-C8), alken lo (C3-C6), -CnH2n-R (7) or 3 'n zero, 1, 2, 3 or 4; R (7) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9); R (8) and R (9) H or C, -C4 alkyl; or R (5 H; R (6 H or alkyl (c c4) or R (5) and R (6) in common 4 or 5 metlene groups, of which a CH? group can be replaced by oxygen, S, NH , N-CH3 or N-benzyl, R (2! -SR (10), -OR (10), -NHR (10), -NR (10) R (11), -CHR (10) R (12) , - [CR (12) R (13) OR (13 ')], - { C- [CH2-OR (13')] R (12) (R (13).} Or - [CR ( 18) R (17)] - (CO) - [CR (19) R (20) qR (14);
R (10) and R (ll) equal or different, - tCHR (16)] s- (CH2) - (CHOH) q- (CH2) p- (CHOH) t-R (21) or
- (CH2) p-0- (CH2-CH20) 2q-R (21), R (21) hydrogen, metallo, p, s, r equal or different, zero, 1, 2, 3 or 4; s zero or 1, - t 1, 2, 3 0 4; R (12) and R (13) equal or different, hydrogen, (C1-C6) alkyl or in common with the carbon atom carrying a C3-C8 cycloalkyl), R (13 ') hydrogen or alkyl?. C.-C4), - R (14) H, alkyl (CrC6), cycloalkyl (C3-C8) or CaH2a-R (15); to zero, 1, 2, 3 or 4; R (15) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9); R (8) and R (9) H or alkyl (C.-C4); or R (15) heteroaryl (CrC9), which is unsubstituted or substituted the same as phenyl, or R (15) alkyl (C -.- C6), which is sm substituted or substituted with 1-3 OH, R (16) , R (17), R (18), R (19) and R (20) hydrogen or (C-C3) alkyl; R (3) as defined R (l), or R (3) alkyl (C, -C6) or -X-R (22);
X oxygen, S or NR (16); R (16) H or alkyl (CrC3); or R (22) and R16) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R (22) is how R (14) has been defined; yes as its pharmaceutically compatible salts.
IHOE 92 / F 405 - EP 602,523, NZ 250,437) i) Benzoylguanidines of Formula I
NH,
where they mean: R (l) hydrogen, F, Cl, Br, I, -NO, -CaN, R (16) -C PH.2P-O, R (4) -SOm or R (5) R (6) N-S02-; m zero, 1 or 2; p zero or 1; q zero, 1, 2 or 3; R (16) CrF2r + 1; r 1, 2 0 3; R (4) and R (5) alkyl (CrC8), alkenyl (C3-C6), -CNH2n-R (7) n null, 1, 2, 3 or 4; R (7) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9); R (8) and R (9) H or alsuyl C.-C4; or R (5! H; R (6) H or (C4) alkyl; or R (5) and R (6) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by oxygen, S, NH, N-CH3 or N-benzyl, R (2) heteroaryl (C, -C9), which is bonded through C or N and is unsubstituted or substituted with 1-3 substituents selected from the group consists of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino, or R (2) -SR (10), -OR (10), -NR (10) R (11), -CR ( 10) R (11) R (12); R (10) -CaH2a-heteroaryl (C.-C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino, at zero, 1 or 2, R (ll) and R (12) independently of one another, as defined R (10) or hydrogen or alkyl (C, -C4) );
R (3) as defined R (l), or (C1-C6) alkyl or -X-R (13); X oxygen, S or NR (14); R (14) H or alkyl (C C3); R (13) H, alkyl (C, -C6), cycloalkyl (C3-Cfl) or -CbH2b-R (15); b zero, 1, 2, 3 or 4, - R (13) and R (14) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R (15) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9); R (8) and R (9) H or alkyl (C.-C4); as well as its pharmaceutically compatible salts;
(HOE 92 / F 411 - NZ 250,450, EP 603,650) k) Benzoylguanidines of Formula I
where they mean: one of the substituents R (l), R (2), R (3) or R (4l)
an amino group -
R (5) hydrogen or C (1.6) alkyl; n zero, 1, 2, 3 or 4; R (6) H or C (1.4) alkyl; wherein a CH2 group may be replaced by 1 S atom or by an NR group (7); R (7) hydrogen, methyl or ethyl; or R (6) C (3.8) cycloalkyl or phenyl, which is unsubstituted or carries 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, methyl, ethoxy, -NR (8) R (9) ); R (8) and R (9) H, methyl or ethyl; or R (5) and R (6) in common with the nitrogen atom a ring of 5, 6 or 7 members, in which 1 C atom can be replaced by oxygen, S or NR (10); R (10) H, C 1 -C 3 alkyl) or benzyl; and the respectively other substituents R (l), R (2), R (3), R (4): hydrogen, F, Cl, Br, I, CN, CF3, N02, CF3-0-, cmF2m + rCH2- ° - or RdD-C ^ -X ,, -; m 1, 2 0 3; q zero, 1, 2, 3 or; p zero or 1; X oxygen or NR (12); R (12) H or C (1.3) alkyl; R (ll) hydrogen, C (1.6) alkyl, C.3.8 cycloalkyl) or phenyl, which is unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, CH3, CH3-0- and NR (13) R (14); R (13) and R (14) H, methyl or ethyl; as well as its pharmaceutically compatible salts.
(HO? 92 / F 422 - EP 604,852) 1) Benzoylguanidms of Formula I
where they mean: R (DR (4) R (5) NC (X) -; X oxygen, S or NR (6), R (4) and R (5) same or different, H, alkyl (C, -CB) alkenyl (C3-Cfi) or -CpH2n • R (7; n null, 1, 2, 3 or 4; R (7I cycloalkyl (C5-C6 or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methoxy, and alkyl (C-C4);
R (4) and R (5) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R (6) as defined R (4) or amidine; R (2) H, F, Cl, Br, I, alkyl (C, -Ca), 1-alkenyl or 1-alkyl, cycloalkyl (C3-C8), cycloalkyl (C3-C8) -alkyl ( C.-C 4), phenyl, C 6 H 5 -alkyl (C, -C 4), naphthyl, biphenylyl, 1,1-d-phenyl-(C 1 -C 4) alkyl, cyclopentadienyl, pipdyl, thiopyridyl, pyrrolyl, furanyl, thienyl , thiazolyl, oxazolyl, mdenyl, qumol lo, indolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl or -WR (8); W oxygen, S or NR (9); R (8) H, alkyl (C, -C6), cycloalkyl (C5-C7), cyclohexylmethyl, cyclopentylmethyl, - (CH? Cp lO-CqH2q-R (10); m zero or 1, - p 1, 2 0 3; q zero, 1, 2, 3 or 4; R (10) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (11) R (12), -R (ll) and R (12) H or (C, -C4) alkyl, R (9) H or alkyl (CrC3), or R (8) and R (9) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, -R (3) H, F, Cl, Br, I, alkyl (C- -C6) or -R (8) as defined for R (2), as well as their pharmaceutically acceptable salts;
^ 93 / F 054 - NZ 250,919, EP-OS 612,723] m) Benzoylguanidmas of Formula I
where they mean: R (l), R (2), R (3) hydrogen, F, Cl, Br, I or alkyl (C.-C12) one of the substituents R (l), R (2) or R (3) N3, CN, OH or alkyloxy (C.-C10), when at least one of the remaining substituents R (l), R (2) or R (3) means a sufficiently lipophilic alkyl radical with 3 to 12 carbon atoms, -or one of the substituents R (l), R (2) or R (3) R (4) -CH, -O-; m zero or 1; n zero, 1, 2 or 3;
p 1, 2 0 3, as long as n is equal to zero or 1; or R (4) (C3-C12) cycloalkyl, phenyl, pyridyl, qumolyl or isoquinolyl, the aromatic and heteroaromatic ring systems being unsubstituted or substituted with a substituent selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (5) R (6); R (5) and R (6) hydrogen or (C-C4) alkyl; or one of the substituents R (l), R (2) or R (3) -C = CR (5) or -C [R (6)] = CR (5); R (5) phenyl, which is unsubstituted or substituted by 1-3 substituents between the group consisting of F, Cl, CF3, methyl, methoxy, hydroxy, animo, methylamino and dimethylammo, heteroaryl (C-C9), which it is unsubstituted or substituted as phenyl; or R (5) alkyl (C.-C6), which is unsubstituted or substituted with 1-3 OH;
R (5) cycloaiquiio (C3-C8), R (6) hydrogen or methyl; as well as its pharmacologically acceptable salts;
(93 / F 153 - EP-OS 627,413, NZ 260,660) o) Benzoylguanidines of Formula I
where they mean: R (l) hydrogen, F, Cl, Br, I, -N02, • C. * N. X "[CH. • CF, R (5) • som, R (6; -co- or R (6) R (7) N-S02-, with X oxygen, S or NR (14 m zero, 1 or 2, or zero or 1; P zero, 1 or 2; q zero, 1, 2, 3 4, 5 or 6; R (5) and R (6) alkyl (C ^ -8) alkenyl: c3-c6) -cnH2n-R ( 8; CF3; n zero, 1, 2, 3 or 4; R (8) cycloalkyl (C3-C7 or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3 , methyl, methoxy and NR (9) R (10); R (9) and R (10) H or C 1 -C 4 alkyl;
R (6) H; R (7) H or alkyl (C C4); or R (6) and R (7) in common 4 or 5 full met groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl,
C) h- (CHOH), - (CH2), - (CHOH) k -R (l 1)
(C) h- (CHOH), - (CH2), - (CHOH) k -R (l 1)
(C) "- (CHOH), - (CH2), - (CHOH) k -R (11)
And oxygen, -S- or -NR (12); R (ll) and R (12) hydrogen or alkyl (C.-C3); h zero or 1; i, j and k independently zero, 1, 2, 3 or 4; but not being h, 1 and k simultaneously zero, R (3) as defined R (l) or alkyl (C.-C6) or -XR (13); X oxygen, S or NR (14); ) H or alkyl (C ^ Cj), R (13) H, (C1-C6) alkyl, cycloalkyl (Cj-C8) or "CbH2b" R 15) b zero, 1, 2, 3 or 4; or R (13) and R (14) in common 4 or 5 methylene groups, whereby a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, R (15) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10); R (9) and R (10) H or alkyl (C.-C); R (4) hydrogen, -0R (16) or -NR (16) R (17); R (16) and R (17) independently hydrogen or alkyl (C.-C-.), As well as their salts armaceutically compatible;
(HOE 93 / F 154 - EP-OS 628,543, NZ 260,681) p) Benzoylguanidines of Formula I
where they mean: R (l) R (6) -CO or R (7) R (8) N-CO; R (6) alkyl (C.-C8), perfluoroalkyl (C ^ Cg), alkenyl (C3-C8) or -CnH2n-R (9); n zero, 1, 2, 3 or 4; R (9) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR ( ) R (11); R (10) and R (ll) H, alkyl (C.-C4) or perfluoroalkyl (C1-C4); R (7) H, (C, -C8) alkyl, perfluoroalkyl (0, -C8), (C3-C8) alkenyl or -CnH2n-R (12); n zero, 1, 2, 3 or 4; R (12) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (13 ) R (14), - R (13) and R (14) H, alkyl (C.-C4) or perfluoroalkyl (C1-C4); R (8) H, alkyl (C.sub.4 -C) or perfluoroalkyl (C.sub.1 -C.sub.4); or R (7) and R (8) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R (2) as defined R (l), or H, F, Cl, Br, I, CN, N02, alkyl (C.-C8), perfluoroalkyl (C.-C8), alkenyl (C3-C8) or -CnH2p-R (15); n zero, 1, 2, 3 or 4; R (15) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (16 ) R (17); R (16) and R (17) H, (C 1 -C 4) alkyl or β-perfluoroalkyl (C, -C 4); or R (2) heteroaryl (C.-C9), which is bonded through C or N and is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy , hydroxy, amino, methylamino and dimethylammo; or R (2) -SR (18), -OR (18), -NR (18) R (19), -CR (18) R (19) R (20); R (18) -CaH2a-heteroaryl (C.-C9), which is substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamine and dime ilamino; to zero, 1 or 2; R (19) and R (20) independently of one another as defined R (18) or hydrogen, alkyl (C ^ -C ^) or perfluoroalkyl (C.C4); or R (2) R (21) -SOm or R (22) R (23) N-S02; m 1 or 2; R (21) alkyl (C.-C8), perfluoroalkyl (C -.- C8), alkenyl (C3-C8), -CNH2n-R (24), n-zero, 1, 2, 3 or 4; R (24) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals SM being substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (27 ) R (28); R (27) and R (28) H, (C4) alkyl or perfluoroalkyl (C.-C4);
R (22) H, alkyl (C.-C8), perfluoroalkyl (C6-C8), alkenyl (C3-C8), -CnH2n-R (29); n zero, 1, 2, 3 or 4; R (29) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR ( ) R (31); R (30) and R (31) H, (C 1 -C 4) alkyl or perfluoro (C 1 -C 4) alkyl; R (23) H, (C-C4) alkyl or perfluoro (C 1 -C 4) alkyl; or R (22) and R (23) in common 4 or 5 methylene groups, of which a group of CH 2 can be replaced by oxygen, S, NH, N-CH 3 or N-benzyl; or R (2) R (33) X-; X oxygen, S, NR (34), (D = 0) A-, NR (34) C = MN (* R (35) -; M oxygen or S; Oxygen or NR (34); DC or SO; R (33) (C-C8) alkyl, (C3-C8) alkenyl, (CH2) bCdF2d + 1, -CnH2n-R (36); b zero or 1; d 1, 2, 3, 4, 5, 6 0 7; n null, 1, 2, 3 or 4; R (36) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group it consists of F, Cl, CF3, methyl, methoxy and NR (37) R (38);
R (37) and R (38) H, (C 1 -C 4) alkyl or perfluoroalkyl (C, -C 4); R (34) H, alkyl (C.-C4) or perfluoroalkyl (C1-C4), R (35) is defined as R (33); or R (33) and R (34) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH *. or N-benzyl; wherein A and (W> are attached to the phenyl nucleus of the fundamental framework of benzoylguanidine, or R (2) -SR (40), -OR (40), -NHR (40), -NR (40) R (41) , -CHR (40) R (42), -C [R (42) R (43) OH], -C = CR (45), -CR (46) = CHR (45), - [CR (47) R (48)] u- (CO) - [CR (49) R (50)] VR (44); R (40), R (41) same or different - (CH2) - (CHOH) q- (CH2 ) r- (CHOH) tR (51) or - (CH2) p-0- (CH2-CH20) qR (51); R (51) hydrogen or methyl; or 1, 2, 3 0 4; v zero, 1 , 2, 3 or 4, P. q, r equal or different zero, 1, 2, 3 or 4, t 1, 2, 3 or 4, R (42) and R (43) equal or different hydrogen or alkyl ( C.-C6), or R (42) and R (43) in common with the carbon atom carrying them, form a cycloalkyl (C3-C8), R (44) H, alkyl (C * -C6), cycloalkyl (C3-C8) or -CeH2e-R (45); e zero, 1, 2, 3 or 4;
R (45) equal to phenyl, which is unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy and NR (52) R (53), with R (52) and R (53) equal to H or (C 1 -C 4) alkyl or R (45) heteroaryl (C, -C 9), which is unsubstituted or substituted the same as phenyl; or R (45) alkyl (C, -C6), which is unsubstituted or substituted with 1-3 OH; R (46), R (47), R (48), R (49) and R (50) hydrogen or methyl; or R (2) R (55) -NH-S02-; R (55) R (56) R (57) N- (C = Y) -; And oxygen, S or N-R (58); R (56) and R (57) equal or different H, (C-C8) alkyl, (C3-C6) alkenyl or -CfH2f-R (59); f zero, 1, 2, 3 or 4; R (59) (C5-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methoxy and alkyl (C * -C4); or R (56) and R (57) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R (58) is defined as R (56) or amidine; R (3), R (4) and R (5) independently of one another, as defined R (1) OR R (2); and their pharmaceutically compatible salts.
(HOE 93 / F 220 - EP-OS 640,593, NZ 264,117) q) Benzoylguanid ace of Formula I
where they mean: R (l) hydrogen, F, Cl, Br, I, -N02, -C = N, -XQ- (CH2) - (CF2) q-CF3, R (5) -SOm-, R (6) -CO-, R (6) R (7) N-CO- OR R (6) R (7) N-S02-; X oxygen, -S- or NR (14); m zero, 1 or 2; or zero or 1; p zero, 1 or 2, - q zero, 1, 2, 3, 4, 5 or 6; R (5) and R (6) alkyl (C, -Ca), alkenyl (C3-C6), -CnH2n-R (8) or CF3; n zero, 1, 2, 3 or 4; R (8) (C3-C7) cycloalkyl, phenyl, which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10); R (9) and R (10) H or (C 1 -C 4) alkyl; or R (6) hydrogen, - R (7) hydrogen or (C-C4) alkyl; or R (6) and R (7) in common 4 or 5 metlene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R (2!
- Y - R < "> ° < p) & ~« Q- R (11) - AND Y -
R (ll) heterolalk (0, -0,), which is bonded through C or N and is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino, dimethylamino and benzyl; And oxygen, -S- or NR (12); R (12) H or alkyl (C.-C4); R (3) as defined R (l); or R (3) alkyl (C.-C6) or -X-R (13); X oxygen, -S- or NR (14); R (14) H or alkyl (CrC3); RR ((1133)) HH ,, aallqquiilloo (< Cc., - "C6, cycloalkyl (C, -C8) or _CbH2b" - R (15); b zero, 1, 2, 3 OR - OR (13 ) and R (14) in common 4 or 5 metlene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl;
R (15) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, ethoxy and NR (9) R (10); R (9) and R (10) H or (C 1 -C 4) alkyl; R (4) hydrogen, -OR (16), -NR (16) R (17) or CrF2r + 1; R (16) and R (17) independently hydrogen or alkyl (C.-C3); r 1, 2, 3 0 4; as well as its pharmaceutically compatible salts;
(HOE 93 / F 223 K - EP 639,573, NZ 264,130) r) Heterocycles with 5-membered rings condensed with benzo of Formula I
where they mean: N or CR (6); oxygen, S or NR (7); in common a link
i both hydrogen, provided that simultaneously X equals CR (6) and Y equals NR (7); one of the substituents R (1) to R (6) a group -CO-N = C (NH 2) 2; the respectively other substituents R (l) to R (6) hydrogen, F, Cl, Br, I or alkyl (C, -C6);
up to two of the other substituents R (l) to R (6) CN, N02, N3, alkyloxy (CrC4) or CF3; to one of the other substituents R (8) -CnH2n-Z-; n from zero to 10; the linear or branched alkylene chain -CnH2n- being and a C atom being able to be displaced by an oxygen or S atom or by an N atom; R (8) hydrogen, (C2-C6) alkenyl or (C3-C10) cycloalkyl, which is unsubstituted or substituted with 1 to 4 methylene groups or an OH group, or may contain an ethylene group -CH = CH-, and wherein a methylene group can be replaced by an oxygen atom or S or by an N atom; or R (8) phenyl, sm substituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, CF3, CH3-S (0) s or R (9) -Wy-; s zero, 1 or 2, - R (9) H, methyl, ethyl, W oxygen or NR (10); R (10) H or methyl; and zero or 1; or R < 8 > Cmp2m + 1'- m from 1 to 3; or R (8) 1- or 2-naphthyl, pipdoyl, quinolyl or isocmolyl; Z -CO-, -CH2- OR - [CR (11) 0H] -; q 1, 2 0 3; R (ll) H or methyl;
or Z oxygen or -NR (12); R (12) H or methyl; or Z -S (0) -; zero, 1 or 2; or Z -S02-NR (13) R (13) H or alkyl (C * -C4); R (7) hydrogen, alkyl (C.-C10), alkenyl (C2-C10) or
R (8) -CnH2n-; as well as its pharmaceutically compatible salts;
(HOE 93 / F 236 - EP-OS 638,548, NZ 264,216) s) Benzoylguanid ace of Formula I
where they mean: R (l), R (3) or R (4) -NR (6) C = X NR (7) R (IX oxygen or S; R (6) hydrogen, alkyl (C ^ Cg) , perfluoroalkyl (C, -C8), (C3-C8) alkenyl or -CnH2n-R (9): n, 1, 2, 3 or 4; R (9) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (10) R (11); R (10) and R (ll) H, (C, -C4) alkyl or (C1-C4) perfluoroalkyl; R (7) hydrogen, (C, -C8) alkyl, perfluoroalkyl (C.-C8), (C3-C8) alkenyl or -C0H2o-R (12), or zero, 1, 2, 3 or 4, R (12) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of group consisting of F, Cl, CF 3, methyl, methoxy and NR (13) R (14); R (13) and R (14) H, (C 1 -C 4) alkyl or perfluoro (C 1 -C 4) alkyl; 8) is defined as R (7), or R (7) and R (8) in common 4 or 5 groups of methylene, of which a CTL group may be replaced by oxygen, S, NH, N-CH3 or N-benzyl; the remaining substituents R (2), R (3), R (4), R (5) OR R (1), R (2), R (4), R (5) OR R (1), R (2), R (3), R (5) independently of one another, hydrogen, F, Cl, Br, I, -Ota-alkyl (C * -C8), -Ott > -alkenyl (C3-C8), - ° tc (CH2> bCdF2d + i '-OtdCpH2pR (18), or up to 2 groups CN, N02, NR (16) R (17), b zero or 1, - d 1 , 2, 3, 4, 5, 6 0 7, ta zero or 1, tb zero or 1;
tc zero or ^, td zero or 1, - P zero, 1, 2, 3 or 4, R (18) cycloalkio (C3-C8 phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents - selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (19) R (20); R (19) and R (20) hydrogen or (C1-C4) alkyl or perfluoroalkyl (C1-) C4), R (16) hydrogen, alkyl (C.-C8), perfluoroalkyl (C.-C8), alkenyl (C3-C8), -CqH2q-R (21), q zero, 1, 2, 3 or 4 R (21) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy or NR (22) ) R (23), R (22) and R (23) hydrogen, (C 1 -C 4) alkyl or perfluoroalkyl (C 1 -C 4); R (17) hydrogen, alkyl (C.-C8), perfluoroalkyl (Cj-C8) ), (C3-C8) alkenyl, -CrH2r-R (24), r zero, 1, 2, 3 or 4; R (24) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being s unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (25) R (26);
R (25) and R (26) hydrogen, (C 1 -C 4) alkyl or perfluoro (C 1 -C 4) alkyl;
R (16) and R (17) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, as well as their pharmaceutically compatible salts;
(HOE 93 / F 249 -? P-OS 640,587, NZ 264,282) t) Guanidmas substituted with diacyl of the Formula I
in which they mean: X (l) and X (2)
TI zero, 1, 2, 3 or 4; R (A) and R (B) independently hydrogen, F, Cl, Br, I, CN, OR (106), alkyl (0., - C8), cycloalkyl (C3-C8), ° Zk (CH2) 2zlCzmF2zm + i 'NR (107) R (108), phenyl or benzyl, the aromatic radicals sm being substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (109 R (110), -R (109) and R (110) hydrogen, (C * -C4) alkyl or perfluoro (C 1 -C 4) alkyl; zl zero, 1, 2, 3 or 4; zk zero or 1; zm 1, 2, 3, 4, 5, 6, 7 or 8; R (Hydrogen 106, alkyl (C.-C8), perfluoroalkyl (C, -C8), (C3-C8) alkenyl, (C3-C8) cycloalkyl, phenyl or benzyl, the aromatic radicals being unsubstituted or substituted by 1- 3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (111) R (112); R (lll) and R (112) hydrogen, (C, -C4) alkyl or perfluoroalkyl (C) - C4), R (107) and R (108) independently of one another are defined as R (106) or R (107) and R (108) in common 4 or 5 methylene groups, of which a CH2 group it may be replaced by oxygen, S, NH, N-CH3 or N-benzyl;
X (l) and X (2)
T2a and T2b independently of one another zero, 1 or 2; the double bond being able to be configured (E) (Z) x (i) and x (2;
R R (U1)
T3 zero, 1 or 2; U, YY and Z independently of each other C or N, being able to carry U, YY, Z the following numbers of substituents:
R (D) hydrogen, (C * -C8) alkyl or perfluoroalkyl (C * -C8), R (U1), R (U2), R (Y1), R (Y2), R (Z1), R (Z2) ) independently of one another hydrogen, F, Cl, Br, I, CN, OR (114), alkyl (C.-C8), cycloalkyl (C3-C8),
Zka (CH2) ztaCzmaF2zma + i 'NR (115) R (116), phenyl or benzyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy, NR (117) R (118), R (117) and R (118) hydrogen, alkyl (C.-C4) or perfluoroalkyl (C, -C4), zka zero or 1, -zla cerc, 1 , 2, 3 or 4; zma 1, 2, 3, 4, 5, 6, 7 or 8; R (114) hydrogen, alkyl (C.-C8), perfluoroalkyl (C * -C8), alkenyl (C3-C8), cycloalkyl (C3-C8), phenyl or benzyl, the aromatic radicals being unsubstituted or substituted -3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (119) R (120); R (119) and R (120) hydrogen, (C, -C 4) alkyl or perfluoro (C 1 -C 4) alkyl; R (115) and R (116) independently of one another, as defined R (114); or R (115) and R (116) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; however, the constitution of U equal to nitrogen (N), YY equal to nitrogen (N) and Z equal to carbon (C),, R (102), R (103), R (104) and R (105) is excluded. ) independently of each other, F, Cl, Br, I, -C == N,
Xzoa- < CH2 > zpa- < CzqaF2Zqa + 1 > 'R < 110a > ~ SOz ^ R (110b) R (110c) N-CO, R (llla) -C0- or R (112a) R (113a) N-S02-, the linear or branched perfluoroalkyl group, X oxygen, S or NR (114a); R (114a) H or alkyl (0, -03);
zoa zero or 1, - zbm zero, 1 or 2; zpa zero, 1, 2, 3 or 4; zqa 1, 2, 3, 4, 5, 6, 7 or 8; R (110a), R (li? B), R (llla) and R (112a) independenalkyl (C ^ Cg), alkenyl (C3-C8), -CznH2zn-R (115a) or perfluoroalkyl (C ^ Cg); zn zero, 1, 2, 3 or 4; R (115a) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR ( 116a) R (117a); R (116a) and R (117a) hydrogen, perfluoroalkyl (C 1 -C 4) or alkyl (C, -C 4); or R (110b), R (llla) and R (112a) hydrogen; R (ll? C) and R (113a) independenhydrogen, perfluoroalkyl (C1-C4) or alkyl (C, -C4); or R (110b) and R (ll? c) as well as R (112a) and R (113a) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N- CH3 or N-benzyl; or R (101), R (102), R (103), R (104), R (105) independenof each other, alkyl (C.-C8), -CzalH2zalR (118a) or alkenyl (C3-C8) , zal zero, 1, 2, 3 or 4; R (118a) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals SM being substituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy or NR (119a) R (119b); R (119a) and R (119b) hydrogen, (C 1 -C 4) alkyl or perfluoro (C 1 -C 4) alkyl; or R (101), R (102), R (103), R (104), R (105) independenof each other, heteropole (C.-C9), which is linked through C or N and is sm substituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; or R (101), R (102), R (103), R (104), R (105) independenof each other -C = C-R (193); R (193) phenyl, which is unsubstituted or substituted with 1-3 its isomers taken between the group consisting of F, Cl, CF3, methyl, methoxy or NR (194) R (195); R (194) and R (195) hydrogen or CH3; or R (101), R (102), R (103), R (104), R (105) independenof each other -Y-for-C6H4- (CO) zh- (CH0H) Z1- (CH2)? J- (CHOH) z | cR (123), - Y-meta-C6H4- (CO) zad- (CHOH) zae- (CH2) zaf- (CHOH) zag-R (124) or -Y-ortho-C6H4 - (CO) zah- (CHOH) zaQ- (CH.,) Zap- (CHOH) zak-R (125);
And oxygen, -S- or -NR (122d) -; zh, zad, zak independenzero or 1; zi, zj, zk, zae, zaf, zag, zao, zap and zak independenzero, 1, 2, 3 or 4; not being however in each case zh, zi and zk at the same time zero, not being zad, zae and zag at the same time zero, and not being zah, zao and zak at the same time zero, R (123), R (124 ), R (125) and R (122d) independenhydrogen or (C, -C3) alkyl; or R (101), R (102), R (103), R (104) and R (105) independenof each other -SR (129), -OR (130); -NR (131) R (132) or -CR (133) R (134) R (135); R (129), R (130), R (131) and R { 133) independen-CazabH2zab-heteroaplo (C, - ^), which is unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamine and dimethylamine, - zab zero, 1 or 2; R (132), R (134) and R (135) independenof one another as defined R (129) or hydrogen, (C-C4) alkyl or perfluoro (C 1 -C 4) alkyl; or R (101), R (102), R (103), R (104) and R (105) independenof each other - -para- (C6H4) -R (196), -W-meta- (C6H4) -R (197) or -W-ortho- (C¿H4) -R (198); R (196), R (197) and R (198) independenheteroaryl (0, -0,), which is bonded through C or N and is either substituted or substituted with 1 to 3 its isomers taken between the group which consists of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamino, dimethylamino and benzyl;
oxygen, S or NR (136) -, - R (136) hydrogen or alkyl (C.-C4); or R (101), R (102), R (103), R (104) and R (105) independenof each other R (146) X (la) -; X (the) oxygen, S, NR (147), (D = 0) A-, NR (148) C = MN (*> R (149) -; M oxygen or sulfur; Oxygen or NR (150); DC or SO; R (146) alkyl (C.-C8), alkenyl (^ -8), (CH2> zbzCzdzF2zdz + 1 O - 2zxaH2zxa - R (1 5 1) '- zbz zero or 1; Zdz 1 , 2, 3, 4, 5, 6, 6, 1, zxa zero, 1, 2, 3 or 4, R (151) cycloalkyl (C3-C8), phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy and NR (152) R (153); R (152) and R (153) hydrogen, alkyl (C.-C4) or perfluoroalkyl (C.-C4); R (147), R (148) and R (150) independently hydrogen, alkyl (C.-C4) or perfluoroalkyl (C-C4); R (149) is defined as R (146 ), or R (146) and R (147) or R (146) and R (148) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N- CH3 or N-benzyl;
where A and N (* 5 are attached to the phenyl nucleus of the fundamental alkanoyl framework, or RÍ101), R (102), α (103), R (104) and R (105) independently of one another, -SR (164 ), -OR (165), -NHR (166), -NR (167) R (168), -CHR (169) R (170), -CR (154) R (155) OH, -CSCR (156) , -CR (158) = CR (157) or - [CR (159) R (160)] zu (C = 0) - [CR (161) R (162) ZV-R (163); R (164), R (165), R (166), R (167), R (169) equal or different - (CH2) zy- (CHOH) zz- (CH2) zaa- (CHOH) It-R ( 171) OR - (H2) zab-0- (CH2-CH2 °) zac-R (172) 'R (171) and R (172) hydrogen or methyl; zu 1, 2, 3 or 4; zv zero, 1, 2, 3 or 4; zy, zz, zaa, zab, zac equal or different zero, 1, 2, 3 or 4; zt 1, 2, 3 or 4; R (168), R (170), R (154), R (155) same or different hydrogen or alkyl (C ^ Cg) or R (169) and R (170) or R (154) and R (155) ) in common with the carbon atom that carries them, a (C3-C8) cycloalkyl; R (163) hydrogen, alkyl (C.-C6), cycloalkyl (C3-Cfl)
° -ze-Hze-R (173) '- zeb zero, 1, 2, 3 or 4; R (156), R (157) and R (173) independently phenyl which is unsubstituted or substituted with 1-3 substituents taken between the group consisting of F, Cl, CF3, methyl, methoxy and NR (174) R ( 175); R (174) and R (175) hydrogen or alkyl (C.-C4);
or R (156), R (157) and R (173) independently heteroaryl (C. ~ C9), which is unsubstituted or substituted the same as phenyl; R (158), R (159), R (160), R (161) and R (162) hydrogen or methyl, or R (101), R (102), R (103), R (104), R (105) independently of one another R (176) -NH-S02-; R (176) R (177) R (178) N- (C = Y ') -; Y 'oxygen, S or N-R (179); R (177) and R (178) equal or different from hydrogen, alkyl (C.-C8), alkenyl (C3-C6) or -faH2zfa-R (180> -zfa zero, 1, 2, 3 or 4; R (180) (C5-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methoxy or alkyl (C.-C4), or R ( 177) and R (178) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl, R (179) as defined R (177) or equal to amidine, or R (101), R (102), R (103), R (104), R (105) independently of each other NR (184a) R (185), OR (184b) ), SR (184c) or -Czn? H2zn? -R (184d); znx zero, 1, 2, 3 or 4; R (184d) cycloalkyl (C3-C7) or phenyl, which is unsubstituted or substituted by 1; -3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy and NR (116k) R (117k); R (116k) and R (117k) hydrogen or C-C4 alkyl; R (184a) , R (184b), R (184c), R (185) independent hydrogen, alkyl (C, -C8), perfluoroalkyl (C.-C8) or (CH > zao-R (1849) 'zero, 1, 2, 3 or 4; R (184g) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy and NR (184u) R (184v); R (184u) and R (184v) hydrogen or C 1 -C 4 alkyl; or R (184a) and R (185) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CHj or N-benzyl; as well as its pharmaceutically compatible salts;
(HOE 93 / F 254 - EP-OS 640,588, NZ 264.307) u) Benzoylguanidines of Formula I
wherein they mean: R (l) H, F, Cl, Br, I, CN, NO, alkyl (C.-C "8, '(C3-C8) cycloalkyl or Xa-CH', 2) 'b - (CF,) -CF, X oxygen, S or NR (5), at zero or 1, - b zero, 1 or 2; c zero, 1, 2 or 3; R (5) H, alkyl (C. -C or CdH2dR (6); d, 1, 2, 3 or 4; R (6) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1 to 3 substitutes; selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (7) R (8), R (7) and R (8) independently H or alkyl (C.-C4), or R ( l) -SR (10), -OR (10) or -CR (10) R (11) R (12); R (10) -CfH2f-cycloalkyl (C3-C8), heteroaryl (C, -C9) or phenyl, the aromatic systems being unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamine and dimethylamino; f zero, 1 or 2, - R (ll) and R (12) independently of one another as defined R (10) or hydrogen or alkyl (C.-C4); or R (l) phenyl, naphthyl, biphenylyl or heteroapel (C.-C9), the latter linked through C or N, and which are unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF 3, CH 3, methoxy, hydroxy, ammo, methylamino and dimethylamino; or R (l) -SR (13), -OR (13), -NH (13), -NR (13) R (14), -CHR (13) R (15), -C [R (15) R (16)] OH, -C = CR (18), -C [R (19)] = CR (18), - [CR (20) R (21)] k- (CO) - [CR (22 ) R (23) R (24)] t R (13) and R (14) equal or different - (CH 2) g- (CHOH) h- (CH 2), - (CHOH) R (17), R (17 ) hydrogen or methyl; - (CH2) g-0- (CH2-CH20) h-R (24), g, h, i equal or different zero, 1, 2, 3 or 4; 3 1, 2, 3 0 4; R (15) and R (16) same or different hydrogen, alkyl (C.-C6) or, in common with the carbon atom carrying them, a (C3-C8) cycloalkyl; R (18) phenyl, which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (25) R (26); R (25) and R (26) H or 'C * c4 alkyl) or R (18) heteroaryl (C * -C9), which is unsubstituted or substituted as phenyl, - or R (18) alkyl (C C6) , which is unsubstituted or substituted with 1 to 3 OH; or R (18) cycloalkyl (C3-C8); R (19), R (20), R (21), R (22) and R (23) hydrogen or methyl; k zero, 1, 2, 3 or 4; 1 zero, 1, 2, 3 or 4; R (24) H, alkyl (C, -C6), cycloalkyl (C3-C8) or -raH2m-R < 1 8 >; m 1, 2, 3 0 4; R (2 and R (3) independently of one another as defined
R (l); R (4 alkyl (C, -C3), F, Cl, Br, I, CN or - (CH2) p- (CF2) Q-CF3; n zero or 1; or zero, 1 or 2, as well as their salts pharmaceutically compatible;
(HOE 93 / F 436 - EP-OS 659,748, NZ 270,264) v) Acylguanidines of Formula I
where they mean:
X carbonyl, sulfonyl, R (l) H, alkyl (CrC8), unsubstituted or substituted by hydroxy, (C3-C8) cycloalkyl, phenyl, which is unsubstituted or substituted by 1-3 substituents taken from the group consisting of F , Cl, CF3, CH3, methoxy, hydroxy, arrimo, methylamino or dimethylamino, R (2) H, alkyl (C, -C4), as well as their pharmaceutically compatible salts;
(HOE 94 / F 014 K-EP-OS 666,252, NZ 270,370)) Guanidides of phenyl-substituted alkylcarboxylic acids, carriers of perfluoroalkyl groups of the Formula I
where they mean: R (A) hydrogen, F, Cl, Br, I, CN, OR (6), alkyl (C * -C8), cycloalkyl (C3-C8), 0p (CH2) gCbF2b + 1 OR NR (7) R (8); r zero or 1; to zero, 1, 2, 3 or 4; b 1, 2, 3, 4, 5, 6, 7 or 8; R (6) hydrogen, alkyl (C ^ Cg), alkenyl (C3-C8), cycloalkyl (Cz-C &), phenyl or benzyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10);
R (9) and R (10) H, (C1-C4) alkyl or perfluoroalkyl (C.-C4); R (7) and R (8) independently of one another, as defined R (6); R (B) independently as defined R (A); X 1, 2 0 3; R (l) hydrogen, alkyl (C.-C8), cycloalkyl (C3-C8), - ^^ "i ^^ ze + i 'F' C1 'Br' t ° CN; t zero or 1, - d zero , 1, 2, 3 or 4, e 1, 2, 3, 4, 5, 6, 7 or 8, R (), R (3), R () and R (5) independently of each other, as Has defined
R (l); but with the proviso that at least one of the substituents R (l), R (2),
R (3), R (4), R (5), R (A) and R (B) are a group -0. { (CH2) dCeF2e + 1 or a group -0p (CH2) aCbF2b + 1, as well as their pharmaceutically compatible salts;
(HOE 94 / F 094 - EP-OS 676,395, NZ 270,894) x) Heteroaroylguanidines of Formula I
where they mean: HA SOm, O or NR (5); m zero, 1 or 2; R (5) hydrogen, alkyl (C.-Cg) or -CamH2ap] R (81), -am, zero or 1; R (81) (C3-C8) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, ethoxy and NR (82) R (83); R (82) and R (83) H or CH3; or R (81) hetero- tile (0, -0,), which is linked through C or N and is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3 , methoxy, hydroxy, arrimo, methylamine and dimethylamino; anus of the substituents R (1) and R (2) -CO-N = C (NH 2) 2; and the respectively another substituent hydrogen, F, Cl, Br, I, alkyl (C.-C3), -0R (6), -CrH2r + 1, -CO-N = C (NH2) 2 or NR (6) R (7); R (6) and R (7) independently hydrogen or alkyl (C.-C3); r 1, 2, 3 or 4; R (3) and R (4) independently of one another hydrogen, F, Cl, Br, I, -C = N, X- (CH2) p- (Cq-F2q + 1), R (9) R (10 ) N-CO-, R (ll) -CO or R (12) R (13) N-S02-, the linear or branched perfluoroalkyl group, X oxygen, S or NR (14); R (14) H or alkyl (C, -C3); bm zero, 1 or 2; p zero, 1 or 2; q zero, 1, 2, 3, 4, 5 or 6; R (8), R (9), R (ll) and R (12) independently alkyl (C.-C8), alkenyl (C3-C6), -CnH2n-R (15), CF3; n zero, 1, 2, 3 or 4; R (15) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy or NR (16) R (17); R (16) and R (17) H or alkyl (C * -C4); or R (9), R (ll) and R (12) H; R (10) and R (13) independently H or alkyl (C.-C4); or R (9) and R (10) as well as R (12) and R (13) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, or R (3) and R (4) independently of one another alkyl (C.-C8) or '- alH2alR (18)' - at zero, 1 or 2; R (18) (C3-C8) cycloalkyl or phenyl; which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (19) R (20); R (19) and R (20) H or CH3; or R (3) and R (4) independently of each other heteroaryl (C, -C9), which is linked through C or N and which is substituted or unsubstituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino;
R (3)) and R (4) independently of each other
-Y- < f V (C) "- (CHOH), - (CH2), - (CHOH) k -R (23) - (C) od- (CHOH) 0, - (CH2) af- (CHOH) -R (24)
-Y
). "- (CHOH), .- (CH2) 0 p- (CH0H) ok-R (25)
And oxygen, -S- or -NR (22) -; h, ad, ah independently zero or 1, - i,, k, ae, af, ag, ao, ap and ak independently zero, 1, 2, 3, 4, however not being in each case h, i and k simultaneously zero, not being ad, ae and ag simultaneously zero, as well as not being ah, ao and ak simultaneously zero, R (23), R (24), R (25) and R (22) independently hydrogen or alkyl (C-C3) ); or R (3) and R (4) independently of one another hydrogen, F, Cl, Br, I, CN, alkyl (C.-C8), perfluoroalkyl (0, -C8), alkeyl (C3-C8) or -CH2gR (26); g zero, 1, 2, 3 or 4; R (26) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (27) R (28); R (27) and R (28) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); or P (3) and R (4) independently of one another -SR (29), -OR (30), -NR (31) R (32) OR -CR (33) R (34) R (35); R (29), R (30), R (31) and R (33) independently -CaH2a-heteroaryl (C-C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamine; to zero, 1 or 2; R (32), R (34) and R (35) independently of one another, as defined R (29) or hydrogen, alkyl (C.-C4) or perfluoroalkyl (^ -C); or R (3) and R (4) independently of each other
R (96), R (97) and R (98) independently heterolalk (C.-C9), which is linked through C or N and which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF 3, CH 3, methoxy, hydroxy, ammo, methylamo, dimethylamino or benzyl; W oxygen, S or NR (36) -: R (36) H or alkyl (C.-C4); or R (3) and R (4) independently of each other R (37) -SOcm or R (38) R (39) N-S02-; cm 1 or 2; R (37) (C-C8) alkyl, perfluoroalkyl (0, -C8), (C3-C8) alkene or -CSH2¡.R (40); s zero, 1, 2, 3 or 4; R (40) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (41 ) R (42); R (41) and R (42) H, alkyl (C.-C4) or perfluoroalkyl (C1-C4); R (38) H, alkyl (C.-C8), perfluoroalkyl (C, -C8), alkenyl (C3-C8) or -CwH2w-R (43); w zero, 1, 2, 3 or 4; R (43) c-chloroalkyl (C3-C8), phenyl, biphenylyl or naphthyl, the aromatic radicals SM being substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl , methoxy and NR (44) R (45); R (44) and R (45) H, (C, -C4) alkyl or perfluoroalkyl (C * -C4); R (39) H, (C, -C4) alkyl or perfluoroalkyl (C-C4); or R (38) and R (39) in common 4 or 5 metlene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; or R (3) and R (4) independently of one another R (46) X (1) -, - X (l) oxygen, S, NR (47), (D = 0) A-, NR (48) C = MN (* 5R (49) -, M oxygen or S, - A oxygen or NR (50), DC or SO; R (46) alkyl (C.-C8), alkenyl (C3-C8), (CH2 ) bCdF2d + 1 or -C? H2? -R (51); b zero or 1, - d 1, 2, 3, 4, 5, 6 0 7; x zero, 1, 2, 3 or 4; R ( 51) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (52) R (53); R (52) and R (53) H, (C, -C4) alkyl or perfluoroalkyl (C * -C4); R (47), R (48) and R (50) independently hydrogen, alkyl ( C-C4) or perfluoroalkyl (C, -C4); R (49) is defined as R (46); or R (46) and R (47) or R (46) and R (48) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, where A and (*.) are attached to the core of the fundamental network the b enzoilguanid a;
or R (3) and R (4) independently of each other -SR (64), -OR (65), -NHR (66), -NR (67) R (68), -CHR (69) R (70) ), -C (OH) R (54) R (55), -C = CR (56), -CR (58) = CR (57), - [CR (59) R (60)] u- (CO ) - [CR (61) R (62)] vR (63); R (64), R (65), R (66), R (67) and R (69) equal or different - (CH2) and- (CHOH) z- (CH2) aa- (CH20) tR (71) or - (CH2) ab-0- (CH2-CH20) ac-R (72), R (71) and R (72) hydrogen or methyl; u 1, 2 3 or 4; V zero 1, 2, 3 or 4; Yy-, zz, aa equal or different zero, 1, 2, 3 or 4; t 1, 2, 3 or 4; R (68), R (70), R (54) and R (55) same or different hydrogen, alkyl (C.-C6); or R (69) and R (70) or R (54) and R (55) in common with the carbon atom carrying them, a (C3-C8) cycloalkyl; R (63) H, (C 1 -C 6) alkyl, (C 3 -C 8) cycloalkyl or -CeH 2e-R (73); e zero, 1, 2, 3 or 4; R (56), R (57) and R (73) independently phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (74) R (75); R (74) and R (75) H or alkyl (C, -C4); or R (56), R (57) and R (73) independently heterolalk (C.-C9), which is unsubstituted or substituted as phenyl; R (58), R (59), R (60), R (61) and R (62) hydrogen or methyl, or R (3) and R (4) independently of each other R (76) -NH-S02 -; R (76) R (77) R (78) N- (C = Y ') -; Y 'oxygen, S or N-R (79); R (77) and R (78) equal or different H, alkyl (C.-C8), alkenyl (C3-Cfi), -CfH2f-R (80); f zero, 1, 2, 3 or 4; R (80) cycloalkyl (C $ -C7) or femlo, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methoxy and (C-C4) alkyl; or R (77) and R (78) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, NH-CH3 or N-benzyl, R (79) is as has defined R (77) or equal to amidine; or R (3) and R (4) independently of one another NR (84) R (85); R (84) and R (85) independently of each other H, alkyl (C.-C4), or in common 4 or 5 metlene groups, of which a CH2 group may be replaced by oxygen, S, NH, NH -CH3 or N-benzyl, or of which one or two CH2 groups can be replaced by CH-C2H2 + 1 'as well as their pharmaceutically compatible salts;
(HOE 94 / F 123 - EP-OS 682,017, NZ 272,058) and) Bicyclic Heteroaroylguanidines of Formula I
where they mean: T, U, V, W, X, Y and Z independently of each other, nitrogen or carbon; but with the limitation that X and Z are not simultaneously nitrogen, and that T, U, V, W, X, Y and Z do not carry any substituent when they are nitrogen, and that no more than four of them are simultaneously nitrogen , RU) and R (2) independently of one another hydrogen, F, Cl, Br, I, alkyl (C, -C3), perfluoroalkyl (0, -03), 0R (8), NR (8) R (9) ) or C (= 0) N- = C (NH2) 2; R (8) and R (9) independently of one another, hydrogen or alkyl (C.-C3) or R (8) and R (9) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by oxygen, S, NH, N-CH3 or N-benzyl;
R (3), R (4), R (5), R (6) and R (7) independently of each other hydrogen, F, Cl, Br, I, -C = N, Xk- (CH2) p- (CqF2q +,), R (10a) -SOta, R (10b) R (10c) N-CO, R (11) -C0- OR (12) R (13) N-S02-, being the linear perfluoroalkyl group or branched; X oxygen, S or NR (14); R (14) H or alkyl (C, -C3); bm zero, 1 or 2, - p zero, 1 or 2; k zero or 1, - q 1, 2, 3, 4, 5 6 6; R (10a), R (10b), R (ll) and R (12) independently of each other alkyl (C, -C8), alkenyl (C3-C6), -CnH2n-R (15) or perfluoroalkyl (C, -C8); n zero, 1, 2, 3 or 4; R (15) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (16) R (17 ); R (16) and R (17) H or alkyl (C, -C4); or R (10b), R (ll) and R (12) hydrogen; R (10c) and R (13) independently hydrogen or alkyl (C, -C4); or R (10b) and R (10c) as well as R (12) and R (13) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl; or R (3), R (4), R (5), R (6) and R (7) independently of one another alkyl (C.-C8), -CalH2alR (18) or (C3-C8) alkenyl; to zero, 1 or 2; R (18) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (19a) ) R (19b); R (19a) and R (19b) hydrogen, (C, -C4) alkyl or perfluoroalkyl (C, -C4); or R (3), R (4), R (5), R (6) and R (7) independently of each other heteroaryl (C, -C9), which is linked through C or N and which is Substituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino or dimethylamino; or R (3), R (4), R (5), R (6) and R (7) independently of each other) h- (CHOH), - (CH2), - (CHOH) k -R (23)
C) od- (CHOH) ß .- (CH2) of- (CHOH) og-R (24)
o). »- (CHOH)., - (CH,) - (CHOH) ßk-R (25)
And oxygen, -S- or -NR (22) -; h, ad, ah independently of each other zero or 1; i, j, k, ae, af, ag, ao, ap and ak independently from each other zero, 1, 2, 3 or 4; not being however in each case h, i, and k simultaneously zero, not being ad, ae and ag simultaneously zero as well as not being ah, ao and ak simultaneously zero, R (23), R (24), R (25) and R (22) independently from each other hydrogen or alkyl (C.-C3); or R (3), R (4), R (5), R (6) and R (7) independently of each other -SR (29), -OR (30), -NR (31) R (32) or -CR (33) R (34) R (35); R (29), R (30), R (31) and R (33) independently of each other -CaH2a-heteropole (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from the group it consists of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamine and dimethylamino; to zero, 1 or 2; R (32), R (34) and R (35) independently of one another as defined R (29) or hydrogen, alkyl (C, -C 4) or perfluoroalkyl (C, -C 4); or R (3), R (4), R (5), R (6) and R (7) independently of each other
(96) - «< 97) < μ_R (98)
R (96), R (97) and R (98) independently of each other heterolalk (C, -C6), which is linked through C or N and which is unsubstituted or substituted with 1 to 3 substituents taken between the a group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamine, dimethylamine or benzyl; W oxygen, S or NR (36) -, - R (36) H or alkyl (C, -C4); or R (3), R (4), R (5), R (6) and R (7) independently of each other R (46) X (1) -; X (l) oxygen, S, NR (47), (D = 0) A- or NR (48) C = MN (*) R (49) -; M oxygen or sulfur; To oxygen or NR (50); D C or SO; R (46) alkyl (C, -C8), (C3-C8) alkenyl, < CH2 > bCdF2d + 1O-CxH2? -R (51"b zero or 1; d 1, 2, 3, 4, 5, 6 or 7; x zero, 1, 2, 3 or 4; R (51) cycloalkyl ( C3-C8), phenyl, biphenylyl or naphthyl, the aromatic radicals SM being substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (52) R (53); R (52) and R (53) hydrogen, (C, -C4) alkyl or perfluoroalkyl (C, -C4), R (47), R (48) and R (50) independently hydrogen, alkyl (C, -C4) ) or perfluoroalkyl (C, -C4), R (49) is defined as R (46), or R (46) and R (47) or R (46) and R (48) in common 4 or 5 groups of methylene, of which a CH2 group may be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl, where A and N (* 5 are attached to the phenyl nucleus of the fundamental heteroaroylguanidine framework; {.3), R (4), R (5), R (6) and R (7) independently of each other -SR (64), -OR (65), -NHR (66), -NR (67 ) R (68), -CHR (69) R (70) OR -CR (54) R (55) OH, -C = CR (56), -CR (58) = CR (57) or - [CR (59) R (60)] u- (CO) - [CR (61) R (62)] and -R (63); R (64), R (65), R (66), R (67) and R (69) equal or different - (CH2) and- (CHOH) z- (CH2) aa- (CH20) tR (71) Ó - (CH2) ab-0- (CH2-CH20) ac-R (72); R (71) and R (72) independently of one another hydrogen or me ilo; u 1, 2, 3 or 4; V zero, 1, 2, 3 or 4; and, z, aa equal or different zero, 1, 2, 3 or 4; t 1, 2, 3 or 4; R (68), R (70, R (54) and R (55) equal or different hydrogen or (C, -C6) alkyl; or R (69) and R (70) or R (54) and R ( 55) in common with the carbon atom carrying them, a (C3-C8) cycloalkyl, R (63) hydrogen, (C, -C6) alkyl, (C3-C8) cycloalkyl, or -CeH2e-R (73); e zero, 1, 2, 3 or 4; R (56), R (57) and R (73) independently phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (74) R (75); R (74) and R (75) hydrogen or alkyl (C, -C4); or R (56), R (57) and R (73) independently heteroaryl (C, -C9), which is unsubstituted or substituted as phenyl, R (58), R (59), R (60), R (61) and R (62) hydrogen or methyl, or R (3) , R (4), R (5), R (6) and R (7) independently of each other R (76) -NH-S02-; R (76) R (77) R (78) N- (C = Y ') -; Y 'oxygen, S or N-R (79); R { 77) and R (78) equal or different from hydrogen, (C, -C8) alkyl, (C3-C6) alkenyl or CfH2f-R (80); f zero, 1, 2, 3 or 4; R (80) cycloalkyl (C5-C7) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methoxy and alkyl (C, -C4); or R (77) and R (78) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl; R (79) is defined as R (77) or is equal to amidine; or R (3), R (4), R (5), R (6) and R (7) independently of each other NR (84a) R (85), OR (84b), SR (84c) or -CnH2n -R (84d); n zero, 1, 2, 3 or 4; R (84d) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy and NR (16) R (17 ); R (16) and R (17) hydrogen or alkyl (C, -C4); R (84a), R (84b), R (84c) and R (85) independently of each other hydrogen, alkyl (C, -C8), perfluoroalkyl (C, -C8) or (CH2) a? -R (84g) ); ax zero, 1, 2, 3 or 4; R (84g) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (84u) R (84v); R (84u) and R (84v) hydrogen or C, -C4 alkyl;
R (84a) and R (85) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl, as well as their pharmaceutically compatible salts;
(HOE 94 / F 134 - EP-OS 686,627, NZ 272.103) z) Benzoylguanidines of Formula I
where they mean: R (l) R (6) -SOm;
m zero, 1 or 2, - R (6) perfluoroalkyl with 1, 2, 3, 4, 5 or 6 C atoms, which is linear or branched; R (2) and R (3) independently of one another hydrogen, F, Cl, Br, I, alkyl with 1, 2, 3 or 4 C atoms, alkoxy with 1, 2, 3 or 4 C atoms or phenoxy , which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, methyl and methoxy; or R (2) and R (3) independently of each other pyrrol-1-yl, pyrrol-2-yl or pyrrol-3-yl, which is unsubstituted or substituted with 1 to 4 substituents selected from the group consisting of F, Cl, Br, I, CN, alkanoyl with 2, 3, 4, 5, 6, 7 or 8 C atoms, alkoxycarbonyl with 2, 3, 4, 5, 6, 7 or 8 C atoms, formyl, carboxy, CF3, methyl and methoxy; R (4) and R (5) independently of each other hydrogen, alkyl having 1, 2 or 3 carbon atoms, F, Cl, Br, I, CN, OR (7), NR. { 8) R (9) or - (CH2) n- (CF2) or-CF3; R (7), R (8) and R (9) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; n zero or 1; or zero, 1 or 2; as well as its pharmacologically acceptable salts;
(HOE 94 / F 168 - EP-OS 690,048, NZ 272,373) ab) Guanidides of phenyl-substituted alkenylcarboxylic acids, carriers of perfluoroalkyl groups, of Formula I
in which they mean: RIA) hydrogen, F, Cl, Br, I, CN, OH, 0R (6), alkyl (C, -C8), Op (CH2) aCbF2b +, cycloalkyl (C3-C8) or
NR (7) R (8); r zero or 1; to zero, 1, 2, 3 or 4; b 1, 2, 3, 4, 5, 6, 7 or 8; R (6) alkyl (C, -C8), perfluoroalkyl (C, -C4), (C3-C8) alkenyl, (C3-C8) cycloalkyl, phenyl or benzyl; the aromatic radicals being unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10); R (9) and R (10) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (7) and R (8) independently of one another as R (6) has been defined; or R (7) and R (8) in common 4 or 5 metlene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl; R (B) independently as defined R (A), -X zero, 1 or 2, -Y zero, 1 or 2, - R (C) hydrogen, F, Cl, Br, I, CN, 0R (12 ), alkyl (C, -C8), 0p (CH2) fCgF2g +, or (C3-C8) cycloalkyl; p zero or 1; f zero, 1, 2, 3 or 4; g 1, 2, 3, 4, 5, 6, 7 or 8; R (12) (C-C8) alkyl, perfluoroalkyl (C, -C4), (C3-C8) alkene, (C3-C8) cycloalkyl, phenyl or benzyl; the phenyl or benzyl aromatic radicals being substituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy and NR (13) R (14); R (13) and R (14) independently of one another H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (D) independently as defined R (C), R (l) hydrogen, alkyl (C, -C8), -Ot (CH2) dCeF2e +,, cycloalkyl (C3-C8), F, Cl, Br, I or CN; t zero or 1; d zero, 1, 2, 3 or 4; e 1, 2, 3, 4, 5, 6, 7 or 8; R (2), R (3), R (4) and R (5) independently of one another as defined R (D), but with the proviso that at least one of the substituents R (A), R (B), R (C), R (D), R (l), R (2), R (4) or R (5) must be a group
R (CH2> aCbF2b + r '° p < CH2 > f CgF2g + 1"Ó ° t < CH2 > dCeF2e + r YR (3) is not a group 0t (CH2) dCeF2e +, -; its pharmaceutically compatible salts;
(HOE 94 / F 182 - EP-OS 690,048, NZ 272,449) ac) Benzoylguanidmas substituted with ammo in ortho of Formula I
where they mean: R (l) NR (50) R (6); R (50) and R (6) independently of one another hydrogen, (C, -C8) alkyl or perfluoroalkyl (C, -C8); R (2), R (3), R (4) and R (5) independently of each other R (10) -SOa-, R (ll) R (12) N-CO-, R (13) -CO - or R (14) R (15) N-SO., -; to zero, 1 or 2; R (10), R (ll), R (12), R (13), R (14) and R (15) independently of each other alkyl (C.-C8), perfluoroalkyl (C, -C8), alkenyl (C3-C6) or - CabH2ab-R < 1 6 > 'ab zero, 1, 2, 3 or 4; R (16) (C3-C7) cycloalkyl, phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy or NR (17) R (18); R (17) and R (18) independently of each other H, CF3 or alkyl (C, -C4);
or R (ll), R (12) as well as R (14) and R (15) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N- CH3 or N-benzyl; or R (ll), R (12), R (14) and R (15) independently of each other hydrogen; or R (2), R (3), R (4) and R (5) independently of each other -SR (21), -OR (22), -NR (23) R (24) or -CR (25) ) R (26) R (27); R (21), R (22), R (23) and R (25) independently of each other -CbH2b-heteroaryl (C, -C9), which is substituted or substituted with 1-3 substituents selected from group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, mood, methylamino and dimethylamine; b zero, 1 or 2; R (24), R (26) and R (27) independently of each other hydrogen, (C, -C4) alkyl or perfluoroalkyl (C, -C4); or R (2), R (3), R (4) and R (5) independently of each other hydrogen, F, Cl, Br, I, CN, - (Xa) dg-CdaH2da +, - (Xb) dh - (CH2) db-CdeF2de +, (C3-C8) alkenyl or -CdfH2dfR (30), - (Xa) 0, S or NR (33); R (33) H, alkyl (C, -C4) or perfluoroalkyl (C-C4); dg zero or 1; (Xb) 0, S or NR (34); R (34) H, (C, -C4) alkyl or perfluoroalkyl (C, -C); dh zero or 1;
gives zero, 1, 2, 3, 4, 5, 6, 7, db zero, 1, 2, 3, 4; from zero, 1, 2, 3, 4, 5, 6, 7; df zero, 1, 2, 3, 4; ROO) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being phenyl, biphenylyl or naphthyl unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (31) R (32); R (31) and R (32) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); or R (2), R (3), R (4) and R (5) independently of each other NR (40) R (41) or - (Xe) - (CH2) cbR (45); R (40) and R (41) independently of each other hydrogen, (C, -C8) alkyl, perfluoroalkyl (C.-C8) or (CH2) e-R (42); e zero, 1, 2, 3 or 4; R (42) (C3-C7) cycloalkyl, phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (43) R (44); R (43) and R (44) independently of one another H, CF3 or alkyl (C, -C4) or R (40) and R (41) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl;
(Xe) O, S or NR (47); R (47) H, (C, -C 4) alkyl or perfluoroalkyl (C, -C 4), - eb zero, 1, 2, 3 or 4; R (45) (C3-C6) cycloalkyl, phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy, NR (50) R (51) and - (Xfa) - (CH2) ed- (Xfb) R (46); Xfa CH2, 0, S or NR (48); Xfb 0, S or NR (49); ed 1, 2, 3 0 4; R (46) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (48), R (49), R (50) and R (51) independently of each other H or (C * -C4) alkyl or perfluoroalkyl (C ^ -C ^); however, R (3) and R (4) can not be hydrogen, as well as their pharmaceutically compatible salts;
(HOE 94 / F 265 - NZ 272,946, EP-OS 700,904) ad) Benzoylguanidines of Formula I
where they mean: one of the three substituents R (l), R (2) and R (3) heteroaryl (C, -C9) -N-oxide, which is linked through C or N and which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino, or one of the three substituents R (l), R (2) and R ( 3) -SR (10), -OR (10), -NR (10) R (11) OR -CR (10) R (11) R (12); R (10) -CaH2a-het.eroaryl (C , -C9) -N-oxide, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino, at zero, 1 or 2; R (ll) and R (12) independently of each other as defined R (10), hydrogen or (C-C4) alkyl, and the respectively other substituents R (l), R (2) and R (3) independently of each other alkyl (C, -C8), alkenyl (C2-C8) or -CmH2 | nR (1); m zero, 1 or 2, - R (14) cycloalkyl (C3-C8) or phenyl , which is without substitution ir or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (15) R (16), R (15) and R (16) hydrogen or CH3; or the respectively other substituents R (1), R (2) and R (3) independently of each other hydrogen, F, Cl, Br,
I, -C = N, X- (CH2) p- (CqF2q +,), R (22) -SOu, R (23) R (24) N-CO, R (25) -CO- or R ((26 ) R (27) N-S02-, the linear or branched perfluoroalkyl group, X a bond, oxygen, S or NR (28), or zero, 1 or 2, p zero, 1 or 2; q zero, 1, 2, 3, 4, 5 or 6, R (22), R (23), R (25) and R (26) independently alkyl (C, -C8), alkene (C2-C6), -CnH2n-R ( 29) or CF3; n null, 1, 2, 3 or 4; R (28) hydrogen or alkyl (C, -C3); R (29) c (C3-C7) alkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (30) R (31); R (30) and R (31) hydrogen or alkyl (C, -C4), or R (23), R (25) and R (26) also hydrogen, R (24) and R (27) independently of each other hydrogen or alkyl (C, -C4), or R (23) and R (24) ) as well as R (26) and R (27) in common 4 or 5 metlene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl;
other substituents R (1), R (2) and R (3) independently of each other 0R (35) or NR (35) R (36); R (35) and R (36) independently from each other hydrogen or alkyl (C, -C6); or R (35) and R (36) in common 4-7 methylene groups, of which a CH2 group can be replaced by oxygen,
S, NH, N-CH3 or N-benzyl, R (4) and R (5) independently of one another hydrogen, alkyl (C, -C4), F, Cl, -OR (32), -NR (33) R (34) or CrF2r +,;
R (32), R (33) and R (34) independently of each other hydrogen or alkyl (C.-C3); r 1, 2, 3 or 4; as well as its pharmaceutically compatible salts;
(HOE 94 / F 266 - EP-OS 702.001, NZ 272 948) ad) Benzoylguanidms of Formula I
where they mean: R (l) hydrogen, F, Cl, Br, I, CN, N02, OH, alkyl (C, -C8), cycloalkyl (C3-C8), Oa- (CH.,) b- ( CF2) C-CF3; to zero or 1, - b zero, 1 or 2; c zero, 1, 2 or 3;
R (l) R (5) -SOm OR R (6) R (7) N-S02- m zero, 1 or 2, - R (5) and R (6) independently of each other alkyl (C, -C8 ), (C3-C6) alkenyl, CF3-CnH.nR (8: n-zero, 1, 2, 3 or 4; R (7) hydrogen or (C, -C) alkyl; R (8) cycloalkyl (C3) -C7) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, ethoxy and NR (9) R (10); R (9) and R ( 10) independently of one another hydrogen or alkyl (C.-C4), or R (6) H; or R (6) and R (7) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, or R (l) -SR (ll), -OR (ll) OR -CR (11) R (12) R (13); ) -C H2-C3-C8-cycloalkyl, hetero-halo (C, -C,) or femlo, the aromatic systems being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3 , methoxy, hydroxy, amino, methylamino and dimethylamino, R (12), R (13) independently from each other as has defined R (ll) or hydrogen or alkyl (C, -C4); p zero, 1 or 2; or R (l) phenyl, naphthyl, biphenylyl or heteroaryl (C, -C9), the latter linked through C or N, which are unsubstituted or substituted with 1-3 its isomers selected from the group consisting of F, Cl, CF 3, CH 3, methoxy, hydroxy, ammo, methylamino and dimethylamino;
R (2! -CF2R? 14; -CF [R (15)] [R (16)], -CF [(CF -CF3] [R (15) 2'q -C [(CF2) r-CF3] = CR (15) R (16), R (14) (C, -C4) alkyl or (C3-C6) cycloalkyl, - R (15) and R (16) independently of each other hydrogen or alkyl! c4) q zero, 1 or 2, r zero, 1 or 2, R (3: as defined R (l), R (4; hydrogen, alkyl (C, -C3) Cl, Br, I, CN, - (CH2) s- (CF2) t-CF3; s zero or 1; t zero, 1 or 2, -as well as its pharmaceutically compatible salts
(HOE 94 / F 267- EP-OS 700,899, NZ 272,947) ae) Benzoylguanidines' of Formula I
where they mean: one of the three substituents R (l), R (2) and R (3) -Y-4- [(CH2) k-CHR (7) - (C = 0) R (8)] -phenyl, -Y- 3- [(CH2) k-CHR (7) - (C = 0) R (8)] -phenyl or -Y-2- [(CH2) k-CHR (7) - (C = 0) R (8)] -phenyl, the phenyl being in each case unsubstituted or substituted with 1-2 substituents taken from the group consisting of F, Cl, CF3, methyl, hydroxy, methoxy or -NR (37) R (38); R (37) and R (38) independently of one another hydrogen or -CH3; And a bond, oxygen, -S- or -NR (9); R (9) hydrogen or alkyl (C, -C4); R (7) -OR (IO) or -NR (10) R (11); R (10) and R (ll) independently of each other hydrogen, alkyl (C.-C8), alkanoyl (C, -C8), alkoxy (C, -C8) -carbonyl, benzyl, benzyloxycarbonyl; or R (10) trityl; R (8) -0R (12) or -NR (12) R (13); R (12) and R (13) independently of each other hydrogen, (C, -C 8) alkyl or benzyl; k zero, 1, 2, 3 or 4; and the respectively other radicals R (1), R (2) and R (3) independently of one another -alkyl (C, -C 8), -alkenyl (C 2 -C 8) or - (CH.,) mR (14); m zero, 1 or 2; R (14) -cycloalkyl (C3-C8) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -CF3, methyl, methoxy and -NR (15) R ( 16); R (15) and R (16) hydrogen or -CH 3; or the respectively other radicals R (l), R (2) and R (3) independently of each other R (18) R (19) N- (C = Y ') -NH-SO., -; Y 'oxygen, -S- or -N-R (20); R (18) and R (19) independently of one another hydrogen, alkyl (C, -C8), to "quenil (C3-C6) or - (CH2) t-R (21); t zero, 1, 2, 3 or 4; R (21) -cycloalkyl (C5-C7) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -CF3, methoxy and alkyl (C, -C4); or R (18) and R (19) in common 4 or 5 methylene groups, of which one group i'I can be replaced by oxygen, -S-, -NH-, -N-CH3 or -N-benzyl; R (20) as defined R (18) or amidine;
respectively other radicals R (l), R (2) and R (3) independently of each other hydrogen, F, Cl, Br, I, -CSN, X- (CH2) - (CF), R (22) -SOu -, R (23) R (24) N-CO-, R (25) -CO- or R (26) R (27) N-S02-, the perfluoroalkyl group being linear or branched; X a bond, oxygen, -S- or -NR (28); u zero, 1 or 2; p zero, 1 or 2; q 1, 2, 3, 4, 5 0 6; R (22), R (23), R (25) and R (26) independently of each other -alkyl (C, -C8), -alkenyl (C3-C6), - (CH2) nR (29) or - CF.,; n zero, 1, 2, 3 or 4; R (28) hydrogen or alkyl (C.-C3); R (29) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -CF3, methyl, methoxy and -NR (30) R (31) ); R (30) and R (31) hydrogen or -alkyl (C, -C4), -o R (23), R (25) and R (26) hydrogen;
R (24) and R (21) independently of one another hydrogen or -alkyl (C, -C4) or R (23) and R (24) as well as R (26) and R (27) in common 4 or 5 groups of methylene, of which a CH2 group may be replaced by oxygen, -S-, -NH-, -N-CH3 or -N-benzyl; or the respectively other radicals R (1), R (2) and R (3) independently of one another -OR (35) or -NR (35) R (36); R (35) and R (36) independently from each other hydrogen or alkyl (C.-C6); or R (35) and R (36) in common 4-7 metlene groups, of which a CH2 group may be replaced by oxygen, -S-, -NH-, -N-CH3 or -N-benzyl; R (4) and R (5) independently of one another hydrogen, -alkyl (C, -C4), F, Cl, -OR (32), -NR (33) R (34) or -CFR (32), R (33) and R (34) independently of one another hydrogen or -alkyl (C, -C3); r 1, 2, 3 or 4; as well as its pharmaceutically compatible salts;
(HOE 94 / F 352 - EP-OS 713,684, NZ 280,517; af) Benzoylguanidomes of Formula I
where they mean: R (l) R (6) -CO or R (7) R (8) N-CO; R (6) alkyl (C, -C8), perfluoroalkyl (C * -C8), alkenyl (C, -C -CnH, 2n- R (9i n zero, 1, 2, 3 or 4; R (9) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (10) R (11) ), R (10) and R (ll) H, (C-C4) alkyl or perfluoroalkyl (C, -C4); R (7] H, (C, -C8) alkyl, perfluoroalkyl (C, -C8) , (C3-C8) alkenyl or -CNH2n-R (12); n-null, 1, 2, 3 or 4-cycloalkyl (C3-C8), phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (13) R (14);
R (13) and R (14) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (8) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4), - or R (7) and R (8) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R (2) as defined R (l), or H, OH, F, Cl, Br, I, CN, N02, alkyl (C, -C8), perfluoroalkyl (C, -C8), alkenyl (C3- C8) or -CnH2nR (15); n zero, 1, 2, 3 or 4; R (15) (C3-C8) cycloalkyl, phenyl, bifemyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (16 ) R (17); R (16) and R (17) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); or R (2) heteroaryl (C, -C9), which is bonded through C or N and which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy , hydroxy, amino, methylamine and dimethylamino; or R (2) -SR (18), -OR (18), -NR (18) R (19) or -CR (18) R (19) R (20); R (18) -CaH2a-heterolalk (C * -C9), which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamino and dimethylammon; to zero, 1 or 2; R (19) and R (20) independently of one another as defined R (18) or hydrogen, alkyl (C, -C 4) or perfluoroalkyl (C, -C 4); or R (2) R (21) -S0m or R (22) R (23) N-S02-; m 1 or 2; R (21) alkyl (C, -C8), perfluoroalkyl (C, -C8), alkenyl (C3-C8) or -CnH2n-R (24); n zero, 1, 2, 3 or 4; R (24) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (27 ) R (28); R (27) and R (28) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (22) H, (C, -C8) alkyl, perfluoroalkyl (C, -C8), alkenyl (C ^ -C ^) or -CnH2n-R (29); n zero, 1, 2, 3 or 4; R (29) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR ( ) R (31); H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (23) hydrogen, (C, -C4) alkyl or perfluoroalkyl (C, -C), or R (22) and R (23) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by oxygen, S, NH, N-CH3 or N-benzyl; or R (2) R (33) X-; X oxygen,?, NR (34), (D = 0) A- or NR (34) C = MN (* 'R (35) -; M oxygen or S; Oxygen or NR (34); DC or SO R (33) alkyl (C, -C8), (C3-C8) alkenyl, (CH2> bCdF2d + 1O-CnH2n-R (3 6) '- b zero or 1; d 1, 2, 3, 4, 5, 6, 7, n zero, 1, 2, 3 or 4, R (36) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 selected substituents between the group consisting of F, Cl, CF3, methyl, methoxy and NR O 7) R (38); R (37) and R (38) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4) ); R (34) hydrogen, (C, -C4) alkyl or perfluoroalkyl (C.-C4); R (35) as defined R (33); or R (33) and R (34) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, • A and N (* 5) being attached to the phenyl nucleus of the fundamental network of the benzoylguanidine;
or R (2) -SR (40), -OR (40), -NHR (40), -NR (40) R (41), -CHR (40) R (42), -CR (42) R ( 43) OH, -CSCR (45), -CR (46) = CR (45) or - [CR (47) R (48)] u-CO- [C (R49) R (50)] vR (44); R (40) and R (41) independently of one another - (CH2) p (CHOH) - (CH2) r- (.CHOH) tR (51) or - (CH2) p-0- (CH2-CH20) qR (51); R (51) hydrogen or methyl; u 1, 2, 3 0 4; v zero, 1, 2, 3 or 4; Pr q y r mdependientementece of others zero, 1, 2, 3 0 4; t 1, 2, 3 0 4; R (42) and R (43) independently of each other hydrogen or (C, -C6) alkyl, - or R (42) and R (43) in common with the carbon atom carrying them, a cycloalkyl (C3-) C8); R (44) hydrogen, (C, -C6) alkyl, (C3-Cfl) cycloalkyl, -CeH2e-R (45); e zero, 1, 2, 3 or 4; R (45) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the 9r? -ipo consisting of F, Cl, CF3, methyl, methoxy and NR (52) R (53); R (52) and R (53) H or alkyl (C, -C4); or R (45) heteroaryl (C, -C9), which is unsubstituted or substituted as phenyl;
or R (45) alkyl (C, -C6), which is unsubstituted or substituted with 1-3 OH; R (46), R (47), R (48), R (49) and R (50) independently of one another, hydrogen or methyl; or R (2) R (55) -NH-S02-; R (55 R (56) R (57) N- (C = Y) -; and oxygen, S or NR (58); R (56) and R (57) independently of one another hydrogen, alkyl (C, - C8), (C3-C6) alkenyl or -CfH2f-R (59); f zero, 1, 2, 3 or 4; R (59) cycloalkyl (C5-C7), phenyl, which is unsubstituted or substituted by 1; -3 substituents selected from the group consisting of F, Cl, CF3, methoxy and alkyl (C, -C4), or R (56) and R (57), in common 4 or 5 methylene groups, of which CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, R (58) as defined R (56) or equal to amidine; (3), R (4) and R (5) are independently from each other as R (l) or R (2) have been defined, however, at least one of the substituents R (2), R (3), R (4) and R ( 5) be equal to OH, as well as its pharmaceutically compatible salts;
(HOE 95 / F 007 K - EP-OS 723,956, NZ 280,887) ag) Benzoylguanidines of Formula I
wherein they mean: one of the three substituents R (l), R (2) and R (3) R (6) -A-B-D-; R (6) a basic protonatable radical, ie an amino group -NR (7) R (8), an amidino group R (7) R (8) N-C [= N-R (9)] - or a guanidino group,
R (7R (8), R (9) and R (10) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (7: and R (8) in common CaH , A; 'a 4, 5, 6 or 7, verifying, in the case that a = 5, 6 or 7, that a methylene group of the CaH2a group can be replaced by a group with heteroatoms O, SOm or NR (ll), or R (8) and R (9) or R (9) and R (10) or R (7) and
R (10) a CaH2a group;
to 2, 3, 4 0 5; verifying, in the case that a = 3, 4 or 5, that a methylene group of the group CgH2a can be replaced by a group with heteroatoms 0, S0m or NR (ll); m zero, 1 or 2; R (ll) hydrogen or methyl; or R (6) a basic heteroaromatic ring system with
1-9 C atoms; A CbH2b; b 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; it being verified in the CbHb group that one or two methylene groups can be replaced by one of the groupings selected from the group consisting of -0-, -CO-, -CH [OR (20)] -, -S0m-, - NR (20) -, -NR (20) -CO-, -NR (20) -CO-NH-, -NR (20) -CO-NH-SO, -
(0) oo II -R (20) H-S- I I NR (19) I bb
and -SOaa [NR (19)] bb-; and verifying in the group CbH2b that a methylene group can be replaced by -CH-R (99), forming R (99) in common with R (7) a pyrrolidine or piperidine ring; aa 1 or 2; bb zero or 1; aa + bb = 2; R (19) hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; R (20) hydrogen or methyl; a phenylene or naphthylene radical
R (12) and R (13) independently of one another hydrogen, methyl, F, Cl, Br, I, CF3 or -SO W-R (14) R (14) methyl or NR (15) R (16); R (15) and R (16) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; w zero, 1 or 2; D ~ CdH2d "Xf"; d zero, 1, 2, 3 or 4; X -O-, -CO-, -CH [OR (21)] -, -SOm- or -NR (21); f zero or 1; R (21) hydrogen or methyl; m zero, 1 or 2; respectively other substituents R (l) and R (2) and R (3) independently of each other hydrogen, F, Cl, Br,
I, -CN, -alkyl (C, -C8), -alkenyl (C2-C8), -NR (35) R (36) or R (17) -C8H2h- Zh-; g zero, 1, 2, 3 or 4; h zero or 1; R (35) and R (36) independently of each other hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C atoms, - R (35) and R (36) in common 4-7 methylene groups , of which a CH2 group may be replaced by oxygen, -S-, -NH-, -NCH3 or -N-benzyl; Z -0-, -CO-, -S0y-, -NR (18) -, -NR (18) -C0-, -NR (18) -CO-NH- OR -NR (18) -S02-; R (18) hydrogen or methyl; v zero, 1 or 2; R (17) hydrogen, cycloalkyl with 3, 5 or 6 CkF2k +, -; k 1, 2 0 3; or R (17) pyrrol-1-? lo, pyrrol-2-? or op-rrol-3-? lo, which is unsubstituted or substituted with 1-4 substituents selected from the group consisting of , Cl, Br, I, -CN, (C2-C8) alkanoyl, (C2-C8) alkoxycarbonyl, foryl, carboxy, -CF3, methyl and ethoxy; or R (17) -cycloalkyl (C3-C8) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, hydroxy, methoxy, -NR (37 ) R (38), CH3S02- and H2N02S-; R (37) and R (38) hydrogen or CH3; R (4) and R (5) independently of one another hydrogen, alkyl with 1, 2, 3 or 4 C atoms, F, Cl, -OR (32), -NR (33) R (34) or -CrFr + i'- R (32), R (33) and R (34) independently of each other hydrogen or alkyl having 1, 2 or 3 C atoms; r 1, 2, 3 0 4; as well as its pharmacologically compatible salts;
(HOE 95 / F 072 - EP-OS 738,712, NZ 286,380) ah) Indenoylguanidines of Formula I
where they mean: R (l) and R (2) independently of one another hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms, cycloalkyl with 3 , 4, 5 or 6 C atoms, O-alkyl with 1, 2, 3 or 4 C atoms, OC (= 0) -alkyl with 1, 2, 3 or 4 C atoms or CH, -NR (12 ) R (13); R (12) and R (13) independently from each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; m zero, 2, 3 or 4; NH-C (= 0) -NH2, C (= 0) -0-alkyl with 1, 2, 3 or 4 C atoms, C (= 0) -NH2, C (= 0) -NH-alkyl with 1, 2, 3 or 4 C atoms, C (= 0) -N (alkyl) 2 with 1, 2, 3 or 4 C atoms in each alkyl, alkenyl group with 2, 3, 4, 5, 6 , 7, 8, 9 or 10 C atoms, alkyl with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms, alkylaryl with 1, 2, 3 or 4 C atoms in the group alkyl, alkenyl-aryl with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms in the alkenyl, alkylaryl group with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms in the alkyl group, aryl substituted with C, -C4 alkyl, heteroaryl substituted with C, -C4 alkyl, C, -C4 alkenyl, heteroaryl, aminoalkylaryl with 1, 2, 3 or 4 C atoms in the alkyl, substituted aplo, heteropole and substituted heteroaryl group;
37 -. 37 - R (3), R (4), R (5) and R (6) independently of one another hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 atoms C, O-alkyl with 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms, halogen (such as F, Cl, Br, I), OH, aryl, substituted aryl, heterolalk , substituted heteroaryl, O-lower alkyl, 0-aryl, 0-lower alkyl-aryl, O-substituted aryl, O-alkyl substituted mfepor-aryl, 0-C (= 0) -alkyl C, -C4 -aplo, OC (= 0) -NH-alkyl crc4 '0-C (= 0) -N (alkyl C, -C4) 2, N02, CN, CF3, NH2, NH-C (= 0) - alkyl C, -C4, NH-C (= 0) -NH2, COOH, C (= 0) -0-alkyl C, -C4, C (= 0) -NH2, C (= 0) -NH- alkyl C, -C4, C (= 0) -N (alkyl C, -C4) 2, alkyl C, -C4-C00H, alkyl C, -C4-C (= 0) -0-alkyl C , -C4, S03H, S02-alkyl, S02-alkyl, S02-N- (alkyl) 2, S02-N (alkyl) (alkylamp), C (= 0) -R (II), alkyl C, -C, 0-C (= 0) -R (ll), C2-C alkenyl, 0-C (= 0) -R (11), C2-C alkylam, 0-C (= 0) - R (11), NH-C (= 0) -alkyl C, -C, 0-C (= O) -R (ll), 0-alk? L C, -C ,, -C (= 0) - R (11); R (ll) C, -C 4 alkyl, C, -C 4 alkyl, aryl, substituted alkyl, NH 2, NH-C-C 4 alkyl, N- (C 1 -C 4 alkyl), S 0 3 H, S 0 2 -alkyl, S02-alkyl, S02-N- (alkyl) 2, S02-N (alkyl) (alkyla); X O, S or NH; R (7), R (8), R (9) and R (10) independently of each other hydrogen, alkyl, cycloalkyl, aplo, alkylaryl; or R (8) and R (9) are common part of a heterocyclic ring of 5, 6 or 7 members, A is absent or is a non-toxic mineral or organic acid.
(HOE 95 / F 109 - EP 748,795, NZ 286,583) ai) Benzoyloxycarbonylguanidms of Formula I
2
in which they mean: R), R (2) and R (3) independently of each other -Y- [4-R (8) -phenyl], -Y- [3-R (8) -phenyl] or - Y- [2-R (8) -phenyl], the phenyl being in each case substituted or substituted with 1-2 substituents taken from the group consisting of F, Cl, -CF3, methyl, hydroxy, methoxy and -NR (96) R (97); R (96) and R (97) independently of one another hydrogen or -CH3; And a bond, CH2, oxygen, -S- or -NR (9); R (9) hydrogen or alkyl with 1, 2, 3 or 4 C atoms; R (8) SOa [NR (98)] bNR (99) R (10); to 1 or 2; b 0 or 1; a + b = 2; R (98), R (99) and R (10) independently of each other hydrogen, -alkyl (C, -C8), benzyl, -alkylene (C2-C8) -NR (II) R (12), -alkylene (C2-C8) -NR (13) -alkylene (C2-C8) -NR (37) R (38) or alkylene (CQ-C8) -CR (39) R (40) -CR (41) R (42) ) -alkylene (C0-C8) -NR (43) R (44); R (ll), R (12), R (13), R (37), R (38), R (43) and R (44) independently of each other hydrogen, -alkyl (C, -C8) or benzyl; R (39), R (40), R (41) and R (42) independently of one another hydrogen, -alkyl (C, -C8) or -alkylene (CQ-C3) -phenyl, the phenyl being substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -CF3, methyl and methoxy; or R (99) and R (10) in common 4-6 metlene groups, of which a CH2- group may be replaced by oxygen, -S-, -NH-, -N-CH3 or -N-benzyl; or R (8) SOa [NR (98)] b NR (95) -C [= N-R (94)] -NR (93) R (92); R (92), R (93), R (94) and R (95) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (l), R (2) and R (3) independently of each other pyrrol-1-? lo, pyrrol-2? or op-rrol-3-? lo, which is unsubstituted or substituted with 1-4 substituents selected from the group consisting of F, Cl, Br, I, -CN, alkanoyl (C2-C8), alkoxy (C2-C8) -carbonyl, formyl, carboxy, -CF3, methyl, methoxy; or R (l), R (2) and R (3) independently of each other hydrogen, alkyl (C.-C8), -alkenyl (C2-C8) or - (CH2) mR (14), - m zero, 1 or 2; R (14) cycloalkyl (C3-C8) or phenyl, which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, methoxy and -NR (15) R (16 ); R (15) and R (16) hydrogen or -CH3, or R (l), R (2) and R (3) independently of each other -Q-4- [(CH2) k-CHR (17) - ( C = O) R (20)] -phenyl, -Q-3- [(CH2) k-CHR (17) - (C = O) R (20)] -femlo or -Q-2- [(CH2) k-CHR (17) - (C = O) R (20)] -phenyl, the phenyl being in each case unsubstituted or substituted with 1-2 substituents taken from the group consisting of F, Cl, -CF3, methyl, hydroxy, methoxy and -NR (35) R (36); R (35) and R (36) independently of one another hydrogen or -CH3; Q a bond, oxygen, -S- or -NR (18); R (18) hydrogen or alkyl (C.-C4); R (17) -0R (21) or -NR (21) R (22); R (21) and R (22) independently of one another hydrogen, -alkyl (C, -C8), -alkanoyl (C, -C8), -alkoxy (C, -C8) -carbonyl, benzyl, benzyloxycarbonyl; or R (21) trityl; R (20) -OR (23) or -NR (23) R (24); R (23) and R (24) independently from each other hydrogen, (C, -C 8) alkyl or benzyl; k zero, 1, 2, 3 or 4; or R (l), R (2) and R (3) independently of each other heteroaryl (C, -C9), which is bonded through C or N and which is unsubstituted or substituted with 1-3 substituents taken between the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamino and dimethylamino; or R (l), R (2) and R (3) -SR (25), -OR (25), -NR (25) R (26), -CR (25) R (26) R (27); R (25) -CfH2f-heterolalk (C, -C9), which is substituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamino and dimethylamino; f zero, 1 or 2; R (26) and R (27) independently of one another as defined R (25) or hydrogen or alkyl (C, -C4), or R (l), R (2) and R (3) independently one of another heteroapl (C, -C9) -N-oxide, which is linked through C or N and which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy , hydroxy, amino, methylamine and dimethylamino; or R (l), R (2) and RO) independently of one another -SR (28), -OR (28), -NR (28) R (29) or -CR (28) R (29) R ( 30); R (28) -C8H2g-heteroapl (C, -C9) -N-oxide, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, arrimo , methylamino and dimethylamino; g zero, 1 or 2; R (29), R (30) independently of one another as defined R (28), hydrogen or alkyl (C, -C4); or R (1), R (2) and R (3) independently of each other hydrogen, F, Cl, Br, I, -C = N, T- (CH2) h- (C.F2. + 1), RODSO.-, R (32) R (33) N-CO-, R (34) -CO- or R (45) R (46) N-S02, the linear or branched perfluoroalkyl group being; T a bond, oxygen, -S- or -NR (47); 1 zero, 1 or 2; h zero, 1 or 2; i 1, 2, 3, 4, 5 0 6; R (31), R (32), R (34) and R (45) independently of each other (C, -C8) alkyl, (C3-C6) alkenyl, (CH2) nR (48) or -CF3; n zero, 1, 2, 3 or 4; R (47) hydrogen or alkyl having 1, 2 or 3 C atoms; R (48) cycloalkyl (Cz-C?) Or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -CF3, methyl, methoxy and -NR (49) R ( 50), - R (49) and R (50) hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (32), R (34) and R (45) hydrogen, - R (33) and R (46) independently of one another hydrogen or
1-alkyl with 1, 2, 3 or 4 C atoms; or R (32) and R (33) as well as R (45) and R (46) in common 5 or 6 methylene groups, of which a CH2 group can be replaced by oxygen, -S-, -NH-, -NCH3 or N-benzyl; or R (l), R (2) and RO) independently of each other R (51) -A-G-D-; R (51) a basic protonatable radical, ie an amino group -NR (52) R (53), an amidino group R (52) R (53) N-C [= N-R (54)] - or a guanidino group
R (52) R (53) N-C [= N-R (54)] -NR (55) -; R (52), R (53), R (54) and R (55) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (52) and R (53) a CH-, a group; to 4, 5, 6 0 7; verifying, in the case that a = 5, 6 or 7, that a C atom of the CaH2a group can be replaced by a group with heteroatoms O, S0d or NR (56), or R (b3) and R (54) or R (54) and R (55) or R (52) and R (55) a C? H2 group; And 2, 3, 4 or 5; verifying, in the case that y = 3, 4 or 5, that a C atom of the C H group can be replaced by a group with 0, SOd or NR (56) heteroatoms, - d zero, 1 or 2; R (56) hydrogen or me ilo; or R (51) a basic heteroaromatic ring system with 1-9 C atoms; To a group CeH2e; e zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
being verified in the group CeH2e that a C atom can be replaced by one of the groupings -0-, -CO-, -CH [OR (57)] -, -S0p-, -NR (57) -, -NR ( 57) -CO-, -NR (57) -CO-NH-, -NR (57) -C0-NH-S02 OR -NR (57) -SO., -; r zero, 1 or 2, - a phenylene radical,
R (58) and R (59) independently of one another hydrogen, methyl, methoxy, F, Cl, Br, I, CF3 or R (60) methyl or NR (61) R (62); R (61) and R (62) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; v zero, 1, 2, 3 or 4; E -0-, -CO-, -CH [OR (63)] -, '-S0aa- or w zero or 1; aa zero, 1 or 2; R (63) hydrogen or methyl, or R (l), R (2) and RO: independently from each other -CF2R (64), -CF [R (65)] [R (66)], -CF [CF2 ) q-CF3)] [R (65)], -C [CF2) p-CF3] = CR (65) R (66); R (64) alkyl having 1, 2, 3 or 4 carbon atoms or cycloalkyl with 3, 4, 5, 6 or 7 carbon atoms, - R (65) and R (66) independently of one another hydrogen or alkyl with 1, 2, 3 or 4 C atoms; q zero, 1 or 2; p zero, 1 or 2; or R (l), R (2) and RO) independently of one another -0R (67) or -NR (67) R (68), -R (67) and Rv68) independently of each other hydrogen or alkyl with 1 , 2, 3, 4, 5 or 6 C atoms; or R (67) and R (68) in common 4, 5, 6 or 7 methylene groups, of which a CH2 group can be replaced by oxygen, -S-, S02, -NH-, -NCH3 or -N -benzyl; R (4) and R (5) independently of one another hydrogen, alkyl with 1, 2, 3 or 4 C atoms, F, Cl, -OR (69), -NR (70) R (71)
6 -. 6 -CzF2z + 1 < - R (69), R (70) and R (71) independently of each other hydrogen or alkyl with 1, 2 or 3 C atoms; z 1, 2, 3 or 4; R (6) and R (7) independently from each other hydrogen or alkyl having 1, 2, 3 or 4 C atoms; X oxygen or NR (72); R (72) hydrogen or alkyl having 1, 2, 3 or 4 C atoms; as well as its pharmaceutically compatible salts;
(HOE 95 / F 115 - EP 744,397, NZ 286,622) ak) Guanidides of alkenylcarboxylic acids carrying fluorophenyl groups, of Formula I 1C6
where they mean R (6) hydrogen, (C, -C8) alkylcycloalkyl (C, -Cfl phenyl, the phenyl group being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10); R (9) and R (10) hydrogen, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (7) independently as defined R (6); R (l), R (2), RO), R (4) and R (5) independently of each other hydrogen or F; while having at least one of the radicals R (1), R (2), R (3), R (4) and R (5) as well as their pharmaceutically compatible salts;
(HOE 95 / F 167 - NZ 299.015) al) Benzoylguanidmas of Formula I
wherein they mean: R (l) R (4) -SOm or R (5) R (6) N-S02-; Ti 1 Ó 2; R (4) and R (5) independently of one another alkyl with 1, 2,
3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 3, 4, 5 or 6 C atoms, CF3 or -CnH2n-R (7); n zero, 1, 2, 3 or 4; R (6) H or alkyl with 1, 2, 3 or 4 C atoms; R (7) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9); R (8) and R (9) H or alkyl with 1, 2, 3 or 4 C atoms; or R (5) also hydrogen; or R (5) and R (6) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; or R (l) -Op- (CH2) q- (CF2) r-CF3; p zero or 1, - q zero, 1 or 2; r zero, 1, 2 or 3; or R (l) -SR (10), -OR (10) or -CR (10) R (11) R (12); R (10), R (ll) and R (12) independently of each other hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, -C3H2¡.-c? cloalkyl (C3-C8) or an aromatic system selected from the group consisting of piphodyl, pyrrolyl, qumolyl, isoquinolyl, imidazolyl or phenyl; s zero, 1 or 2; the aromatic systems of pipidyl, pyrrolyl, quinolyl, isoquinolyl, imidazolyl and phenyl being unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamine and dimethylammon; R (2) - (CH2) U- (CF2) t-CF3; t zero, 1, 2 or 3; u zero or 1; R (3) hydrogen or independently as defined RU); as well as its pharmaceutically compatible salts;
(HOE 95 / F 173 - NZ 299,052) am) Substituted cinnamic acid guanidides of the Formula
I
wherein they mean: at least one of the substituents R (l), R (2), R (3), R (4l and R (5) - U 'X CR (16) R (17), O, S OR NR (18), R (16), R (17) and R (18) independently of each other H, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 atoms from C to zero or 1; and alkylene with 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, alkylene-T with 1, 2, 3, 4, 5, 6, 7 or 8 atoms of C in the alkylene group, T, T-alkylene with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms in the alkylene group, T NR (20), 0, S or phenylene, the phenylene unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (21) R (22); R (20), R (21) and R (22) independently of one another H, alkyl with 1, 2, 3 or 4 carbon atoms or perfluoroalkyl with 1, 2, 3 or 4 carbon atoms; b zero or 1; 0, S, NR (23) Ó CkH2k k 1, 2, 3, 4, 5, 6, 7, 8, n zero or 1, U NR (24) R (25) or a heterocycle containing N with
1, 2, 3, 4, 5, 6, 7, 8 0 9 C atoms; R (24) and R (25) independently of one another, hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6 , 7 or 8 C atoms; or R (24) and R (25) in common 4 or 5 methylene groups, of which one CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, • the heterocycles containing N being bridged in N or C, and being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, ethoxy and NR (27) R (28); R (23), R (27) and R (28) independently of each other H, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; and the respectively other substituents R (1), R (2), R (3), R (4) and R (5) independently of each other H, F, Cl, Br, I, CN,
-0 n-C mH; 2nm? T + "l '-O p} CH 2 s - C q F 2 -q ++ 11 or - C rH, ZrR (10); n zero or 1; m zero, 1, 2, 3, 4, 5, 6, 7 or 8; p zero or 1; q 1, 2, 3, 4, 5, 6, 7 or 8; s zero, 1, 2, 3 or 4; r zero, 1, 2, 3 or 4; R (10) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, or phenyl, the phenyl being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3 , methyl, methoxy and NR (11) R (12); R (ll) and R (12) independently of each other H, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; R (6) and R (7) independently of one another hydrogen, F, Cl, Br, I, CN, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms
C, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (14) R (15); R (14) and R (15) independently of each other H, alkyl having 1, 2, 3 or 4 C atoms or perfluoroalylsilyl with 1, 2, 3 or 4 C atoms; as well as its pharmaceutically compatible salts;
(HOE 95 / F 220 - NZ 299,052) an) Benzoylguanidines of Formula I
wherein they mean: at least one of the substituents R (l), R (2) and R (3) R (6) -C (0H) 2-; R (6) perfluoroalkyl having 1, 2 or 3 carbon atoms, which is linear or branched; and the other substituents R (l), R (2) and R (3) independently of each other hydrogen, OH, F, Cl, Br, I, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms. , cycloalkyl with 3, 4, 5 or 6 carbon atoms, alkoxy with 1, 2, 3 or 4 carbon atoms or phenoxy, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl , methyl and methoxy; or the other substituents R (l), R (2) and R (3) independently of one another alkyl-SO, -CR (7) = CR (8) R (9) or -C = CR (9); x zero, 1 or 2, R (7) hydrogen or methyl; R (8) and R (9) independently of one another hydrogen, alkyl with 1, 2, 3 or 4 C atoms, cycloalkyl with 3, 1, 5, 6, 7 or 8 C atoms or phenyl, which is replace or replace with 1 3 substituents selected from the group consisting of F, Cl, CF3, methyl and tietoxy; or the other substituents R (1), R (2) and R (3) independently of each other, phenyl, C 6 H 5 -alkyl (C, -C 4), naphthyl, biphenylyl, qumolyl, isoquinolyl or amidezolyl, the qumolyl being , iso-molyl or imidazolyl bonded through C or N, and the phenyl, C6H5-alkyl (C, -C4), naphthyl, biphenylyl, qumolyl, isoquinolyl and imidazolyl being unsubstituted or substituted with 1-3 substituents selected between the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamino and dimethylamino; or the other substituents R (l), R (2) and R (3) independently of each other -SR (10), -OR (10), -CR (10) R (11) R (12); R (10) -CfH2f-c? -alkalkyl (C3-Cfl), quinolyl, isoquinol, pipdmyl, imidazolyl or phenyl, the aromatic systems being qumolmyl, iso-molmyl, pipdinyl, imidazolyl and phenyl substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CFJ; CH 3, methoxy, hydroxy, amino, methylamino and dimethylammo; f zero, 1 or 2, - R (ll) and R (12) independently of one another as defined R (10), hydrogen or alkyl with 1, 2, 3 or 4 C atoms; R (4) and R (5) independently of one another hydrogen, alkyl having 1, 2 or 3 carbon atoms, F, Cl, Br, I, CN, OR (13), NR (14) R (15), - (CH2) n- (CF2) or-CF3; R (13), R (14) and R (15) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; n zero or 1, - or zero, 1 or 2, - as well as their pharmacologically acceptable salts;
(HOE 95 / F 253 - NZ 299,682) ao) Sulfonimido-amides of Formula I
where they mean: at least one of the three substituents R (l), R (2) and R (3) a benzoylguanidine,
that in the phenyl part is unsubstituted or substituted with 1-4 radicals selected from the group consisting of alkyl with 1, 2, 3, 4,, 6, 7 or 8 C atoms, alkenyl with 2, 3, 4 , r. , G, 7 n 8? Blots of C, - (CII2) mR (14), F, Cl, Br, 1, -C = N, CF3, R (22) S02-, R (23) R (24) N-CO-, R (25) -CO-, R (26) R (27) N-S02, -OR (35), -SR (35) or
NK (•; '.) K' (', (,); m zero, 1 or 2; R (14) -cycloalkyl (C3-C8) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, methoxy and -NR (15) R (16); R (15) and R (16) independently of one another hydrogen or -CH3; R (22), R (23), R (25) and R (26) independently of each other with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 2, 3, 4, 5, 6, 7 or 8 C atoms, (CH2) nR (29) or -CF3; n null, 1, 2, 3 or 4; R (29) -cycloalkyl (C3-C7) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -CF3, methyl, methoxy and -NR (30) R (31); ROO) and ROI) hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; C; or R (23), R (25) and R (26) hydrogen; R (24) and R (27) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (23) and R (24) as well as R (26) and R (27) in common 5 or 6 methylene groups, of which a CH2 group can be replaced by oxygen, -S-, -NH-, -NCH3 or -N-benzyl; R (35) and R (36) independently from each other hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C atoms; or R (35) and R (36) in common 4-7 methylene groups, of which a CH2 group can be replaced by oxygen, -S-, -NH-, -NCH3 or -N-benzyl; or R (35) phenyl, which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, -CF3, methyl, methoxy, S02R (5), S02NR (6) R (7) and -NR (32) R (33); R (5) alkyl with 1, 2, 3, 4, 5 or 6 C atoms; R (6) and R (7) independently of one another hydrogen or alkyl with 1, 2, 3 or 4 C atoms, R (32) and R (33) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms;
R (35) heteroaryl (C.-C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, arrimo, methylamino and dimethylamino; and the respectively other substituents R (1), R (2) and R (3) independently of each other with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, (CH 2) pR (10) ) p zero, 1, 2, 3 or 4; R (10) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -CF3, methyl, methoxy, -S02NR (17) R (8) and -S02R (9); R (17) and R (8) independently from each other hydrogen or alkyl having 1, 2, 3 or 4 C atoms; R (9) alkyl having 1, 2, 3 or 4 C atoms; or the respectively other radical R (l) and R (3) hydrogen, R (4) hydrogen or alkyl having 1, 2, 3 or 4 C atoms; as well as its pharmaceutically compatible salts;
(HOE 95 / F 265 - NZ 299.739) ap) Benzoylguanidmas of Formula I
where they mean R (l- alkyl with], 2, 3, 4, 5, 6, 7 or 8 C atoms or
NR (7) R (8), R (7) and R (8) independently of another hydrogen or alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms,
R (2: hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or -S02R (9) R (9) independently as defined R (l); RO: hydrogen, -SR (25), -OR (25), -NR (25) R (26) or -CR (25) R (26) R (27); R (25) hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamino and dimethylamino; or R (25) -heteroappe (C, -C9), which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of the groups F, Cl, CF3, CH, methoxy, hydroxy, ammo, methylamino and dimethylammon; R (26) and R (27) independently of one another as defined R (25) or hydrogen or alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms; R (4) hydrogen, F, Cl, Br, I, OH, -C = N, CF3, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 2, 3, 4, 5, 7 or 8 C atoms or - (CH 2) mR (14); m zero, 1 or 2; R (14) -cycloalkyl (Cj-C8) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, methoxy and -NR (15) R ( 16); R (15) and R (16) independently of one another hydrogen or -CH 3; R (5) and R (6) independently of each other hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl, -0RO2), -NR (33) R (34) or CF3; R (32), R (33) and R (34) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; as well as their pharmaceutically compatible salts, - (HOE 95 / F 269 K) aq) Benzenedicarboxylic acid diguanidides of the Formula
I
where they mean: one of the radicals R (l), R (2), R (3) and R (4) C0-N = C (NH2) 2, and the respectively other radicals R (l), R ( 2), R (3) and R (4). R (l) hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl, Br, I, -0RO2), -NR (33) R (34) or CF3; R (32), R (33) and R (34) independently of each other hydrogen or alkyl with 1, 2, 3, or 4 C atoms, R (2) and R (4) independently of each other hydrogen, F , Cl, Br, I, OH, -CN, CF3, -CO-N = C (NH2) 2, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 2, 3, 4, 5, 6, 7 or 8 C atoms or - (CH 2) mR (14); m zero, 1 or 2, - R (14) cycloalkyl (C3-C8) or phenyl, which is substituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, methoxy and -NR (15) R (16); R (15) and R (16) hydrogen or -CH 3; or R (2) and R (4) independently of each other pyrrol-1-? lo, pyrrol-2? -opyrrol-3-? lo, which is unsubstituted or substituted with 1-4 substituents selected from the group consisting of F, Cl, Br, I, -CN, (C2-C8) alkanoyl, (C2-C8) alkoxycarbonyl, formyl, carboxy, -CF3, methyl, methoxy; or R (2) and R (4) independently of one another R (22) -S02-, R (23) R (24) N-C0-, R (28) -C0- or R (29) R (30) ) N-S02; R (22) and R (28) independently of one another methyl or -CF3;
R (23), R (24), R (29) and R (30) independently of each other hydrogen or metal, -or R (2) and R (4) independently of each other -OR (35) or -NR (35) R (36), -R (35) and R (36) independently of one another hydrogen or alkyl with 1, 2,,? , 5 or C atoms; or R (35) and R (36) in common 4-7 methylene groups, of which a CH2 group can be replaced by oxygen, -S-, -NH-, -NCH3 or -N-benzyl; R (3) hydrogen, -SR (25), -0R (25), -NR (25) R (26), -CR (25) R (26) R (27); R (25) hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl , CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; or R (25) -heteroaryl (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; R (26) and R (27) independently of one another as defined R (25) or hydrogen or alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms; R (5) alkyl having 1, 2, 3 or 4 C, F, Cl, Br, I, X- (CH2) and-CF3 or femlo atoms, which is unsubstituted or substituted with 1-3 substituents selected from group consisting of F and Cl, -CF3, methyl, methoxy and -NR (6) R (7); R (6) and R (7) independently of one another hydrogen or -CH 3; X a bond or oxygen, - and zero, 1 or 2; as well as its pharmaceutically compatible salts;
(HOE 95 / F 269 BK) ar) Diguanidides of benzenedicarboxylic acids of the
Formula I
in which they mean: one of the radicals R (l), R (2), R (3) and R (5) -CO-N = C (NH2) 2; and the respectively other radicals R (l), R. (. 2), R (3) and
R (5): R (l) and R (5) independently of one another hydrogen, alkyl with 1, 2, 3 or 4 C atoms, F, Cl, -OR (32), -NR (33) R ( 34) Ó CF3; R (32), R (33) and R (34) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; R (2) hydrogen, F, Cl, Br, I, OH, -CN, CF3, -CO-N = C (NH2) 2, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 atoms of C, alkenyl with 2, 3, 4, 5, 6, 7 or 8 C atoms or (CHJ R (14 im zero, 1 or 2, - R (14) -cycloalkyl (C3-C8) or phenyl, which is substituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, methoxy and -NR (15) R (16); R (15) and R (16) independently one of other hydrogen or -CH3; or R (2) R (22) -S02-, RR ((223) R (24) N-CO-, R (28) -CO- or R (2 9) R (3 0) ) N- SO2 R (22) and R (28) independently of one another methyl or -CF3; R (23), R. (24), R (29) and R (30) independently of each other hydrogen or methyl or R (2) -OR (35) or -NR (35) R (36); R (35) and R (36) independently of one another hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 atoms of C, or R (35) and R (36) in common 4-7 methylene groups, of which a CH2 group may be replaced by oxygen, -S-, -NH-, -NCH3 or -N-benzyl; R (3) hydrogen, -SR (25), -OR (25), -NR (25) R (26), -CR (25) R (26) R (27); R (25) hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl , CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino;
or R (25) -heteroappe (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; R (26) and R (27) independently of one another as defined R (25) or hydrogen or alkyl with 1, 2, 3, 4,
, 6, 7 or 8 C atoms; R (4) CF3, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl (C3-) CB) or - (CH2) mR (14); m 1 or 2; R (14) -cycloalkyl (C3-C8) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, methoxy and -NR (15) R ( 16); R (15) and R (16) independently of one another hydrogen or -CH 3; or R (4) phenyl, which is substituted with 2, 3, 4 or 5 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and -NR (15) R (16); R (15) and R (16) independently of one another hydrogen or CH 3; as well as its pharmaceutically compatible salts;
(HOE 96 / F 013) as) Diguaids of diaryldicarboxylic acids of Formula I
in which they mean: one of the radicals R (l), R (2), RO), R (4) and R (5) -CO-N = C (NH2) 2, the respectively other radicals R (l) and R (5) independently of each other hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl, -OR (32), -NR (33) R (34) or CF3; R (32), R (33) and R (34) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; the respectively other radicals R (2) and R (4) independently of one another hydrogen, F, Cl, Br, I, OH, -CN, CF3, -CO-N = C (NH2) 2, alkyl with 1, 2 , 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 2, 3, 4, 5, 6, 7 or 8 C atoms or - (CH 2) fflR (14); m zero, 1 or 2; R (14! -cycloalkyl (C3-C8) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, methoxy and -NR (15) P ( 16), R (15) and R (16) hydrogen or -CH3, or ios respectively other radicals R (2) and R (4) independently of each other pyrrole-1-iole, pyrrol-2-? ρROL-3-io, which is unsubstituted or substituted with 1-4 substituents selected from the group consisting of F, Cl, Br, I, -CH, alkanoyl (C2-C8), alkoxycarbonyl (C2-C8), formyl, carboxy, -CF3, methyl, methoxy, or the respectively other radicals R (2) and R (4) R (22) -S02-, R (23) R (24) N-CO-, R (28) -CO- or R (29) R (30) N-SO2; R (22) and R (28) independently of one another methyl or -CF3; R (23), R (24), R (29) and R (30) independently of one another hydrogen or methyl, or the respective other radicals R (2) and R (4) independently of each other -OR (35) or -NR (35) R (36); R (35) and R (36) independently of one another hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C atoms; or R (35) and R (36) in common 4-7 methylene groups, of which a CH2 group can be replaced by oxygen, -S-, -NH-, -NCH3 or -N-benzyl; the respectively other radical R (3) hydrogen, -SR (25), -OR (25), -NR (25) R (26), -CR (25) R (26) R (27); R (25) hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl , CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; or R (25) -heteroaryl (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; R (26) and R (27) independently of one another as defined R (25) or hydrogen or alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms; one of the radicals R (6), R (7), R (8), R (9) and R (10) -CO-N = C (NH 2) 2; the respectively other radicals R (6) and R (10) independently of one another hydrogen, alkyl with 1, 2, 3 or 4 atoms of C, F, Cl, -OR (132), -NR (133) RÍ134) or CF.,; R (1 '2), R (1 -, 3) and K (lJ-1) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; the respectively other radicals R (7) and R (9) independently of one another hydrogen, F, Cl, Br, I, OH, -CN, CF3, -CO-N- = C (NH2) 2, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 2, 3, 4, 5, 6,
7 or 8 C atoms or - (CH 2) R (114); mm zero, 1 or 2; R (114) -cycloalkyl (C3-C8) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, methoxy and -NR (115) R ( 116); R (115) and R (116) hydrogen or -CH3; or the respectively other radicals R (7) and R { 9) independently of one another, eg, pyrrolidol, pyrrol-2-opyrrolidol, which is unsubstituted or substituted with 1-4 substituents selected from the group consisting of F, Cl, Br, I, -CN, (C2-C8) alkanoyl, (C2-C8) alkoxycarbonyl, formyl, carboxy, -CF3, methyl and methoxy; or the respectively other radicals R (7) and R (9) R (122) -S02-, R (123) R (124) N-CO-, R (128) -CO- or R (129) R (130 ) N-SO2; R (122) and R (128) independently of one another methyl or -CF3; R (123), R (124), R (129) and R (130) independently of each other hydrogen or meth i, or the respectively other radicals R (7) and R (9) independently of each other -OR (135) or NR (135) R (136); R (135) and R (136) independently of each other hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C atoms; or R (135) and R (136) in common 4-7 methylene groups, of which a CH2 group can be replaced by oxygen, -S-, -NH-, -NCH3 or -N-benzyl; the respectively other radical R (8) hydrogen, -SR (125), -OR (125), -NR (125) R (126) or -CR (125) R (126) R (127); R (125) hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl , CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; or R (125) -heteroappe (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; R (126) and R (127) independently of one another as defined R (125) or hydrogen or alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, -A is absent or means -NR (ll) -CO-, -NR (12) -C0-NR (13) -, -NR (17) -CO-NR (18i -so2-, -NR (19) -S02-, -S02 -NR (1 -SO, -SO, -NR (19) -CO-, -0-CO-NR (19) -S02 or -CR (20) = CR (21) -; R (ll), R ( 12), R (13), R (17), R (18), R (19), R (20) and R (21) independently of each other hydrogen or alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, as well as their pharmaceutically compatible salts;
(HOE 96 / F 026) at) Guanidides of substituted thiophenylalkenylcarboxylic acids of the Formula I
wherein they mean: at least one of the substituents R (l), R (2) and R (3) -Op- (CH2) s-CqF2q +, R (40) CO- OR R (31) SOk-; p zero or 1; s zero, 1, 2, 3 or 4;
q 1, 2, 3, 4, 5, 6, 7 or 8; k zero, 1 or 2; R (40) alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl and methoxy; R (31) alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl or methoxy; or ROÍ) NR (41) R (42); R (41) and R (42) independently of one another hydrogen, alkyl with 1, 2, 3 or 4 carbon atoms, perfluoroalkyl with 1, 2, 3 or 4 carbon atoms, or R (41) and R (42 ) in common 4 or 5 methylene groups, of which one CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, • respectively other substituents R (l), R (2) and R (3) independently of each other H, F, Cl, Br, I, CN,
-0na-CmaH, 2ma + .1 or -OgaCraH, 2raR (10) '; 'na zero or 1; ma zero, 1, 2, 3, 4, 5, 6, 7 or 8; ga zero or 1; zero, 1, 2, 3 or 4;
R (10) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms or phenyl, the phenyl being substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl and raetoxi; R (4) and R (5) independently of one another hydrogen, F, Cl, Br, I, CN, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from group consisting of F, Cl, CF3, methyl, methoxy and NR (14) R (15); R (14) and R (15) independently of each other H, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl with 1, 2, 3 or 4 carbon atoms; as well as its pharmaceutically compatible salts;
(HOE 96 / F 032) au) Ortho-substituted benzoylguanidines of Formula I
wherein they mean: R (2) and RO) independently of one another hydrogen, Cl, Br, I, alkyl (C.-C, cycloalkyl (C, -CJ or -OR (5);
R (5) alkyl (C, -C8) or -CdH2d-cycloalkyl (C3-C8); d zero, 1 or 2; hydrogen being always one of the two substituents R (2) and R (3), but not simultaneously hydrogen being both substituents R (2) and R (3), as well as their pharmaceutically compatible salts;
(HOE 96 / F 042) av) Benzoylguanidmas of Formula I
where they mean: R (l) H, F, Cl, Br, I, CN, N02, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkoxy with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, cycloalkoxy with 3, 4, 5, 6, 7 or 8 C atoms or X.; cH2) b-: CF2) C-CF3, X oxygen S, NR (5); to zero or 1; b zero, 1 or 2; c zero, 1, 2 or 3; R (5) H, alkyl having 1, 2, 3 or 4 carbon atoms or -CdH2dR (6); d zero, 1, 2, 3 or 4; R (6) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, phenyl, biphenylyl or naphthyl, the aromatic radicals being phenyl, biphenylyl or naphthyl unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and R (7) R (8); R (7) and R (8) independently H or alkyl with 1, 2, 3 or 4 C atoms; or R (l) -SR (10), -OR (10) or -CR (10) R (11) R (12); R (10) -CfH2f-c? Cloalkyl with 3, 4, 5, 6, 7 or 8 C atoms in the cycloalkyl or phenyl ring, the phenyl being substituted or substituted with 1-3 substituents selected between the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylammon, f zero, 1 or 2; R (ll) and R (12) independently of one another as defined R (10) or hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (l) phenyl, naphthyl, biphenylyl or heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, the latter linked through a C atom or an N atom of the ring, which in each case are substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3, CH 3, methoxy, hydroxy, ammo, methylamino and dimethylamino, or R (1) -SR (13 ), -OR (13), -NHR (13), -NR (13) R (14), -CHR (13) R (15), -C [R (15) R (16) OH], -C = CR (18), -CR [R (19)] = CHR (18), -C [R (20) R ((21)] k- (CO) - [CR (22) R (23)] tR (24), zero k, 1, 2, 3 or 4;
i zero, 1, 2, 3 or 4; R (13) and R (14) same or different - (CH2) - (CHOH) h- (CH2) .- (CHOH) * -R (17) or - (CH2) g-0- (CH2-CH20) HR (24); R (17) hydrogen or methyl; g, h and i equal or different zero, 1, 2, 3 or 4; j 1, 2, 3 or 4; R (15) and R (16) equal or different hydrogen, alkyl with 1,
2, 3, 4, 5 or 6 C atoms, or in common with the carbon atom that carries them, cycloalkyl with
3, 4, 5, 6, 7 or 8 C atoms; R (18) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (25) R (26); R (25) and R (26) H or alkyl with 1, 2, 3 or 4 C atoms; or R (18) heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, which is unsubstituted or substituted as phenyl; or R (18) alkyl having 1, 2, 3, 4, 5 or 6 C atoms, which is unsubstituted or substituted with 1-3 OH; or R (18) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms;
R (19), R (20), R (21), R (22) and R (23) equal or different hydrogen or methyl, - R (24) H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms -CMH2mR (18); m 1, 2, 3 0 4; R (2) and R (3) as defined R (l), -R (4) alkyl with 1, 2, 3 or 4 C atoms; as well as its pharmaceutically compatible salts;
(HOE 96 / F 043) aw) Ortho-substituted benzoylguanidines of Formula I
where they mean: R (l) H, F, Cl, Br, I, CN, NO., alkyl with 1, 2, 3, 4, 5, 6,
7 or 8 C atoms, alkoxy with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, cycloalkoxy with 3, 4 , 5, 6, 7 or 8 C atoms or
Xa- (CH2) b- (CF2) c-CF3; X oxygen, S, NR (5), zero or 1; b zero, 1 or 2; c zero, 1, 2 or 3; R (5) H, alkyl with 1, 2, 3 or 4 C atoms or -CdH2dR? d zero, 1, 2, 3 or 4; R (6) cycloalkyl with 3, 4, 5, 7 or 8 C atoms, phenyl, biphenylyl or naphthyl, the aromatic radicals being phenyl, biphenylyl or naphthyl unsubstituted or substituted with 1-3 substituents selected from the group consisting of group consisting of F, Cl, CF3, methyl, methoxy and NR (7) R (8); R (7) and R (8) independently H or alkyl with 1, 2, 3 or 4 C atoms; or R (l) -SR (10), -OR (10) or -CR (10) R (11) R (12); R (10) -CfH2f-cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms in the cycloalkyl or phenyl ring, the phenyl being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; f zero, 1 or 2; R (ll) and R (12) independently of one another as defined R (10) or hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (l) phenyl, naphthyl, biphenylyl or heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, the latter being linked through a C atom or an N atom. of the ring, which in each case are unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; or R (l) -SR (13), -OR (13), -NHR (13), -NR (13) R (14), -CHR (13) R (15), -C [R (15) R (16) OH], -C = CR (18), -CR [R (19)] = CHR (18), -C [R (20) R (21)] k- (CO) - [CR ( 22) R (23)] rR (24), zero k, 1, 2, 3 or 4; 1 zero, 1, 2, 3 or 4; R (13) and R (14) equal or different - (CH2) g- (CHOH) h- (CH2), - (CHOH). -R (17) or - (CH2) g-0- (CH2-CH20 ) hR (24); R (17) hydrogen or methyl, - g, h and i equal or different zero, 1, 2, 3 or 4; 1 1, 2, 3 or 4; and R (16) equal or different hydrogen, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, or in common with the carbon atom bearing them, cycloalkyl with 3, 4, 5, 6, 7 u 8 C atoms; R (18) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (25) R (26); R (25) and R (26) H or alkyl with 1, 2, 3 or 4 C atoms; or R (18) heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, which is unsubstituted or substituted as phenyl; or R (18) alkyl having 1, 2, 3, 4, 5 or 6 C atoms, which is unsubstituted or substituted with 1-3 OH; or R (18) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms; R (19), ROO), R (21), R (22) and R (23) equal or different hydrogen or methyl; R (24) H, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms -cmH2m-R < 18); m 1, 2, 3 0 4; one of both R (2) and R (3) hydroxyl substituents; and the respectively one of the substituents R (2) and R (3) is defined as R (l); R (4) alkyl having 1, 2, 3 or 4 C atoms; alkoxy with 1, 2, 3 or 4 C atoms; F, Cl, Br, I or - (CH2) n- (CF2) 0-CF3; n zero or 1, - or zero or 1; as well as its pharmaceutically compatible salts;
(HOE 96 / F 135) ax) Bis-substituted benzoylguanidines in ortho of the Formula
wherein they mean: R (l), R (2) and RO) independently of one another R (10) -SO-R (14) R (15) N-S02-; to zero, 1 or 2; R (10), R (14) and R (15) independently of each other with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, perfluoroalkyl with 1, 2, 3, 4, 5 , 6, 7 or 8 C atoms, alkenyl with 3, 4, 5 or 6 C atoms or -CabH2ab-R (16); ab zero, 1, 2, 3 or 4; R (16) cycloalkyl with 3, 4, 5, 6, 6, or C atoms, which is substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (17) R (18); R (17) and R (18) independently of each other hydrogen, CF3 or alkyl with 1, 2, 3 or 4 C atoms; or R (14) and R (15) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl; or R (14) and R (15) hydrogen; or R (l), R (2) and RO) independently of each other -SR (21), -OR (22), -NR (23) R (24) or -CR (25) R (26) R ( 27), R (21), R (22), R (23) and R (25) independently of each other -CbH2b-heterolalk (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamino and dimethylamino; b zero, 1 or 2, - R (24), R (26) and R { 27) independently of one another hydrogen, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; or R (l), R (2) and R (3) independently of each other hydrogen, F, Cl, Br, I-N < - < Xa CdaH2da + 1 '- (Xb Oh - (H2> d - d F2de + 1' alkenyl with 3, 4, 5, 6, 7 or 8 C atoms or -CdfH2dfR (30); (Xa) oxygen, sulfur or NR (33); R (33) hydrogen, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; dg zero or 1; (Xb) oxygen, sulfur or NR (34); R (34) hydrogen, alkyl with 1, 2, 3 or 4 carbon atoms or perfluoroalkyl with 1, 2, 3 or 4 carbon atoms; dh zero or 1 / da zero, 1, 2, 3 , 4, 5, 6, 7 or db zero, 1, 2, 3 or 4, zero, 1, 2, 3, 4, 5, 6 6 1, df zero, i, 2, 3 or 4, ROO) cycloalkilyl with 3, 4, 5, 6, phenyl, biphenylyl or naphthyl, the aromatic radicals being phenyl, biphenylyl or naphthyl unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (31) R (32); R (31) and R (32) hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl with 1, 2, 3 or 4 carbon atoms;
R (l), R (2) and R (3) independently of each other NR (40) R (41) or - (Xe) - (CH2) gbR (45); R (40) and R (41) independently of one another alkyl with 1, 2,
3, 4, 5, 6, 7 or 8 C atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or (pk v1 (iJ, e zero, 1, 2, 3 or 4; R (42) cycloalkyl with 3, 4, 5, 6 or 7 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (43) R (44); R (43) and R (44) independently of one another hydrogen, CF3 or alkyl with 1, 2, 3 or 4 carbon atoms; or R (40) and R (41 ) in common 4 or 5 methylene groups, of which one CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl, (Xe) oxygen, sulfur or NR (47), R (47) hydrogen, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 carbon atoms; zero eb, 1, 2, 3 or 4; R (45) cycloalkyl with 3, 4, 5 , 6 or 7 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy, NR (50) R (51) and - (Xfa ) - (CH2) ed- (Xfb) R (46); Xfa CH ?, oxygen, sulfur or NR (48);
Xfb oxygen, sulfur or NR (49); R (48), R (49), R (50) and R (51) independently of each other hydrogen, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; ed 1, 2, 3 0 4; R (46) hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl with 1, 2, 3 or 4 carbon atoms; or R (l), R (2) and RO) independently of one another -CHR (52) R (53); R (52) - (CH2) g- (CHOH) h- (CH) .- (CHOH) k -R (54) or - (CH2) g-0- (CH2-CH20) h-R (54); R (54) hydrogen or methyl; 9, h, i equal or different zero, 1, 2, 3 or 4; k 1, 2, 3 0 4; R (53) hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (l), R (2) and R (3) independently of each other -C (OH) R (55) R (56), -R (55) and R (56) equal or different from hydrogen or alkyl with 1, 2, 3 0 4 C atoms; or R (55) and R (56) in common cycloalkyl with 3, 4, 5 or 6 atoms
C; or R (55) -CH2OH; and R (4) and R (5) independently of one another alkyl with 1, 2, 3 or 4 C atoms, alkoxy with 1, 2, 3 or 4 C atoms, OH, F, Cl, Br, I, CN, -On- (CH.,) Or- (CF2) p-CF3; n zero or 1; or zero, 1 or 2, - p zero, 1 or 2; as well as its pharmaceutically compatible salts.
(96 / F 136) a and) substituted 1-Naphthoylguanidines of Formula I
where they mean: R2, R3, R4, R5, R6, R7 and R8 independently of one another H, F, Cl, Br, I, CN,
N02, CF3, C2F5 or XaYbZ; XO, S, NR (10), CR (11) R (12), C = 0, C (= 0) NR (10), C (= 0) 0, SO, S02, SO2NR (10), OC = 0, NR (10) C = O or NR (10) SO2, bonding with the naphthalene ring in each case through the atom on the left; R (10), R (ll) and R (12) independently of each other H, alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms, perfluoroalkyl with 1, 2, 3 or 4 carbon atoms or cycloalkyl with 3, 4, 5, 6 or 7 C atoms; to zero or 1; And alkylene with 1, 2, 3, 4, 5, 6, 7 or 8 CH2 groups, one of these CH2 groups being able to be replaced by 0, S, NR (13) or by o-, p- or m-phenylene; R (13) H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, perfluoroalkyl with 1, 2, 3 or 4 C atoms or cycloalkyl with 3, 4, 5 or 6 C atoms, b zero or 1; ZH, alkyl with 1, 2, 3, 4, 5, 6 or 7 C atoms, cycloalkyl with 3, 4, 5, 6 6 1 C atoms, C (= 0) R (15), S02R (15) , NR (16) R (17) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, Br, CF3, methyl, methoxy, NR (21) R (22); R (21) and R (22) independently of each other H or alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; R (15) N = C (NH2) 2, NR (18) R (19), N (CH2) CNR (18) R (19) or OR (20); C 2 OR 3; R (18) and R (19) independently of each other H, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; or R (18) and R (19) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3, N-benzyl or N- (p-chlorophenyl);
R (20) H, alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms, perfluoroalkyl with 1, 2, 3 or 4 carbon atoms or cycloalkyl with 3, 4, 5, 6, or 7 carbon atoms C; R (16) and R (17) independently of each other H, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; or R (16) and R (17) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3, N-benzyl or N- (p-chlorophenyl) , - or Z a heterocycle containing N with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, the N-containing heterocycle being linked through N or C, and being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, Br, CF3, methyl, methoxy and NR (21) R (22); but in the case where R (4) represents an alkoxy radical, at least one of the substituents R (2), RO), R (5), R (6), R (7) and R (8) are other than hydrogen, as well as their pharmaceutically compatible salts.
(96 / F 137) az) 2-Substituted naphthoylguanidines of Formula I
wherein at least one of the substituents R1, R3, R4, R5, R6, R7 and R8 XYa Z or X'YWZ 'XO, S, NR (10) or CR (11) R (12), R (10), R (ll) and R (12) independently of each other H, alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms, perfluoroalkyl with 1, 2, 3 or 4 carbon atoms, or cycloalkyl with 3, 4, 5, 6 or 7 C atoms, alkylene with 1, 2, 3, 4, 5, 6, 7 or 8 CH2 groups, one of these CH2 groups being able to be replaced by O, S, NR ( 13) or either o-, p- or m-phenylene; R (13) H, alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms, perfluoroalkyl with 1, 2, 3 or 4 carbon atoms or cycloalkyl with 3, 4, 5 or 6 carbon atoms; to zero or 1, - CH2, S02, S (= 0) (= NH) or - if W does not immediately follow a heteroatom of the group XY - also O or NR (14); R (14) H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, perfluoroalkyl with 1, 2, 3 or 4 C atoms or cycloalkyl with 3, 4, 5 or 6 C atoms, (= 0) R (15), S02R (15) or - in the case that W does not mean O or NR (14) - also NR (16) R (17); R (15) N = C (NH2) 2, NR (18) R (19), N (CH2) bNR (18) R (19) or OR (20); b 2 or 3; R (18) and R (19) independently of each other H, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; or R (18) and R (19) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S,
NH, N-CH3, N-benzyl or N- (p-chlorophenyl); R (20) H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, perfluoroalkyl with
1, 2, 3 or 4 C atoms or cycloalkyl with 3, 4, 5, 6 or 7 C atoms; R (16) and R (17) independently of each other H, alkyl with 1, 2, 3, 4, 5, 6, 7 -u 8 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; or R (16) and R (17) in common 4 or 5 methylene groups, of which one CH2 group can be replaced by oxygen, S, NH, N-CH3, N-benzyl or N- (p-chlorophenyl) , -C = 0, C (= O) NR (30), C (= 0) 0, SO, S02, SO2NR (30), OC = 0, NR (30) C = O or NR (30) SO2, bonding with the naphthalene ring in each case through the atom on the left; ROO) H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, perfluoroalkyl with 1, 2, 3 or 4 C atoms or cycloalkyl with 3, 4, 5, 6 or 7 C atoms; C (= 0) R (15), S02R (15), a heterocycle containing N with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, the heterocycle containing N being bound to through N or C and being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, Br, CF3, methyl, methoxy and
NR (21) R (22); R (21) and R (22) independently of each other H, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; R (15) N = C (NH2) 2, NR (18) R (19), N (CH.,) FaNR (18) R (19) or OR O); R (18) and R (19) independently of each other H, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; or R (18) and R (19) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3, N-benzyl or N- (p-chlorophenyl); b 2 or 3, - ROO) H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, perfluoroalkyl with 1, 2, 3 or 4 C atoms or cycloalkyl with 3, 4, 5, 6 or 7 C atoms; or Z '- in case it does not mean O or NR (14) - NR (16) R (17); R (16) and R (17) independently of each other H, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; or R (16) and R (17) in common 4 or 5 methylene groups, of which one CH2 group can be replaced by oxygen, S, NH, N-CH3, N-benzyl or N- (p-chlorophenyl); and the respectively other remaining substituents R1, R3, R4, R5, R6, R7 and R8, which are not yet covered by the definitions given above, independently of each other H, F, Cl, Br, I, CN, N02, CF3, C2F5 or VpQqU; V O, S, SO, S02, NR (60), OC = 0, C = 0, C (= 0) NR (60), C (= 0) 0 or CR (66) R (67); R (60), R (66) and R (67) independently of each other H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, perfluoroalkyl with 1, 2, 3 or 4 carbon atoms. C or cycloalkyl with 3, 4, 5, 6 or 7 C atoms; p zero or 1, - Q alkylene with 1, 2, 3, 4, 5, 6, 7 or 8 groups
CH2, one of these CH2 groups being able to be replaced by 0, S, NR (68) or by o-, p- or m-phenylene; R (68) H, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, perfluoroalkyl having 1, 2, 3 or 4 carbon atoms, or cycloalkyl having 3, 4, 5 or 6 carbon atoms; q zero or 1; UH, alkyl with 1, 2, 3, 4, 5, 6 or 7 C atoms, cycloalkyl with 3, 4, 5, 6 or 7 C atoms, C (= 0) R (65), S02R (65) , NR (61) R (62) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, Br, CF3, methyl, methoxy and NR (63) R (64); R (63) and R (64) independently of each other H, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; R (65) N = C (NH2) 2, NR (61) R (62) OR OR (60); R (61) and R (62) independently of each other H, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or perfluoroalkyl with 1, 2, 3 or 4 carbon atoms
C; or R (61) and R (62) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3, N-benzyl or N- (p-chlorophenyl); or U a heterocycle containing N with 1, 2, 3, 4, 5,
6, 7, 8 or 9 C atoms, the heterocycle containing N being linked through N or C, and being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, Br , CF3, methyl, methoxy and NR (63) R (64), but different from hydrogen being at least one of the substituents R5, R6, R7 and R8, - as well as their pharmaceutically compatible salts,
(96 / F 141) ba) Benzoylguanid as substituted in ortho of Formula I
where they mean: R (l) H, F, Cl, Br, I, CN, NO, ,, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkoxy with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms or X. (CH2) b-! CF2) c-CF3; X oxygen, sulfur or NR (9) at zero or 1, - b zero, 1 or 2; c zero, 1, 2 OR 3; R (9) H, alkyl having 1, 2, 3 or 4 C atoms or CdH2dR (6); d zero, 1, 2, 3 or 4; R (6) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, phenyl, biphenylyl or naphthyl, the aromatic radicals being phenyl, biphenylyl or naphthyl unsubstituted or substituted with 1-3 selected substituents between the group consisting of F, Cl, CF3, methyl, methoxy and NR (7) R (8); R (7) and R (8) independently H or alkyl with 1, 2, 3 or 4 C atoms; or R (l) -SR (10), -OR (10) OR -CR (10) R (11) R (12); R (10) -CfH2f with 3, 4, 5, 6, 7 or 8 C atoms in the cycloalkyl ring, heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms or phenyl, the heteroaryl and phenyl being substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3, CH 3, methoxy, hydroxy, ammo, methylamine and dimethylamino; f zero, 1 or 2; R (ll) and R (12) independently of one another as defined R (10) or hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (l) phenyl, naphthyl, biphenylyl or heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, the latter linked through a C atom or an N atom. of the ring, which in each case are unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino, or R (l) -SR ( 13), -0R (13). -NHR (13), -NR (13) R (14), -CHR (13) R (15), -C [R (15) R (16)] 0H, -C = CR (18), -CR [R (19)] = CHR (18), -C [R (20) R (21)] k- (CO) - [CR (22) R (23)]. -R (24), k zero, 1, 2, 3 or 4; 1 zero, 1, 2, 3 or 4; R (13) and R (14) the same or different - (CH2) g- (CHOH) h- (CH2) 1- (CH0H) | ck-R (17) OR - (CH2) g-0- (CH2- CH20) hR (24); R (17) hydrogen or methyl, g, h and i equal or different zero, 1, 2, 3 or 4; kk 1, 2, 3 or 4; R (15) and R (16) equal or different hydrogen, alkyl with 1,
2, 3, 4, 5 or 6 C atoms, or in common with the carbon atom that carries them, cycloalkyl with
3, 4, 5, 6, 7 or 8 C atoms; R (18) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF., methyl, methoxy and NR (25) R (26); R (25) and R (26) H or alkyl with 1, 2, 3 or 4 C atoms; or R (18) heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, which is unsubstituted or substituted as phenyl, -or R (18) alkyl with 1, 2, 3 , 4, 5 or 6 C atoms, which is unsubstituted or substituted with 1-3 OH; or R (18) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms;
R (19), R (20), R (21), R (22) and R (23) are the same or different hydrogen or methyl; R (24) H, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms or -CmH2m-R (18); 1, 2, 3 0 4; one of the two substituents R (2) and R (3) -0-CO-R (27); R (27) alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, phenyl, biphenylyl, naphthyl, pyridyl or quinolinyl, the phenyl, biphenylyl, naphthyl, pyridyl or quinolinyl being unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (7) R (8); R (7) and R (8) independently from each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; always being one of the substituents R (2) and R (3) defined as R (l); R (4) and R (5) independently of one another hydrogen, alkyl with
1, 2, 3 or 4 C atoms; alkoxy with 1, 2, 3 or 4 atoms of C, F, Cl, Br, I, CN or - (CH2) n- (CF2) 0"CF3; n zero or 1, or zero or 1, as well as its salts pharmaceutically compatible
(96 / F 154) bb) Benzoylguanidines of Formula I
where they mean: R (l) R (13) -SOm or R (14) R (15) N-SO m 1 or 2; R (13) alkyl with 1, 2, 3,, 5, 6, 7 or 8 C atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 3, 4 , 5, 6, 7 or 8 C atoms or -CnH2nR (16), n zero, 1, 2, 3 or 4, - R (16) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms , phenyl, biphenylyl or naphthyl, the phenyl, biphenylyl and naphthyl being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (25) R (26); R (25) and R (26) independently of each other hydrogen, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; R (14) hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 3, 4, 5, 6, 7 or 8 C atoms or -CnH2n ~ R (27), n zero, 1, 2, 3 or 4; R (27) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, phenyl, biphenylyl or naphthyl, the phenyl, biphenylyl and naphthyl being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (28) R (29); R (28) and R (29) independently of each other hydrogen, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; R (15) hydrogen, alkyl with 1, 2, 3 or 4 carbon atoms or perfluoroalkyl with 1, 2, 3 or 4 carbon atoms, or R (14) and R (15) in common 4 or 5 methylene groups , of which a CH2 group may be replaced by oxygen, S, NH, N-CH3 or N-benzyl; one of the substituents R (2) and R (3) hydrogen; and the respectively another substituent R (2) and R (3) -CHR (30) R (31); ROO) - (CH2) g- (CHOH) h- (CH2), - (CHOH) k -R (32) or - (CH2) g-0- (CH2-CH20) h-R (24); R (24) and R (32) independently of one another hydrogen or methyl; g, h, i equal or different, zero, 1, 2, 3 or 4; k 1, 2, 3 or 4; or the respectively another substituent R (2) and R (3) -C (OH) R (33) R (34); same or different hydrogen or alkyl with 1, 2, 3 or 4 C or R atoms (33) and R (34) in common cycloalkyl with 3, 4, 5 or 6 C atoms; or R (33) -CH20H; R (4) alkyl with 1, 2, 3 or 4 C atoms, alkoxy with 1, 2, 3 or 4 C atoms, F, Cl, Br, I, CN, - (CH2) n- (CF2) 0 -CF3; n zero or 1, or zero, 1 or 2; as well as its pharmaceutically compatible salts.
(96 / F 202) be) Indanilidmacetilguanidmas of Formula I
wherein R 1, R 2, R 3, R 4, R 5 and R 6 are independently from each other, H, C, -C, 0 alkyl; haloalkyl with 1-6 carbon atoms, O-alkyl ^ -Cw, haloalkoxy with 1-6 carbon atoms, F,
Cl, Br, I, aryl, substituted aryl, heteroaryl, substituted heteroaryl, OH, O-lower alkyl, 0-aryl, O-lower alkyl-aryl, O-substituted aryl,
0-Alkyl-substituted aryl, 0-C (= 0) -alkyl C, -C4-aplo, OC (= 0) -alkyl C, -C4, OC (= 0) -N (C-alkyl, - C4) 2, NO, CN, CF, NH, NH-C (= 0) -alkyl C, -C4, NH-C (= 0) -NH2, COOH, C (= 0) -0-alkyl C.-C4, C (= 0) -NH2, C (= 0) -NH-C-alkyl, -C4, C (= 0) -N (C-C4-alkyl) 2, C-alkyl, -C4-C00H , alkyl C, -C4-C (= 0) -O-C, -C4, S03H, S02-alkyl; S02-alkaryl, S02-N- (alkyl) 2, S02-N (alkyl) (alkylaryl), C (= 0) -R11, alkyl C, -C, 0-C (= 0) -Rll , C2-C10 alkenyl (= 0) -Rll, C2-C alkyI, QC (= 0) -Rll, NH-C (= 0) -alkyl C, -C, QC (= 0) -Rll or 0-alkyl C, -C "-C (= 0) -Rll; Rll C, -C 4 alkyl, C, -C 4 alkynyl, aryl, substituted aryl, NH 2, NH-C, -C 4 alkyl, N- (C 1 -C 4 alkyl), S 0 3 H, S 0 2 -alkyl, S 0-2 alkylaryl, S 0 2 -N- (alkyl) 2 or S02-N (alkyl) (alkylaryl); X 0, S OR NH; R7, R8, R9 and RIO independently of each other H, alkyl, cycloalkyl, aryl, alkylaryl, or R8 and R9 in common are part of a heterocyclic ring of
, 6 or 7 members; or their pharmaceutically acceptable salts.
(96 / F 226) bd) Phenyl-substituted alkenylcarboxylic acid guanidides of Formula I
where they mean:
T
R (A) hydrogen, F, Cl, Br, I, CN, OH, OR (6), alkyl (C, -C4), 0p (CH2) aCbF2b +,, (C3-C8) cycloalkyl or NR (7) R (8) r zero or 1; to zero, 1, 2, 3 or 4; b 1, 2, 3 or 4; R (6) alkyl (C, -C4), perfluoroalkyl (C, -C4), alkenyl (C3-C6), cycloalkyl (C3-C8), phenyl or benzyl, the phenyl nucleus being unsubstituted or substituted with 1- 3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10); R (9) and R (10) H, alkyl '(C, -C4) or perfluoroalkyl (C, -C4); R (7) and R (8) independently of one another as defined R (6); or R (7) and R (8) in common 4 or 5 metlene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl; R (B), R (C) and R (D) independently as defined R (A); x zero, 1 or 2; and zero, 1 or 2; R (F) hydrogen, F, Cl, Br, I, CN, 0R (12), alkyl (C, -C8), 0p (CH2) fCgF2g +,, (C3-C8) cycloalkyl or heteroaryl (C, -C9); p zero or 1; f zero, 1, 2, 3 or 4; g 1, 2, 3, 4, 5, 6, 7 or 8; R (12) alkyl (C, -C8), perfluoroalkyl (C ^ -C ^), alkenyl (C3-C8), cycloalkyl (C3-C8), phenyl or benzyl, the phenyl nucleus being unsubstituted or substituted -3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (13) R (14); R (13) and R (14) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4);
R (E) independently as defined R (F); R (I) independently as T is defined; or R (l) hydrogen, -OkCmH2m +, -0n (CH2) pCqF2q +,, F, Cl, Br, I, CN, - (C = 0) -N = C (NH2) 2, -SOrR (17), -SOr2NR (31) R (32); -Ou (CH2) vC6H5, -Ou2-heteroaryl (C, -C9) or Su2"-heteroaryl (C.-C8); k zero or 1; m zero, 1, 2, 3, 4 5, 6, 7 a zero or 1; P zero 1, 2, 3 or 4 q 1, 2, 3, 4, 5, 6 7 ur zero, 1, 2, r2 zero, 1, 2, independently of one another, hydrogen, alkyl (C, -C8) or perfluoroalkyl (C, -C8), - or ROI) and R (32) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by oxygen, S, NH , N-CH3 or N-benzyl, R (17) (C1-C8) alkyl, or zero or 1, - u2 zero or 1, - v zero, 1, 2, 3 or 4, the phenyl nucleus being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy, - (CHJ NR (21) R (22), NR (18) R (19) and heteroaryl (C, - C9), R (18), R (19), R (21) and R (22) independently of each other alkyl (C, -C4) or perfluoroalkyl (C, -C4); w 1, 2, 3 0 4; the heteroaryl heterocycle (C, -C8) being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl or methoxy; R (2), RO), R (4) and R (5) independently of one another as defined R (l), or R (l) and R ((2) or R (2) and RO) in each case in common -CH-CH = CH-CH-, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy, - (CH2) w2NR (24) R (25) and NR (26) R (27); R (24), R (25), R (26) and R (27) H, (C, -C4) alkyl or perfluoroalkyl (C.-C4); w2 1, 2, 3 0 4; the radical T being present in the molecule at least twice but only at most three times; as well as its pharmaceutically compatible salts
Í97 / F 082) be) Benzoylguanidines of Formula I
R (1)
where they mean: R (1) CF3; one of the substituents R (2) and R (3) hydrogen; and the respectively another substituent R (2) and R (3) -C (OH) (CH3) -CH2OH, -CH (CH3) -CH20H or -C (OH) (CH3) 2; R (4) methyl, methoxy, Cl or CF3; as well as its pharmaceutically compatible salts;
(DE 195.02.895, DE 44.30.212, EP 667.341, DE 44.04.184, EP 708.088, EP 723.963, EP 0.694.537, DE 44.21.495, EP 699,660, EP 699,663, EP 699,666, DE 43.37.611, EP 0.719.766, WO 94/26709, WO 96/04241, EP 726,254, US 4,251,545, DE 35.02.629, WO 84/00875, Kumamoto et al., Pharm. Bull. [1966], 7-13; .027; JP 8225513; EP 743,301)
II. The compounds of the Formula are also suitable
where they mean: W, Y and Z a nitrogen atom or a C atom substituted with
R (2) or R (3) or R (4); R (l) hydrogen, A, Hal, -CF, • CH2F, -CHF, -CHpCF-,, -CF -CN, -N02, ethynyl, or an X-R '; A alkyl with 1 to 6 C atoms; Hal F, Cl, Br or I; X oxygen, S or NR "; R" hydrogen, A or a cyclic methylene chain with 3 to 7 C atoms; R 'H, A, HO-A-, HOOC-A-, cycloalkyl (Cz-C7), cycloalkyl (C6-C &) -alkyl, CF3, CH2F, CHF2, CH2-CF3, Ph, -CH2-Ph or Het; Ph phenyl, naphthyl or biphenylyl unsubstituted or substituted one, two or three times with A, OA, NR'R ", Hal or CF3; Het a saturated, unsaturated or aromatic heterocycle of one or two nuclei with 1 to 4 N atoms , O and / or S, which is unsubstituted or substituted one, two or three times with Hal, CF3, A, OH, OA, -XR ', -CN, -N02, and / or carboni1 -oxygen, the Het being bound through N or of an alkylene chain C 'mH, 2m with m = zero to 6; or R' and R "in common alkylene with 4-5 C atoms, with a CH2 group also being replaced by oxygen, S , NH, NA, N-Ph and N-CH2-Ph; RO) and R (3) independently of one another hydrogen, Hal, A, HO-A-, X-R ', -C (= N-OH) -A, A-0-CO-alkyl (C.-C -, CN, N02, COOH, A substituted with halogen, especially CF3, CH2F, CHF2, C2F5, CH., CF3, or S (0) nR "', R' '' A, Ph or Het; n zero, 1 or 2; or RO) and R (3) independently of one another S02NR'R ", Ph or -O-Ph, -0-CH2-Ph, -CO-A, -CHO, -COOA, -CSNR'R '', -CONR'R '-CH = CH-COOH, -CH = CH-COOA, indenyl, indanyl, decahydronaphthyl, cyclopentenyl, dihydrothienyl, dihydrofuryl, heterobicyclic, alkylthienyl, halothienyl, haloalkylthienyl, acylthienyl, halofuryl, haloalkylfuryl or pyrrolyl; or R (2) and R (3) independently of one another R (5) -0 -, - R (5) hydrogen, A, alkenyl (C, -C6) or cycloalkyl (C3-C7), -R (4) Ph, Het, -O-Het, CF3, S (0) nR "'# -S02NR'R", Alk;
or two of the substituents R (l) to R (4) form one another with an -O-CR (6) R (7) -CO-NR (8) group
with R (2) in the indicated meaning, - R (6) "R (7), R (8) and R (9) independently of each other H or A; or R (8) cycloalkyl (C5-C7);
R (9) cyano; Alk alkyl (C, -C8) linear or branched or cycloalkyl (C3-C8) which is unsubstituted or substituted with A one, two or three times;
Alk an ethenyl or ethyl radical substituted with H, A, Ph or Het;
(DE 41.27.026, DE 43.37.609, JP 07025768, Edward J. Cragoe, Jr., DIURETICS [Chemistry, Pharmacology and Medicine], J. Wiley & Sons (1983), 303-341], - III. Compounds of the Formula
in which they mean: XH, Hal, (Hal) 3C-, alkyl (C, -C6), cycloalkyl (C3-C6), substituted phenyl, alkyl (C, -C5) -S- or alkyl (C, -C5) ) -S02-; And NH2 or substituted amino; or X and Z in common a chain of -1CH2) 4- or a chain of 1,3-butadienylene; or Z H, Hal, OH, HS, (C-C5) alkyl, (C3-C6) cycloalkyl, substituted phenyl; or Z an arrimo group -NR (1) R (2); R (1) H, straight or branched chain (C, -C 8) alkyl, optionally substituted, which may be interrupted by oxygen; or R (l) alkenyl (C3-C8), alkyl (C3-C8), cycloalkyl (C3-C7) or phenyl substituted with OH or phenyl-alkyl (C, -C4) substituted with OH or cycloalkyl (C3-C7) substituted with OH; R (2) 1-morpholmo, hydrogen or a linear or branched alkyl chain 'C.-C8), which may be interrupted by oxygen, an amino group, (u and ii linear or branched alkyl (C, Cg) alkyl is unsubstituted or substituted with a substituted or unsubstituted uni- or plup-nuclear heterocycle, containing nitrogen, oxygen or sulfur atoms; or whose alkyl chain is substituted with phenyl, optionally substituted once or multiple times with (C 4 -C) alkoxy, optionally substituted with OH, alkylamine, alkyl or phenyl; or with an aminocarbonyl group or with hydroxy groups or (C, -C4) alkoxy or R (2) phenyl, sm substituted or substituted with alkyl, alkoxy, an ammo group, which bears as substituents: H, a heterocyclic uni- or plup -nu- clear, which contains nitrogen, oxygen or sulfur atoms, which is unsubstituted or substituted with H, Hal or alkyl (C, -C4); a phenyl radical, sm substituted or substituted with a substituent, selected from the group consisting of (C, -C4) alkyl, (C, -C4) alkoxy, Hal and OH; or R (2) 1-p? per?, unsubstituted or substituted in position 4 with an acyl radical of an aliphatic, alicyclic, aromatic or heteroaromatic carboxylic acid, alkyl (C, -C8), which in turn it may be substituted with OH or (C, -C4) alkoxy or with a phenyl radical substituted with (C, -C4) alkoxy; or R (2) amide, which is unsubstituted or substituted with phenyl, which is unsubstituted or substituted with Hal or alkyl; or R (2) an acyl radical of an aliphatic, alicyclic, aromatic or heteroaromatic carboxylic acid, or R (2) an alkyl chain (C, -C8), which may be substituted with a phenyl radical bearing OH radicals, alkoxy or alkyl; or R (l) and R (2) in common with the N atom, to which they are attached, a piperazine ring, which is unsubstituted or carries, through a methylene chain (C, -C6), a single- or pluri-nuclear heterocycle, containing nitrogen, oxygen or sulfur (DE 41.27.026 and DE 43.37.609); Hal F, Cl, Br or I;
(EP 708,091, EP 622,356, JP 5-125085) IV. Also suitable are indoloylguanidine derivatives of the Formula
wherein they mean: R (2) hydrogen, unsubstituted or substituted (C, -C8) alkyl, (C3-C7) cycloalkyl, OH, (C, -C6) -0- alkyl, an aromatic radical or a group - CH2-R (20); R (20) (C2-C6) alkenyl or (C2-C6) alkynyl; R (l) from 1 to 5 identical or different substituents, which mean: hydrogen, unsubstituted or substituted (C, -C8) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, (C3-C7) cycloalkyl ), halogen, -N02, (C2-C8) alkanoyl, arylalkanoyl with up to 10 carbon atoms, aroyl with up to 11 carbon atoms, -COOH, alkoxycarbonyl (C2-C6), an aromatic group, one of the groups indicated below : -ORO), -NR (6) R (7) or -S (O) nR (40); RO) hydrogen, (C, -C8) alkyl, substituted (C, -C8) alkyl, (C3-C7) cycloalkyl, an aromatic radical or a -CH2-R (30) ROO) alkenyl or alkyl group; R (6) and R (7) independently of one another hydrogen, unsubstituted or substituted (C, -C8) alkyl, (C3-C7) cycloalkyl, (C2-C8) alkanoyl, an aplalcanoyl group with up to 10 C atoms , an aroyl group with up to 11 carbon atoms, an aromatic group or -CH2-R (60); R (60) (C2-C6) alkenyl or (C2-C6) alkyl; or R (6) and R (7) in common with the N atom, a cyclic amine of 5-7 members, which may also contain other heteroatoms in the ring; zero, 1 or 2, R (40) unsubstituted or substituted alkyl (C, -C8), or an aromatic group or a group _A- ^ H ~ "R1
To oxygen, -S (0) n. or -NR (50) -; R (50) hydrogen or alkyl (C, -C8); R 'hydrogen, (C, -C8) alkyl substituted or substituted, wherein the ring represents a 3-8 membered saturated heterocycle with an N atom; said substituted alkyl bears one or more groups selected from the group consisting of halogen, -OH, (C, -Ci) alkoxy, -CN, -COOH, (C2-C6) alkoxycarbon, (C2-C8) alkanoyl, arylalkanoyl with up to 10 carbon atoms, aroyl with up to 11 carbon atoms, an aromatic group, equal or different, R (5), R (4) and R (5) -CONR (4), hydrogen or alkyl (C, - C8), -or R (4) and R (5) are linked together and form in common a cyclic amine of 5-7 links, which may also contain other heteroatoms in the ring, or the said substituted alkyl carries a group
where they mean: E an N atom or a CH group; R "hydrogen, (C, -C8) alkyl unsubstituted or substituted with OH or substituted (C, -C8) alkyl, (C, -C6) alkoxy, -CN, -COOH, (C2-C6) alkoxycarbonyl, alkanoyl (C2-C8), aralkanoyl with up to 10 carbon atoms, aroyl with up to 11 carbon atoms, an aromatic group, -NR (6) R (7), -CONR (4) R (5); R (4) and R (5) independently from each other hydrogen or alkyl (C, -C8), meaning the cyclic system of the Formula
an aliphatic or heterocyclic saturated 3-8 membered ring system with an N atom, and the aromatic groups mentioned being an aplo radical with up to 10 C atoms, a 5- or 6-membered hetero-radical with 1-4 atoms of N, a 5- or 6-membered heteroaryl group containing 1 or 2 N atoms and a heteroatom meaning oxygen or sulfur, or furyl, and the said aryl radicals being unsubstituted or substituted with alkyl (C, - C8) unsubstituted or substituted (C, -C8) alkyl, halogen, -N02, alkoxycarbonyl (C2-C6), COOH, -ORO), NR (6) R (7), -CONR (4) R (5) , -SO..NR (6) R (7) or S (O) nR (40), where R (l) and the guanidinocarbonyl radical can be located in any place of the 5 or 6 member ring of the mdol system, as well as the corresponding pharmaceutically compatible salts.
V. In addition, the heterocyclic guanidine derivatives of the Formula are suitable
wherein they mean: X -O-, -S-, -NH-, -N [(C-C4) alkyl- or -N (phenyl); R (l), R (2) and R (3) hydrogen, halogen, alkyl (C, -C4), alkyl (C, -C4) -O-, phenyl, benzyl; or two of the substituents R (l), R. (. 2) and R (3) in common with one side of the benzo system, a 4-6 membered carbocyclic ring, -R (4) and R (5) independently of one another hydrogen, alkyl (C.-C, 2) ), benzhydryl, aralkyl, which is unsubstituted or substituted by one or more substituents taken from the groups formed by halogen, alkyl (C.sub.4 -C.sub.4), alkyl (C.sub.4 -C.sub.4) -0- or -CF.sub.3, - (CH.sub.2) ) m-CH2-T, m zero up to 3, - T -CO-OT (l); T (l) hydrogen or alkyl (C, -C4); C and an unsaturated heterocycle condensed with benzo or a dihydro-heterocycle with 5-membered ring,
R (6) a pyrazole or an amiazole ring of the Formula
a naphthyl radical or a dihydro- or tetrahydro-naphthyl radical
a radical 2-, 3- or 4-p? r? d? lo R (8) - < <
R (T)
Z N- or CH; a thienyl radical - - - < 7) \ -g
R (6) hydrogen, halogen, hydroxy, alkyl (C, -C 10), alkyl (C, -C 10) -O-, phenoxy, alkyloxy (C, -C 10) -methyloxy or - (O) nS-R (9) ); R (9) (C, -C, 0) alkyl, thienyl, pyridyl, thiazolyl, thiadiazolyl, imidazolyl, pyrazolyl or phenyl, which is unsubstituted or substituted once or twice by halogen, (C, -C4) alkyl or alkyl (C, -C4) -0-; R (7) and R (8) hydrogen, halogen, hydroxyl, alkyl (C.-C10), alkyl (C, -C, 0) -0-, phenyl, phenoxy or alkoxy (C, -C, 0) - methyloxy; or Cy phenyl, which is unsubstituted or substituted once or twice with halogen, alkyl (C, -C4) or alkyl (C, -C4) -0-;
or Cy -Gr-Am; Gr -R (13) -R (12) - (CH2) q-C [W] [W (1)] - (CH2) q-; R (13) R (14) - or -R (15) -; R (12) a single bond, -O-, - (0) nS -, - CO- or -CONH-, R (13) a single bond, phenyl, thienyl, pipdoyl, thiazolyl, thiadiazolyl, imidazolyl or pyrazolyl; 14) a single bond or S02 ~; R (15) alkenyl (C2-C, 0) or alkyl (C2-C10); W and W (l) independently of each other hydrogen, (C-C4) alkyl; W and W (l) linked cyclically to each other, a (C3-C8) hydrocarbon ring, q and q 'from zero to 9, - Am -NR (10) R (11), R (10) hydrogen, alkyl (C, -C4) or benzyl, R (ll) alkyl (C, -C4), phenyl or benzyl, or R (10) and R (ll) in common an alkylene group (C3-C10), which is unsubstituted or substituted with -COOH, (C, -C5) alkoxycarbonyl, (C2-C4) hydroxyalkylene or benzyl, or pyrrolyl, pyridyl, pyrazolyl, morpholyl, dihydropipyl, tetrahydropipyl, qumuclidemiyl, imidazolyl, 3-azab? C? Clo [3.2 .1] o, which is unsubstituted or substituted with alkyl (C.-C4), Am azabicyclo [3.2.2] nonyl, or Am a piperaz group or of the formula
R (16) hydrogen, (C, -C 4) alkyl, (C 3 -C 6) cycloalkyl, phenyl, tolyl, methoxyphenyl, halophenyl, diphenylmethylene, benzyl or pyridyl; or Am a azido group - (O) t- (CH2) -C [W] [W (l)] - (CH2) -N3; t zero or 1, - W and W (l) possessing the previously indicated meanings; as well as optical enantiomers and pharmacologically compatible salts.
SAW. Guanidine compounds, which are described in EP-743,301 (DE 195 17 848), EP 758,644 (DE 195,29,612), EP 760,365 (DE 195.31.138), are also suitable.
with R1 = R2 equal to H, halo, alkyl, CN, N02, perfluoroalkyl, SOnCF3; R3 = CH = CH2, CH2-CH = CH2, CH2-CH2-CH = CH2, cycloalkenyl, cycloalkenylalkyl; R4 = alkyl, phenyl (substituted), or as described in DE 195.48.708, WO 97.25.310, WO 97.27.183, DE 196.01.303, EP 787.728, JP 82.25.513, JP 090.59.245, JP 090.67.332, JP 090.67.340,
WO 97.11.055 and EP 743,301.
Examples of classes of active substances on the heart and circulation, which can be therapeutically combined advantageously with NHE inhibitors, are beta-receptor blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, receptor blockers of angiotensin, loop diuretics of Henle, thiazide diuretics, potassium-sparing diuretics, aldosterone antagonists, as used for example in blood hypotension, as well as cardioglycosides or other contraction-strengthening agents in the treatment of Heart failure and congestive heart failures as well as antiarrhythmic agents of Classes I-IV, nitrates, KATp openers, KA? p blockers, inhibitors of the ileo-activable sodium channel by veratridine, etc. Thus, for example: beta-blockers propranolol, atenolol, metoprolol; calcium channel blockers, hydrochloride dihydrochloride, nifenidipine, inhibitors of ACE (angiotensin-converting enzyme) captopril, enalapril, ramipril; angiotensma losartan; the loop diuretics of Henle furosemide, piretanide, torasemide; the diuretics of the thiazide type, hydrochlorothiazide, etolazone, indapamide; the potassium-sparing diuretics amiloride, triamterene, spironolactone; the cardioglycosides digoxin, digitoxin, strophanthin; the antiarrhythmic agents amiodarone, sotalol, bretylium, flecainide; glycerol trinitrate nitrate; the openers of the K + channel (ATP) cromakalim, lemakalim, nocorandil, pinacidil, minoxidil; inhibitors of the Na + channel activated by veratridine. An example of one such partner in the combination, especially advantageous with NHE inhibitors, is the blockers of the non-inactivable sodium channel (sodium channel activatable by veratridine). Both classes of active substances present in the therapeutic application surprisingly combined the aforementioned synergistic effects in the treatment of pathological conditions, which have to be attributed to ischemic states or episodes of reperfusion. Accordingly, combinations of an NHE inhibitor with a non-activatable sodium channel blocker (sodium channel activatable by veratridine) are outstandingly suitable for the prophylaxis of infarcts and re-infarcts and the treatment of infarcts, as well as for the treatment of angina pectoris and the inhibition of ischemically induced cardiac arrhythmias, of tachycardia and of the formation and maintenance of ventpcular fibrillation, verifying that combinations of an NHE inhibitor with a non-activable sodium channel blocker also inhibit or diminish greatly preventive the pathophysiological processes to result in ischemically induced lesions. Because of their reinforced protective effects against hypoxic and pathological ischemic situations, the combinations according to the invention of an NHE inhibitor with a non-inactivatable sodium channel blocker can be used, as a consequence of the increased inhibition of the Na + influx in the cell, as drugs for the treatment of all acute or chronic injuries, caused by ischemia, or diseases induced primarily or secondarily by these lesions. This implies its use as medicines for surgical interventions, p. ex. in the case of organ transplants, combinations of an inhibitor of the
NHE with a non-inactivable sodium channel blocker used both for the protection of the organs in the donor before, and during, the extraction, for the protection of extracted organs, for example also in the case of their storage in bath liquids as well as when transferring to the recipient's organism. Combinations of an NHE inhibitor with a non-inactivatable sodium channel blocker are also valuable drugs, which act protectively, in the performance of angioplastic surgical interventions, for example in the heart as well as in peripheral vessels. Corresponding to their protective effect against ischemically induced lesions, combinations of an NHE inhibitor with a non-activable sodium channel blocker are also suitable as medicaments for the treatment of ischemias of the nervous system, especially of the central nervous system, being appropriate for the treatment of stroke or cerebral edema. In addition, the combinations according to the invention of an NHE inhibitor with a non-inactivatable sodium channel blocker are also suitable for the treatment of forms of shock, such as, for example, allergic, cardiogenic, hypovolemic and bacterial shocks. Thus, it was surprisingly found for example that the combination of the NHE inhibitor caripopda (HOE 642)
which is described, for example, in U.S. Pat. No. 5,591,754, with the non-inactivatable sodium channel inhibitor (sodium channel activatable by veratpdma) R56865 [N- [1- [4- (4-fluoro-phenoxy) butyl] -4-p? Per? D? ml] -N-met? l-2-benzot? azol-ammas (see Verdonck F, Bielen F, See Donck L: Preferential hlock of the veratridine-induced, nonmactivating Na + current by R56865 m single cardiac Purkmj e cells. J. Pharmacol 1991; 203: 311-378)} had an essentially greater effect than the additive in a model of experimental cardiac infarction in a rat. The decrease in infarct size, which was achieved with the combination of cariporide and R56865, far exceeded the maximum effect of the individual substances in this model. The study was carried out as described below.
Preparation of the animals Male rats with a body weight of 280 to 410 g were classified into four groups and anesthetized. After having opened the rib cage near the sternum, a silk thread (Ethicon "; 1.0 tnetric, 5-0) was placed around the left cardiac coronary artery and both loose ends of the thread were removed through a small ipaii'jweia of plastic Mi.iLei ial.For the application of the substance was placed a catheter in the left jugular vein.System blood pressure was recorded in the left carotid artery with a pressure recorder (Combitrans®, B. Braun Me sungen AG) while the determination of the electrocardiogram (ECG) was performed using subcutaneous electrodes.The data were recorded in a computer after digital conversion and the ECG was evaluated corresponding to the guidelines of the Lambeth Assembly (6. Walker MJA , Curtis MJ, Hearse DJ, Campbell RWF, Janse MJ, Yellon DM, Cohibe SM, Cokes SJ, Harness JB, Harron DWG, Higgins SK, Julián DG, Lab MJ, Manning AS, Northover BJ, Parratt JR, Riemersma RA, Rieva AND, Rusell DG, Sheridan DJ, Winslow E, Woodward B; The Lambeth convention: Guidelines for the study of arrhythmias in ischemia, infarction and reperfusion. Cardiovasx. Res 1988; 33: 447-455).
Experiment protocol HOE 642 was dissolved in bidistilled water and R56865 was dissolved in tartaric acid (0.6%), diluted with double distilled water and 4% mannitol was added. After preparing the animals, the substances were administered intravenously individually or in combination. The control animals received only the solvent. The injection volume was 1 ml per kg of body weight. Five minutes later the silk thread was tied by pushing the plastic hose and the coronary artery was closed for an hour. A clip attached to the plastic hose. After having reopened the coronary artery, reperfusion was performed for two hours of the tissue.
Determination of the size of the infarct The previously bound coronary artery was closed again and through the tip of the heart ink was injected into the left ventricle, in order to mark the heart tissue normally traveled by the blood. After having sacrificed the animals, the hearts were removed, the left ventricle was prepared and cut into discs perpendicular to the axis of the heart. The discs were washed in a sodium chloride solution and then incubated at 37 ° C for 5-7 min in triphenyl tetrazolium chloride, in order to dye the tissue still alive. The discs were then weighed and planimetrically measured (Imaging Res., Inc. Brock, University, St. Catherines, Ontario, Canada, Phoenix Technologies, Matrox Electronic Systems OS / 2). First, the size of the tissue normally traversed by the blood was determined, secondly, the region that had not been traversed by the blood after closing the loop (risk region) and, thirdly, the size of the blood. the region in which the cells died (infarct size). The statistical evaluation of the differences between the individual groups was carried out using the Student t test.
Results The administration of the substances did not modify the blood flow in the tissue normally traveled by the blood. Therefore, there was also no change in the size of the risk region, on average 59.3% of the left ventricle. In the control group, as a consequence of the blockage during one hour of the blood circulation and the renewal of the blood circulation, a tissue death was reached. The infarct size was, in the control group, 63.4 ± 4.3% (n = 8) of the risk region. The administration of 10 mg / kg of body weight of HOE 642 decreased to 33.2 ± 3.7% (n = 7) the infarct size and the administration of 3 mg / kg of body weight of R56865 decreased it to 38, 9 ± 3.1% (n = 8). On the contrary, the combination of both substances in the respective dosage was in a position to reduce the infarction to 10.5 ± 2.6% (n = 10) of the risk region. The data are given on average ± the ETM (typical error of the mean).
Claims (16)
1. Combined pharmaceutical preparation, characterized in that it contains an inhibitor of the exchanger between Na + and H + and an active substance on the heart and circulation,
2. Combined pharmaceutical preparation, characterized in that it contains an inhibitor of the exchanger between Na + and H + and an active substance on the heart and circulation, and because the inhibitor of the exchanger between Na + and Bt is selected from the following compounds: guanidma derivatives as they are described in the work of Edward J. Cragoe, Jr., "DIURETICS, Che i stry, Pharmaco logy and Medicine", J. WILEY & Sons (1983), 303-341, and in addition they are compounds of the following formulas: I a) Benzoylguanidmas of Formula I wherein they mean: R (l) or R (2) R (6) -S (0) n- or R (7) R (8) N-02S; and the respectively another substituent R (l) or R (2) H, F, Cl, Br, alkyl (C, -C4), alkoxy (C, -C4) or phenoxy, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of fluoro, chloro, methyl and methoxy; or the respectively another substituent R (l) or R (2) R (6) -S (0) n or R (7) R (8) N-; n zero, 1 or 2; R (6) alkyl (C, -C6), (C5-C7) cycloalkyl, cyclopentylmethyl, cyclohexylmethyl or phenyl, which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of fluoro, chloro, methyl and methoxy; R (7) and R (8) equal or different, H or alkyl (C, -C6); or R (7) phenyl- (CH2) m; m 1 -4; or R (7) phenyl, which is unsubstituted or substituted with 1-2 substituents selected from the group consisting of fluoro, chloro, methyl and me oxy, - or R (7) and R (8) in common a chain ( C4-C7) linear or branched or, the chain being able to be interrupted additionally by O, S or NR (9), - R (9) H or methyl; or R (7) and R (8) in common with the nitrogen atom, to which they are attached, a system of dihydroindole, tetrahydroquinolma or tetrahydroisoquinol; RO), R (4) and R (5) independently of each other, H or alkyl (C, -C2), or RO) and R (4) in common, an alkylene chain (C2-C4), -o R (4) and R (5) in common, an alkylene chain (C4-C7), -as well as their pharmaceutically compatible salts, -b)? Enzoylguanidines of Formula I where they mean: R (l) R (4; -SOm or R (5) R (6) N-S02-; m zero, 1 or 2; R (4) and R (5) C, -C8 alkyl , C3-C6 alkenyl or CnH2n-R (7); n null, 1, 2, 3 or 4; R (7) C5-C6 cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9); R (8) and R (9) H or C, -C4 alkyl; or R (5) H; R (6) H or C1-C4 alkyl, or R (5) and R (6) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by an O, S, NH, N-CH3 or N-benzyl; R (2) hydrogen, F, Cl, Br, alkyl (C, -C4), O- (CH2) mCpF2p + 1 or -XR (IO); m zero or 1; p 1, 2 0 3; X 0 , S or NR (ll), R (10) H, C, -C6 alkyl, C5-C6 cycloalkyl, cyclohexylmethyl, cyclopentylmethyl or -CH2-R (12); n, 1, 2, 3 or 4; R (12) femium, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9); R (8) and R ( 9) equal to H or alqu ilo C, -C4; (1 I) 11 i (11 oqeno o, il¡¡ui Lo C, (OR (10) and R (ll) in common 4 or 5 methylene groups, of which a CH2 group can to be replaced by 0, S, NH, N-CH3 or N-benzyl; R (3) as defined R (l), or C, -C6 alkyl, nitro, cyano, trifluoromethyl, F, Cl, Br, I or -X-R (IO); X 0, S OR NR (11); R (10) equal to H, C, -C6 alkyl, C5_C7 cycloalkyl 'cyclohexylmethyl, cyclopentylmethyl or -CnH2n-R (12); n from zero to 4; R (12) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9); R (8) and R (9) H or C, -C4 alkyl; R (ll) alkyl C, -C3, or R (10) and R (ll) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by 0, S, NH, N-CH3 or N-benzyl; as well as their physiologically compatible salts; c) Benzoylguanid as substituted in ortho of Formula I wherein they mean: R (l) F, Cl, Br, I, C, -C6 alkyl and -X-R (6); X O, S, NR (7) or Y-ZO; And O or NR (7); Z C O SO; R (6) H, C, -C6 alkyl, C5-C7 cycloalkyl, cyclohexylmethyl, cyclopentylmethyl, - (CH2) C F? , or -CnH2n-R (8); m zero or 1, - p 1-3; n from zero to 4, - R (8) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of the groups F, Cl, CF3, methyl, methoxy and NR (9) R (10) ); R (9) and R (10) H or C, -C4 alkyl; R (7) H or C, -C3 alkyl; or R (6) and R (7) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by O, S, NH, N-CH3 or N-benzyl; R (3) H or -X-R (6); X O, S, NR (7) OR Y-ZO; R (7) H or C, -C3 alkyl; AND 0 OR NR (7); wherein Y is attached to the phenyl radical of Formula I, Z C or SO; R (6) H, C, -C6 alkyl, C5-C7 cycloalkyl, cyclohexylmethyl, cyclopentylmethyl, - (CH2) CF2, O -CnH2n-R (8); m zero or 1; P 1-3; n from zero to 4; R (8) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10); R (9) and R (10) H or C, -C4 alkyl; or R (6) and R (7) in common 4 or 5 metlene groups, of which a CH2 group can be replaced by O, S, NH, N-CH3 or N-benzyl; R (2) and R (4) equal or different, R (11) -S0- or R (12) R (13) N-S02-; q zero - 2; R (ll) C, -C4 alkyl, which is unsubstituted or carries phenyl as a substituent, the phenyl being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl-CF3, methyl, methoxy and NR (9) R (10), - R (9) and R (10) H or C, -C4 alkyl; R (12) and R (13) as defined R (6) and R (7); or one of the two radicals R (2) or R (4) hydrogen or as defined R (l); R (5) H, methyl, F, Cl or methoxy, as well as their pharmaceutically compatible salts; d) Benzoylguanidines of Formula I where they mean: R (l) or R (2) an amino group -NR (3) R. { 4); RO) and R (4) equal or different, H, C, -C6 alkyl or C3-C7 cycloalkyl; or RO) phenyl- (CH 2'P 'P zero, 1, 2, 3 or 4; or RO) phenyl, the phenyl being in each case unsubstituted or carrying one to two substituents selected from the group consisting of fluoro , chlorine, methyl and methoxy; or RO) and R (4) may be in common a linear or branched C4-C7 methylene chain, wherein one member -CH2- of the methylene chain may be replaced by oxygen, S or NR (5); R (5) H or lower alkyl; respectively another substituent R (I) or R (2) H, F, Cl, C, -C4 alkyl, C, -C4 alkoxy, CF3, CmF2pt, -CH2-, benzyl or phenoxy, the respective phenyl radical being unsubstituted or carrying from one to two substituents selected from the group consisting of methyl, methoxy, fluoro and chloro; m 1, 2 0 3; as well as its pharmaceutically compatible salts; e) Benzoylguanidines of Formula I where they mean: R (l) R (4: • SOm OR R (5) R (6) NM-S02-; m zero, 1 or 2; R (4) and R (5) C, -C8 alkyl alken C3-C6 or 'CnH2p-R:?: n zero, 1, 2, 3 or 4; RO: c? cloalkyl-C5-C7 or phenyl, which is sm substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9), R (8) and R (9) H or C, -C4 alkyl, or R (5) H; R (6) H or C, -C4 alkyl, or R (5) and R (6) in common 4 or 5 metlene groups, of which a CH2 group may be replaced by a 0, S, NH, N- CH3 or N-benzyl, R (2) hydrogen, straight or branched (C5-C8) alkyl, -CR (13) = CHR (12) OR -C = CR (12); R (12) phenyl, which is substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (14) R (15); R (14) and R (15) H or alkyl (C, - C4), or R (12) heterolalk (C, -C9), which is unsubstituted or substituted like phenyl, - or R (12) alkyl (C, -C6) which is unsubstituted or substituted with 1-3 OH; or R (12) cycloalkyl (C3-C8); R (13) hydrogen or methyl, or R (12) cycloalkyl (C3-C8), (C3-C8) cycloalkyl (C, -C4) alkyl, phenyl, C6H5- (C, -C4) alkyl, naphthyl, biphenylyl, 1, 1-diphenyl-alkyl (C * -C4), cyclopentadienyl, pyridyl, pyrrolyl, furanyl, thienyl, thiazolyl, oxazolyl, mdenyl, quinolyl, indolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, isoxazolyl, isothiazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, indazolyl, isoquinolyl, phthalazinyl, qumoxalinyl, quinazolinyl or cinolinyl; RO) as defined R (2); and the aromatic substituents R (2) or R (3) being unsubstituted or substituted with 1-3 substituents taken between the groups of F, Cl, CF3, alkyl (C, -C4), alkoxy (C, -C4), or NR (10) R (11) with R (1G) and R (ll) in the meaning of H or alkyl (C, -C4); as well as its pharmaceutically compatible salts. f) Benzoylguanidines of Formula I R (1) c NH2 0 where they mean: R (l) or R (2) R (3) -S (0) n- o R (N-02S- respectively another substituent R (l) or R (2) H, OH, F, Cl, Br, I, C, -C 4 alkyl, C, -C 4 alkoxy, benzyloxy or phenoxy, which is unsubstituted or leads from one to three substituents selected from the group consisting of fluoro, chloro, methyl, methoxy, hydroxy or benzyloxy, R (3) -S (0) n, -NR (4) R (5) or 3,4-dehydropiperidine RO) alkyl C, -C6, C5-C7 cycloalkyl, cyclopentylmethyl, cyclohexylmethyl or phenyl, which is unsubstituted or leads from one to are substituents selected from the group consisting of fluoro, chloro, methyl and methoxy; R (4) and R (5) equal or different, H or C, -C6 alkyl; or R (4) phenyl- (CH2) m-; m 1, 2, 3 0 4; or R (4) phenyl, which is unsubstituted or carries one to two substituents selected from the group consisting of fluoro, chloro, methyl and methoxy; or R (4) and R (5) in common a linear or branched C4-C7 chain, the chain being able to be further interrupted by O, S or NR (6), R (6) H or methyl; or R (4) and R (5) in common with the nitrogen atom, to which they are attached, a system of dihydroindole, tetrahydroquinoline or tetrahydroisoquinoline; n zero, 1 or 2; or its pharmaceutically compatible salts. quinolines of Formula I where they mean R (l) hydrogen, alkyl, cycloalkyl, aplaxyl, alkenyl, substituted ammoalkyl or an aryl or heteroaryl ring; the rings being unsubstituted or substituted with 1-3 groups selected from the group consisting of halogen, nitro, amino, mono (lower alkyl) ammo, lower di (lower alkyl), lower alkyl, lower alkoxy, benzyloxy, phenoxy, hydroxy , trifluoromethyl, R (2) hydrogen, halogen, alkyl or ring; which is unsubstituted or substituted with 1-3 groups selected from the group consisting of halogen, nitro, arrimo, mono (lower alkyl) amino, di (lower alkyl) ino, lower alkyl, lower alkoxy, benzyloxy, phenoxy, hydroxy, X (2), X (3) and X (4) independently of one another, hydrogen, halogen, nitro, amino, alkyl, sulfonamido, mono (lower alkyl) amino, di (lower alkyl) ammo, lower alkyl, benzyl , hydroxy; X (l) hydrogen, oxygen, sulfur or NR (7); R (7) hydrogen, alkyl, cycloalkyl, arylalkyl, alkenyl, substituted ammoalkyl or an aplo or heteroaryl ring; which rings are unsubstituted or substituted with 1-3 groups selected from the group consisting of halogen, nitro, amino, mono (lower alkyl) amino, di (lower alkyl) amino, lower alkyl, lower alkoxy, benzyloxy, phenoxy, hydroxy and trifluoromethyl; in which substituents each alkyl chain or alkenyl chain may be interrupted by oxygen, sulfur or NR (8); R (8) hydrogen, alkyl, cycloalkyl, arylalkyl, alkenyl, substituted aminoalkyl or an aryl or heteroaryl ring, which rings are unsubstituted or substituted with 1-3 groups selected from the group consisting of halogen, nitro, amino, mono (lower alkyl) amino, di (lower alkyl) amino, lower alkyl, lower alkoxy, benzyloxy, phenoxy, hydroxy and trifluoromethyl; and their pharmaceutically accepe salts; h) Compounds of Formula I NH where they mean: R (l) hydrogen, F, Cl, Br, I, -NO. -C = N, -CF ,, R (4) -SOm or R (5) R (6) N-SO, -; m zero, 1 or 2; R (4) and R (5) alkyl (C, -C8), alkene (C3-C6), -CnH2n-R (7) or CF3; n zero, 1, 2, 3 or 4; R (7) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9); R (8) and R (9) H or C, -C4 alkyl; or R (5) H; R (6) H or alkyl (C, -C4); or R (5) and R (6) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R (2) -SR (10), -OR (10), -NHR (10), -NR (10) R (11), -CHR (10) R (12), - [CR (12) R ( 13) OR (13 ')], -. { C- [CH2-OR (13 ')] R (12) (R (13).}. Or - [CR (18) R (17)] - (CO) - [CR (19) R (20) - R (14); R (10) and R (ll) equal or different, - [CHR (16)] s- (CH2) - (CHOH) q- (CH2) p- (CHOH) tR (21) or - (CH2) p-0- (CH2-CH20) 2q-R (21), R (21) hydrogen, methyl, p, q, r equal or different, zero, 1, 2, 3 or 4; s zero or 1; t 1, 2, 3 or 4; R (12) and R (13) equal or different, hydrogen, alkyl (C.-C6) or in common with the carbon atom carrying a (C3-C8) cycloalkyl, R (13 ') hydrogen or alkyl "; , C, -C4); R (14) H, (C, -C6) alkyl, (C3-C8) cycloalkyl or CaH2a-R (15); to zero, 1, 2, 3 or 4; R (15) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9); R (8) and R (9) H or alkyl (C, -C4); or R (15) heterolalk (C, -C9), which is unsubstituted or substituted like phenyl, or R (15) alkyl (C, -C6), which is unsubstituted or substituted with 1-3 OH, R ( 16), R (17), R (18), R (19) and R (20) hydrogen or alkyl (C, -C3); R (3) as defined R (l), or R (3) alkyl (C, -C6) or -X-R (22); X oxygen, S or NR (16); R (16) H or alkyl (C, -C3); or R (22) and R (16) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R (22) is how R (14) has been defined; as well as its pharmaceutically compatible salts. i) Benzoylguanidomes of the Formula I-196 - the cuai is linked through C or N and is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamine and dimethylamine; or R (2) -SR (10), -OR (10), -NR (10) R (11), -CR (10) R (11) R (12); R (10) -CaH2a-heterolalk (C, -C9), which is substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamino and dimethylamino , - to zero, 1 or 2; R (ll) and R (12) independently of one another, as defined R (10) or hydrogen or alkyl (C, -C4); RO) as defined R (l), or alkyl (C, -C6) or -X-R (13); X oxygen, S or NR (14); R (14) H or alkyl (C, -C3); R (13) H, (C, -C6) alkyl, (C3-C8) cycloalkyl or -CbH2b-R (15); b zero, 1, 2, 3 or 4; or R (13) and R (14) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R (15) phenyl, which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9); R (8) and R (9) H or (C-C4) alkyl; as well as its pharmaceutically compatible salts; - 197 -k) Benzoylguanidines of Formula I wherein they mean: one of the substituents R (l), R (2), R (3) or R (4; an amino group - (6) R (5) hydrogen or C 6 alkyl; n zero, 1, 2, 3 or 4; R (6) H or C (, 4) alkyl; wherein a CH2 group may be replaced by 1 S atom or by an NR group (7); R (7) hydrogen, methyl or ethyl; or R (6) C (3.8) cycloalkyl or phenyl, which is unsubstituted or carries 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, methyl, methoxy, -NR (8) R (9) ); R (8) and R (9) H, methyl or ethyl; R (5) and R (6) in common with the nitrogen atom a ring of 5, 6 or 7 members, in which 1 C atom can be replaced by oxygen, S or NR (10); R (10) H, C (1-3) alkyl or benzyl; and the respectively other substituents R (l), R (2), R (3), R (4): hydrogen, F, Cl, Br, I, CN, CF3, N02, CF3-0-, m 1, 2 0 3; q zero, 1, 2, 3 or 4; p zero or 1; X oxygen or NR (12); R (12) H or alkyl C (1.3> R (ll) hydrogen, C (, 6) alkyl, C (3_8) cycloalkyl or phenyl, which is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, CH3, CH3-0- and NR (13) R (14); R (13) and R (14) H, methyl or ethyl, as well as their pharmaceutically compatible salts. 1) Benzoylguanidines of Formula I where they mean: R (l) R (4) R (5) N-C (X) -; X oxygen, S or N-R (6); R (4) and R (5) equal or different, H, alkyl (C.-C8) alkenyl (C, -C, C 'nH, 2n-R (7) n-zero, 1, 2, 3 or 4; - 199 - R (7) (C5-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methoxy, and alkyl (C * -C4); or R (4) and R (5) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R (6) as defined R (4) or amidine; R (2) H, F, Cl, Br, I, (C, -C8) alkyl, 1-alkenyl or 1-alkynyl, (C3-C8) cycloalkyl, (C3-C8) cycloalkyl-alkyl (C, -C4) ), phenyl, C 6 H 5 -alkyl (C, -C 4), naphthyl, biphenylyl, 1,1-diphenyl-alkyl (C, -C 4), cyclopentadienyl, pyridyl, thiopyridyl, pyrrolyl, furanyl, thienyl, thiazolyl, oxazolyl, indenyl, quinolyl, indolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl or -WR (8); W oxygen, S or NR (9); R (8) H, (C, -C6) alkyl, (C5-C7) cycloalkyl, cyclohexylmethyl, cyclopentylmethyl, m zero or 1; p 1, 2 0 3; q zero, 1, 2, 3 or 4; R (10) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (11) R (12); R (ll) and R (12) H or alkyl (C, -C4); R (9) H or alkyl (C, -C3); or - 200 - R (8) and R (9) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; RO) H, F, Cl, Br, I, alkyl (C, -C6) or -W-R (8) as defined for R (2), as well as their pharmaceutically acceptable salts; m) Benzoylguanidmas of Formula I wherein they mean: R (l), R (2), R (3) hydrogen, F, Cl, Br, I or alkyl (C, -C, 2); one of the substituents R (l), R (2) or R (3) N3, CN, OH or alkyloxy (C, -C, 0), when at least one of the remaining substituents R (l), R ( 2) or R (3) means a sufficiently lipophilic alkyl radical with 3 to 12 carbon atoms; one of the substituents R (l), R (2) or R (3) m zero or 1; n zero, 1, 2 or 3; R (4) C F p 1, 2 or 3, provided that n is equal to zero or 1; or R (4) (C3-C12) cycloalkyl, phenyl, pyridyl, quinolyl or isoquinolyl, the aromatic and heteroaromatic ring systems 201 being unsubstituted or substituted with a substituent selected from the group consisting of F, Cl, CF3 , methyl, methoxy and NR (5) R (6); R (5) and R (6) hydrogen or alkyl (C, -C4), - or one of the substituents R (l), R (2) or R (3) -C = CR (5) or -C [ R (6)] = CR (5); R (5) phenyl, which is unsubstituted or substituted with 1-3 substituents between the group consisting of F, Cl, CF3, methyl, methoxy, hydroxy, amino, methylamino and dimethylamino, heteroaryl (C, -C6), which is unsubstituted or substituted as phenyl; or R (5) alkyl (C, -C6), which is unsubstituted or substituted with 1-3 OH; or R (5) (C3-C8) cycloalkyl, R (6) hydrogen or methyl; as well as its pharmacologically acceptable salts; o) Benzoylguanidines of Formula I - 202 - in which they mean: R (l) hydrogen, F, Cl, Br, I, -N02, -C = N, XQ- (CH2) p-CF3, R (5) -SOm, R (6) -CO- or R (6) R (7) N-S02-, with X oxygen, S or NR (14); m zero, 1 or 2; or zero or 1, - p zero, 1 or 2; q zero, 1, 2, 3, 4, 5 or 6; R (5) and R (6) alkyl (C, -C8), alkenyl (C3-C6), -CnH2n-R (8) or CF3; n zero, 1, 2, 3 or 4; R (8) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10); R (9) and R (10) H or C, -C4 alkyl; or R (6) H; R (7) H or alkyl (C, -C4); or R (6) and R (7) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, RO: // - Y - - CC) h- (CH0H) l- < CH2) f- (CH0H) fa-RCl 1) CHOH), - (CH2) (CHOH) k -R (l 1) - 203 C) h- (CH0H) I- (CH2) | - (CH0H) k -R (11) And oxygen, -S- or -NR (12); R (ll) and R (12) hydrogen or alkyl (C, -C3); h zero or 1; i, 1 and k independently zero, 1, 2, 3 or 4, - but not being h, i and k simultaneously zero, R (3) as defined R (l) or alkyl (C, -C6) or -XR ( 13); X oxygen, S or NR (14); R (14) H or alkyl (C, -C3); R (13) H, (C, -C6) alkyl, (C3-C8) cycloalkyl or -CbH2b-R (15); b zero, 1, 2, 3 or 4, - or R (13) and R (14) in common 4 or 5 methylene groups, being able a CH2 group to be replaced by oxygen, S, NH, N-CH3 or N- benzyl; R (15) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10); R (9) and R (10) H or (C, -C4) alkyl, -R (4) hydrogen, -0R (16) or -NR (16) R (17); R (16) and R (17) independently hydrogen or (C-C3) alkyl; as well as its pharmaceutically compatible salts; 204 p) Benzoylguanidmas of Formula I where they mean: R (l) R (6) -CO or R 11) R (8) N-CO; R (6) alkyl (C, -C8), perfluoroalkyl (C, -C8), alkenyl (C, -CR or -CnH2n-R (9); n n0, 1, 2, 3 or 4; R (9) (C3-C8) cycloalkyl, phenyl, bifemyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (10) R (11) ); R (10) and R (ll) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (7) H, (C, -C8) alkyl, perfluoroalkyl (C, -C8) , (C3-C8) alkenyl or -CnH2n-R (12); n, 1, 2, 3 or 4; R (12) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, ethoxy and NR (13) R (14); R (13) and R (14) -205-H, alkyl (C) , -C4) or perfluoroalkyl (C, -C4); R (8) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); or R (7) and R (8) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R (2) as defined R (l), or H, F, Cl, Br, I, CN, N02, alkyl (C, -C8), perfluoroalkyl (C, -C8), alkenyl (C3-C8) or -CnH2n-R (15); n zero, 1, 2, 3 or 4; R (15) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (16 ) R (17); R (16) and R (17) H, (C, -C4) alkyl or perfluoroalkyl (C, -C); or R (2) heteroaryl (C, -C9), which is bonded through C or N and is unsubstituted or substituted with -1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; or R (2) -SR (18), -OR (18), -NR (18) R (19), -CR (18) R (19) R (20); R (18) -CaH2a-heteroaryl (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; - 206 - to zero, 1 or 2; R (19) and R (20) independently of one another as defined R (18) or hydrogen, alkyl (C, -C 4) or perfluoroalkyl (C, -C 4), - or R (2) R (21) -SOm or R (22) R (23) N-S02; 1 or 2; R (21) alkyl (C, -C8), perfluoroalkyl (C, -C8), alkenyl (C3-C8), -CNH2n-R (24), n-zero, 1, 2, 3 or 4; R (24) C3-C8 cycloalkyl), phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (27) R (28); R (27) and R (28) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4), - R (22) H, (C, -C8) alkyl, perfluoroalkyl (C, -C8), alkenyl (C3-C8), -CNH2n-R (29); n zero, 1, 2, 3 or 4; R (29) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR ( ) R (31); ROO) and R (31) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (23) H, (C, -C 4) alkyl or perfluoroalkyl (C, -C 4); or R (22) and R (23) -207 - in common 4 or 5 methylene groups, of which a group of CH2 can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, • or R (2) R (33) X-; X oxygen, S, NR (34), (D = 0) A-, NR (34) C = MN (* > R (35) -; M oxygen or S; A oxygen or NR (34); SO; R (33) alkyl (C, -C8), alkenyl (C3-CB), (CH2) bCdF2d +,, -CnH2n-R (36); b zero or 1; d 1, 2, 3, 4, 5, 6 0 7; n zero, 1, 2, 3 or 4; R (36) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (37) ) R (38); R (37) and R (38) H, (C, -C4) alkyl or perfluoroalkyl (C.-C4); R (34) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4), R (35) is defined as R (33); or R (33) and R (34) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; A and N (* 5) being attached to the phenyl nucleus of the fundamental framework of benzoylguanidine, or R (2) -SR (40), -OR (40), -NHR (40), -NR (40) R (41) , -CHR (40) R (42), -C [R (42) R (43) OH], -C = CR (45), -208 -CR (46) = CHR (45), - [CR (47) R (48)] u- (CO) - [CR (49, R (50)] VR (44); R (40), R (41) same or different - (CH2) p- (CHOH) q- (CH2) r- vCHOH) tR (51) or - (CH2) -O- (CH2-CH20) qR (51); R (51) hydrogen or methyl; or 1, 2, 3 0 4, v zero , 1, 2, 3 or 4, p, q, r equal or different zero, 1, 2, 3 or 4, - t 1, 2, 3 or 4, R (42) and R (43) equal or different hydrogen or alkyl (C, -C6), -or R (42) and R (43) in common with the carbon atom carrying them, form a cycloalkyl (Cz-Ca); R (44) H, alkyl (C, -C6), cycloalkyl (CZ ~ C &) or -CeH2e-R (45); e zero, 1, 2, 3 or 4, - R (45) equal to phenyl, which is unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy and NR (52) R (53), with R (52) and R (53) equal to H or (C, -C4) alkyl or R (45) heteroaryl (C, -C9), which is unsubstituted or substituted like what femlo; or R (45) alkyl (C, -C6), which is unsubstituted or substituted with 1-3 OH; R (46), R (47), R (48), R (49) and R (50) hydrogen or methyl, - 209 or R (2] R (55) -NH-SO, R (55) R ( 56) R (57) N- (C = Y) -; and oxygen, S or NR (58), R (56) and R (57) equal or different H, alkyl (C, -C8), alkenyl (C3) -C6) or -CfH2f-R (59); f zero, 1, 2, 3 or 4; R (59) cycloalkyl (C5-C7) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from group consisting of F, Cl, CF3, methoxy and alkyl (C.-C4), or R (56) and R (57) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by oxygen , S, NH, N-CH3 or N-benzyl, - R (58) is defined as R (56) or amidma, - R (3), R (4) and R (5) independently of each other, as have defined R (1) or R (2), - as well as their pharmaceutically compatible salts. q) Benzoylguanidmas of Formula I - 210 - in which they mean: R (l) hydrogen, F, Cl, Br, I, -N02, -C = N, -Xo- (CH2) p- (CF2) q-CF3, R (5) - S0m-, R (6) -C0-, R (6) R (7) N-CO- or R (6) R (7) N-S02-; X oxygen, -S- or NR (14); m zero, 1 or 2; or zero or 1; p zero, 1 or 2; q zero, 1, 2, 3, 4, 5 or 6; R (5) and R (6) (C-C8) alkyl, (C3-C6) alkenyl, -CnH2n-R (8) or CF3; n zero, 1, 2, 3 or; R (8) (C3-C7) cycloalkyl, phenyl, which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10); R (9) and R (10) H or alkyl (C, -C4); or R (6) hydrogen; R (7) hydrogen or alkyl (C, -C4); or R (6) and R (7) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R O; R (ll) heteroaryl (C, -C9), which is bonded through C or N and is - 211 - s substituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino, dimethylamine and benzyl; And oxygen, -S- or NR (12); R (12) H or (C 1 -C 4) alkyl; R (3) as defined R (l); or R (3) alkyl (C.-C6) or -X-R (13); X oxygen, -S- or NR (14); R (14) H or alkyl (C, -C3); R (13) H, (C, -C6) alkyl, (C3-C8) cycloalkyl or -CbH2b-R (15); b zero, 1, 2, 3 or 4; or R (13) and R (14) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, R (15) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10); R (9) and R (10) H or alkyl ^ -C ^); R (4) hydrogen, -0R (16), -NR (16) R (17) or CrF2r + 1; R (16) and R (17) independently hydrogen or alkyl (C.-C3); r 1, 2, 3 or 4; as well as its pharmaceutically compatible salts; r) Heterocycles with 5-membered rings condensed with benzo of Formula I 212 where they mean: X N or CR (6); And oxygen, S or NR (7); A, B in common a bond or A, B both hydrogen, provided that simultaneously X is equal to CRO) and Y equals NR (7); one of the substituents R (l) to R (6) a group -C0-N = C (NH2) 2; the respectively other substituents R (l) to R (6) hydrogen, F, Cl, Br, I or alkyl (C, -C6); up to two of the other substituents R (l) to R (6) CN, N02, N3, or CF, to one of the other substituents R (8n nn from zero to 10, with the alkylene chain being -CNH2n- linear or branched and a C atom may be replaced by an oxygen or S atom or by an atom of N; R (8) hydrogen, alkenyl (C2-C6) or cycloalkyl (C3-C, 0), which is unsubstituted or substituted with 1 to 4 methylene groups or an OH group, or it may contain an ethylene group -CH = CH-, and in which a methylene group may be replaced by an oxygen atom or S or by an atom of N; - 213 - or R (8) phenyl, unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, Br, I, CF3, CH3-S (0) or R (9) - and-; s zero, 1 or 2; R (9) H, methyl, ethyl, W oxygen or NR (10); R (10) H or methyl; and zero or 1; or R < 8 > CmF2 ^ v m from 1 to 3, -o R (8) 1- or 2-naphthyl, pyridyl, quinolyl or isoquinolyl; Z -CO-, -CH2- OR - [CR (ll) OH] -; q 1, 2 0 3; R (ll) H or methyl; or Z oxygen or -NR (12); R (12) H or methyl; or -S (0) s-; zero, 1 or 2; Z -S02-NR (13) -: R (13) H or alkyl (C, -C); R (7) hydrogen, (C, -C 10) alkyl, (C 2 -C 10) alkenyl or R (8) -CnH2n-; or its pharmaceutically compatible salts; - 214 -s) Benzoylguanidmas of Formula I where they mean: R (l), R (3) or R (4) -NR (6) C = X NR (7) R (8); X oxygen or S; R (6) hydrogen, (C, -C8) alkyl, perfluoroalkyl (C, -C8), alkenyl (c3-c8) O-CnH2n-R (9); n zero, 1, 2, 3 or 4; R (9) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR ( ) R (11); R (10) and R (ll) H, alkyl (C.-C4) or perfluoroalkyl (C, -C); R (7) hydrogen, (C, -C8) alkyl, perfluoroalkyl (C, -C8), (C3-C8) alkenyl or -CoH2o-R (12); or zero, 1, 2, 3 or 4; R (12) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (13) R (14); R (13) and R (14) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (8) is defined as R (7), or R (7) and R (8) in common 4 or 5 metlene groups, of which a CH2 group may be replaced by oxygen, S, NH, N-CH3 or N-benzyl; the remaining substituents R (2), R (3), R (4), R (5) OR R (1), R (2), R (4), R (5) OR R (1), R (2), R (3), R (5) independently of each other, hydrogen, F, Cl, Br, I, -Ota-alkyl (C, -C8), -Otb-alkene (C3-C8) , -Otc (CH2) bCdF2d +, -OtdCpH2pR (18), or up to 2 groups CN, N02, NR (16) R (17), b zero or 1; d 1, 2, 3, 4, 5, 6 or 7; ta zero or 1, tb zero or 1 tc zero or 1; td zero or 1, p zero, 1, 2, 3 or 4; R (18) (C3-C8) cycloalkyl, phenyl, bifemyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (19) R (20); R (19) and R (20) hydrogen or (C, -C4) alkyl or perfluoroalkyl (C.-C4); R (16) hydrogen, (C, -C8) alkyl, -216 perfluoroalkyl (C, -C8), (C3-C8) alkenyl, -CqH2q-R (21), q zero, 1, 2, 3 or 4; R (21) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy or NR (22) R (23), R (22) and R (23) hydrogen, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (17) hydrogen, (C, -C8) alkyl, perfluoroalkyl (C, -C8), (C3-C8) alkenyl, -CrH2r-R (24); r zero, 1, 2, 3 or 4; R (24) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR ( ) R (26); R (25) and R (26) hydrogen, (C-C4) alkyl or perfluoroalkyl (C, -C4); or R (16) and R (17) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; or its pharmaceutically compatible salts; - 217 -t) Guanidines substituted with diacyl of the Formula I where they mean: X (l) and X (2) TI zero, 1, 2, 3 or 4; R (A) and R (B) independently hydrogen, F, Cl, Br, I, CN, OR (106), alkyl (C-C8), cycloalkyl (C3-C8), 0zk (CH2) 2ziCzmF2zm + i ' NR (107) R (108), phenyl or benzyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (109) R (110 ); R (109) and R (110) hydrogen, (C, -C4) alkyl or perfluoroalkyl (C, -C4); zl zero, 1, 2, 3 or 4; zk zero or 1; zm 1, 2, 3, 4, 5, 6, 7 or 8; R (106) hydrogen, (C, -C8) alkyl, perfluoro (C, -C8) alkyl, (C3-C8) alkenyl, (C3-C8) cycloalkyl, phenyl or benzyl, the aromatic radicals being unsubstituted or substituted -3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (111) R (112); R (lll) and R (112) hydrogen, (C, -C 4) alkyl or perfluoroalkyl (C 1 -C 4); R (107) and R (108) independently of one another are defined as R (106) or R (107) and R (108) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by oxygen , S, NH, N-CH3 or N-benzyl; xd) and xo; T2a and T2b independently of one another zero, 1 or 2; the double link can be configured (E) or (Z); X (l) and xo; R R (U1) - 219 - T3 zero, 1 or 2; U, YY and Z independently of each other C or N, being able to carry U, YY, Z the following numbers of substituents: R (D) hydrogen, (C * -C8) alkyl or perfluoroalkyl (C, -C8), R (U1), R (U2), R (Y1), R (Y2), R (Z1), R (Z2) independently of each other hydrogen, F, Cl, Br, I, CN, OR (114), alkyl (C.-C8), cycloalkyl (C3-C8), 0? Ka (CH 2 'zla C zma F 2zma + 1' NR (115) R (116), phenyl or benzyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy, NR (117) R (118), R (117) and R (118) hydrogen, alkyl (C, -C4) or perfluoroalkyl (C, -C), zka zero or 1; zla zero, 1, 2, 3 or 4; zma 1, 2, 3, 4, 5, 6, 7 or 8; R (114) hydrogen, alkyl (C, -C8), perfluoroalkyl (C-C8), alkenyl (C3-C8), (C3-C8) cycloalkyl, phenyl or benzyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents - 220-selected from the group consisting of F, Cl, CF3, methyl, ethoxy and NR (119) R (120); R (119) and R (120) hydrogen, C ^ -C ^ alkyl) or perfluoroalkyl (C, -C4), -R (115) and R (116) independently one from another, as defined R (114); or R (115) and R (116) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; however, the constitution of U equal to nitrogen (N), YY equal to nitrogen (N) and Z equal to carbon (C),, R (102), R (103), R (104) R (105) is excluded. independently of each other, F, Cl, Br, I, -C = N, Xzoa- < H2 > zpa "< z, aF2zqa + 1> 'R < 110a > -SOzvp,' R (110b) R (110c) N-CO, R (llla) -CO- or R (112a) R (113a) N-S02-, the linear or branched perfluoroalkyl group, X oxygen, S or NR (114a), R (114a) H or alkyl (C, -C3); zoa zero or 1; zbm zero, 1 or 2; zpa zero, 1, 2, 3 or 4; zqa 1, 2, 3, 4, 5, 6, 7 or 8; R (110a), R (110b), R (llla) and R (112a) independently alkyl (C , -C8), alkenyl (C3-C8), -CznH2? NR (115a) or perfluoroalkyl (C, -C8); zn zero, 1, 2, 3 or 4; R (115a) cycloalkyl (C3-C8), phenyl, biphenylyl or naphthyl, - 222 - the aromatic radicals being sm substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (116a) R (117a), - R (116a) and R (117a) hydrogen, perfluoroalkyl (C.-C or alkyl (^ - C ^), or R (110b), R (llla) and R (112a) hydrogen; R (ll? C) and R (113a) independently hydrogen, perfluoroalkyl (C, -C4) or alkyl (C, -C4), or R (110b) and R (ll? C) as well as R (112) a) and R (113a) in common 4 or 5 metlene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl; or R (101), R (102), R (103), R (104), R (105) independently of each other, alkyl (C, -C8), -CzßlH2zalR (118a) or alkenyl (C3-C8) , zal zero, 1, 2, 3 or 4; R (118a) (C3-C8) cycloalkyl, phenyl, bifemyl or naphyl, the aromatic radicals being unsubstituted or substituted by 1-3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy or NR (119a) R (119b); R (119a) and R (119b) hydrogen, (C 1 -C 4) alkyl or perfluoroalkyl (C, -C 4); or R (101), R (102), R (103), R (104), R (105) -222 - independently of each other, hetero-tile (C, -C9), which is attached through C or N and is unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, mood, methylamino and dimethylamino; or R (101), R (102), R (103), R (104), R (105) independently of each other -C = C-R (193); R (193) phenyl, which is unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy or NR (194) R (195); R (194) and R (195) hydrogen or CH3; or R (101), R (102), R (103), R (104), R (105) independently of each other -Y-for-C6H4- (CO) zh- (CHOH) Z1 - (CH2) ZJ - (CHOH) zk-R (123), -Y-meta-C6H4- (CO) zad- (CHOH) zge- (CH2) Mf- (CHOH) zag-R (124) or -Y-ortho-C6H4- (CO) zah- (CHOH) zaQ- (CH2) zap- (CHOH) zak-R (125); And oxygen, -S- or -NR (122d) -; zh, zad, zak independently zero or 1; zi, zj, zk, zae, zaf, zag, zao, zap and zak independently zero, 1, 2, 3 or 4; however, in each case zh, zi and zk at the same time zero, not being zad, zae and zag at the same time zero, and not being zah, zao and zak at the same time zero, R (123), R (124 ), R (125) and R (122d) independently hydrogen or (C, -C3) alkyl; or R (101), R (102), R (103), R (104) and R (105) -223 - independently of each other -SR (129), -OR (130); -NR (131) R (132) or -CR (133) R (134) R (135); R (129), R (130), R (131) and R (133) independently -CzabH2zab-heteroaryl (C, -C9), which is unsubstituted or substituted with 1-3 substituents taken from the group consisting of of F, Cl, CF3, CH ... methoxy, hydroxy, amino, methylamino and dimethylamino; zab zero, 1 or 2; R (132), R (134) and R (135) independently of one another as defined R (129) or hydrogen, alkyl (C, -C) or perfluoroalkyl (C, -C4); or R (101), R (102), R (103), R (104) and R (105) independently of each other -W-para- (CfiH4) -R (196), -W-meta- (C6H4) ) -R (197) or -W-ortho- (C6H4) -R (198); R (196), R (197) and R (198) independently heteroaryl (C, -C9), which is bonded through C or N and is unsubstituted or substituted with 1 to 3 substituents taken from the group consisting of of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamine, dimethylamino and benzyl, - W oxygen, S or NR (136) -; R (136) hydrogen or alkyl (C, -C4); or R (101), R (102), R (103), R (104) and R (105) independently of each other R (146) X (la) -; X (the) oxygen, S, NR (147), (D = 0) A-, NR (148) C = MN < *) R (149) -; M oxygen or sulfur; To oxygen or NR (150); D C or SO; R (146) 224 ali lo? C, - C8), alkenyl (C3-C (CH2) zbzCzdzF2zdz + 1 or - C2zxaH2z a - R (1 5 1 zbz zero or 1 / zdz 1, 2, 3, 4, 5, 6 Ó 7; zxa zero, 1, 2, 3 or 4, R (151) cycloalkyl (C3-C8), phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3 , methyl, methoxy and NR (152) R (153); R (152) and R (153) hydrogen, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (147), R (148) and R (150) independently hydrogen, (C, -C4) alkyl or perfluoroalkyl (C, -C4): R (149) is defined as R (146), or R (146) and R (147) or R ( 146) and R (148) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl, with A and N ^ 5 being bound to phenyl nucleus of the fundamental framework of alkanoyl, or R (101), R (102), R (103), R (104) and R (105) independently of each other, -SR (164), -OR (165) , -NHR (166), -NR (167) R (168) ), -CHR (169) R (170), -CR (154) R (155) OH, -C = CR (156), -CR (158) = CR (157) or - [CR (159) R ( 160)] zu (C = 0) - [CR (161) R (162) zy-R (163); R (164), R (165), R (166), R (167), R (169) same or different - (CH2) zy- (CHOH) zz- (CH2) zaa- (CHOH) zt-R ( 171) or - (CH2) zab-0- (CH2-CH20) zac-R (172); - 225 - R (171) and R (172) hydrogen or methyl; zu 1, 2, 3 0 4; zv zero, 1, 2, 3 or 4; zy, zz, zaa, zab, zac equal or different zero, 1, 2, 3 or 4; zt 1, 2, 3 or 4; R (168), R (170), R (154), R (155) same or different hydrogen or (C, -C8) alkyl or R (169) and R (170) or R (154) and R ( 155) in common with the carbon atom that carries them, a (C3-C8) cycloalkyl; R (163) hydrogen, alkyl (C, -C6), cycloalkyl (C3-C8) ° -Czeb-H2zeb-R < 173 > 'zero zeb, 1, 2, 3 or 4; R (156), R (157) and R (173) independently phenyl which is unsubstituted or substituted with 1-3 substituents taken between the group consisting of F, Cl, CF3, methyl, methoxy and NR (174) R ( 175); R (174) and R (175) hydrogen or alkyl (C, -C4); or R (156), R (157) and R (173) independently heteroaryl (C, -C9), which is unsubstituted or substituted like phenyl; R (158), R (159), R (160), R (161) and R (162) hydrogen or methyl, or R (101), R (102), R (103), R (104), R (105) independently of one another R (176) -NH-S02-; R (176) R (177) R (178) N- (C = Y ') -; - 226 - Y 'oxygen, S or N-R (179); R (177) and R (178) equal or different from hydrogen, (C, -C8) alkyl, (C3-C6) alkenyl or -CzfaH2zfa-R (180> zfa zero, 1, 2, 3 or 4; (180) (C5-C7) cycloalkyl or phenyl, which is substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methoxy or alkyl (C, -C4); (177) and R (178) in common 4 or 5 metlene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl, R (179) as defined R (177) or equal to amidine, or R (101), R (102), R (103), R (104), R (105) independently of each other NR (184a) R (185), OR (184b) , SR (184c) or -Czn? H2zn? -R (184d); znx zero, 1, 2, 3 or 4; R (184d) cycloalkyl (C3-C7) or phenyl, which is unsubstituted or substituted with 1- 3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy and NR (116k) R (117k); R (116k) and R (117k) hydrogen or C-C4 alkyl, R (184a), R (184b), R (184c), R (185) independently a other hydrogen, - 227 - (C, -C8) alkyl, perfluoro (C, -C8) or (CH2) zao-R (184g); zero, 1, 2, 3 or 4; R (184g) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy and NR (184u) R (184v), - R (184u) and R (184v) hydrogen or C, -C4 alkyl; or R (184a) and R (185) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl; as well as its pharmaceutically compatible salts; LI) üen oilguanid ace of Formula 1 where they mean: R (l) H, F, Cl, Br, I, CN, N02, alkyl (C-C8 cycloalkyl (C3-c8 'or X - (CH2 .b (CF2) C-CF3 X oxygen, S or NR (5), zero or 1, - - 228 - b zero, 1 or 2, c zero, 1, 2 or 3, R (5) H, alkyl (C, -C4) or CdH2dR (6); d zero, 1, 2, 3 or 4; R (6) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being substituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (7) R (8); R (7) and R (8) independently H or alkyl (C, -C4), -or R (l) -SR (10), -OR (10) or -CR (10) R (11) R (12); R (10) -CfH2f-c? Cloalkyl (Cj-C8), heteroaryl (C, -C9) ) or phenyl, the aromatic systems being unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; f zero, 1 or 2; (ll) and R (12) independently of one another as defined R (10) or hydrogen or alkyl (C, - C4), or R (l) phenyl, naphthyl, biphenylyl or heteroaryl (C, -C9), the latter linked through C or N, and which are unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamino and dimethylamino; - 229 - R (1 -SR (13), -0R (13), -NHR (13), -NR (13) R (14), -CHR (13) R (15), -C [R (15 ) R (16)] 0H, -C = CR (18), -C [R (19)] = CR (18), - [CROO) R (21)] k- (CO) - [CR (22) R (23) R (24)]. R (13) and R (14) equal or different - (CH2) g- (CHOH) h- (CH2) (CHOH) j-R (17), R (17) hydrogen or methyl; - (CH2) g-0- (CH2-CH20) h-R (24), g, h, i equal or different zero, 1, 2, 3 or 4; 3 1, 2, 3 or 4; R (15) and R (16) same or different hydrogen, (C, -C6) alkyl or, in common with the carbon atom carrying them, a (C3-C8) cycloalkyl; R (18) phenyl, which is unsubstituted or substituted by 1 to 3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (25) R (26), - R (25) and R (26) H or alkyl (C, -C4); or R (18) heteroaryl (C, -C6), which is unsubstituted or substituted as phenyl; or R (18) alkyl (C, -C6), which is unsubstituted or substituted by 1 to 3 OH; or R (18) cycloalkyl (C3-C8); R (19), R (20), R (21), R (22) and R (23) hydrogen or methyl; k zero, 1, 2, 3 or 4; 1 zero, 1, 2, 3 or 4; 230 R (24) H, alkyl (C.-C,), cycloalkyl (C, -CJ or m 1 m, 2, 3 or 4; R (2) and R (3) independently from each other as has defined R (l); R (4) alkyl (C Cz), F, Cl, Br, I, CN or - (CH2) n- (CF2) 0-CF3; n zero or 1; or zero, 1 or 2, as well as their pharmaceutically compatible salts; v) Acylguanidines of Formula I wherein they mean: X carbonyl, sulfonyl, R (l) H, (C-C8) alkyl, unsubstituted or substituted by hydroxy, (C3-C8) cycloalkyl, phenyl, which is unsubstituted or substituted by 1-3 substituents taken from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamine or dimethylamino, R (2) H, alkyl (C, -C4), as well as their pharmaceutically compatible salts; w) Guanidides of phenyl-substituted alkylcarboxylic acids, carriers of perfluoroalkyl groups of the Formula I 231 wherein they mean: R (A) hydrogen, F, Cl, Br, I, CN, OR (6alkyl (C, -C8), cycloalkyl (C3-C8! Op (CH2) or NR (7) R (8 R zero or]; to zero, 1, 2, 3 or 4; b 1, 2, 3, 4, 5, 6, 7 or 8; R (6) hydrogen, alkyl (C, -C8), alkenyl ( C • c8), (C3-C8) cycloalkyl, phenyl or benzyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR ( 9) R (10); R (9) and R (10) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (7) and R (8) independently of each other, as has defined R (6); R (B) independently as defined R (A); X 1, 2 or 3; Rd) hydrogen, alkyl (C, -C8), cycloalkyl (C3-C8), -Ot ( CH2) dCeF2e +, F, Cl, Br, I or CN, t zero or 1; d zero, 1, 2 3 or 4; e 1, 2, 3, 4 5, 6, 7 or 8; R (2! R (3), R (4) and R (5) independently of each other, as defined R (l); - 232 - but with the proviso that at least one of the substituents R (l), R (2), RO), R (4), R (5), RIA) and R (B) are a group -0t (CH2) dCeF2e +, or a group -0p (CH2) gCbF2b +, as well as their pharmaceutically compatible salts; ?) Heteroaroylguanidines of Formula I where they mean: HA SOm, O or NR (5); m zero, 1 or 2, - R (5) hydrogen, (C-C8) alkyl or -CamH2amR (81); am zero, 1 or 2; R (81) (C3-C8) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (82) R (83); R (82) and R (83) H or CH 3; or R (81) heterolalk (C, -C9), which is linked through C or N and is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamine and dimethylamino; one of both R (l) and R (2) -CO-N = C (NH2) 2 substituents; and the respective other substituent hydrogen, F, Cl, Br, I, alkyl (C, -C3), -OR (6), -233 - -CrH2r + 1, -CO-N = C (NH2) 2 or NR (6) R (7); R (6) and R (7) independently hydrogen or alkyl (C, -C; r 1, 2, 3 0 4; R (3) and R (4) independently of each other hydrogen, F, Cl, Br, I , -Ca-N, X- (CH2) p- (Cq-F2q +,), R J-SO ^, R (9) R (10) N-CO-, R (ll) -CO or R (12) R (13) N-S02-, the linear or branched perfluoroalkyl group, X oxygen, S or NR (14), R (14) H or (C, -C3) alkyl, bm zero, 1 or 2; p zero, 1 or 2; q zero, 1, 2, 3, 4, 5 or 6; R (8), R (9), R (ll) and R (12) independently alkyl (C, -C8), alkenyl (C3-C6), -CNH2n-R (15), CF3; n-zero, 1, 2, 3 or 4; R (15) cycloalkyl (C3-C7) or phenyl, which is unsubstituted or substituted by 1- 3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy or NR (16) R (17), -R (16) and R (17) H or alkyl '(C, -C4); R (9), R (ll) and R (12) H; R (10) and R (13) independently H or alkyl (C, -C4); or R (9) and R (10) as well as R ( 12) and R (13) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by or X, S, NH, N-CH3 or N-benzyl, -234 RO) and R (4) independently of one another alkyl (C, -C8) or - aLH2alR < lf to zero, 1 or 2; R (L-cycloalkyl (C -C &) or phenyl, which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (19) R (20); R (19) and R (20) H or CH3; R (3) and R (4) independently of each other heteroaryl (C, -C9), which is linked through C or N and which is substituted or unsubstituted with 1-3 substituents selected from the group consisting of F , Cl, CF3, CH3, methoxy, hydroxy, arrimo, methylamino and dimethylamino; or RO)) and R (4) independently of each other ) h- (CHOH), - (CH2), - (CHOH) k -R (23) (C) oh- (CHOH) 00- (CH2) op- (CHOH) ßk-R (25) - 235 - And oxygen, -S- or -NR (22) -; h, ad, ah independently zero or 1, - i,, k, ae, af, ag, ao, ap and ak independently zero, 1, 2, 3, 4, however not being in each case h, i and k simultaneously zero, not being ad, ae and ag simultaneously zero, as well as not being ah, ao and ak simultaneously zero, R (23), R (24), R (25) and R (22) independently hydrogen or (C1-C3) alkyl; or RO) and R (4) independently of one another hydrogen, F, Cl, Br, I, CN, alkyl (C, -C8), perfluoroalkyl (C, -C8), alkenyl (C3-C8) or -C8H2gR ( 26); g zero, 1, 2, 3 or 4; R (26) cycloalkyl (C3-Cfl), phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (27) R (28); R (27) and R (28) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); or RO) and R (4) independently of one another -SR (29), -OR (30), -NR (31) R (32) or -CR (33) R (34) R (35); R (29), R (30), R (31) and R (33) independently -CaH2a-hetero-halo (C, -C6), which is substituted or substituted with 1-3 substituents selected from the group consisting of F , Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylammon, -236- to zero, 1 or 2; R (32), R34) and R (35) independently of one another, as defined R (29) or hydrogen, (C, -C4) alkyl or perfluoroalkyl (C, -C4); or RO) and R (4) independently of each other R (96), R (97) and R (98) independently heteroaryl (C, -C9), which is linked through C or N and which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, arrimo, methylamino, dimethylamino or benzyl; W oxygen, S or NR (36) -: R (36) H or alkyl (C., - C4); or R (3) and R (4) independently of each other R (37) -SOcm or R (38) R (39) N-S02-; cm 1 or 2; R (37) alkyl (C, -C8), perfluoroalkyl (C, -C8), alkenyl (C3-C8) or -C3H2¡JR (40); s zero, 1, 2, 3 or 4; R (40) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, -237-methyl, methoxy and NR (41) R (42), -R (41) and R (42) H, (C-C4) alkyl or perfluoroalkyl (C, -C4); R (38) H, (C, -C8) alkyl, perfluoroalkyl (C, -C8), (C3-C8) alkenyl or -CwH2w-R (43); zero, 1, 2, 3 or 4; R (43) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (44 ) R (45); R (44) and R (45) H, (C * -C4) alkyl or perfluoroalkyl (C, -C4); R (39) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); or R (38) and R (39) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; or R (3) and R (4) independently of one another R (46) X (1) -; X (l) oxygen, S, NR (47), (D = 0) A-, NR (48) C = MN (*) R (49) -, M oxygen or S; To oxygen or NR (50); D C or SO; R (46) alkyl (C, -C8), alkenyl (C3-C8), (CH2) bCdF2d +, or -C? H2? -R (51); b zero or 1; d 1, 2, 3, 4, 5, 6 or 7; x zero, 1, 2, 3 or 4; R (51) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, - 238 - the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (52) R (53); R (52) and R (53) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (47), R (48) and R (50) independently hydrogen, (C, -C4) alkyl or perfluoroalkyl (C.-C4); R (49) is defined as R (46); or R (46) and R (47) or R (46) and R (48) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, where A and N (* 5 are attached to the phenyl nucleus of the fundamental framework of benzoylguanidine; R (4) independently of one another -SR (64), -OR (65), -NHRÍ66), -NR (67) R (68), -CHR (69) R (70), -C (OH) R (54) R (55), -C = CR (56), -CR (58) = CR (57), - [CR (59) R (60)] u- (CO) - [CR (61) R (62)] VR (63); R (64), R (65), R (66), R (67) and R (69) equal or different - (CH2) and- (CHOH) z- (CH2) aa- (CH20) tR (71) or - (CH2) ab-0- (CH2-CH20) a? -R (72), R (71) and R (72) hydrogen or methyl; u 1, 2 3 or 4; v zero 1, 2, 3 or 4; y- z a to the same or different zero, 1, 2, 3 or 4; t 1, 2, 3 0 4; R (68), R (70), R (54) and R (55) -239 - same or different hydrogen, (C, -C6) alkyl; or R (69) and R (70) or R (54) and R (55) in common with the carbon atom carrying them, a (C3-C8) cycloalkyl; R (63) H, alkyl (C, -C6), cycloalkyl (Cj-C 8 'e zero, 1, 2, 3 or 4; R (56), R (57) and R (73) independently phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (74) R (75); R (74) and R (75) H or alkyl (C) , -C4), or R (56), R (57) and R (73) independently heteroaryl (C, -C9), which is unsubstituted or substituted as phenyl; RÍ58), R (59), R (60) , R (61) and R (62) hydrogen or methyl, R (4) independently of one another R (76) -NH-S02-; R (76) R (77) R (78) N- (C = Y ') -; Y 'oxygen, S or N-R (79); R (77) and R (78) equal or different H, (C, -C8) alkyl, (C3-C6) alkenyl, -CfH2f-R (80); f zero, 1, 2, 3 or 4; R (80) (C5-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -240-CF3, methoxy and alkyl (C.-C4); or R (77) and R (78) in common 4 or 5 metlene groups, of which a CH2 group can be replaced by oxygen, S, NH, NH-CH3 or N-benzyl, R (79) is as has defined R (77) or equal to amidine; or RO) and R (4) independently of one another NR (84) R (85); R (84) and R (85) independently of each other H, (C, -C4) alkyl, or in common 4 or 5 methylene groups, of which a CH2 group may be replaced by oxygen, S, NH, NH -CH3 or N-benzyl, or of which one or two CH2 groups may be replaced by CH ~ Cdh? H2A? +1 'as well as their pharmaceutically compatible salts; y) Bicyclic Heteroaroylguanidines of Formula I - 241 - in which they mean: T, U, V, W, X, Y and Z independently of each other, nitrogen or carbon; but with the limitation that X and Z are not simultaneously nitrogen, and that T, U, V, W, X, Y and Z do not carry any substituent when they are nitrogen, and that no more than four of them are simultaneously nitrogen , R (l) and R (2) independently of one another hydrogen, F, Cl, Br, I, alkyl (C, -C3), perfluoroalkyl (C.-C3), OR (8), NR (8) R (9) or C (= 0) N = C (NH2) 2; R (8) and R (9) independently of one another, hydrogen or (C, -C3) alkyl or R (8) and R (9) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R (3), R (4), R (5), R (6) and R (7) independently of each other hydrogen, F, Cl, Br, I, -C-N. Xk- (CH2) p- (CqF2q + 1), (10a) -SOta (R (10b) R (10c) N-CO, R (ll) -CO- or R (12) R (13) N-SO ., -, the linear or branched perfluoroalkyl group, X oxygen, S or NR (14), R (14) H or alkyl (C, -C3), bm zero, 1 or 2, P zero, 1 or 2; k zero O 1; q 1, 2, 3, 4, 5 or 6 R (10a), R (10b), R (ll) and R (12) independently of each other alkyl (C, -C8), alkenyl ( C3-C6), -CNH2n-R (15) or perf luoroalkyl (C, -Ca); - 242 - n zero, 1, 2, 3 or 4; R (15) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (16) R (17 ); R (16) and R (17) H or alkyl (^ -C ^), - or R (10b), R (ll) and R (12) hydrogen; R (l? C) and R (13) independently hydrogen or alkyl (C, -C4); or R (10b) and R (10c) as well as R (12) and R (13) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl; or R (3), R (4), R (5), R (6) and R (7) independently of one another alkyl (C, -C8), -Ca | _H2alR (18) or alkenyl (C3-C8) ); at zero, 1 or 2, - R (18) cycloalkyl (C3-C8), phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3 , methyl, methoxy and NR (19a) R (19b); R (19a) and R (19b) hydrogen, (C, -C4) alkyl or perfluoroalkyl (C, -C4); or R (3), R (4), R (5), R (6) and R (7) independently of each other heteroaryl (C, -C9), which is linked through C or N and which is Substituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, CH3, methoxy, -243-hydroxy, amino, methylamino or dimethylamino; or RO), R (4), R (5), R (6) and R (7) independently of each other C) h- (CHOH), - (CH2), - (CHOH) "- R (23) - (C") / oodd- (CHOH) /"ß.t-(V CH "22) / ooff- ( V CvHpOwHp) og -R (24) -Y 0 C «). *" (CHOH) oe- (CH,) qp- (CHOH) flk-R (25) And oxygen, -S- or -NR (22) -; h, ad, ah independently of each other zero or 1; i, j, k, ae, af, ag, ao, ap and ak independently from each other zero, 1, 2, 3 or 4; not being however in each case h, i, and k simultaneously zero, not being ad, ae and ag simultaneously zero as well as not being ah, ao and ak simultaneously zero, R (23), R (24), R (25) and R (22) independently of each other hydrogen or (C, -C3) alkyl; or RO), R (4), R (5), R (6) and R (7) independently of each other -SR (29), -OR 0), -NR (31) R (32) or -CR (33) R (34) R (35); R (29), ROO), R (31) and R (33) -244 - independently of each other -CaH2a-heteroaryl (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylammo; to zero, 1 or 2; R (32), R (34) and R (35) independently of one another as defined R (29) or hydrogen, alkyl (C * -C4) or perfluoroalkyl (C, -C4); or RO), R (4), R (5), R (6) and R (7) independently of each other R (96), R (97) and R (98) independently of one another heterolalk (C, -C9), which is linked through C or N and which is unsubstituted or substituted with 1 to 3 substituents taken between a group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamine, dimethylamine or benzyl; W oxygen, S or NR (36) -; R (36) H or alkyl (C, -C4); or R (3), R (4), R (5), R (6) and R (7) independently of each other R (46) X (1) -, - X (l) oxygen, S, NR ( 47), (D = 0) A- or NR (48) C = MN (* R (49) -, - M oxygen or sulfur, A oxygen or NR (50), DC or SO, R (46) alkyl ( C, -C8), alkenyl (C3-C8), -245- < CH2 > b dF2d + l OR - xH2? - R < 5 1 > 'b zero or 1; d 1, 2, 3, 4, 5, 6 0 7; x zero, 1, 2, 3 or 4; R (51) cycloalicyl (C3-C8), phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (52 ) R (53); R (52) and R (53) hydrogen, alkyl (C, -C4) or perfluoroalkyl (C, -C4), R (47), R (48) and R (50) independently hydrogen, alkyl (C, -C4) ) or perfluoroalkium (CC ^); R (49) is defined as R (46); or R (46) and R (47) or R (46) and R (48) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl; A and N () being attached to the phenyl nucleus of the fundamental framework of the heteroaroylguanidine; or R (3), R (4), R (5), R (6) and R (7) independently of each other -SR (64), -OR (65), -NHR (66), -NR ( 67) R (68), -CHR (69) R (70) or -CR (54) R (55) OH, -C = CR (56), -CR (58) = CR (57) or - [CR (59) R (60)] u- (CO) - [CR (61) R (62)] vR (63); R (64), R (65), R (66), R (67) and R (69) equal or different - (CH2) and- (CHOH) z- (CH2) aa- (CH20) tR (71) or - (CH2) ab-0- (CH2-CH20) ac-R (72); R (71) and R (72) independently of one another hydrogen or methyl; - 246 - U 1 1, 2 2, 3 or 4; v cceerroo ,, 1, 2, 3 or 4; And l z, aa equal or different zero, 1, 2, 3 or 4; t 1, 2, 3 0 4; R (68), RR ((7700), R (54) and R (55) same or different hydrogen or alkyl (C, -C6), - or R (69) and R (70) or R (54) and R (55) in common with the carbon atom carrying them, a (C3-C8) cycloalkyl; R (63: hydrogen, alkyl (C, -C6), cycloalkyl (C3-CO-C eH2e-R (73)) e, zero, 1, 2, 3 or 4, R (b6), R (57) and R (73) independently phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl , CF3, methyl, methoxy and NR (74) R (75); R (74) and R (75) hydrogen or alkyl (C, -C4); or R (56), R (57) and R (73) independently hetero (C, -C9), which is substituted or substituted as phenyl, R (58), R (59), R (60), R (61) and R (62) hydrogen or methyl, or R (3) ), R (4), R (5), R (6) and R (7) independently of each other R (76) -NH-S02-; R (76) R (77) R (78) N- ( C = Y ') -; Y' oxygen, S or NR (79), R (77) and R (78) equal or different hydrogen, (C-C8) alkyl, alkenyl (Cz-C6) 6 CfH2f-R (80); - 247 - f zero, 1, 2, 3 or 4; R (80) cycloalkyl (C5-C6) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methoxy and alkyl (C, -C4); or R (77) and R (78) in common 4 or 5 metlene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl; R (79) is defined as R (77) or is equal to amidma; or R (3), R (4), R (5), R (6) and R (7) independently of each other NR (84a) R (85), OR (84b), SR (84c) Ó -CnH2n -R (84d); n zero, 1, 2, 3 or 4; R (84d) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy and NR (16) R (17 ), - R (16) and R (17) hydrogen or alkyl (C, -C4); R (84a), R (84b), R (84c) and R (85) independently of each other hydrogen, alkyl (C, -C8), perfluoroalkyl (C, -C8) or (CH2) a? -R (84g) ); ax zero, 1, 2, 3 or 4; R (84g) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (84u) R (84v); R (84u) and R (84v) hydrogen or C, -C4 alkyl; - 248 - or R (84a) and R (85) in common 4 or 5 methylene groups, of which a CH2 group may be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl, as well as their salts pharmaceutically compatible; z) Benzoylguanidines of Formula I where they mean: R (l) R (6) -SOm; m zero, 1 or 2; R (6) perfluoroalkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, which is linear or branched; R (2) and R (3) independently of one another hydrogen, F, Cl, Br, 1, alkyl with 1, 2, 3 or 4 atoms of C, alkoxy with 1, 2, 3 or 4 C atoms or phenoxy, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, methyl and methoxy; or R (2) and R (3) independently of each other pyrrol-1-yl, pyrrol-2-yl or pyrrol-3-yl, which is unsubstituted or substituted with 1 to 4 substituents selected from the group consisting of F, Cl, Br, I, CN, alkanoyl with 2, 3, 249 4, 5, 6, 7 or 8 C atoms, alkoxycarbonyl with 2, 3, 4, 5, 6, 7 or 8 C atoms, formyl , carboxy, CF3, methyl and methoxy; R (4) and R (5) independently of one another hydrogen, alkyl with 1, 2 or 3 atoms of C, F, Cl, Br, I, CN, OR (7), NR (8) R (9) or - (CH2) n- (CF2) o-CF3; R (7), R (8) and R (9) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; n zero or 1, - or zero, 1 or 2; as well as its pharmacologically acceptable salts; ab) Guanidides of phenyl-substituted alkenylcarboxylic acids, carriers of perfluoroalkyl groups, of Formula I in which they mean: RIA) hydrogen, F, Cl, Br, I, CN, OH, 0R (6), alkylo (C.-C8), Or (CH2) aCbF2b +, cycloalkyl (C3-C8) or NR (7) R (8); r zero or 1; to zero, 1, 2, 3 or 4; - 250 - b 1, 2, 3, 4, 5, 6, 7 or 8; R (6) alkyl (C.-C8), perfluoroalkyl (C, -C), alkenyl (C3-C8), cycloalkyl (C3-C8), phenyl or benzyl, - the aromatic radicals being unsubstituted or substituted with 1- 3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10); R (9) and R (10) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (7) and R (8) independently of one another as R (6) has been defined; or R (7) and R (8) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl; R (B) independently as RIA has been defined); X zero, 1 or 2; And zero, 1 or 2; RIVER hydrogen, F, Cl, Br, I, CN, OR (12), alkyl (0, -03), ° P ^ CH2 ^ fCgF2g +? Cycloalkyl (C3-C8); p zero or 1; f zero, 1, 2, 3 or 4; g 1, 2, 3, 4, 5, 6, 7 or 8; R (12) alkyl (C, -C8), perfluoroalkyl (C, -C4), (C3-C8) alkenyl, (C3-C8) cycloalkyl, phenyl or benzyl; the phenyl or benzyl aromatic radicals being unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, methyl, methoxy and NR (13) R (14); - 251 - R (13) and RÍ14) independently of each other H, (C, -C 4) alkyl or perfluoroalkyl (C, -C 4); RID) independently as defined R (C), R (l) hydrogen, alkyl (C, -C8), -0t (CH2) dCeF2e + 1, cycloalkyl (C3-C8), F, Cl, Br, I or CN; t zero or 1; d zero, 1, 2, 3 or 4; e 1, 2, 3, 4, 5, 6, 7 or 8; R (2), R (3), R (4) and R (5) independently of one another as defined R (1); but with the proviso that at least one of the substituents R (A), R (B), R (C), RID), R (l), R (2), R (4) or R (5) It has to be a group ° r (CH2) to bF2b + r '0p < fV f gF2g + r 6 ° t < H2 > dCeF2e + r and R { 3) is not any group Ot (CH2) dCeF2e +, -; as well as its pharmaceutically compatible salts; ac) Benzoylguanidmas substituted with amino in ortho of the Formula I where they mean: R (l) NR (50) R (6); R50) and R (6) independently of one another hydrogen, (C, -C8) alkyl or perfluoroalkyl (C, -C8); R { 2), R (3), R (4) and R (5) -252 - independently of each other R (10) -SOa-, R (11) R (12) N-C0-, R (13) - C0- or R (14) R (15) N-S02 ~; to zero, 1 or 2; R (10), R (ll), R (12), R (13), R (14) and R (15) independently of each other alkyl (C.-C8), perfluoroalkyl (C, -C8), (C3-C6) alkenyl or -CabH ab'R (16) 'ib «_ero, 1, 2, 3 or 4, R (16) (C3-C7) cycloalkyl, phenyl, which is unsubstituted or substituted by 1- 3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy or NR (17) R (18); R17) and R18) independently of one another H, CF3 or alkyl (C, -C4); or R (ll), R (12) as well as R (14) and R (15) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; or R (ll), R (12), R (14) and R (15) independently of each other hydrogen; or R (2), R (3), R (4) and R (5) independently of each other -SR (21), -OR (22), -NR (23) R (24) or -CR (25) ) R (26) R (27); R (21), R (22), R (23) and R (25) independently of each other -CbH2b-heteroaryl (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; b zero, 1 or 2; R (24), R (26) and R (27) -253 - independently of one another hydrogen, (C, -C4) alkyl or perfluoroalkyl (C, -C4); or R (2), RO), R (4) and R (5) independently of each other hydrogen, F, Cl, Br, I, CN, - (Xa) dg-CdaH2da + 1, - (Xb) dh- (CH2) db-CdeF2de + 1, (C3-C8) alkenyl or -CdfH2dfR (30); (Xa) O, S or NR (33); RI33) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4), - dg zero or 1, - (Xb) O, S or NR (34); R34) H, alkyl (C, -C4) or perfluoroalkyl (C, -C4); dh zero or 1; gives zero, 1, 2, 3, 4, 5, 6, 7, 8; db zero, 1, 2, 3, 4; from zero, 1, 2, 3, 4, 5, 6, 7; df zero, 1, 2, 3, 4; ROO) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being phenyl, biphenylyl or naphthyl unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, 'Cl, CF3, methyl, methoxy and NR (31) R (32); R (31) and R (32) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); or R (2), RO), R (4) and R (5) independently of each other NR (40) R (41) or -ÍXe) - (CH2) ebR (45); R (40) and R (41) independently of each other hydrogen, alkyl (C, -C8), perfluoroalkyl (C, -C8) or -254! CH2) eR (42; e zero, 1, 2, 3 or 4; R (42) (C3-C7) cycloalkyl, phenyl which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (43) R (44 ); R (43) and R (44) independently of one another H, CF3 or alkyl (C, -C4) or R (40) and R (41) in common 4 or 5 methylene groups, of which one group CH2 may be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl, (Xe) 0, S or NR (47), - RÍ47) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4) ); eb zero, 1, 2, 3 or 4; R (45) (C3-C7) cycloalkyl, phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy, NR (50) R (51) and - (Xfa) - (CH2) ed- (Xfb) R (46); Xfa CH2, 0, S or NR (48); Xfb 0, S OR NR (49); ed 1, 2, 3 0 4; R (46) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (48), R (49), R (50) and R (51) independently of one another H or (C, -C4) alkyl or perfluoroalkyl (C, -C4); however, R (3) and R (4) are hydrogen, - and their pharmaceutically compatible salts; ad) Benzoylguanidmas of Formula I where they mean: one of the three substituents R (l), R (2) and R (3) heteroapl (C, -C9) -N-oxide, which is linked through C or N and which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamine and dimethylamino; or one of the three substituents R (l), R (2) and R (3) -SR (10), -OR (10), -NRIL) R (ll) or -CR (10) R (11) R (12); RÍ10) -C 3H C, a-heteroanl (CI-CVJ -N-oxide, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3, CH 3, methoxy, hydroxy, ammo , methylamino and dimethylammon, at zero, 1 or 2, R (ll) and R (12) independently of one another as defined R (10), hydrogen or alkyl (C.-C4), and the respectively other substituents R (l), R (2) and R (3) as well as their pharmaceutically compatible salts; ad) Benzoylguanidines of Formula I where they mean: one of the three substituents R (l), R (2) and R (3) heteroaryl (C.-C9) -N-oxide, which is linked through C or N and which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamine and dimethylamino; or one of the three substituents R (l), R (2) and R (3) -SRÍ10), -ORÍ10), -NRdO) R (ll) or -CR (10) R (11) R (12); R (10) -CaH2a-heteroaryl (C, -C9) -N-oxide, which is substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, ethoxy, hydroxy , ammo, methylamino and dimethylamino; to zero, 1 or 2, - R (ll) and R (12) independently of one another as defined R (10), hydrogen or alkyl (C, -C4); and the respectively other substituents R (1), R (2) and R (3) independently of each other (C, -CJ, (C2-C8) alkenyl or -CmH2mR (14); m zero, 1 or 2; R (14) (C3-C8) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (15) R (16), R (15) and R (16) hydrogen or CH3; other substituents R (l), R (2) and R (3) independently of each other hydrogen, F, Cl, Br, I, -C = N, X- (CH2) p- (CqF2q + 1), R (22) -SOu, R (23) R (24) N-CO, R (25) -CO- or R ((26) R (27) N-S02-, the linear or branched perfluoroalkyl group, X being bond, oxygen, S or NR (28), zero, 1 or 2, p zero, 1 or 2, q zero, 1, 2, 3, 4, 5 or 6, R (22), R (23), R (25) and R (26) independently alkyl (C, -C8), alkenyl (C2-C6), -CNH2r | -R (29) or CF3; n null, 1, 2, 3 or 4; R (28 ) hydrogen or (C, -C3) alkyl, R (29) cycloalkyl (C ^ -C) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl , methoxy and NR (30) R (31); ROO) and R (31) hydrogen or (C, -C4) alkyl, or R (23), R (25) and R (26) also hydrogen; R (24) and R (27) independently from each other hydrogen or alkyl (C, -C4); or R (23) and R (24) as well as R (26) and R (27) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or -benzyl, or IOE, respectively, other substituents R (l), R (2) and R (3) independently of each other OR (35) or NR (35) R (36); R (35) and R (36) independently from each other hydrogen or alkyl (C, -C6); or R (35) and R (36) in common 4-7 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, R (4) and R (5) ) independently of one another from hydrogen, alkyl (C, -C4), F, Cl, -OR (32), -NR (33) R (34) or CrF2r +,; R (32), R (33) and R (34) independently of each other hydrogen or alkyl (C, -C3); r 1, 2, 3 0 4; as well as its pharmaceutically compatible salts; ad) Benzoylguanidines of Formula I in which they mean: R) hydrogen, F, Cl, Br, I, CN, N02, OH, alkyl (C.-C8), cycloalkyl (C3-C8), 0a- (CH2) b- (CF2) c- CF3; to zero or 1; b zero, 1 or 2; c zero, 1, 2 or 3; or R) R (5) -S0m or R (6) R (7) N-S02-; m zero, 1 or 2; R (5) and R (6) independently from each other alkyl (C, -C8), alkenyl (C3-C6), CF3 or -CnH2n-R (8); n zero, 1, 2, 3 or 4; R (7) hydrogen or alkyl (C, -C4); R (8) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10); R (9) and R (10) independently of each other hydrogen or alkyl (C, -C4); or R (6) H; or R (6) and R (7) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, or R (l) -SR (ll), -OR (ll) OR -CR (11) R (12) R (13); R (ll) -CH. -cycloalkyl (C3-C8), heteroaryl (C, -C6) or phenyl, the aromatic systems being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; R (12), R (13) independently of one another as defined R (ll) or hydrogen or alkyl (^ -C ^); p zero, 1 or 2; or R (I): phenyl, naphthyl, biphenylyl or hetero (C, -C9), the latter linked through C or N, which are substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl , CF3, CH3, methoxy, hydroxy, amino, methylamine and dimethylamine, - R (2! -CF2R (14; -CF [R (15)] [R (16)], -CF [(CF, iq-CF3) [RÍ15)] -C [(CF2) p-CF3] = CR (15) R (16); R (14) alkyl (C, -C4) or cycloalkyl (C3-C6); R (15) and RÍ16) independently of one another hydrogen or alkyl (C, -C4); q zero, 1 or 2; r zero, 1 or 2, - RO: as defined R (l); R (4) hydrogen, alkyl (C, -C3), F, Cl, Br, I, CN, -CH2) s- (CF2) t-CF3; s zero or 1; t zero, 1 or 2, -as well as their pharmaceutically compatible salts; ae) Benzoylguanidmas of Formula I where they mean: one of the three substituents R (l), R (2) and R (3) -Y-4- [(CH2) k-CHR (7) - (C = 0) R (8)] -phenyl, -Y-3- [(CH2) k-CHR (7) - (C = 0) R (8)] -phenyl or -Y-2- [(CH2) k-CHR (7) - (C = 0) R (8)] -phenyl, the phenyl being in each case unsubstituted or substituted with 1-2 substituents taken from the group consisting of F, Cl, CF3, methyl, hydroxy, methoxy or -NR (37) R (38); R (37) and R (38) independently of one another hydrogen or -CH3; And a bond, oxygen, -S- or -NR (9); R (9) hydrogen or alkyl (C, -C4); R (7) -OR (IO) OR -NR (10) R (11); R (10) and R (ll) independently of one another hydrogen, (C, -C 8) alkyl, (C, -C 8) alkanoyl, (C, -C 8) alkoxycarbonyl, benzyl, benzyloxycarbonyl; or R (10) trifly; RÍ8) -ORÍ12) or -NR (12) R (13); R (12) and R (13) independently of each other hydrogen, (C, -C 8) alkyl or benzyl; k zero, 1, 2, 3 or 4; and the respectively other radicals R (1), R (2) and R (3) independently of one another -alkyl (C, -C 8), -alchemyl (C 2 -C 8) or - (CH 2) mR (14); m zero, 1 or 2; R14) -cycloalkyl (C3-C8) or femlo, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -CF3, methyl, methoxy and -NR (15) R (16); R (15) and R (16) hydrogen or -CH 3; or the respectively other radicals R (l), R (2) and R (3) independently of each other R (18) R (19) N- (C = Y ') -NH-S02-; Y 'oxygen, -S- or -N-R (20); R (18) and R (19) independently of each other hydrogen, alkyl (C, -C8), alkenyl (C3-C6) or - (CH2) tR (21), - t zero, 1, 2, 3 or 4; R (21) -cycloalkyl (C5-C7) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -CF3, methoxy and alkyl (C, -C4); or R (18) and R (19) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, -S-, -NH-, -N-CH3 or -N-benzyl; R (20) as defined R (18) or amidine; or the respectively other radicals Ríl), R (2) and R (3) independently of each other hydrogen, F, Cl, Br, I, -C = N, X- (CH2) p- (CqF2q +,), R (22) -SO-, 'R (23) R (24) N-CO-, R (25) -CO- or R (26) R (27) N-S02-, the linear or branched perfluoroalkyl group being; X a bond, oxygen, -S- or -NR (28); u zero, 1 or 2; p zero, 1 or 2; q 1, 2, 3, 4, 5 0 6; R (22), R (23), R (25) and R (26) independently of each other -alkyl (C, -C8), -alkenyl (C3-C6), - (CH2) nR (29) or - CF3; n zero, 1, 2, 3 or 4; R (28) hydrogen or alkyl (C, -C3); R (29) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -CF3, methyl, methoxy and -NRI30) R (31); ROO) and ROI) hydrogen or -alkyl (C, -C4); or R (23), R (25) and R (26) hydrogen; R (24) and R (27) independently of one another hydrogen or -alkyl (C, -C4) or RÍ23) and R (24) as well as R (26) and R (27) in common 4 or 5 methylene groups , of which a CH2 group may be replaced by oxygen, -S-, -NH-, -N-CH3 or -N-benzyl; or the respectively other radicals R (l), R (2) and R (3) independently of each other -0RO5) or -NR (35) R (36); RI35) and R (36) independently of one another hydrogen or (C, -C6) alkyl, - or R (35) and R (36) in common 4-7 methylene groups, of which a CH2 group may be replaced by oxygen, -S-, -NH-, -N-CH3 or -N-benzyl; R (4) and R (5) independently from each other hydrogen, -alkyl (C-C4), F, Cl, -OR (32), -NR (33) R (34) or -CrF2rt1; RI32), R (33) and R (34) independently of one another hydrogen or -alkyl (C-C3); r 1, 2, 3 0 4; as well as its pharmaceutically compatible salts; af) Benzoylguanidines of Formula I in which they mean: R) R (6) -CO or R (7) R (8) N-CO; R (6) alkyl (C, -CJ, perfluoroalkyl (C "C8 > alkenyl (C3-C8) p -R Zp (9) n zero, 1, 2, 3 or 4; R (9) (C3 C8), phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (10) R (11) R (10) and R (ll) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (7) H, (C, -C8) alkyl, perfluoroalkyl (C, -C8), alkenyl (c3-c8) or -CnH2n-R (12); n zero, 1, 2, 3 or 4; R (12) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals SM being substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (13 ) R (14); R (13) and R (14) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (8) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4); or RO) and R (8) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R (2) as defined R (l), or H, OH, F, Cl, Br, I, CN, N02, alkyl (C, -C8), perfluoroalkyl (C, -C8), alkenyl (C3- C8) or -CnH2nR (15); n zero, 1, 2, 3 or 4; R (15) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (16) R (17); R (16) and R (17) H, (C, -C4) alkyl or perfluoroalkyl (C-C4); or R (2) heteroaryl (C, -C9), which is bonded through C or N and which is sm substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy , hydroxy, ammo, methylamino and dimethylamino; or R (2) -SRÍ18), -0R (18), -NR (18) R (19) OR -CR (18) R (19) R (20); R (18) -CH, -heteroaryl (C.-C0), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; to zero, 1 or 2; R (19) and R (20) independently of one another as defined R (18) or hydrogen, alkyl (C, -C 4) or perfluoroalkyl (C, -C 4); or R (2) R (21) -SOm or R (22) R (23) N-S02-; m 1 or 2; R21) alkyl (C, -C8), perfluoroalkyl (C, -C8), alkenyl (C3-C8) or -CnH2n-R (24); n zero, 1, 2, 3 or 4; R (24) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (27 ) R (28), -R (27) and R (28) H, alkyl (C.-C4) or perfluoroalkyl (C-C4); R (22) H, (C, -C8) alkyl, perfluoroalkyl (C, -C8), alkenyl (C3-Ca) or -CnH2n-R (29), - n n0, 1, 2, 3 or 4; R (29) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR ( ) R (31); ROO) and R (31) H, (C * -C4) alkyl or perfluoroalkyl (C, -C4); R (23) hydrogen, (C, -C4) alkyl or perfluoroalkyl (C, -C4); or R (22) and R (23) in common 4 or 5 metlene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; or R (2) R (33) X-; X oxygen, S, NR (34), (D = 0) A- or NR (34) C = MN (* R (35) -; M oxygen or S; Oxygen or NR (34); DC or SO; R (33) alkyl (C, -C8), alkenyl (C3-C8), (CH2) bCdF2d +, or -CnH2n-R (36); b zero or 1, -d 1, 2, 3, 4, 5, 6 0 7; n null, 1, 2, 3 or 4; R (36) (C3-C8) cycloalkyl, phenyl, biphenylyl or naphthyl, the aromatic radicals being unsubstituted or substituted with 1-3 substituents selected from the group consists of F, Cl, CF3, methyl, methoxy and NR (3) R (38); R (37) and R (38) H, (C-C4) alkyl or perfluoroalkyl (C, -C4); 34) hydrogen, (C, -C 4) alkyl or perfluoroalkyl (C, -C 4); R (35) as defined R (33); or RÍ33) and RÍ34) in common 4 or 5 methylene groups, which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; A and Nc * 5 being attached to the phenyl nucleus of the fundamental framework of the benzoylguanidma; or R (2) -SR (40), -OR (40), -NHR (40), -NR (40) R (41), -CHR (40) R (42), -CR (42) R ( 43) OH, -C = CR (45), -CRÍ46) = CR (45) or - [CR (47) R (48)] u-CO- [C (R49) R (50)] and R (44); R (40) and RÍ41) independently of one another - (CH2) - (CHOH) q- (CH2) p- (CHOH) t-R (51) or - (CH2) -O- (CH2-CH20) q-R (51); R (51) hydrogen or methyl; u 1, 2, 3 or 4; v zero, 1, 2, 3 or 4; p. q And r independently of each other zero, 1, 2, 3 or 4; t 1, 2, 3 or 4; R (42) and R (43) independently from each other hydrogen or alkyl (C, -C6); or R (42) and RÍ43) in common with the carbon atom carrying them, a (C3-C8) cycloalkyl, - R (44) hydrogen, (C, -C6) alkyl, (C3-C8) cycloalkyl, -CeH2e-R (45); e zero, 1, 2, 3 or 4, - R (45) phenyl, which is substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, ethoxy and NR (52) R (53); R52) and R (53) H or (C, -C4), - or R (45) heteroaryl (C, -C9) alkyl, which is unsubstituted or substituted as phenyl; or R (45) alkyl (C, -C6), which is unsubstituted or substituted with 1-3 OH; R (46), R47), R (48), R (49) and R (50) independently of one another, hydrogen or me ilo; or R (2) R (55) -NH-S02-; R (55 R (56) R (57) N- (C = Y) -; and oxygen, S or NR (58); R (56) and R (57) independently of one another hydrogen, alkyl (C. C8), (C3-C6) alkenyl or -CfH2f-R (59); f zero, 1, 2, 3 or 4; R (59) cycloalkyl (C5-C7), phenyl, which is unsubstituted or substituted by 1; -3 substituents selected from the group consisting of F, Cl, CF3, methoxy and alkyl (C, -C4), or R (56) and R (57), in common 4 or 5 methylene groups, of which CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, • R (5i as defined R (56) or equal to amidine; R (3), R (4) and R (5 ) are independently of each other as R (l) or R (2) have been defined, however, at least one of the substituents R (2), R (3), R (4) and R (5) must be equal to OH; as well as its pharmaceutically compatible salts; ag) Benzoylguanidines of Formula I wherein they mean: one of the three R l substituents), R (2) and R (3) R (6) -A-B-D-; R (6) a basic protonatable radical, ie an amino group -NR (7) R (8), an amidino group R (7) R (8) N-C [= N-R (9)] - or a guanidino group, R (7), R (8), R (9) and R (10) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (7) and R (8) in common CaH, C.a; to 4, 5, 6 0 7; verifying, in the case that a = 5, 6 or 7, that a methylene group of the CaH2a group can be replaced by a group with heteroatoms O, SOm or NR (ll); or R (8) and R (9) or R (9) and R (10) or R (7) and RÍ10) a CaH2a group; to 2, 3, 4 or 5; verifying, in the case that a = 3, 4 or 5, that a methylene group of the CaH2a group can be replaced by a group with heteroatoms O, SOm or NR (ll); m zero, 1 or 2, - R (ll) hydrogen or methyl; or R (6) a basic heteroaromatic ring system with 1-9 C atoms; A CbH2b; b 1, 2, 3, 4, 5, 6, 7, 8, 9 0 10; it being verified in the CbHb group that one or two methylene groups can be replaced by one of the groupings selected from the group consisting of -O-, -CO-, -CH [OR (20)] -, -SO (n- , -NR (20) -, -NR (20) -CO-, -NR (20) -CO-NH-, -NR (20) -CO-NH-SO, - (0) ao II -R (20) H-S-II INR (19) lbb and -S0aa [NR (19)] bb-; and verifying in the group CbH2b that a methylene group can be replaced by -CH-R (99), forming R (99) in common with R (7) a pyrrolidine or piperidine ring; aa 1 or 2; bb zero or 1; aa + bb = 2; R (19) hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms; R (20) hydrogen or methyl; a phenylene or naphthylene radical R12) and R (13) independently of one another hydrogen, methyl, F, Cl, Br, I, CF3 or -S0W-R (14); R (14) methyl or NR (15) R (16); R15) and R16) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; zero, 1 or 2; D -CdH2d-Xf-; d zero, 1, 2, 3 or 4; X -0-, -CO-, -CH [OR (21)] -, -S0m- or -NR (21); f zero or 1; R (21) hydrogen or methyl; m zero, 1 or 2, -and the respectively other substituents R (l) and R (2) and R (3) independently of each other hydrogen, F, Cl, Br, I, -CN, -alkyl (C, - C8) -alkenyl (C6-C '8' -NR (35) R (36) or R (17) -C8H2h-Zh- g zero, 1, 2, 3 or 4, - h zero or 1, - R ( 35) and R (36) independently of one another hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms, or R (35) and R (36) in common 4-7 methylene groups, which a CH2 group can be replaced by oxygen, -S-, -NH-, -NCH3 or -N-benzyl; Z -0-, -CO-, -S0V-, -NR (18) -, -NR ( 18) -C0-, -NR (18) -CO-NH- or -NR (18) -S02-; R (18) hydrogen or methyl; v zero, 1 or 2; R (17) hydrogen, cycloalkyl with 3; , 5 or 6 atoms of k 1, 2 or 3; or R (17) pyrrol-1-yl, pyrrol-2-yl or pyrrol-3-yl, which is unsubstituted or substituted by 1-4 substituents selected from the group consisting of F, Cl, Br, I, - CN, alkanoyl (C2-C8), (C2-C8) alkoxycarbonyl, formyl, carboxy, -CF3, methyl and methoxy; or R (17) -cycloalkyl (C3-C8) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, hydroxy, methoxy, -NR (37 ) R (38), CH3S02- and H2N02S -, - R (37) and R (38) hydrogen or CH3; R (4) and R (5) independently of one another hydrogen, alkyl with 1, 2, 3 or 4 C atoms, F, Cl, -OR (32), -NR (33) R (34) or -CrFr +1; RÍ32), R (33) and R (34) independently of each other hydrogen or alkyl with 1, 2 or 3 C atoms; r 1, 2, 3 0 4; as well as its pharmacologically compatible salts; ah) Indenoilguanidines of Formula I 9) where they mean: R (l) and R (2) independently of one another hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms, cycloalkyl with 3, 4 , 5 or 6 C atoms, O-alkyl with 1, 2, 3 or 4 C atoms, OC (= 0) -alkyl with 1, 2, 3 or 4 C atoms or CmH2m-NR (12) R ( 13); R (12) and R (13) independently from each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; m zero, 2, 3 or 4; NH-C (= 0) -NH2, C (= 0) -O-alkyl with 1, 2, 3 or 4 C atoms, C (= 0) -NH2, C (= 0) -NH-alkyl with 1 , 2, 3 or 4 C atoms, C (= 0) -N (alkyl) 2 with 1, 2, 3 or 4 C atoms in each alkyl, alkenyl group with 2, 3, 4, 5, 6, 7 , 8, 9 or 10 C atoms, alkynyl with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms, alkylaryl with 1, 2, 3 or 4 C atoms in the alkyl group, alkenyl-aryl with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms in the alkenyl, alkynyl-aryl group with 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms in the alkyl group, aryl substituted with C-C4 alkyl, heteroaryl substituted with C, -C4 alkyl, C-C4 alkenyl-heteroaryl, aminoalkyl-aplo with 1, 2, 3 or 4 C atoms in the group alkyl, substituted aryl, heteropole and substituted heteroaryl; R (3), R (4), R (5) and R (6) independently of each other hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms, 0-alkyl with 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms, halogen (such as F, Cl, Br, I), OH, aryl, substituted aplo, heteroaryl , substituted heteroaryl, O-lower alkyl, 0-aryl, O-alkyl-aryl-aryl, substituted 0-aryl, O-lower alkyl-substituted aryl, OC (- = 0) -alkyl C, -C4- ar? lo, OC (= 0) -NH-C, -C4, 0-C (= 0) -N (C-C4) alkyl, N02, CN, CF3, NH2, NH-C (= 0) ) -alkyl C, -C, NH-C (= 0) -NH2, COOH, C (= 0) -0-alkyl C, -C4, C (= 0) -NH2, C (= 0) - NH-C-C4 alkyl, C (= 0) -N (C-C4 alkyl) 2, C-alkyl, -C4-C00H, C-alkyl, -C4-C (= 0) -0-alkyl C , -C4, S03H, S02-alkyl, S02-alkyl, S02-N- (alkyl) 2, S02-N (alkyl) (alkyl), C (= 0) -R (II), alkyl C , -C, 0-C (= 0) -R (11), C2-C alkenyl, 0-C (= 0) -R (11), C2-C alkylam, 0-C (= 0) -R ( 11), NH-C (= 0) -alkyl C, -C, 0-C (= 0) -R (11), 0-alk? L C, -C ,, -C (= 0) -R ( eleven); R (ll) C, -C 4 alkyl, C, C 4 alkyl, aplo, substituted alkyl, NH 2, NH-C, -C, N- alkyl (C, -C 4 alkyl), S 0 3 H, S 0 2 -alkyl, S02-alkyl, S02-N- (alkyl) 2, S02-N (alkyl) (alkylaryl); X 0, S or NH; R (7), R (8), R (9) and R (10) independently of each other hydrogen, alkyl, cycloalkyl, aryl, alkylaryl; or R (8) and R (9) are common part of a heterocyclic ring of 5, 6 or 7 members, A is absent or is a non-toxic mineral or organic acid. ai) Benzoyloxycarbonylguanidmas of Formula I in which they mean: R), R (2) and RO) independently of each other -Y- [4-R (8) -phenyl], -Y- [3-RÍ8) -phenyl] or -Y- [2 -R (8) -phenyl], the phenyl being in each case substituted or substituted with 1-2 substituents taken from the group consisting of F, Cl, -CF3, methyl, hydroxy, methoxy and -NR (96) R (97); R (96) and R97) independently of one another hydrogen or -CH3; And a bond, CH2, oxygen, -S- or -NR (9); R (9) hydrogen or alkyl with 1, 2, 3 or 4 C atoms; R (8) SOa [NR (98)] bNR (99) R (10); to 1 or 2; b 0 or 1; a + b = 2; R (98), R (99) and R (10) independently of each other hydrogen, -alkyl (C, -C8), benzyl, -alkylene (C2-C8) -NR (11) R (12), -alkylene (C2-C8) -NR (13) -alkylene (C2-C8) -NR (37) R (38) or alkylene (CQ-C8) -CR (39) R (40) -CR (41) R (42) ) -alkylene (C-C-) -NR (43) R (44); R (ll), R (12), R (13), R (37), R (38), R (43) and R (44) independently of each other hydrogen, -alkyl (C, -C8) or benzyl; RI39), R (40), R (41) and R (42) independently of one another hydrogen, -alkyl (C, -C8) or -alkylene (C0-C3) -phenyl, the phenyl being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -CF3, methyl and methoxy; or R (99) and R (10) in common 4-6 methylene groups, of which a CH2- group can be replaced by oxygen, -S-, -NH-, -N-CH3 or -N-benzyl; or R (8) SOa [NR (98)] faNR (95) -C [= N-R (94)] -NR (93) R (92); R (92), R (93), R (94) and R (95) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (l), R (2) and R (3) independently of each other pyrrol-1-yl, pyrrol-2-yl or pyrrol-3-yl, which is unsubstituted or substituted with 1-4 substituents selected from the group consisting of F, Cl, Br, I, -CN, (C2-C8) alkanoyl, (C2-C8) alkoxycarbonyl, formyl, carboxy, -CF3, methyl, methoxy; or R (l), R (2) and R (3) independently of each other hydrogen, -alkyl (C, -C8), -alkenyl (C2-C8) or - (CH2) mR (14); m zero, 1 or 2; RÍ14) (C3-C8) cycloalkyl or phenyl, which is unsubstituted or substituted with 1 substituents selected from the group consisting of F and Cl, -CF3, methyl, methoxy and -NR (15) R (16); R (15) and R16) hydrogen or -CH3; or R (l), R (2) and RO) independently of each other -Q-4- [(CH2) k-CHR (17) - (C = O) R (20)] -phenyl, -Q-3 - [(CH2) k-CHR (17) - (C = O) R (20)] -phenyl or -Q-2- [(CH2) k-CHR (17) - (C = O) R (20) ] -phenyl, the phenyl being in each case unsubstituted or substituted with 1-2 substituents taken from the group consisting of F, Cl, -CF3, methyl, hydroxy, methoxy and -NR (35) R (36); R (35) and R (36) independently of one another hydrogen or -CH3; Q a bond, oxygen, -S- or -NR (18); RIV18) hydrogen or alkyl (C, -C4); R (17) -0R (21) or -NR (21) R (22); R (21) and R (22) independently of each other hydrogen, -alkyl (C, -C8), -alkanoyl (C, -C8), -alkoxy (C, -C8) -carbonyl, benzyl, benzyloxycarbom; or R (21) trifly; RÍ20) -OR (23) or -NR (23) R (24); R (23) and R (24) independently from each other hydrogen, (C, -C 8) alkyl or benzyl; k zero, 1, 2, 3 or 4; R), R (2) and RO) independently of each other heterolabe (C, -CJ, which is linked through C or N and which is unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino, -o R (l), R (2) and RO) -SR25), -OR (25), -NR (25) R (26), -CR (25) ) R (26) R (27); R (25) -CfH2f-heterolalk (C, -C9), which is unsubstituted or substituted with 1-3 substituents taken from the group consisting of F, Cl, CF3, CHJ; methoxy, hydroxy, ammo, methylamino and dimethylamino; f zero, 1 or 2; R (26) and R (27) independently of one another as defined R (25) or hydrogen or alkyl (C-C4), or R (l), R (2) and R (3) independently one of another heteroaryl (C, -C9) -N-oxide, which is linked through C or N and which is sm substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy , hydroxy, amino, methylamino and dimethylamino; or R (l), R (2) and R (3) independently of each other -SR (28), -OR (28), -NR (28) R (29) or -CR (28) R (29) R (30); R (28) -C8H2g-heteroaryl (C, -C9) -N-oxide, which is substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, ethoxy, hydroxy , arrimo, methylamine and dimethylamino; g zero, 1 or 2; R (29), R30) independently of one another as defined R (28), hydrogen or alkyl (C, -C4), -o R (l), R (2) and R (3) independently of each other hydrogen, F, Cl, Br, I, -CBN, T- (CH2) h- (C, F2 | +1), RODSO, -, R (32) R (33) N-CO-, R (34) -CO- or R (45) R (46) N-S02, the linear or branched perfluoroalkyl group being - T a bond, oxygen, -S- or -NR (47); 1 zero, 1 or 2; h zero, 1 or 2; i 1, 2, 3, 4, 5 0 6; ROÍ), R (32), R (34) and R (45) independently of each other (C, -C 8) alkyl, (C 3 -C 6) alkenyl, (CH 2) n R (48) or -CF 3; n zero, 1, 2, 3 or 4; R (47) hydrogen or alkyl having 1, 2 or 3 C atoms; R (48) (C3-C7) cycloalkyl or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -CF3, methyl, methoxy and -NR (49) R (50 ); R (49) and R (50) hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (32), R (34) and R (45) hydrogen; R (33) and R (46) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms, or R (32) and RÍ33) as well as R (45) and R (46) in common or 6 methylene groups, of which a CH2 group may be replaced by oxygen, -S-, -NH-, -NCH3 or N-benzyl; or R), R (2) and R (3) independently of each other R (51) -A-G-D-; R (51) a basic protonatable radical, ie an amino group -NR (52) R (53), an amidino group R (52) R (53) NC [= NR (54)] - or a guanidino group R (52) R (53) NC [= NR (54)] -NR (55) RÍ52), R (53), R54) and R (55) independently of one another hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (52) and R (53) a CaH2a group; to 4, 5, 6, 6 1; verifying, in the case that a = 5, 6 or 7, that a C atom of the CaH2a group can be replaced by a group with heteroatoms 0, S0d or NR (56), or R (53) and R (54) or R (54) and R (55) or R (52) and R (55) a group C? H2 ?; And 2, 3, 4 or 5; verifying itself, in the event that? = 3, 4 or 5, that a C atom of the group C? H2 can be replaced by a group with 0, SOd or NR heteroatoms (56); d zero, 1 or 2, - R (56) hydrogen or methyl; or R (51) a basic heteroaromatic ring system with 1-9 C atoms; To a group CeH2e; e zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; verifying in the group CgH2e that a C atom can be replaced by one of the groupings -0-, -CO-, -CH [OR (57)] -, -S0p-, -NRÍ57) -, -NR (57) -CO-, -NR (57) -CO-NH-, -NR (57) -C0-NH-S02 or -NR (57) -S02-; r zero, 1 or 2; a phenylene radical, R (58) and R59) independently of one another hydrogen, methyl, methoxy, F, Cl, Br, I, CF3 or -SOs-R (60); RÍ60) methyl or NR (61) R (62); R (61) and R (62) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; D -C H2v-E - v zero, 1, 2, 3 or 4; E -0-, -CO-, -CH [OR (63)] -, -S0aa- or -NR (63) -; w zero or 1; aa zero, 1 or 2; R (63) hydrogen or methyl, or R (l), R (2) and R (3) independently of each other -CF2R (64), -CF [R (65)] [RÍ66)], -CF [CFE ) q-CF3)] [R (65)], -C [CF2) p-CF3] = CR (65) R (66); R (64) alkyl having 1, 2, 3 or 4 C atoms or cycloalkyl with 3, 4, 5, 6 or 7 C atoms; R (65) and R (66) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; q zero, 1 or 2; p zero, 1 or 2, -or R (l), R (2) and R (3) independently of one another -OR (67) or -NR (67) R (68), - R (67) and R (68) independently of one another from hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C atoms; or R (67) and R (68) in common 4, 5, 6 or 7 methylene groups, of which a CH2 group can be replaced by oxygen, -S-, S02, -NH-, -NCH3 or -N -benzyl; R (4) and R (5) independently of one another hydrogen, alkyl with 1, 2, 3 or 4 C atoms, F, Cl, -OR (69), -NR (70) R (71) 6"ZF2Z + 1'- R (69), R (70) and R (71) independently of each other hydrogen or alkyl having 1, 2 or 3 carbon atoms; z 1, 2, 3 0 4; ) and R (7) independently of one another hydrogen or alkyl with 1, 2, 3 or 4 C atoms; X oxygen or NR (72); R (72) hydrogen or alkyl having 1, 2, 3 or 4 C atoms; as well as its pharmaceutically compatible salts; ak) Guanidides of alkenylcarboxylic acids carrying fluorophenyl groups, of Formula I wherein they mean: R (6) hydrogen, (C, -C 8) alkyl, (C 3 -C 8) cycloalkyl or phenyl, the phenyl group being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10); R (9) and R (10) hydrogen, (C, -C4) alkyl or perfluoroalkyl (C, -C4); R (7) independently as defined R (6); R), R (2), R (3), R (4) and R (5) independently of each other hydrogen or F; while having at least one of the radicals R (1), R (2), R (3), R (4) and R (5) as well as their pharmaceutically compatible salts; a) Benzoylguanidines of Formula I NH where they mean: R { 1) R (4) -SOm or k (5) R (6) N-S02-; m 1 or 2; R (4) and R (5) independently of each other with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 3, 4, 5 or 6 C atoms, CF3 or -CnH2n-R (7); n zero, 1, 2, 3 or 4; R (6) H or alkyl with 1, 2, 3 or 4 C atoms; Rt7) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (8) R (9); R (8) and R (9) H or alkyl with 1, 2, 3 or 4 C atoms; or R (5) also hydrogen; or R (5) and R (6) in common 4 or 5 metlene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; or R (l) -Op- (CH2) q- (CF2) r-CF3; p zero or 1; q zero, 1 or 2; r zero, 1, 2 or 3; or R (l) -SR (IO), -OR (10) or -CR (10) R (11) R (12); RÍ10), R (ll) and R (12) independently of each other hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, -C3H2s-c? Cloalkyl (C3-) C8) or an aromatic system selected from the group consisting of pipldyl, pyrrolyl, quinolyl, isoquinolyl, idolzolyl or phenyl, - s zero, 1 or 2; the aromatic pyridyl, pyrrolyl, quinolyl, isoquinolyl, ylidazolyl and phenyl aromatic systems being substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, ethoxy, hydroxy, amino, methylamino and dimethylamino; R (2) - (CH2) u- (CF2) t-CF3; t zero, 1, 2 or 3; u zero or 1; RO) hydrogen or independently as defined Ríl), - as well as their pharmaceutically compatible salts; am) Substituted cinnamic acid guanidides of Formula I wherein they mean: at least one of the substituents R (l), R (2), R (3), R (4) and R (5) X CR (16) R (17), O, S or NR (18); R (16), R (17) and R (18) independently of each other H, alkyl having 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; to zero or 1; And alkylene with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkylene-T with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms in the alkylene group, T , T-alkylene with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms in the alkylene group, - T NR (20), 0, S or phenylene, the phenylene being unsubstituted or substituted with 1 -3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (21) R (22); R (20), R (21) and R (22) independently of each other H, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; b zero or 1; 0, S, NR (23) or CkH2k; k 1, 2, 3, 4, 5, 6, 7, 8; n zero or 1; U NR (24) R (25) or a heterocycle containing N with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms; R (24) and R (25) independently of one another, hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6 , 7 or 8 C atoms; or R (24) and R (25) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; wherein the N containing heterocycles bridged in N or C, and being unsubstituted or substituted with 1-3 substituents selected - 237 - from the group consisting of F, Cl, CF3, methyl, methoxy and NR (27) R (28) ); R (23), R (27) and R (28) independently of each other H, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; and the respectively other substituents R (1), R (2), R (3), R (4) and R (5) independently of each other H, F, Cl, Br, I, CN, - ° n- Ap, * 1 '- CH2 > s-CqF2 +1 Ó "? rR <10) n zero or 1; m zero, 1, 2, 3, 4, 5, 6, 7 or 8; p zero or 1; q 1, 2, 3, 4, 5, 6, 7 or 8; s zero, 1, 2, 3 or 4; r zero, 1, 2, 3 or 4; R (10) cycloalkyl with 3, 4, 5, 6, 7 or 8 atoms of C, or phenyl, the phenyl being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (11) R (12); R (ll) and R (12) independently of one another H, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms: R (6) and R (7) independently of each other hydrogen, F, Cl, Br, I, CN, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms C, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (14) R (15), - R (14) and R (15) independently of each other H, alkyl with 1, 2 , 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; as well as its pharmaceutically compatible salts; an) Benzoylguanidines of Formula I wherein they mean: at least one of the substituents R (l), R (2) and R (3) R (6) -C (OH) 2-; R (6) perfluoroalkyl having 1, 2 or 3 carbon atoms, which is linear or branched; and the other substituents R (l), R (2) and R (3) independently of each other hydrogen, OH, F, Cl, Br, I, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl with 3, 4, 5 or 6 C atoms, alkoxy with 1, 2, 3 or 4 C atoms or phenoxy, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, methyl and methoxy; or the other substituents R (l), R (2) and R (3) independently of each other alkyl -S0 ?, -CR (7) = CR (8) R (9) or -C = CR (9); x zero, 1 or 2, - R (7) hydrogen or methyl; R (8) and R (9) independently of one another hydrogen, alkyl with 1, 2, 3 or 4 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms or phenyl, which is replace or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl and methoxy; or the other substituents R (l), R (2) and R (3) independently of each other, phenyl, C &H5-alkyl (C, -C4), naphthyl, biphenylyl, qumolyl, iso-molyl or imidazolyl, the chloro, isobutyl or amidazolyl linked through C or N, and the phenyl, C6H5-alkyl (C, -C4), naphthyl, biphenylyl, qumolyl, isoquinolyl and i.midazolyl being unsubstituted or substituted. -3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, arrimo, methylamino and dimethylamine; or the other substituents R (l), R (2) and R (3) independently of each other -SR (10), -OR (10), -CR (10) R (11) R (12); R (10) -CfH 2f-c (C 3 -C 8) -cycloalkyl, qumolyl, isoquinolyl, pipdinyl, imidazolyl or phenyl, the aromatic systems being quinolimol, isoquinolinyl, pipdinyl, imidazolyl and phenyl substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamino and dimethylamino; f zero, 1 or 2; R (ll) and R12) independently of one another as defined R (10), hydrogen or alkyl having 1, 2, 3 or 4 C atoms; R (4) and R (5) independently of one another hydrogen, alkyl having 1, 2 or 3 carbon atoms, F, Cl, Br, I, CN, OR (13), NR (14) R (15), - (CH2) n- (CF2) 0-CF3; R (13), R (14) and R (15) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; n zero or 1, - or zero, 1 or 2; as well as its pharmacologically acceptable salts; ao) Sulfonimido-amides of Formula I where they mean: at least one of the three substituents R (l), R (2) and R (3) a benzoylguanidine, that in the phenyl part is unsubstituted or substituted with 1-4 radicals selected from the group consisting of alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 2, 3, 4, 5, 6, 7 or 8 C atoms, - (CH2) mR (14), F, Cl, Br, I, -C = N, CF3, R (22) SO -, -, R (23) R (24) N-CO-, R (25) -CO-, R (26) R (27) N-S02, -OR (35) ), -SR (35) or -NR (35) R (36); m zero, 1 or 2; R (14) -cycloalkyl (C3-C8) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, methoxy and -NR (15) R ( 16); R (15) and R (16) independently of one another hydrogen or -CH 3; R (22), R (23), R (25) and R (26) independently of each other with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 2, 3, 4, 5, 6, 7 or 8 C atoms, (CH2) nR (29) or -CF3; n zero, 1, 2, 3 or 4; R (29) -cycloalkyl (C3-C7) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -CF3, methyl, methoxy and -NR (30) R ( 31); ROO) and R (31) hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (23), R (25) and R (26) hydrogen; R (24) and R (27) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (23) and R (24) as well as R (26) and R (27) in common 5 or 6 metlene groups, of which a CH2 group can be replaced by oxygen, -S-, -NH-, -NCH3 or -N-benzyl, • RI35) and RI36) independently of each other hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C atoms; or R35) and R (36) in common 4-7 methylene groups, of which a CH2 group can be replaced by oxygen, -S-, -NH-, -NCH3 or -N-benzyl; or R (35) phenyl, which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F, Cl, -CF3, methyl, methoxy, S02R (5), S02NR (6) R (7) and -NR (32) R (33); R (5) alkyl with 1, 2, 3, 4, 5 or 6 C atoms; R (6) and R (7) independently of one another hydrogen or alkyl with 1, 2, 3 or 4 C atoms, R (32) and R (33) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R35) heteroaryl (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, ethoxy, hydroxy, amino, methylamino and dimethylamino; and the other substituents Ríl), R (2) and R (3) each independently of each other alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, (CH 2) pR (10) p zero, 1, 2, 3 or 4; R (10) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, -CF3, methyl, methoxy, -S02NR (17) R (8) and -S02R (9); R17) and R (8) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; R (9) alkyl having 1, 2, 3 or 4 C atoms; or the respectively other radical R (l) and R (3) hydrogen, R (4) hydrogen or alkyl having 1, 2, 3 or 4 C atoms; as well as its pharmaceutically compatible salts; ap) Benzoylguanidines of Formula I wherein they mean: R (l) alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or NR (7) R (8); R (7) and R (8) independently from each other hydrogen or alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms; R (2) hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or -S02R (9) R (9) independently as defined R (l); R (3) hydrogen, # SR (25), -OR (25), -NR (25) R (26) or -CR (25) R (26) R (27); R (25) hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF 3, CH 3, methoxy, hydroxy, amino, methylamino and dimethylamino; or R (25) -heteroaryl (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of the groups F, Cl, CF3, CH, methoxy, hydroxy, amino, methylamino and dimethylamino; R (26) and R (27) independently of one another as defined R (25) or hydrogen or alkenyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms; R (4) hydrogen, F, Cl, Br, I, OH, -CsN, CF3, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 2, 3, 4, 5, 7 or 8 C atoms or - (CH 2) mR (14); m zero, 1 or 2; R (14) -cycloalkyl (C3-C8) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, methoxy and -NR (15) R ( 16); R (15) and R (16) independently of one another hydrogen or -CH 3; R (5) and R (6) independently of each other hydrogen, alkyl with 1, 2, 3 or 4 C atoms, F, Cl, -OR (32), -NR (33) R (34) or CF3; R (32), R (33) and R (34) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; as well as its pharmaceutically compatible salts; aq) Diguanidides of benzenedicarboxylic acid of the Formula I in which they mean: one of the radicals R (l), R (2), R (3) and R (4) -CO-N = C (NH2) 2; and the respectively other radicals R (l), R (2), R (3) and R (4): R (l) hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl, Br, I, -OR (32), -NR (33) R (34) or CF3; RÍ32), R (33) and R (34) independently of each other hydrogen or alkyl with 1, 2, 3, or 4 C atoms; R (2) and R (4) independently of one another hydrogen, F, Cl, Br, I, OH, -CN, CF3, -CO-N = C (NH2) 2, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 2, 3, 4, 5, 6, 7 or 8 C atoms or - (CH 2) mR (14); m zero, 1 or 2; R (14) (C3-C8) cycloalkyl or femlo, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, methoxy and -NR (15) R (16 ); R (15) and R (16) hydrogen or -CH 3; or R (2) and R (4) independently of each other pyrrole-1-yl, pyrrol-2-yl or pyrrole-3-lily, which is unsubstituted or substituted by 1-4 substituents selected from the group it consists of F, Cl, Br, I, -CN, (C2-C8) alkanoyl, (C2-C8) alkoxycarbonyl, formyl, carboxy, -CF3, methyl, methoxy; or R (2) and R (4) independently of one another R (22) -S02-, R (23) R (24) N-CO-, R (28) -CO- or R (29) R (30) ) N-S02; R (22) and R (28) independently of one another methyl or -CF3; R (23), R (24), R (29) and R (30) independently of each other hydrogen or meth i, -o R (2) and R (4) independently of each other -OR (35) or - NR (35) R (36); R (35) and R (36) independently from each other hydrogen or alkyl with 1, 2, 3, 4, 5 or C atoms; or R (35) and R (36) in common 4-7 methylene groups, of which a CH2 group may be replaced by oxygen, -S-, -NH-, -NCH3 or -N-benzyl; R (3) hydrogen, -SR (25), -0R25), -NR (25) R (26), -CR (25) R (26) R (27); R (25) hydroquinone, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or phenyl, which is substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl , CF3, CH3, methoxy, hydroxy, ammo, methylamine and dime11lamino, - or RI25) -heteroappe (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamine and dimethylamino; R (26) and R (27) independently of one another as defined R (25) or hydrogen or alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms; R (5) alkyl having 1, 2, 3 or 4 carbon atoms, F, Cl, Br, I, X- (CH2) and-CF3 or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from group consisting of F and Cl, -CF3, methyl, methoxy and -NR (6) R (7); R (6) and R (7) independently of one another hydrogen or -CH 3; X a bond or oxygen; and zero, 1 or 2; as well as its pharmaceutically compatible salts; ar) Diguanidides of benzenedicarboxylic acids of the Formula I where they mean: one of the radicals R (l), R (2), R (3) and R (5) -C0-N = C (NH2) 2; and the respective other radicals R (1), R (2), R (3) and R (5): R) and R (5) independently of each other hydrogen, alkyl with 1, 2, 3 or 4 C atoms , F, Cl, -OR (32), -NR (33) R (34) or CF3; R (32), R (33) and R (34) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; R (2) hydrogen, F, Cl, Br, I, OH, -CN, CF3, -C0-N = C (NH?) 2, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkenyl having 2, 3, 4, 5, 6, 7 or 8 carbon atoms or - (CH2) mR (14); m zero, 1 or 2; R (14) -cycloalkyl (C3-C8) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, methoxy and -NR (15) R ( 16); R (15) and R (16) independently of one another hydrogen or -CH 3; or R (2) R (22) -S02-, R (23) R (24) N-CO-, R (28) -CO- OR (29) R (30) N-SO2; R (22) and R (28) independently of one another methyl or -CF3; R (23), R (24), R (29) and R (30) independently of each other hydrogen or methyl; or R (2) -ORÍ35) OR -NR (35) R (36); R (35) and R (36) independently of each other hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms, or RI35) and R (36) in common 4-7 methylene groups, which a CH2 group may be replaced by oxygen, -S-, -NH-, -NCH3 or -N-benzyl; R (3) hydrogen, -SR (25), -OR (25), -NR (25) R (26), -CR (25) R (26) R (27); R (25) hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl , CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamine; or R (25) -heteroaryl (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; R (26) and R (27) independently of one another as defined R (25) or hydrogen or alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms; R (4) CF3, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl (C3- C8) or - (CH2) mR (14); m 1 or 2; R (14) -cycloalkyl (C3-C8) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, methoxy and -NR (15) R ( 16); R (15) and R (16) independently of one another hydrogen or -CH 3; or R (4-phenyl), which is substituted with 2, 3, 4 or 5 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and -NR (15) R (16); ) and R16) independently of one another hydrogen or CH3; as well as its pharmaceutically compatible salts; as) Diguanidides of diaryldicarboxylic acids of Formula I where they mean: one of the radicals R (l), R (2), R (3), R (4) and R (5) -CO-N = C (NH2) 2; the respectively other radicals R (1) and R (5) independently of one another hydrogen, alkyl with 1, 2, 3 or 4 C atoms, F, Cl, -OR (32), -NR (33) R (34) ) or CF ,; R (32), RI33) and R (34) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; the respectively other radicals R (2) and R (4) independently of one another hydrogen, F, Cl, Br, I, OH, -CN, CF3, -CO-N = C (NH2) 2, alkyl with 1, 2 , 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 2, 3, 4, 5, 6, 7 or 8 C atoms or - (CH 2) mR (14); m zero, 1 or 2; R (14) -cycloalkyl (C3-C8) or phenyl, which is unsubstituted or substituted by 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, methoxy and -NR (15) R ( 16); R (15) and R (16) hydrogen or -CH 3; or the respectively other radicals R (2) and R (4) independently of each other pyrrol-1-? lo, pyrrol-2? -oproprol-3 -lio, which is unsubstituted or substituted with 1-4 substituents selected from the group consisting of F, Cl, Br, I, -CH, (C2-C8) alkanoyl, (C2-C8) alkoxycarbonyl, formyl, carboxy, -CF3, methyl, methoxy; or the respectively other radicals R (2) and R (4) R (22) -S02-, R (23) R (24) N-CO-, R (28) -CO- or RÍ29) R (30) N -SO2; R (22) and R (28) independently of one another methyl or -CF3; R 23), R (24), R (29) and R (30) independently of each other hydrogen or metal; or the respectively other radicals R (2) and R (4) independently of one another -OR (35) or -NR (35) R (36); RI35) and RI36) independently of one another from hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms; or R (35) and R (36) in common 4-7 methylene groups, of which a CH2 group can be replaced by oxygen, -S-, -NH-, -NCH3 or -N-benzyl; the respectively other radical R (3) hydrogen, -SR (25), -OR (25), -NR (25) R (26), -CR (25) R (26) R (27); R (25) hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl , CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; or R (25) -heteroaryl (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; R (26) and R (27) independently of one another as defined R (25) or hydrogen or alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms; one of the radicals R (6), R (7), R (8), R (9) and R (10) -CO-N = C (NH 2) 2; the respectively other radicals R (6) and R (10) independently of one another hydrogen, alkyl with 1, 2, 3 or 4 C atoms, F, Cl, -OR (132), -NR (133) R (134 ) or CF3; RI132), R (133) and R (134) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms; the respectively other radicals R (7) and R (9) independently of one another hydrogen, F, Cl, Br, I, OH, -CN, CF3, -CO-N = C (NH2) 2, alkyl with 1, 2 , 3, 4, 5, 6, 7 or 8 C atoms, alkenyl with 2, 3, 4, 5, 6, 7 or 8 carbon atoms or - (CH.,) R (114); mm zero, 1 or 2, - R (114) -cycloalkyl (C3-C8) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F and Cl, -CF3, methyl, ethoxy and -NR (115) R (116), -R115) and R116) hydrogen or -CH3; or the respectively other radicals R (7) and R (9) independently of each other pyrrole-1α, pyrrol-2? or 3-pyrrolidone, which is unsubstituted or substituted with 1 -4 substituents selected from the group consisting of F, Cl, Br, I, -CN, alkanoyl (C2-C8), alkoxycarbonyl (C2-C8), formyl, carboxy, -CF3, methyl and methoxy; or the respectively other radicals R (7) and R (9) R (122) -S02-, R (123) R (124) N-CO-, R (128) -CO- or R (129) R (130 ) N-SO2; R122) and R (128) independently of one another methyl or -CF3; R123), R124), R (129) and R (130) independently of each other hydrogen or methyl; or the respectively other radicals R (7) and R (9) independently of one another -OR (135) or NR (135) R (136); R133) and R (136) independently of one another from hydrogen or alkyl with 1, 2, 3, 4, 5 or 6 C atoms; or R133) and R (136) in common 4-7 methylene groups, of which a CH2 group can be replaced by oxygen, -S-, -NH-, -NCH3 or -N-benzyl; the respectively other radical R (8) hydrogen, -SR125), -OR (125), -NR (125) R (126) or -CR (125) R (126) R (127); R (125) hydrogen, alkyl having 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, ' Cl, CF 3, CH 3, methoxy, hydroxy, amino, methylamino and dimethylamino; or R125) -heteroaryl (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CFJ; CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; R126) and R127) independently of one another as defined by R (125) or hydrogen or alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms; A is absent or means -NR (ll) -CO-, -NR (12) -CO-NR 13) -, -NR (17) -CO-NR (18) -S02-, -NR (19) -S02- , -S02-NR (19) -S02-, -S02-NR (19) -CO-, -0-CO-NRH19) -S02 or -CR (20) = CR (21) -; R (ll), R (12), R (13), R (17), R (18), R (19), R (20) and R (21) independently of each other hydrogen or alkyl with 1, 2 , 3, 4, 5, 6, 7 or 8 C atoms; as well as its pharmaceutically compatible salts; at) Guanidides of thiophene substituted alkenylcarboxylic acids of the Formula I wherein they mean: at least one of the substituents R (l), R (2) and R (3) -Op- (CH2) s-CqF2q +, R (40) CO- or R (31) SOk-; p zero or 1; s zero, 1, 2, 3 or 4; q 1, 2, 3, 4, 5, 6, 7 or 8; k zero, 1 or 2; R (40) alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl and methoxy; R (31) alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl or methoxy; or RÍ41) and R (42) independently of one another hydrogen, alkyl with 1, 2, 3 or 4 carbon atoms, perfluoroalkyl with 1, 2, 3 or 4 carbon atoms, or R (41) and R (42) in common 4 or 5 methylene groups, of which one CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl, and the respectively other substituents R (l), R (2) and R (3) independently of each other H, F, Cl, Br, I, CN, -Ona-CmaH, 2max + 11 or -0gaCraH, 2raR (10) ';' na zero or 1; ma zero, 1, 2, 3, 4, 5, 6, 7 or 8; ga zero or 1; zero, 1, 2, 3 or 4; R (10) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms or phenyl, the phenyl being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl and methoxy; R (4) and R (5) independently of one another hydrogen, F, Cl, Br, I, CN, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms C, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms or phenyl, which is unsubstituted or substituted by 1 -3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (14) R (15); R (14) and R15) independently of each other H, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; as well as its pharmaceutically compatible salts; au) Substituted ortho-substituted benzoylguanidines of Formula I wherein they mean: R (2) and RO) independently of one another hydrogen, Cl, Br, I, alkyl (C, -C8), cycloalkyl (C3-C8) or -OR (5); R (5) alkyl (C.-C8) or -CdH2cj-cycloalkyl (C3-C8); d zero, 1 or 2; hydrogen being always one of the two substituents R (2) and R (3), but not simultaneously hydrogen being both substituents R (2) and R (3), as well as their pharmaceutically compatible salts; av) Benzoylguamdines of Formula I in which they mean: R) H, F, Cl, Br, I, CN, N02, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkoxy with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, cycloalkoxy with 3, 4, 5, 6, 7 or 8 C atoms or Xa- ( CH2) b- (CF2) c-CF3; X oxygen S, NR (5); to zero or 1; b zero, 1 or 2; c zero, 1, 2 or 3, - R (5) H, alkyl having 1, 2, 3 or 4 C atoms or -CdH2dR (6); d zero, 1, 2, 3 or 4; R (6) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, phenyl, biphenylyl or naphthyl, the aromatic radicals phenyl, biphenyl or naphthyl being substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and R (7) R (8); R (7) and R (8) independently H or alkyl with 1, 2, 3 or 4 C atoms; or R (l) -SR (10), -OR (10) or -CR (10) R (11) R (12); R (10) -CfH2f-c? -alkalkyl with 3, 4, 5, 6, 7 or 8 C atoms in the cycloalkyl or phenyl ring, the phenyl being unsubstituted or substituted with 1-3 substituents selected from the group consisting of group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamino and dimet lamino, f zero, 1 or 2; R (ll) and R (12) independently of one another as defined R (10) or hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R) phenyl, naphthyl, bifemyl or heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, the latter linked through a C atom or an N atom of the ring, which in each case are unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamine and dimethylamine, or R (l) -SRÍ13), -OR (13), -NHR (13), -NR (13) R (14), -CHR (13) R (15), -C [R (15) R (16) OH], -C = * CR ( 18), -CR [R (19)] = CHR (18), -C [R (20) R ((21)] k- (CO) - [CR (22) R (23)]. -R ( 24), zero, 1, 2, 3 or 4, 1 zero, 1, 2, 3 or 4, R (13) and R (14) equal or different - (CH2) g- (CHOH) h- (CH2 ), - (CHOH) jR (17) or - (CH2) g-0- (CH2-CH20) hR (24); R (17) hydrogen or methyl; g, hei equal or different zero, 1, 2, 3 or 4; D 1, 2, 3 or 4; R (15) and R (16) equal or different hydrogen, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, or in common with the carbon atom that carries them, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms; R (18) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (25) R (26); R (25) and R (26) H or alkyl with 1, 2, 3 or 4 C atoms; or R (18) heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, which is unsubstituted or substituted as phenyl; or R (18) alkyl having 1, 2, 3, 4, 5 or 6 C atoms, which is unsubstituted or substituted with 1-3 OH; or R (18) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms; R (19), R (20), ROI), RI22) and R (23) are the same or different hydrogen or methyl; R (24) H, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms or -CmH2fflR (18); m 1, 2, 3 0 4; R (2) and R (3) as defined R (l); R (4) alkyl having 1, 2, 3 or 4 C atoms; as well as its pharmaceutically compatible salts; aw) Ortho-substituted benzoylguanidines of Formula I in which they mean: R) H, F, Cl, Br, I, CN, N02, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkoxy with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, cycloalicyloxy with 3, 4, 5, 6, 7 or 8 C atoms or V (CH2) b- (CF2) c-CF3; X oxygen, S, NR (5), at zero or 1, - b zero, 1 or 2; c zero, 1, 2 or 3; R (5) H, alkyl with 1, 3 or 4 C atoms or -CdH2dR (6) d zero, 1, 2, 3 or 4, - R (6) cycloalkyl with 3, 4, 5, 7 or 8 atoms of C, phenyl, biphenylyl or naphthyl, the aromatic radicals being phenyl, biphenylyl or naphthyl unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR ( 7) R (8); R (7) and R (8) independently H or alkyl with 1, 2, 3 or 4 C atoms; or R) -SR (10), -OR (10) or -CR (10) R (11) R (12); R (10) -CfH2f-cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms in the cycloalkyl or phenyl ring, the phenyl being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino; f zero, 1 or 2; R (ll) and R (12) independently of one another as defined R (10) or hydrogen or alkyl with 1, 2, 3 or 4 C atoms; R (l) phenyl, naphthyl, biphenylyl or heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, the latter being linked through a C atom or an N atom of the ring, which in each case are unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, arrimo, methylamino and dimethylamino; or R) -SR (13), -0RÍ13), -NHR (13), -NR (13) R (14), -CHR (13) R (15), -C [R (15) R (16) OH], -C = CR (18), -CR [R (19)] = CHR (18), -C [R (20) R (21)] k- (CO) - [CR (22) R ( 23)] .- R (24), zero k, 1, 2, 3 or 4; 1 zero, 1, 2, 3 or 4; R (13) and R (14) equal or different - (CH2) g- (CH0H) h- (CH2) .- (CHOH), -R (17) or - (CH2) g-0- (CH2-CH20 ) hR (24); R (17) hydrogen or methyl; g, h and i equal or different zero, 1, 2, 3 or 4; j 1, 2, 3 or 4; R (15) and R (16) equal or different hydrogen, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, or in common with the carbon atom that carries them, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms; R (18) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (25) R (26); R25) and R (26) H or alkyl with 1, 2, 3 or 4 C atoms; or R18) heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, which is unsubstituted or substituted as phenyl; or R (18) alkyl having 1, 2, 3, 4, 5 or 6 C atoms, which is unsubstituted or substituted with 1-3 OH; or R (18) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms; R (19), R (20), R (21), R (22) and R (23) are the same or different hydrogen or methyl; R (24) H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms ° -CmH2m-R < 18 > 'm 1, 2, 3 0 4; one of both R (2) and R (3) hydroxyl substituents; and the respectively one of the substituents R (2) and R (3) is defined as R (l); R (4) alkyl having 1, 2, 3 or 4 C atoms; alkoxy with 1, 2, 3 or 4 C atoms; F, Cl, Br, I or - (CH2) n- (CF2) Q-CF3; n zero or 1, - or zero or 1; as well as its pharmaceutically compatible salts; ax) Benzoylguanid as bis-substituted as ortho of Formula I in which they mean: R), R (2) and R (3) independently of one another R (10) -SOa- or R (14) R (15) N-S02-; to zero, 1 or 2; R (10), R (14) and R (15) independently of each other with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, perfluoroalkyl with 1, 2, 3, 4, 5 , 6, 7 or 8 C atoms, alkenyl with 3, 4, 5 or 6 C atoms or -CabH2jjb-R (16); ab zero, 1, 2, 3 or 4; R (16) cycloalkyl with 3, 4, 5, 6 or 7 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (17) R (18); R (17) and R (18) independently of each other hydrogen, CF3 or alkyl with 1, 2, 3 or 4 C atoms; R (14) and R (15) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl; or R (14) and R (15) hydrogen; or R), R (2) and RO) independently of each other -SR21), -OR (22), -NR (23) R (24) or -CR (25) R (26) R (27); R (21), R (22), R (23) and R (25) independently of each other -CbH2b-heteroaryl (C, -C9), which is unsubstituted or substituted with 1-3 substituents selected from group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, ammo, methylamine and dimethylamino; b zero, 1 or 2; RÍ24), R (26) and R (27) independently of each other hydrogen, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; or R (1), RÍ2) and R (3) independently of each other hydrogen, F, Cl, Br, X 'CN' - < Xa CdaH gives + 1 '- (Xb > dh - (CH2) db- deF2 +1' alkenyl with 3, 4, 5, 6, 7 or 8 C atoms or -CdfH2dfR (30); (Xa) oxygen, sulfur or NR (33); R (33) hydrogen, alkyl with 1, 2, 3 or 4 carbon atoms or perfluoroalkyl with 1, 2, 3 or 4 carbon atoms; dg zero or 1; (Xb) oxygen, sulfur or NR (34); R (34) hydrogen, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; dh zero or 1; gives zero, 1, 2, 3, 4, 5, 6, 7 or 8; db zero, 1, 2, 3 or 4; from zero, 1, 2, 3, 4, 5, 6 6 1; df zero, 1, 2, 3 or 4; R (30) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, phenyl, biphenylyl or naphthyl, the aromatic radicals being phenyl, biphenylyl or naphthyl unsubstituted or substituted with 1-3 substituents selected from the group consists of F, Cl, CF3, methyl, methoxy and NR (31) R (32); R (31) and R (32) hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl with 1, 2, 3 or 4 carbon atoms; or R), R (2) and RO) independently of each other NR (40) R (41) or -. { Xe) - (CH2) ebR (45); R (40) and R (41) independently of one another alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or (CH 2) e R (42); e zero, 1, 2, 3 or 4, - R (42) cycloalkyl with 3, 4, 5, 6 or 7 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (43) R (44); R (43) and R (44) independently of each other hydrogen, CF3 or alkyl with 1, 2, 3 or 4 C atoms; or R (40) and R (41) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl; (Xe) oxygen, sulfur or NR (47); R (47) hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms; eb zero, 1, 2, 3 or 4; R (45) cycloalkyl with 3, 4, 5, 6 or 7 C atoms or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy, NR (50) R (51) and - (Xfa) - (CH2) ed- (Xfb) R (46); Xfa CH2, oxygen, sulfur or NR (48); Xfb oxygen, sulfur or NR (49); R (48), R (49), R (50) and R (51) independently of each other hydrogen, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; ed 1, 2, 3 0 4; R (46) hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl with 1, 2, 3 or 4 carbon atoms; or R (l), R (2) and RO) independently of one another -CHR (52) R (53); R52) - (CH2) g- (CHOH) h- (CH) .- (CHOH) k -R (54) or - (CH2) g-0- (CH2-CH20) h-R (54); R (54) hydrogen or methyl; g, h, i equal or different zero, 1, 2, 3 or 4; k 1, 2, 3 0 4; R (53) hydrogen or alkyl with 1, 2, 3 or 4 C atoms; R (l), R (2) and R (3) independently of each other -C (OH) R (55) R (56); RÍ55) and R (56) equal or different from hydrogen or alkyl with 1, 2, 3 or 4 C atoms; or R (55) and R56) in common cycloalkyl with 3, 4, 5 or 6 C atoms; or R (55) -CH20H; and R 4) and R (5) independently of one another with 1, 2, 3 or 4 carbon atoms, alkoxy with 1, 2, 3 or 4 C atoms, OH, F, Cl, Br, I, CN, -On- (CH2) 0- (CF2) p-CF3; n zero or 1; or zero, 1 or 2; p zero, 1 or 2; as well as its pharmaceutically compatible salts. ay) 1-Substituted naphthoylguanidines of Formula I wherein they mean: R2, R3, R4, R5, R6, R7 and R8 independently of one another H, F, Cl, Br, I, CN, N02, CF3, C2 5 or XaYbZ; XO, S, NR (10), CR (11) R (12), C = 0, C (= O) NR (10), C (= 0) 0, SO, S02, SO2NR (10), OC = 0, NR (10) C = O or NR (10) SO2, bonding with the naphthalene ring in each case through the atom on the left; R (10), R (ll) and R (12) independently of each other H, alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms, perfluoroalkyl with 1, 2, 3 or 4 carbon atoms C or cycloalkyl with 3, 4, 5, 6 or 7 C atoms; to zero or 1; And alkylene with 1, 2, 3, 4, 5, 6, 7 or 8 CH2 groups, one of these CH2 groups being able to be replaced by 0, S, NR (13) or by o-, p- or m-phenylene; R (13) H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, perfluoroalkyl with 1, 2, 3 or 4 C atoms or cycloalkyl with 3, 4, 5 or 6 C atoms, b zero or 1, - ZH, alkyl with 1, 2, 3, 4, 5, 6 or 7 C atoms, cycloalkyl with 3, 4, 5, 6 or 7 C atoms, C (= 0) R (15) , S02R (15), NR (16) R (17) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, Br, CF3, methyl, methoxy, NR (21) ) R (22); R (21) and R (22) independently of each other H or alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; R (15) N = C (NH 2) 2, NR (18) R (19), N (CH.,) CNR (18) R (19) or OR (20); C 2 or 3; RÍ18) and R (19) independently of each other H, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; or RÍ18) and R (19) in common 4 or 5 methylene groups, of which one CH2 group can be replaced by oxygen, S, NH, N-CH3, N-benzyl or N- (p-chlorophenol); R (20) H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, perfluoroalkyl with 1, 2, 3 or 4 C atoms or cycloalkyl with 3, 4, 5, 6, or 7 C atoms; R16) and R (17) independently of each other H, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms, or R ( 16) and R (17) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3, N-benzyl or N- (p-chlorophenyl); or Z is a heterocycle containing N with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, the heterocycle containing N being linked through N or C, and being substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, Br, CF3, methyl, methoxy and NR (21) R (22); but in the case where R (4) represents an alkoxy radical, at least one of the substituents R (2), R (3), R (5), R (6), R. (. 7) and R (8) are other than hydrogen, as well as their pharmaceutically compatible salts. az) 2-Substituted naphthoylguanidines of Formula I wherein they mean: at least one of the substituents R1, R3, R4, R5, R6, R7 and R8 XY to WZ or X'Y to WZ '; 'X 0, S, NR (10) or CR (11) R (12); R (10), Ríll) and R (12) independently of each other H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, perfluoroalkyl with 1, 2, 3 or 4 C atoms, or cycloalkyl with 3, 4, 5, 6 or 7 C atoms; And alkylene with 1, 2, 3, 4, 5, 6, 7 or 8 CH2 groups, one of these CH2 groups being able to be replaced by O, S, NR (13) or either o-, p- or m-femlene; R (13) H, alkyl with 1, 2, 3, 4, 5 or 6 carbon atoms, perfluoroalkyl with 1, 2, 3 or 4 carbon atoms or cycloalkyl with 3, 4, 5 or 6 carbon atoms; to zero or 1; CH2, S02, S (= 0) (= NH) or - if W does not immediately follow a heteroatom of the group XY - also O or NR (14); R (14) H, alkyl with 1, 2, 3, 4, 5 or 6 atoms C, perfluoroalkyl with 1, 2, 3 or 4 C atoms or cycloalkyl with 3, 4, 5 or 6 C atoms; Z C (= 0) R (15), S02R (15) or - in the case that W does not mean O or NR (14) - also NR (16) R (17); R15) N = C (NH2) 2, NR (18) R (19), N (CH2) bNR (18) R (19) OR OR (20); b 2 OR 3; R (18) and R (19) independently of each other H, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; or R (18) and R (19) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3, N-benzyl or N- (p-chlorophenyl); ' R (20) H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, perfluoroalkyl with 1, 2, 3 or 4 C atoms or cycloalkyl with 3, 4, 5, 6 or 7 C atoms; R (16) and R17) independently of each other H, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; or R (16) and R (17) in common 4 or 5 methylene groups, of which one CH2 group can be replaced by oxygen, S, NH, N-CH3, N-benzyl or N- (p-chlorophenyl); X 'C = 0, C (= O) NR (30), C (= 0) 0, SO, S02, SO-, NR (30), 0C = 0, NR (30) C = O or NR (30 ) SO2, bonding with the naphthalene ring in each case through the atom on the left; ROO) H, alkyl with 1, 2, 3, 4, 5 or 6 atoms C, perfluoroalkyl with 1, 2, 3 or 4 C atoms or cycloalkyl with 3, 4, 5, 6 or 7 C atoms; Z 'C (= 0) R (15), S02R (15), a heterocycle containing N with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, the heterocycle containing N through N or C and being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, Br, CF3, methyl, methoxy and NR (21) R (22); R (21) and R (22) independently of each other H, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; R (15) N = C (NH 2, 2, NR (18) R (19), N (CH2) bNR (18) R (19) or OR (20), R (18) and R (19) independently one of another H, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; or R (18) and R (19) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3, N-benzyl or N- (p-chlorophenyl), - b 2 or 3; ) H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, perfluoroalkyl with 1, 2, 3 or 4 C atoms or cycloalkyl with 3, 4, 5, 6 or 7 C atoms; '- in the case that W does not mean O or NR (14) - NR (16) R (17); RÍ16) and R (17) independently of each other H, alkyl with 1, 2, 3, 4, 5 , 6, 7 or 8 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; or R16) and R (17) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3, N-benzyl or N- (p-chlorophenyl); and the respectively other remaining substituents R1, R3, R4, R5, R6, R7 and R8, which are not yet covered by the definitions given above, independently of each other H, F, Cl, Br, I, CN, N02, CF3, C2F5 or VpQqU; V O, S, SO, S02, NR (60), 0C = 0, C = 0, C (= 0) R (60), C (= 0) 0 or CR (66) R (67); RÍ60), R (66) and R (67) independently of each other H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, perfluoroalkyl with 1, 2, 3 or 4 C atoms or cycloalkyl with 3, 4, 5, 6 or 7 C atoms; p zero or 1; Q alkylene with 1, 2, 3, 4, 5, 6, 7 or 8 CH2 groups, one of these CH2 groups being able to be replaced by O, S, NR (68) or by o-, p- or m-phenylene, - RÍ68) H, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, perfluoroalkyl with 1, 2, 3 or 4 C atoms, or cycloalkyl with 3, 4, 5 or 6 C atoms; q zero or 1; UH, alkyl with 1, 2, 3, 4, 5, 6 6 1 C atoms, cycloalkyl with 3, 4, 5, 6 or 7 C atoms, C (= 0) R (65), S02R (65) , NR (61) R (62) or phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, Br, CF3, methyl, methoxy and NR (63) R (64); R63) and R (64) independently of each other H, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; R (65) N = C (NH2) 2, NR (61) R (62) OR OR (60); R61) and R (62) independently of each other H, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; OR (61) and R (62) in common 4 or 5 methylene groups, of which one CH2 group can be replaced by oxygen, S, NH, N-CH3, N-benzyl or N- (p-chlorophenyl), - or U a heterocycle containing N with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, the heterocycle containing N being linked through N or C, and being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, Br, CF3, methyl, methoxy and NR (63) R (64), but other than hydrogen being at least one of the substituents R5, R6 , R7 and R8; as well as its pharmaceutically compatible salts, ba) O-substituted benzoylguanidines of Formula I in which they mean: R) H, F, Cl, Br, I, CN, N02, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, alkoxy with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms or Xa- ( CH2) b- (CF 2 ', c -C-FPZ> • X oxygen, sulfur or NR (9), - at zero or 1; b zero, 1 or 2, - c zero, 1, 2 or 3; R (9) H, alkyl with 1, 2, 3 or 4 C atoms or CdH2dR (6); d zero, 1, 2, 3 or 4; R (6) cycloalkyl with 3, 4, 5, 6, 7 or 8 C, phenyl, biphenylyl or naphthyl atoms, the aromatic radicals being phenyl, bifemyl or naphthyl unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (7) R (8); R (7) and R (8) independently H or alkyl with 1, 2, 3 or 4 C atoms; or R (l) -SR (IO), -OR (10) or -CR (10) R (11) R (12); R (10) -CfH2f-c? Cloalkyl with 3, 4, 5, 6, 7 or 8 C atoms in the cycloalkyl ring, heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms or phenyl, the heteroaryl and phenyl being substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl , CF3, CH3, methoxy, hydroxy, ammo, methylamino and dimethylamino; f zero, 1 or 2; R (ll) and R (12) independently of one another as defined R (10) or hydrogen or alkyl with 1, 2, 3 or 4 C atoms, or R (l) phenyl, naphthyl, bifemyl or heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, the latter linked through a C atom or an N ring atom, which in each case are unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, CH3, methoxy, hydroxy, amino, methylamino and dimethylamino, or R (l) -SRÍ13), -0R (13), -NHR (13), -NR (13) R (14), -CHR (13) R (15), -C [R (15) R (16)] 0H, -C = CR (18), -CR [R (19)] = CHR (18), -C [R (20) R (21)] k- (CO) - [CR (22) R (23)]. -R (24), k zero, 1, 2, 3 or 4; 1 zero, 1, 2, 3 or 4; R13) and R (14) equal or different - (CH2) g- (CHOH) h- (CH2) r (CH0H) kk-R (17) or - (CH2) g-0- (CH2-CH20) hR ( 24); R (17) hydrogen or methyl, g, h and i equal or different zero, 1, 2, 3 or 4; kk 1, 2, 3 or 4; R (15) and R (16) equal or different hydrogen, alkyl with 1, 2, 3, 4, 5 or 6 C atoms, or in common with the carbon atom that carries them, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms; R (18) phenyl, which is unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (25) R (26); R (25) and R (26) H or alkyl with 1, 2, 3 or 4 C atoms; or R (18) heteroaryl with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, which is unsubstituted or substituted as phenyl; or R (18) alkyl having 1, 2, 3, 4, 5 or 6 C atoms, which is unsubstituted or substituted with 1-3 OH; or R (18) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms; RI19), ROO), R (21), R (22) and R (23) equal or different hydrogen or methyl; R (24) H, alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 carbon atoms -cmH2m-R (18 > < - m 1, 2, 3 0 4, one of the two substituents R (2) and R (3) -0-CO-R (27), R (27) alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 C atoms, cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, phenyl, bifemyl, naphthyl, pyridyl or quinolinyl, the phenyl, biphenylyl, naphthyl, pyridyl or quinolyl being sm substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (7) R (8); R (7) and R (8) independently of each other hydrogen or alkyl with 1, 2, 3 or 4 C atoms, one of the substituents R (2) and R (3) being defined as R (l); R (4) and R (5) independently of one another hydrogen, alkyl with 1, 2, 3 or 4 carbon atoms, alkoxy with 1, 2, 3 or 4 carbon atoms, F, Cl, Br, I, CN or - (CH2) n- (CF2) 0-CF3; zero or 1; or zero or 1; as well as its pharmaceutically compatible salts. bb) Benzoylguanidines of Formula I in which they mean: R) R (13) -SOm or R (14) R (15) N-S02-; m 1 or 2; R (13) alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, alkenyl with 3, 4, 5, 6, 7 or 8 C atoms or -CnH2nR (16), n zero, 1, 2, 3 or 4; R (16) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, phenyl, biphenylyl or naphthyl, the phenyl, biphenylyl and naphthyl being substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (25) R (26); R (25) and R (26) independently of each other hydrogen, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; R (14) hydrogen, alkyl with 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, perfluoroalkyl with 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms, alkenyl with 3, 4, 5, 6, 7 or 8 C atoms or -CnH, nR (27), n zero, 1, 2, 3 or 4; R (27) cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, phenyl, biphenylyl or naphthyl, the phenyl, biphenylyl and naphthyl being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (28) R (29); R (28) and R (29) independently of each other hydrogen, alkyl with 1, 2, 3 or 4 C atoms or perfluoroalkyl with 1, 2, 3 or 4 C atoms; R (15) hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms or perfluoroalkyl having 1, 2, 3 or 4 carbon atoms; or R (14) and R (15) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; one of the substituents R (2) and R (3) hydrogen; and the respectively another substituent R (2) and R (3) -CHR (30) R (31); ROO) - (CH2) g- (CHOH) h- (CH2) .- (CHOH) k -R (32) or - (CH2) g-0- (CH2-CH20) h-R (24); R (24) and R (32) independently of one another hydrogen or methyl; g, h, i equal or different, zero, 1, 2, 3 or 4, - k 1, 2, 3 0 4; or the respectively another substituent R (2) and RO) -C (OH) R (33) R (34); same or different hydrogen or alkyl with 1, 2, 3 or 4 C or R atoms (33) and RÍ34) in common cycloalkyl with 3, 4, 5 or 6 C atoms; or R (33) -CH2OH; R (4) alkyl with 1, 2, 3 or 4 C atoms, alkoxy with 1, 2, 3 or 4 C atoms, F, Cl, Br, I, CN, - (CH-,) R- (CF2 ) 0-CF3; n zero or 1; or zero, 1 or 2; as well as its pharmaceutically compatible salts. be) Indanilidinacetilguanidinas of the Formula I wherein R 1, R 2, R 3, R 4, R 5 and R 6 are independently of one another, H, C, -C, 0 alkyl; haloalkyl with 1-6 carbon atoms, O-alkyl C.-C, 0, haloalkoxy with 1-6 carbon atoms, F, Cl, Br, I, aryl, substituted aryl, heteroaryl, substituted heteroaryl, OH, O- lower alkyl, O-aryl, O-lower alkyl-aryl, O-substituted aryl, O-lower alkyl-substituted aryl, OC (= 0) -alkyl C.-C4-aryl, OC (= 0) -alkyl C, -C, OC (= 0) -N (C1-C4 alkyl) 2, NO, ,, CN, CF3, NH2, NH-C (= 0) -alkyl C, -C4, NH-C (= 0) - NH., COOH, C (= 0) -O-C alkyl, -C4, C (= 0) -NH2, C (= 0) -NH-C alkyl, -C4, C (= 0) -N ( C, -C4 alkyl) 2, C, -C4-COOH alkyl, C, -C4 alkyl (= 0) -O-C, -C4, S03H, S02-alkyl; S02-alkylaryl, S02-N- (alkyl) 2, S02-N (alkyl) (alkylaryl), C (= 0) -Rll, alkyl C, -C, 0-C (= 0) -Rll, alkenyl C2- C10-C (= 0) -Rll, C2-C2 alkyl, 0-C (= 0) -Rll, NH-C (= 0) -alkyl C, -C10-C (= 0) -Rll or 0-alqu ? l C, -C., - C (= 0) -Rll; Rll C, -C 4 alkyl, C, -C 4 alkynyl, aryl, substituted aryl, NH 2, NH-C alkyl, -C 4, N- (C 1 -C 4 alkyl), S 0 3 H, S 0 2 -alkyl, S 0 2 -alkyl ? laryl, S02-N- (alkyl) 2 or S02-N (alkyl) (alkyla); X 0, S or NH; R7, R8, R9 and RIO independently of each other H, alkyl, cycloalkyl, aryl, alkylaryl, or R8 and R9 in common are part of a 5-, 6- or 7-membered heterocyclic ring, or their pharmaceutically acceptable salts. bd) Phenyl-substituted alkenylcarboxylic acid guanidides of Formula I where they mean; T RIA) hydrogen, F, Cl, Br, I, CN, OH, OR (6), alkyl (C, -C4), Op (CH.,) ACbF2b +, cycloalkyl (C3-C8) or NR (7) R (8) r zero or 1; to zero, 1, 2, 3 or 4; b 1, 2, 3 or 4; R (6) alkyl (C, -C4), perfluoroalkyl (C, -C4), alkenyl (C3-C6), cycloalkyl (C3-C8), phenyl or benzyl, the phenyl nucleus being unsubstituted or substituted with 1- 3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (9) R (10); R (9) and R (10) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4), -R (7) and R (8) independently of one another as defined R (6); or R (7) and R (8) in common 4 or 5 methylene groups, of which a CH2 group can be replaced by oxygen, sulfur, NH, N-CH3 or N-benzyl; R (B), R (C) and R (D) independently as defined R (A); x zero, 1 or 2, - and zero, 1 or 2; R (F) hydrogen, F, Cl, Br, I, CN, 0R (12), alkyl (C, -C8), 0p (CH2) fCgF2g + 1, cycloalkyl (C3-C8) or heteroaryl (C-C9) ); p zero or 1; f zero, 1, 2, 3 or 4; g 1, 2, 3, 4, 5, 6, 7 or 8; R (12) alkyl (C, -C8), perfluoroalkyl (C, -C4), alkenyl (C3-C8), cycloalkyl (C3-C8), phenyl or benzyl, the phenyl nucleus being unsubstituted or substituted by 1- 3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy and NR (13) R (14); R (13) and R (14) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4), -R (E) independently as defined R (F); R (I) independently as T is defined; or R (l) hydrogen, -OkCmH2m +, -On (CH2) pCqF2q + 1, F, Cl, Br, I, CN, - (C = 0) -N = C (NH 2) 2, -SOrR (17), -SOr 2 NR (31) R (32); -Ou (CH2) vC6H5, -Ou2-heterolalk (C, -C9) or Su2-heteroaryl (C, -C9); kk cceerroo óó 11, / - mm cceerroo ,, 1 1 ,. 2 2, 3 3, 4 4, 5 5, 6, 7 or 8; n zero or 1 P zero i, 2, 3 or 4; q 1, 2, 3, 4, 5, 6, 7 u r zero, 1, 2; r2 zero, -1, 2; ROÍ) and R (32) independently of one another, hydrogen, (C-C8) alkyl or perfluoroalkyl (C, -C8); or ROI) and RI32) in common 4 or 5 metlene groups, of which a CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; R17) alkyl (C * -C8); u zero or 1; u2 zero or 1, - v zero, 1, 2, 3 or 4; the phenyl nucleus being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy, - (CH2) WNR (21) R (22), NR (18) R ( 19) and heteroaryl (C, -C9); R (18), R (19), R (21) and R (22) independently of each other alkyl (C, -C4) or perfluoroalkyl (C, -C4); w 1, 2, 3 or 4; the heteroaryl heterocycle (C.-C9) being unsubstituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl or methoxy; R (2), R (3), R (4) and R (5) independently of one another as defined R (D, or R (l) and R ((2) or R (2) and R ( 3) in each case in common -CH-CH = CH-CH-, which is substituted or substituted with 1-3 substituents selected from the group consisting of F, Cl, CF3, methyl, methoxy, - (CH2) w2NR (24) R (25) and NR (26) R (27); RÍ24), R (25), R (26) and R (27) H, (C, -C4) alkyl or perfluoroalkyl (C, -C4) ); w2 1, 2, 3 0 4; the radical T being present in the molecule at least twice but only at most three times; as well as its pharmaceutically compatible salts. be) Benzoylguanidines of Formula I R (1) where they mean: R (1) CF3; one of the substituents R (2) and R { 3) hydrogen; and the respectively another substituent R (2) and R (3) -C (OH) (CH 3) -CH 2 OH, -CH (CH 3) -CH 2 OH or -C (OH) (CH 3 < 2. R (4) methyl) , methoxy, Cl or CF3, as well as their pharmaceutically compatible salts; (DE 195.02.895, DE 44.30.212, EP 667.341, DE 44.04.184, EP 708.088, EP 723.963, EP 0.694.537, DE 44.21.495, EP 699,660, EP 699,663, EP 699,666, DE 43.37.611, EP 0.719.766, WO 94/26709, WO 96/04241, EP 726,254, US 4,251,545, DE 35.02.629, WO 84/00875, Kumamoto et al., Pharm. Bull. [1966], 7-13; .027; JP 8225513; EP 743,301) II. or compounds of the Formula where they mean: W, Y and Z a nitrogen atom or a C atom substituted with R (2) or R (3) or R (4); R (l) hydrogen, A, Hal, -CF3, -CH..F, -CHF2, -CH2CF3, -C2F5, -CN, -N02, ethynyl, or an X-R ', - A alkyl having 1 to 6 C atoms; Hal F, Cl, Br or I; X oxygen, S or NR "; R" hydrogen, A or a cyclic methylene chain with 3 to 7 C atoms; R 'H, A, HO-A-, HOOC-A-, cycloalkyl (C3-C7), cycloalkyl (C6-C8) -alkyl, CF3, CH2F, CHF2, CH2-CF3, Ph, -CH2-Ph or Het; Ph phenyl, naphthyl or biphenylyl unsubstituted or substituted one, two or three times with A, OA, NR'R ", Hal or CF3; Het a saturated, unsaturated or aromatic heterocyclic of one or two nuclei with 1 to 4 N atoms , O and / or S, which is unsubstituted or substituted one, two or three times with Hal, CF3, A, OH, OA, -XR ', -CN, -N02, and / or carbo-il-oxygen, the Het linked through N or of an alkylene chain CmH2m with m = zero to 6; R 'and R "in common alkylene with 4-5 C atoms, whereby a CH2 group can also be replaced by oxygen, S, NH, NA, N-Ph and N-CH2-Ph; R (2) and RO) independently one of other hydrogen, Hal, A, HO-A-, X-R ', -C (= N-OH) -A, A-0-CO-alkyl (C, -C4) -, CN, N02, COOH, A substituted with halogen, especially CF3, CH2F, CHF2, C2F5, CH2CF3, or S (0) nR '' ', R' "A, Ph O Het; n zero, 1 or 2; or RO) and RO) independently of one another S02NR'R ", Ph or -O-Ph, -0-CH2-Ph, -CO-A, -CHO, -COOA, -CSNR'R", -CONR'R " ', -CH = CH-COOH, -CH = CH-COOA, mdenyl, indanyl, decahydronaphthyl, cyclopentenyl, dihydrothienyl, dihydrofuplo, heterobicyclyl, alkylthienyl, halothienyl, haloalkylthienyl, acylthienyl, halofuryl, haloalkylpupyl or pyrrolyl, or R (2) and RO) independently of one another R (5) -0-; R (5) hydrogen, A, alkenyl (C, -C6) or cycloalkyl (C3-C7); R (4) Ph, Het, O-Het; CF3, S (0) nR '' ', -S02NR'R ", Alk; Or two of the substituents R (l) to R (4) form one-other group -O-CR (6) R (7) -CO-NR (8) with R (2) in the indicated meaning; R (6), R (7), R (8) and R (9) independently of each other H or A; or R (8) cycloalkyl (C5-C7); or R (9) cyano; Alk (C, -C8) straight or branched alkyl or (C3-C8) cycloalkyl which is unsubstituted or substituted with A one, two or three times; or Alk an ethenyl or ethynyl radical substituted with H, A, Ph or Het, -or III. compounds of the Formula in which they mean: XH, Hal, (Hal) 3C-, alkyl (C.-C6), cycloalkyl (C3-C6), substituted phenyl, alkyl (C, -C5) -S- or alkyl (C, -C5) ) -S02-; And NH2 or substituted amino; or X and Z in common a chain of - (CH2) 4- or a 1,3-butadienylene chain; or Z H, Hal, OH, HS, (C, -C5) alkyl, (C3-C6) cycloalkyl, substituted phenyl; or Z an ammo group -NR (1) R (2); R (l) H, straight or branched chain (C-C8) alkyl, optionally substituted, which may be interrupted by oxygen; or R (l) (C3-C8) alkenyl, (C3-Cfl) alkyl, (C3-C7) cycloalkyl or phenyl substituted with OH or phenyl-(C, -C4) alkyl substituted with OH or (C3-C7) cycloalkyl substituted with OH; R (2) 1 -morpholyl, hydrogen or a straight or branched alkyl chain (C, -C8), which may be interrupted by oxygen, a lower group, whose linear or branched (C, -C8) alkyl chain is unsubstituted or substituted with a substituted or unsubstituted uni- or pluri-nuclear heterocycle, containing nitrogen, oxygen or sulfur atoms; or whose alkyl chain is substituted by phenyl, optionally substituted once or multiple times with (C, -C4) alkoxy, optionally substituted by OH, alkylamine, alkyl or phenyl; or with an aminocarbonyl group or with hydroxy or (C, -C 4) alkoxy or RO) phenyl groups, unsubstituted or substituted by alkyl, alkoxy, an amino group, which bears as substituents: H, a uni- or pluri-nuclear heterocycle, containing nitrogen, oxygen or sulfur atoms, which is unsubstituted or substituted with H, Hal or alkyl (C, -C4); a phenyl radical, unsubstituted or substituted by a substituent, selected from the group consisting of (C, -C4) alkyl, (C, -C4) alkoxy, Hal and OH; or R (2) 1-piperidino, unsubstituted or substituted in position 4 with an acyl radical of an aliphatic, alicyclic, aromatic or heteroaromatic carboxylic acid, (C, -C8) alkyl, which in turn may be substituted with OH or alkoxy (C, -C4) or with a phenyl radical substituted by (C, -C4) alkoxy; or R (2) amidino, which is unsubstituted or substituted with phenyl, which is unsubstituted or substituted with Hal or alkyl; or R (2) an acyl radical of an aliphatic, alicyclic, aromatic or heteroaromatic carboxylic acid, or R (2) an alkyl chain (C, -C8), which may be substituted with a phenyl radical bearing OH radicals, alkoxy or alkyl; or R (l) and RO) in common with the N atom, to which they are attached, a piperazine ring, which is unsubstituted or carries, through a methylene chain (C, -C6), a heterocyclic uni - or pluri-nuclear, containing nitrogen, oxygen or sulfur (DE 41.27.026 and DE 43.37.609); Hal F, Cl, Br or I; or IV. indoloylguanidine derivatives of the Formula wherein they mean: R (2) hydrogen, unsubstituted or substituted (C, -C8) alkyl, (C3-C7) cycloalkyl, OH, (C, -C6) -0- alkyl, an aromatic radical or a group - CH2-R (20), - ROO) (C2-C6) alkenyl or (C2-C6) alkynyl; R (l) from 1 to 5 identical or different substituents, which mean: hydrogen, unsubstituted or substituted (C, -C8) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, (C3-C7) cycloalkyl ), halogen, -N02, (C2-C8) alkanoyl, arylalkanoyl with up to 10 carbon atoms, aroyl with up to 11 carbon atoms, -COOH, alkoxycarbonyl (C2-C6), an aromatic group, one of the groups indicated below : -ORO), -NR (6) R (7) or -S (O) pR (40); R (3) hydrogen, (C, -C8) alkyl, substituted (C, -C8) alkyl, (C3-C7) cycloalkyl, an aromatic radical or a -CH2-R (30) ROO) alkenyl or alkynyl group; R (6) and R (7) independently of one another hydrogen, unsubstituted or substituted (C, -C8) alkyl, (C3-C7) cycloalkyl, (C2-C8) alkanoyl, an aplalcanoyl group with up to 10 C atoms , an aroyl group with up to 11 carbon atoms, an aromatic group or -CH2-R (60); R (60) (C2-C6) alkenyl or (C2-C6) alkynyl; or R (6) and R (7) in common with the N atom, a cyclic amine of 5-7 members, which may also contain other heteroatoms in the ring; n zero, 1 or 2; R (40) unsubstituted or substituted (C, -C8) alkyl, or an aromatic group or a group. ^ Jj "" "^ R- To oxygen, -S (0) n. or -NR (50) -; R (50) hydrogen or alkyl (C.-C8); R 'is hydrogen, unsubstituted or substituted (C, -C8) alkyl, in which the ring represents a saturated 3-8 membered heterocycle with an N atom; said substituted alkyl carries one or several groups selected from the group consisting of halogen, -OH, (C, -C6) alkoxy, -CN, -COOH, (C2-C6) alkoxycarbon, (C2-C8) alkanoyl, aplakanoyl with up to 10 carbon atoms, aroyl with up to 11 carbon atoms, an aromatic group, equal or different, RON (4) R (5), R (4) and R (5), hydrogen or alkyl (C.-C8) ); or R (4) and R (5) are linked together and form in common a cyclic amine of 5-7 links, which may also contain other heteroatoms in the ring, or the said substituted alkyl bears a group -34b- -A- € Z > R " where they mean: E an N atom or a CH group; R "hydrogen, (C, -C8) alkyl, substituted or substituted by OH or substituted (C, -C8) alkyl, (C, -C6) alkoxy, -CN, -COOH, (C2-C6) alkoxycarbon, alkanoyl (C2-C8), aralkanoyl with up to 10 carbon atoms, aroyl with up to 11 carbon atoms, an aromatic group, -NR (6) R (7), -CONR (4) R (5); R (4) and R (5) independently from each other hydrogen or alkyl (C, -C8), meaning the cyclic system of the Formula a 3- to 8-membered aliphatic or heterocyclic ring system with an N atom, and the aromatic groups mentioned being an aplo radical with up to 10 C atoms, a 5- or 6-membered heteroaryl radical with 1-4 atoms of N, a 5- or 6-membered heteroaryl group containing 1 or 2 N atoms and a heteroatom meaning oxygen or sulfur, or furyl, and the said aryl radicals being unsubstituted or substituted with alkyl (C, - C8) unsubstituted or substituted (C, -C8) alkyl, halogen, -N02, (C2-C6) alkoxycarbonyl, COOH, -0R (3), NR (6) R (7), -CONR (4) R ( 5), -SO., NR (6) R (7) or S (O) nR (40), where R (l) and the guanidmocarbonyl radical can be located at any place in the 5 or 6 member ring of the system. mdol, as well as the corresponding pharmaceutically compatible salts, or V. heterocyclic guanidine derivatives of the Formula wherein they mean: X -O-, -S-, -NH-, -N [alkyl (C, -C4)] - or -N (phenol); R (I: RO) and RO) hydrogen, halogen, alkyl (C, -C 4), alkyl (C, -C 4) -O-, phenyl, benzyl; or two of the substituents R (1), R (2) and R (3) in common with one side of the benzo system, a 4-6 membered carbocyclic ring; R (4) and R (5) independently of each other hydrogen, (C, -C, 2) alkyl, benzhydryl, aralkyl, which is unsubstituted or substituted by one or more substituents taken from the groups formed by halogen, alkyl ( C, -C4), alkyl (C, -C4) -0- or -CF3, (H2 CH2-T, m zero up to 3; T -CO-OT (l); T (l) hydrogen or alkyl (c, -c4) C and a methylated heterocycle condensed with benzo or a dihydro-heterocycle with 5-membered ring, -R $ (6) Ú? a pyrazole or imidazole ring of the Formula Rl6) «(7) R (ß) a naphthyl radical or a dihydro- or tetrahydro-naphthyl radical a radical 3- or 4-p? r? d? lo Z N- or CH; a thienyl radical R (6) hydrogen, halogen, hydroxy, alkyl (C, -C, 0), alkyl (C, -C, 0) -O-, phenoxy, alkyloxy (C, -C, 0) -methyloxy or - (0) ) nS-R (9); R (9) (C, -C, 0) alkyl, thienyl, pyridyl, thiazolyl, thiadiazolyl, imidazolyl, pyrazolyl or phenyl, which is unsubstituted or substituted once or twice by halogen, (C, -C4) alkyl or alkyl (C-C4) -O-; R (7) and R (8) hydrogen, halogen, hydroxy, alkyl (C, -C, 0), alkyl (0, -0 ^) -0-, phenyl, phenoxy or (C, -C 10) alkoxy -methyloxy; or Cy phenyl, which is unsubstituted or substituted once or twice with halogen, alkyl (C, -C 4) or alkyl (C, -C 4) -O-; -Gr-Am; Gr -R (13) -R12) - (CH2) q-C [W] [W (1)] - (CH2) q-; R (13) R (14) - OR -R (15) -; R (12) a single bond, -O-, - (0) nS -, - CO- or -CONH-, R (13) a single bond, phenyl, thienyl, pyridyl, thiazolyl, thiadiazolyl, imidazolyl or pyrazolyl; 14) a single bond or S02-; R (15) alkenyl (C2-C1Q) or alkynyl (C2-C, Q); W and W (l) independently of one another hydrogen, alkyl (C.-C4); W and W (l) linked cyclically to each other, a ring of hydrocarbon (C3-C8), q and q 'from zero to 9, Am -NR (10) R (11), R (10) hydrogen, alkyl (C, - C4) or benzyl, R (ll) alkyl (C, -C4), phenyl or benzyl, or R (10) and R (ll) in common an alkylene group (C3-C10), which is unsubstituted or substituted with - COOH, (C-C5) alkoxycarbonyl, (C2-C4) hydroxyalkylene or benzyl; or Am pyrrolyl, pyridyl, pyrazolyl, morpholinyl, dihydropyridyl, tetrahydropyridyl, quinuclidinyl, imidazolyl, 3-azabicyclo [3.2.1] octyl, which is unsubstituted or substituted by alkyl (C, -C4), or Am azabicyclo [3.2.2] nonyl; or Am a piperazino group of the formula r and R (16) hydrogen, (C, -C4) alkyl, (C3-C6) cycloalkyl, phenyl, tolyl, methoxyphenyl, halophenyl, diphenylmethylene, benzyl or pyridyl; or Am a azido group - (0) t- (CH 2) q-C [W] [W (1)] - (CH 2), -N 3; t zero or 1; possessing W and W (l) the previously indicated meanings; as well as optical enantiomers and pharmacologically compatible salts, or VI. Guanidma compounds, which are described in EP-743,301 (DE 195 17 848), EP 758,644 (DE 195,29,612), EP 760,365 (DE 195.31.138) with R1 = R2 equal to H, halo, alkyl, CN, N02, perfluoroalkyl, SOnCF3; R3 = CH = CH2, CH2-CH = CH2, CH2-CH2-CH = CH2, cycloalkenyl, cycloalkenylalkyl; R4 = alkyl, phenyl (substituted), or as described in DE 195.48.708, WO 97.25.310, WO 97.27.183, DE 196.01.303, EP 787.728, JP 82.25.513, JP 090.59.245, JP 090.67.332, JP 090.67.340, WO 97.11.055 and EP 743.301. Combined pharmaceutical preparation according to claim 2, characterized in that it contains an inhibitor of NHE and a hypotensive drug for the treatment of blood hypertension under protective conditions of the heart. Combined pharmaceutical preparation according to claim 2, characterized in that it contains an NHE inhibitor and a beta-receptor blocker for the treatment of hypertension and the treatment of arrhythmia under protective conditions of the heart. Combined pharmaceutical preparation according to claim 2, characterized in that it contains an NHE inhibitor and a calcium antagonist for the treatment of hypertension under protective conditions of the heart. Combined pharmaceutical preparation according to claim 2, characterized in that it contains an inhibitor of NHE and an inhibitor of the angiotensin-converting enzyme for the treatment of blood hypertension under protective conditions of the heart. Combined pharmaceutical preparation according to claim 2, characterized in that it contains an NHE inhibitor and a diuretic or aldosterone antagonist for the treatment of hypertension and heart failure under protective conditions of the heart. Combined pharmaceutical preparation according to claim 2, characterized in that it contains an NHE inhibitor and a medicament that increases the force of contraction of the heart, for the treatment of heart failure and congestive failure of the heart under protective conditions of the heart. Combined pharmaceutical preparation according to claim 2, characterized in that it contains an NHE inhibitor and a cardioglycoside for the treatment of heart failure and congestive heart failure under protective conditions of the heart. Combined pharmaceutical preparation according to claim 2, characterized in that it contains an NHE inhibitor and an antiarrhythmic agent for the treatment of cardiac arrhythmias of different genesis under protective conditions of the heart. Combined pharmaceutical preparation according to claim 2, characterized in that it contains an NHE inhibitor and an antiarrhythmic agent of classes I, II, III and IV for the treatment of cardiac arrhythmias of different genesis under protective conditions of the heart. Combined pharmaceutical preparation according to claim 2, characterized in that it contains an inhibitor of NHE and an active nitrate on the heart and the circulation. 1
3. Combined pharmaceutical preparation according to claim 2, characterized in that it contains an NHE inhibitor and a K channel (ATP) opener. Combined pharmaceutical preparation according to claim 2, characterized in that it contains an NHE inhibitor and a K (ATP) blocker. 15. Combined pharmaceutical preparation according to claim 2, characterized in that it contains the NHP inhibitor cariporide (HOE 642) in combination with a non-inactivatable sodium channel inhibitor. 16. Commercial container, which as a pharmaceutical active substance contains an inhibitor of the Na + and H + exchanger and another active substance on the heart and circulation, in common with instructions for the use of these active substances in combination for simultaneous application, separately or staggered in time, in the treatment or prophylaxis of cardio-circulatory diseases.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19737224.4 | 1997-08-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA98006923A true MXPA98006923A (en) | 1999-09-20 |
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