SK281442B6 - Bicyklické amidínové deriváty, spôsob ich prípravy, farmaceutické kompozície s ich obsahom a ich použitie - Google Patents
Bicyklické amidínové deriváty, spôsob ich prípravy, farmaceutické kompozície s ich obsahom a ich použitie Download PDFInfo
- Publication number
- SK281442B6 SK281442B6 SK390-97A SK39097A SK281442B6 SK 281442 B6 SK281442 B6 SK 281442B6 SK 39097 A SK39097 A SK 39097A SK 281442 B6 SK281442 B6 SK 281442B6
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- SK
- Slovakia
- Prior art keywords
- formula
- compound
- amino
- methyl
- nxy
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- -1 Bicyclic amidine Chemical class 0.000 title claims abstract description 113
- 238000000034 method Methods 0.000 title claims abstract description 36
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 142
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims abstract description 25
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims abstract description 25
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 11
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 11
- 150000002367 halogens Chemical class 0.000 claims abstract description 11
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 5
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 5
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract description 4
- 238000011282 treatment Methods 0.000 claims description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 17
- 230000008569 process Effects 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 229910052720 vanadium Inorganic materials 0.000 claims description 12
- 125000002947 alkylene group Chemical group 0.000 claims description 8
- 230000009467 reduction Effects 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 238000011321 prophylaxis Methods 0.000 claims description 6
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 230000004770 neurodegeneration Effects 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 208000019695 Migraine disease Diseases 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 206010013663 drug dependence Diseases 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 206010027599 migraine Diseases 0.000 claims description 3
- FSNBBHZBGAINMY-UHFFFAOYSA-N n'-isoquinolin-7-ylthiophene-2-carboximidamide Chemical compound C=1C=C2C=CN=CC2=CC=1NC(=N)C1=CC=CS1 FSNBBHZBGAINMY-UHFFFAOYSA-N 0.000 claims description 3
- 208000011117 substance-related disease Diseases 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 230000004075 alteration Effects 0.000 claims description 2
- 239000004305 biphenyl Substances 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- HOIWHCDSLPRGJX-UHFFFAOYSA-N n'-(2,3,4,5-tetrahydro-1h-3-benzazepin-7-yl)thiophene-2-carboximidamide Chemical compound C=1C=C2CCNCCC2=CC=1NC(=N)C1=CC=CS1 HOIWHCDSLPRGJX-UHFFFAOYSA-N 0.000 claims description 2
- 229940127240 opiate Drugs 0.000 claims description 2
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000002576 diazepinyl group Chemical class N1N=C(C=CC=C1)* 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- DSUJFGCBGLEURC-UHFFFAOYSA-N n'-(1,2,3,4-tetrahydroisoquinolin-5-yl)thiophene-2-carboximidamide Chemical compound C=1C=CC=2CNCCC=2C=1NC(=N)C1=CC=CS1 DSUJFGCBGLEURC-UHFFFAOYSA-N 0.000 claims 1
- DPSVOOANJDJEKL-UHFFFAOYSA-N n'-(1,2,3,4-tetrahydroisoquinolin-6-yl)thiophene-2-carboximidamide Chemical compound C=1C=C2CNCCC2=CC=1NC(=N)C1=CC=CS1 DPSVOOANJDJEKL-UHFFFAOYSA-N 0.000 claims 1
- YAUBARALXQKENX-UHFFFAOYSA-N n'-(1,2,3,4-tetrahydroisoquinolin-7-yl)thiophene-2-carboximidamide Chemical compound C=1C=C2CCNCC2=CC=1NC(=N)C1=CC=CS1 YAUBARALXQKENX-UHFFFAOYSA-N 0.000 claims 1
- JCFGWXMWCZYJFO-UHFFFAOYSA-N n'-(2-amino-2,3-dihydro-1h-inden-5-yl)thiophene-2-carboximidamide Chemical compound C1=C2CC(N)CC2=CC=C1NC(=N)C1=CC=CS1 JCFGWXMWCZYJFO-UHFFFAOYSA-N 0.000 claims 1
- IIRUWZJHKYFTNN-UHFFFAOYSA-N n'-(3-amino-2,3-dihydro-1h-inden-5-yl)thiophene-2-carboximidamide Chemical compound C1=C2C(N)CCC2=CC=C1NC(=N)C1=CC=CS1 IIRUWZJHKYFTNN-UHFFFAOYSA-N 0.000 claims 1
- XBUOLXTXRVVURN-UHFFFAOYSA-N n'-(8-amino-5,6,7,8-tetrahydronaphthalen-2-yl)thiophene-2-carboximidamide Chemical compound C1=C2C(N)CCCC2=CC=C1NC(=N)C1=CC=CS1 XBUOLXTXRVVURN-UHFFFAOYSA-N 0.000 claims 1
- WNSXOIUVJHWWPX-UHFFFAOYSA-N n'-[1-[(2-methylphenyl)methylamino]-2,3-dihydro-1h-inden-5-yl]thiophene-2-carboximidamide Chemical compound CC1=CC=CC=C1CNC1C2=CC=C(N=C(N)C=3SC=CC=3)C=C2CC1 WNSXOIUVJHWWPX-UHFFFAOYSA-N 0.000 claims 1
- QSELGEUCFNFITD-UHFFFAOYSA-N thiophene-2-carboximidamide Chemical compound NC(=N)C1=CC=CS1 QSELGEUCFNFITD-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 75
- 239000003112 inhibitor Substances 0.000 abstract description 4
- 238000002560 therapeutic procedure Methods 0.000 abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 111
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 84
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 78
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 66
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- 239000000284 extract Substances 0.000 description 40
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 39
- 235000019341 magnesium sulphate Nutrition 0.000 description 39
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- 239000007787 solid Substances 0.000 description 33
- 239000000243 solution Substances 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- 239000000047 product Substances 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 230000000694 effects Effects 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 19
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
- 238000000354 decomposition reaction Methods 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 14
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 230000003197 catalytic effect Effects 0.000 description 10
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 229910052763 palladium Inorganic materials 0.000 description 9
- 238000001228 spectrum Methods 0.000 description 9
- 239000006228 supernatant Substances 0.000 description 9
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 8
- 210000004556 brain Anatomy 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 238000012216 screening Methods 0.000 description 8
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 7
- 229930064664 L-arginine Natural products 0.000 description 7
- 235000014852 L-arginine Nutrition 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 229960002173 citrulline Drugs 0.000 description 7
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 7
- 239000006188 syrup Substances 0.000 description 7
- 235000020357 syrup Nutrition 0.000 description 7
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 6
- MLQQVSKLPBROCW-UHFFFAOYSA-N 7-nitro-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1=C([N+]([O-])=O)C=C2CC(N)CCC2=C1 MLQQVSKLPBROCW-UHFFFAOYSA-N 0.000 description 6
- 239000004475 Arginine Substances 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000007995 HEPES buffer Substances 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- KWSNKIIHXGOOSA-UHFFFAOYSA-N n-(7-nitro-1,2,3,4-tetrahydronaphthalen-2-yl)benzamide Chemical compound C1C2=CC([N+](=O)[O-])=CC=C2CCC1NC(=O)C1=CC=CC=C1 KWSNKIIHXGOOSA-UHFFFAOYSA-N 0.000 description 6
- 235000006408 oxalic acid Nutrition 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 5
- 150000001409 amidines Chemical class 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 230000001537 neural effect Effects 0.000 description 5
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- FFGLVSGGGJOMQY-UHFFFAOYSA-N 5-nitro-2,3-dihydro-1h-inden-2-amine;hydrochloride Chemical compound Cl.C1=C([N+]([O-])=O)C=C2CC(N)CC2=C1 FFGLVSGGGJOMQY-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
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- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 4
- 108010029485 Protein Isoforms Proteins 0.000 description 4
- 102000001708 Protein Isoforms Human genes 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
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- YKMYDLPAGPNDEZ-UHFFFAOYSA-N n-benzyl-7-nitro-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1C2=CC([N+](=O)[O-])=CC=C2CCC1NCC1=CC=CC=C1 YKMYDLPAGPNDEZ-UHFFFAOYSA-N 0.000 description 4
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 4
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- YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 description 3
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- AIDUBMXHTVPHAG-UHFFFAOYSA-N 2-(5-amino-2,3-dihydro-1h-inden-1-yl)-n-benzyl-n,2,2-trifluoroacetamide Chemical compound C1CC2=CC(N)=CC=C2C1C(F)(F)C(=O)N(F)CC1=CC=CC=C1 AIDUBMXHTVPHAG-UHFFFAOYSA-N 0.000 description 3
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- DAYRGFHXWCSBQP-UHFFFAOYSA-N 7-nitro-1,2,3,4-tetrahydronaphthalen-2-amine;hydrochloride Chemical compound Cl.C1=C([N+]([O-])=O)C=C2CC(N)CCC2=C1 DAYRGFHXWCSBQP-UHFFFAOYSA-N 0.000 description 3
- NYHHIPIPUVLUFF-UHFFFAOYSA-N 7-nitroisoquinoline Chemical compound C1=CN=CC2=CC([N+](=O)[O-])=CC=C21 NYHHIPIPUVLUFF-UHFFFAOYSA-N 0.000 description 3
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- 102000014150 Interferons Human genes 0.000 description 3
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- MRAUNPAHJZDYCK-BYPYZUCNSA-N L-nitroarginine Chemical compound OC(=O)[C@@H](N)CCCNC(=N)N[N+]([O-])=O MRAUNPAHJZDYCK-BYPYZUCNSA-N 0.000 description 3
- JYFJSHWLDNUPJN-UHFFFAOYSA-N N'-(8-amino-5,6,7,8-tetrahydronaphthalen-2-yl)thiophene-2-carboximidamide oxalic acid Chemical compound OC(=O)C(O)=O.OC(=O)C(O)=O.C1=C2C(N)CCCC2=CC=C1NC(=N)C1=CC=CS1 JYFJSHWLDNUPJN-UHFFFAOYSA-N 0.000 description 3
- NPZSMIUTDDKPRF-UHFFFAOYSA-N NC1C2=CC([N+]([O-])=O)=CC=C2CCC1CC1=CC=CC=C1 Chemical compound NC1C2=CC([N+]([O-])=O)=CC=C2CCC1CC1=CC=CC=C1 NPZSMIUTDDKPRF-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 3
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- 230000009286 beneficial effect Effects 0.000 description 1
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
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- 230000001506 immunosuppresive effect Effects 0.000 description 1
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- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- JALPFCYOLPWOIJ-UHFFFAOYSA-N n'-(7-amino-5,6,7,8-tetrahydronaphthalen-2-yl)thiophene-2-carboximidamide;dihydrobromide Chemical compound Br.Br.C1=C2CC(N)CCC2=CC=C1NC(=N)C1=CC=CS1 JALPFCYOLPWOIJ-UHFFFAOYSA-N 0.000 description 1
- AZXCAZDYBUNSRH-UHFFFAOYSA-N n-(3-oxo-1,2-dihydroinden-5-yl)acetamide Chemical compound CC(=O)NC1=CC=C2CCC(=O)C2=C1 AZXCAZDYBUNSRH-UHFFFAOYSA-N 0.000 description 1
- GRUBFWLPYHPBJN-UHFFFAOYSA-N n-[(3-chlorophenyl)methyl]-7-nitro-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1C2=CC([N+](=O)[O-])=CC=C2CCC1NCC1=CC=CC(Cl)=C1 GRUBFWLPYHPBJN-UHFFFAOYSA-N 0.000 description 1
- ZQVCLBNTPVUYPF-UHFFFAOYSA-N n-benzyl-5-nitro-2,3-dihydro-1h-inden-2-amine Chemical compound C1C2=CC([N+](=O)[O-])=CC=C2CC1NCC1=CC=CC=C1 ZQVCLBNTPVUYPF-UHFFFAOYSA-N 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
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- 238000007911 parenteral administration Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
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- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 235000019231 riboflavin-5'-phosphate Nutrition 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
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- 238000007790 scraping Methods 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 150000004763 sulfides Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- HDXYHAPUCGQOBX-UHFFFAOYSA-N thiophene-2-carbothioamide Chemical compound NC(=S)C1=CC=CS1 HDXYHAPUCGQOBX-UHFFFAOYSA-N 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- 238000012418 validation experiment Methods 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/GB1995/001896 WO1997006158A1 (en) | 1995-08-10 | 1995-08-10 | Bicyclic amidine derivatives useful in therapy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK39097A3 SK39097A3 (en) | 1998-08-05 |
| SK281442B6 true SK281442B6 (sk) | 2001-03-12 |
Family
ID=10768883
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK390-97A SK281442B6 (sk) | 1995-08-10 | 1995-08-10 | Bicyklické amidínové deriváty, spôsob ich prípravy, farmaceutické kompozície s ich obsahom a ich použitie |
Country Status (7)
| Country | Link |
|---|---|
| KR (1) | KR970706272A (cs) |
| BR (1) | BR9509297A (cs) |
| CZ (1) | CZ287969B6 (cs) |
| EE (1) | EE9700207A (cs) |
| IS (1) | IS4452A (cs) |
| SK (1) | SK281442B6 (cs) |
| WO (1) | WO1997006158A1 (cs) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9701681D0 (sv) * | 1997-05-05 | 1997-05-05 | Astra Ab | New compounds |
| US6166030A (en) * | 1997-05-05 | 2000-12-26 | Astra Aktiebolag | Compounds |
| DE19844291A1 (de) * | 1998-09-18 | 2000-03-23 | Schering Ag | Benzoxazin- und Benzothiazin-Derivate und deren Verwendung in Arzneimitteln |
| SE9803710L (sv) | 1998-09-25 | 2000-03-26 | A & Science Invest Ab | Användning av vissa substanser för behandling av nervrotsskador |
| US7115557B2 (en) | 1998-09-25 | 2006-10-03 | Sciaticon Ab | Use of certain drugs for treating nerve root injury |
| EP1283199A4 (en) | 2000-05-16 | 2003-12-17 | Takeda Chemical Industries Ltd | MELANINE CONCENTRATING HORMONE ANTAGONISTS |
| TWI243164B (en) | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
| MY136316A (en) | 2001-02-13 | 2008-09-30 | Sanofi Aventis Deutschland | Acylated 6,7,8,9-tetrahydro-5h-benzocycloheptenyl amines and their use as pharmaceutical. |
| DE60325025D1 (de) | 2002-02-15 | 2009-01-15 | Glaxo Group Ltd | Modulatoren des vanilloidrezeptors |
| EP1388535A1 (en) * | 2002-08-07 | 2004-02-11 | Aventis Pharma Deutschland GmbH | Acylated arylcycloalkylamines and their use as pharmaceuticals |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0690851B1 (en) * | 1993-03-23 | 1999-05-19 | Astra Aktiebolag | Guanidine derivatives useful in therapy |
| ATE231126T1 (de) * | 1993-08-12 | 2003-02-15 | Astrazeneca Ab | Amidin-derivate mit stickstoffoxid-synthease- aktivität |
| JPH10500138A (ja) * | 1994-05-07 | 1998-01-06 | アストラ・アクチエボラーグ | 酸化窒素合成酵素阻害剤としての２環アミジン誘導体 |
-
1995
- 1995-08-10 BR BR9509297A patent/BR9509297A/pt unknown
- 1995-08-10 SK SK390-97A patent/SK281442B6/sk unknown
- 1995-08-10 CZ CZ19971086A patent/CZ287969B6/cs not_active IP Right Cessation
- 1995-08-10 EE EE9700207A patent/EE9700207A/xx unknown
- 1995-08-10 KR KR1019970702315A patent/KR970706272A/ko not_active Ceased
- 1995-08-10 WO PCT/GB1995/001896 patent/WO1997006158A1/en not_active Application Discontinuation
-
1997
- 1997-03-25 IS IS4452A patent/IS4452A/is unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SK39097A3 (en) | 1998-08-05 |
| EE9700207A (et) | 1998-02-16 |
| CZ287969B6 (cs) | 2001-03-14 |
| BR9509297A (pt) | 1998-07-07 |
| KR970706272A (ko) | 1997-11-03 |
| WO1997006158A1 (en) | 1997-02-20 |
| IS4452A (is) | 1997-03-25 |
| CZ108697A3 (cs) | 1998-04-15 |
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