NO324065B1 - Nye 2-(iminometyl)amino-fenyl-derivater, fremstilling, medikamenter inneholdende disse, farmasoytiske preparater inneholdende disse og anvendelse av disse for fremstilling av medikament - Google Patents
Nye 2-(iminometyl)amino-fenyl-derivater, fremstilling, medikamenter inneholdende disse, farmasoytiske preparater inneholdende disse og anvendelse av disse for fremstilling av medikament Download PDFInfo
- Publication number
- NO324065B1 NO324065B1 NO19994620A NO994620A NO324065B1 NO 324065 B1 NO324065 B1 NO 324065B1 NO 19994620 A NO19994620 A NO 19994620A NO 994620 A NO994620 A NO 994620A NO 324065 B1 NO324065 B1 NO 324065B1
- Authority
- NO
- Norway
- Prior art keywords
- phenyl
- dimethylethyl
- bis
- hydroxy
- amino
- Prior art date
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- -1 2- (iminomethyl) amino-phenyl Chemical class 0.000 title claims description 94
- 239000003814 drug Substances 0.000 title claims description 15
- 238000002360 preparation method Methods 0.000 title claims description 11
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 149
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 123
- 229930192474 thiophene Natural products 0.000 claims description 74
- 150000001875 compounds Chemical class 0.000 claims description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 52
- 125000004432 carbon atom Chemical group C* 0.000 claims description 51
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 42
- 150000003839 salts Chemical class 0.000 claims description 37
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 21
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 20
- NSMWYRLQHIXVAP-UHFFFAOYSA-N 2,5-dimethylpiperazine Chemical compound CC1CNC(C)CN1 NSMWYRLQHIXVAP-UHFFFAOYSA-N 0.000 claims description 20
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical compound NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 claims description 20
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 19
- JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 9
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 9
- 150000003254 radicals Chemical class 0.000 claims description 9
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 230000003859 lipid peroxidation Effects 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 239000004202 carbamide Substances 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- CLNBSVLNDIEZNG-UHFFFAOYSA-N 3,5-ditert-butyl-4-hydroxy-n-(4-nitrophenyl)benzamide Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C(=O)NC=2C=CC(=CC=2)[N+]([O-])=O)=C1 CLNBSVLNDIEZNG-UHFFFAOYSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000002837 carbocyclic group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- UKBQQBCMLNRWIN-UHFFFAOYSA-N (6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)-[4-(4-nitrophenyl)-1,4-diazepan-1-yl]methanone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)N(CC1)CCCN1C1=CC=C([N+]([O-])=O)C=C1 UKBQQBCMLNRWIN-UHFFFAOYSA-N 0.000 claims description 3
- JUQKRIWOSXGFLP-UHFFFAOYSA-N (6-methoxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)-[4-(4-nitrophenyl)piperazin-1-yl]methanone Chemical compound C1CC2=C(C)C(OC)=C(C)C(C)=C2OC1(C)C(=O)N(CC1)CCN1C1=CC=C([N+]([O-])=O)C=C1 JUQKRIWOSXGFLP-UHFFFAOYSA-N 0.000 claims description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
- QNDSPOBREIQSKR-UHFFFAOYSA-N [4-(4-aminophenyl)-1,4-diazepan-1-yl]-(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)methanone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)N(CC1)CCCN1C1=CC=C(N)C=C1 QNDSPOBREIQSKR-UHFFFAOYSA-N 0.000 claims description 3
- HOVSLBDUXWBLDA-UHFFFAOYSA-N [4-(4-aminophenyl)piperazin-1-yl]-(6-methoxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)methanone Chemical compound C1CC2=C(C)C(OC)=C(C)C(C)=C2OC1(C)C(=O)N(CC1)CCN1C1=CC=C(N)C=C1 HOVSLBDUXWBLDA-UHFFFAOYSA-N 0.000 claims description 3
- 230000001537 neural effect Effects 0.000 claims description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 claims description 2
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- STCYUKSGPHEXDI-LJAQVGFWSA-N n'-[4-[4-[(2s)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carbonyl]piperazin-1-yl]phenyl]thiophene-2-carboximidamide Chemical compound O=C([C@@]1(C)OC=2C(C)=C(C(=C(C)C=2CC1)O)C)N(CC1)CCN1C(C=C1)=CC=C1N=C(N)C1=CC=CS1 STCYUKSGPHEXDI-LJAQVGFWSA-N 0.000 claims description 2
- 125000004001 thioalkyl group Chemical group 0.000 claims description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims 1
- 150000005840 aryl radicals Chemical class 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 claims 1
- HAXSKIIUSSBTBT-UHFFFAOYSA-N n'-[4-[4-[(3,5-ditert-butyl-4-hydroxyphenyl)methyl]piperazin-1-yl]phenyl]thiophene-2-carboximidamide Chemical group CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(CN2CCN(CC2)C=2C=CC(NC(=N)C=3SC=CC=3)=CC=2)=C1 HAXSKIIUSSBTBT-UHFFFAOYSA-N 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 153
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 150
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 118
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
- 239000000843 powder Substances 0.000 description 79
- 239000000243 solution Substances 0.000 description 71
- 239000000543 intermediate Substances 0.000 description 70
- 238000002844 melting Methods 0.000 description 69
- 230000008018 melting Effects 0.000 description 69
- 238000002474 experimental method Methods 0.000 description 53
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
- 239000000203 mixture Substances 0.000 description 38
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 38
- 239000000047 product Substances 0.000 description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 239000012429 reaction media Substances 0.000 description 26
- 230000002829 reductive effect Effects 0.000 description 26
- 238000001704 evaporation Methods 0.000 description 25
- 230000008020 evaporation Effects 0.000 description 25
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 23
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
- 238000001914 filtration Methods 0.000 description 21
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
- 239000012074 organic phase Substances 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 19
- 150000001412 amines Chemical class 0.000 description 18
- 229910052938 sodium sulfate Inorganic materials 0.000 description 18
- 235000011152 sodium sulphate Nutrition 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- GLEVLJDDWXEYCO-UHFFFAOYSA-N Trolox Chemical compound O1C(C)(C(O)=O)CCC2=C1C(C)=C(C)C(O)=C2C GLEVLJDDWXEYCO-UHFFFAOYSA-N 0.000 description 17
- 239000003480 eluent Substances 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 17
- QLTNXPAYDGYHTP-UHFFFAOYSA-N n-(4-aminophenyl)-3,5-ditert-butyl-4-hydroxybenzamide Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C(=O)NC=2C=CC(N)=CC=2)=C1 QLTNXPAYDGYHTP-UHFFFAOYSA-N 0.000 description 17
- 239000002244 precipitate Substances 0.000 description 16
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 239000002585 base Substances 0.000 description 14
- 238000001035 drying Methods 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- 229940125904 compound 1 Drugs 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 238000010586 diagram Methods 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000013877 carbamide Nutrition 0.000 description 11
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 10
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 10
- 150000001408 amides Chemical class 0.000 description 10
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- INXDQKJHQRWWPG-UHFFFAOYSA-N 3,5-ditert-butyl-4-hydroxy-n-[(4-nitrophenyl)methyl]benzamide Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C(=O)NCC=2C=CC(=CC=2)[N+]([O-])=O)=C1 INXDQKJHQRWWPG-UHFFFAOYSA-N 0.000 description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000012047 saturated solution Substances 0.000 description 8
- 235000017550 sodium carbonate Nutrition 0.000 description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 150000003672 ureas Chemical class 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 7
- 239000012948 isocyanate Substances 0.000 description 7
- 150000002513 isocyanates Chemical class 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- VWOJSRICSKDKAW-UHFFFAOYSA-N 1-(4-nitrophenyl)piperazine Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1CCNCC1 VWOJSRICSKDKAW-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 150000001409 amidines Chemical class 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
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- JMSVCTWVEWCHDZ-UHFFFAOYSA-N syringic acid Chemical compound COC1=CC(C(O)=O)=CC(OC)=C1O JMSVCTWVEWCHDZ-UHFFFAOYSA-N 0.000 description 6
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 5
- YEXOWHQZWLCHHD-UHFFFAOYSA-N 3,5-ditert-butyl-4-hydroxybenzoic acid Chemical compound CC(C)(C)C1=CC(C(O)=O)=CC(C(C)(C)C)=C1O YEXOWHQZWLCHHD-UHFFFAOYSA-N 0.000 description 5
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- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 5
- 238000009833 condensation Methods 0.000 description 5
- 230000005494 condensation Effects 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
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- 239000000377 silicon dioxide Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 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 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
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- 208000035475 disorder Diseases 0.000 description 4
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 4
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- DERJYEZSLHIUKF-UHFFFAOYSA-N procarbazine hydrochloride Chemical compound Cl.CNNCC1=CC=C(C(=O)NC(C)C)C=C1 DERJYEZSLHIUKF-UHFFFAOYSA-N 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical class NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 4
- GHCYPKJZUAHFHJ-UHFFFAOYSA-N 1-(3,5-ditert-butyl-4-hydroxyphenyl)-3-[(4-nitrobenzoyl)amino]urea Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(NC(=O)NNC(=O)C=2C=CC(=CC=2)[N+]([O-])=O)=C1 GHCYPKJZUAHFHJ-UHFFFAOYSA-N 0.000 description 3
- UWGVPUPXODIERK-UHFFFAOYSA-N 1-[(4-aminophenyl)methyl]-3-(3,5-ditert-butyl-4-hydroxyphenyl)urea Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(NC(=O)NCC=2C=CC(N)=CC=2)=C1 UWGVPUPXODIERK-UHFFFAOYSA-N 0.000 description 3
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- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/56—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
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- C07C275/34—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms having nitrogen atoms of urea groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C275/36—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms having nitrogen atoms of urea groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with at least one of the oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. N-aryloxyphenylureas
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- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
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- 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
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- 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
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9703528A FR2761066B1 (fr) | 1997-03-24 | 1997-03-24 | Nouveaux derives du 2-(iminomethyl)amino-phenyle, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant |
PCT/FR1998/000288 WO1998042696A1 (fr) | 1997-03-24 | 1998-02-16 | Nouveaux derives du 2-(iminomethyl)amino-phenyle, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant |
Publications (3)
Publication Number | Publication Date |
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NO994620D0 NO994620D0 (no) | 1999-09-23 |
NO994620L NO994620L (no) | 1999-11-10 |
NO324065B1 true NO324065B1 (no) | 2007-08-06 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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NO19994620A NO324065B1 (no) | 1997-03-24 | 1999-09-23 | Nye 2-(iminometyl)amino-fenyl-derivater, fremstilling, medikamenter inneholdende disse, farmasoytiske preparater inneholdende disse og anvendelse av disse for fremstilling av medikament |
Country Status (30)
Country | Link |
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US (1) | US6340700B1 (ru) |
EP (1) | EP0973763B1 (ru) |
JP (1) | JP4469424B2 (ru) |
KR (1) | KR100431917B1 (ru) |
CN (1) | CN1143854C (ru) |
AR (1) | AR012102A1 (ru) |
AT (1) | ATE241612T1 (ru) |
AU (1) | AU733173B2 (ru) |
BR (1) | BR9808427B1 (ru) |
CA (1) | CA2285037C (ru) |
CZ (1) | CZ297562B6 (ru) |
DE (1) | DE69815094T2 (ru) |
DK (1) | DK0973763T3 (ru) |
ES (1) | ES2200318T3 (ru) |
FR (1) | FR2761066B1 (ru) |
HK (1) | HK1027563A1 (ru) |
HU (1) | HU228929B1 (ru) |
IL (1) | IL131915A (ru) |
MY (1) | MY124146A (ru) |
NO (1) | NO324065B1 (ru) |
NZ (1) | NZ338016A (ru) |
PL (1) | PL194688B1 (ru) |
PT (1) | PT973763E (ru) |
RU (1) | RU2183211C2 (ru) |
SK (1) | SK282773B6 (ru) |
TR (1) | TR199902382T2 (ru) |
TW (1) | TW587080B (ru) |
UA (1) | UA56219C2 (ru) |
WO (1) | WO1998042696A1 (ru) |
ZA (1) | ZA982203B (ru) |
Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6809088B2 (en) * | 1997-03-24 | 2004-10-26 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Derivatives of 2-(iminomethyl)amino-phenyl, their preparation, their use as medicaments and the pharmaceutical compositions containing them |
US6335445B1 (en) * | 1997-03-24 | 2002-01-01 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Derivatives of 2-(iminomethyl)amino-phenyl, their preparation, their use as medicaments and the pharmaceutical compositions containing them |
AR019190A1 (es) * | 1998-07-08 | 2001-12-26 | Sod Conseils Rech Applic | Derivados de 2-aminopiridinas, productos intermedios para su preparacion, medicamentos y composiciones farmaceuticas que los contienen y su uso para preparar medicamentos |
AU754529B2 (en) | 1998-09-22 | 2002-11-21 | Yamanouchi Pharmaceutical Co., Ltd. | Cyanophenyl derivatives |
FR2784678B1 (fr) * | 1998-09-23 | 2002-11-29 | Sod Conseils Rech Applic | Nouveaux derives de n-(iminomethyl)amines, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant |
FR2783519B1 (fr) | 1998-09-23 | 2003-01-24 | Sod Conseils Rech Applic | Nouveaux derives d'amidines, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant |
FR2798127A1 (fr) * | 1999-09-03 | 2001-03-09 | Expansia Sa | Nouveau procede de preparation d'amidines derivees de l'acide 6-hydroxy-2,5,7,8-tetramethylchrommane-2-carboxy- lique |
RU2380362C2 (ru) * | 1999-10-11 | 2010-01-27 | Сосьете Де Консей Де Решерш З | Производные пятичленных гетероциклов, способ их получения и их применение в качестве лекарственных средств |
FR2801053B1 (fr) * | 1999-11-16 | 2004-06-25 | Sod Conseils Rech Applic | Nouveaux derives d'amidines, leur preparation et leur application a titre de medicaments |
SE9904677D0 (sv) * | 1999-12-20 | 1999-12-20 | Astra Ab | Novel compounds |
SE9904676D0 (sv) * | 1999-12-20 | 1999-12-20 | Astra Ab | Novel compounds |
AU2001241128A1 (en) * | 2000-03-14 | 2001-09-24 | Fujisawa Pharmaceutical Co. Ltd. | Novel amide compounds |
EP1265891B1 (fr) * | 2000-03-16 | 2004-12-29 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Nouveaux derives heterocycliques ou benzeniques de l'acide lipoique, leur preparation et leur application a titre de medicaments |
FR2812198B1 (fr) | 2000-07-28 | 2008-07-18 | Sod Conseils Rech Applic | DERIVES D'AMIDINES INHIBITEURS DE PHOSPHATASES cdc25 |
AU2001282829A1 (en) * | 2000-09-05 | 2002-03-22 | Astrazeneca Ab | Amidine derivatives which are inhibitors of nitric oxide synthase |
US7078407B2 (en) * | 2001-11-23 | 2006-07-18 | Korea Research Institute Of Chemical Technology | 4-hydroxycinnamamide derivatives as antioxidants and pharmaceutical compositions containing them |
DE10162114A1 (de) * | 2001-12-12 | 2003-06-26 | Schering Ag | Neue Amidin-Derivate und deren Verwendung in Arzneimitteln |
DE10240735A1 (de) * | 2002-08-29 | 2004-03-18 | Eberhard-Karls-Universität Tübingen Universitätsklinikum | Verwendung von Modulatoren der NO-Signalkaskade und pharmazeutische Zusammensetzung |
EP1577289A1 (en) * | 2004-03-18 | 2005-09-21 | Revotar Biopharmaceuticals AG | Non-glycosylated/-glycosidic/-peptidic small molecule selectin inhibitors for the treament of inflammatory disorders |
WO2006129164A1 (en) | 2005-05-31 | 2006-12-07 | Pfizer Japan Inc. | Substituted aryloxy-n-bicyclomethyl acetamide compounds as vr1 antagonists |
EP1764094A1 (en) * | 2005-09-20 | 2007-03-21 | Revotar Biopharmaceuticals AG | Novel multi-cyclic compounds and their use |
EP1764096A1 (en) * | 2005-09-20 | 2007-03-21 | Revotar Biopharmaceuticals AG | Novel phloroglucinol derivatives having selectin ligand activity |
EP1764095A1 (en) * | 2005-09-20 | 2007-03-21 | Revotar Biopharmaceuticals AG | Novel nitrocatechol derivatives having selectin ligand activity |
EP1764093A1 (en) * | 2005-09-20 | 2007-03-21 | Revotar Biopharmaceuticals AG | Novel aromatic compounds and their use in medical applications |
HUE033757T2 (en) * | 2012-07-12 | 2017-12-28 | Khondrion Ip B V | Chromanil derivatives for the treatment of mitochondrial disease |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
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WO1994021621A1 (en) * | 1993-03-23 | 1994-09-29 | Astra Aktiebolag | Guanidine derivatives useful in therapy |
ATE231126T1 (de) * | 1993-08-12 | 2003-02-15 | Astrazeneca Ab | Amidin-derivate mit stickstoffoxid-synthease- aktivität |
CA2188680A1 (en) * | 1994-05-07 | 1996-01-25 | James Edwin Macdonald | Bicyclic amidine derivatives as inhibitors of nitric oxide synthetase |
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1997
- 1997-03-24 FR FR9703528A patent/FR2761066B1/fr not_active Expired - Fee Related
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1998
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- 1998-02-16 JP JP54510998A patent/JP4469424B2/ja not_active Expired - Fee Related
- 1998-02-16 CA CA002285037A patent/CA2285037C/fr not_active Expired - Fee Related
- 1998-02-16 KR KR10-1999-7008716A patent/KR100431917B1/ko not_active IP Right Cessation
- 1998-02-16 EP EP98909540A patent/EP0973763B1/fr not_active Expired - Lifetime
- 1998-02-16 PT PT98909540T patent/PT973763E/pt unknown
- 1998-02-16 CN CNB988045826A patent/CN1143854C/zh not_active Expired - Fee Related
- 1998-02-16 RU RU99122343/04A patent/RU2183211C2/ru not_active IP Right Cessation
- 1998-02-16 ES ES98909540T patent/ES2200318T3/es not_active Expired - Lifetime
- 1998-02-16 HU HU0001438A patent/HU228929B1/hu not_active IP Right Cessation
- 1998-02-16 WO PCT/FR1998/000288 patent/WO1998042696A1/fr active IP Right Grant
- 1998-02-16 IL IL13191598A patent/IL131915A/en not_active IP Right Cessation
- 1998-02-16 DK DK98909540T patent/DK0973763T3/da active
- 1998-02-16 AT AT98909540T patent/ATE241612T1/de active
- 1998-02-16 TR TR1999/02382T patent/TR199902382T2/xx unknown
- 1998-02-16 UA UA99095297A patent/UA56219C2/ru unknown
- 1998-02-16 PL PL98335838A patent/PL194688B1/pl not_active IP Right Cessation
- 1998-02-16 DE DE69815094T patent/DE69815094T2/de not_active Expired - Lifetime
- 1998-02-16 NZ NZ338016A patent/NZ338016A/xx not_active IP Right Cessation
- 1998-03-07 TW TW087103327A patent/TW587080B/zh not_active IP Right Cessation
- 1998-03-16 ZA ZA982203A patent/ZA982203B/xx unknown
- 1998-03-18 AR ARP980101221A patent/AR012102A1/es active IP Right Grant
- 1998-03-24 MY MYPI98001259A patent/MY124146A/en unknown
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1999
- 1999-09-23 NO NO19994620A patent/NO324065B1/no not_active IP Right Cessation
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2000
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