NO315321B1 - Nye 2-(iminometyl)amino-fenylderivater, fremstilling og anvendelse derav, samt farmasoytisk preparat - Google Patents
Nye 2-(iminometyl)amino-fenylderivater, fremstilling og anvendelse derav, samt farmasoytisk preparat Download PDFInfo
- Publication number
- NO315321B1 NO315321B1 NO19996208A NO996208A NO315321B1 NO 315321 B1 NO315321 B1 NO 315321B1 NO 19996208 A NO19996208 A NO 19996208A NO 996208 A NO996208 A NO 996208A NO 315321 B1 NO315321 B1 NO 315321B1
- Authority
- NO
- Norway
- Prior art keywords
- general formula
- methyl
- thienyl
- imino
- amino
- Prior art date
Links
- -1 2- (iminomethyl) amino-phenyl Chemical class 0.000 title claims description 82
- 238000002360 preparation method Methods 0.000 title claims description 12
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 76
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 75
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 73
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 71
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 56
- 150000001412 amines Chemical group 0.000 claims description 45
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 45
- 239000000203 mixture Substances 0.000 claims description 32
- 238000009833 condensation Methods 0.000 claims description 28
- 230000005494 condensation Effects 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 28
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 26
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 24
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 23
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 22
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 21
- 125000000623 heterocyclic group Chemical group 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 20
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 claims description 16
- 230000002378 acidificating effect Effects 0.000 claims description 14
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 12
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 12
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 11
- 125000006239 protecting group Chemical group 0.000 claims description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 10
- 230000003859 lipid peroxidation Effects 0.000 claims description 10
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 8
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 150000004657 carbamic acid derivatives Chemical class 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 claims description 4
- 125000006000 trichloroethyl group Chemical group 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- 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 claims description 3
- 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 239000000543 intermediate Substances 0.000 description 236
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 135
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 111
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
- 239000000243 solution Substances 0.000 description 75
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 66
- 238000002844 melting Methods 0.000 description 64
- 230000008018 melting Effects 0.000 description 64
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 60
- 239000000843 powder Substances 0.000 description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 44
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 43
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
- 230000015572 biosynthetic process Effects 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 36
- 238000003786 synthesis reaction Methods 0.000 description 35
- 239000011541 reaction mixture Substances 0.000 description 34
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
- 150000001409 amidines Chemical class 0.000 description 24
- 239000012074 organic phase Substances 0.000 description 23
- 239000007787 solid Substances 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 21
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 21
- 235000019341 magnesium sulphate Nutrition 0.000 description 21
- 229930192474 thiophene Natural products 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- 150000001408 amides Chemical class 0.000 description 17
- 239000012267 brine Substances 0.000 description 17
- 239000003480 eluent Substances 0.000 description 17
- 239000003921 oil Substances 0.000 description 17
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- 238000001035 drying Methods 0.000 description 16
- 239000013067 intermediate product Substances 0.000 description 16
- 239000002585 base Substances 0.000 description 15
- 238000000034 method Methods 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 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 14
- 238000001704 evaporation Methods 0.000 description 14
- 230000008020 evaporation Effects 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 14
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 13
- 239000000377 silicon dioxide Substances 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 150000003857 carboxamides Chemical class 0.000 description 12
- 150000001735 carboxylic acids Chemical class 0.000 description 12
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 12
- 238000010908 decantation Methods 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 235000013877 carbamide Nutrition 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000010647 peptide synthesis reaction Methods 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 150000001448 anilines Chemical class 0.000 description 7
- 150000002513 isocyanates Chemical class 0.000 description 7
- 235000015320 potassium carbonate Nutrition 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 239000012429 reaction media Substances 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 238000013019 agitation Methods 0.000 description 6
- 239000004202 carbamide Substances 0.000 description 6
- 239000006260 foam Substances 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000012948 isocyanate Substances 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 239000012047 saturated solution Substances 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- SNGMJMWZOCFLSK-UHFFFAOYSA-N 2-(3,5-ditert-butyl-4-hydroxyphenyl)-3-(4-nitrophenyl)-1,3-thiazolidin-4-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C2N(C(=O)CS2)C=2C=CC(=CC=2)[N+]([O-])=O)=C1 SNGMJMWZOCFLSK-UHFFFAOYSA-N 0.000 description 5
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 5
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 5
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 229940118019 malondialdehyde Drugs 0.000 description 5
- 150000003138 primary alcohols Chemical class 0.000 description 5
- 238000007127 saponification reaction Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 4
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 4
- WLHISESTWLOVMB-UHFFFAOYSA-N 4-(1,3-thiazolidin-3-ylmethyl)aniline Chemical compound C1=CC(N)=CC=C1CN1CSCC1 WLHISESTWLOVMB-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-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
- SLNWZAKZOMMXGJ-UHFFFAOYSA-N I.CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(NC(=O)C=2OC(=CC=2)C=2C=CC(=CC=2)N(C=N)C=2SC=CC=2)=C1 Chemical compound I.CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(NC(=O)C=2OC(=CC=2)C=2C=CC(=CC=2)N(C=N)C=2SC=CC=2)=C1 SLNWZAKZOMMXGJ-UHFFFAOYSA-N 0.000 description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 210000003710 cerebral cortex Anatomy 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 150000002460 imidazoles Chemical class 0.000 description 4
- 125000002883 imidazolyl group Chemical group 0.000 description 4
- 150000002547 isoxazolines Chemical class 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 4
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 4
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 4
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 4
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 4
- 150000003672 ureas Chemical class 0.000 description 4
- FCGKUUOTWLWJHE-UHFFFAOYSA-N 2,6-ditert-butyl-4-nitrophenol Chemical compound CC(C)(C)C1=CC([N+]([O-])=O)=CC(C(C)(C)C)=C1O FCGKUUOTWLWJHE-UHFFFAOYSA-N 0.000 description 3
- 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 description 3
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical group O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 3
- 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 3
- MNDTVJMRXYKBPV-UHFFFAOYSA-N 4-amino-2,6-ditert-butylphenol Chemical compound CC(C)(C)C1=CC(N)=CC(C(C)(C)C)=C1O MNDTVJMRXYKBPV-UHFFFAOYSA-N 0.000 description 3
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 3
- FCSLIAQLRYIFSN-UHFFFAOYSA-N N'-[4-[2-[3-(3,5-ditert-butyl-4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]ethoxy]phenyl]thiophene-2-carboximidamide Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C=2CC(CCOC=3C=CC(NC(=N)C=4SC=CC=4)=CC=3)ON=2)=C1 FCSLIAQLRYIFSN-UHFFFAOYSA-N 0.000 description 3
- JZWHBWIGESHFQG-UHFFFAOYSA-N N-[4-[[amino(thiophen-2-yl)methylidene]amino]phenyl]-2-[3-(3,5-ditert-butyl-4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetamide hydroiodide Chemical compound I.CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C=2CC(CC(=O)NC=3C=CC(NC(=N)C=4SC=CC=4)=CC=3)ON=2)=C1 JZWHBWIGESHFQG-UHFFFAOYSA-N 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 3
- 229910007161 Si(CH3)3 Inorganic materials 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 230000001476 alcoholic effect Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 210000001638 cerebellum Anatomy 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000006482 condensation reaction Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 239000001530 fumaric acid Substances 0.000 description 3
- 229940091173 hydantoin Drugs 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 150000002545 isoxazoles Chemical class 0.000 description 3
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
- HWHWGKNPOKIITF-UHFFFAOYSA-N n'-[4-[1-(2-hydroxy-5-methoxybenzoyl)azetidin-3-yl]oxyphenyl]thiophene-2-carboximidamide;hydrochloride Chemical compound Cl.COC1=CC=C(O)C(C(=O)N2CC(C2)OC=2C=CC(NC(=N)C=3SC=CC=3)=CC=2)=C1 HWHWGKNPOKIITF-UHFFFAOYSA-N 0.000 description 3
- FGIFARQELZKUDD-UHFFFAOYSA-N n'-[4-[1-(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carbonyl)azetidin-3-yl]oxyphenyl]thiophene-2-carboximidamide Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)N(C1)CC1OC(C=C1)=CC=C1NC(=N)C1=CC=CS1 FGIFARQELZKUDD-UHFFFAOYSA-N 0.000 description 3
- SDFLIYHPRHLZCH-UHFFFAOYSA-N n'-[4-[3-(3,5-ditert-butyl-4-hydroxyphenyl)-2-oxoimidazolidin-3-ium-1-carbonyl]phenyl]thiophene-2-carboximidamide;iodide Chemical compound I.CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(N2C(N(C(=O)C=3C=CC(NC(=N)C=4SC=CC=4)=CC=3)CC2)=O)=C1 SDFLIYHPRHLZCH-UHFFFAOYSA-N 0.000 description 3
- JTKQBMBDNVKISZ-UHFFFAOYSA-N n'-[4-[[4-(3,5-ditert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl-methylamino]phenyl]thiophene-2-carboximidamide;hydrochloride Chemical compound Cl.C=1C=C(NC(=N)C=2SC=CC=2)C=CC=1N(C)CC(SC=1)=NC=1C1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 JTKQBMBDNVKISZ-UHFFFAOYSA-N 0.000 description 3
- JICZYQGPQONWGN-UHFFFAOYSA-N n-[1-[4-[[amino(thiophen-2-yl)methylidene]amino]phenyl]pyrrolidin-3-yl]-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)NC(C1)CCN1C(C=C1)=CC=C1NC(=N)C1=CC=CS1 JICZYQGPQONWGN-UHFFFAOYSA-N 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 229940072033 potash Drugs 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 150000003512 tertiary amines Chemical class 0.000 description 3
- 150000003557 thiazoles Chemical class 0.000 description 3
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 3
- JOZSYOPADROCMP-UHFFFAOYSA-N 1,3-thiazol-2-ylmethanamine Chemical compound NCC1=NC=CS1 JOZSYOPADROCMP-UHFFFAOYSA-N 0.000 description 2
- PUCOOPJLAXJKOO-UHFFFAOYSA-N 1-(4-nitrophenyl)imidazole Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1C=NC=C1 PUCOOPJLAXJKOO-UHFFFAOYSA-N 0.000 description 2
- MMAJXKGUZYDTHV-UHFFFAOYSA-N 1-benzhydrylazetidin-3-ol Chemical compound C1C(O)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 MMAJXKGUZYDTHV-UHFFFAOYSA-N 0.000 description 2
- BCMYXYHEMGPZJN-UHFFFAOYSA-N 1-chloro-2-isocyanatoethane Chemical compound ClCCN=C=O BCMYXYHEMGPZJN-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- GFNKTLQTQSALEJ-UHFFFAOYSA-N 1-isocyanato-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(N=C=O)C=C1 GFNKTLQTQSALEJ-UHFFFAOYSA-N 0.000 description 2
- GMETUHFKFADYGW-UHFFFAOYSA-N 1-methyl-3-(4-nitrophenyl)imidazolidine-2,4-dione Chemical compound O=C1N(C)CC(=O)N1C1=CC=C([N+]([O-])=O)C=C1 GMETUHFKFADYGW-UHFFFAOYSA-N 0.000 description 2
- ZXYKUPPWJMOKGE-UHFFFAOYSA-N 2-[4-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]acetic acid Chemical compound CC(C)(C)OC(=O)NC1=CC=C(CC(O)=O)C=C1 ZXYKUPPWJMOKGE-UHFFFAOYSA-N 0.000 description 2
- UYPXQSLSPUBZQW-UHFFFAOYSA-N 2-bromo-1-(3,5-ditert-butyl-4-hydroxyphenyl)ethanone Chemical compound CC(C)(C)C1=CC(C(=O)CBr)=CC(C(C)(C)C)=C1O UYPXQSLSPUBZQW-UHFFFAOYSA-N 0.000 description 2
- DOZRDZLFLOODMB-UHFFFAOYSA-N 3,5-di-tert-Butyl-4-hydroxybenzaldehyde Chemical compound CC(C)(C)C1=CC(C=O)=CC(C(C)(C)C)=C1O DOZRDZLFLOODMB-UHFFFAOYSA-N 0.000 description 2
- NRJFXTMWBVXNCU-UHFFFAOYSA-N 3-(4-aminophenyl)-1-(3,5-ditert-butyl-4-hydroxyphenyl)imidazolidine-2,4-dione Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(N2C(N(C(=O)C2)C=2C=CC(N)=CC=2)=O)=C1 NRJFXTMWBVXNCU-UHFFFAOYSA-N 0.000 description 2
- YDGFDWPBGDCMIM-UHFFFAOYSA-N 3-(4-aminophenyl)-2-(3,5-ditert-butyl-4-hydroxyphenyl)-1,3-thiazolidin-4-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C2N(C(=O)CS2)C=2C=CC(N)=CC=2)=C1 YDGFDWPBGDCMIM-UHFFFAOYSA-N 0.000 description 2
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 2
- ZESWUEBPRPGMTP-UHFFFAOYSA-N 4-nitrobenzamide Chemical compound NC(=O)C1=CC=C([N+]([O-])=O)C=C1 ZESWUEBPRPGMTP-UHFFFAOYSA-N 0.000 description 2
- SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 description 2
- SQGDSOUZXUYAPF-UHFFFAOYSA-N 5-(4-aminophenyl)-n-(3,5-ditert-butyl-4-hydroxyphenyl)furan-2-carboxamide Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(NC(=O)C=2OC(=CC=2)C=2C=CC(N)=CC=2)=C1 SQGDSOUZXUYAPF-UHFFFAOYSA-N 0.000 description 2
- IZZIWIAOVZOBLF-UHFFFAOYSA-N 5-methoxysalicylic acid Chemical compound COC1=CC=C(O)C(C(O)=O)=C1 IZZIWIAOVZOBLF-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 208000014644 Brain disease Diseases 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- 208000032274 Encephalopathy Diseases 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 229930064664 L-arginine Natural products 0.000 description 2
- 235000014852 L-arginine Nutrition 0.000 description 2
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 101710138657 Neurotoxin Proteins 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 108010077895 Sarcosine Proteins 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000002393 azetidinyl group Chemical group 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- PVEOYINWKBTPIZ-UHFFFAOYSA-N but-3-enoic acid Chemical compound OC(=O)CC=C PVEOYINWKBTPIZ-UHFFFAOYSA-N 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical compound Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 2
- VICYTAYPKBLQFB-UHFFFAOYSA-N ethyl 3-bromo-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CBr VICYTAYPKBLQFB-UHFFFAOYSA-N 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 150000001469 hydantoins Chemical class 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- 125000003971 isoxazolinyl group Chemical group 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical compound NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 description 2
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 2
- MNZOTOBMAPCCOO-UHFFFAOYSA-N n-(3,5-ditert-butyl-4-hydroxyphenyl)-5-(4-nitrophenyl)furan-2-carboxamide Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(NC(=O)C=2OC(=CC=2)C=2C=CC(=CC=2)[N+]([O-])=O)=C1 MNZOTOBMAPCCOO-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 239000002581 neurotoxin Substances 0.000 description 2
- 231100000618 neurotoxin Toxicity 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 238000005502 peroxidation Methods 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 150000003147 proline derivatives Chemical class 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 229940043230 sarcosine Drugs 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 2
- 125000001984 thiazolidinyl group Chemical group 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 125000005490 tosylate group Chemical group 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- VVIXOTCTYAILNP-UHFFFAOYSA-N (2-amino-2-oxoethyl)-methylazanium;chloride Chemical compound Cl.CNCC(N)=O VVIXOTCTYAILNP-UHFFFAOYSA-N 0.000 description 1
- CVJUZDFIEUELRB-QMTHXVAHSA-N (2R,4R)-2-methyl-4-(4-methylphenyl)sulfonyloxypyrrolidine-1,2-dicarboxylic acid Chemical class C1=CC(C)=CC=C1S(=O)(=O)O[C@@H]1C[C@](C)(C(O)=O)N(C(O)=O)C1 CVJUZDFIEUELRB-QMTHXVAHSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- LTKWMFNXJNKDTR-UHFFFAOYSA-N (3,5-ditert-butyl-n-ethyl-4-hydroxyanilino) acetate Chemical compound CC(=O)ON(CC)C1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 LTKWMFNXJNKDTR-UHFFFAOYSA-N 0.000 description 1
- JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical compound O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 1
- VPXNWRRWISNHME-JTQLQIEISA-N (3s)-3-(4-nitrophenoxy)pyrrolidine Chemical compound C1=CC([N+](=O)[O-])=CC=C1O[C@@H]1CNCC1 VPXNWRRWISNHME-JTQLQIEISA-N 0.000 description 1
- WHEHQPOUIXMETN-IENPIDJESA-N (4r)-2-(4-nitrophenyl)-1,3-thiazolidine-4-carboxylic acid Chemical compound N1[C@H](C(=O)O)CSC1C1=CC=C([N+]([O-])=O)C=C1 WHEHQPOUIXMETN-IENPIDJESA-N 0.000 description 1
- OLBOENQKGKQCJD-XOTMQJHLSA-N (5Z)-3-ethyl-5-[[4-[7-[7-[(Z)-(3-ethyl-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-2,1,3-benzothiadiazol-4-yl]-9,9-dioctylfluoren-2-yl]-2,1,3-benzothiadiazol-7-yl]methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one Chemical compound C(CCCCCCC)C1(C2=CC(=CC=C2C=2C=CC(=CC1=2)C1=CC=C(C=2C1=NSN=2)\C=C/1\C(N(C(S\1)=S)CC)=O)C1=CC=C(C=2C1=NSN=2)\C=C/1\C(N(C(S\1)=S)CC)=O)CCCCCCCC OLBOENQKGKQCJD-XOTMQJHLSA-N 0.000 description 1
- PFVFXDVOCHMQDU-UHFFFAOYSA-N 1,2,3,4-tetrahydropyridine-4-carboxylic acid Chemical compound OC(=O)C1CCNC=C1 PFVFXDVOCHMQDU-UHFFFAOYSA-N 0.000 description 1
- FHSMIGMIMUBFHS-UHFFFAOYSA-N 1-(3,5-ditert-butyl-4-hydroxyphenyl)-3-(4-nitrobenzoyl)imidazolidin-2-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(N2C(N(C(=O)C=3C=CC(=CC=3)[N+]([O-])=O)CC2)=O)=C1 FHSMIGMIMUBFHS-UHFFFAOYSA-N 0.000 description 1
- NBYGZRYWDBOFOL-UHFFFAOYSA-N 1-(3,5-ditert-butyl-4-hydroxyphenyl)-3-(4-nitrophenyl)imidazolidine-2,4-dione Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(N2C(N(C(=O)C2)C=2C=CC(=CC=2)[N+]([O-])=O)=O)=C1 NBYGZRYWDBOFOL-UHFFFAOYSA-N 0.000 description 1
- HRUQKBAASCCROQ-UHFFFAOYSA-N 1-(4-aminobenzoyl)-3-(3,5-ditert-butyl-4-hydroxyphenyl)imidazolidin-2-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(N2C(N(C(=O)C=3C=CC(N)=CC=3)CC2)=O)=C1 HRUQKBAASCCROQ-UHFFFAOYSA-N 0.000 description 1
- IXQSJUBRGIJRCV-UHFFFAOYSA-N 1-(4-nitrophenyl)pyrrolidine Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1CCCC1 IXQSJUBRGIJRCV-UHFFFAOYSA-N 0.000 description 1
- IPHUDFZAYFEHCJ-UHFFFAOYSA-N 1-[4-[[amino(thiophen-2-yl)methylidene]amino]phenyl]-n-(3,5-ditert-butyl-4-hydroxyphenyl)pyrrole-2-carboxamide Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(NC(=O)C=2N(C=CC=2)C=2C=CC(NC(=N)C=3SC=CC=3)=CC=2)=C1 IPHUDFZAYFEHCJ-UHFFFAOYSA-N 0.000 description 1
- LORSYFARRPOZPH-UHFFFAOYSA-N 1-benzhydryl-3-(4-nitrophenoxy)azetidine Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 LORSYFARRPOZPH-UHFFFAOYSA-N 0.000 description 1
- SFWZZSXCWQTORH-UHFFFAOYSA-N 1-methyl-2-phenylindole Chemical compound C=1C2=CC=CC=C2N(C)C=1C1=CC=CC=C1 SFWZZSXCWQTORH-UHFFFAOYSA-N 0.000 description 1
- FGOJCPKOOGIRPA-UHFFFAOYSA-N 1-o-tert-butyl 4-o-ethyl 5-oxoazepane-1,4-dicarboxylate Chemical compound CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CCC1=O FGOJCPKOOGIRPA-UHFFFAOYSA-N 0.000 description 1
- NKWCGTOZTHZDHB-UHFFFAOYSA-N 1h-imidazol-1-ium-4-carboxylate Chemical compound OC(=O)C1=CNC=N1 NKWCGTOZTHZDHB-UHFFFAOYSA-N 0.000 description 1
- CRZDNISJUXVSKX-UHFFFAOYSA-N 1h-imidazol-2-ylmethanamine Chemical compound NCC1=NC=CN1 CRZDNISJUXVSKX-UHFFFAOYSA-N 0.000 description 1
- NPNLTHPVLNUJEV-UHFFFAOYSA-N 2,2,4,4-tetramethylpentan-3-ylbenzene Chemical class CC(C)(C)C(C(C)(C)C)C1=CC=CC=C1 NPNLTHPVLNUJEV-UHFFFAOYSA-N 0.000 description 1
- DKCPKDPYUFEZCP-UHFFFAOYSA-N 2,6-di-tert-butylphenol Chemical compound CC(C)(C)C1=CC=CC(C(C)(C)C)=C1O DKCPKDPYUFEZCP-UHFFFAOYSA-N 0.000 description 1
- QSMYAUJWSXKKDS-UHFFFAOYSA-N 2-(1,2-oxazol-3-yl)acetic acid Chemical compound OC(=O)CC=1C=CON=1 QSMYAUJWSXKKDS-UHFFFAOYSA-N 0.000 description 1
- VDNWQEGRROHMFE-UHFFFAOYSA-N 2-(1,2-oxazol-5-yl)acetamide Chemical compound NC(=O)CC1=CC=NO1 VDNWQEGRROHMFE-UHFFFAOYSA-N 0.000 description 1
- KIMOWELLZBPFDS-UHFFFAOYSA-N 2-(4-aminophenyl)-n-(3,5-ditert-butyl-4-hydroxyphenyl)-1,3-thiazole-4-carboxamide Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(NC(=O)C=2N=C(SC=2)C=2C=CC(N)=CC=2)=C1 KIMOWELLZBPFDS-UHFFFAOYSA-N 0.000 description 1
- XQBNPFPSRBLFHV-UHFFFAOYSA-N 2-(4-nitrophenyl)-4-thiazolecarboxylic acid ethyl ester Chemical compound CCOC(=O)C1=CSC(C=2C=CC(=CC=2)[N+]([O-])=O)=N1 XQBNPFPSRBLFHV-UHFFFAOYSA-N 0.000 description 1
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 1
- CBBFWSMELCDMPZ-UHFFFAOYSA-N 2-(methylamino)acetamide Chemical compound CNCC(N)=O CBBFWSMELCDMPZ-UHFFFAOYSA-N 0.000 description 1
- BQMXMASGJOJWSR-UHFFFAOYSA-N 2-[4-[[amino(thiophen-2-yl)methylidene]amino]phenyl]-n-(3,5-ditert-butyl-4-hydroxyphenyl)-1,3-thiazole-4-carboxamide;hydroiodide Chemical compound I.CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(NC(=O)C=2N=C(SC=2)C=2C=CC(NC(=N)C=3SC=CC=3)=CC=2)=C1 BQMXMASGJOJWSR-UHFFFAOYSA-N 0.000 description 1
- 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 1
- AAUQLHHARJUJEH-UHFFFAOYSA-N 2-hydroxy-5-methoxybenzoic acid Natural products COC1=CC=CC(O)=C1C(O)=O AAUQLHHARJUJEH-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
- DKMQRVMLIIURDI-UHFFFAOYSA-N 3,5-ditert-butyl-N,4-dihydroxybenzenecarboximidoyl chloride Chemical compound CC(C)(C)C1=CC(C(Cl)=NO)=CC(C(C)(C)C)=C1O DKMQRVMLIIURDI-UHFFFAOYSA-N 0.000 description 1
- XXJWTFWPJRKBGX-UHFFFAOYSA-N 3-(4-aminophenyl)-5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]-1-methylimidazolidine-2,4-dione Chemical compound CN1C(=O)N(C=2C=CC(N)=CC=2)C(=O)C1=CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 XXJWTFWPJRKBGX-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- FJNDKRBJUJWHRN-UHFFFAOYSA-N 4-(1-benzhydrylazetidin-3-yl)oxyaniline Chemical compound C1=CC(N)=CC=C1OC1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 FJNDKRBJUJWHRN-UHFFFAOYSA-N 0.000 description 1
- JAHDECSRUJTQCB-UHFFFAOYSA-N 4-(4-nitrophenoxy)piperidine Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1CCNCC1 JAHDECSRUJTQCB-UHFFFAOYSA-N 0.000 description 1
- XWGZIZNOKZMWTP-UHFFFAOYSA-N 4-[2-[(4-amino-n-methylanilino)methyl]-1,3-thiazol-4-yl]-2,6-ditert-butylphenol Chemical compound C=1C=C(N)C=CC=1N(C)CC(SC=1)=NC=1C1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 XWGZIZNOKZMWTP-UHFFFAOYSA-N 0.000 description 1
- LVOASPZGXNAHJI-UHFFFAOYSA-N 4-imidazol-1-ylaniline Chemical compound C1=CC(N)=CC=C1N1C=NC=C1 LVOASPZGXNAHJI-UHFFFAOYSA-N 0.000 description 1
- BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 1
- MDBQPBMIZPCKAJ-UHFFFAOYSA-N 4-nitrobenzenecarbothioamide Chemical compound NC(=S)C1=CC=C([N+]([O-])=O)C=C1 MDBQPBMIZPCKAJ-UHFFFAOYSA-N 0.000 description 1
- FXZTYDPWMQBTDH-UHFFFAOYSA-N 5-(4-nitrophenyl)furan-2-carboxylic acid Chemical compound O1C(C(=O)O)=CC=C1C1=CC=C([N+]([O-])=O)C=C1 FXZTYDPWMQBTDH-UHFFFAOYSA-N 0.000 description 1
- DXDPZUPSLJAFQK-UHFFFAOYSA-N 5-[(3,5-ditert-butyl-4-hydroxyphenyl)methylidene]-1-methyl-3-(4-nitrophenyl)imidazolidine-2,4-dione Chemical compound CN1C(=O)N(C=2C=CC(=CC=2)[N+]([O-])=O)C(=O)C1=CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 DXDPZUPSLJAFQK-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- MNVKOXVIWWOCLO-UHFFFAOYSA-N 6-hydroxy-2,5,7,8-tetramethyl-n-[1-(4-nitrophenyl)pyrrolidin-3-yl]-3,4-dihydrochromene-2-carboxamide Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)C(=O)NC(C1)CCN1C1=CC=C([N+]([O-])=O)C=C1 MNVKOXVIWWOCLO-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- ULMVEPGXHPTFJX-UHFFFAOYSA-N C[S+]=C(C1=CC=CS1)N.I Chemical compound C[S+]=C(C1=CC=CS1)N.I ULMVEPGXHPTFJX-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000000584 Calmodulin Human genes 0.000 description 1
- 108010041952 Calmodulin Proteins 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241001573498 Compacta Species 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical class O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 229910021577 Iron(II) chloride Inorganic materials 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 108700003203 N-methylglycinamide Proteins 0.000 description 1
- ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
- 101150050048 SNCB gene Proteins 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000018839 Wilson disease Diseases 0.000 description 1
- QKFMCSYPRBWTTI-UHFFFAOYSA-N [2-(3,5-ditert-butyl-4-hydroxyphenyl)-2-[(4-nitrophenyl)carbamoylamino]ethyl] acetate Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1C(COC(=O)C)NC(=O)NC1=CC=C([N+]([O-])=O)C=C1 QKFMCSYPRBWTTI-UHFFFAOYSA-N 0.000 description 1
- RFBOBDDKZMZCPX-UHFFFAOYSA-N [4-(4-aminophenyl)piperidin-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)CCC1C1=CC=C(N)C=C1 RFBOBDDKZMZCPX-UHFFFAOYSA-N 0.000 description 1
- VLSOAXRVHARBEQ-UHFFFAOYSA-N [4-fluoro-2-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=C(F)C=C1CO VLSOAXRVHARBEQ-UHFFFAOYSA-N 0.000 description 1
- UKKSHBJODXBXSO-UHFFFAOYSA-N [5-amino-1-(azetidin-1-yloxy)cyclohexa-2,4-dien-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)C1(ON2CCC2)CC(N)=CC=C1 UKKSHBJODXBXSO-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 230000002225 anti-radical effect Effects 0.000 description 1
- 229940053202 antiepileptics carboxamide derivative Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 208000037849 arterial hypertension Diseases 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- 231100001018 bone marrow damage Toxicity 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 201000008247 brain infarction Diseases 0.000 description 1
- NHYXMAKLBXBVEO-UHFFFAOYSA-N bromomethyl acetate Chemical compound CC(=O)OCBr NHYXMAKLBXBVEO-UHFFFAOYSA-N 0.000 description 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012916 chromogenic reagent Substances 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229960002433 cysteine Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 210000005064 dopaminergic neuron Anatomy 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000000835 electrochemical detection Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000001856 erectile effect Effects 0.000 description 1
- KTVFFGXFVSYVCC-UHFFFAOYSA-N ethyl 1-(4-nitrophenyl)pyrrole-2-carboxylate Chemical compound CCOC(=O)C1=CC=CN1C1=CC=C([N+]([O-])=O)C=C1 KTVFFGXFVSYVCC-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000011536 extraction buffer Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 150000002463 imidates Chemical class 0.000 description 1
- QVDMVKFJDXTSGM-UHFFFAOYSA-N imidazolidine-2,4-dione;hydrochloride Chemical compound Cl.O=C1CNC(=O)N1 QVDMVKFJDXTSGM-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 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
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
- MMSZJHDFBMKZLW-UHFFFAOYSA-N methyl 2-[3-(3,5-ditert-butyl-4-hydroxyphenyl)-4,5-dihydro-1,2-oxazol-5-yl]acetate Chemical compound O1C(CC(=O)OC)CC(C=2C=C(C(O)=C(C=2)C(C)(C)C)C(C)(C)C)=N1 MMSZJHDFBMKZLW-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 208000013435 necrotic lesion Diseases 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000005181 nitrobenzenes Chemical class 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 150000002916 oxazoles Chemical class 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical class BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 208000007232 portal hypertension Diseases 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 235000013930 proline Nutrition 0.000 description 1
- 150000003148 prolines Chemical class 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 210000002637 putamen Anatomy 0.000 description 1
- JUJWROOIHBZHMG-RALIUCGRSA-N pyridine-d5 Chemical compound [2H]C1=NC([2H])=C([2H])C([2H])=C1[2H] JUJWROOIHBZHMG-RALIUCGRSA-N 0.000 description 1
- DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Natural products OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 description 1
- VONGYFFEWFJHNP-UHFFFAOYSA-N pyrrolecarboxylic acid methyl ester Natural products COC(=O)C1=CC=CN1 VONGYFFEWFJHNP-UHFFFAOYSA-N 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- OAWXZFGKDDFTGS-UHFFFAOYSA-N pyrrolidine-1,2-dicarboxylic acid Chemical compound OC(=O)C1CCCN1C(O)=O OAWXZFGKDDFTGS-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000035806 respiratory chain Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- APCBTRDHCDOPNY-SSDOTTSWSA-N tert-butyl (3r)-3-hydroxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](O)C1 APCBTRDHCDOPNY-SSDOTTSWSA-N 0.000 description 1
- SGQPXIZHVCLLRP-ZDUSSCGKSA-N tert-butyl (3s)-3-(4-nitrophenoxy)pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]1OC1=CC=C([N+]([O-])=O)C=C1 SGQPXIZHVCLLRP-ZDUSSCGKSA-N 0.000 description 1
- QNPWCQAKVFBVML-XADRRFQNSA-N tert-butyl (4R)-4-[(3,5-ditert-butyl-4-hydroxyphenyl)carbamoyl]-2-(4-nitrophenyl)-1,3-thiazolidine-3-carboxylate Chemical compound CC(C)(OC(=O)N1C(SC[C@H]1C(=O)NC1=CC(=C(C(=C1)C(C)(C)C)O)C(C)(C)C)C1=CC=C(C=C1)[N+](=O)[O-])C QNPWCQAKVFBVML-XADRRFQNSA-N 0.000 description 1
- OKIPVLDHIDUTOG-UHFFFAOYSA-N tert-butyl 3-amino-4-(1-benzhydrylazetidin-3-yl)oxybenzoate Chemical compound NC1=CC(C(=O)OC(C)(C)C)=CC=C1OC1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 OKIPVLDHIDUTOG-UHFFFAOYSA-N 0.000 description 1
- ZVUQAXUPDWVVQL-UHFFFAOYSA-N tert-butyl 3-amino-4-[1-(2-hydroxy-5-methoxybenzoyl)azetidin-3-yl]oxybenzoate Chemical compound COC1=CC=C(O)C(C(=O)N2CC(C2)OC=2C(=CC(=CC=2)C(=O)OC(C)(C)C)N)=C1 ZVUQAXUPDWVVQL-UHFFFAOYSA-N 0.000 description 1
- UNNMTKGKCWNQNU-UHFFFAOYSA-N tert-butyl 4-(4-nitrophenoxy)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OC1=CC=C([N+]([O-])=O)C=C1 UNNMTKGKCWNQNU-UHFFFAOYSA-N 0.000 description 1
- PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
- VXMJEMJQRVMGNS-UHFFFAOYSA-N tert-butyl n-[2-(methylamino)acetyl]carbamate Chemical compound CNCC(=O)NC(=O)OC(C)(C)C VXMJEMJQRVMGNS-UHFFFAOYSA-N 0.000 description 1
- JWZVYMQCCBCGLA-UHFFFAOYSA-N tert-butyl n-[4-(azetidin-3-yloxy)phenyl]carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1OC1CNC1 JWZVYMQCCBCGLA-UHFFFAOYSA-N 0.000 description 1
- WDNMTCPYOJPZBJ-UHFFFAOYSA-N tert-butyl n-[[4-(3,5-ditert-butyl-4-hydroxyphenyl)-1,3-thiazol-2-yl]methyl]-n-methylcarbamate Chemical compound S1C(CN(C)C(=O)OC(C)(C)C)=NC(C=2C=C(C(O)=C(C=2)C(C)(C)C)C(C)(C)C)=C1 WDNMTCPYOJPZBJ-UHFFFAOYSA-N 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical class CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- ULSZVNJBVJWEJE-UHFFFAOYSA-N thiazolidine-2-carboxylic acid Chemical class OC(=O)C1NCCS1 ULSZVNJBVJWEJE-UHFFFAOYSA-N 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D521/00—Heterocyclic compounds containing unspecified hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Obesity (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9707701A FR2764889B1 (fr) | 1997-06-20 | 1997-06-20 | Nouveaux derives du 2-(iminomethyl)amino-phenyle, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant |
| PCT/FR1998/001250 WO1998058934A1 (fr) | 1997-06-20 | 1998-06-15 | 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 |
|---|---|
| NO996208D0 NO996208D0 (no) | 1999-12-15 |
| NO996208L NO996208L (no) | 2000-02-15 |
| NO315321B1 true NO315321B1 (no) | 2003-08-18 |
Family
ID=9508226
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19996208A NO315321B1 (no) | 1997-06-20 | 1999-12-15 | Nye 2-(iminometyl)amino-fenylderivater, fremstilling og anvendelse derav, samt farmasoytisk preparat |
Country Status (29)
| Country | Link |
|---|---|
| EP (1) | EP0991654B1 (zh) |
| JP (1) | JP2002507965A (zh) |
| KR (2) | KR100618478B1 (zh) |
| CN (1) | CN1195762C (zh) |
| AR (1) | AR012250A1 (zh) |
| AT (1) | ATE297935T1 (zh) |
| AU (1) | AU737964B2 (zh) |
| BR (1) | BR9810197B1 (zh) |
| CA (1) | CA2294809C (zh) |
| CZ (1) | CZ299237B6 (zh) |
| DE (1) | DE69830584T2 (zh) |
| DK (1) | DK0991654T3 (zh) |
| ES (1) | ES2244068T3 (zh) |
| FR (1) | FR2764889B1 (zh) |
| HK (1) | HK1030218A1 (zh) |
| HU (1) | HUP0002425A3 (zh) |
| IL (1) | IL133223A (zh) |
| MY (1) | MY123193A (zh) |
| NO (1) | NO315321B1 (zh) |
| NZ (1) | NZ501656A (zh) |
| PL (1) | PL191987B1 (zh) |
| PT (1) | PT991654E (zh) |
| RU (1) | RU2202543C2 (zh) |
| SK (1) | SK286911B6 (zh) |
| TR (1) | TR199903175T2 (zh) |
| TW (1) | TW422842B (zh) |
| UA (1) | UA70921C2 (zh) |
| WO (1) | WO1998058934A1 (zh) |
| ZA (1) | ZA985392B (zh) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9801990D0 (sv) | 1998-06-04 | 1998-06-04 | Astra Ab | New 3-aryl propionic acid derivatives and analogs |
| 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 |
| US6355672B1 (en) * | 1998-08-07 | 2002-03-12 | Takeda Chemical Industries, Ltd. | Benzothiepin derivatives, process for the preparation of the same and uses thereof |
| 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 |
| FR2799461B1 (fr) * | 1999-10-11 | 2002-01-04 | Sod Conseils Rech Applic | Derives d'heterocycles a 5 chainons, leur preparation et leur application a titre de medicaments |
| 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 |
| FR2812546B1 (fr) * | 2000-08-01 | 2008-11-21 | Sod Conseils Rech Applic | Derives d'heterocycles a 5 chainons, leur preparation et leur application a titre de medicaments |
| TWI283577B (en) | 1999-10-11 | 2007-07-11 | Sod Conseils Rech Applic | Pharmaceutical composition of imidazole derivatives acting as modulators of sodium channels and the use thereof |
| 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 |
| GB0019006D0 (en) * | 2000-08-04 | 2000-09-20 | Astrazeneca Ab | Novel compounds |
| AU2001282829A1 (en) * | 2000-09-05 | 2002-03-22 | Astrazeneca Ab | Amidine derivatives which are inhibitors of nitric oxide synthase |
| TWI248438B (en) * | 2001-04-10 | 2006-02-01 | Sod Conseils Rech Applic | Derivatives of heterocycles with 5 members, their preparation and their use as medicaments |
| JP4410553B2 (ja) | 2001-06-08 | 2010-02-03 | サイトカイン・ファーマサイエンシズ・インコーポレーテッド | Ｍｉｆアンタゴニスト活性を有するイソオキサゾリン化合物 |
| HU228783B1 (en) | 2001-07-26 | 2013-05-28 | Greenearth Cleaning | Dry cleaning apparatus and method capable of utilizing a siloxane solvent |
| FR2842808B1 (fr) * | 2002-07-25 | 2004-09-10 | Sod Conseils Rech Applic | Nouveaux derives d'arylimidazoles, leur preparation et leurs applications therapeutiques |
| US7141561B2 (en) | 2002-07-25 | 2006-11-28 | Sanofi-Aventis Deutschland Gmbh | Substituted diaryl heterocycles, process for their preparation and their use as medicaments |
| DE10233817A1 (de) * | 2002-07-25 | 2004-02-12 | Aventis Pharma Deutschland Gmbh | Substituierte Diarylheterocyclen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| BRPI0507818A (pt) * | 2004-03-26 | 2007-07-10 | Cytokine Pharmasciences Inc | composto e métodos de inibição |
| WO2006022442A1 (ja) * | 2004-08-24 | 2006-03-02 | Santen Pharmaceutical Co., Ltd. | ジヒドロオロテートデヒドロゲナーゼ阻害活性を有する新規複素環アミド誘導体 |
| NZ560633A (en) | 2005-03-11 | 2011-08-26 | Neuprotect Pty Ltd | Flavonoid compounds and uses thereof |
| EP2473055A4 (en) | 2009-09-04 | 2013-02-13 | Univ Vanderbilt | ALLOSTERIC MGLUR4 POTENTIATORS, COMPOSITIONS, AND METHODS OF TREATING NEUROLOGICAL DYSFUNCTIONS |
| US9051296B2 (en) | 2009-11-16 | 2015-06-09 | Raqualia Pharma Inc. | Aryl carboxamide derivatives as TTX-S blockers |
| PL2872497T5 (pl) * | 2012-07-12 | 2020-02-28 | Khondrion Ip B.V. | Pochodne chromanylowe do leczenia choroby mitochondrialnej |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9127376D0 (en) * | 1991-12-24 | 1992-02-19 | Wellcome Found | Amidino derivatives |
| SK16396A3 (en) * | 1993-08-12 | 1996-09-04 | Astra Ab | Amidine derivatives with nitric oxide synthetase activities |
| CA2188680A1 (en) * | 1994-05-07 | 1996-01-25 | James Edwin Macdonald | Bicyclic amidine derivatives as inhibitors of nitric oxide synthetase |
-
1997
- 1997-06-20 FR FR9707701A patent/FR2764889B1/fr not_active Expired - Fee Related
-
1998
- 1998-06-10 TW TW087109245A patent/TW422842B/zh not_active IP Right Cessation
- 1998-06-15 RU RU2000101328/04A patent/RU2202543C2/ru not_active IP Right Cessation
- 1998-06-15 PT PT98932205T patent/PT991654E/pt unknown
- 1998-06-15 WO PCT/FR1998/001250 patent/WO1998058934A1/fr active IP Right Grant
- 1998-06-15 CA CA002294809A patent/CA2294809C/fr not_active Expired - Fee Related
- 1998-06-15 BR BRPI9810197-8A patent/BR9810197B1/pt not_active IP Right Cessation
- 1998-06-15 TR TR1999/03175T patent/TR199903175T2/xx unknown
- 1998-06-15 CZ CZ0459799A patent/CZ299237B6/cs not_active IP Right Cessation
- 1998-06-15 PL PL337499A patent/PL191987B1/pl not_active IP Right Cessation
- 1998-06-15 IL IL13322398A patent/IL133223A/en not_active IP Right Cessation
- 1998-06-15 AU AU82189/98A patent/AU737964B2/en not_active Ceased
- 1998-06-15 DK DK98932205T patent/DK0991654T3/da active
- 1998-06-15 ES ES98932205T patent/ES2244068T3/es not_active Expired - Lifetime
- 1998-06-15 SK SK1796-99A patent/SK286911B6/sk not_active IP Right Cessation
- 1998-06-15 EP EP98932205A patent/EP0991654B1/fr not_active Expired - Lifetime
- 1998-06-15 KR KR1020057016237A patent/KR100618478B1/ko not_active IP Right Cessation
- 1998-06-15 CN CNB988073927A patent/CN1195762C/zh not_active Expired - Fee Related
- 1998-06-15 JP JP50387199A patent/JP2002507965A/ja active Pending
- 1998-06-15 KR KR1019997012010A patent/KR100545946B1/ko not_active IP Right Cessation
- 1998-06-15 NZ NZ501656A patent/NZ501656A/en not_active IP Right Cessation
- 1998-06-15 HU HU0002425A patent/HUP0002425A3/hu unknown
- 1998-06-15 AT AT98932205T patent/ATE297935T1/de active
- 1998-06-15 UA UA99126913A patent/UA70921C2/uk unknown
- 1998-06-15 DE DE69830584T patent/DE69830584T2/de not_active Expired - Lifetime
- 1998-06-18 AR ARP980102907A patent/AR012250A1/es active IP Right Grant
- 1998-06-19 ZA ZA985392A patent/ZA985392B/xx unknown
- 1998-06-19 MY MYPI98002787A patent/MY123193A/en unknown
-
1999
- 1999-12-15 NO NO19996208A patent/NO315321B1/no not_active IP Right Cessation
-
2001
- 2001-02-21 HK HK01101230A patent/HK1030218A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO315321B1 (no) | Nye 2-(iminometyl)amino-fenylderivater, fremstilling og anvendelse derav, samt farmasoytisk preparat | |
| US7553976B2 (en) | Derivatives of 2-(iminomethyl)amino-phenyl, their preparation, their use as medicaments and the pharmaceutical compositions containing them | |
| US6586454B2 (en) | Derivatives of 2-(iminomethyl)amino-phenyl, their preparation, their use as medicaments and the pharmaceutical compositions containing them | |
| EP0544819A1 (en) | INDOLE DERIVATIVES INHIBITING THE BIOSYNTHESIS OF LEUCOTRIENE. | |
| KR20130004257A (ko) | 제조 방법 | |
| CA2344223A1 (fr) | Derives de n-(iminomethyl)amines, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant | |
| EP1385840B1 (en) | Sulfonamides | |
| NO324065B1 (no) | Nye 2-(iminometyl)amino-fenyl-derivater, fremstilling, medikamenter inneholdende disse, farmasoytiske preparater inneholdende disse og anvendelse av disse for fremstilling av medikament | |
| FR2911136A1 (fr) | Derives de n-(4-cyano-1h-pyrazol-3-yl)methylamine substitues leur preparation et leur application en therapeutique. | |
| MXPA99011971A (en) | Novel 2-(iminomethyl)amino-phenyl derivatives, preparation, application as medicines and compositions containing same | |
| KR20070018816A (ko) | 제조 방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |