DE60130628T2 - Aminophenoxyacetamid derivate und diese enthaltende pharmazeutische zusammensetzungen - Google Patents
Aminophenoxyacetamid derivate und diese enthaltende pharmazeutische zusammensetzungen Download PDFInfo
- Publication number
- DE60130628T2 DE60130628T2 DE60130628T DE60130628T DE60130628T2 DE 60130628 T2 DE60130628 T2 DE 60130628T2 DE 60130628 T DE60130628 T DE 60130628T DE 60130628 T DE60130628 T DE 60130628T DE 60130628 T2 DE60130628 T2 DE 60130628T2
- Authority
- DE
- Germany
- Prior art keywords
- group
- compound
- substituted
- branched
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- AHZPJIGLXKMUCO-UHFFFAOYSA-N 2-amino-2-phenoxyacetamide Chemical class NC(=O)C(N)OC1=CC=CC=C1 AHZPJIGLXKMUCO-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 230000002490 cerebral effect Effects 0.000 claims abstract description 16
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 6
- 102000016838 Calbindin 1 Human genes 0.000 claims description 27
- 108010028310 Calbindin 1 Proteins 0.000 claims description 27
- 125000005843 halogen group Chemical group 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 208000035475 disorder Diseases 0.000 claims description 17
- 230000015572 biosynthetic process Effects 0.000 claims description 15
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 102000014914 Carrier Proteins Human genes 0.000 claims description 12
- 108091008324 binding proteins Proteins 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 9
- 230000001939 inductive effect Effects 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 210000004556 brain Anatomy 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 6
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 6
- 206010008118 cerebral infarction Diseases 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 206010065559 Cerebral arteriosclerosis Diseases 0.000 claims description 4
- 206010039966 Senile dementia Diseases 0.000 claims description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 201000005851 intracranial arteriosclerosis Diseases 0.000 claims description 4
- 238000001356 surgical procedure Methods 0.000 claims description 4
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 3
- 208000029028 brain injury Diseases 0.000 claims description 3
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 3
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 198
- 238000000034 method Methods 0.000 abstract description 34
- 239000000203 mixture Substances 0.000 abstract description 15
- 125000004450 alkenylene group Chemical group 0.000 abstract description 5
- 125000002947 alkylene group Chemical group 0.000 abstract description 5
- 125000000547 substituted alkyl group Chemical group 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 71
- -1 methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy Chemical group 0.000 description 46
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 230000000324 neuroprotective effect Effects 0.000 description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 28
- 238000011156 evaluation Methods 0.000 description 28
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- WYQVNCBEKHLQMI-UHFFFAOYSA-N 2-(4-amino-2,3,5,6-tetramethylphenoxy)-n-methyl-n-piperidin-4-ylacetamide Chemical compound CC=1C(C)=C(N)C(C)=C(C)C=1OCC(=O)N(C)C1CCNCC1 WYQVNCBEKHLQMI-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000011575 calcium Substances 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 17
- WUUGFSXJNOTRMR-IOSLPCCCSA-N 5'-S-methyl-5'-thioadenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CSC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 WUUGFSXJNOTRMR-IOSLPCCCSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 102000005962 receptors Human genes 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 229930195712 glutamate Natural products 0.000 description 12
- 239000012442 inert solvent Substances 0.000 description 12
- 230000004083 survival effect Effects 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 108091008794 FGF receptors Proteins 0.000 description 10
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 10
- 238000011534 incubation Methods 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- XVQWECOXNZBRRU-UHFFFAOYSA-N N-[2-(4-amino-2,3,5,6-tetramethylphenoxy)-1-methylpiperidin-4-yl]propanamide Chemical compound CCC(=O)NC1CCN(C)C(C1)Oc1c(C)c(C)c(N)c(C)c1C XVQWECOXNZBRRU-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 230000004913 activation Effects 0.000 description 8
- 125000000217 alkyl group Chemical group 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
- 239000013543 active substance Substances 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 230000004770 neurodegeneration Effects 0.000 description 7
- 210000002569 neuron Anatomy 0.000 description 7
- 238000006366 phosphorylation reaction Methods 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- ZIBVYDHPNWVHJL-UHFFFAOYSA-N 2-(4-amino-2,3,5,6-tetramethylanilino)-n-[1-(4-fluorophenyl)piperidin-4-yl]-n-methylacetamide Chemical compound CC=1C(C)=C(N)C(C)=C(C)C=1NCC(=O)N(C)C(CC1)CCN1C1=CC=C(F)C=C1 ZIBVYDHPNWVHJL-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 230000000692 anti-sense effect Effects 0.000 description 6
- 239000000074 antisense oligonucleotide Substances 0.000 description 6
- 238000012230 antisense oligonucleotides Methods 0.000 description 6
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 230000026731 phosphorylation Effects 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- YDRFQQVPXSSBGA-UHFFFAOYSA-N 2-(4-amino-2,3,5,6-tetramethylphenoxy)-n-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-n-methylacetamide Chemical compound CC=1C(C)=C(N)C(C)=C(C)C=1OCC(=O)N(C)C(CC1)CCN1CC1=CC=C(C#N)C=C1 YDRFQQVPXSSBGA-UHFFFAOYSA-N 0.000 description 5
- WOLVXYYAHYZXOQ-UHFFFAOYSA-N 2-(4-amino-2,3,5,6-tetramethylphenoxy)-n-methyl-n-(1-phenacylpiperidin-4-yl)acetamide Chemical compound CC=1C(C)=C(N)C(C)=C(C)C=1OCC(=O)N(C)C(CC1)CCN1CC(=O)C1=CC=CC=C1 WOLVXYYAHYZXOQ-UHFFFAOYSA-N 0.000 description 5
- OICMGNGTONQTBQ-UHFFFAOYSA-N 2-(4-amino-2,3,5,6-tetramethylphenoxy)-n-methyl-n-[1-(2-phenylethyl)piperidin-4-yl]acetamide Chemical compound CC=1C(C)=C(N)C(C)=C(C)C=1OCC(=O)N(C)C(CC1)CCN1CCC1=CC=CC=C1 OICMGNGTONQTBQ-UHFFFAOYSA-N 0.000 description 5
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 5
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 5
- 101150021185 FGF gene Proteins 0.000 description 5
- 101000996663 Homo sapiens Neurotrophin-4 Proteins 0.000 description 5
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 5
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 5
- 108090000742 Neurotrophin 3 Proteins 0.000 description 5
- 102100029268 Neurotrophin-3 Human genes 0.000 description 5
- 102100033857 Neurotrophin-4 Human genes 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 125000001246 bromo group Chemical group Br* 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 150000007529 inorganic bases Chemical class 0.000 description 5
- 230000000302 ischemic effect Effects 0.000 description 5
- 238000010187 selection method Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- NHVWISFIIPIKSZ-UHFFFAOYSA-N tert-butyl n-[4-(methylamino)piperidin-1-yl]carbamate Chemical compound CNC1CCN(NC(=O)OC(C)(C)C)CC1 NHVWISFIIPIKSZ-UHFFFAOYSA-N 0.000 description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- IWKJJUYABKYBOY-UHFFFAOYSA-N 2-(2-amino-3,4,5,6-tetramethylanilino)-n-[1-[4-[(4-fluorophenyl)methyl]phenyl]piperidin-4-yl]-n-methylacetamide Chemical compound CC=1C(C)=C(C)C(C)=C(N)C=1NCC(=O)N(C)C(CC1)CCN1C(C=C1)=CC=C1CC1=CC=C(F)C=C1 IWKJJUYABKYBOY-UHFFFAOYSA-N 0.000 description 4
- PSOHDCHTEDEPTH-UHFFFAOYSA-N 2-(2-amino-3,4,5,6-tetramethylphenoxy)-n-methyl-n-(1-phenacylpiperidin-4-yl)acetamide Chemical compound CC=1C(C)=C(C)C(C)=C(N)C=1OCC(=O)N(C)C(CC1)CCN1CC(=O)C1=CC=CC=C1 PSOHDCHTEDEPTH-UHFFFAOYSA-N 0.000 description 4
- KBHSSVGGBLKWTP-UHFFFAOYSA-N 2-(3-amino-2,4,5,6-tetramethylphenoxy)-n-(1-benzoylpiperidin-4-yl)-n-methylacetamide Chemical compound CC=1C(C)=C(C)C(N)=C(C)C=1OCC(=O)N(C)C(CC1)CCN1C(=O)C1=CC=CC=C1 KBHSSVGGBLKWTP-UHFFFAOYSA-N 0.000 description 4
- WWQLRDRJTDELQF-UHFFFAOYSA-N 2-(3-amino-2,4,5,6-tetramethylphenoxy)-n-[1-[(4-cyanophenyl)methyl]piperidin-4-yl]-n-methylacetamide Chemical compound CC=1C(C)=C(C)C(N)=C(C)C=1OCC(=O)N(C)C(CC1)CCN1CC1=CC=C(C#N)C=C1 WWQLRDRJTDELQF-UHFFFAOYSA-N 0.000 description 4
- OISJBMQWFVZTLU-UHFFFAOYSA-N 2-(3-amino-2,4,6-trimethylanilino)-n-[1-(4-fluorophenyl)piperidin-4-yl]-n-methylacetamide Chemical compound CC=1C=C(C)C(N)=C(C)C=1NCC(=O)N(C)C(CC1)CCN1C1=CC=C(F)C=C1 OISJBMQWFVZTLU-UHFFFAOYSA-N 0.000 description 4
- LULWRQOJPGCJQR-UHFFFAOYSA-N 2-(4-amino-2,3,5,6-tetramethylanilino)-n-[1-(1,3-benzothiazol-2-yl)piperidin-4-yl]-n-methylacetamide Chemical compound C1CN(C=2SC3=CC=CC=C3N=2)CCC1N(C)C(=O)CNC1=C(C)C(C)=C(N)C(C)=C1C LULWRQOJPGCJQR-UHFFFAOYSA-N 0.000 description 4
- JQUASWQGXZQJJY-UHFFFAOYSA-N 2-(4-amino-2,3,5,6-tetramethylanilino)-n-methyl-n-[1-(4-phenylphenyl)piperidin-4-yl]propanamide Chemical compound C1CN(C=2C=CC(=CC=2)C=2C=CC=CC=2)CCC1N(C)C(=O)C(C)NC1=C(C)C(C)=C(N)C(C)=C1C JQUASWQGXZQJJY-UHFFFAOYSA-N 0.000 description 4
- XPGDCWMZZUVRGW-UHFFFAOYSA-N 2-(4-amino-2,3,5,6-tetramethylphenoxy)-n-(1-butylpiperidin-4-yl)-n-methylacetamide Chemical compound C1CN(CCCC)CCC1N(C)C(=O)COC1=C(C)C(C)=C(N)C(C)=C1C XPGDCWMZZUVRGW-UHFFFAOYSA-N 0.000 description 4
- SDYHZOJCWKPIOX-UHFFFAOYSA-N 2-(4-amino-2,3,5,6-tetramethylphenoxy)-n-(1-butylpiperidin-4-yl)-n-methylpropanamide Chemical compound C1CN(CCCC)CCC1N(C)C(=O)C(C)OC1=C(C)C(C)=C(N)C(C)=C1C SDYHZOJCWKPIOX-UHFFFAOYSA-N 0.000 description 4
- BPJOCLOMZJDGFR-UHFFFAOYSA-N 2-(4-amino-2,3,5,6-tetramethylphenoxy)-n-[1-(cyclopropylmethyl)piperidin-4-yl]-n-methylacetamide Chemical compound CC=1C(C)=C(N)C(C)=C(C)C=1OCC(=O)N(C)C(CC1)CCN1CC1CC1 BPJOCLOMZJDGFR-UHFFFAOYSA-N 0.000 description 4
- QMZKXWYKUUUNSU-UHFFFAOYSA-N 2-(4-amino-2,3,5,6-tetramethylphenoxy)-n-[1-(cyclopropylmethyl)piperidin-4-yl]-n-methylpropanamide Chemical compound C1CN(CC2CC2)CCC1N(C)C(=O)C(C)OC1=C(C)C(C)=C(N)C(C)=C1C QMZKXWYKUUUNSU-UHFFFAOYSA-N 0.000 description 4
- QWAOSKYULAXJST-UHFFFAOYSA-N 2-(4-amino-2,3,5,6-tetramethylphenoxy)-n-[1-[2-(2-hydroxy-2-phenylethoxy)ethyl]piperidin-4-yl]-n-methylacetamide Chemical compound CC=1C(C)=C(N)C(C)=C(C)C=1OCC(=O)N(C)C(CC1)CCN1CCOCC(O)C1=CC=CC=C1 QWAOSKYULAXJST-UHFFFAOYSA-N 0.000 description 4
- RIGOKHDXWCNWEY-UHFFFAOYSA-N 2-(4-amino-2,3,5-trimethylphenoxy)-n-[1-(4-fluorophenyl)piperidin-4-yl]-n-methylacetamide Chemical compound C=1C(C)=C(N)C(C)=C(C)C=1OCC(=O)N(C)C(CC1)CCN1C1=CC=C(F)C=C1 RIGOKHDXWCNWEY-UHFFFAOYSA-N 0.000 description 4
- VXISLODNDOWMDA-UHFFFAOYSA-N 2-[4-[[2-(4-amino-2,3,5,6-tetramethylphenoxy)acetyl]-methylamino]piperidin-1-yl]-n-methyl-n-phenylacetamide Chemical compound CC=1C(C)=C(N)C(C)=C(C)C=1OCC(=O)N(C)C(CC1)CCN1CC(=O)N(C)C1=CC=CC=C1 VXISLODNDOWMDA-UHFFFAOYSA-N 0.000 description 4
- MSXFYGVHHAEESK-UHFFFAOYSA-N 2-[4-[[2-(4-amino-2,3,5,6-tetramethylphenoxy)acetyl]-methylamino]piperidin-1-yl]-n-phenylacetamide Chemical compound CC=1C(C)=C(N)C(C)=C(C)C=1OCC(=O)N(C)C(CC1)CCN1CC(=O)NC1=CC=CC=C1 MSXFYGVHHAEESK-UHFFFAOYSA-N 0.000 description 4
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- 206010048962 Brain oedema Diseases 0.000 description 4
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 241000700157 Rattus norvegicus Species 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 235000010724 Wisteria floribunda Nutrition 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 230000035578 autophosphorylation Effects 0.000 description 4
- 208000006752 brain edema Diseases 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 4
- 102000014823 calbindin Human genes 0.000 description 4
- 108060001061 calbindin Proteins 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 238000006482 condensation reaction Methods 0.000 description 4
- 229940011871 estrogen Drugs 0.000 description 4
- 239000000262 estrogen Substances 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 150000007530 organic bases Chemical class 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- AUSNPJYBXBQNMN-UHFFFAOYSA-N 1-(4-fluorophenyl)-n-methylpiperidin-4-amine Chemical compound C1CC(NC)CCN1C1=CC=C(F)C=C1 AUSNPJYBXBQNMN-UHFFFAOYSA-N 0.000 description 3
- POJZHYBAFJGWHT-UHFFFAOYSA-N 2-(4-amino-2,3,5,6-tetramethylphenoxy)-n-[1-(2-hydroxy-2-phenylethyl)piperidin-4-yl]-n-methylacetamide Chemical compound CC=1C(C)=C(N)C(C)=C(C)C=1OCC(=O)N(C)C(CC1)CCN1CC(O)C1=CC=CC=C1 POJZHYBAFJGWHT-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 108090000526 Papain Proteins 0.000 description 3
- 239000004365 Protease Substances 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 210000003710 cerebral cortex Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
- 230000001605 fetal effect Effects 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 229940055729 papain Drugs 0.000 description 3
- 235000019834 papain Nutrition 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 3
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 3
- 229910000105 potassium hydride Inorganic materials 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 2
- UQGCIEYGWAFZHZ-UHFFFAOYSA-N 2-(4-amino-2,3,5,6-tetramethylphenoxy)-n-(1-benzoylpiperidin-4-yl)-n-methylacetamide Chemical compound CC=1C(C)=C(N)C(C)=C(C)C=1OCC(=O)N(C)C(CC1)CCN1C(=O)C1=CC=CC=C1 UQGCIEYGWAFZHZ-UHFFFAOYSA-N 0.000 description 2
- ATNAUEZINXEPNY-UHFFFAOYSA-N 2-[2,3,5,6-tetramethyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]anilino]acetic acid Chemical compound CC1=C(C)C(NC(=O)OC(C)(C)C)=C(C)C(C)=C1NCC(O)=O ATNAUEZINXEPNY-UHFFFAOYSA-N 0.000 description 2
- HTLVOROVFVBQDE-UHFFFAOYSA-N 2-[2,3,5,6-tetramethyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]anilino]propanoic acid Chemical compound OC(=O)C(C)NC1=C(C)C(C)=C(NC(=O)OC(C)(C)C)C(C)=C1C HTLVOROVFVBQDE-UHFFFAOYSA-N 0.000 description 2
- YLDILLQKQASWBA-UHFFFAOYSA-N 2-bromo-n-methyl-n-phenylacetamide Chemical compound BrCC(=O)N(C)C1=CC=CC=C1 YLDILLQKQASWBA-UHFFFAOYSA-N 0.000 description 2
- JLCGPSNHSULUGI-UHFFFAOYSA-N 4-(2-bromoethyl)morpholine;hydrochloride Chemical compound Cl.BrCCN1CCOCC1 JLCGPSNHSULUGI-UHFFFAOYSA-N 0.000 description 2
- UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 2
- 229920001342 Bakelite® Polymers 0.000 description 2
- KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical compound C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 2
- 208000022306 Cerebral injury Diseases 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 206010019133 Hangover Diseases 0.000 description 2
- 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 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- QYDBZVRKADDLFQ-UWVGGRQHSA-N [(1r,2r)-2-(bromomethyl)cyclopropyl]benzene Chemical compound BrC[C@@H]1C[C@H]1C1=CC=CC=C1 QYDBZVRKADDLFQ-UWVGGRQHSA-N 0.000 description 2
- MUWIANZPEBMVHH-VIFPVBQESA-N [(2s)-oxiran-2-yl]methyl 4-nitrobenzoate Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)OC[C@H]1OC1 MUWIANZPEBMVHH-VIFPVBQESA-N 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 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
- QUKIBKAKNWZJNT-UHFFFAOYSA-N benzyl n-(2-amino-4,5-dimethylphenyl)carbamate Chemical compound C1=C(C)C(C)=CC(N)=C1NC(=O)OCC1=CC=CC=C1 QUKIBKAKNWZJNT-UHFFFAOYSA-N 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000003139 buffering effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 210000004720 cerebrum Anatomy 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000002993 cycloalkylene group Chemical group 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 229940102223 injectable solution Drugs 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- CDGNLUSBENXDGG-UHFFFAOYSA-N meta-Cresidine Chemical compound COC1=CC=C(N)C(C)=C1 CDGNLUSBENXDGG-UHFFFAOYSA-N 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- IJCMVCULMWNIGC-UHFFFAOYSA-N n-methyl-1-(4-phenoxyphenyl)piperidin-4-amine Chemical compound C1CC(NC)CCN1C(C=C1)=CC=C1OC1=CC=CC=C1 IJCMVCULMWNIGC-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 230000016273 neuron death Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229910003446 platinum oxide Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 108091006082 receptor inhibitors Proteins 0.000 description 2
- 210000004761 scalp Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- AVAMDLBTVJVCRL-UHFFFAOYSA-N tert-butyl n-(2-amino-4,5-dimethylphenyl)carbamate Chemical compound CC1=CC(N)=C(NC(=O)OC(C)(C)C)C=C1C AVAMDLBTVJVCRL-UHFFFAOYSA-N 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 2
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- BRLQWZUYTZBJKN-GSVOUGTGSA-N (+)-Epichlorohydrin Chemical compound ClC[C@@H]1CO1 BRLQWZUYTZBJKN-GSVOUGTGSA-N 0.000 description 1
- BRLQWZUYTZBJKN-VKHMYHEASA-N (-)-Epichlorohydrin Chemical compound ClC[C@H]1CO1 BRLQWZUYTZBJKN-VKHMYHEASA-N 0.000 description 1
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 125000005837 1,2-cyclopentylene group Chemical group [H]C1([H])C([H])([H])C([H])([*:1])C([H])([*:2])C1([H])[H] 0.000 description 1
- AWLPPBTWBUUEPP-UHFFFAOYSA-N 1-(1,3-benzothiazol-2-yl)-n-methylpiperidin-4-amine Chemical compound C1CC(NC)CCN1C1=NC2=CC=CC=C2S1 AWLPPBTWBUUEPP-UHFFFAOYSA-N 0.000 description 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- ONJHLIZFULGOGV-UHFFFAOYSA-N 2-(2-chloroethoxy)-1-phenylethanol Chemical compound ClCCOCC(O)C1=CC=CC=C1 ONJHLIZFULGOGV-UHFFFAOYSA-N 0.000 description 1
- QOXHMBCVARLUEF-UHFFFAOYSA-N 2-[2,3,4,5-tetramethyl-6-[(2-methylpropan-2-yl)oxycarbonylamino]phenoxy]acetic acid Chemical compound CC1=C(C)C(C)=C(OCC(O)=O)C(NC(=O)OC(C)(C)C)=C1C QOXHMBCVARLUEF-UHFFFAOYSA-N 0.000 description 1
- ZEYDWSUXIXOJPT-UHFFFAOYSA-N 2-[2,3,4,6-tetramethyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]phenoxy]acetic acid Chemical compound CC1=C(C)C(NC(=O)OC(C)(C)C)=C(C)C(OCC(O)=O)=C1C ZEYDWSUXIXOJPT-UHFFFAOYSA-N 0.000 description 1
- ZBKPCQCXZKTLCO-UHFFFAOYSA-N 2-[2,3,5,6-tetramethyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]phenoxy]acetic acid Chemical compound CC1=C(C)C(OCC(O)=O)=C(C)C(C)=C1NC(=O)OC(C)(C)C ZBKPCQCXZKTLCO-UHFFFAOYSA-N 0.000 description 1
- MZWJLUWWPCUIBO-UHFFFAOYSA-N 2-[2,3,5,6-tetramethyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]phenoxy]propanoic acid Chemical compound OC(=O)C(C)OC1=C(C)C(C)=C(NC(=O)OC(C)(C)C)C(C)=C1C MZWJLUWWPCUIBO-UHFFFAOYSA-N 0.000 description 1
- AMWAOYFQVLSCPA-UHFFFAOYSA-N 2-[2,3,5-trimethyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]phenoxy]acetic acid Chemical compound CC1=CC(OCC(O)=O)=C(C)C(C)=C1NC(=O)OC(C)(C)C AMWAOYFQVLSCPA-UHFFFAOYSA-N 0.000 description 1
- XJRMDMBRZAZDHI-UHFFFAOYSA-N 2-[2,4,6-trimethyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]anilino]acetic acid Chemical compound CC1=CC(C)=C(NC(=O)OC(C)(C)C)C(C)=C1NCC(O)=O XJRMDMBRZAZDHI-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
- GHHAECMTIJUPAT-UHFFFAOYSA-N 2-amino-2-anilinoacetamide Chemical class NC(=O)C(N)NC1=CC=CC=C1 GHHAECMTIJUPAT-UHFFFAOYSA-N 0.000 description 1
- AMVRSHNTGTWNLY-UHFFFAOYSA-N 2-amino-2-phenoxyacetic acid Chemical class OC(=O)C(N)OC1=CC=CC=C1 AMVRSHNTGTWNLY-UHFFFAOYSA-N 0.000 description 1
- DCPLOIFDMMEBQZ-UHFFFAOYSA-N 2-bromo-n-phenylacetamide Chemical compound BrCC(=O)NC1=CC=CC=C1 DCPLOIFDMMEBQZ-UHFFFAOYSA-N 0.000 description 1
- JJFOBACUIRKUPN-UHFFFAOYSA-N 2-bromoethoxybenzene Chemical compound BrCCOC1=CC=CC=C1 JJFOBACUIRKUPN-UHFFFAOYSA-N 0.000 description 1
- NVYOCAOZCSNIHR-UHFFFAOYSA-N 2-bromopropylbenzene Chemical compound CC(Br)CC1=CC=CC=C1 NVYOCAOZCSNIHR-UHFFFAOYSA-N 0.000 description 1
- DNLCKLGEGRKRIC-UHFFFAOYSA-M 2-iodo-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1I DNLCKLGEGRKRIC-UHFFFAOYSA-M 0.000 description 1
- JNOQAJRNAIUOQD-UHFFFAOYSA-N 2-methyl-2-[2,3,5,6-tetramethyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]phenoxy]propanoic acid Chemical compound CC1=C(C)C(OC(C)(C)C(O)=O)=C(C)C(C)=C1NC(=O)OC(C)(C)C JNOQAJRNAIUOQD-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 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
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 239000012583 B-27 Supplement Substances 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 241000050051 Chelone glabra Species 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 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
- 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 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 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
- 241001465754 Metazoa Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- AIHIHVZYAAMDPM-MRVPVSSYSA-N [(2r)-oxiran-2-yl]methyl 3-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=CC(S(=O)(=O)OC[C@@H]2OC2)=C1 AIHIHVZYAAMDPM-MRVPVSSYSA-N 0.000 description 1
- NOQXXYIGRPAZJC-SECBINFHSA-N [(2r)-oxiran-2-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@@H]1OC1 NOQXXYIGRPAZJC-SECBINFHSA-N 0.000 description 1
- AIHIHVZYAAMDPM-QMMMGPOBSA-N [(2s)-oxiran-2-yl]methyl 3-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=CC(S(=O)(=O)OC[C@H]2OC2)=C1 AIHIHVZYAAMDPM-QMMMGPOBSA-N 0.000 description 1
- NOQXXYIGRPAZJC-VIFPVBQESA-N [(2s)-oxiran-2-yl]methyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC[C@H]1OC1 NOQXXYIGRPAZJC-VIFPVBQESA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 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
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012042 active reagent Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
- ABJXYGAKPOUWBL-UHFFFAOYSA-N benzyl n-(2-amino-4,5-dichlorophenyl)carbamate Chemical compound NC1=CC(Cl)=C(Cl)C=C1NC(=O)OCC1=CC=CC=C1 ABJXYGAKPOUWBL-UHFFFAOYSA-N 0.000 description 1
- XDSUWQKBDJSWEG-UHFFFAOYSA-N benzyl n-(2-chloro-5-hydroxy-4-methoxyphenyl)carbamate Chemical compound C1=C(O)C(OC)=CC(Cl)=C1NC(=O)OCC1=CC=CC=C1 XDSUWQKBDJSWEG-UHFFFAOYSA-N 0.000 description 1
- NNMRUWNFJNEETH-UHFFFAOYSA-N benzyl n-(2-hydroxy-3,4,5,6-tetramethylphenyl)carbamate Chemical compound OC1=C(C)C(C)=C(C)C(C)=C1NC(=O)OCC1=CC=CC=C1 NNMRUWNFJNEETH-UHFFFAOYSA-N 0.000 description 1
- RRGSHBFSMQSUGM-UHFFFAOYSA-N benzyl n-(2-hydroxy-3,5-dimethylphenyl)carbamate Chemical compound CC1=CC(C)=C(O)C(NC(=O)OCC=2C=CC=CC=2)=C1 RRGSHBFSMQSUGM-UHFFFAOYSA-N 0.000 description 1
- HTUPVJMFLHZEOQ-UHFFFAOYSA-N benzyl n-(3,5-dichloro-4-hydroxyphenyl)carbamate Chemical compound C1=C(Cl)C(O)=C(Cl)C=C1NC(=O)OCC1=CC=CC=C1 HTUPVJMFLHZEOQ-UHFFFAOYSA-N 0.000 description 1
- KOPFOTREQYIFTR-UHFFFAOYSA-N benzyl n-(3-amino-2,4,6-trimethylphenyl)carbamate Chemical compound CC1=C(N)C(C)=CC(C)=C1NC(=O)OCC1=CC=CC=C1 KOPFOTREQYIFTR-UHFFFAOYSA-N 0.000 description 1
- QRBQFSYFWDHCMV-UHFFFAOYSA-N benzyl n-(3-chloro-4-hydroxy-2,5,6-trimethylphenyl)carbamate Chemical compound ClC1=C(O)C(C)=C(C)C(NC(=O)OCC=2C=CC=CC=2)=C1C QRBQFSYFWDHCMV-UHFFFAOYSA-N 0.000 description 1
- UAKHSJJOYILFBM-UHFFFAOYSA-N benzyl n-(3-hydroxy-2,4,5,6-tetramethylphenyl)carbamate Chemical compound CC1=C(C)C(O)=C(C)C(NC(=O)OCC=2C=CC=CC=2)=C1C UAKHSJJOYILFBM-UHFFFAOYSA-N 0.000 description 1
- GAIZNRUAAWEQHV-UHFFFAOYSA-N benzyl n-(3-hydroxy-4-methoxyphenyl)carbamate Chemical compound C1=C(O)C(OC)=CC=C1NC(=O)OCC1=CC=CC=C1 GAIZNRUAAWEQHV-UHFFFAOYSA-N 0.000 description 1
- SRNRWHCSGUTQJE-UHFFFAOYSA-N benzyl n-(4-amino-1,3,5,6-tetramethylcyclohexa-2,4-dien-1-yl)carbamate Chemical compound CC1C(C)=C(N)C(C)=CC1(C)NC(=O)OCC1=CC=CC=C1 SRNRWHCSGUTQJE-UHFFFAOYSA-N 0.000 description 1
- UYETZAQAFMUNAA-UHFFFAOYSA-N benzyl n-(4-amino-2,5-dichlorophenyl)carbamate Chemical compound C1=C(Cl)C(N)=CC(Cl)=C1NC(=O)OCC1=CC=CC=C1 UYETZAQAFMUNAA-UHFFFAOYSA-N 0.000 description 1
- BNHCQCUOQIHNPR-UHFFFAOYSA-N benzyl n-(4-amino-2,5-dimethoxyphenyl)carbamate Chemical compound C1=C(N)C(OC)=CC(NC(=O)OCC=2C=CC=CC=2)=C1OC BNHCQCUOQIHNPR-UHFFFAOYSA-N 0.000 description 1
- NZANBBBTVYSJDN-UHFFFAOYSA-N benzyl n-(4-amino-2,5-dimethylphenyl)carbamate Chemical compound C1=C(N)C(C)=CC(NC(=O)OCC=2C=CC=CC=2)=C1C NZANBBBTVYSJDN-UHFFFAOYSA-N 0.000 description 1
- QIJHAHYHTYTWPM-UHFFFAOYSA-N benzyl n-(4-amino-3,5-dichlorophenyl)carbamate Chemical compound C1=C(Cl)C(N)=C(Cl)C=C1NC(=O)OCC1=CC=CC=C1 QIJHAHYHTYTWPM-UHFFFAOYSA-N 0.000 description 1
- BJEDLHNTOKHRJA-UHFFFAOYSA-N benzyl n-(4-amino-5-methoxy-2-methylphenyl)carbamate Chemical compound C1=C(N)C(OC)=CC(NC(=O)OCC=2C=CC=CC=2)=C1C BJEDLHNTOKHRJA-UHFFFAOYSA-N 0.000 description 1
- PFBFHMTYQRNHJJ-UHFFFAOYSA-N benzyl n-(4-hydroxy-2,3,5,6-tetramethylphenyl)carbamate Chemical compound CC1=C(O)C(C)=C(C)C(NC(=O)OCC=2C=CC=CC=2)=C1C PFBFHMTYQRNHJJ-UHFFFAOYSA-N 0.000 description 1
- QQMBRPHYIIQRJD-UHFFFAOYSA-N benzyl n-(4-hydroxy-2,3,5-trimethylphenyl)carbamate Chemical compound CC1=C(O)C(C)=CC(NC(=O)OCC=2C=CC=CC=2)=C1C QQMBRPHYIIQRJD-UHFFFAOYSA-N 0.000 description 1
- FXIHRIRPOQTINM-UHFFFAOYSA-N benzyl n-(4-hydroxy-2,3,6-trimethylphenyl)carbamate Chemical compound CC1=CC(O)=C(C)C(C)=C1NC(=O)OCC1=CC=CC=C1 FXIHRIRPOQTINM-UHFFFAOYSA-N 0.000 description 1
- HPSBFMVPKMAKCH-UHFFFAOYSA-N benzyl n-(4-hydroxy-2,3-dimethylphenyl)carbamate Chemical compound CC1=C(O)C=CC(NC(=O)OCC=2C=CC=CC=2)=C1C HPSBFMVPKMAKCH-UHFFFAOYSA-N 0.000 description 1
- CAYDAEFJEMSBTQ-UHFFFAOYSA-N benzyl n-(4-hydroxy-2,5-dimethylphenyl)carbamate Chemical compound C1=C(O)C(C)=CC(NC(=O)OCC=2C=CC=CC=2)=C1C CAYDAEFJEMSBTQ-UHFFFAOYSA-N 0.000 description 1
- JZBJRJOBCACFQX-UHFFFAOYSA-N benzyl n-(4-hydroxyphenyl)carbamate Chemical compound C1=CC(O)=CC=C1NC(=O)OCC1=CC=CC=C1 JZBJRJOBCACFQX-UHFFFAOYSA-N 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 125000005619 boric acid group Chemical group 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 1
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 1
- IOLQWGVDEFWYNP-UHFFFAOYSA-N ethyl 2-bromo-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)Br IOLQWGVDEFWYNP-UHFFFAOYSA-N 0.000 description 1
- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- KXTPTVGNLXFEIK-UHFFFAOYSA-N n-methyl-1-(4-phenylphenyl)piperidin-4-amine Chemical compound C1CC(NC)CCN1C1=CC=C(C=2C=CC=CC=2)C=C1 KXTPTVGNLXFEIK-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940105631 nembutal Drugs 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- NOQXXYIGRPAZJC-UHFFFAOYSA-N oxiran-2-ylmethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1OC1 NOQXXYIGRPAZJC-UHFFFAOYSA-N 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 210000003455 parietal bone Anatomy 0.000 description 1
- 230000001936 parietal effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 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
- 239000008117 stearic acid Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- YXOAVPVMMQLKMV-UHFFFAOYSA-N tert-butyl n-(2-amino-4,5-dichlorophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(Cl)C=C1N YXOAVPVMMQLKMV-UHFFFAOYSA-N 0.000 description 1
- AZZBVTHZXQTGPG-UHFFFAOYSA-N tert-butyl n-(2-chloro-5-hydroxy-4-methoxyphenyl)carbamate Chemical compound COC1=CC(Cl)=C(NC(=O)OC(C)(C)C)C=C1O AZZBVTHZXQTGPG-UHFFFAOYSA-N 0.000 description 1
- RVXNBKSCVAMXIP-UHFFFAOYSA-N tert-butyl n-(2-hydroxy-3,4,5,6-tetramethylphenyl)carbamate Chemical compound CC1=C(C)C(C)=C(NC(=O)OC(C)(C)C)C(O)=C1C RVXNBKSCVAMXIP-UHFFFAOYSA-N 0.000 description 1
- KHDKJCIUPNLMFQ-UHFFFAOYSA-N tert-butyl n-(2-hydroxy-3,5-dimethylphenyl)carbamate Chemical compound CC1=CC(C)=C(O)C(NC(=O)OC(C)(C)C)=C1 KHDKJCIUPNLMFQ-UHFFFAOYSA-N 0.000 description 1
- GUEFWIPNCZYUAR-UHFFFAOYSA-N tert-butyl n-(3,5-dichloro-4-hydroxyphenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(O)C(Cl)=C1 GUEFWIPNCZYUAR-UHFFFAOYSA-N 0.000 description 1
- IOGMTGBAYKVBCS-UHFFFAOYSA-N tert-butyl n-(3-amino-2,4,6-trimethylphenyl)carbamate Chemical compound CC1=CC(C)=C(NC(=O)OC(C)(C)C)C(C)=C1N IOGMTGBAYKVBCS-UHFFFAOYSA-N 0.000 description 1
- NWXDAAJTOCFVEL-UHFFFAOYSA-N tert-butyl n-(3-chloro-4-hydroxy-2,5,6-trimethylphenyl)carbamate Chemical compound CC1=C(C)C(NC(=O)OC(C)(C)C)=C(C)C(Cl)=C1O NWXDAAJTOCFVEL-UHFFFAOYSA-N 0.000 description 1
- HWGOZDUQTSAICL-UHFFFAOYSA-N tert-butyl n-(3-hydroxy-2,4,5,6-tetramethylphenyl)carbamate Chemical compound CC1=C(C)C(O)=C(C)C(NC(=O)OC(C)(C)C)=C1C HWGOZDUQTSAICL-UHFFFAOYSA-N 0.000 description 1
- SDARJEUFSMUKMA-UHFFFAOYSA-N tert-butyl n-(3-hydroxy-4-methoxyphenyl)carbamate Chemical compound COC1=CC=C(NC(=O)OC(C)(C)C)C=C1O SDARJEUFSMUKMA-UHFFFAOYSA-N 0.000 description 1
- CBNKCBPRLGNVRV-UHFFFAOYSA-N tert-butyl n-(4-amino-1,3,5,6-tetramethylcyclohexa-2,4-dien-1-yl)carbamate Chemical compound CC1C(C)=C(N)C(C)=CC1(C)NC(=O)OC(C)(C)C CBNKCBPRLGNVRV-UHFFFAOYSA-N 0.000 description 1
- FXELLIXBUYYOQX-UHFFFAOYSA-N tert-butyl n-(4-amino-2,5-dichlorophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(N)C=C1Cl FXELLIXBUYYOQX-UHFFFAOYSA-N 0.000 description 1
- QZLYYEOBDDHCDT-UHFFFAOYSA-N tert-butyl n-(4-amino-2,5-dimethoxyphenyl)carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C(OC)C=C1N QZLYYEOBDDHCDT-UHFFFAOYSA-N 0.000 description 1
- PDVYKGNQYPQALA-UHFFFAOYSA-N tert-butyl n-(4-amino-2,5-dimethylphenyl)carbamate Chemical compound CC1=CC(NC(=O)OC(C)(C)C)=C(C)C=C1N PDVYKGNQYPQALA-UHFFFAOYSA-N 0.000 description 1
- IHSIFALCHVNSNY-UHFFFAOYSA-N tert-butyl n-(4-amino-3,5-dichlorophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(Cl)=C(N)C(Cl)=C1 IHSIFALCHVNSNY-UHFFFAOYSA-N 0.000 description 1
- GVWPULGIVBRUMS-UHFFFAOYSA-N tert-butyl n-(4-amino-5-methoxy-2-methylphenyl)carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=C(C)C=C1N GVWPULGIVBRUMS-UHFFFAOYSA-N 0.000 description 1
- VZMBTSBTKXWMRP-UHFFFAOYSA-N tert-butyl n-(4-hydroxy-2,3,5,6-tetramethylphenyl)carbamate Chemical compound CC1=C(C)C(NC(=O)OC(C)(C)C)=C(C)C(C)=C1O VZMBTSBTKXWMRP-UHFFFAOYSA-N 0.000 description 1
- GNLWEQIJQBMIQP-UHFFFAOYSA-N tert-butyl n-(4-hydroxy-2,3,5-trimethylphenyl)carbamate Chemical compound CC1=CC(NC(=O)OC(C)(C)C)=C(C)C(C)=C1O GNLWEQIJQBMIQP-UHFFFAOYSA-N 0.000 description 1
- JEVIOGKIJOREOJ-UHFFFAOYSA-N tert-butyl n-(4-hydroxy-2,3,6-trimethylphenyl)carbamate Chemical compound CC1=CC(O)=C(C)C(C)=C1NC(=O)OC(C)(C)C JEVIOGKIJOREOJ-UHFFFAOYSA-N 0.000 description 1
- MDGMIJLHJMGQPK-UHFFFAOYSA-N tert-butyl n-(4-hydroxy-2,3-dimethylphenyl)carbamate Chemical compound CC1=C(O)C=CC(NC(=O)OC(C)(C)C)=C1C MDGMIJLHJMGQPK-UHFFFAOYSA-N 0.000 description 1
- HYAXOCCNXTUFSN-UHFFFAOYSA-N tert-butyl n-(4-hydroxy-2,5-dimethylphenyl)carbamate Chemical compound CC1=CC(NC(=O)OC(C)(C)C)=C(C)C=C1O HYAXOCCNXTUFSN-UHFFFAOYSA-N 0.000 description 1
- YRQMBQUMJFVZLF-UHFFFAOYSA-N tert-butyl n-(4-hydroxyphenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(O)C=C1 YRQMBQUMJFVZLF-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- PUVAFTRIIUSGLK-UHFFFAOYSA-M trimethyl(oxiran-2-ylmethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1CO1 PUVAFTRIIUSGLK-UHFFFAOYSA-M 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000001262 western blot Methods 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
-
- 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
- C07D417/06—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 carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Physical Education & Sports Medicine (AREA)
- Psychology (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000112100 | 2000-04-13 | ||
| JP2000112100 | 2000-04-13 | ||
| PCT/JP2001/003198 WO2001079170A2 (en) | 2000-04-13 | 2001-04-13 | Aminophenoxyacetamide derivatives and pharmaceutical composition containing thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60130628D1 DE60130628D1 (de) | 2007-11-08 |
| DE60130628T2 true DE60130628T2 (de) | 2008-07-10 |
Family
ID=18624324
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60130628T Expired - Fee Related DE60130628T2 (de) | 2000-04-13 | 2001-04-13 | Aminophenoxyacetamid derivate und diese enthaltende pharmazeutische zusammensetzungen |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US7067533B2 (OSRAM) |
| EP (1) | EP1228367B1 (OSRAM) |
| JP (1) | JP2004501079A (OSRAM) |
| KR (1) | KR100853968B1 (OSRAM) |
| CN (1) | CN1264821C (OSRAM) |
| AT (1) | ATE374366T1 (OSRAM) |
| AU (1) | AU784930B2 (OSRAM) |
| CA (1) | CA2370487A1 (OSRAM) |
| DE (1) | DE60130628T2 (OSRAM) |
| ES (1) | ES2291308T3 (OSRAM) |
| HU (1) | HUP0203383A3 (OSRAM) |
| WO (1) | WO2001079170A2 (OSRAM) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60234616D1 (de) * | 2001-09-14 | 2010-01-14 | High Point Pharmaceuticals Llc | Substituierte piperidinen mit selektiver bindungsfähigkeit zu histamin h3-rezeptoren |
| US20030186963A1 (en) | 2001-09-14 | 2003-10-02 | Dorwald Florencio Zaragoza | Substituted piperidines |
| AU2006333522A1 (en) | 2005-12-21 | 2007-07-12 | Decode Genetics, Ehf. | Biaryl nitrogen heterocycle inhibitors of LTA4H for treating inflammation |
| DE102005062990A1 (de) * | 2005-12-28 | 2007-07-05 | Grünenthal GmbH | Substituierte Thiazole und ihre Verwendung zur Herstellung von Arzneimitteln |
| EP2151439B1 (en) | 2007-04-27 | 2014-02-26 | Daiichi Sankyo Company, Limited | Nitrogenated aromatic 6-membered ring derivative, and pharmaceutical agent comprising the same |
| WO2017066705A1 (en) * | 2015-10-14 | 2017-04-20 | Aquinnah Pharmaceuticals, Inc. | Compounds, compositions and methods of use against stress granules |
| CN109563071B (zh) | 2016-06-08 | 2021-08-03 | 葛兰素史密斯克莱知识产权发展有限公司 | 作为atf4途径抑制剂的化学化合物 |
| CN111285820A (zh) * | 2018-12-07 | 2020-06-16 | 成都康弘药业集团股份有限公司 | 一种枸橼酸莫沙必利有关物质及其制备方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW204411B (OSRAM) * | 1991-06-05 | 1993-04-21 | Tokyo Electron Co Ltd | |
| EP0982026B1 (en) | 1998-08-18 | 2006-05-17 | F. Hoffmann-La Roche Ag | Use of aryl-cyclohexylamine derivatives in the manufacture of NMDA receptor blockers |
| JP2002527477A (ja) * | 1998-10-16 | 2002-08-27 | サントリー株式会社 | 神経細胞保護作用物質としてのアミノフェノキシ酢酸誘導体 |
-
2001
- 2001-04-13 WO PCT/JP2001/003198 patent/WO2001079170A2/en not_active Ceased
- 2001-04-13 JP JP2001576772A patent/JP2004501079A/ja not_active Abandoned
- 2001-04-13 AU AU48762/01A patent/AU784930B2/en not_active Ceased
- 2001-04-13 KR KR1020017015979A patent/KR100853968B1/ko not_active Expired - Fee Related
- 2001-04-13 AT AT01921835T patent/ATE374366T1/de not_active IP Right Cessation
- 2001-04-13 CN CNB018009085A patent/CN1264821C/zh not_active Expired - Fee Related
- 2001-04-13 CA CA002370487A patent/CA2370487A1/en not_active Abandoned
- 2001-04-13 US US10/009,566 patent/US7067533B2/en not_active Expired - Fee Related
- 2001-04-13 ES ES01921835T patent/ES2291308T3/es not_active Expired - Lifetime
- 2001-04-13 HU HU0203383A patent/HUP0203383A3/hu unknown
- 2001-04-13 DE DE60130628T patent/DE60130628T2/de not_active Expired - Fee Related
- 2001-04-13 EP EP01921835A patent/EP1228367B1/en not_active Expired - Lifetime
-
2006
- 2006-01-24 US US11/337,664 patent/US20060178401A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| KR100853968B1 (ko) | 2008-08-25 |
| WO2001079170A3 (en) | 2002-06-13 |
| US7067533B2 (en) | 2006-06-27 |
| CA2370487A1 (en) | 2001-10-25 |
| KR20020016830A (ko) | 2002-03-06 |
| JP2004501079A (ja) | 2004-01-15 |
| CN1264821C (zh) | 2006-07-19 |
| ES2291308T3 (es) | 2008-03-01 |
| HUP0203383A3 (en) | 2003-11-28 |
| US20030139447A1 (en) | 2003-07-24 |
| US20060178401A1 (en) | 2006-08-10 |
| EP1228367A2 (en) | 2002-08-07 |
| EP1228367B1 (en) | 2007-09-26 |
| CN1449493A (zh) | 2003-10-15 |
| ATE374366T1 (de) | 2007-10-15 |
| WO2001079170A2 (en) | 2001-10-25 |
| AU4876201A (en) | 2001-10-30 |
| DE60130628D1 (de) | 2007-11-08 |
| AU784930B2 (en) | 2006-08-03 |
| HUP0203383A2 (hu) | 2003-02-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69918404T2 (de) | Aminophenoxyessigsäure derivate als neuroschützende mittel | |
| DE69623899T2 (de) | Behandlung von Tinnitus mit neuroprotektiven Wirkstoffen | |
| DE69925730T2 (de) | 4-benzyl-piperidin-alkylsulfoxid-heterozyklen und ihre verwendung als subtyp-selektive nmda rezeptor antagonisten | |
| DE69620191T2 (de) | (1s,2s)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanol-methansulfonat trihydrat | |
| DE60029634T2 (de) | Substituierte Piperazin-und Piperidin-Calciumkanalblocker | |
| DE69525355T2 (de) | 1-acyl-4-aliphatische aminopiperidin verbindungen | |
| DE69633016T2 (de) | Optisch reines (-) norcisaprid zur behandlung von krankheiten des verdauungstrakt | |
| DE69703617T2 (de) | Verwendung von optisch reines (+) norcisapride zur behandlung von erbrechen und zns-störungen | |
| DE69332718T2 (de) | Enantiomere von carbazolderivaten als 5-ht1-ähnliche agonisten | |
| DE60213629T2 (de) | Piperidinverbindungen als muscarinantagonisten | |
| DE60130628T2 (de) | Aminophenoxyacetamid derivate und diese enthaltende pharmazeutische zusammensetzungen | |
| DE69935331T2 (de) | Verfahren und verbindungen zur behandlung der depression | |
| JP2007518742A (ja) | Ｎ型カルシウムチャネル遮断薬としての３−アミノピロリジン誘導体 | |
| DE60029954T2 (de) | Dermale anästhetika | |
| DE19602964A1 (de) | Neue Morphinderivate, Verfahren zu deren Herstellung und deren Verwendung | |
| DE60025348T2 (de) | Ethansulfonyl-piperidin-derivate | |
| DE60009287T2 (de) | Neuartige isoquinolin-derivate oder salze davon | |
| DE69926776T2 (de) | Quinalozinon-derivate | |
| DE69230498T2 (de) | 2-Pyrazinylethylamin-Derivate und ihre Verwendung als Arzneimittel. | |
| DE3153030C2 (de) | Verwendung von (2S,3R)-3-Amino-2-hydroxy-4-phenylbutansäureverbindungen als Immunverstärkungsmittel | |
| KR20070044803A (ko) | 칼슘 채널 차단제로서 디아릴아민 유도체 | |
| DD139842A5 (de) | Verfahren zur herstellung quaternaerer ammoniumsalze von phenylpropylaminen und phenylbutylaminen | |
| DE69024385T2 (de) | Verbindung zur Behandlung von Störungen des Neurotransmittersystems im Gehirn | |
| DE60307049T2 (de) | Verwendung von Piperazin- Phenothiazin- Derivaten zur Herstellung eines Arzneimittels mit neuroprotektiven und/oder neurotropischen Wirkungen auf das ZNS und/oder PNS | |
| DD253616A5 (de) | Verfahren zur herstellung von neuen pleunromutilinderivaten |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |