TW438800B - N-(2-benzothiazolyl)-1-piperidineethanamine derivatives, their preparation and their use in therapy - Google Patents
N-(2-benzothiazolyl)-1-piperidineethanamine derivatives, their preparation and their use in therapy Download PDFInfo
- Publication number
- TW438800B TW438800B TW086114229A TW86114229A TW438800B TW 438800 B TW438800 B TW 438800B TW 086114229 A TW086114229 A TW 086114229A TW 86114229 A TW86114229 A TW 86114229A TW 438800 B TW438800 B TW 438800B
- Authority
- TW
- Taiwan
- Prior art keywords
- general formula
- patent application
- compound
- scope
- item
- Prior art date
Links
- 238000002560 therapeutic procedure Methods 0.000 title claims abstract description 5
- 238000002360 preparation method Methods 0.000 title claims description 4
- SLDOBMOFHWAPFE-UHFFFAOYSA-N n-(2-piperidin-1-ylethyl)-1,3-benzothiazol-2-amine Chemical class N=1C2=CC=CC=C2SC=1NCCN1CCCCC1 SLDOBMOFHWAPFE-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 62
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 8
- 125000005843 halogen group Chemical group 0.000 claims abstract description 6
- 239000001257 hydrogen Substances 0.000 claims abstract 3
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 3
- 239000000203 mixture Substances 0.000 claims description 34
- -1 methylfluorenyl Chemical group 0.000 claims description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 19
- 238000011049 filling Methods 0.000 claims description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 8
- 235000015170 shellfish Nutrition 0.000 claims description 8
- 230000027455 binding Effects 0.000 claims description 7
- 239000007789 gas Substances 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical group [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 229910052786 argon Inorganic materials 0.000 claims description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 4
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 4
- 230000002079 cooperative effect Effects 0.000 claims description 4
- 239000012458 free base Substances 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- 239000002798 polar solvent Substances 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- 208000010496 Heart Arrest Diseases 0.000 claims description 3
- 206010021143 Hypoxia Diseases 0.000 claims description 3
- 230000005856 abnormality Effects 0.000 claims description 3
- 150000001409 amidines Chemical class 0.000 claims description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 3
- 206010008118 cerebral infarction Diseases 0.000 claims description 3
- 238000012937 correction Methods 0.000 claims description 3
- 229960003638 dopamine Drugs 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 230000007954 hypoxia Effects 0.000 claims description 3
- 230000004770 neurodegeneration Effects 0.000 claims description 3
- NJAHGEUFOYIGKR-UHFFFAOYSA-N 2-chloroethanimidamide Chemical compound NC(=N)CCl NJAHGEUFOYIGKR-UHFFFAOYSA-N 0.000 claims description 2
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 206010008027 Cerebellar atrophy Diseases 0.000 claims description 2
- 235000015510 Cucumis melo subsp melo Nutrition 0.000 claims description 2
- 208000020401 Depressive disease Diseases 0.000 claims description 2
- 208000027776 Extrapyramidal disease Diseases 0.000 claims description 2
- 208000010412 Glaucoma Diseases 0.000 claims description 2
- 206010028923 Neonatal asphyxia Diseases 0.000 claims description 2
- 208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 claims description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 2
- 206010038669 Respiratory arrest Diseases 0.000 claims description 2
- 206010039966 Senile dementia Diseases 0.000 claims description 2
- 208000032109 Transient ischaemic attack Diseases 0.000 claims description 2
- 241000700605 Viruses Species 0.000 claims description 2
- FJJCIZWZNKZHII-UHFFFAOYSA-N [4,6-bis(cyanoamino)-1,3,5-triazin-2-yl]cyanamide Chemical compound N#CNC1=NC(NC#N)=NC(NC#N)=N1 FJJCIZWZNKZHII-UHFFFAOYSA-N 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 230000036506 anxiety Effects 0.000 claims description 2
- 244000309464 bull Species 0.000 claims description 2
- 230000000747 cardiac effect Effects 0.000 claims description 2
- 235000013339 cereals Nutrition 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 230000001684 chronic effect Effects 0.000 claims description 2
- 230000001149 cognitive effect Effects 0.000 claims description 2
- 210000003016 hypothalamus Anatomy 0.000 claims description 2
- 125000003453 indazolyl group Chemical class N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 208000014674 injury Diseases 0.000 claims description 2
- 208000028867 ischemia Diseases 0.000 claims description 2
- 201000003102 mental depression Diseases 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 230000003533 narcotic effect Effects 0.000 claims description 2
- 210000005036 nerve Anatomy 0.000 claims description 2
- 208000033300 perinatal asphyxia Diseases 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 230000007101 progressive neurodegeneration Effects 0.000 claims description 2
- 208000020016 psychiatric disease Diseases 0.000 claims description 2
- 201000000980 schizophrenia Diseases 0.000 claims description 2
- 229940125723 sedative agent Drugs 0.000 claims description 2
- 239000000932 sedative agent Substances 0.000 claims description 2
- 201000010875 transient cerebral ischemia Diseases 0.000 claims description 2
- 230000008733 trauma Effects 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 5
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims 3
- 125000004429 atom Chemical group 0.000 claims 2
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims 2
- VUTBELPREDJDDH-UHFFFAOYSA-N 4-amino-5-hydroxymethyl-2-methylpyrimidine Chemical compound CC1=NC=C(CO)C(N)=N1 VUTBELPREDJDDH-UHFFFAOYSA-N 0.000 claims 1
- ROVQGRPLADKXPX-UHFFFAOYSA-N CN1[CH-]OC2=C1C=CC=C2 Chemical compound CN1[CH-]OC2=C1C=CC=C2 ROVQGRPLADKXPX-UHFFFAOYSA-N 0.000 claims 1
- 244000241257 Cucumis melo Species 0.000 claims 1
- 206010012289 Dementia Diseases 0.000 claims 1
- 206010012335 Dependence Diseases 0.000 claims 1
- 101150043870 Drd4 gene Proteins 0.000 claims 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims 1
- 208000023105 Huntington disease Diseases 0.000 claims 1
- 240000007817 Olea europaea Species 0.000 claims 1
- 230000002490 cerebral effect Effects 0.000 claims 1
- 230000000302 ischemic effect Effects 0.000 claims 1
- 208000015122 neurodegenerative disease Diseases 0.000 claims 1
- 238000012856 packing Methods 0.000 claims 1
- 230000000750 progressive effect Effects 0.000 claims 1
- 230000002441 reversible effect Effects 0.000 claims 1
- 210000003625 skull Anatomy 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 230000002792 vascular Effects 0.000 claims 1
- 208000019553 vascular disease Diseases 0.000 claims 1
- 238000007631 vascular surgery Methods 0.000 claims 1
- 238000005406 washing Methods 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 238000012360 testing method Methods 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- 230000008018 melting Effects 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 230000004083 survival effect Effects 0.000 description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 210000001715 carotid artery Anatomy 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 3
- IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 201000006474 Brain Ischemia Diseases 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 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
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 210000003657 middle cerebral artery Anatomy 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- UOUUKBKHBOFSJV-UHFFFAOYSA-N 1,2-dimethylpyrene Chemical compound C1=CC=C2C=CC3=C(C)C(C)=CC4=CC=C1C2=C43 UOUUKBKHBOFSJV-UHFFFAOYSA-N 0.000 description 1
- WHHYMBKESAOOSX-UHFFFAOYSA-N 1,3-benzoxazole-2-carboxamide Chemical compound C1=CC=C2OC(C(=O)N)=NC2=C1 WHHYMBKESAOOSX-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- NGQQUXXTDZADNX-UHFFFAOYSA-N 2,3,4,5-tetrachlorofuran Chemical compound ClC=1OC(Cl)=C(Cl)C=1Cl NGQQUXXTDZADNX-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
- BBDCCXMBOJDLMO-UHFFFAOYSA-N 4-benzyl-1-(2-chloroethyl)piperidine Chemical compound C1CN(CCCl)CCC1CC1=CC=CC=C1 BBDCCXMBOJDLMO-UHFFFAOYSA-N 0.000 description 1
- ABGXADJDTPFFSZ-UHFFFAOYSA-N 4-benzylpiperidine Chemical compound C=1C=CC=CC=1CC1CCNCC1 ABGXADJDTPFFSZ-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000219112 Cucumis Species 0.000 description 1
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-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
- 206010061216 Infarction Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- PWUBONDMIMDOQY-UHFFFAOYSA-N acetonitrile;hydrochloride Chemical compound Cl.CC#N PWUBONDMIMDOQY-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- FJTKCFSPYUMXJB-UHFFFAOYSA-N bevantolol hydrochloride Chemical compound [Cl-].C1=C(OC)C(OC)=CC=C1CC[NH2+]CC(O)COC1=CC=CC(C)=C1 FJTKCFSPYUMXJB-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000001627 cerebral artery Anatomy 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- IRXRGVFLQOSHOH-UHFFFAOYSA-L dipotassium;oxalate Chemical compound [K+].[K+].[O-]C(=O)C([O-])=O IRXRGVFLQOSHOH-UHFFFAOYSA-L 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- OUAQKVIBEFYQDD-UHFFFAOYSA-N ethanamine;oxalic acid Chemical compound CCN.OC(=O)C(O)=O OUAQKVIBEFYQDD-UHFFFAOYSA-N 0.000 description 1
- WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 238000002309 gasification Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- VEIWYFRREFUNRC-UHFFFAOYSA-N hydron;piperidine;chloride Chemical compound [Cl-].C1CC[NH2+]CC1 VEIWYFRREFUNRC-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000007654 ischemic lesion Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- UPKIHOQVIBBESY-UHFFFAOYSA-N magnesium;carbanide Chemical compound [CH3-].[CH3-].[Mg+2] UPKIHOQVIBBESY-UHFFFAOYSA-N 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
- UWTNRIHEKDEGRW-UHFFFAOYSA-N methane methanol Chemical compound [H]C[H].[H]C[H].[H]CO[H] UWTNRIHEKDEGRW-UHFFFAOYSA-N 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- BYYLVIMOFHNUDJ-UHFFFAOYSA-N n-(1,3-benzothiazol-2-yl)formamide Chemical compound C1=CC=C2SC(NC=O)=NC2=C1 BYYLVIMOFHNUDJ-UHFFFAOYSA-N 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- ILXAOQAXSHVHTM-UHFFFAOYSA-M sodium;2-amino-2-(hydroxymethyl)propane-1,3-diol;chloride Chemical compound [Na+].[Cl-].OCC(N)(CO)CO ILXAOQAXSHVHTM-UHFFFAOYSA-M 0.000 description 1
- 229950001675 spiperone Drugs 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000004992 toluidines Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 230000008016 vaporization Effects 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
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9611925A FR2753970B1 (fr) | 1996-10-01 | 1996-10-01 | Derives de n-(benzothiazol-2-yl) piperidine-1-ethanamine, leur preparation et leur application en therapeutique |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW438800B true TW438800B (en) | 2001-06-07 |
Family
ID=9496217
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW086114229A TW438800B (en) | 1996-10-01 | 1997-09-30 | N-(2-benzothiazolyl)-1-piperidineethanamine derivatives, their preparation and their use in therapy |
Country Status (23)
| Country | Link |
|---|---|
| EP (1) | EP0929550A1 (cs) |
| JP (1) | JP2001501217A (cs) |
| KR (1) | KR20000048767A (cs) |
| CN (1) | CN1230959A (cs) |
| AR (1) | AR009105A1 (cs) |
| AU (1) | AU722147B2 (cs) |
| BG (1) | BG103271A (cs) |
| BR (1) | BR9711842A (cs) |
| CA (1) | CA2266510A1 (cs) |
| CO (1) | CO4650030A1 (cs) |
| CZ (1) | CZ112699A3 (cs) |
| EE (1) | EE9900135A (cs) |
| FR (1) | FR2753970B1 (cs) |
| HU (1) | HUP9904091A3 (cs) |
| IL (1) | IL128902A (cs) |
| NO (1) | NO991581L (cs) |
| NZ (1) | NZ334553A (cs) |
| PL (1) | PL332648A1 (cs) |
| SK (1) | SK42299A3 (cs) |
| TR (1) | TR199900634T2 (cs) |
| TW (1) | TW438800B (cs) |
| WO (1) | WO1998014444A1 (cs) |
| ZA (1) | ZA978772B (cs) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9725541D0 (en) * | 1997-12-02 | 1998-02-04 | Pharmacia & Upjohn Spa | Amino-benzothiazole derivatives |
| US6107313A (en) * | 1998-10-02 | 2000-08-22 | Combichem, Inc. | Dopamine receptor antagonists |
| RU2251419C2 (ru) | 2000-06-21 | 2005-05-10 | Ф. Хоффманн-Ля Рош Аг | Производные бензотиазола |
| US7087761B2 (en) | 2003-01-07 | 2006-08-08 | Hoffmann-La Roche Inc. | Cyclization process for substituted benzothiazole derivatives |
| EP1680408A2 (en) * | 2003-10-24 | 2006-07-19 | F. Hoffmann-La Roche Ag | Ccr3 receptor antagonists |
| AU2005247567B2 (en) | 2004-05-24 | 2010-09-02 | F. Hoffmann-La Roche Ag | 4-hydroxy-4-methyl-piperidine-1-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide |
| EP1812392B1 (en) | 2004-11-05 | 2008-07-09 | F.Hoffmann-La Roche Ag | Process for preparation of isonicotinic acid derivatives |
| PT1863818E (pt) | 2005-03-23 | 2010-04-09 | Hoffmann La Roche | Derivados de acetilenil-pirazolo-pirimidina como antagonistas de mglur2 |
| ATE463495T1 (de) | 2005-09-27 | 2010-04-15 | Hoffmann La Roche | Oxadiazolylpyrazolopyrimidine als mglur2- antagonisten |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1260474A (en) * | 1984-12-03 | 1989-09-26 | Raymond A. Stokbroekx | Benzoxazol- and benzothiazolamine derivatives |
| KR930005004B1 (ko) * | 1985-04-15 | 1993-06-11 | 쟈안센 파아마슈우티카 엔. 부이. | 치환된 n-[(4-피페리디닐)알킬]이환 축합 옥사졸아민 및 티아졸아민의 제조방법 |
-
1996
- 1996-10-01 FR FR9611925A patent/FR2753970B1/fr not_active Expired - Fee Related
-
1997
- 1997-09-26 HU HU9904091A patent/HUP9904091A3/hu unknown
- 1997-09-26 BR BR9711842A patent/BR9711842A/pt not_active Application Discontinuation
- 1997-09-26 EE EEP199900135A patent/EE9900135A/xx unknown
- 1997-09-26 JP JP10516272A patent/JP2001501217A/ja active Pending
- 1997-09-26 AU AU44638/97A patent/AU722147B2/en not_active Ceased
- 1997-09-26 IL IL12890297A patent/IL128902A/en not_active IP Right Cessation
- 1997-09-26 PL PL97332648A patent/PL332648A1/xx unknown
- 1997-09-26 CO CO97056315A patent/CO4650030A1/es unknown
- 1997-09-26 KR KR1019990702753A patent/KR20000048767A/ko not_active Withdrawn
- 1997-09-26 WO PCT/FR1997/001692 patent/WO1998014444A1/fr not_active Ceased
- 1997-09-26 CA CA002266510A patent/CA2266510A1/en not_active Abandoned
- 1997-09-26 SK SK422-99A patent/SK42299A3/sk unknown
- 1997-09-26 NZ NZ334553A patent/NZ334553A/xx unknown
- 1997-09-26 CN CN97198112A patent/CN1230959A/zh active Pending
- 1997-09-26 CZ CZ991126A patent/CZ112699A3/cs unknown
- 1997-09-26 TR TR1999/00634T patent/TR199900634T2/xx unknown
- 1997-09-26 EP EP97943001A patent/EP0929550A1/fr not_active Ceased
- 1997-09-30 ZA ZA9708772A patent/ZA978772B/xx unknown
- 1997-09-30 TW TW086114229A patent/TW438800B/zh active
- 1997-09-30 AR ARP970104493A patent/AR009105A1/es not_active Application Discontinuation
-
1999
- 1999-03-22 BG BG103271A patent/BG103271A/xx unknown
- 1999-03-30 NO NO991581A patent/NO991581L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| BG103271A (en) | 2000-05-31 |
| SK42299A3 (en) | 1999-12-10 |
| JP2001501217A (ja) | 2001-01-30 |
| TR199900634T2 (xx) | 1999-06-21 |
| PL332648A1 (en) | 1999-09-27 |
| AU722147B2 (en) | 2000-07-20 |
| KR20000048767A (ko) | 2000-07-25 |
| EE9900135A (et) | 1999-12-15 |
| NZ334553A (en) | 2000-11-24 |
| CN1230959A (zh) | 1999-10-06 |
| IL128902A0 (en) | 2000-02-17 |
| FR2753970B1 (fr) | 1998-10-30 |
| CZ112699A3 (cs) | 1999-06-16 |
| IL128902A (en) | 2001-07-24 |
| BR9711842A (pt) | 1999-08-24 |
| CO4650030A1 (es) | 1998-09-03 |
| HUP9904091A2 (hu) | 2000-05-28 |
| WO1998014444A1 (fr) | 1998-04-09 |
| NO991581L (no) | 1999-06-01 |
| NO991581D0 (no) | 1999-03-30 |
| AR009105A1 (es) | 2000-03-08 |
| FR2753970A1 (fr) | 1998-04-03 |
| HUP9904091A3 (en) | 2000-07-28 |
| EP0929550A1 (fr) | 1999-07-21 |
| AU4463897A (en) | 1998-04-24 |
| ZA978772B (en) | 1998-03-27 |
| CA2266510A1 (en) | 1998-04-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101694551B1 (ko) | 로티고틴의 다형 형태 | |
| WO2024008129A1 (zh) | 作为kat6抑制剂的化合物 | |
| WO1988002365A1 (fr) | Derives d'amines cycliques | |
| JP2017538712A (ja) | 細胞壊死の抑制剤及びそれに関連する方法 | |
| TW541307B (en) | 1,4-diazabicyclo [3.2.2] nonabenzoxazole, -benzothiazole and -benzimidazole derivatives, their preparation and their therapeutic application | |
| TW438746B (en) | New phenylamidine derivatives, processes for preparing them and their use as pharmaceutical compositions | |
| WO2025007938A1 (zh) | 一类细胞程序性坏死抑制剂及其制备方法和用途 | |
| JP2005516898A (ja) | Ｓｓｔ１アンタゴニスト活性を有するピペラジン誘導体 | |
| CN110172058B (zh) | 7-氮杂螺[5.6]十二烷-10-酮类化合物及其制备方法与用途 | |
| CN120302969A (zh) | 可用作iap抑制剂的化合物和组合物 | |
| TW219329B (cs) | ||
| AU722147B2 (en) | N-(benzothiazol-2-yl) piperidine-1-ethanamine derivatives, their preparation and application in therapeutics | |
| JPH02178263A (ja) | アザアズレン誘導体、その製造法およびそれを有効成分とする抗アレルギー剤および抗炎症剤 | |
| Zhang et al. | A drug–drug cocrystal and a co-amorphous form, prepared from honokiol and ligustrazine, inspired by Chinese patent medicine | |
| TW520370B (en) | Benzooxazole derivatives and a pharmaceutical composition containing the derivatives as an active ingredient | |
| CN112939864B (zh) | 螺[苯并[c]氮杂-1,1’-环己基]-3-酮类化合物 | |
| TW206230B (cs) | ||
| CN101307043A (zh) | 6,8-二羟甲基白杨素和6,8-二羟甲基醚白杨素及其制备方法与药物用途 | |
| CN112457265A (zh) | 四氮唑类衍生物、制备、含其的药物组合物及其应用 | |
| EP3677581A1 (en) | Deuterated indoleamine 2,3-dioxygenase inhibitor and application thereof | |
| JPH0558998A (ja) | カルバゾール誘導体 | |
| JP4796622B2 (ja) | （３，４−ジヒドロ−キナゾリン−２−イル）−インダン−１−イル−アミン | |
| JPH03505456A (ja) | ３―［２―（４―アリールピペラジン―１―イル）エトキシ］―ｐ―シメン、フェニル環上のオルトー、メターおよびパラーモノ置換またはジ置換された該生成物の誘導体、該誘導体の調製法および活性素として存在する該化合物の医薬 | |
| TW434230B (en) | 5-aminoethoxy-1,4-dihydroquinoxaline-2,3-diones | |
| WO2024056079A1 (zh) | 内匹司他酸加成盐的多晶型及其制备方法和用途 |