CA2266510A1 - N-(benzothiazol-2-yl) piperidine-1-ethanamine derivatives, their preparation and application in therapeutics - Google Patents
N-(benzothiazol-2-yl) piperidine-1-ethanamine derivatives, their preparation and application in therapeutics Download PDFInfo
- Publication number
- CA2266510A1 CA2266510A1 CA002266510A CA2266510A CA2266510A1 CA 2266510 A1 CA2266510 A1 CA 2266510A1 CA 002266510 A CA002266510 A CA 002266510A CA 2266510 A CA2266510 A CA 2266510A CA 2266510 A1 CA2266510 A1 CA 2266510A1
- Authority
- CA
- Canada
- Prior art keywords
- general formula
- compound
- methyl
- mixture
- reacted
- 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.)
- Abandoned
Links
- 239000003814 drug Substances 0.000 title claims abstract 3
- 238000002360 preparation method Methods 0.000 title 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 48
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- 125000005843 halogen group Chemical group 0.000 claims abstract description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 3
- 239000001257 hydrogen Substances 0.000 claims abstract description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 33
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 9
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- QVKPPRYUGJFISN-UHFFFAOYSA-N n-methyl-1,3-benzothiazol-2-amine Chemical compound C1=CC=C2SC(NC)=NC2=C1 QVKPPRYUGJFISN-UHFFFAOYSA-N 0.000 claims description 6
- IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 claims description 4
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 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
- 239000002253 acid Substances 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- CXLNKIFVGQZLQR-UHFFFAOYSA-N n-(1,3-benzothiazol-2-yl)-2-chloroacetamide;hydrochloride Chemical compound Cl.C1=CC=C2SC(NC(=O)CCl)=NC2=C1 CXLNKIFVGQZLQR-UHFFFAOYSA-N 0.000 description 4
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
- 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
- 229910010277 boron hydride Inorganic materials 0.000 description 3
- 208000026106 cerebrovascular disease Diseases 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 210000003657 middle cerebral artery Anatomy 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000001953 recrystallisation Methods 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
- 229950001675 spiperone Drugs 0.000 description 3
- 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 2
- UHGULLIUJBCTEF-UHFFFAOYSA-N 2-aminobenzothiazole Chemical compound C1=CC=C2SC(N)=NC2=C1 UHGULLIUJBCTEF-UHFFFAOYSA-N 0.000 description 2
- BBDCCXMBOJDLMO-UHFFFAOYSA-N 4-benzyl-1-(2-chloroethyl)piperidine Chemical compound C1CN(CCCl)CCC1CC1=CC=CC=C1 BBDCCXMBOJDLMO-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- YBCVSNPQNYTAIT-UHFFFAOYSA-N C(C(=O)O)(=O)O.S1C(=NC2=C1C=CC=C2)N(CCN2CCC(CC2)CC2=CC=CC=C2)C Chemical compound C(C(=O)O)(=O)O.S1C(=NC2=C1C=CC=C2)N(CCN2CCC(CC2)CC2=CC=CC=C2)C YBCVSNPQNYTAIT-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-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
- 208000010496 Heart Arrest Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-L Oxalate Chemical compound [O-]C(=O)C([O-])=O MUBZPKHOEPUJKR-UHFFFAOYSA-L 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 206010038669 Respiratory arrest Diseases 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 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 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 210000004004 carotid artery internal Anatomy 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 206010008118 cerebral infarction Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 230000003291 dopaminomimetic effect Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- 238000000338 in vitro Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- MMBISVWHTPKGSJ-UHFFFAOYSA-N n-(1,3-benzothiazol-2-yl)-2-(4-phenylpiperidin-1-yl)acetamide Chemical compound N=1C2=CC=CC=C2SC=1NC(=O)CN(CC1)CCC1C1=CC=CC=C1 MMBISVWHTPKGSJ-UHFFFAOYSA-N 0.000 description 2
- PSLLPDLRUUYRGN-UHFFFAOYSA-N n-(1,3-benzothiazol-2-yl)-2-[4-[2-(4-fluorophenyl)ethyl]piperidin-1-yl]acetamide Chemical compound C1=CC(F)=CC=C1CCC1CCN(CC(=O)NC=2SC3=CC=CC=C3N=2)CC1 PSLLPDLRUUYRGN-UHFFFAOYSA-N 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- PKDBCJSWQUOKDO-UHFFFAOYSA-M 2,3,5-triphenyltetrazolium chloride Chemical compound [Cl-].C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 PKDBCJSWQUOKDO-UHFFFAOYSA-M 0.000 description 1
- ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-UHFFFAOYSA-N 0.000 description 1
- OJKWWANXBGLGQN-UHFFFAOYSA-N 4-[(4-fluorophenyl)methyl]piperidine;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1CC1CCNCC1 OJKWWANXBGLGQN-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
- UTBULQCHEUWJNV-UHFFFAOYSA-N 4-phenylpiperidine Chemical compound C1CNCCC1C1=CC=CC=C1 UTBULQCHEUWJNV-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
- 208000027776 Extrapyramidal disease Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- VMYRZYSUYHDNMI-UHFFFAOYSA-N N-(1,3-benzothiazol-2-yl)-2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]acetamide Chemical compound S1C(=NC2=C1C=CC=C2)NC(CN2CCC(CC2)CC2=CC=C(C=C2)F)=O VMYRZYSUYHDNMI-UHFFFAOYSA-N 0.000 description 1
- VOKQQIVOVIBLDU-UHFFFAOYSA-N N-[2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]ethyl]-1,3-benzothiazol-2-amine oxalic acid Chemical compound C(C(=O)O)(=O)O.S1C(=NC2=C1C=CC=C2)NCCN2CCC(CC2)CC2=CC=C(C=C2)F VOKQQIVOVIBLDU-UHFFFAOYSA-N 0.000 description 1
- 206010028923 Neonatal asphyxia Diseases 0.000 description 1
- 208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 206010033664 Panic attack Diseases 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910000091 aluminium hydride Inorganic materials 0.000 description 1
- QXAITBQSYVNQDR-UHFFFAOYSA-N amitraz Chemical compound C=1C=C(C)C=C(C)C=1N=CN(C)C=NC1=CC=C(C)C=C1C QXAITBQSYVNQDR-UHFFFAOYSA-N 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 238000001949 anaesthesia Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000007675 cardiac surgery Methods 0.000 description 1
- 210000001168 carotid artery common Anatomy 0.000 description 1
- 210000000269 carotid artery external Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 230000001146 hypoxic effect Effects 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
- 208000014674 injury Diseases 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- KDXZREBVGAGZHS-UHFFFAOYSA-M methohexital sodium Chemical compound [Na+].CCC#CC(C)C1(CC=C)C(=O)N=C([O-])N(C)C1=O KDXZREBVGAGZHS-UHFFFAOYSA-M 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- MVPUGXJYDXAIOD-UHFFFAOYSA-N n-[2-(4-phenylpiperidin-1-yl)ethyl]-1,3-benzothiazol-2-amine Chemical compound N=1C2=CC=CC=C2SC=1NCCN(CC1)CCC1C1=CC=CC=C1 MVPUGXJYDXAIOD-UHFFFAOYSA-N 0.000 description 1
- HOPVACMFVYCYHG-UHFFFAOYSA-N n-[2-[4-[2-(4-fluorophenyl)ethyl]piperidin-1-yl]ethyl]-1,3-benzothiazol-2-amine Chemical compound C1=CC(F)=CC=C1CCC1CCN(CCNC=2SC3=CC=CC=C3N=2)CC1 HOPVACMFVYCYHG-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 208000031237 olivopontocerebellar atrophy Diseases 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 208000033300 perinatal asphyxia Diseases 0.000 description 1
- 208000019899 phobic disease Diseases 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 201000000980 schizophrenia Diseases 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
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 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
- 238000001890 transfection Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000008096 xylene Substances 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 (3)
| 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 |
| FR96/11925 | 1996-10-01 | ||
| PCT/FR1997/001692 WO1998014444A1 (fr) | 1996-10-01 | 1997-09-26 | Derives de n-(benzothiazol-2-yl)piperidine-1-ethanamine, leur preparation et leur application en therapeutique |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2266510A1 true CA2266510A1 (en) | 1998-04-09 |
Family
ID=9496217
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002266510A Abandoned CA2266510A1 (en) | 1996-10-01 | 1997-09-26 | N-(benzothiazol-2-yl) piperidine-1-ethanamine derivatives, their preparation and application in therapeutics |
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 |
| HRP20020962A2 (en) | 2000-06-21 | 2005-02-28 | F. Hoffmann - La Roche Ag | Benzothiazole derivatives |
| US7087761B2 (en) | 2003-01-07 | 2006-08-08 | Hoffmann-La Roche Inc. | Cyclization process for substituted benzothiazole derivatives |
| KR20060061393A (ko) * | 2003-10-24 | 2006-06-07 | 에프. 호프만-라 로슈 아게 | Ｃｃｒ3 수용체 길항제 |
| PT1753760E (pt) | 2004-05-24 | 2008-02-12 | Hoffmann La Roche | '' - metoxi - 7 - morfolin - 4 - il - benzotiazol - 2 - il) - amida do ácido 4 - hidroxi - 4 - metil - piperidina - 1 - carboxílico'' |
| DE602005008095D1 (de) | 2004-11-05 | 2008-08-21 | Hoffmann La Roche | Verfahren zur herstellung von isonikotinsäurederivaten |
| ES2339477T3 (es) | 2005-03-23 | 2010-05-20 | F.Hoffmann-La Roche Ag | Derivados de acetilenil-pirazolo-pirimidina como antagonistas de mglur2. |
| DE602006013493D1 (de) | 2005-09-27 | 2010-05-20 | 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 EE EEP199900135A patent/EE9900135A/xx unknown
- 1997-09-26 TR TR1999/00634T patent/TR199900634T2/xx unknown
- 1997-09-26 CZ CZ991126A patent/CZ112699A3/cs unknown
- 1997-09-26 AU AU44638/97A patent/AU722147B2/en not_active Ceased
- 1997-09-26 KR KR1019990702753A patent/KR20000048767A/ko not_active Withdrawn
- 1997-09-26 WO PCT/FR1997/001692 patent/WO1998014444A1/fr not_active Application Discontinuation
- 1997-09-26 CA CA002266510A patent/CA2266510A1/en not_active Abandoned
- 1997-09-26 SK SK422-99A patent/SK42299A3/sk unknown
- 1997-09-26 HU HU9904091A patent/HUP9904091A3/hu unknown
- 1997-09-26 CN CN97198112A patent/CN1230959A/zh active Pending
- 1997-09-26 IL IL12890297A patent/IL128902A/en not_active IP Right Cessation
- 1997-09-26 BR BR9711842A patent/BR9711842A/pt not_active Application Discontinuation
- 1997-09-26 EP EP97943001A patent/EP0929550A1/fr not_active Ceased
- 1997-09-26 CO CO97056315A patent/CO4650030A1/es unknown
- 1997-09-26 NZ NZ334553A patent/NZ334553A/xx unknown
- 1997-09-26 PL PL97332648A patent/PL332648A1/xx unknown
- 1997-09-26 JP JP10516272A patent/JP2001501217A/ja active Pending
- 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 |
|---|---|
| WO1998014444A1 (fr) | 1998-04-09 |
| EE9900135A (et) | 1999-12-15 |
| CO4650030A1 (es) | 1998-09-03 |
| PL332648A1 (en) | 1999-09-27 |
| KR20000048767A (ko) | 2000-07-25 |
| HUP9904091A2 (hu) | 2000-05-28 |
| FR2753970A1 (fr) | 1998-04-03 |
| CN1230959A (zh) | 1999-10-06 |
| CZ112699A3 (cs) | 1999-06-16 |
| BR9711842A (pt) | 1999-08-24 |
| IL128902A0 (en) | 2000-02-17 |
| HUP9904091A3 (en) | 2000-07-28 |
| AU722147B2 (en) | 2000-07-20 |
| TR199900634T2 (xx) | 1999-06-21 |
| SK42299A3 (en) | 1999-12-10 |
| TW438800B (en) | 2001-06-07 |
| NO991581L (no) | 1999-06-01 |
| NZ334553A (en) | 2000-11-24 |
| BG103271A (en) | 2000-05-31 |
| AR009105A1 (es) | 2000-03-08 |
| ZA978772B (en) | 1998-03-27 |
| FR2753970B1 (fr) | 1998-10-30 |
| EP0929550A1 (fr) | 1999-07-21 |
| AU4463897A (en) | 1998-04-24 |
| NO991581D0 (no) | 1999-03-30 |
| JP2001501217A (ja) | 2001-01-30 |
| IL128902A (en) | 2001-07-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2756742B2 (ja) | Ｎ−アシル−２，３−ベンゾジアゼピン誘導体、その製造法、それを含有する医薬組成物、およびその製造法 | |
| ES2288839T3 (es) | Compuestos del triazol con afinidad para el receptor de la dopamina-d3. | |
| US20060223861A1 (en) | Derivatives of N-[phenyl(alkylpiperidine-2-yl)methyl]benzamide, preparation method thereof and application of same in therapeutics | |
| HUP0004422A2 (hu) | 2-Aril-8-oxohidropurin-származékok, eljárás előállításukra, ilyen vegyületeket tartalmazó gyógyászati készítmények | |
| MX2008016492A (es) | Derivados de urea de tropano, su preparacion y su aplicacion terapeutica. | |
| US4879300A (en) | Novel piperidine derivatives | |
| JP2017538712A (ja) | 細胞壊死の抑制剤及びそれに関連する方法 | |
| JPS63146874A (ja) | インドール誘導体 | |
| NZ230068A (en) | Indazole-3-carboxylic acid esters and amides of diaza compounds having 6,7, or 8 ring members: preparatory processes and pharmaceutical compositions | |
| EP0337767B1 (en) | Cyclic amides | |
| SK283833B6 (sk) | Deriváty benzoxadiazolu, benzotiadiazolu, benzotriazolu a chinoxalínu, spôsob ich prípravy, farmaceutická kompozícia, ktorá ich obsahuje, a ich použitie | |
| GB2203431A (en) | Psychotropic bicyclic imides | |
| CA2266510A1 (en) | N-(benzothiazol-2-yl) piperidine-1-ethanamine derivatives, their preparation and application in therapeutics | |
| EP1581522B1 (en) | Flavaxate derivatives as muscarinic receptor antagonists | |
| JP2005516898A (ja) | Ｓｓｔ１アンタゴニスト活性を有するピペラジン誘導体 | |
| US5712288A (en) | Quaternary basic amides, method of preparing them and pharmaceutical compositions in which they are present | |
| RU2418794C2 (ru) | ПРОИЗВОДНЫЕ ИЗОХИНОЛИНА И БЕНЗО[h]ИЗОХИНОЛИНА, ИХ ПОЛУЧЕНИЕ И ИХ ПРИМЕНЕНИЕ В ТЕРАПИИ В КАЧЕСТВЕ АНТАГОНИСТОВ РЕЦЕПТОРА ГИСТАМИНА H3 | |
| 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 | |
| US4659731A (en) | 2-(4,5-Dihydro-1H-imidazol-2-yl)-2,3-dihydroindole derivatives and their application as α2 receptor antagonist or α1 receptor agonists | |
| PT2297148E (pt) | Novos derivados de (piperazinilo em ponte)-1-alcanona e sua utilização como inibidores de p75 | |
| CA2317515A1 (en) | Oxazole derivatives as serotonin-1a receptor agonists | |
| WO1988002751A1 (en) | Pyridine derivatives | |
| JPH0733744A (ja) | インダゾール誘導体およびその塩 | |
| JPH05247052A (ja) | Ｎ−アルキルグルタールイミドの４−（４−ピペリジニル）−チエノ〔３，２−ｃ〕ピリジン誘導体 | |
| JPH06228095A (ja) | カルバゾール誘導体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |