CA2241845C - 4,5-dihydronaphth[1,2-c]isoxazoles et leurs derives ayant une activite au niveau du systeme nerveux central - Google Patents
4,5-dihydronaphth[1,2-c]isoxazoles et leurs derives ayant une activite au niveau du systeme nerveux central Download PDFInfo
- Publication number
- CA2241845C CA2241845C CA002241845A CA2241845A CA2241845C CA 2241845 C CA2241845 C CA 2241845C CA 002241845 A CA002241845 A CA 002241845A CA 2241845 A CA2241845 A CA 2241845A CA 2241845 C CA2241845 C CA 2241845C
- Authority
- CA
- Canada
- Prior art keywords
- dihydronaphth
- compound according
- isoxazole
- isomer
- salt
- 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
- IHHJKWJJZUXWFI-UHFFFAOYSA-N 4,5-dihydrobenzo[g][2,1]benzoxazole Chemical class C1=CC=C2C3=NOC=C3CCC2=C1 IHHJKWJJZUXWFI-UHFFFAOYSA-N 0.000 title abstract 2
- 230000000694 effects Effects 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 67
- 239000003814 drug Substances 0.000 claims abstract description 14
- 229940079593 drug Drugs 0.000 claims abstract description 11
- 206010047700 Vomiting Diseases 0.000 claims abstract description 6
- 208000020016 psychiatric disease Diseases 0.000 claims abstract description 6
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 5
- 206010028813 Nausea Diseases 0.000 claims abstract description 5
- 230000036506 anxiety Effects 0.000 claims abstract description 5
- 230000008693 nausea Effects 0.000 claims abstract description 5
- 230000008673 vomiting Effects 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims description 69
- 150000003839 salts Chemical class 0.000 claims description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 11
- 239000002904 solvent Substances 0.000 claims description 10
- -1 2-oxo-1-benzimidazolinyl Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical group [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- IEUPVQXQJANHRN-UHFFFAOYSA-N 3-chloro-4,5-dihydrobenzo[g][2,1]benzoxazole Chemical compound C1=CC=C2C3=NOC(Cl)=C3CCC2=C1 IEUPVQXQJANHRN-UHFFFAOYSA-N 0.000 claims description 4
- SAUJGUBHKSGTCV-UHFFFAOYSA-N 3-chloro-8-methoxy-4,5-dihydrobenzo[g][2,1]benzoxazole Chemical compound C1CC2=C(Cl)ON=C2C2=CC(OC)=CC=C21 SAUJGUBHKSGTCV-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- YUKUDJRCHPSDGC-UHFFFAOYSA-N 1,2-oxazole;hydrochloride Chemical compound Cl.C=1C=NOC=1 YUKUDJRCHPSDGC-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 claims description 3
- MGRNRSCWZHDWFW-UHFFFAOYSA-N 3-(1,4-diazepan-1-yl)-4,5-dihydrobenzo[g][2,1]benzoxazole Chemical compound C=12CCC3=CC=CC=C3C2=NOC=1N1CCCNCC1 MGRNRSCWZHDWFW-UHFFFAOYSA-N 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 4
- 125000005843 halogen group Chemical group 0.000 claims 4
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 claims 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical group CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims 2
- 230000001668 ameliorated effect Effects 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 2
- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 claims 2
- PLIWWIJUNIZKFR-UHFFFAOYSA-N 2-[4-(4,5-dihydrobenzo[g][2,1]benzoxazol-3-yl)piperazin-1-yl]ethanol Chemical compound C1CN(CCO)CCN1C1=C(CCC=2C3=CC=CC=2)C3=NO1 PLIWWIJUNIZKFR-UHFFFAOYSA-N 0.000 claims 1
- UAXZAHBCTWKSAE-UHFFFAOYSA-N 3-(1,4-diazepan-1-yl)-8-methoxy-4,5-dihydrobenzo[g][2,1]benzoxazole Chemical compound O1N=C2C3=CC(OC)=CC=C3CCC2=C1N1CCCNCC1 UAXZAHBCTWKSAE-UHFFFAOYSA-N 0.000 claims 1
- YROOYCNRZJIDQR-UHFFFAOYSA-N 3-(1-methylpiperidin-4-yl)oxy-4,5-dihydrobenzo[g][2,1]benzoxazole Chemical compound C1CN(C)CCC1OC1=C(CCC=2C3=CC=CC=2)C3=NO1 YROOYCNRZJIDQR-UHFFFAOYSA-N 0.000 claims 1
- IKWPESZGRAQXEO-UHFFFAOYSA-N 3-(4-benzylpiperazin-1-yl)-4,5-dihydrobenzo[g][2,1]benzoxazole Chemical compound C1CN(C2=C3C(C4=CC=CC=C4CC3)=NO2)CCN1CC1=CC=CC=C1 IKWPESZGRAQXEO-UHFFFAOYSA-N 0.000 claims 1
- RXJNGDHQROMVIP-UHFFFAOYSA-N 3-(4-methylpiperazin-1-yl)-4,5-dihydrobenzo[g][2,1]benzoxazole Chemical compound C1CN(C)CCN1C1=C(CCC=2C3=CC=CC=2)C3=NO1 RXJNGDHQROMVIP-UHFFFAOYSA-N 0.000 claims 1
- ZWQWKLOHOWXEEW-UHFFFAOYSA-N 3-piperazin-1-yl-4,5-dihydrobenzo[g][2,1]benzoxazole Chemical compound C1CNCCN1C1=C(CCC=2C3=CC=CC=2)C3=NO1 ZWQWKLOHOWXEEW-UHFFFAOYSA-N 0.000 claims 1
- AHVAIXWPBSICKC-UHFFFAOYSA-N 8-methoxy-3-piperazin-1-yl-4,5-dihydrobenzo[g][2,1]benzoxazole Chemical compound O1N=C2C3=CC(OC)=CC=C3CCC2=C1N1CCNCC1 AHVAIXWPBSICKC-UHFFFAOYSA-N 0.000 claims 1
- AGFCOKPEXTUECZ-UHFFFAOYSA-N C1CC2=C(O)ON=C2C2=CC(OC)=CC=C21 Chemical compound C1CC2=C(O)ON=C2C2=CC(OC)=CC=C21 AGFCOKPEXTUECZ-UHFFFAOYSA-N 0.000 claims 1
- RYPCQPCSRWYWKE-UHFFFAOYSA-N C1CCC2=CC=CC=C2C2=NOC(O)=C21 Chemical compound C1CCC2=CC=CC=C2C2=NOC(O)=C21 RYPCQPCSRWYWKE-UHFFFAOYSA-N 0.000 claims 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical group [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000012312 sodium hydride Substances 0.000 claims 1
- 229910000104 sodium hydride Inorganic materials 0.000 claims 1
- 229940127360 Serotonin 5HT-3 Antagonists Drugs 0.000 abstract 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 41
- 239000007787 solid Substances 0.000 description 38
- 238000004809 thin layer chromatography Methods 0.000 description 38
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 25
- 239000000047 product Substances 0.000 description 22
- 239000000377 silicon dioxide Substances 0.000 description 22
- 239000012258 stirred mixture Substances 0.000 description 21
- 235000019439 ethyl acetate Nutrition 0.000 description 20
- 238000000921 elemental analysis Methods 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 18
- 239000007858 starting material Substances 0.000 description 16
- 238000005481 NMR spectroscopy Methods 0.000 description 15
- 238000010438 heat treatment Methods 0.000 description 15
- 238000001819 mass spectrum Methods 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 238000003556 assay Methods 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000007792 addition Methods 0.000 description 12
- 230000027455 binding Effects 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 239000005557 antagonist Substances 0.000 description 9
- 125000003545 alkoxy group Chemical group 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 229960005343 ondansetron Drugs 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- FELGMEQIXOGIFQ-UHFFFAOYSA-N Ondansetron Chemical compound CC1=NC=CN1CC1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FELGMEQIXOGIFQ-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 150000002367 halogens Chemical group 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 150000002923 oximes Chemical class 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- FELGMEQIXOGIFQ-CYBMUJFWSA-N (3r)-9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one Chemical compound CC1=NC=CN1C[C@@H]1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FELGMEQIXOGIFQ-CYBMUJFWSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 210000001353 entorhinal cortex Anatomy 0.000 description 3
- 150000002431 hydrogen Chemical group 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 230000011514 reflex Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- FUOSTELFLYZQCW-UHFFFAOYSA-N 1,2-oxazol-3-one Chemical class OC=1C=CON=1 FUOSTELFLYZQCW-UHFFFAOYSA-N 0.000 description 2
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 2
- XQJMXPAEFMWDOZ-UHFFFAOYSA-N 3exo-benzoyloxy-tropane Natural products CN1C(C2)CCC1CC2OC(=O)C1=CC=CC=C1 XQJMXPAEFMWDOZ-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 101150041968 CDC13 gene Proteins 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 244000287680 Garcinia dulcis Species 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- QQXLDOJGLXJCSE-UHFFFAOYSA-N N-methylnortropinone Natural products C1C(=O)CC2CCC1N2C QQXLDOJGLXJCSE-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- QIZDQFOVGFDBKW-DHBOJHSNSA-N Pseudotropine Natural products OC1C[C@@H]2[N+](C)[C@H](C1)CC2 QIZDQFOVGFDBKW-DHBOJHSNSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000011670 long-evans rat Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- CYHOMWAPJJPNMW-JIGDXULJSA-N tropine Chemical compound C1[C@@H](O)C[C@H]2CC[C@@H]1N2C CYHOMWAPJJPNMW-JIGDXULJSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 1
- BAUWRHPMUVYFOD-UHFFFAOYSA-N 1-methylpiperidin-4-ol Chemical compound CN1CCC(O)CC1 BAUWRHPMUVYFOD-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 1
- AJRGDQWFWJDYDP-UHFFFAOYSA-N 3-chloro-1,2-oxazole Chemical class ClC=1C=CON=1 AJRGDQWFWJDYDP-UHFFFAOYSA-N 0.000 description 1
- BYNBAMHAURJNTR-UHFFFAOYSA-N 3-piperidin-4-yl-1h-benzimidazol-2-one Chemical compound O=C1NC2=CC=CC=C2N1C1CCNCC1 BYNBAMHAURJNTR-UHFFFAOYSA-N 0.000 description 1
- IVLICPVPXWEGCA-UHFFFAOYSA-N 3-quinuclidinol Chemical compound C1C[C@@H]2C(O)C[N@]1CC2 IVLICPVPXWEGCA-UHFFFAOYSA-N 0.000 description 1
- FEROPKNOYKURCJ-UHFFFAOYSA-N 4-amino-N-(1-azabicyclo[2.2.2]octan-3-yl)-5-chloro-2-methoxybenzamide Chemical compound COC1=CC(N)=C(Cl)C=C1C(=O)NC1C(CC2)CCN2C1 FEROPKNOYKURCJ-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 229920002261 Corn starch Polymers 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
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000001953 Hypotension Diseases 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
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- WUKZPHOXUVCQOR-UHFFFAOYSA-N N-(1-azabicyclo[2.2.2]octan-3-yl)-6-chloro-4-methyl-3-oxo-1,4-benzoxazine-8-carboxamide Chemical compound C1N(CC2)CCC2C1NC(=O)C1=CC(Cl)=CC2=C1OCC(=O)N2C WUKZPHOXUVCQOR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 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
- 239000003708 ampul Substances 0.000 description 1
- 210000004727 amygdala Anatomy 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000003693 atypical antipsychotic agent Substances 0.000 description 1
- 229940127236 atypical antipsychotics Drugs 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- MNJNPLVXBISNSX-WDNDVIMCSA-N bemesetron Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C1=CC(Cl)=CC(Cl)=C1 MNJNPLVXBISNSX-WDNDVIMCSA-N 0.000 description 1
- 229950007840 bemesetron Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 208000006218 bradycardia Diseases 0.000 description 1
- 230000036471 bradycardia Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 230000003205 diastolic effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 150000002238 fumaric acids Chemical class 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000002695 general anesthesia Methods 0.000 description 1
- 230000002070 germicidal effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002545 isoxazoles Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000002197 limbic effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
- 229940012189 methyl orange Drugs 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 210000001009 nucleus accumben Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 150000002913 oxalic acids Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- HDDNYFLPWFSBLN-ZSHCYNCHSA-N tropanyl 3,5-dimethylbenzoate Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C1=CC(C)=CC(C)=C1 HDDNYFLPWFSBLN-ZSHCYNCHSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000001631 vena cava inferior Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 229950004681 zacopride Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/20—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
4,5-dihydronaphth[1,2-c]isoxazoles et leurs dérivés, de formule générale (I), dans laquelle A, X et n sont tels que définis dans la description. Ces composés sont utiles comme antagonistes 5-HT¿3? de la sérotonine. Ces composés sont utiles pour traiter l'anxiété, les troubles psychiatriques, la nausée, les vomissements et la toxicomanie.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US58331996A | 1996-01-05 | 1996-01-05 | |
US08/583,319 | 1996-01-05 | ||
PCT/US1996/019569 WO1997025317A1 (fr) | 1996-01-05 | 1996-12-12 | 4,5-dihydronaphth[1,2-c]isoxazoles et leurs derives ayant une activite au niveau du systeme nerveux central |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2241845A1 CA2241845A1 (fr) | 1997-07-17 |
CA2241845C true CA2241845C (fr) | 2002-10-01 |
Family
ID=24332609
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002241845A Expired - Fee Related CA2241845C (fr) | 1996-01-05 | 1996-12-12 | 4,5-dihydronaphth[1,2-c]isoxazoles et leurs derives ayant une activite au niveau du systeme nerveux central |
Country Status (14)
Country | Link |
---|---|
EP (1) | EP0874833A1 (fr) |
JP (1) | JP3161737B2 (fr) |
KR (1) | KR100308748B1 (fr) |
CN (1) | CN1214046A (fr) |
AR (1) | AR005347A1 (fr) |
AU (1) | AU710059B2 (fr) |
BR (1) | BR9612578A (fr) |
CA (1) | CA2241845C (fr) |
HU (1) | HUP9903706A3 (fr) |
IL (1) | IL125197A0 (fr) |
NO (1) | NO983100L (fr) |
NZ (1) | NZ325587A (fr) |
WO (1) | WO1997025317A1 (fr) |
ZA (1) | ZA9725B (fr) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2420235A1 (fr) * | 2000-08-21 | 2002-02-28 | Georgetown University | Quinuclidines 2-3-disubstituees servant de modulateurs de transporteur de monoamine et procedes therapeutiques et diagnostiques se basant sur celles-ci |
US7265103B2 (en) * | 2002-04-02 | 2007-09-04 | Janssen Pharmaceutica Nv. | Substituted amino isoxazoline derivatives and their use as anti-depressants |
AR040967A1 (es) | 2002-08-12 | 2005-04-27 | Janssen Pharmaceutica Nv | Derivados de isoxazolina triciclicos c- sustituidos y su uso como anti- depresivos |
EP1554286B1 (fr) | 2002-08-15 | 2010-01-27 | Janssen Pharmaceutica N.V. | Derives d'isoxazoline heterocycliques fusionnes et leur utilisation en tant qu'antidepresseurs |
MY134287A (en) * | 2002-08-21 | 2007-11-30 | Janssen Pharmaceutica Nv | C6- and c9-substituted isoxazoline derivatives and their use as anti-depressants |
US8025859B2 (en) | 2007-05-18 | 2011-09-27 | Cesl Limited | Process for gold and silver recovery from a sulphide concentrate |
EP2493866A1 (fr) | 2009-10-29 | 2012-09-05 | Bristol-Myers Squibb Company | Composés hétérocycliques tricycliques |
US10633354B2 (en) | 2016-09-02 | 2020-04-28 | Bristol-Myers Squibb Company | Substituted tricyclic heterocyclic compounds |
US11059784B2 (en) | 2017-08-09 | 2021-07-13 | Bristol-Myers Squibb Company | Oxime ether compounds |
US11046646B2 (en) | 2017-08-09 | 2021-06-29 | Bristol-Myers Squibb Company | Alkylphenyl compounds |
KR102002633B1 (ko) | 2018-07-19 | 2019-07-22 | 김태효 | 완충이격부가 구비된 논슬립 발의류 |
KR102429797B1 (ko) | 2019-12-31 | 2022-08-05 | 주식회사 제이패션 | 기능성 무재봉 덧신 및 이를 제조하는 제조방법 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2119977A1 (en) * | 1971-04-23 | 1971-12-16 | Teikoku Hormone Manufacturing Co , Ltd, Tokio | Antiphlogistic and antisecretory napththisoxazoles - from 1-hydroxyim - 2-carbonyl derivs by intramolecular condensation |
EP0402644B1 (fr) * | 1989-05-19 | 1995-08-16 | Hoechst-Roussel Pharmaceuticals Incorporated | N-(aryloxyalkyl)hétéroarylpipéridines et -hétéroarylpipérazines, leur procédé de préparation et leur application comme médicaments |
US5670522A (en) * | 1992-10-23 | 1997-09-23 | Merck Sharp & Dohme Limited | Dopamine receptor subtype ligands |
-
1996
- 1996-12-12 BR BR9612578A patent/BR9612578A/pt not_active Application Discontinuation
- 1996-12-12 WO PCT/US1996/019569 patent/WO1997025317A1/fr not_active Application Discontinuation
- 1996-12-12 CN CN96180175A patent/CN1214046A/zh active Pending
- 1996-12-12 HU HU9903706A patent/HUP9903706A3/hu unknown
- 1996-12-12 JP JP52519797A patent/JP3161737B2/ja not_active Expired - Fee Related
- 1996-12-12 NZ NZ325587A patent/NZ325587A/xx unknown
- 1996-12-12 KR KR1019980705166A patent/KR100308748B1/ko not_active IP Right Cessation
- 1996-12-12 IL IL12519796A patent/IL125197A0/xx unknown
- 1996-12-12 EP EP96944274A patent/EP0874833A1/fr not_active Withdrawn
- 1996-12-12 AU AU14126/97A patent/AU710059B2/en not_active Ceased
- 1996-12-12 CA CA002241845A patent/CA2241845C/fr not_active Expired - Fee Related
-
1997
- 1997-01-02 ZA ZA9725A patent/ZA9725B/xx unknown
- 1997-01-03 AR ARP970100015A patent/AR005347A1/es unknown
-
1998
- 1998-07-03 NO NO983100A patent/NO983100L/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
CN1214046A (zh) | 1999-04-14 |
AU1412697A (en) | 1997-08-01 |
NZ325587A (en) | 1999-02-25 |
WO1997025317A1 (fr) | 1997-07-17 |
BR9612578A (pt) | 1999-07-27 |
KR19990077033A (ko) | 1999-10-25 |
AU710059B2 (en) | 1999-09-09 |
IL125197A0 (en) | 1999-03-12 |
KR100308748B1 (ko) | 2001-12-12 |
HUP9903706A3 (en) | 2000-09-28 |
ZA9725B (en) | 1997-07-07 |
AR005347A1 (es) | 1999-04-28 |
JP3161737B2 (ja) | 2001-04-25 |
NO983100L (no) | 1998-09-04 |
NO983100D0 (no) | 1998-07-03 |
EP0874833A1 (fr) | 1998-11-04 |
JPH11510816A (ja) | 1999-09-21 |
CA2241845A1 (fr) | 1997-07-17 |
HUP9903706A2 (hu) | 2000-08-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR910000439B1 (ko) | 벤족사진 화합물 및 그의 약제학적 용도 | |
JP2656702B2 (ja) | ペプチド性キヌクリジン | |
RU2092486C1 (ru) | Замещенные 3-аминохинуклидины | |
CA2241845C (fr) | 4,5-dihydronaphth[1,2-c]isoxazoles et leurs derives ayant une activite au niveau du systeme nerveux central | |
KR100263414B1 (ko) | 티에노 [3,2-b] 피리딘 유도체 | |
BG61975B1 (bg) | Индолови производни, методи и междинни съединения за тяхнотополучаване, фармацевтични състави, които ги съдържат, иприложението им | |
WO1996020194A1 (fr) | Nouveaux derives de quinuclidine et composition pharmaceutique les contenant | |
EA010887B1 (ru) | Тетрагидроиндазольные модуляторы каннабиноидов | |
AU2010337837B2 (en) | Alpha4beta2 neuronal nicotinic acetylcholine receptor ligands | |
AU2003262420A1 (en) | Derivatives of N-[phenyl(piperidin-2-yl)methyl]benzamide, the preparation method thereof and application of same in therapeutics | |
CA2878006C (fr) | Derives de carbamate/uree | |
MXPA05000435A (es) | Derivados de azabiciclo como antagonistas de receptor muscarinico. | |
JPH01258674A (ja) | イミダゾ〔1,2−a〕ピリジン誘導体 | |
RU2162848C2 (ru) | Производные окса- или тиадиазола, способ их получения (варианты), фармацевтическая композиция | |
PT89381B (pt) | Processo para a preparacao de oxadiazoles lipofilicos | |
JP2006522787A (ja) | ムスカリン様受容体アンタゴニストとしてのアザビシクロ誘導体 | |
DE69031111T2 (de) | Indolderivate | |
US5880121A (en) | 4,5-dihydronaphth (1,2-c) isoxazoles and derivatives thereof | |
WO2014146486A1 (fr) | Inhibiteur d'amine alk kinase cyclique à trois niveaux pour le traitement de cancers | |
EP2989104B1 (fr) | Composés pyrazino[1,2-a]indoliques, leur préparation et utilisation dans des médicaments | |
KR100824506B1 (ko) | 퀴나졸리논 유도체 | |
EP0639568A1 (fr) | Dérivés de pipéridine, leur préparation et leur utilisation dans le traitement des maladies neurodégénératives | |
JP7138799B2 (ja) | コリンエステラーゼ阻害剤結晶多形及びその使用 | |
CA3199269A1 (fr) | Derives d'isoxazole en tant que modulateurs du recepteur serotoninergique 5-ht2a utiles pour le traitement de troubles associes a celui-ci | |
JPH0710851A (ja) | アミノアルコール誘導体及びその用途 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
MKLA | Lapsed | ||
MKLA | Lapsed |
Effective date: 20071212 |