IL123656A - History of isoxazolidine, process for preparation and pharmaceutical preparations containing these histories - Google Patents
History of isoxazolidine, process for preparation and pharmaceutical preparations containing these historiesInfo
- Publication number
- IL123656A IL123656A IL12365697A IL12365697A IL123656A IL 123656 A IL123656 A IL 123656A IL 12365697 A IL12365697 A IL 12365697A IL 12365697 A IL12365697 A IL 12365697A IL 123656 A IL123656 A IL 123656A
- Authority
- IL
- Israel
- Prior art keywords
- formula
- alkyl
- independently
- hydrogen
- hydroxy
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 14
- 230000008569 process Effects 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title description 13
- 239000008194 pharmaceutical composition Substances 0.000 title description 7
- 150000002546 isoxazolidines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 97
- -1 cyano, hydroxy Chemical group 0.000 claims abstract description 44
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 239000001257 hydrogen Substances 0.000 claims abstract description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 22
- 125000004953 trihalomethyl group Chemical group 0.000 claims abstract description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 12
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims abstract description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 11
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 11
- 125000001424 substituent group Chemical group 0.000 claims abstract description 10
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims abstract description 6
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims abstract description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims abstract description 3
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims abstract description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims abstract description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000005129 aryl carbonyl group Chemical group 0.000 claims abstract description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 3
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims abstract description 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical group C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229930192474 thiophene Chemical group 0.000 claims abstract description 3
- 125000001475 halogen functional group Chemical group 0.000 claims abstract 6
- 125000000815 N-oxide group Chemical group 0.000 claims abstract 4
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical group C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims abstract 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims abstract 2
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims abstract 2
- 150000003852 triazoles Chemical group 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims description 36
- 239000000543 intermediate Substances 0.000 claims description 32
- 239000002253 acid Substances 0.000 claims description 20
- 239000002585 base Substances 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 239000004480 active ingredient Substances 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 231100000252 nontoxic Toxicity 0.000 claims description 4
- 230000003000 nontoxic effect Effects 0.000 claims description 4
- 230000009466 transformation Effects 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
- 101710179738 6,7-dimethyl-8-ribityllumazine synthase 1 Proteins 0.000 claims 1
- 101710186608 Lipoyl synthase 1 Proteins 0.000 claims 1
- 101710137584 Lipoyl synthase 1, chloroplastic Proteins 0.000 claims 1
- 101710090391 Lipoyl synthase 1, mitochondrial Proteins 0.000 claims 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- RJEFMSTXZPSRKS-UHFFFAOYSA-N diazepin-1-ylmethanamine Chemical compound NCN1C=CC=CC=N1 RJEFMSTXZPSRKS-UHFFFAOYSA-N 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 claims 1
- 238000000844 transformation Methods 0.000 claims 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 abstract description 4
- 125000004951 trihalomethoxy group Chemical group 0.000 abstract description 4
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 abstract description 3
- 125000004391 aryl sulfonyl group Chemical group 0.000 abstract description 2
- 125000000168 pyrrolyl group Chemical group 0.000 abstract description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 14
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 abstract 5
- 125000003545 alkoxy group Chemical group 0.000 abstract 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 5
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 abstract 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 abstract 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 22
- 239000002904 solvent Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
- 150000003254 radicals Chemical class 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 150000001204 N-oxides Chemical group 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 239000002287 radioligand Substances 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 208000028017 Psychotic disease Diseases 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- MKHGVMIXRPGHOO-UHFFFAOYSA-N 2-(benzenesulfonyl)-3-phenyloxaziridine Chemical compound C=1C=CC=CC=1S(=O)(=O)N1OC1C1=CC=CC=C1 MKHGVMIXRPGHOO-UHFFFAOYSA-N 0.000 description 3
- 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 3
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 208000019695 Migraine disease Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000036506 anxiety Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 3
- 206010027599 migraine Diseases 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 150000002978 peroxides Chemical class 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical compound N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 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 2
- 101150104779 HTR2A gene Proteins 0.000 description 2
- 101150013372 Htr2c gene Proteins 0.000 description 2
- 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229960001040 ammonium chloride Drugs 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000000935 antidepressant agent Substances 0.000 description 2
- 229940005513 antidepressants Drugs 0.000 description 2
- 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 2
- 230000037396 body weight Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 229940097362 cyclodextrins Drugs 0.000 description 2
- 229960004132 diethyl ether Drugs 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- VYFOAVADNIHPTR-UHFFFAOYSA-N isatoic anhydride Chemical compound NC1=CC=CC=C1CO VYFOAVADNIHPTR-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 229940100688 oral solution Drugs 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical group OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- XXQBEVHPUKOQEO-UHFFFAOYSA-N potassium superoxide Chemical compound [K+].[K+].[O-][O-] XXQBEVHPUKOQEO-UHFFFAOYSA-N 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 238000010956 selective crystallization Methods 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- POILWHVDKZOXJZ-ARJAWSKDSA-M (z)-4-oxopent-2-en-2-olate Chemical compound C\C([O-])=C\C(C)=O POILWHVDKZOXJZ-ARJAWSKDSA-M 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- ZCXLTWVZYXBHJS-UHFFFAOYSA-N 1,2-benzoxazepine Chemical compound O1N=CC=CC2=CC=CC=C12 ZCXLTWVZYXBHJS-UHFFFAOYSA-N 0.000 description 1
- CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical class C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 description 1
- OMIVCRYZSXDGAB-UHFFFAOYSA-N 1,4-butanediyl Chemical group [CH2]CC[CH2] OMIVCRYZSXDGAB-UHFFFAOYSA-N 0.000 description 1
- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 description 1
- ZPSILBKWQHDXLE-UHFFFAOYSA-N 1-pyrrolidin-1-yl-5h-benzo[d][1]benzazepine Chemical compound C1CCCN1C1=CC=CC2=C1C1=CC=CC=C1C=CN2 ZPSILBKWQHDXLE-UHFFFAOYSA-N 0.000 description 1
- XLKISLYZRCKBEW-UHFFFAOYSA-N 2-(3-nitropyridin-2-yl)oxybenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CN=C1OC1=CC=CC=C1C=O XLKISLYZRCKBEW-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- ZONBMWRPZHKNBV-UHFFFAOYSA-N 2-[methyl(prop-2-enyl)amino]ethanol Chemical compound OCCN(C)CC=C ZONBMWRPZHKNBV-UHFFFAOYSA-N 0.000 description 1
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Addiction (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Photoreceptors In Electrophotography (AREA)
- Developing Agents For Electrophotography (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP96200991 | 1996-04-12 | ||
| PCT/EP1997/001830 WO1997039001A1 (en) | 1996-04-12 | 1997-04-09 | Isoxazolidine derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL123656A0 IL123656A0 (en) | 1998-10-30 |
| IL123656A true IL123656A (en) | 2001-09-13 |
Family
ID=8223869
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL12365697A IL123656A (en) | 1996-04-12 | 1997-04-09 | History of isoxazolidine, process for preparation and pharmaceutical preparations containing these histories |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US6156747A (hu) |
| EP (1) | EP0892804B1 (hu) |
| JP (1) | JP4299884B2 (hu) |
| KR (1) | KR100598724B1 (hu) |
| CN (1) | CN1082963C (hu) |
| AT (1) | ATE222911T1 (hu) |
| AU (1) | AU716470B2 (hu) |
| DE (1) | DE69714980T2 (hu) |
| DK (1) | DK0892804T3 (hu) |
| ES (1) | ES2182064T3 (hu) |
| HU (1) | HU221608B (hu) |
| IL (1) | IL123656A (hu) |
| MY (1) | MY117456A (hu) |
| NO (1) | NO310077B1 (hu) |
| NZ (1) | NZ329954A (hu) |
| PL (1) | PL186541B1 (hu) |
| PT (1) | PT892804E (hu) |
| TW (1) | TW514637B (hu) |
| WO (1) | WO1997039001A1 (hu) |
| ZA (1) | ZA973122B (hu) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AUPO588297A0 (en) | 1997-03-26 | 1997-04-24 | Luminis Pty Limited | Mediation in melatonin production |
| US20050148018A1 (en) | 1999-10-07 | 2005-07-07 | David Weiner | Methods of identifying inverse agonists of the serotonin 2A receptor |
| UA77650C2 (en) | 1999-12-06 | 2007-01-15 | Lundbeck & Co As H | Use of serotonin reuptake inhibitor in combination with deramcyclane |
| EE200300398A (et) * | 2001-02-21 | 2003-12-15 | Janssen Pharmaceutica N.V. | Isoksasoliini derivaat, selle saamine ja kasutamine depresioonivastase ravimi valmistamiseks ning seda sisaldav ravimkompositsioon |
| EA013595B1 (ru) * | 2005-01-27 | 2010-06-30 | Янссен Фармацевтика Н.В. | Гетероциклические, тетрациклические производные гидрофурана в качестве ингибиторов 5htв терапии расстройств цнс |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL7414038A (nl) * | 1974-10-28 | 1976-05-03 | Akzo Nv | Nieuwe tetracyclische pyrrolidino derivaten. |
| TW206227B (hu) * | 1989-10-05 | 1993-05-21 | Sankyo Co | |
| WO1996014321A1 (en) * | 1994-11-02 | 1996-05-17 | Janssen Pharmaceutica N.V. | Substituted tetracyclic oxazepine and thiazepine derivatives with 5-ht2 receptor affinity |
| US5552399A (en) * | 1994-11-02 | 1996-09-03 | Janssen Pharmaceutica N.V. | Substituted tetracyclic azepine derivatives |
-
1997
- 1997-04-09 WO PCT/EP1997/001830 patent/WO1997039001A1/en not_active Application Discontinuation
- 1997-04-09 DE DE69714980T patent/DE69714980T2/de not_active Expired - Lifetime
- 1997-04-09 HU HU9901875A patent/HU221608B/hu unknown
- 1997-04-09 DK DK97919344T patent/DK0892804T3/da active
- 1997-04-09 PL PL97326871A patent/PL186541B1/pl unknown
- 1997-04-09 ES ES97919344T patent/ES2182064T3/es not_active Expired - Lifetime
- 1997-04-09 AT AT97919344T patent/ATE222911T1/de active
- 1997-04-09 JP JP53673497A patent/JP4299884B2/ja not_active Expired - Lifetime
- 1997-04-09 US US09/155,839 patent/US6156747A/en not_active Expired - Lifetime
- 1997-04-09 PT PT97919344T patent/PT892804E/pt unknown
- 1997-04-09 EP EP97919344A patent/EP0892804B1/en not_active Expired - Lifetime
- 1997-04-09 CN CN97191421A patent/CN1082963C/zh not_active Expired - Lifetime
- 1997-04-09 NZ NZ329954A patent/NZ329954A/xx not_active IP Right Cessation
- 1997-04-09 AU AU23852/97A patent/AU716470B2/en not_active Expired
- 1997-04-09 KR KR1019980703537A patent/KR100598724B1/ko not_active IP Right Cessation
- 1997-04-09 IL IL12365697A patent/IL123656A/en not_active IP Right Cessation
- 1997-04-10 TW TW086104562A patent/TW514637B/zh not_active IP Right Cessation
- 1997-04-11 MY MYPI97001599A patent/MY117456A/en unknown
- 1997-04-11 ZA ZA973122A patent/ZA973122B/xx unknown
-
1998
- 1998-03-11 NO NO981077A patent/NO310077B1/no not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| US6156747A (en) | 2000-12-05 |
| DE69714980T2 (de) | 2003-04-10 |
| EP0892804A1 (en) | 1999-01-27 |
| PT892804E (pt) | 2003-01-31 |
| JP2000508328A (ja) | 2000-07-04 |
| TW514637B (en) | 2002-12-21 |
| ZA973122B (en) | 1998-10-12 |
| DE69714980D1 (de) | 2002-10-02 |
| PL326871A1 (en) | 1998-10-26 |
| CN1205010A (zh) | 1999-01-13 |
| WO1997039001A1 (en) | 1997-10-23 |
| JP4299884B2 (ja) | 2009-07-22 |
| NO310077B1 (no) | 2001-05-14 |
| AU2385297A (en) | 1997-11-07 |
| HU221608B (hu) | 2002-11-28 |
| ES2182064T3 (es) | 2003-03-01 |
| DK0892804T3 (da) | 2002-12-02 |
| IL123656A0 (en) | 1998-10-30 |
| ATE222911T1 (de) | 2002-09-15 |
| KR19990067515A (ko) | 1999-08-25 |
| AU716470B2 (en) | 2000-02-24 |
| NO981077L (no) | 1998-10-12 |
| NO981077D0 (no) | 1998-03-11 |
| NZ329954A (en) | 1999-07-29 |
| MY117456A (en) | 2004-06-30 |
| PL186541B1 (pl) | 2004-01-30 |
| KR100598724B1 (ko) | 2006-10-25 |
| EP0892804B1 (en) | 2002-08-28 |
| HUP9901875A3 (en) | 2000-06-28 |
| HUP9901875A2 (hu) | 1999-09-28 |
| CN1082963C (zh) | 2002-04-17 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| EXP | Patent expired |