NO820937L - 9-(2-(3-indolyl)etyl)-1-oksa-4,9-diazaspiro(5,5)-undekan-3-oner og fremgangsmaate for deres fremstilling - Google Patents
9-(2-(3-indolyl)etyl)-1-oksa-4,9-diazaspiro(5,5)-undekan-3-oner og fremgangsmaate for deres fremstillingInfo
- Publication number
- NO820937L NO820937L NO820937A NO820937A NO820937L NO 820937 L NO820937 L NO 820937L NO 820937 A NO820937 A NO 820937A NO 820937 A NO820937 A NO 820937A NO 820937 L NO820937 L NO 820937L
- Authority
- NO
- Norway
- Prior art keywords
- compound
- ethyl
- hydrogen
- oxa
- acid addition
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 29
- 238000000034 method Methods 0.000 title claims description 19
- -1 2- (3-INDOLYL) ETHYL Chemical class 0.000 title claims description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 125
- 239000002253 acid Substances 0.000 claims abstract description 41
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 239000001257 hydrogen Substances 0.000 claims abstract description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 37
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 29
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 27
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 206010020772 Hypertension Diseases 0.000 claims abstract description 13
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 10
- 208000035475 disorder Diseases 0.000 claims abstract description 10
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 9
- 206010027599 migraine Diseases 0.000 claims abstract description 9
- 230000002455 vasospastic effect Effects 0.000 claims abstract description 9
- 206010019280 Heart failures Diseases 0.000 claims abstract description 8
- 206010003119 arrhythmia Diseases 0.000 claims abstract description 8
- 230000006793 arrhythmia Effects 0.000 claims abstract description 8
- 208000006673 asthma Diseases 0.000 claims abstract description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- YNMZZHPSYMOGCI-UHFFFAOYSA-N undecan-3-one Chemical compound CCCCCCCCC(=O)CC YNMZZHPSYMOGCI-UHFFFAOYSA-N 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- SPALXTYNFFFDEM-UHFFFAOYSA-N 9-[2-(1h-indol-3-yl)ethyl]-1-oxa-4,9-diazaspiro[5.5]undecan-3-one Chemical compound C1NC(=O)COC11CCN(CCC=2C3=CC=CC=C3NC=2)CC1 SPALXTYNFFFDEM-UHFFFAOYSA-N 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 8
- 239000012458 free base Substances 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- XJLDYKIEURAVBW-UHFFFAOYSA-N 3-decanone Chemical compound CCCCCCCC(=O)CC XJLDYKIEURAVBW-UHFFFAOYSA-N 0.000 claims 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- RUQIRXLHSREWNG-UHFFFAOYSA-N 2-ethyl-9-[2-(1h-indol-3-yl)ethyl]-1-oxa-4,9-diazaspiro[5.5]undecan-3-one Chemical compound C1NC(=O)C(CC)OC11CCN(CCC=2C3=CC=CC=C3NC=2)CC1 RUQIRXLHSREWNG-UHFFFAOYSA-N 0.000 claims 1
- JTVBYLQKZNXSHK-UHFFFAOYSA-N 2-ethyl-9-[2-(1h-indol-3-yl)ethyl]-4-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one Chemical compound C1N(C)C(=O)C(CC)OC11CCN(CCC=2C3=CC=CC=C3NC=2)CC1 JTVBYLQKZNXSHK-UHFFFAOYSA-N 0.000 claims 1
- REVBORKBBSOPNG-UHFFFAOYSA-N 4-ethyl-9-[2-(1h-indol-3-yl)ethyl]-1-oxa-4,9-diazaspiro[5.5]undecan-3-one Chemical compound O1CC(=O)N(CC)CC11CCN(CCC=2C3=CC=CC=C3NC=2)CC1 REVBORKBBSOPNG-UHFFFAOYSA-N 0.000 claims 1
- XPOYPEGICVZFLM-UHFFFAOYSA-N 5-ethyl-9-[2-(1h-indol-3-yl)ethyl]-4-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one Chemical compound CCC1N(C)C(=O)COC11CCN(CCC=2C3=CC=CC=C3NC=2)CC1 XPOYPEGICVZFLM-UHFFFAOYSA-N 0.000 claims 1
- TWXMNMCWVZGJOB-UHFFFAOYSA-N 9-[2-(1h-indol-3-yl)ethyl]-2-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one Chemical compound C1NC(=O)C(C)OC11CCN(CCC=2C3=CC=CC=C3NC=2)CC1 TWXMNMCWVZGJOB-UHFFFAOYSA-N 0.000 claims 1
- CXFXJZUPHCJQHE-UHFFFAOYSA-N 9-[2-(1h-indol-3-yl)ethyl]-4,5-dimethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one Chemical compound CC1N(C)C(=O)COC11CCN(CCC=2C3=CC=CC=C3NC=2)CC1 CXFXJZUPHCJQHE-UHFFFAOYSA-N 0.000 claims 1
- WYXCCMFMCYVMOD-UHFFFAOYSA-N 9-[2-(1h-indol-3-yl)ethyl]-4-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one Chemical group O1CC(=O)N(C)CC11CCN(CCC=2C3=CC=CC=C3NC=2)CC1 WYXCCMFMCYVMOD-UHFFFAOYSA-N 0.000 claims 1
- SWUIOIMFTISPRN-UHFFFAOYSA-N 9-[2-(1h-indol-3-yl)ethyl]-4-propyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one Chemical compound O1CC(=O)N(CCC)CC11CCN(CCC=2C3=CC=CC=C3NC=2)CC1 SWUIOIMFTISPRN-UHFFFAOYSA-N 0.000 claims 1
- YMWCHFVKNLRUOY-UHFFFAOYSA-N 9-[2-(1h-indol-3-yl)ethyl]-5-methyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one Chemical compound CC1NC(=O)COC11CCN(CCC=2C3=CC=CC=C3NC=2)CC1 YMWCHFVKNLRUOY-UHFFFAOYSA-N 0.000 claims 1
- CVVLNQAVUXXQPL-UHFFFAOYSA-N 9-[2-(1h-indol-3-yl)ethyl]-5-propyl-1-oxa-4,5-diazaspiro[5.5]undecan-3-one Chemical compound CCCN1NC(=O)COC11CCC(CCC=2C3=CC=CC=C3NC=2)CC1 CVVLNQAVUXXQPL-UHFFFAOYSA-N 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 206010007559 Cardiac failure congestive Diseases 0.000 abstract description 2
- 230000002265 prevention Effects 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 230000008018 melting Effects 0.000 description 14
- 238000002844 melting Methods 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- JZYHZABGLQFCHU-UHFFFAOYSA-N Hydroxyethylindole Chemical compound C1=CC=C2NC(CCO)=CC2=C1 JZYHZABGLQFCHU-UHFFFAOYSA-N 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 7
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 6
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- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
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- 239000000543 intermediate Substances 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
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- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001516 alkali metal iodide Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 230000003182 bronchodilatating effect Effects 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229940005991 chloric acid Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- KDSNLYIMUZNERS-UHFFFAOYSA-N isobutyl amine Natural products CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- RMIODHQZRUFFFF-UHFFFAOYSA-N methoxyacetic acid Chemical compound COCC(O)=O RMIODHQZRUFFFF-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002900 organolithium compounds Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 238000005502 peroxidation Methods 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000010956 selective crystallization Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- NRZWQKGABZFFKE-UHFFFAOYSA-N trimethylsulfonium Chemical compound C[S+](C)C NRZWQKGABZFFKE-UHFFFAOYSA-N 0.000 description 1
- 235000013311 vegetables Nutrition 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/48—Oxygen atoms attached in position 4 having an acyclic carbon atom attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Saccharide Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Photoreceptors In Electrophotography (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/246,459 US4332804A (en) | 1981-03-23 | 1981-03-23 | 9-[2-(3-Indolyl)ethyl]-1oxa-4,9-diazaspiro[5.5]undecan-3-ones |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO820937L true NO820937L (no) | 1982-09-24 |
Family
ID=22930776
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO820937A NO820937L (no) | 1981-03-23 | 1982-03-22 | 9-(2-(3-indolyl)etyl)-1-oksa-4,9-diazaspiro(5,5)-undekan-3-oner og fremgangsmaate for deres fremstilling |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US4332804A (de) |
| EP (1) | EP0061333B1 (de) |
| JP (1) | JPS57169485A (de) |
| KR (1) | KR830009094A (de) |
| AT (1) | ATE17249T1 (de) |
| AU (1) | AU557094B2 (de) |
| BR (1) | BR8201589A (de) |
| DE (1) | DE3268225D1 (de) |
| DK (1) | DK129282A (de) |
| ES (1) | ES510649A0 (de) |
| FI (1) | FI820998L (de) |
| IE (1) | IE52652B1 (de) |
| IL (1) | IL65310A (de) |
| NO (1) | NO820937L (de) |
| NZ (1) | NZ200085A (de) |
| PH (1) | PH17233A (de) |
| PL (1) | PL235561A1 (de) |
| PT (1) | PT74626B (de) |
| ZA (1) | ZA821929B (de) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4861880A (en) * | 1982-09-20 | 1989-08-29 | Pfizer Inc. | 1-phenyl-2(1H,3H)-indolone psycho-therapeutic agents |
| US4879391A (en) * | 1982-09-20 | 1989-11-07 | Pfizer Inc. | 1-Phenyl-2(1H,3H)-indolone psychotherapeutic agents |
| US4977178A (en) * | 1982-09-20 | 1990-12-11 | Pfizer Inc. | Method of treating anxiety and depression with 1-phenyl-2(1H,3H)-indolone psycho-therapeutic agents |
| GB8808433D0 (en) * | 1988-04-11 | 1988-05-11 | Merck Sharp & Dohme | Therapeutic agents |
| EP1263729B1 (de) * | 2000-03-06 | 2006-12-20 | Acadia Pharmaceuticals Inc. | Azacyclische verbindungen zur verwendung in der behandlung von mit serotonin verwandten krankheiten |
| US6911452B2 (en) * | 2001-12-28 | 2005-06-28 | Acadia Pharmaceuticals Inc. | Spiroazacyclic compounds as monoamine receptor modulators |
| US7253186B2 (en) * | 2002-06-24 | 2007-08-07 | Carl-Magnus Andersson | N-substituted piperidine derivatives as serotonin receptor agents |
| US7538222B2 (en) * | 2002-06-24 | 2009-05-26 | Acadia Pharmaceuticals, Inc. | N-substituted piperidine derivatives as serotonin receptor agents |
| MXPA04012893A (es) * | 2002-06-24 | 2005-03-31 | Acadia Pharm Inc | Derivados de piperidina n-substituidos como agentes receptores de serotonina. |
| KR101095939B1 (ko) | 2003-01-16 | 2011-12-19 | 아카디아 파마슈티칼스 인코포레이티드 | 신경퇴행성 질환에 대한 치료제로서 선택적 세로토닌2ａ／2ｃ 리셉터 역작용제 |
| US7820695B2 (en) * | 2004-05-21 | 2010-10-26 | Acadia Pharmaceuticals, Inc. | Selective serotonin receptor inverse agonists as therapeutics for disease |
| US20050261278A1 (en) | 2004-05-21 | 2005-11-24 | Weiner David M | Selective serotonin receptor inverse agonists as therapeutics for disease |
| US7790899B2 (en) * | 2004-09-27 | 2010-09-07 | Acadia Pharmaceuticals, Inc. | Synthesis of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl)carbamide and its tartrate salt and crystalline forms |
| AU2005289635A1 (en) * | 2004-09-27 | 2006-04-06 | Acadia Pharmaceuticals Inc. | Salts of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide and their preparation |
| CN101677971A (zh) | 2007-03-19 | 2010-03-24 | 阿卡蒂亚药品公司 | 5-ht2a反向激动剂和拮抗剂与抗精神病药物的组合 |
| DK2200610T3 (en) * | 2007-09-21 | 2018-04-23 | Acadia Pharm Inc | ADMINISTRATION OF PIMAVANSERIN WITH OTHER AGENTS |
| TWI685497B (zh) * | 2014-06-02 | 2020-02-21 | 西班牙商伊史帝夫製藥公司 | 具有多重模式抗疼痛活性的１-氧雜-４,９-二氮雜螺十一烷化合物之烷基衍生物 |
| SI3325444T1 (sl) | 2015-07-20 | 2021-11-30 | Acadia Pharmaceuticals Inc. | Postopki za pripravo N-(4-fluorobenzil)-N-(1-metilpiperidin-4-il)-N'- (4-(2-metilpropiloksi)fenilmetil)karbamida in njegove tartratne soli in polimorfne oblike C |
| CN108349999A (zh) | 2015-11-16 | 2018-07-31 | 埃斯蒂文博士实验室股份有限公司 | 用于治疗药物滥用和成瘾的氧杂二氮杂螺环化合物 |
| US10953000B2 (en) | 2016-03-25 | 2021-03-23 | Acadia Pharmaceuticals Inc. | Combination of pimavanserin and cytochrome P450 modulators |
| WO2017165635A1 (en) | 2016-03-25 | 2017-09-28 | Acadia Pharmaceuticals Inc. | Combination of pimavanserin and cytochrome p450 modulators |
| WO2018118626A1 (en) | 2016-12-20 | 2018-06-28 | Acadia Pharmaceuticals Inc. | Pimavanserin alone or in combination for use in the treatment of alzheimer's disease psychosis |
| US11135211B2 (en) | 2017-04-28 | 2021-10-05 | Acadia Pharmaceuticals Inc. | Pimavanserin for treating impulse control disorder |
| EP3675827A1 (de) | 2017-08-30 | 2020-07-08 | Acadia Pharmaceuticals Inc. | Formulierungen von pimavanserin |
| AR113770A1 (es) | 2017-10-17 | 2020-06-10 | Esteve Pharmaceuticals Sa | Sales de (r)-9-(2,5-difluorofenetil)-4-etil-2-metil-1-oxa-4,9-diazaspiro[5.5]undecan-3-ona |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3481942A (en) * | 1968-09-06 | 1969-12-02 | Smithkline Corp | Oxa-diazaspiro(4.5)decane compounds |
| US3574204A (en) * | 1969-07-03 | 1971-04-06 | Yoshitomi Pharmaceutical | Piperidine spiro compounds |
| CA952908A (en) * | 1970-02-27 | 1974-08-13 | Yoshitomi Pharmaceutical Industries | Benzodioxane derivatives |
| US3723442A (en) * | 1970-12-31 | 1973-03-27 | Yoshitomi Pharmaceutical | 3-oxo-1-oxa-4,8-diazaspiro(4.5)decanes |
| US4255432A (en) * | 1979-09-06 | 1981-03-10 | Syntex (U.S.A.) Inc. | 8-[2-3-Indolyl)ethyl]-1-oxa-3-,8-diazaspiro[4.5]decan-2-ones, pharmaceutical compositions thereof and methods of use thereof |
-
1981
- 1981-03-23 US US06/246,459 patent/US4332804A/en not_active Expired - Fee Related
-
1982
- 1982-02-22 BR BR8201589A patent/BR8201589A/pt unknown
- 1982-03-22 PL PL23556182A patent/PL235561A1/xx unknown
- 1982-03-22 DK DK129282A patent/DK129282A/da not_active Application Discontinuation
- 1982-03-22 IE IE648/82A patent/IE52652B1/en unknown
- 1982-03-22 ZA ZA821929A patent/ZA821929B/xx unknown
- 1982-03-22 DE DE8282301460T patent/DE3268225D1/de not_active Expired
- 1982-03-22 NZ NZ200085A patent/NZ200085A/en unknown
- 1982-03-22 ES ES510649A patent/ES510649A0/es active Granted
- 1982-03-22 EP EP82301460A patent/EP0061333B1/de not_active Expired
- 1982-03-22 PT PT74626A patent/PT74626B/pt unknown
- 1982-03-22 AT AT82301460T patent/ATE17249T1/de not_active IP Right Cessation
- 1982-03-22 AU AU81769/82A patent/AU557094B2/en not_active Expired - Fee Related
- 1982-03-22 IL IL65310A patent/IL65310A/xx unknown
- 1982-03-22 PH PH27035A patent/PH17233A/en unknown
- 1982-03-22 NO NO820937A patent/NO820937L/no unknown
- 1982-03-22 KR KR1019820001218A patent/KR830009094A/ko unknown
- 1982-03-22 FI FI820998A patent/FI820998L/fi not_active Application Discontinuation
- 1982-03-23 JP JP57044755A patent/JPS57169485A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| DE3268225D1 (de) | 1986-02-13 |
| IE820648L (en) | 1982-09-23 |
| AU557094B2 (en) | 1986-12-04 |
| KR830009094A (ko) | 1983-12-17 |
| DK129282A (da) | 1982-09-24 |
| ES8306373A1 (es) | 1983-06-01 |
| ZA821929B (en) | 1983-11-30 |
| EP0061333A1 (de) | 1982-09-29 |
| IL65310A (en) | 1985-03-31 |
| ATE17249T1 (de) | 1986-01-15 |
| PH17233A (en) | 1984-07-03 |
| BR8201589A (pt) | 1983-02-08 |
| AU8176982A (en) | 1982-09-30 |
| IL65310A0 (en) | 1982-05-31 |
| FI820998L (fi) | 1982-09-24 |
| PT74626A (en) | 1982-04-01 |
| US4332804A (en) | 1982-06-01 |
| IE52652B1 (en) | 1988-01-06 |
| PL235561A1 (de) | 1982-10-25 |
| ES510649A0 (es) | 1983-06-01 |
| JPS57169485A (en) | 1982-10-19 |
| NZ200085A (en) | 1985-07-12 |
| PT74626B (en) | 1983-12-19 |
| EP0061333B1 (de) | 1986-01-02 |
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