CA1090805A - Propionic acid derivatives and a process for producing the same - Google Patents
Propionic acid derivatives and a process for producing the sameInfo
- Publication number
- CA1090805A CA1090805A CA292,226A CA292226A CA1090805A CA 1090805 A CA1090805 A CA 1090805A CA 292226 A CA292226 A CA 292226A CA 1090805 A CA1090805 A CA 1090805A
- Authority
- CA
- Canada
- Prior art keywords
- dihydro
- formula
- compound
- thiepin
- oxepin
- 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
Links
- 238000000034 method Methods 0.000 title claims description 54
- 150000005599 propionic acid derivatives Chemical class 0.000 title abstract description 8
- 229940111131 antiinflammatory and antirheumatic product propionic acid derivative Drugs 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 77
- -1 hydroxy, amino Chemical group 0.000 claims abstract description 18
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 17
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 15
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 15
- 229910052760 oxygen Inorganic materials 0.000 claims abstract 22
- 239000001301 oxygen Substances 0.000 claims abstract 22
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims abstract 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 89
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 60
- 229940080818 propionamide Drugs 0.000 claims description 36
- 239000000126 substance Substances 0.000 claims description 33
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 30
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 229920000137 polyphosphoric acid Polymers 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 8
- 229910021529 ammonia Inorganic materials 0.000 claims description 8
- WWVUREJQSBMBLL-UHFFFAOYSA-N 2-(5,6-dihydro-[1]benzoxepino[2,3-b]pyridin-8-yl)propanoic acid Chemical compound C1CC2=CC(C(C(O)=O)C)=CC=C2OC2=NC=CC=C21 WWVUREJQSBMBLL-UHFFFAOYSA-N 0.000 claims description 7
- XBWNHVYUSPOILP-UHFFFAOYSA-N 2-(5-oxo-6h-benzo[b][1]benzoxepin-3-yl)propanamide Chemical compound C1C(=O)C2=CC(C(C(N)=O)C)=CC=C2OC2=CC=CC=C21 XBWNHVYUSPOILP-UHFFFAOYSA-N 0.000 claims description 7
- 229960003424 phenylacetic acid Drugs 0.000 claims description 7
- 239000003279 phenylacetic acid Substances 0.000 claims description 7
- DFTCFMRQIVXWMJ-UHFFFAOYSA-N 2-(5,6-dihydro-[1]benzothiepino[2,3-b]pyridin-8-yl)propanoic acid Chemical compound C1CC2=CC(C(C(O)=O)C)=CC=C2SC2=NC=CC=C21 DFTCFMRQIVXWMJ-UHFFFAOYSA-N 0.000 claims description 6
- IUMFZGGXXASGEZ-UHFFFAOYSA-N 2-(5-oxo-6h-benzo[b][1]benzothiepin-3-yl)propanamide Chemical compound C1C(=O)C2=CC(C(C(N)=O)C)=CC=C2SC2=CC=CC=C21 IUMFZGGXXASGEZ-UHFFFAOYSA-N 0.000 claims description 6
- HHMVMSNPBYGGOD-UHFFFAOYSA-N 2-(5-oxo-6h-benzo[b][1]benzoxepin-3-yl)propanoic acid Chemical compound C1C(=O)C2=CC(C(C(O)=O)C)=CC=C2OC2=CC=CC=C21 HHMVMSNPBYGGOD-UHFFFAOYSA-N 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 229910000497 Amalgam Inorganic materials 0.000 claims description 4
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 claims description 4
- ZSWAUGWFLJZVHF-UHFFFAOYSA-N ethyl 2-(5-oxo-6h-benzo[b][1]benzothiepin-3-yl)propanoate Chemical compound C1C(=O)C2=CC(C(C)C(=O)OCC)=CC=C2SC2=CC=CC=C21 ZSWAUGWFLJZVHF-UHFFFAOYSA-N 0.000 claims description 4
- KYFWKENNYDFYEC-UHFFFAOYSA-N ethyl 2-(5-oxo-6h-benzo[b][1]benzoxepin-3-yl)propanoate Chemical compound C1C(=O)C2=CC(C(C)C(=O)OCC)=CC=C2OC2=CC=CC=C21 KYFWKENNYDFYEC-UHFFFAOYSA-N 0.000 claims description 4
- BNRBUMZXZZZSLK-UHFFFAOYSA-N 2-(5,6-dihydro-[1]benzothiepino[2,3-b]pyridin-8-yl)propanamide Chemical compound C1CC2=CC(C(C(N)=O)C)=CC=C2SC2=NC=CC=C21 BNRBUMZXZZZSLK-UHFFFAOYSA-N 0.000 claims description 3
- SYAQOFMDWGBFSQ-UHFFFAOYSA-N 2-(5,6-dihydro-[1]benzoxepino[2,3-b]pyridin-8-yl)propanamide Chemical compound C1CC2=CC(C(C(N)=O)C)=CC=C2OC2=NC=CC=C21 SYAQOFMDWGBFSQ-UHFFFAOYSA-N 0.000 claims description 3
- QFPXOAVHVAULOC-UHFFFAOYSA-N 2-(6-oxo-5h-[1]benzoxepino[2,3-b]pyridin-8-yl)propanamide Chemical compound C1C(=O)C2=CC(C(C(N)=O)C)=CC=C2OC2=NC=CC=C21 QFPXOAVHVAULOC-UHFFFAOYSA-N 0.000 claims description 3
- SYBBXDVUXFRMLQ-UHFFFAOYSA-N ethyl 2-(5,6-dihydro-[1]benzoxepino[2,3-b]pyridin-8-yl)propanoate Chemical compound C1CC2=CC(C(C)C(=O)OCC)=CC=C2OC2=NC=CC=C21 SYBBXDVUXFRMLQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- CEKOSBUFSYPRAD-UHFFFAOYSA-N ethyl 2-(5,6-dihydro-[1]benzothiepino[2,3-b]pyridin-8-yl)propanoate Chemical compound C1CC2=CC(C(C)C(=O)OCC)=CC=C2SC2=NC=CC=C21 CEKOSBUFSYPRAD-UHFFFAOYSA-N 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- XPGXTIRPGQZKIA-UHFFFAOYSA-N 2-(5-oxo-6h-benzo[b][1]benzothiepin-3-yl)propanoic acid Chemical compound C1C(=O)C2=CC(C(C(O)=O)C)=CC=C2SC2=CC=CC=C21 XPGXTIRPGQZKIA-UHFFFAOYSA-N 0.000 claims 2
- 230000003301 hydrolyzing effect Effects 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 129
- 239000000203 mixture Substances 0.000 description 103
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 90
- 239000000243 solution Substances 0.000 description 73
- 239000002904 solvent Substances 0.000 description 72
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 67
- 239000003921 oil Substances 0.000 description 51
- 235000019198 oils Nutrition 0.000 description 51
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 47
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 42
- 125000003118 aryl group Chemical group 0.000 description 42
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 38
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- 239000000741 silica gel Substances 0.000 description 36
- 229910002027 silica gel Inorganic materials 0.000 description 36
- 239000013078 crystal Substances 0.000 description 31
- 238000001816 cooling Methods 0.000 description 26
- 238000002844 melting Methods 0.000 description 26
- 230000008018 melting Effects 0.000 description 26
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 25
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
- 235000011118 potassium hydroxide Nutrition 0.000 description 17
- 229940093932 potassium hydroxide Drugs 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 125000004325 thiepin-2-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C(*)S1 0.000 description 13
- 239000005457 ice water Substances 0.000 description 12
- 125000005605 benzo group Chemical group 0.000 description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- RNJXWQXPIWMGTH-UHFFFAOYSA-N 2-(5,6-dihydrobenzo[b][1]benzoxepin-3-yl)propanoic acid Chemical compound C1CC2=CC(C(C(O)=O)C)=CC=C2OC2=CC=CC=C21 RNJXWQXPIWMGTH-UHFFFAOYSA-N 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- WYUBRHODQMJKDP-UHFFFAOYSA-N 2-(5,6-dihydrobenzo[b][1]benzothiepin-3-yl)propanoic acid Chemical compound C1CC2=CC(C(C(O)=O)C)=CC=C2SC2=CC=CC=C21 WYUBRHODQMJKDP-UHFFFAOYSA-N 0.000 description 4
- VSKFNIFDPFYFDC-UHFFFAOYSA-N 2-(5-oxo-6h-benzo[b][1]benzothiepin-2-yl)propanoic acid Chemical compound S1C2=CC=CC=C2CC(=O)C2=CC=C(C(C(O)=O)C)C=C12 VSKFNIFDPFYFDC-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical compound CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 229950007593 homonicotinic acid Drugs 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- YZXWVFUQKLZUKD-UHFFFAOYSA-N 2-(5,6-dihydro-[1]benzothiepino[2,3-b]pyridin-9-yl)propanoic acid Chemical compound C1CC2=CC=CN=C2SC2=CC(C(C(O)=O)C)=CC=C21 YZXWVFUQKLZUKD-UHFFFAOYSA-N 0.000 description 3
- HADGTNPPBGMAGJ-UHFFFAOYSA-N 2-(5,6-dihydrobenzo[b][1]benzoxepin-3-yl)propanamide Chemical compound C1CC2=CC(C(C(N)=O)C)=CC=C2OC2=CC=CC=C21 HADGTNPPBGMAGJ-UHFFFAOYSA-N 0.000 description 3
- VSLFCAQKQXDSIU-UHFFFAOYSA-N 2-(5-oxo-6h-benzo[b][1]benzoxepin-2-yl)propanamide Chemical compound O1C2=CC=CC=C2CC(=O)C2=CC=C(C(C(N)=O)C)C=C12 VSLFCAQKQXDSIU-UHFFFAOYSA-N 0.000 description 3
- FLFCQRUKDPDTGG-UHFFFAOYSA-N 2-(5-oxo-6h-benzo[b][1]benzoxepin-2-yl)propanoic acid Chemical compound O1C2=CC=CC=C2CC(=O)C2=CC=C(C(C(O)=O)C)C=C12 FLFCQRUKDPDTGG-UHFFFAOYSA-N 0.000 description 3
- QKBVNUGMUDRQPN-UHFFFAOYSA-N 2-(6-oxo-5h-[1]benzothiepino[2,3-b]pyridin-8-yl)propanoic acid Chemical compound C1C(=O)C2=CC(C(C(O)=O)C)=CC=C2SC2=NC=CC=C21 QKBVNUGMUDRQPN-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- UHORFYOZEIEHRL-UHFFFAOYSA-N ethyl 2-(5,6-dihydrobenzo[b][1]benzothiepin-2-yl)propanoate Chemical compound C1CC2=CC=CC=C2SC2=CC(C(C)C(=O)OCC)=CC=C21 UHORFYOZEIEHRL-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000003701 inert diluent Substances 0.000 description 3
- 125000004323 oxepin-2-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C(*)O1 0.000 description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- DFCCDTQVGQHGOY-UHFFFAOYSA-N 2-(5,6-dihydro-[1]benzothiepino[2,3-b]pyridin-9-yl)propanamide Chemical compound C1CC2=CC=CN=C2SC2=CC(C(C(N)=O)C)=CC=C21 DFCCDTQVGQHGOY-UHFFFAOYSA-N 0.000 description 2
- NVRLZQOZLGAFTM-UHFFFAOYSA-N 2-(5,6-dihydrobenzo[b][1]benzothiepin-2-yl)propanoic acid Chemical compound C1CC2=CC=CC=C2SC2=CC(C(C(O)=O)C)=CC=C21 NVRLZQOZLGAFTM-UHFFFAOYSA-N 0.000 description 2
- KCIINCSMSGFIBF-UHFFFAOYSA-N 2-(5,6-dihydrobenzo[b][1]benzothiepin-3-yl)propanamide Chemical compound C1CC2=CC(C(C(N)=O)C)=CC=C2SC2=CC=CC=C21 KCIINCSMSGFIBF-UHFFFAOYSA-N 0.000 description 2
- JIORKZONIUCUMA-UHFFFAOYSA-N 2-(5-oxo-6h-benzo[b][1]benzoxepin-1-yl)propanamide Chemical compound O1C2=CC=CC=C2CC(=O)C2=C1C(C(C(N)=O)C)=CC=C2 JIORKZONIUCUMA-UHFFFAOYSA-N 0.000 description 2
- CEHQFNJGLHENBY-UHFFFAOYSA-N 2-(5-oxo-6h-benzo[b][1]benzoxepin-1-yl)propanoic acid Chemical compound O1C2=CC=CC=C2CC(=O)C2=C1C(C(C(O)=O)C)=CC=C2 CEHQFNJGLHENBY-UHFFFAOYSA-N 0.000 description 2
- GIELBKDQHZEJHX-UHFFFAOYSA-N 2-(6-oxo-5h-[1]benzothiepino[2,3-b]pyridin-8-yl)propanamide Chemical compound C1C(=O)C2=CC(C(C(N)=O)C)=CC=C2SC2=NC=CC=C21 GIELBKDQHZEJHX-UHFFFAOYSA-N 0.000 description 2
- CSMLBHIIUZRBBZ-UHFFFAOYSA-N 2-(6-oxo-5h-[1]benzoxepino[2,3-b]pyridin-8-yl)propanoic acid Chemical compound C1C(=O)C2=CC(C(C(O)=O)C)=CC=C2OC2=NC=CC=C21 CSMLBHIIUZRBBZ-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- ASGJEMPQQVNTGO-UHFFFAOYSA-N benzene chloroform Chemical compound C(Cl)(Cl)Cl.C1=CC=CC=C1.C1=CC=CC=C1 ASGJEMPQQVNTGO-UHFFFAOYSA-N 0.000 description 2
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- BZDCLFBUXCDHMK-UHFFFAOYSA-N ethyl 2-(5,6-dihydrobenzo[b][1]benzoxepin-3-yl)propanoate Chemical compound C1CC2=CC(C(C)C(=O)OCC)=CC=C2OC2=CC=CC=C21 BZDCLFBUXCDHMK-UHFFFAOYSA-N 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 239000012442 inert solvent Substances 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
- NJJMPCSJXNFLLF-UHFFFAOYSA-N methyl 2-(6-oxo-5h-[1]benzothiepino[2,3-b]pyridin-8-yl)propanoate Chemical compound C1C(=O)C2=CC(C(C)C(=O)OC)=CC=C2SC2=NC=CC=C21 NJJMPCSJXNFLLF-UHFFFAOYSA-N 0.000 description 2
- HXHIDGRMHJPMMC-UHFFFAOYSA-N methyl 2-(6-oxo-5h-[1]benzothiepino[2,3-b]pyridin-9-yl)propanoate Chemical compound S1C2=NC=CC=C2CC(=O)C2=CC=C(C(C)C(=O)OC)C=C12 HXHIDGRMHJPMMC-UHFFFAOYSA-N 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003385 sodium Chemical class 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- GHPYJLCQYMAXGG-WCCKRBBISA-N (2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid hydrochloride Chemical compound Cl.N[C@@H](CSCCB(O)O)C(O)=O GHPYJLCQYMAXGG-WCCKRBBISA-N 0.000 description 1
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 1
- IEQNRFOVQTYGJA-UHFFFAOYSA-N 2-(5,6-dihydrobenzo[b][1]benzoxepin-1-yl)propanoic acid Chemical compound C1CC2=CC=CC=C2OC2=C1C=CC=C2C(C(O)=O)C IEQNRFOVQTYGJA-UHFFFAOYSA-N 0.000 description 1
- ZLKOYPYEKBVCNO-UHFFFAOYSA-N 2-(5,6-dihydrobenzo[b][1]benzoxepin-2-yl)propanoic acid Chemical compound C1CC2=CC=CC=C2OC2=CC(C(C(O)=O)C)=CC=C21 ZLKOYPYEKBVCNO-UHFFFAOYSA-N 0.000 description 1
- RGGBUHVQRZLOSN-UHFFFAOYSA-N 2-(5-oxo-6h-benzo[b][1]benzothiepin-2-yl)propanamide Chemical compound S1C2=CC=CC=C2CC(=O)C2=CC=C(C(C(N)=O)C)C=C12 RGGBUHVQRZLOSN-UHFFFAOYSA-N 0.000 description 1
- RIAUJEJDRULXLX-UHFFFAOYSA-N 2-(6-oxo-5h-[1]benzothiepino[2,3-b]pyridin-9-yl)propanamide Chemical compound S1C2=NC=CC=C2CC(=O)C2=CC=C(C(C(N)=O)C)C=C12 RIAUJEJDRULXLX-UHFFFAOYSA-N 0.000 description 1
- QVGGKVYJBQYGLV-UHFFFAOYSA-N 2-(6-oxo-5h-[1]benzothiepino[2,3-b]pyridin-9-yl)propanoic acid Chemical compound S1C2=NC=CC=C2CC(=O)C2=CC=C(C(C(O)=O)C)C=C12 QVGGKVYJBQYGLV-UHFFFAOYSA-N 0.000 description 1
- ASCOLIXOQPMRDG-UHFFFAOYSA-N 2-(6-oxo-5h-[1]benzoxepino[2,3-b]pyridin-9-yl)propanamide Chemical compound O1C2=NC=CC=C2CC(=O)C2=CC=C(C(C(N)=O)C)C=C12 ASCOLIXOQPMRDG-UHFFFAOYSA-N 0.000 description 1
- UBFSVJZLZUBKJD-UHFFFAOYSA-N 2-(6-oxo-5h-[1]benzoxepino[2,3-b]pyridin-9-yl)propanoic acid Chemical compound O1C2=NC=CC=C2CC(=O)C2=CC=C(C(C(O)=O)C)C=C12 UBFSVJZLZUBKJD-UHFFFAOYSA-N 0.000 description 1
- WSNKEJIFARPOSQ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(1-benzothiophen-2-ylmethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCC2=CC3=C(S2)C=CC=C3)C=CC=1 WSNKEJIFARPOSQ-UHFFFAOYSA-N 0.000 description 1
- TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 description 1
- 101100496169 Arabidopsis thaliana CLH1 gene Proteins 0.000 description 1
- 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000243251 Hydra Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 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
- 241000124008 Mammalia Species 0.000 description 1
- 101100044057 Mesocricetus auratus SYCP3 gene Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- UQONAEXHTGDOIH-AWEZNQCLSA-N O=C(N1CC[C@@H](C1)N1CCCC1=O)C1=CC2=C(NC3(CC3)CCO2)N=C1 Chemical compound O=C(N1CC[C@@H](C1)N1CCCC1=O)C1=CC2=C(NC3(CC3)CCO2)N=C1 UQONAEXHTGDOIH-AWEZNQCLSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101100080600 Schizosaccharomyces pombe (strain 972 / ATCC 24843) nse6 gene Proteins 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 150000008062 acetophenones Chemical class 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 1
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 101150111293 cor-1 gene Proteins 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- DXRTWZNAHLOMRH-UHFFFAOYSA-N ethyl 2-(5,6-dihydro-[1]benzothiepino[2,3-b]pyridin-9-yl)propanoate Chemical compound C1CC2=CC=CN=C2SC2=CC(C(C)C(=O)OCC)=CC=C21 DXRTWZNAHLOMRH-UHFFFAOYSA-N 0.000 description 1
- IYFLOYFFXTVJGD-UHFFFAOYSA-N ethyl 2-(5,6-dihydrobenzo[b][1]benzothiepin-3-yl)propanoate Chemical compound C1CC2=CC(C(C)C(=O)OCC)=CC=C2SC2=CC=CC=C21 IYFLOYFFXTVJGD-UHFFFAOYSA-N 0.000 description 1
- FIMDILQZXUGZQM-UHFFFAOYSA-N ethyl 2-(5-oxo-6h-benzo[b][1]benzothiepin-2-yl)propanoate Chemical compound S1C2=CC=CC=C2CC(=O)C2=CC=C(C(C)C(=O)OCC)C=C12 FIMDILQZXUGZQM-UHFFFAOYSA-N 0.000 description 1
- DSSHLDMWAOGZDZ-UHFFFAOYSA-N ethyl 2-(5-oxo-6h-benzo[b][1]benzoxepin-2-yl)propanoate Chemical compound O1C2=CC=CC=C2CC(=O)C2=CC=C(C(C)C(=O)OCC)C=C12 DSSHLDMWAOGZDZ-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 1
- 229960004369 flufenamic acid Drugs 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- GKUYYYHRSVUUCK-UHFFFAOYSA-N methyl 2-(5,6-dihydrobenzo[b][1]benzoxepin-2-yl)propanoate Chemical compound C1CC2=CC=CC=C2OC2=CC(C(C)C(=O)OC)=CC=C21 GKUYYYHRSVUUCK-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- ATYBXHSAIOKLMG-UHFFFAOYSA-N oxepin Chemical compound O1C=CC=CC=C1 ATYBXHSAIOKLMG-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
- 150000007659 semicarbazones Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
- C07D313/02—Seven-membered rings
- C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D313/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D313/14—[b,f]-condensed
-
- 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
- C07D495/02—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 two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP51-145403 | 1976-12-03 | ||
| JP14540476A JPS6019310B2 (ja) | 1976-12-03 | 1976-12-03 | ベンゾオキセピン誘導体およびその製法 |
| JP51-145404 | 1976-12-03 | ||
| JP51145403A JPS6021156B2 (ja) | 1976-12-03 | 1976-12-03 | ベンゾチエピン誘導体およびその製法 |
| JP7169077A JPS545992A (en) | 1977-06-17 | 1977-06-17 | Dibenzoxopin derivatives and process for thier preparation |
| JP52-71690 | 1977-06-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1090805A true CA1090805A (en) | 1980-12-02 |
Family
ID=27300727
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA292,226A Expired CA1090805A (en) | 1976-12-03 | 1977-12-02 | Propionic acid derivatives and a process for producing the same |
Country Status (11)
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT7850376A0 (it) * | 1977-07-26 | 1978-07-19 | Merck & Co Inc | Composizioni di dibenzo(b.f)tiepina e procedimento per la loro preparazione |
| US4536507A (en) * | 1977-07-26 | 1985-08-20 | Merck & Co., Inc. | Prostaglandin antagonists |
| JPS54122284A (en) * | 1978-02-17 | 1979-09-21 | Dainippon Pharmaceut Co Ltd | Dibenzb,foxepin derivative |
| JPS54115388A (en) * | 1978-03-01 | 1979-09-07 | Nippon Chemiphar Co Ltd | Acetic acid derivative and its preparation |
| JPS54157583A (en) * | 1978-06-02 | 1979-12-12 | Nippon Chemiphar Co Ltd | Dibenzothiepin derivative and its preparation |
| JPS5553282A (en) * | 1978-10-17 | 1980-04-18 | Nippon Chemiphar Co Ltd | Dibenzothiepin derivative and its preparation |
| EP0029587B1 (en) * | 1979-11-27 | 1984-06-13 | Merck Sharp & Dohme (I.A.) Corp. | 3-hydroxymethyldibenzo(b,f)thiepins and dibenzo(b,f)thiepin-3-carboxaldehydes as prostaglandin antagonists, process for their preparation and pharmaceutical compositions |
| US4417063A (en) * | 1981-05-18 | 1983-11-22 | Hoechst-Roussel Pharmaceuticals Inc. | Process for preparation of 6,11-dihydro-11-oxodibenz[b,e]oxepinacetic acids |
| US4576960A (en) * | 1981-12-23 | 1986-03-18 | Hoechst Roussel Pharmaceuticals Incorporated | 6,11-Dihydro-11-oxo-dibenz[b,e]oxepin derivatives |
| US4515946A (en) * | 1981-12-23 | 1985-05-07 | Hoechst-Roussel Pharmaceuticals Inc. | 6,11-Dihydro-11-oxo-dibenz-[b,e]oxepin derivatives |
| US4526891A (en) * | 1983-03-10 | 1985-07-02 | Hoechst Roussel Pharmaceuticals Inc. | Substituted alkyl amine derivatives of 6,11-dihydro-11-oxodibenz[b,e]oxepins |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1403487A (en) * | 1972-07-21 | 1975-08-28 | Yoshitomi Pharmaceutical | Heterocyclic substituted alkanoic acids and derivatives |
| DE2442979A1 (de) * | 1973-09-13 | 1975-03-20 | Sandoz Ag | Verfahren zur herstellung neuer heterocyclischer verbindungen |
| JPS5253876A (en) * | 1975-10-28 | 1977-04-30 | Nippon Chemiphar Co Ltd | Process for preparing dibenzothiepin derivatives |
| GB1475950A (en) * | 1975-05-30 | 1977-06-10 | Nippon Chemiphar Co | Benzo-b,f-thiepin derivatives and a process for producing the same |
-
1977
- 1977-11-28 US US05/855,076 patent/US4205170A/en not_active Expired - Lifetime
- 1977-12-01 GB GB50028/77A patent/GB1546258A/en not_active Expired
- 1977-12-02 FR FR7736348A patent/FR2372836A1/fr active Granted
- 1977-12-02 NL NL7713373A patent/NL7713373A/xx not_active Application Discontinuation
- 1977-12-02 CH CH1478077A patent/CH630623A5/fr not_active IP Right Cessation
- 1977-12-02 SE SE7713704A patent/SE7713704L/xx unknown
- 1977-12-02 CA CA292,226A patent/CA1090805A/en not_active Expired
- 1977-12-02 DK DK537677A patent/DK537677A/da unknown
- 1977-12-03 ES ES464728A patent/ES464728A1/es not_active Expired
- 1977-12-05 DE DE19772754561 patent/DE2754561A1/de active Granted
- 1977-12-05 AR AR270250A patent/AR221836A1/es active
-
1978
- 1978-10-26 ES ES474543A patent/ES474543A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| FR2372836B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1980-08-22 |
| US4205170A (en) | 1980-05-27 |
| GB1546258A (en) | 1979-05-23 |
| DE2754561A1 (de) | 1978-06-08 |
| AR221836A1 (es) | 1981-03-31 |
| SE7713704L (sv) | 1978-06-04 |
| DK537677A (da) | 1978-06-04 |
| CH630623A5 (fr) | 1982-06-30 |
| FR2372836A1 (fr) | 1978-06-30 |
| NL7713373A (nl) | 1978-06-06 |
| DE2754561C2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1988-08-04 |
| ES464728A1 (es) | 1980-12-16 |
| ES474543A1 (es) | 1979-04-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1090805A (en) | Propionic acid derivatives and a process for producing the same | |
| EP0350846B1 (de) | Neue kondensierte heterocyclische Verbindungen und ihre Verwendung für Heilmittel | |
| Ukawa et al. | SYNTHESIS OF 5-OXO-5H-[IlBENZOPYRANO~ 4, 3-blPYRIDINE DERIVATIVES | |
| US4156726A (en) | 4-Oxo-2-carboxyl quinoline derivatives used as antiallergic compounds | |
| US4377702A (en) | Acetic acid derivatives | |
| US4474787A (en) | 7,6 Dioxo-4H,6H-pyrano[3,2-g]quinoline dicarboxylic acids and anti-allergic use thereof | |
| US3931239A (en) | 6-Oxo-7-substituted-6H-indeno-[5,4-b]furan(and thiophene)-carboxylic acids | |
| EP0497201B1 (en) | Tricyclic compounds and intermediates thereof | |
| US4122092A (en) | Total synthesis of (±)-picropodophyllone and (±)-4'-demethylpicropodophyllone | |
| EP0089781B1 (en) | Bicyclic benzo fused compounds | |
| CA1168233A (en) | Thioalkanoyl amino acids | |
| CA1134359A (en) | Substituted pyrido [1,2-a] pyrimidines | |
| FI67080B (fi) | Foerfarande foer framstaellning av nya farmaceutiskt aktiva :6-benso-ny-pyronderivat | |
| Philipp et al. | Synthesis and antiallergic properties of some 4H, 5H-pyrano [3, 2-c][1] benzopyran-4-one, 4H, 5H-[1] benzothiopyrano [4, 3-b] pyran-4-one, and 1, 4-dihydro-5H-[1] benzothiopyrano [4, 3-b] pyridin-4-one derivatives | |
| US4434295A (en) | Anti-atherosclerotic 6,7-dihydro-7,7-disubstituted-khellin analogs | |
| US4335048A (en) | 5-(2-Hydroxypropoxy)-8-propyl-4H-1-benzopyran-4-one-2-carboxylic acid | |
| EP0150966B1 (en) | Benzopyran derivatives, compositions containing them and processes for their preparation | |
| US3979513A (en) | 1'-Substituted-9,10-dihydroanthracene-9-spiro-4'-piperidine derivatives | |
| US4873349A (en) | Ruthenium catalyst for biarylic coupling; new steganolides | |
| CA1112644A (en) | Dioxopyranoquinoline dicarboxylic acid derivatives | |
| KR810000611B1 (ko) | 프로피온산 유도체의 제조방법 | |
| US3985731A (en) | 2H-2-benzazepin-1,3-diones | |
| EP0003084B1 (en) | Spirobenzofuranone compounds, processes for their preparation and their use as medicines | |
| Walraven et al. | Synthesis of 1, 5‐and l, 7‐naphthyridin‐4 (1H)‐ones | |
| Cassis et al. | Dienone-phenol rearrangement of naphthalenetriones. A route to 10-acetoxy5, 6, 7, 8-tetra hydrophenanthrene-1, 4-diones |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |