CA1113113A - Cycloalkane-substituted phenylacetic acid derivatives, their use and preparation - Google Patents
Cycloalkane-substituted phenylacetic acid derivatives, their use and preparationInfo
- Publication number
- CA1113113A CA1113113A CA300,479A CA300479A CA1113113A CA 1113113 A CA1113113 A CA 1113113A CA 300479 A CA300479 A CA 300479A CA 1113113 A CA1113113 A CA 1113113A
- Authority
- CA
- Canada
- Prior art keywords
- compound
- formula
- acid
- ylmethyl
- produced
- 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
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 97
- 238000000034 method Methods 0.000 claims abstract description 86
- 230000008569 process Effects 0.000 claims abstract description 76
- -1 phenylacetic acid ester Chemical class 0.000 claims abstract description 39
- 239000002253 acid Substances 0.000 claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 150000002148 esters Chemical class 0.000 claims abstract description 22
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 15
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims abstract description 12
- 150000002923 oximes Chemical class 0.000 claims abstract description 7
- 230000000911 decarboxylating effect Effects 0.000 claims abstract description 6
- 150000002081 enamines Chemical class 0.000 claims abstract description 6
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 4
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 51
- 239000000203 mixture Substances 0.000 claims description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 41
- 239000002904 solvent Substances 0.000 claims description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 35
- 239000000126 substance Substances 0.000 claims description 33
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 21
- 238000006460 hydrolysis reaction Methods 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- 230000007062 hydrolysis Effects 0.000 claims description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- 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 claims description 15
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical group Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 14
- 235000019260 propionic acid Nutrition 0.000 claims description 14
- 238000010992 reflux Methods 0.000 claims description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 10
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 7
- 238000006114 decarboxylation reaction Methods 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical group OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 claims description 6
- HGXRYRVHSWACKC-UHFFFAOYSA-N 2-[4-[(2-oxocyclohexyl)methyl]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1CC1C(=O)CCCC1 HGXRYRVHSWACKC-UHFFFAOYSA-N 0.000 claims description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 239000001117 sulphuric acid Substances 0.000 claims description 5
- 235000011149 sulphuric acid Nutrition 0.000 claims description 5
- 239000004475 Arginine Substances 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- ZTILNNBAMDTFFE-UHFFFAOYSA-N 2-[4-[(2-oxocyclopentyl)methyl]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1CC1C(=O)CCC1 ZTILNNBAMDTFFE-UHFFFAOYSA-N 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 229940040526 anhydrous sodium acetate Drugs 0.000 claims description 3
- YCQDXOVSZLROEG-UHFFFAOYSA-N ethyl 2-[4-(iodomethyl)phenyl]propanoate Chemical compound CCOC(=O)C(C)C1=CC=C(CI)C=C1 YCQDXOVSZLROEG-UHFFFAOYSA-N 0.000 claims description 3
- 125000004494 ethyl ester group Chemical group 0.000 claims description 3
- 150000002900 organolithium compounds Chemical class 0.000 claims description 3
- 235000017281 sodium acetate Nutrition 0.000 claims description 3
- JXUBTJKWKFRPQY-UHFFFAOYSA-N 2-[4-[(2-hydroxyiminocyclohexyl)methyl]phenyl]acetic acid Chemical compound ON=C1CCCCC1CC1=CC=C(CC(O)=O)C=C1 JXUBTJKWKFRPQY-UHFFFAOYSA-N 0.000 claims description 2
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 claims description 2
- 239000012298 atmosphere Substances 0.000 claims description 2
- MZQXTMGJTYTKJN-UHFFFAOYSA-N ethyl 2-[4-(chloromethyl)phenyl]acetate Chemical compound CCOC(=O)CC1=CC=C(CCl)C=C1 MZQXTMGJTYTKJN-UHFFFAOYSA-N 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 claims description 2
- YGNXYFLJZILPEK-UHFFFAOYSA-N n-cyclopentylidenehydroxylamine Chemical compound ON=C1CCCC1 YGNXYFLJZILPEK-UHFFFAOYSA-N 0.000 claims description 2
- 229940049953 phenylacetate Drugs 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 4
- 239000001257 hydrogen Substances 0.000 claims 4
- 239000001301 oxygen Substances 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- VCLMVNTWRRBQPX-UHFFFAOYSA-N 2-[4-[(2-hydroxyiminocyclopentyl)methyl]phenyl]propanoic acid Chemical compound C1=CC(C(C(O)=O)C)=CC=C1CC1C(=NO)CCC1 VCLMVNTWRRBQPX-UHFFFAOYSA-N 0.000 claims 2
- JLGLDJKSKWKYNN-UHFFFAOYSA-N 2-[4-[(2-oxocyclohexyl)methyl]phenyl]propanoic acid Chemical compound C1=CC(C(C(O)=O)C)=CC=C1CC1C(=O)CCCC1 JLGLDJKSKWKYNN-UHFFFAOYSA-N 0.000 claims 2
- VEZUQRBDRNJBJY-UHFFFAOYSA-N cyclohexanone oxime Chemical compound ON=C1CCCCC1 VEZUQRBDRNJBJY-UHFFFAOYSA-N 0.000 claims 2
- JCKJFGHNPRDOMZ-UHFFFAOYSA-N ethyl 2-[4-[(2-hydroxyiminocyclohexyl)methyl]phenyl]propanoate Chemical compound C1=CC(C(C)C(=O)OCC)=CC=C1CC1C(=NO)CCCC1 JCKJFGHNPRDOMZ-UHFFFAOYSA-N 0.000 claims 2
- YMBXTVYHTMGZDW-UHFFFAOYSA-N loxoprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1CC1C(=O)CCC1 YMBXTVYHTMGZDW-UHFFFAOYSA-N 0.000 claims 2
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 claims 1
- KWNVJIHRVMOOPH-UHFFFAOYSA-N 2-[4-[(2-hydroxyiminocyclohexyl)methyl]phenyl]propanoic acid Chemical compound C1=CC(C(C(O)=O)C)=CC=C1CC1C(=NO)CCCC1 KWNVJIHRVMOOPH-UHFFFAOYSA-N 0.000 claims 1
- LEEYBUPIUCHURK-UHFFFAOYSA-N 2-[4-[(2-hydroxyiminocyclopentyl)methyl]phenyl]acetic acid Chemical compound ON=C1CCCC1CC1=CC=C(CC(O)=O)C=C1 LEEYBUPIUCHURK-UHFFFAOYSA-N 0.000 claims 1
- 238000009833 condensation Methods 0.000 claims 1
- 230000005494 condensation Effects 0.000 claims 1
- PSYLICHAEOTQCN-UHFFFAOYSA-N ethyl 1-[[4-(1-ethoxy-1-oxopropan-2-yl)phenyl]methyl]-2-oxocyclopentane-1-carboxylate Chemical compound C1=CC(C(C)C(=O)OCC)=CC=C1CC1(C(=O)OCC)C(=O)CCC1 PSYLICHAEOTQCN-UHFFFAOYSA-N 0.000 claims 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims 1
- NXPHCVPFHOVZBC-UHFFFAOYSA-N hydroxylamine;sulfuric acid Chemical compound ON.OS(O)(=O)=O NXPHCVPFHOVZBC-UHFFFAOYSA-N 0.000 claims 1
- 150000002642 lithium compounds Chemical class 0.000 claims 1
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 claims 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 claims 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 claims 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 claims 1
- 229960003424 phenylacetic acid Drugs 0.000 abstract description 8
- 239000003279 phenylacetic acid Substances 0.000 abstract description 8
- 150000007513 acids Chemical class 0.000 abstract description 5
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract 1
- 239000002260 anti-inflammatory agent Substances 0.000 abstract 1
- SMBQBQBNOXIFSF-UHFFFAOYSA-N dilithium Chemical class [Li][Li] SMBQBQBNOXIFSF-UHFFFAOYSA-N 0.000 abstract 1
- 230000032050 esterification Effects 0.000 abstract 1
- 238000005886 esterification reaction Methods 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 76
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 239000002585 base Substances 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 17
- 239000003960 organic solvent Substances 0.000 description 16
- 229940095574 propionic acid Drugs 0.000 description 15
- 238000004821 distillation Methods 0.000 description 12
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- 238000000921 elemental analysis Methods 0.000 description 11
- 239000013078 crystal Substances 0.000 description 10
- 239000005457 ice water Substances 0.000 description 10
- 238000005292 vacuum distillation Methods 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 7
- 230000035484 reaction time Effects 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 239000011707 mineral Substances 0.000 description 5
- 235000010755 mineral Nutrition 0.000 description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- 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 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 125000002059 L-arginyl group Chemical class O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])C(=N[H])N([H])[H] 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 229940125773 compound 10 Drugs 0.000 description 3
- 229940125758 compound 15 Drugs 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- LJRSKOFNPMYRSO-UHFFFAOYSA-N ethyl 2-[4-(chloromethyl)phenyl]propanoate Chemical compound CCOC(=O)C(C)C1=CC=C(CCl)C=C1 LJRSKOFNPMYRSO-UHFFFAOYSA-N 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 150000002334 glycols Chemical class 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 229960002895 phenylbutazone Drugs 0.000 description 3
- 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 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 125000001176 L-lysyl group Chemical class [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C([H])([H])C(N([H])[H])([H])[H] 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- JHZPNBKZPAWCJD-UHFFFAOYSA-N ethyl 2-oxocyclopentane-1-carboxylate Chemical compound CCOC(=O)C1CCCC1=O JHZPNBKZPAWCJD-UHFFFAOYSA-N 0.000 description 2
- 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 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- OGNVQLDIPUXYDH-ZPKKHLQPSA-N (2R,3R,4S)-3-(2-methylpropanoylamino)-4-(4-phenyltriazol-1-yl)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid Chemical compound CC(C)C(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)OC(C(O)=O)=C[C@@H]1N1N=NC(C=2C=CC=CC=2)=C1 OGNVQLDIPUXYDH-ZPKKHLQPSA-N 0.000 description 1
- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 241001535291 Analges Species 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 235000014328 Schoenoplectus acutus var occidentalis Nutrition 0.000 description 1
- 244000136421 Scirpus acutus Species 0.000 description 1
- 235000014326 Scirpus californicus Nutrition 0.000 description 1
- 235000017913 Scirpus lacustris Nutrition 0.000 description 1
- 239000004133 Sodium thiosulphate Substances 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 241000193803 Therea Species 0.000 description 1
- KQNKJJBFUFKYFX-UHFFFAOYSA-N acetic acid;trihydrate Chemical compound O.O.O.CC(O)=O KQNKJJBFUFKYFX-UHFFFAOYSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 229910052785 arsenic Inorganic materials 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 1
- 229930007927 cymene Natural products 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- IYWTVDXXPCVQTO-UHFFFAOYSA-N ethyl 1-[[4-(2-ethoxy-2-oxoethyl)phenyl]methyl]-2-oxocyclopentane-1-carboxylate Chemical compound C1=CC(CC(=O)OCC)=CC=C1CC1(C(=O)OCC)C(=O)CCC1 IYWTVDXXPCVQTO-UHFFFAOYSA-N 0.000 description 1
- FGSGHBPKHFDJOP-UHFFFAOYSA-N ethyl 2-oxocyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCCCC1=O FGSGHBPKHFDJOP-UHFFFAOYSA-N 0.000 description 1
- BAQKJENAVQLANS-UHFFFAOYSA-N fenbutrazate Chemical compound C=1C=CC=CC=1C(CC)C(=O)OCCN(C1C)CCOC1C1=CC=CC=C1 BAQKJENAVQLANS-UHFFFAOYSA-N 0.000 description 1
- 229960002533 fenbutrazate Drugs 0.000 description 1
- 238000001914 filtration Methods 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
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical class [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- YFNKIDBQEZZDLK-UHFFFAOYSA-N triglyme Chemical compound COCCOCCOCCOC YFNKIDBQEZZDLK-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
- C07C279/14—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/46—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- C07C251/50—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals
- C07C251/60—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP38907/77 | 1977-04-05 | ||
| JP3890677A JPS584699B2 (ja) | 1977-04-05 | 1977-04-05 | 置換フエニル酢酸誘導体及びその製法 |
| JP38906/77 | 1977-04-05 | ||
| JP3890777A JPS6034539B2 (ja) | 1977-04-05 | 1977-04-05 | オキシム置換フエニル酢酸誘導体及びその製法 |
| JP68468/77 | 1977-06-10 | ||
| JP6846877A JPS6034540B2 (ja) | 1977-06-10 | 1977-06-10 | オキシム置換フエニル酢酸誘導体の製造法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1113113A true CA1113113A (en) | 1981-11-24 |
Family
ID=27289981
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA300,479A Expired CA1113113A (en) | 1977-04-05 | 1978-04-05 | Cycloalkane-substituted phenylacetic acid derivatives, their use and preparation |
Country Status (11)
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DD141422A5 (de) * | 1978-01-27 | 1980-04-30 | Schering Ag | Verfahren zur herstellung von phenylessigsaeure-derivaten |
| DE2861078D1 (en) * | 1978-07-21 | 1981-12-03 | Schering Ag | Indan-1-carboxylic acid derivatives,process for their preparation and pharmaceutical preparations containing these compounds |
| CH645539A5 (de) * | 1980-06-09 | 1984-10-15 | Sankyo Co | Antiinflammatorische mittel fuer die aeusserliche anwendung. |
| US4423068A (en) * | 1982-07-14 | 1983-12-27 | Syntex (U.S.A.) Inc. | (3.2.0) Bicycloheptanone oxime ethers with therapeutic properties |
| JPS59196839A (ja) * | 1983-04-21 | 1984-11-08 | Sankyo Co Ltd | フエニル酢酸誘導体 |
| JPS6038323A (ja) * | 1983-08-10 | 1985-02-27 | Sankyo Co Ltd | 眼科用消炎剤 |
| SE8400239D0 (sv) * | 1984-01-19 | 1984-01-19 | Pharmacia Ab | Nya arylettiksyraderivat |
| JPS61268621A (ja) * | 1985-05-21 | 1986-11-28 | Sankyo Co Ltd | シロツプ製剤 |
| US4968718A (en) * | 1988-01-25 | 1990-11-06 | University Of Iowa Research Foundation | Topically effective, nonsteroidal drug for use in external and internal eye inflammations |
| US5179124A (en) * | 1988-01-25 | 1993-01-12 | University Of Iowa Research Foundation | Anti-inflammatory for use in external and internal eye inflammations |
| HU218923B (hu) * | 1993-10-06 | 2000-12-28 | Nicox S.A. | Gyulladásgátló és/vagy fájdalomcsillapító hatású nitrát-észterek, ezeket tartalmazó gyógyszerkészítmények és eljárás a vegyületek előállítására |
| IT1282660B1 (it) * | 1996-02-21 | 1998-03-31 | Chemi Spa | Processo per produrre l'acido (t) 2- 4-2-oxociclopentilmetil) fenilpropionico ed i suoi sali |
| IT1308633B1 (it) | 1999-03-02 | 2002-01-09 | Nicox Sa | Nitrossiderivati. |
| KR100695334B1 (ko) * | 2000-02-10 | 2007-03-15 | 니뽄 세키유 가가쿠 가부시키가이샤 | 2-치환 프로피온산의 제조방법 |
| IT1318673B1 (it) * | 2000-08-08 | 2003-08-27 | Nicox Sa | Farmaci per le disfunzioni sessuali. |
| IT1318674B1 (it) * | 2000-08-08 | 2003-08-27 | Nicox Sa | Faramaci per l'incontinenza. |
| CN100378145C (zh) * | 2001-06-21 | 2008-04-02 | 花王株式会社 | 研磨液组合物 |
| ITMI20020773A1 (it) * | 2002-04-11 | 2003-10-13 | Nicox Sa | Farmaci per il trattamento dell'artrite |
| TW200827343A (en) | 2006-09-11 | 2008-07-01 | Fuji Yakuhin Co Ltd | Novel phenylacetic acid derivative |
| JP5390883B2 (ja) | 2009-02-26 | 2014-01-15 | 国立大学法人 熊本大学 | ロキソプロフェン誘導体及びそれを含有する医薬 |
| WO2014167509A2 (en) * | 2013-04-10 | 2014-10-16 | Shasun Pharmaceuticals Limited | Loxoprofen polymorphs and process for preparation of the same |
| EP2926810A1 (en) | 2014-03-31 | 2015-10-07 | Sanovel Ilac Sanayi ve Ticaret A.S. | Oral liquid pharmaceutical formulations of loxoprofen |
| EP2926832A1 (en) | 2014-03-31 | 2015-10-07 | Sanovel Ilac Sanayi ve Ticaret A.S. | Pharmaceutical formulations of loxoprofen for topical use |
| EP2939666A1 (en) | 2014-04-29 | 2015-11-04 | Sanovel Ilac Sanayi ve Ticaret A.S. | Pharmaceutical formulations of loxoprofen |
| EP2959889A1 (en) | 2014-06-25 | 2015-12-30 | Sanovel Ilac Sanayi ve Ticaret A.S. | Orally disintegrating formulations of loxoprofen |
| US20170151177A1 (en) | 2014-06-30 | 2017-06-01 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Loxoprofen and gamma-aminobutiric acid receptor agonist combinations |
| WO2016046189A1 (en) | 2014-09-24 | 2016-03-31 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Loxoprofen and antispastic drug combinations |
| WO2016156354A1 (en) | 2015-03-31 | 2016-10-06 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Pharmaceutical composition comprising loxoprofen, glucosamine, chondroitin, hyaluronic acid for joint and cartilage disorders |
| CN109467506B (zh) | 2017-09-07 | 2021-12-07 | 江苏瑞科医药科技有限公司 | 一种取代苯乙酸衍生物的制备方法 |
| CN108997119B (zh) * | 2018-07-13 | 2020-10-20 | 湖北迅达药业股份有限公司 | 洛索洛芬钠合成工艺中缩合反应中间体的纯化方法 |
| CN112851500B (zh) * | 2021-02-10 | 2022-11-29 | 南京知和医药科技有限公司 | S-洛索洛芬衍生物及其制备方法、药物组合物和用途 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB971700A (en) * | 1961-02-02 | 1964-09-30 | Boots Pure Drug Co Ltd | Anti-Inflammatory Agents |
| US4008269A (en) * | 1970-05-05 | 1977-02-15 | William H. Rorer, Inc. | Phenylacetic acids |
| US3864384A (en) * | 1970-05-05 | 1975-02-04 | Rorer Inc William H | Substituted phenylacetic acid compounds |
| US3894080A (en) * | 1970-05-05 | 1975-07-08 | Rorer Inc William H | Phenylacetic acids |
| US3825587A (en) * | 1970-05-05 | 1974-07-23 | Rorer Inc William H | Substituted phenylacetic acid compounds |
| GB1364075A (en) * | 1971-09-04 | 1974-08-21 | Logeais Labor Jacques | Phenylacetic acid derivatives process for their preparation and therapeutic compositions |
| FR2243680B2 (US08087162-20120103-C00010.png) * | 1973-09-17 | 1977-01-28 | Logeais Labor Jacques |
-
1978
- 1978-03-10 US US05/885,527 patent/US4161538A/en not_active Expired - Lifetime
- 1978-04-04 DK DK148478A patent/DK150472C/da not_active IP Right Cessation
- 1978-04-04 DE DE2814556A patent/DE2814556C2/de not_active Expired
- 1978-04-05 GB GB13355/78A patent/GB1580113A/en not_active Expired
- 1978-04-05 ES ES468578A patent/ES468578A1/es not_active Expired
- 1978-04-05 NL NLAANVRAGE7803644,A patent/NL190519C/xx not_active IP Right Cessation
- 1978-04-05 CA CA300,479A patent/CA1113113A/en not_active Expired
- 1978-04-05 SE SE7803848A patent/SE437261B/sv not_active IP Right Cessation
- 1978-04-05 FR FR7810126A patent/FR2395256A1/fr active Granted
- 1978-04-05 CH CH367678A patent/CH633515A5/de not_active IP Right Cessation
- 1978-07-18 BE BE189363A patent/BE869097A/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DE2814556A1 (de) | 1978-10-12 |
| NL190519C (nl) | 1994-04-05 |
| US4161538A (en) | 1979-07-17 |
| BE869097A (fr) | 1979-01-18 |
| FR2395256B1 (US08087162-20120103-C00010.png) | 1982-12-10 |
| FR2395256A1 (fr) | 1979-01-19 |
| SE437261B (sv) | 1985-02-18 |
| GB1580113A (en) | 1980-11-26 |
| CH633515A5 (de) | 1982-12-15 |
| DK148478A (da) | 1978-10-06 |
| DE2814556C2 (de) | 1987-03-12 |
| DK150472C (da) | 1987-12-14 |
| DK150472B (da) | 1987-03-09 |
| NL7803644A (nl) | 1978-10-09 |
| ES468578A1 (es) | 1979-09-16 |
| SE7803848L (sv) | 1978-10-06 |
| NL190519B (nl) | 1993-11-01 |
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