CA1255657A - Derives de substitution en 1,3 de 2-oxindoles, agents analgesiques et anti-inflammatoires - Google Patents

Derives de substitution en 1,3 de 2-oxindoles, agents analgesiques et anti-inflammatoires

Info

Publication number: CA1255657A
Authority: CA; Canada
Prior art keywords: carbons; alkyl; oxindole; hydrogen; chloro
Prior art date: 1984-02-07
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

Application number

CA000473576A

Other languages

English (en)

Inventor

Saul B. Kadin

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Pfizer Ltd Great Britain

Original Assignee

Pfizer Ltd Great Britain

Priority date (The priority date 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 date listed.)

1984-02-07

Filing date

1985-02-05

Publication date

1989-06-13

1985-02-05 Application filed by Pfizer Ltd Great Britain filed Critical Pfizer Ltd Great Britain

1989-02-27 Priority to CA000592243A priority Critical patent/CA1289556C/fr

1989-06-13 Application granted granted Critical

1989-06-13 Publication of CA1255657A publication Critical patent/CA1255657A/fr

Status Expired legal-status Critical Current

Links

-1 1,3-disubstituted 2-oxindoles Chemical class 0.000 title claims description 110
230000000202 analgesic effect Effects 0.000 title abstract description 13
239000000730 antalgic agent Substances 0.000 title abstract description 7
239000002260 anti-inflammatory agent Substances 0.000 title abstract description 7
229940121363 anti-inflammatory agent Drugs 0.000 title abstract description 7
150000001875 compounds Chemical class 0.000 claims description 90
125000000217 alkyl group Chemical group 0.000 claims description 67
238000000034 method Methods 0.000 claims description 60
239000001257 hydrogen Substances 0.000 claims description 37
229910052739 hydrogen Inorganic materials 0.000 claims description 37
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
238000006243 chemical reaction Methods 0.000 claims description 36
125000001309 chloro group Chemical group Cl* 0.000 claims description 31
238000002360 preparation method Methods 0.000 claims description 27
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 22
JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims description 22
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 20
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
125000000753 cycloalkyl group Chemical group 0.000 claims description 18
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 17
125000001153 fluoro group Chemical group F* 0.000 claims description 17
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 15
125000003545 alkoxy group Chemical group 0.000 claims description 15
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
150000003839 salts Chemical class 0.000 claims description 15
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
239000003795 chemical substances by application Substances 0.000 claims description 9
CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
125000004414 alkyl thio group Chemical group 0.000 claims description 8
125000001246 bromo group Chemical group Br* 0.000 claims description 8
239000002904 solvent Substances 0.000 claims description 8
125000001544 thienyl group Chemical group 0.000 claims description 8
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 7
239000012442 inert solvent Substances 0.000 claims description 7
239000012948 isocyanate Substances 0.000 claims description 7
HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 7
IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 6
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 6
125000002541 furyl group Chemical group 0.000 claims description 6
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
150000003254 radicals Chemical class 0.000 claims description 6
239000000126 substance Substances 0.000 claims description 6
LURYMYITPCOQAU-UHFFFAOYSA-N benzoyl isocyanate Chemical compound O=C=NC(=O)C1=CC=CC=C1 LURYMYITPCOQAU-UHFFFAOYSA-N 0.000 claims description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
NFPZMLAKARIPMY-UHFFFAOYSA-N n-benzoyl-3-(furan-2-carbonyl)-2-oxo-3h-indole-1-carboxamide Chemical compound O=C1C(C(=O)C=2OC=CC=2)C2=CC=CC=C2N1C(=O)NC(=O)C1=CC=CC=C1 NFPZMLAKARIPMY-UHFFFAOYSA-N 0.000 claims description 5
125000001624 naphthyl group Chemical group 0.000 claims description 5
125000005359 phenoxyalkyl group Chemical group 0.000 claims description 5
125000003884 phenylalkyl group Chemical group 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical compound C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 claims description 3
OFTKFKYVSBNYEC-UHFFFAOYSA-N 2-furoyl chloride Chemical compound ClC(=O)C1=CC=CO1 OFTKFKYVSBNYEC-UHFFFAOYSA-N 0.000 claims description 3
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 3
QQMMNSFDWAYBFL-UHFFFAOYSA-N 5-chloro-n-(cyclohexanecarbonyl)-2-oxo-3-(thiophene-2-carbonyl)-3h-indole-1-carboxamide Chemical compound O=C1C(C(=O)C=2SC=CC=2)C2=CC(Cl)=CC=C2N1C(=O)NC(=O)C1CCCCC1 QQMMNSFDWAYBFL-UHFFFAOYSA-N 0.000 claims description 3
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 3
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 3
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 3
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
239000000010 aprotic solvent Substances 0.000 claims description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
125000001589 carboacyl group Chemical group 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 3
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
229910052760 oxygen Inorganic materials 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
229910052717 sulfur Chemical group 0.000 claims description 3
239000011593 sulfur Chemical group 0.000 claims description 3
RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 3
229930192474 thiophene Natural products 0.000 claims description 3
150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
QIQITDHWZYEEPA-UHFFFAOYSA-N thiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CS1 QIQITDHWZYEEPA-UHFFFAOYSA-N 0.000 claims description 2
150000002431 hydrogen Chemical group 0.000 claims 14
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims 4
UDGKZGLPXCRRAM-UHFFFAOYSA-N 1,2,5-thiadiazole Chemical compound C=1C=NSN=1 UDGKZGLPXCRRAM-UHFFFAOYSA-N 0.000 claims 2
125000000168 pyrrolyl group Chemical group 0.000 claims 2
MVZPGVKQORMMNZ-UHFFFAOYSA-N 3-(furan-2-carbonyl)-1,3-dihydroindol-2-one Chemical compound O=C1NC2=CC=CC=C2C1C(=O)C1=CC=CO1 MVZPGVKQORMMNZ-UHFFFAOYSA-N 0.000 claims 1
150000001338 aliphatic hydrocarbons Chemical class 0.000 claims 1
150000002170 ethers Chemical class 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
IOMSWISKMUXPLV-UHFFFAOYSA-N n-benzoyl-2-oxo-3h-indole-1-carboxamide Chemical compound O=C1CC2=CC=CC=C2N1C(=O)NC(=O)C1=CC=CC=C1 IOMSWISKMUXPLV-UHFFFAOYSA-N 0.000 claims 1
208000002193 Pain Diseases 0.000 abstract description 10
102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 abstract description 6
108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 abstract description 6
230000001154 acute effect Effects 0.000 abstract description 5
150000005623 oxindoles Chemical class 0.000 abstract description 5
UYINJAQCJCYCGO-UHFFFAOYSA-N 2-oxo-3h-indole-1-carboxamide Chemical class C1=CC=C2N(C(=O)N)C(=O)CC2=C1 UYINJAQCJCYCGO-UHFFFAOYSA-N 0.000 abstract description 4
102000003820 Lipoxygenases Human genes 0.000 abstract description 4
108090000128 Lipoxygenases Proteins 0.000 abstract description 4
229910052757 nitrogen Inorganic materials 0.000 abstract description 4
208000024891 symptom Diseases 0.000 abstract description 4
208000017667 Chronic Disease Diseases 0.000 abstract description 3
230000001684 chronic effect Effects 0.000 abstract description 3
208000014674 injury Diseases 0.000 abstract description 3
239000000543 intermediate Substances 0.000 abstract description 3
201000008482 osteoarthritis Diseases 0.000 abstract description 3
206010039073 rheumatoid arthritis Diseases 0.000 abstract description 3
230000008733 trauma Effects 0.000 abstract description 3
239000003112 inhibitor Substances 0.000 abstract description 2
238000001356 surgical procedure Methods 0.000 abstract description 2
102000004190 Enzymes Human genes 0.000 abstract 1
108090000790 Enzymes Proteins 0.000 abstract 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
239000000243 solution Substances 0.000 description 43
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
239000007787 solid Substances 0.000 description 33
239000000203 mixture Substances 0.000 description 31
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
238000001914 filtration Methods 0.000 description 26
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
239000000047 product Substances 0.000 description 17
238000003756 stirring Methods 0.000 description 17
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
239000002253 acid Substances 0.000 description 15
235000011167 hydrochloric acid Nutrition 0.000 description 15
229960000443 hydrochloric acid Drugs 0.000 description 15
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
238000010992 reflux Methods 0.000 description 11
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
239000000460 chlorine Substances 0.000 description 10
239000002244 precipitate Substances 0.000 description 10
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 9
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 9
238000002844 melting Methods 0.000 description 9
230000008018 melting Effects 0.000 description 9
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 8
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 7
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
239000002002 slurry 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
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-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 5
241000124008 Mammalia Species 0.000 description 5
229910052783 alkali metal Inorganic materials 0.000 description 5
238000004458 analytical method Methods 0.000 description 5
229960002327 chloral hydrate Drugs 0.000 description 5
150000002500 ions Chemical class 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
239000011734 sodium Substances 0.000 description 5
PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 4
HSYFISNDMZKGRS-UHFFFAOYSA-N 4-chloro-1h-indole-2,3-dione Chemical compound ClC1=CC=CC2=C1C(=O)C(=O)N2 HSYFISNDMZKGRS-UHFFFAOYSA-N 0.000 description 4
RVXLBLSGEPQBIO-UHFFFAOYSA-N 6-chloro-1h-indole-2,3-dione Chemical compound ClC1=CC=C2C(=O)C(=O)NC2=C1 RVXLBLSGEPQBIO-UHFFFAOYSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 4
230000003187 abdominal effect Effects 0.000 description 4
125000005605 benzo group Chemical group 0.000 description 4
RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 4
239000013078 crystal Substances 0.000 description 4
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 4
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
230000035484 reaction time Effects 0.000 description 4
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
238000005303 weighing Methods 0.000 description 4
JUPOEJXDARZUBY-UHFFFAOYSA-N 3-(thiophene-2-carbonyl)-1,3-dihydroindol-2-one Chemical compound O=C1NC2=CC=CC=C2C1C(=O)C1=CC=CS1 JUPOEJXDARZUBY-UHFFFAOYSA-N 0.000 description 3
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
CENVPIZOTHULGJ-UHFFFAOYSA-N 6-chloro-1,3-dihydroindol-2-one Chemical compound ClC1=CC=C2CC(=O)NC2=C1 CENVPIZOTHULGJ-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
206010061218 Inflammation Diseases 0.000 description 3
AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 3
101150005971 PREPL gene Proteins 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
229910052784 alkaline earth metal Inorganic materials 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
230000000694 effects Effects 0.000 description 3
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
230000004054 inflammatory process Effects 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
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MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
239000007832 Na2SO4 Substances 0.000 description 1
206010030113 Oedema Diseases 0.000 description 1
206010030124 Oedema peripheral Diseases 0.000 description 1
229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
208000004550 Postoperative Pain Diseases 0.000 description 1
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241001455617 Sula Species 0.000 description 1
241000891463 Tetraedron Species 0.000 description 1
230000009102 absorption Effects 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
125000002252 acyl group Chemical group 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
150000001340 alkali metals Chemical class 0.000 description 1
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical group CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
150000001722 carbon compounds Chemical class 0.000 description 1
QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000007810 chemical reaction solvent Substances 0.000 description 1
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
238000005660 chlorination reaction Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 description 1
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
125000000950 dibromo group Chemical group Br* 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
NJAONFWUEGWOPG-UHFFFAOYSA-N dimethyl 2-(4-bromo-2-nitrophenyl)propanedioate Chemical compound COC(=O)C(C(=O)OC)C1=CC=C(Br)C=C1[N+]([O-])=O NJAONFWUEGWOPG-UHFFFAOYSA-N 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
238000003255 drug test Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
238000005837 enolization reaction Methods 0.000 description 1
HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
238000003304 gavage Methods 0.000 description 1
239000011521 glass Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
150000004679 hydroxides Chemical class 0.000 description 1
239000005457 ice water Substances 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
239000011872 intimate mixture Substances 0.000 description 1
QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000002609 medium Substances 0.000 description 1
KHXUTOLCCFWPDH-UHFFFAOYSA-N methyl 2-(4-bromo-2-nitrophenyl)acetate Chemical compound COC(=O)CC1=CC=C(Br)C=C1[N+]([O-])=O KHXUTOLCCFWPDH-UHFFFAOYSA-N 0.000 description 1
IGBYIHDGXCCONV-UHFFFAOYSA-N n-benzoyl-2-oxo-3-(thiophene-2-carbonyl)-3h-indole-1-carboxamide Chemical compound O=C1C(C(=O)C=2SC=CC=2)C2=CC=CC=C2N1C(=O)NC(=O)C1=CC=CC=C1 IGBYIHDGXCCONV-UHFFFAOYSA-N 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Substances [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
ZCYXXKJEDCHMGH-UHFFFAOYSA-N nonane Chemical compound CCCC[CH]CCCC ZCYXXKJEDCHMGH-UHFFFAOYSA-N 0.000 description 1
BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 1
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
UWBHMRBRLOJJAA-UHFFFAOYSA-N oxaluric acid Chemical compound NC(=O)NC(=O)C(O)=O UWBHMRBRLOJJAA-UHFFFAOYSA-N 0.000 description 1
BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
239000004926 polymethyl methacrylate Substances 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
229910052709 silver Inorganic materials 0.000 description 1
239000004332 silver Substances 0.000 description 1
150000003385 sodium Chemical class 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
238000002211 ultraviolet spectrum Methods 0.000 description 1
PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
239000008096 xylene Substances 0.000 description 1
150000003738 xylenes Chemical class 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CA000473576A 1984-02-07 1985-02-05 Derives de substitution en 1,3 de 2-oxindoles, agents analgesiques et anti-inflammatoires Expired CA1255657A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000592243A CA1289556C (fr)	1984-02-07	1989-02-27	Intermediaires de 2-indoles monosubstitues en 1 ou 3, utiles pour la production d'analgesiques ou d'anti-inflammatoires

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date
US57790384A	1984-02-07	1984-02-07
US577,903		1984-02-07
US61986184A	1984-06-12	1984-06-12
US619,861		1984-06-12

Related Child Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000592243A Division CA1289556C (fr)	1984-02-07	1989-02-27	Intermediaires de 2-indoles monosubstitues en 1 ou 3, utiles pour la production d'analgesiques ou d'anti-inflammatoires

Publications (1)

Publication Number	Publication Date
CA1255657A true CA1255657A (fr)	1989-06-13

Family

ID=27077370

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000473576A Expired CA1255657A (fr)	1984-02-07	1985-02-05	Derives de substitution en 1,3 de 2-oxindoles, agents analgesiques et anti-inflammatoires

Country Status (12)

Country	Link
AU (1)	AU552760B2 (fr)
CA (1)	CA1255657A (fr)
EG (1)	EG17329A (fr)
ES (3)	ES8605232A1 (fr)
FI (1)	FI81796C (fr)
HU (2)	HUT39159A (fr)
IL (1)	IL74251A (fr)
NO (1)	NO165798C (fr)
NZ (1)	NZ211052A (fr)
PH (2)	PH20395A (fr)
PT (1)	PT79926B (fr)
ZW (1)	ZW1585A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
PH23498A (en) *	1984-08-06	1989-08-16	Sterling Drug Inc	3-carbonyl-1-aminoalkyl-1h-indoles,composition and use thereof

1985
- 1985-02-05 CA CA000473576A patent/CA1255657A/fr not_active Expired
- 1985-02-05 PH PH31819A patent/PH20395A/en unknown
- 1985-02-05 PT PT7992685A patent/PT79926B/pt unknown
- 1985-02-05 ZW ZW1585A patent/ZW1585A1/xx unknown
- 1985-02-05 NZ NZ21105285A patent/NZ211052A/xx unknown
- 1985-02-05 IL IL74251A patent/IL74251A/xx not_active IP Right Cessation
- 1985-02-05 ES ES540133A patent/ES8605232A1/es not_active Expired
- 1985-02-06 FI FI850491A patent/FI81796C/fi not_active IP Right Cessation
- 1985-02-06 AU AU38467/85A patent/AU552760B2/en not_active Expired
- 1985-02-06 HU HU45285D patent/HUT39159A/hu unknown
- 1985-02-06 EG EG7185A patent/EG17329A/xx active
- 1985-02-06 HU HU45285A patent/HU193942B/hu unknown
- 1985-02-06 NO NO850443A patent/NO165798C/no not_active IP Right Cessation
- 1985-11-15 ES ES548944A patent/ES8605776A1/es not_active Expired
- 1985-11-15 ES ES548943A patent/ES8606273A1/es not_active Expired
1986
- 1986-07-01 PH PH33969A patent/PH23393A/en unknown

Also Published As

Publication number	Publication date
AU3846785A (en)	1985-08-15
HU193942B (en)	1987-12-28
ES548943A0 (es)	1986-04-16
NO165798B (no)	1991-01-02
ES548944A0 (es)	1986-04-01
PT79926B (en)	1987-02-05
IL74251A (en)	1990-01-18
FI850491A0 (fi)	1985-02-06
NO165798C (no)	1991-04-10
PH20395A (en)	1986-12-12
NZ211052A (en)	1988-08-30
ES8605232A1 (es)	1986-03-16
EG17329A (en)	1991-11-30
AU552760B2 (en)	1986-06-19
IL74251A0 (en)	1985-05-31
FI850491L (fi)	1985-08-08
FI81796B (fi)	1990-08-31
ES8605776A1 (es)	1986-04-01
PT79926A (en)	1985-03-01
ES8606273A1 (es)	1986-04-16
PH23393A (en)	1989-07-26
NO850443L (no)	1985-08-08
HUT37753A (en)	1986-02-28
ZW1585A1 (en)	1985-06-19
FI81796C (fi)	1990-12-10
HUT39159A (en)	1986-08-28
ES540133A0 (es)	1986-03-16

Legal Events

Date	Code	Title	Description
2006-06-13	MKEX	Expiry

Publication	Publication Date	Title
US4556672A (en)	1985-12-03	3-Substituted 2-oxindole-1-carboxamides as analgesic and anti-inflammatory agents
US4569942A (en)	1986-02-11	N,3-Disubstituted 2-oxindole-1-carboxamides as analgesic and antiinflammatory agents
US4690943A (en)	1987-09-01	Analgesic and antiinflammatory 1,3-diacyl-2-oxindole compounds
US4721712A (en)	1988-01-26	1,3-disubstituted 2-oxindoles as analgesic and anti-inflammatory agents
EP0208510B1 (fr)	1991-09-11	Oxindole-3-carboxamines substituées utilisées analgésiques et anti-inflammatoires
US4658037A (en)	1987-04-14	Intermediates for 1,3-disubstituted 2-oxindoles as analgesic and antiinflammatory agents
EP0153818B1 (fr)	1989-03-15	2-Oxindoles 1,3-disubstitués et leur utilisation comme agents analgésiques et anti-inflammatoires
KR860001874B1 (ko)	1986-10-24	2-옥스인돌-1-카복스 아미드의 제조방법
US4665194A (en)	1987-05-12	Process for making 2-oxindole-1-carboxamides and intermediates therefor
CA1255657A (fr)	1989-06-13	Derives de substitution en 1,3 de 2-oxindoles, agents analgesiques et anti-inflammatoires
US4752609A (en)	1988-06-21	Analgesic and antiinflammatory 1,3-diacyl-2-oxindole compounds
US4808601A (en)	1989-02-28	Analgesic and antiinflammatory 1,3-diacyl-2-oxindole compounds
US4652658A (en)	1987-03-24	Process for making 2-oxindole-1-carboxamides and intermediates therefor
CA1289556C (fr)	1991-09-24	Intermediaires de 2-indoles monosubstitues en 1 ou 3, utiles pour la production d'analgesiques ou d'anti-inflammatoires
CA1253490A (fr)	1989-05-02	Procede de production de 2-oxindole-1-carboxamides
PL145950B1 (en)	1988-12-31	Method of obtaining 1,3-diacyl-2-ketoindoles
CA1287626C (fr)	1991-08-13	Derives de substitution en n de 2-oxo-indole-1- carboxamides, utiles comme produits intermediaires pour la preparation d'analgesiques et d'anti-inflammatoires
JPH0335315B2 (fr)	1991-05-27
IE850288L (en)	1985-08-07	Analgesic oxindoles.
BG60375B2 (bg)	1995-02-28	Заместени на 3-то място 2-оксиндол-1-карбоксамиди като аналгетични и противовъзпалителни вещества
CS252847B2 (cs)	1987-10-15	Způsob výroby N,3-disubstituovaných 2-oxindol-1-karboxamidů