NO122372B - - Google Patents

Download PDF

Info

Publication number: NO122372B
Authority: NO; Norway
Prior art keywords: methyl; indolyl; methoxy; acetate; ether
Prior art date: 1961-03-22

Application number

NO445869A

Other languages

English (en)

Norwegian (no)

Inventor

Tsung-Ying Shen

Original Assignee

Merck & Co Inc

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.)

1961-03-22

Filing date

1969-11-11

Publication date

1971-06-21

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=27584499&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NO122372(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1963-06-11 Priority claimed from US28693563 external-priority patent/US3161654A/en

1963-07-22 Priority claimed from US296451A external-priority patent/US3201414A/en

1963-10-07 Priority claimed from US314503A external-priority patent/US3242185A/en

1969-11-11 Application filed by Merck & Co Inc filed Critical Merck & Co Inc

1971-06-21 Publication of NO122372B publication Critical patent/NO122372B/no

Links

-1 biphenylyl Chemical group 0.000 claims description 83
150000001875 compounds Chemical class 0.000 claims description 24
238000000034 method Methods 0.000 claims description 20
125000000217 alkyl group Chemical group 0.000 claims description 18
239000002253 acid Substances 0.000 claims description 13
239000001257 hydrogen Substances 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 12
125000003545 alkoxy group Chemical group 0.000 claims description 9
150000002148 esters Chemical class 0.000 claims description 9
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
125000002905 alkanoylamido group Chemical group 0.000 claims description 6
125000003282 alkyl amino group Chemical group 0.000 claims description 5
150000002431 hydrogen Chemical class 0.000 claims description 5
125000001931 aliphatic group Chemical group 0.000 claims description 4
229910052783 alkali metal Inorganic materials 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 4
125000004414 alkyl thio group Chemical group 0.000 claims description 4
150000008064 anhydrides Chemical class 0.000 claims description 4
150000001540 azides Chemical class 0.000 claims description 4
125000001589 carboacyl group Chemical group 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
150000004820 halides Chemical class 0.000 claims description 3
238000002360 preparation method Methods 0.000 claims description 3
125000004423 acyloxy group Chemical group 0.000 claims description 2
150000001340 alkali metals Chemical class 0.000 claims description 2
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
125000002757 morpholinyl group Chemical group 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
125000003396 thiol group Chemical class [H]S* 0.000 claims description 2
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 96
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 75
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 42
239000000203 mixture Substances 0.000 description 27
239000000243 solution Substances 0.000 description 24
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 14
239000012312 sodium hydride Substances 0.000 description 14
229910000104 sodium hydride Inorganic materials 0.000 description 14
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 13
229910052757 nitrogen Inorganic materials 0.000 description 13
239000011541 reaction mixture Substances 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
239000003921 oil Substances 0.000 description 12
239000003208 petroleum Substances 0.000 description 12
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
239000002480 mineral oil Substances 0.000 description 11
235000010446 mineral oil Nutrition 0.000 description 11
239000000047 product Substances 0.000 description 11
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
238000005917 acylation reaction Methods 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 8
230000010933 acylation Effects 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 8
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 7
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 7
TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 7
239000008188 pellet Substances 0.000 description 7
RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
239000007858 starting material Substances 0.000 description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
230000000694 effects Effects 0.000 description 5
238000003756 stirring Methods 0.000 description 5
NNVGRWTYRUNMRQ-UHFFFAOYSA-N (5-methoxy-2,4-dimethyl-1h-indol-3-yl) acetate Chemical compound COC1=CC=C2NC(C)=C(OC(C)=O)C2=C1C NNVGRWTYRUNMRQ-UHFFFAOYSA-N 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
238000001816 cooling Methods 0.000 description 4
238000001914 filtration Methods 0.000 description 4
238000004452 microanalysis Methods 0.000 description 4
239000012299 nitrogen atmosphere Substances 0.000 description 4
239000002904 solvent Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
239000007868 Raney catalyst Substances 0.000 description 3
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
229910000564 Raney nickel Inorganic materials 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
235000019445 benzyl alcohol Nutrition 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
238000004821 distillation Methods 0.000 description 3
239000005457 ice water Substances 0.000 description 3
125000001041 indolyl group Chemical group 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
150000003839 salts Chemical class 0.000 description 3
159000000000 sodium salts Chemical class 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
IGKCFJIMROHCRQ-UHFFFAOYSA-N 2-(1-benzoyl-5-methoxy-2-methylindol-3-yl)-3-phenylpropanoic acid Chemical compound CC1=C(C(CC=2C=CC=CC=2)C(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=CC=C1 IGKCFJIMROHCRQ-UHFFFAOYSA-N 0.000 description 2
BAFSYRUXYADRNK-UHFFFAOYSA-N 2-(5-methoxy-2-methyl-1h-indol-3-yl)-3-phenylpropanoic acid Chemical compound C12=CC(OC)=CC=C2NC(C)=C1C(C(O)=O)CC1=CC=CC=C1 BAFSYRUXYADRNK-UHFFFAOYSA-N 0.000 description 2
NWPBFGWVZQGAHM-UHFFFAOYSA-N 4-methylbenzenecarbothioyl chloride Chemical compound CC1=CC=C(C(Cl)=S)C=C1 NWPBFGWVZQGAHM-UHFFFAOYSA-N 0.000 description 2
JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
206010018691 Granuloma Diseases 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
TXWGINUZLBAKDF-UHFFFAOYSA-N N-Deschlorobenzoyl indomethacin Chemical compound COC1=CC=C2NC(C)=C(CC(O)=O)C2=C1 TXWGINUZLBAKDF-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
125000005907 alkyl ester group Chemical group 0.000 description 2
150000001350 alkyl halides Chemical class 0.000 description 2
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
230000003110 anti-inflammatory effect Effects 0.000 description 2
125000003435 aroyl group Chemical group 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
239000002585 base Substances 0.000 description 2
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
150000001732 carboxylic acid derivatives Chemical group 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
239000003480 eluent Substances 0.000 description 2
238000010828 elution Methods 0.000 description 2
239000012259 ether extract Substances 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
229910000042 hydrogen bromide Inorganic materials 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
BZOYDXSFKAXISN-UHFFFAOYSA-N methyl 2-[1-(4-chlorobenzoyl)-2-methyl-5-nitroindol-3-yl]acetate Chemical compound ClC1=CC=C(C(=O)N2C(=C(C3=CC(=CC=C23)[N+](=O)[O-])CC(=O)OC)C)C=C1 BZOYDXSFKAXISN-UHFFFAOYSA-N 0.000 description 2
OKHORWCUMZIORR-UHFFFAOYSA-N methyl 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetate Chemical compound C12=CC=C(OC)C=C2C(CC(=O)OC)=C(C)N1C(=O)C1=CC=C(Cl)C=C1 OKHORWCUMZIORR-UHFFFAOYSA-N 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
229940067157 phenylhydrazine Drugs 0.000 description 2
150000004031 phenylhydrazines Chemical class 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000000376 reactant Substances 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
239000007787 solid Substances 0.000 description 2
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
GMKZBFFLCONHDE-UHFFFAOYSA-N (4-nitrophenyl) benzoate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC(=O)C1=CC=CC=C1 GMKZBFFLCONHDE-UHFFFAOYSA-N 0.000 description 1
ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 1
OEHYXZZWECLGIA-UHFFFAOYSA-N 2,4-dimethylbenzenecarbothioyl chloride Chemical compound CC1=CC=C(C(Cl)=S)C(C)=C1 OEHYXZZWECLGIA-UHFFFAOYSA-N 0.000 description 1
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 description 1
AEJAPRPYYAHEJH-UHFFFAOYSA-N 2-[5-(dimethylamino)-2-methyl-1H-indol-3-yl]acetic acid Chemical compound CC=1NC2=CC=C(C=C2C1CC(=O)O)N(C)C AEJAPRPYYAHEJH-UHFFFAOYSA-N 0.000 description 1
CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical class [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 1
PLAZTCDQAHEYBI-UHFFFAOYSA-N 2-nitrotoluene Chemical class CC1=CC=CC=C1[N+]([O-])=O PLAZTCDQAHEYBI-UHFFFAOYSA-N 0.000 description 1
BSNNYLYELGBSBA-UHFFFAOYSA-N 4-(difluoromethoxy)benzoic acid Chemical compound OC(=O)C1=CC=C(OC(F)F)C=C1 BSNNYLYELGBSBA-UHFFFAOYSA-N 0.000 description 1
OXZYBOLWRXENKT-UHFFFAOYSA-N 4-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=C(C(Cl)=O)C=C1 OXZYBOLWRXENKT-UHFFFAOYSA-N 0.000 description 1
XRHGYUZYPHTUJZ-UHFFFAOYSA-N 4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-N 0.000 description 1
125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 1
PJHWTWHVCOZCPU-UHFFFAOYSA-N 4-methylbenzenecarbothioic s-acid Chemical compound CC1=CC=C(C(O)=S)C=C1 PJHWTWHVCOZCPU-UHFFFAOYSA-N 0.000 description 1
BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
OZFPSOBLQZPIAV-UHFFFAOYSA-N 5-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2NC=CC2=C1 OZFPSOBLQZPIAV-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
229920000742 Cotton Polymers 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical class C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
238000006683 Mannich reaction Methods 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
235000013832 Valeriana officinalis Nutrition 0.000 description 1
244000126014 Valeriana officinalis Species 0.000 description 1
210000000683 abdominal cavity Anatomy 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 1
229960001138 acetylsalicylic acid Drugs 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
125000003368 amide group Chemical group 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
230000001754 anti-pyretic effect Effects 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
125000003710 aryl alkyl group Chemical group 0.000 description 1
125000004391 aryl sulfonyl group Chemical group 0.000 description 1
NHVHYFAWHCJELN-UHFFFAOYSA-N benzene;n,n-dimethylformamide Chemical compound CN(C)C=O.C1=CC=CC=C1 NHVHYFAWHCJELN-UHFFFAOYSA-N 0.000 description 1
230000037396 body weight Effects 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000006482 condensation reaction Methods 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000008098 formaldehyde solution Substances 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000000295 fuel oil Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
ICYOLCFDSJJLAC-UHFFFAOYSA-N gramine Chemical class C1=CC=C[C]2C(CN(C)C)=CN=C21 ICYOLCFDSJJLAC-UHFFFAOYSA-N 0.000 description 1
GOERTRUXQHDLHC-UHFFFAOYSA-N gramine Natural products COC1=CC=C2NC=C(CN(C)C)C2=C1 GOERTRUXQHDLHC-UHFFFAOYSA-N 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
229940040102 levulinic acid Drugs 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
238000002844 melting Methods 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
HYNDOCFHNYVELW-UHFFFAOYSA-N methyl 2-[1-(2-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetate Chemical compound C12=CC=C(OC)C=C2C(CC(=O)OC)=C(C)N1C(=O)C1=CC=CC=C1Cl HYNDOCFHNYVELW-UHFFFAOYSA-N 0.000 description 1
NLDCIKQKIOJTTR-UHFFFAOYSA-N methyl 2-[5-methoxy-2-methyl-1-(4-nitrobenzoyl)indol-3-yl]acetate Chemical compound C12=CC=C(OC)C=C2C(CC(=O)OC)=C(C)N1C(=O)C1=CC=C([N+]([O-])=O)C=C1 NLDCIKQKIOJTTR-UHFFFAOYSA-N 0.000 description 1
CYXSQCVTSSQJHM-UHFFFAOYSA-N methyl 2-[5-methoxy-2-methyl-1-(4-phenylbenzoyl)indol-3-yl]acetate Chemical compound C12=CC=C(OC)C=C2C(CC(=O)OC)=C(C)N1C(=O)C(C=C1)=CC=C1C1=CC=CC=C1 CYXSQCVTSSQJHM-UHFFFAOYSA-N 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
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 1
230000035484 reaction time Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
239000000523 sample Substances 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
238000005809 transesterification reaction Methods 0.000 description 1
235000016788 valerian Nutrition 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000008096 xylene Substances 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Indole Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

NO445869A 1961-03-22 1969-11-11 NO122372B (de)

Applications Claiming Priority (14)

Application Number	Priority Date	Filing Date	Title
US9743461A	1961-03-22	1961-03-22
US16461562A	1962-01-05	1962-01-05
NO14373562		1962-03-21
US28693563 US3161654A (en)	1962-01-05	1963-06-11	alpha-(1-aroyl-3-indolyl) alkanoic acids
US296451A US3201414A (en)	1963-07-22	1963-07-22	New 1-heteroacyl-3-indolyl aliphatic acids
US31045463A	1963-09-20	1963-09-20
US31047763A	1963-09-20	1963-09-20
US314503A US3242185A (en)	1963-10-07	1963-10-07	Lower aliphatic acids, salts and derivatives thereof
US32386363A	1963-11-04	1963-11-04
US321328A US3275644A (en)	1962-01-05	1963-11-04	Certain 1-azolylindol-3-ylaliphatic acids
US321686A US3275645A (en)	1962-01-05	1963-11-06	N-(1-acyl-3-indolyl)-acids
US437338A US3338921A (en)	1962-01-05	1965-01-26	Thenoic and furoic acids
US442152A US3328423A (en)	1962-01-05	1965-03-23	alpha-(3-indolyl)-cyclopropyl lower aliphatic acids
US528020A US3316267A (en)	1962-01-05	1966-02-15	Indolyl acids

Publications (1)

Publication Number	Publication Date
NO122372B true NO122372B (de)	1971-06-21

Family

ID=27584499

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
NO1234/68A NO135064C (de)	1961-03-22	1968-04-01
NO445869A NO122372B (de)	1961-03-22	1969-11-11

Family Applications Before (1)

Application Number	Title	Priority Date	Filing Date
NO1234/68A NO135064C (de)	1961-03-22	1968-04-01

Country Status (9)

Country	Link
CH (8)	CH426822A (de)
CY (1)	CY348A (de)
DE (3)	DE1795543C3 (de)
DK (5)	DK111959B (de)
FI (2)	FI41158B (de)
GB (1)	GB997638A (de)
MY (1)	MY6600092A (de)
NO (2)	NO135064C (de)
SE (5)	SE315592B (de)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
HU176215B (en)	1978-01-27	1981-01-28	Chinoin Gyogyszer Es Vegyeszet	Process for preparing a cyclodextrin-indomethacin inclusion complex with a ratio of at about 2:1
US7135495B2 (en)	2000-03-09	2006-11-14	Ono Pharmaceutical Co., Ltd.	Indole derivatives
CA2459515A1 (en)	2001-09-07	2003-03-20	Kazuhiko Torisu	Indole derivatives
US20230218644A1 (en)	2020-04-16	2023-07-13	Som Innovation Biotech, S.A.	Compounds for use in the treatment of viral infections by respiratory syndrome-related coronavirus
CN113248419A (zh) *	2021-06-09	2021-08-13	云南中医药大学	一种新型HuR抑制剂1-苯磺酰基-3-苯基吲哚-4,5-二酮的合成方法
CN115417804A (zh) *	2022-09-16	2022-12-02	天津药明康德新药开发有限公司	一种7-甲基-1h-吲哚-5-羧酸的合成方法

1962
- 1962-03-16 DE DE1795543A patent/DE1795543C3/de not_active Expired
- 1962-03-16 FI FI0561/62A patent/FI41158B/fi active
- 1962-03-16 DE DE1962M0070802 patent/DE1620030B1/de active Pending
- 1962-03-16 DE DE1962M0070803 patent/DE1620031B1/de active Pending
- 1962-03-20 GB GB10695/62A patent/GB997638A/en not_active Expired
- 1962-03-21 CH CH335362A patent/CH426822A/de unknown
- 1962-03-21 SE SE11783/66A patent/SE315592B/xx unknown
- 1962-03-21 CH CH1737266A patent/CH445493A/de unknown
- 1962-03-21 CH CH1736966A patent/CH445490A/de unknown
- 1962-03-21 CH CH1736766A patent/CH450419A/de unknown
- 1962-03-21 CH CH1737066A patent/CH445491A/de unknown
- 1962-03-21 CH CH1737166A patent/CH445492A/de unknown
- 1962-03-21 CH CH1737366A patent/CH449018A/de unknown
- 1962-03-21 CH CH1736866A patent/CH450420A/de unknown
1966
- 1966-05-25 DK DK268166AA patent/DK111959B/da unknown
- 1966-06-03 CY CY34866A patent/CY348A/xx unknown
- 1966-09-01 SE SE1178266A patent/SE314984B/xx unknown
- 1966-09-01 SE SE1178466A patent/SE315593B/xx unknown
- 1966-09-01 SE SE1178166A patent/SE315282B/xx unknown
- 1966-09-01 SE SE1178062A patent/SE315281B/xx unknown
- 1966-11-11 DK DK586266AA patent/DK116737B/da unknown
- 1966-11-11 DK DK586366AA patent/DK120637B/da unknown
- 1966-11-11 DK DK586166AA patent/DK120340B/da unknown
- 1966-12-28 FI FI3456/66A patent/FI41159B/fi active
- 1966-12-31 MY MY196692A patent/MY6600092A/xx unknown
1967
- 1967-02-13 DK DK77067AA patent/DK114975B/da unknown
1968
- 1968-04-01 NO NO1234/68A patent/NO135064C/no unknown
1969
- 1969-11-11 NO NO445869A patent/NO122372B/no unknown

Also Published As

Publication number	Publication date
DE1795543A1 (de)	1972-01-13
SE314984B (de)	1969-09-22
DE1620030B1 (de)	1970-03-05
DE1795543B2 (de)	1979-09-20
SE315592B (de)	1969-10-06
DK111959B (da)	1968-10-28
CH426822A (de)	1966-12-31
FI41159B (de)	1969-06-02
CH450419A (de)	1968-01-31
SE315282B (de)	1969-09-29
DK116737B (da)	1970-02-09
DE1620031B1 (de)	1971-04-08
NO135064B (de)	1976-10-25
GB997638A (en)	1965-07-07
CH450420A (de)	1968-01-31
CH445490A (de)	1967-10-31
CH445491A (de)	1967-10-31
MY6600092A (en)	1966-12-31
CH445493A (de)	1967-10-31
DK120637B (da)	1971-06-28
CH449018A (de)	1967-12-31
NO135064C (de)	1977-02-02
CH445492A (de)	1967-10-31
DK114975B (da)	1969-08-25
DK120340B (da)	1971-05-17
FI41158B (de)	1969-06-02
CY348A (en)	1966-06-03
DE1795543C3 (de)	1980-06-04
SE315281B (de)	1969-09-29
SE315593B (de)	1969-10-06

Publication	Publication Date	Title
US3161654A (en)	1964-12-15	alpha-(1-aroyl-3-indolyl) alkanoic acids
US4393062A (en)	1983-07-12	Pharmaceutical compositions and method for the production of an anti-inflammatory effect
DE69717537T2 (de)	2003-11-06	6-Benzyl-2H-pyridazin-3-on Derivate,deren Herstellung und deren Verwendung als Inhibitoren der Prostaglandin G/H Synthase I and II (COX I and COX II)
US3471515A (en)	1969-10-07	(2-hydroxy-3-substituted aminopropoxy)indoles
US4402968A (en)	1983-09-06	Antifungal benzofuranyl imidazole compounds
US3316260A (en)	1967-04-25	Derivatives of alpha amino-indole-3-acetic and propionic acids
US3586694A (en)	1971-06-22	1-benzoylbenzimidazol-2-ylacetic acids
NO141687B (no)	1980-01-14	Analogifremgangsmaate ved fremstilling av terapeutisk aktive 1-oxo-2,2-disubstituerte-5-indanyloxy-eddiksyrer
CA1073907A (en)	1980-03-18	3-(biphenylyl and phenyloxy) butane-1-amine derivatives
Paragamian et al.	1968	A study of the synthesis and some reactions of perimidines
NO122372B (de)	1971-06-21
EP0598754A1 (de)	1994-06-01	Indole
Cavill et al.	1957	The chemistry of ants. II. Structure and configuration of iridolactone (isoiridomyrmecin)
NO157637B (no)	1988-01-11	Gelformig anode og elektrokjemisk celle inneholdende denne
NO823587L (no)	1983-04-29	Laktoner.
US3242163A (en)	1966-03-22	Indolyl aliphatic acids
US4160032A (en)	1979-07-03	Oxindoles as sleep-inducers
EP0033614A1 (de)	1981-08-12	Derivate der Phenylalkansäure, Verfahren zu deren Herstellung und sie enthaltende pharmazeutische Zusammensetzungen
GB2110210A (en)	1983-06-15	Benzofuranones
DK151957B (da)	1988-01-18	Analogifremgangsmaade til fremstilling af 3-substituerede 2-oxo-1-benzimidazolinalkansyrer eller estere eller amider deraf eller salte deraf med baser
NO179513B (no)	1996-07-15	2-substituerte kinolylmetoksy-fenyleddiksyrederivater, legemidler inneholdende dem samt deres anvendelse for fremstilling av legemidler
NO166911B (no)	1991-06-10	Baktericid og fungicid middel paa basis av tributyltinnforbindelser og prochloraz, samt anvendelser derav.
EP0080271A1 (de)	1983-06-01	Indomethacinphenylester-Derivate, ihre Verwendung und diese enthaltende Zusammensetzungen
FI62057C (fi)	1982-11-10	Foerfarande foer framstaellning av nya substituerade diaminobensofenoner
NO134522B (de)	1976-07-19