NO324750B1 - Substituerte N-benzylindol-3-yl-glyokylinsyrederivater med anti-tumoreffekt, og farmasoytiske preparater som inneholder slike. - Google Patents
Substituerte N-benzylindol-3-yl-glyokylinsyrederivater med anti-tumoreffekt, og farmasoytiske preparater som inneholder slike. Download PDFInfo
- Publication number
- NO324750B1 NO324750B1 NO20023039A NO20023039A NO324750B1 NO 324750 B1 NO324750 B1 NO 324750B1 NO 20023039 A NO20023039 A NO 20023039A NO 20023039 A NO20023039 A NO 20023039A NO 324750 B1 NO324750 B1 NO 324750B1
- Authority
- NO
- Norway
- Prior art keywords
- acid
- salts
- compounds
- general formula
- indol
- Prior art date
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- -1 N-benzylindol-3-yl Chemical group 0.000 title claims description 17
- 239000002253 acid Substances 0.000 title claims description 14
- 230000000259 anti-tumor effect Effects 0.000 title claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000000725 suspension Substances 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 229940093915 gynecological organic acid Drugs 0.000 claims description 4
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 235000005985 organic acids Nutrition 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 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
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- FVSYLLUZSRCXEH-UHFFFAOYSA-N 2-[1-[(4-aminophenyl)methyl]indol-3-yl]-2-oxo-n-pyridin-4-ylacetamide Chemical compound C1=CC(N)=CC=C1CN1C2=CC=CC=C2C(C(=O)C(=O)NC=2C=CN=CC=2)=C1 FVSYLLUZSRCXEH-UHFFFAOYSA-N 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- HRYYIVZPPROGAN-UHFFFAOYSA-N 2-[1-[(4-nitrophenyl)methyl]indol-3-yl]-2-oxo-n-pyridin-4-ylacetamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1CN1C2=CC=CC=C2C(C(=O)C(=O)NC=2C=CN=CC=2)=C1 HRYYIVZPPROGAN-UHFFFAOYSA-N 0.000 claims description 2
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
- 239000000174 gluconic acid Substances 0.000 claims description 2
- 235000012208 gluconic acid Nutrition 0.000 claims description 2
- 238000001802 infusion Methods 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000004310 lactic acid Substances 0.000 claims description 2
- 235000014655 lactic acid Nutrition 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 239000011664 nicotinic acid Substances 0.000 claims description 2
- 235000001968 nicotinic acid Nutrition 0.000 claims description 2
- 229960003512 nicotinic acid Drugs 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- MRDIZANPJLYUKO-UHFFFAOYSA-N 2-(1-benzylindol-3-yl)-2-oxoacetic acid Chemical class C12=CC=CC=C2C(C(=O)C(=O)O)=CN1CC1=CC=CC=C1 MRDIZANPJLYUKO-UHFFFAOYSA-N 0.000 claims 1
- 239000011230 binding agent Substances 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- 238000000034 method Methods 0.000 description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
- 239000012299 nitrogen atmosphere Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 239000000010 aprotic solvent Substances 0.000 description 8
- 238000005984 hydrogenation reaction Methods 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
- 239000012454 non-polar solvent Substances 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 150000003141 primary amines Chemical class 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229960004979 fampridine Drugs 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 150000002475 indoles Chemical class 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- KGCNHWXDPDPSBV-UHFFFAOYSA-N p-nitrobenzyl chloride Chemical compound [O-][N+](=O)C1=CC=C(CCl)C=C1 KGCNHWXDPDPSBV-UHFFFAOYSA-N 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 239000003586 protic polar solvent Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- RVPTXIBMGYNFNG-UHFFFAOYSA-N 1-[(4-nitrophenyl)methyl]indole Chemical compound C1=CC([N+](=O)[O-])=CC=C1CN1C2=CC=CC=C2C=C1 RVPTXIBMGYNFNG-UHFFFAOYSA-N 0.000 description 1
- MQLACMBJVPINKE-UHFFFAOYSA-N 10-[(3-hydroxy-4-methoxyphenyl)methylidene]anthracen-9-one Chemical compound C1=C(O)C(OC)=CC=C1C=C1C2=CC=CC=C2C(=O)C2=CC=CC=C21 MQLACMBJVPINKE-UHFFFAOYSA-N 0.000 description 1
- BVRCPMXFRMVPNG-UHFFFAOYSA-N 2-(1h-indol-3-yl)-2-oxo-n-pyridin-4-ylacetamide Chemical compound C=1NC2=CC=CC=C2C=1C(=O)C(=O)NC1=CC=NC=C1 BVRCPMXFRMVPNG-UHFFFAOYSA-N 0.000 description 1
- AWMLDBKLOPNOAR-UHFFFAOYSA-N 2-(1h-indol-3-yl)-2-oxoacetamide Chemical class C1=CC=C2C(C(=O)C(=O)N)=CNC2=C1 AWMLDBKLOPNOAR-UHFFFAOYSA-N 0.000 description 1
- FPEGGKCNMYDNMW-UHFFFAOYSA-N 2-(1h-indol-3-yl)-2-oxoacetyl chloride Chemical compound C1=CC=C2C(C(=O)C(=O)Cl)=CNC2=C1 FPEGGKCNMYDNMW-UHFFFAOYSA-N 0.000 description 1
- DJFPJDMKYOGJGU-UHFFFAOYSA-N 2-hydroxy-2-(1h-indol-3-yl)acetic acid Chemical class C1=CC=C2C(C(C(O)=O)O)=CNC2=C1 DJFPJDMKYOGJGU-UHFFFAOYSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 102000000587 Glycerolphosphate Dehydrogenase Human genes 0.000 description 1
- 108010041921 Glycerolphosphate Dehydrogenase Proteins 0.000 description 1
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 1
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 102000005473 Secretory Phospholipases A2 Human genes 0.000 description 1
- 108010031873 Secretory Phospholipases A2 Proteins 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000005574 benzylation reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000000368 destabilizing effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- CBFZWGRQXZYRRR-UHFFFAOYSA-N pyridin-4-amine;hydrochloride Chemical compound Cl.NC1=CC=NC=C1 CBFZWGRQXZYRRR-UHFFFAOYSA-N 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19962300A DE19962300A1 (de) | 1999-12-23 | 1999-12-23 | Substituierte N-Benzyl-Indol-3-yl-glyoxylsäure-Derivate mit Antitumorwirkung |
| PCT/EP2000/012947 WO2001047913A2 (de) | 1999-12-23 | 2000-12-19 | Substituierte n-benzyl-indol-3-yl- glyoxylsäure-derivate antitumorwirkung |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20023039D0 NO20023039D0 (no) | 2002-06-21 |
| NO20023039L NO20023039L (no) | 2002-08-09 |
| NO324750B1 true NO324750B1 (no) | 2007-12-03 |
Family
ID=7934006
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20023039A NO324750B1 (no) | 1999-12-23 | 2002-06-21 | Substituerte N-benzylindol-3-yl-glyokylinsyrederivater med anti-tumoreffekt, og farmasoytiske preparater som inneholder slike. |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US6432987B2 (sk) |
| EP (1) | EP1240157B1 (sk) |
| JP (1) | JP2003519137A (sk) |
| KR (1) | KR100747425B1 (sk) |
| CN (1) | CN1283637C (sk) |
| AR (1) | AR027098A1 (sk) |
| AT (1) | ATE259364T1 (sk) |
| AU (1) | AU772745B2 (sk) |
| BG (1) | BG106924A (sk) |
| BR (1) | BR0016712A (sk) |
| CA (1) | CA2395259A1 (sk) |
| CO (1) | CO5251472A1 (sk) |
| CZ (1) | CZ20022094A3 (sk) |
| DE (2) | DE19962300A1 (sk) |
| DK (1) | DK1240157T3 (sk) |
| ES (1) | ES2215768T3 (sk) |
| HK (1) | HK1054038B (sk) |
| HU (1) | HUP0203716A3 (sk) |
| IL (1) | IL150235A0 (sk) |
| MX (1) | MXPA02006229A (sk) |
| NO (1) | NO324750B1 (sk) |
| NZ (2) | NZ533731A (sk) |
| PL (1) | PL195014B1 (sk) |
| PT (1) | PT1240157E (sk) |
| RU (1) | RU2266280C2 (sk) |
| SK (1) | SK8752002A3 (sk) |
| TR (1) | TR200400601T4 (sk) |
| TW (1) | TWI284128B (sk) |
| UA (1) | UA75060C2 (sk) |
| WO (1) | WO2001047913A2 (sk) |
| ZA (1) | ZA200204896B (sk) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19946301A1 (de) * | 1998-04-02 | 2001-04-19 | Asta Medica Ag | Indolyl-3-glyoxylsäure-Derivate mit therapeutisch wertvollen Eigenschaften |
| DE19814838C2 (de) * | 1998-04-02 | 2001-01-18 | Asta Medica Ag | Indolyl-3-glyoxylsäure-Derivate mit Antitumorwirkung |
| DE10037310A1 (de) * | 2000-07-28 | 2002-02-07 | Asta Medica Ag | Neue Indolderivate und deren Verwendung als Arzneimittel |
| DE10318609A1 (de) * | 2003-04-24 | 2004-11-11 | Elbion Ag | 5-Hydroxyindole mit N-Oxidgruppen und deren Verwendung als Therapeutika |
| DE10318611A1 (de) * | 2003-04-24 | 2004-11-11 | Elbion Ag | 4-, 6- oder 7-Hydroxyindole mit N-Oxidgruppen und deren Verwendung als Therapeutika |
| EP1641777A1 (de) * | 2003-06-05 | 2006-04-05 | Zentaris GmbH | Indolderivate mit apoptose induzierender wirkung |
| US7211588B2 (en) * | 2003-07-25 | 2007-05-01 | Zentaris Gmbh | N-substituted indolyl-3-glyoxylamides, their use as medicaments and process for their preparation |
| CN102060806A (zh) | 2003-09-11 | 2011-05-18 | iTherX药品公司 | 细胞因子抑制剂 |
| US7268159B2 (en) * | 2003-09-25 | 2007-09-11 | Wyeth | Substituted indoles |
| DE102004031538A1 (de) * | 2004-06-29 | 2006-02-09 | Baxter International Inc., Deerfield | Pharmazeutische Darreichungsform zur oralen Verabreichung eines schwerlöslichen Wirkstoffs, Verfahren zu deren Herstellung und Kit |
| WO2006073973A2 (en) | 2004-12-31 | 2006-07-13 | Reddy Us Therapeutics, Inc. | Novel benzylamine derivatives as cetp inhibitors |
| US8604055B2 (en) | 2004-12-31 | 2013-12-10 | Dr. Reddy's Laboratories Ltd. | Substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors |
| US8242149B2 (en) * | 2005-03-11 | 2012-08-14 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-binding cassette transporters |
| AU2007281747B2 (en) * | 2006-08-07 | 2013-11-07 | Ironwood Pharmaceuticals, Inc. | Indole compounds |
| EP2091532A1 (en) * | 2006-11-28 | 2009-08-26 | Ziopharm Oncology, Inc. | Use of indolyl-3-glyoxylic acid derivatives including indibulin, alone or in combination with further agents for treating cancer |
| NZ624963A (en) | 2009-04-29 | 2016-07-29 | Amarin Pharmaceuticals Ie Ltd | Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same |
| AR084433A1 (es) | 2010-12-22 | 2013-05-15 | Ironwood Pharmaceuticals Inc | Inhibidores de la faah y composiciones farmaceuticas que los contienen |
| US9199967B2 (en) | 2011-08-18 | 2015-12-01 | Dr. Reddy's Laboratories Ltd. | Substituted heterocyclic amine compounds as cholestryl ester-transfer protein (CETP) inhibitors |
| CA2850022C (en) | 2011-09-27 | 2018-05-01 | Dr. Reddy's Laboratories, Ltd. | 5 - benzylaminomethyl - 6 - aminopyrazolo [3,4-b] pyridine derivatives as cholesteryl ester-transfer protein (cetp) inhibitors useful for the treatment of atherosclerosis |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2135160A1 (en) * | 1992-05-08 | 1993-11-25 | Masatoshi Inai | Indole derivative |
| IL109311A0 (en) * | 1993-04-16 | 1994-07-31 | Lilly Co Eli | 1H-indole-3-acetamide sPla2 inhibitors |
| JP3536258B2 (ja) * | 1994-02-22 | 2004-06-07 | メレルファーマスーティカルズ インコーポレイテッド | エストロゲンに関連する新生物及び病気の処置に有用な新規なインドール誘導体類 |
| KR100368707B1 (ko) * | 1994-04-01 | 2003-06-02 | 일라이 릴리 앤드 캄파니 | 1H-인돌-3-글리옥실아미드sPLA2억제제 |
| DE19636150A1 (de) * | 1996-09-06 | 1998-03-12 | Asta Medica Ag | N-substituierte Indol-3-glyoxylamide mit antiasthmatischer, antiallergischer und immunsuppressiver/immunmodulierender Wirkung |
| AU6229298A (en) * | 1997-02-20 | 1998-09-09 | Shionogi & Co., Ltd. | Indole dicarboxylic acid derivatives |
| US5972988A (en) * | 1997-03-26 | 1999-10-26 | Eli Lilly And Company | Method for treatment of chronic bronchitis using indole compounds |
| WO1998047507A1 (en) * | 1997-04-24 | 1998-10-29 | Shionogi & Co., Ltd. | Method for the treatment of stroke using n-heterocyclic glyoxylamide compounds |
| TW455581B (en) * | 1997-06-26 | 2001-09-21 | Lilly Co Eli | Process for preparing 4-substituted-1H-indole-3-glyoxamides |
| EP1011670A4 (en) * | 1997-08-28 | 2004-10-27 | Lilly Co Eli | PROCESS FOR TREATING NON-RHUMATOID POLYARTHRITIS |
| EP1007056A1 (en) * | 1997-09-26 | 2000-06-14 | Eli Lilly And Company | Method for the treatment of cystic fibrosis |
| US6177426B1 (en) * | 1997-10-27 | 2001-01-23 | Eli Lilly And Company | Morpholino-N-ethyl ester prodrugs of indole sPLA2 inhibitors |
| WO1999021545A1 (en) * | 1997-10-27 | 1999-05-06 | Eli Lilly And Company | ISOPROPYL ESTER PRODRUGS OF INDOLE sPLA2 INHIBITORS |
| JP2001520991A (ja) * | 1997-10-27 | 2001-11-06 | イーライ・リリー・アンド・カンパニー | インドールｓＰＬＡ２阻害剤のＮ，Ｎ−ジエチルグリコールアミドエステルプロドラッグ |
| WO1999024033A1 (en) * | 1997-11-12 | 1999-05-20 | Shionogi & Co., Ltd. | Method for the treatment of disorders associated with apoptosis using n-heterocyclic glyoxylamide compounds |
| CA2310249A1 (en) * | 1997-11-14 | 1999-05-27 | August Masaru Watanabe | Treatment for alzheimer's disease |
| CA2322162A1 (en) * | 1998-02-25 | 1999-09-02 | Genetics Institute, Llc | Inhibitors of phospholipase enzymes |
| DE19814838C2 (de) * | 1998-04-02 | 2001-01-18 | Asta Medica Ag | Indolyl-3-glyoxylsäure-Derivate mit Antitumorwirkung |
| DZ2770A1 (fr) * | 1998-04-17 | 2003-12-01 | Lilly Co Eli | Procédé de préparation de 1h-indol-3 glyoxamides substituées en position 4. |
| DE19818964A1 (de) * | 1998-04-28 | 1999-11-04 | Dresden Arzneimittel | Neue Hydroxyindole, deren Verwendung als Inhibitoren der Phospodiesterase 4 und Verfahren zu deren Herstellung |
| ES2262072T3 (es) * | 1998-04-28 | 2006-11-16 | Elbion Ag | Derivados de indol y su utilizacion como inhibidores de la fosfodiesterasa 4. |
| CA2331036A1 (en) * | 1998-05-01 | 1999-11-11 | Daniel Jon Sall | Spla2 inhibitor ester |
| WO1999057100A1 (en) * | 1998-05-01 | 1999-11-11 | Eli Lilly And Company | Spla2 inhibitor compounds for treatment of disease |
| WO2000067802A1 (en) * | 1999-05-10 | 2000-11-16 | Protarga, Inc. | Fatty acid-n-substituted indol-3-glyoxyl-amide compositions and uses thereof |
| TWI269654B (en) * | 1999-09-28 | 2007-01-01 | Baxter Healthcare Sa | N-substituted indole-3-glyoxylamide compounds having anti-tumor action |
-
1999
- 1999-12-23 DE DE19962300A patent/DE19962300A1/de not_active Withdrawn
-
2000
- 2000-12-15 US US09/736,431 patent/US6432987B2/en not_active Expired - Fee Related
- 2000-12-19 EP EP00983349A patent/EP1240157B1/de not_active Expired - Lifetime
- 2000-12-19 NZ NZ533731A patent/NZ533731A/en unknown
- 2000-12-19 WO PCT/EP2000/012947 patent/WO2001047913A2/de active IP Right Grant
- 2000-12-19 SK SK875-2002A patent/SK8752002A3/sk unknown
- 2000-12-19 RU RU2002120462/04A patent/RU2266280C2/ru not_active IP Right Cessation
- 2000-12-19 DE DE50005284T patent/DE50005284D1/de not_active Expired - Fee Related
- 2000-12-19 NZ NZ519977A patent/NZ519977A/en unknown
- 2000-12-19 IL IL15023500A patent/IL150235A0/xx not_active IP Right Cessation
- 2000-12-19 CZ CZ20022094A patent/CZ20022094A3/cs unknown
- 2000-12-19 PT PT00983349T patent/PT1240157E/pt unknown
- 2000-12-19 KR KR1020027007933A patent/KR100747425B1/ko not_active IP Right Cessation
- 2000-12-19 TR TR2004/00601T patent/TR200400601T4/xx unknown
- 2000-12-19 AT AT00983349T patent/ATE259364T1/de not_active IP Right Cessation
- 2000-12-19 AU AU20119/01A patent/AU772745B2/en not_active Ceased
- 2000-12-19 ES ES00983349T patent/ES2215768T3/es not_active Expired - Lifetime
- 2000-12-19 CA CA002395259A patent/CA2395259A1/en not_active Abandoned
- 2000-12-19 MX MXPA02006229A patent/MXPA02006229A/es active IP Right Grant
- 2000-12-19 BR BR0016712-6A patent/BR0016712A/pt not_active Application Discontinuation
- 2000-12-19 CN CNB008182094A patent/CN1283637C/zh not_active Expired - Fee Related
- 2000-12-19 DK DK00983349T patent/DK1240157T3/da active
- 2000-12-19 HU HU0203716A patent/HUP0203716A3/hu unknown
- 2000-12-19 JP JP2001549383A patent/JP2003519137A/ja not_active Withdrawn
- 2000-12-19 UA UA2002076107A patent/UA75060C2/uk unknown
- 2000-12-19 TW TW089127265A patent/TWI284128B/zh not_active IP Right Cessation
- 2000-12-19 PL PL355684A patent/PL195014B1/pl unknown
- 2000-12-22 CO CO00097375A patent/CO5251472A1/es not_active Application Discontinuation
- 2000-12-22 AR ARP000106916A patent/AR027098A1/es not_active Application Discontinuation
-
2002
- 2002-06-19 ZA ZA200204896A patent/ZA200204896B/en unknown
- 2002-06-21 NO NO20023039A patent/NO324750B1/no unknown
- 2002-07-16 BG BG106924A patent/BG106924A/bg unknown
-
2003
- 2003-09-09 HK HK03106408.0A patent/HK1054038B/zh not_active IP Right Cessation
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