LT3064B - Indolineamide derivatives, process for the preparation thereof and pharmaceutical compositions containing the same - Google Patents
Indolineamide derivatives, process for the preparation thereof and pharmaceutical compositions containing the same Download PDFInfo
- Publication number
- LT3064B LT3064B LTIP114A LTIP114A LT3064B LT 3064 B LT3064 B LT 3064B LT IP114 A LTIP114 A LT IP114A LT IP114 A LTIP114 A LT IP114A LT 3064 B LT3064 B LT 3064B
- Authority
- LT
- Lithuania
- Prior art keywords
- group
- substituted
- alkyl
- dcm
- compound
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 26
- 230000008569 process Effects 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 6
- OFLWZAHKUJNRML-UHFFFAOYSA-N 2,3-dihydroindole-1-carboxamide Chemical class C1=CC=C2N(C(=O)N)CCC2=C1 OFLWZAHKUJNRML-UHFFFAOYSA-N 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 193
- -1 5-dimethylamino-1-naphthyl Chemical group 0.000 claims abstract description 59
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 40
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 34
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 30
- 150000002367 halogens Chemical class 0.000 claims abstract description 29
- 125000003277 amino group Chemical group 0.000 claims abstract description 24
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
- 239000001257 hydrogen Substances 0.000 claims abstract description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 20
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 18
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims abstract description 16
- 125000001424 substituent group Chemical group 0.000 claims abstract description 13
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 11
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims abstract description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 8
- 125000006501 nitrophenyl group Chemical group 0.000 claims abstract description 8
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims abstract description 7
- SNPQRYOQWLOTFA-UHFFFAOYSA-N 2,2-dimethyl-1,3-thiazolidine Chemical compound CC1(C)NCCS1 SNPQRYOQWLOTFA-UHFFFAOYSA-N 0.000 claims abstract description 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims abstract description 5
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims abstract description 5
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims abstract description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims abstract description 5
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims abstract description 5
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims abstract description 4
- 150000001925 cycloalkenes Chemical class 0.000 claims abstract description 4
- 125000005843 halogen group Chemical group 0.000 claims abstract description 4
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims abstract description 4
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims abstract description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 3
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 78
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 72
- 239000002253 acid Substances 0.000 claims description 24
- 239000000460 chlorine Substances 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 15
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- NYGZLYXAPMMJTE-UHFFFAOYSA-M metanil yellow Chemical group [Na+].[O-]S(=O)(=O)C1=CC=CC(N=NC=2C=CC(NC=3C=CC=CC=3)=CC=2)=C1 NYGZLYXAPMMJTE-UHFFFAOYSA-M 0.000 claims description 5
- 230000000144 pharmacologic effect Effects 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 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 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- 150000008065 acid anhydrides Chemical class 0.000 claims description 2
- 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 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- CPHXLFKIUVVIOQ-UHFFFAOYSA-N 2-(trifluoromethoxy)benzaldehyde Chemical group FC(F)(F)OC1=CC=CC=C1C=O CPHXLFKIUVVIOQ-UHFFFAOYSA-N 0.000 claims 2
- 125000003282 alkyl amino group Chemical group 0.000 claims 2
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims 2
- XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims 1
- 102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 claims 1
- 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 229910002091 carbon monoxide Inorganic materials 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 1
- 125000004663 dialkyl amino group Chemical group 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
- 150000004885 piperazines Chemical group 0.000 claims 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims 1
- 150000001408 amides Chemical class 0.000 abstract description 13
- 238000011282 treatment Methods 0.000 abstract description 11
- 210000003169 central nervous system Anatomy 0.000 abstract description 5
- 241001465754 Metazoa Species 0.000 abstract description 2
- 210000000748 cardiovascular system Anatomy 0.000 abstract description 2
- 230000002496 gastric effect Effects 0.000 abstract description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 381
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 190
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 111
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 88
- 239000000203 mixture Substances 0.000 description 75
- 239000000047 product Substances 0.000 description 69
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 68
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
- 229960001701 chloroform Drugs 0.000 description 44
- 239000000243 solution Substances 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- 239000000377 silicon dioxide Substances 0.000 description 30
- 239000012965 benzophenone Substances 0.000 description 28
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 27
- 229940024874 benzophenone Drugs 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- 238000004587 chromatography analysis Methods 0.000 description 21
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 238000007792 addition Methods 0.000 description 18
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 12
- 239000012312 sodium hydride Substances 0.000 description 12
- 229910000104 sodium hydride Inorganic materials 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 229910052782 aluminium Inorganic materials 0.000 description 11
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- 238000002425 crystallisation Methods 0.000 description 10
- 238000001953 recrystallisation Methods 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 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 9
- 230000008025 crystallization Effects 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 239000000155 melt Substances 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- 239000012429 reaction media Substances 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 8
- 108010004977 Vasopressins Proteins 0.000 description 8
- 102000002852 Vasopressins Human genes 0.000 description 8
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 8
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 229960003726 vasopressin Drugs 0.000 description 8
- 239000002585 base Substances 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- BLWYXBNNBYXPPL-YFKPBYRVSA-N methyl (2s)-pyrrolidine-2-carboxylate Chemical compound COC(=O)[C@@H]1CCCN1 BLWYXBNNBYXPPL-YFKPBYRVSA-N 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 235000011121 sodium hydroxide Nutrition 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 150000002431 hydrogen Chemical class 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 235000008504 concentrate Nutrition 0.000 description 4
- 238000006114 decarboxylation reaction Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
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Classifications
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- 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
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- A—HUMAN NECESSITIES
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- 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
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9109908A FR2679903B1 (fr) | 1991-08-02 | 1991-08-02 | Derives de la n-sulfonyl indoline portant une fonction amidique, leur preparation, les compositions pharmaceutiques en contenant. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| LTIP114A LTIP114A (en) | 1994-06-15 |
| LT3064B true LT3064B (en) | 1994-10-25 |
Family
ID=9415909
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LTIP114A LT3064B (en) | 1991-08-02 | 1992-07-31 | Indolineamide derivatives, process for the preparation thereof and pharmaceutical compositions containing the same |
Country Status (28)
| Country | Link |
|---|---|
| EP (1) | EP0526348B1 (de) |
| JP (1) | JP2633085B2 (de) |
| KR (1) | KR100241583B1 (de) |
| AT (1) | ATE163289T1 (de) |
| AU (2) | AU658664B2 (de) |
| BR (1) | BR9205336A (de) |
| CA (2) | CA2093221C (de) |
| CZ (1) | CZ288173B6 (de) |
| DE (1) | DE69224450T2 (de) |
| DK (1) | DK0526348T3 (de) |
| ES (1) | ES2117038T3 (de) |
| FI (2) | FI104069B (de) |
| FR (1) | FR2679903B1 (de) |
| HU (2) | HUT68927A (de) |
| IL (3) | IL117592A (de) |
| LT (1) | LT3064B (de) |
| LV (1) | LV10091B (de) |
| MX (1) | MX9204487A (de) |
| MY (1) | MY110517A (de) |
| NO (1) | NO180047C (de) |
| NZ (1) | NZ243795A (de) |
| PH (1) | PH30661A (de) |
| RU (1) | RU2104268C1 (de) |
| SG (1) | SG47501A1 (de) |
| SK (1) | SK283463B6 (de) |
| UA (1) | UA27238C2 (de) |
| WO (1) | WO1993003013A1 (de) |
| ZA (1) | ZA925781B (de) |
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2665441B1 (fr) * | 1990-07-31 | 1992-12-04 | Sanofi Sa | Derives de la n-sulfonyl indoline, leur preparation, les compositions pharmaceutiques en contenant. |
| FR2708608B1 (fr) * | 1993-07-30 | 1995-10-27 | Sanofi Sa | Dérivés de N-sulfonylbenzimidazolone, leur préparation, les compositions pharmaceutiques en contenant. |
| FR2756736B1 (fr) * | 1996-12-05 | 1999-03-05 | Sanofi Sa | Compositions pharmaceutiques contenant des derives de n-sulfonyl indoline |
| CN1265669A (zh) * | 1997-07-31 | 2000-09-06 | 伊兰药品公司 | 抑制由vla－4介导的白细胞粘着的化合物 |
| US6489300B1 (en) | 1997-07-31 | 2002-12-03 | Eugene D. Thorsett | Carbamyloxy compounds which inhibit leukocyte adhesion mediated by VLA-4 |
| US6559127B1 (en) | 1997-07-31 | 2003-05-06 | Athena Neurosciences, Inc. | Compounds which inhibit leukocyte adhesion mediated by VLA-4 |
| US6939855B2 (en) | 1997-07-31 | 2005-09-06 | Elan Pharmaceuticals, Inc. | Anti-inflammatory compositions and method |
| BR9812111A (pt) * | 1997-07-31 | 2000-07-18 | Elan Pharm Inc | Dipeptìdeo e compostos correlatos que inibem adesão de leucócito mediada por vla-4 |
| US6492421B1 (en) | 1997-07-31 | 2002-12-10 | Athena Neurosciences, Inc. | Substituted phenylalanine type compounds which inhibit leukocyte adhesion mediated by VLA-4 |
| US6423688B1 (en) | 1997-07-31 | 2002-07-23 | Athena Neurosciences, Inc. | Dipeptide and related compounds which inhibit leukocyte adhesion mediated by VLA-4 |
| US7030114B1 (en) | 1997-07-31 | 2006-04-18 | Elan Pharmaceuticals, Inc. | Compounds which inhibit leukocyte adhesion mediated by VLA-4 |
| HUP0003921A3 (en) * | 1997-07-31 | 2001-03-28 | Wyeth Corp | Sulfonylated dipeptide compounds which inhibit leukocyte adhesion mediated by vla-4, pharmaceutical compositions comprising thereof and their use |
| US6291453B1 (en) | 1997-07-31 | 2001-09-18 | Athena Neurosciences, Inc. | 4-amino-phenylalanine type compounds which inhibit leukocyte adhesion mediated by VLA-4 |
| US6362341B1 (en) | 1997-07-31 | 2002-03-26 | Athena Neurosciences, Inc. | Benzyl compounds which inhibit leukocyte adhesion mediated by VLA-4 |
| US6583139B1 (en) | 1997-07-31 | 2003-06-24 | Eugene D. Thorsett | Compounds which inhibit leukocyte adhesion mediated by VLA-4 |
| FR2775598A1 (fr) * | 1998-03-06 | 1999-09-10 | Sanofi Sa | Compositions pharmaceutiques contenant en association un antagoniste selectif des recepteurs v1a de l'arginine-vasopressine et un antagoniste selectif des recepteur v2 de l'arginine-vasopressine |
| FR2778103A1 (fr) * | 1998-04-29 | 1999-11-05 | Sanofi Sa | Compositions pharmaceutiques contenant en association un antagoniste v1a de l'arginine-vasopressine et un antagoniste des recepteurs at1 de l'angiotensine ii |
| FR2786486B3 (fr) * | 1998-11-16 | 2000-12-08 | Sanofi Sa | Procede de preparation du (2s)-1-[(2r,3s)-5-chloro-3-(2- chlorophenyl)-1-(3,4-dimethoxy benzenesulfonyl)-3-hydroxy- 2,3-dihydro-1h-indole-2-carbonyl]pyrrolidine-2-carboxamide, de ses solvats et/ou hydrates |
| US6492372B1 (en) | 1999-01-22 | 2002-12-10 | Elan Pharmaceuticals, Inc. | Heteroaryl, heterocyclic and aryl compounds which inhibit leukocyte adhesion mediated by VLA-4 |
| IL143928A0 (en) | 1999-01-22 | 2002-04-21 | Elan Pharm Inc | Fused ring heteroaryl and heterocyclic compounds which inhibit leukocyte adhesion mediated by vla-4 |
| CA2359114A1 (en) * | 1999-01-25 | 2000-07-27 | Elan Pharmaceuticals, Inc. | Compounds which inhibit leukocyte adhesion mediated by vla-4 |
| US6436904B1 (en) | 1999-01-25 | 2002-08-20 | Elan Pharmaceuticals, Inc. | Compounds which inhibit leukocyte adhesion mediated by VLA-4 |
| US6407066B1 (en) | 1999-01-26 | 2002-06-18 | Elan Pharmaceuticals, Inc. | Pyroglutamic acid derivatives and related compounds which inhibit leukocyte adhesion mediated by VLA-4 |
| GB9902461D0 (en) * | 1999-02-05 | 1999-03-24 | Zeneca Ltd | Chemical compounds |
| FR2792834A1 (fr) * | 1999-04-29 | 2000-11-03 | Sanofi Sa | Utilisation du sr 49059, de ses solvats et/ou hydrates pharmaceutiquement acceptables, pour la preparation de medicaments utiles dans le traitement ou la prevention du phenomene de raynaud |
| FR2805536B1 (fr) * | 2000-02-25 | 2002-08-23 | Sanofi Synthelabo | Nouveaux derives de 1,3-dihydro-2h-indol-2-one, un procede pour leur preparation et les compositions pharmaceutiques en contenant |
| FR2805992A1 (fr) * | 2000-03-08 | 2001-09-14 | Sanofi Synthelabo | Compositions pharmaceutiques orales contenant des derives de n-sulfonylindoline |
| US7312358B2 (en) | 2000-10-17 | 2007-12-25 | Laboratoires Serono Sa | Pharmaceutically active sulfanilide derivatives |
| CA2425892A1 (en) | 2000-11-28 | 2003-04-11 | Hiroyuki Koshio | 1,4,5,6-tetrahydroimidazo[4,5-d]diazepine derivative or salt thereof |
| JP4044740B2 (ja) * | 2001-05-31 | 2008-02-06 | 信越化学工業株式会社 | レジスト材料及びパターン形成方法 |
| WO2003053437A1 (en) | 2001-12-20 | 2003-07-03 | Applied Research Systems Ars Holding N.V. | Triazoles as oxytocin antagonists |
| TWI281470B (en) | 2002-05-24 | 2007-05-21 | Elan Pharm Inc | Heterocyclic compounds which inhibit leukocyte adhesion mediated by alpha4 integrins |
| EP2399903A1 (de) | 2002-05-24 | 2011-12-28 | Millennium Pharmaceuticals, Inc. | CCR9-Hemmer und Verwendungsverfahren dafür |
| TW200307671A (en) | 2002-05-24 | 2003-12-16 | Elan Pharm Inc | Heteroaryl compounds which inhibit leukocyte adhesion mediated by α 4 integrins |
| PT1587788E (pt) * | 2002-09-17 | 2007-08-20 | Hoffmann La Roche | ''indoles 2,7-substituídos e a sua utilização como moduladores de 5-ht6'' |
| NZ538047A (en) * | 2002-09-17 | 2007-10-26 | Hoffmann La Roche | 2,4-substituted indoles and their use as 5-HT6 modulators |
| BR0315115A (pt) * | 2002-10-11 | 2005-08-16 | Actelion Pharmaceuticals Ltd | Compostos, composições farmacêuticas, método para tratar ou prevenir doenças ou distúrbios em que se requer um antagonista de receptores de orexina humana, processo para a fabricação de composições farmacêuticas, e, uso de um ou mais compostos em combinação com outros compostos farmacologicamente ativos |
| US7741519B2 (en) | 2007-04-23 | 2010-06-22 | Chemocentryx, Inc. | Bis-aryl sulfonamides |
| US7227035B2 (en) | 2002-11-18 | 2007-06-05 | Chemocentryx | Bis-aryl sulfonamides |
| US7420055B2 (en) | 2002-11-18 | 2008-09-02 | Chemocentryx, Inc. | Aryl sulfonamides |
| AU2003298661B2 (en) | 2002-11-18 | 2007-05-10 | Chemocentryx, Inc. | Aryl sulfonamides |
| EP1806340B1 (de) * | 2004-10-27 | 2011-05-04 | Kissei Pharmaceutical Co., Ltd. | Indolinverbindung und verfahren zu deren herstellung |
| BRPI0616643A2 (pt) | 2005-09-29 | 2011-06-28 | Elan Pharm Inc | compostos de carbamato que inibem a adesão leucocitária mediada por vla-4 |
| NZ567270A (en) | 2005-09-29 | 2011-06-30 | Elan Pharm Inc | Pyrimidinyl amide compounds which inhibit leukocyte adhesion mediated by VLA-4 |
| KR20080100271A (ko) | 2006-02-27 | 2008-11-14 | 엘란 파마슈티칼스, 인크. | Ｖｌａ-4에 의해 매개되는 백혈구 부착을 억제하는 피리미디닐 술폰아미드 화합물 |
| EP2424841A1 (de) | 2009-04-27 | 2012-03-07 | Elan Pharmaceuticals Inc. | Pyridinonantagonisten von alpha-4-integrinen |
| TW201938171A (zh) | 2017-12-15 | 2019-10-01 | 匈牙利商羅特格登公司 | 作為血管升壓素Ｖ１ａ受體拮抗劑之三環化合物 |
| HU231206B1 (hu) | 2017-12-15 | 2021-10-28 | Richter Gedeon Nyrt. | Triazolobenzazepinek |
| WO2025132542A1 (en) | 2023-12-19 | 2025-06-26 | Idorsia Pharmaceuticals Ltd | Macrocyclic orexin agonists |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3838167A (en) | 1972-08-01 | 1974-09-24 | Lilly Co Eli | Process for preparing indoles |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4479963A (en) * | 1981-02-17 | 1984-10-30 | Ciba-Geigy Corporation | 1-Carboxyalkanoylindoline-2-carboxylic acids |
| DE3705934A1 (de) * | 1987-02-25 | 1988-09-08 | Nattermann A & Cie | Indolyl-derivate, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| FR2665441B1 (fr) * | 1990-07-31 | 1992-12-04 | Sanofi Sa | Derives de la n-sulfonyl indoline, leur preparation, les compositions pharmaceutiques en contenant. |
-
1991
- 1991-08-02 FR FR9109908A patent/FR2679903B1/fr not_active Expired - Fee Related
-
1992
- 1992-07-31 ZA ZA925781A patent/ZA925781B/xx unknown
- 1992-07-31 CA CA002093221A patent/CA2093221C/en not_active Expired - Fee Related
- 1992-07-31 KR KR1019930701034A patent/KR100241583B1/ko not_active Expired - Fee Related
- 1992-07-31 UA UA93002340A patent/UA27238C2/uk unknown
- 1992-07-31 HU HU9300951A patent/HUT68927A/hu unknown
- 1992-07-31 BR BR9205336A patent/BR9205336A/pt not_active Application Discontinuation
- 1992-07-31 MX MX9204487A patent/MX9204487A/es not_active IP Right Cessation
- 1992-07-31 NZ NZ243795A patent/NZ243795A/en unknown
- 1992-07-31 IL IL11759292A patent/IL117592A/xx not_active IP Right Cessation
- 1992-07-31 RU RU93005168A patent/RU2104268C1/ru not_active IP Right Cessation
- 1992-07-31 CA CA002206776A patent/CA2206776C/en not_active Expired - Fee Related
- 1992-07-31 LV LVP-92-87A patent/LV10091B/lv unknown
- 1992-07-31 WO PCT/FR1992/000758 patent/WO1993003013A1/fr not_active Ceased
- 1992-07-31 IL IL102703A patent/IL102703A/xx not_active IP Right Cessation
- 1992-07-31 JP JP5503337A patent/JP2633085B2/ja not_active Expired - Fee Related
- 1992-07-31 AU AU24758/92A patent/AU658664B2/en not_active Ceased
- 1992-07-31 LT LTIP114A patent/LT3064B/lt not_active IP Right Cessation
- 1992-07-31 MY MYPI92001379A patent/MY110517A/en unknown
- 1992-07-31 PH PH44760A patent/PH30661A/en unknown
- 1992-07-31 SK SK426-93A patent/SK283463B6/sk unknown
- 1992-07-31 CZ CZ1993682A patent/CZ288173B6/cs not_active IP Right Cessation
- 1992-08-03 DE DE69224450T patent/DE69224450T2/de not_active Expired - Fee Related
- 1992-08-03 DK DK92402213T patent/DK0526348T3/da active
- 1992-08-03 SG SG1996002367A patent/SG47501A1/en unknown
- 1992-08-03 ES ES92402213T patent/ES2117038T3/es not_active Expired - Lifetime
- 1992-08-03 EP EP92402213A patent/EP0526348B1/de not_active Expired - Lifetime
- 1992-08-03 AT AT92402213T patent/ATE163289T1/de not_active IP Right Cessation
-
1993
- 1993-04-01 NO NO931262A patent/NO180047C/no not_active IP Right Cessation
- 1993-04-01 FI FI931476A patent/FI104069B/fi not_active IP Right Cessation
-
1995
- 1995-02-03 AU AU11541/95A patent/AU691223B2/en not_active Ceased
- 1995-06-28 HU HU95P/P00474P patent/HU211884A9/hu unknown
-
1996
- 1996-03-21 IL IL11759296A patent/IL117592A0/xx unknown
-
1998
- 1998-01-27 FI FI980175A patent/FI107048B/fi not_active IP Right Cessation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3838167A (en) | 1972-08-01 | 1974-09-24 | Lilly Co Eli | Process for preparing indoles |
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Legal Events
| Date | Code | Title | Description |
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Free format text: 1. INDOLINO SU AMIDINE FUNKCIJA DARINIAI STRUKTURINES FORMULES: (I),KURIOJE - R1 TAI HALOGENO ATOMAS, ALKILAS C1-C4, HIDROKSILAS, ALKOKSILAS C1-C4, BENZILOKSI GRUPE, CIANO GRUPE, TRIFLUORMETILO GRUPE, NITRO GRUPE ARBA AMINO GRUPE;- R2 TAI ALKILAS C1-C6, CIKLOALKILAS C3-C7, CIKLOALKENAS C5-C7, FENILAS, NEPAKEISTAS ARBA PAKEISTAS VIENA AR KELIS KARTUS ALKILU C1-C4, ALKOKSILU C1-C4, HALOGENU, TRIFLUORMETILO GRUPE, AMINO GRUPE, ARBA R2 TAI NITROFENILAS, NEPAKEISTAS ARBA PAKEISTAS VIENA KARTA TRIFLUORMETILO GRUPE ARBA VIENA AR KELIS KARTU |
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Free format text: SANOFI,32-34 RUE MARBEUF, 75008 PARIS,FR,19971113 |
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Effective date: 20040731 |