CA2403605A1 - Heterocycle derivatives and drugs - Google Patents
Heterocycle derivatives and drugs Download PDFInfo
- Publication number
- CA2403605A1 CA2403605A1 CA002403605A CA2403605A CA2403605A1 CA 2403605 A1 CA2403605 A1 CA 2403605A1 CA 002403605 A CA002403605 A CA 002403605A CA 2403605 A CA2403605 A CA 2403605A CA 2403605 A1 CA2403605 A1 CA 2403605A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- alkyl
- compound
- hydrogen atom
- alkoxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 125000000623 heterocyclic group Chemical group 0.000 title claims abstract description 25
- 239000003814 drug Substances 0.000 title description 7
- 229940079593 drug Drugs 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 227
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 60
- -1 nitro, hydroxy Chemical group 0.000 claims abstract description 60
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 42
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 31
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 21
- 230000000202 analgesic effect Effects 0.000 claims abstract description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 20
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 19
- 150000002367 halogens Chemical class 0.000 claims abstract description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 18
- 125000002993 cycloalkylene group Chemical group 0.000 claims abstract description 15
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 12
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims abstract description 10
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 8
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- 125000001424 substituent group Chemical group 0.000 claims description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 125000005117 dialkylcarbamoyl group Chemical group 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 125000002947 alkylene group Chemical group 0.000 claims description 11
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 11
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 239000004480 active ingredient Substances 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- PAFZNILMFXTMIY-UHFFFAOYSA-N Cyclohexylamine Natural products NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 6
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000004546 quinazolin-4-yl group Chemical group N1=CN=C(C2=CC=CC=C12)* 0.000 claims description 6
- 125000005650 substituted phenylene group Chemical group 0.000 claims description 6
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 125000006294 amino alkylene group Chemical group 0.000 claims description 4
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- RVNUEBBCFRLWHL-KZJIUNCISA-N 2-[(1s,2r)-2-[[2-[(z)-2-(4-chlorophenyl)ethenyl]-6-methoxyquinazolin-4-yl]amino]cyclohexyl]guanidine;dihydrochloride Chemical compound Cl.Cl.N1=C(N[C@H]2[C@H](CCCC2)N=C(N)N)C2=CC(OC)=CC=C2N=C1\C=C/C1=CC=C(Cl)C=C1 RVNUEBBCFRLWHL-KZJIUNCISA-N 0.000 claims description 2
- UJOCZXHYKLJJJB-UHFFFAOYSA-N 2-[6-[[6-methoxy-2-(2-pyridin-2-ylethenyl)quinazolin-4-yl]amino]hexyl]guanidine;trihydrochloride Chemical compound Cl.Cl.Cl.N1=C(NCCCCCCNC(N)=N)C2=CC(OC)=CC=C2N=C1C=CC1=CC=CC=N1 UJOCZXHYKLJJJB-UHFFFAOYSA-N 0.000 claims description 2
- KMLUBVZGTQLNRK-QNCHGCKQSA-N 4-chloro-n-[4-[[(1r,2s)-2-(diaminomethylideneamino)cyclohexyl]amino]-6-methoxyquinazolin-2-yl]benzamide;dihydrochloride Chemical compound Cl.Cl.N1=C(N[C@H]2[C@H](CCCC2)N=C(N)N)C2=CC(OC)=CC=C2N=C1NC(=O)C1=CC=C(Cl)C=C1 KMLUBVZGTQLNRK-QNCHGCKQSA-N 0.000 claims description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 claims description 2
- OCBSXEUWBMDOEQ-UHFFFAOYSA-N 2-[6-[[6-methyl-2-(2-pyridin-2-ylethenyl)quinazolin-4-yl]amino]hexyl]guanidine;trihydrochloride Chemical compound Cl.Cl.Cl.N1=C(NCCCCCCNC(N)=N)C2=CC(C)=CC=C2N=C1C=CC1=CC=CC=N1 OCBSXEUWBMDOEQ-UHFFFAOYSA-N 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 102100028646 Nociceptin receptor Human genes 0.000 abstract description 10
- 108010020615 nociceptin receptor Proteins 0.000 abstract description 10
- 208000002193 Pain Diseases 0.000 abstract description 8
- 208000000094 Chronic Pain Diseases 0.000 abstract description 4
- 208000004454 Hyperalgesia Diseases 0.000 abstract description 4
- 208000007514 Herpes zoster Diseases 0.000 abstract description 3
- 206010053552 allodynia Diseases 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 144
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 116
- 239000000243 solution Substances 0.000 description 113
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 81
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 67
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 60
- 239000002904 solvent Substances 0.000 description 55
- 238000000034 method Methods 0.000 description 52
- 238000006243 chemical reaction Methods 0.000 description 49
- 239000000843 powder Substances 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- 239000000741 silica gel Substances 0.000 description 34
- 229910002027 silica gel Inorganic materials 0.000 description 34
- 238000004440 column chromatography Methods 0.000 description 31
- 239000000203 mixture Substances 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 19
- 238000009835 boiling Methods 0.000 description 19
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 150000001412 amines Chemical class 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
- 238000010511 deprotection reaction Methods 0.000 description 16
- 239000007864 aqueous solution Substances 0.000 description 15
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 238000009472 formulation Methods 0.000 description 14
- 125000006239 protecting group Chemical group 0.000 description 13
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 12
- 239000003826 tablet Substances 0.000 description 12
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 230000003287 optical effect Effects 0.000 description 11
- 239000013078 crystal Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 10
- 238000001816 cooling Methods 0.000 description 9
- 150000002430 hydrocarbons Chemical group 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 150000002170 ethers Chemical class 0.000 description 8
- 229930195733 hydrocarbon Natural products 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000012300 argon atmosphere Substances 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- PULGYDLMFSFVBL-SMFNREODSA-N nociceptin Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)[C@@H](C)O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 PULGYDLMFSFVBL-SMFNREODSA-N 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000006188 syrup Substances 0.000 description 5
- 235000020357 syrup Nutrition 0.000 description 5
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 4
- 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 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 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
- 239000007983 Tris buffer Substances 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 4
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 4
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 4
- 238000011049 filling Methods 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000004084 narcotic analgesic agent Substances 0.000 description 4
- 230000009871 nonspecific binding Effects 0.000 description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 4
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 241000699670 Mus sp. Species 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000012320 chlorinating reagent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 3
- 150000008282 halocarbons Chemical class 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 238000003801 milling Methods 0.000 description 3
- 229960005181 morphine Drugs 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 2
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
- RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 208000000044 Amnesia Diseases 0.000 description 2
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- XVROWZPERFUOCE-RKDXNWHRSA-N tert-butyl n-[(1r,2r)-2-hydroxycyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCCC[C@H]1O XVROWZPERFUOCE-RKDXNWHRSA-N 0.000 description 1
- MOYILOWCZPYTQW-HZPDHXFCSA-N tert-butyl n-[(1r,2r)-2-phenylmethoxycyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCCC[C@H]1OCC1=CC=CC=C1 MOYILOWCZPYTQW-HZPDHXFCSA-N 0.000 description 1
- NPFQKJGOPNBNCU-JKSUJKDBSA-N tert-butyl n-[(1r,2s)-2-[(2-chloro-6-methoxyquinazolin-4-yl)amino]cyclohexyl]carbamate Chemical compound C12=CC(OC)=CC=C2N=C(Cl)N=C1N[C@H]1CCCC[C@H]1NC(=O)OC(C)(C)C NPFQKJGOPNBNCU-JKSUJKDBSA-N 0.000 description 1
- VWOVVZWSGCHNCI-BJKOFHAPSA-N tert-butyl n-[(1r,2s)-2-[[6-methoxy-2-[(4-methoxyphenyl)methylamino]quinazolin-4-yl]amino]cyclohexyl]carbamate Chemical compound C1=CC(OC)=CC=C1CNC1=NC(N[C@@H]2[C@@H](CCCC2)NC(=O)OC(C)(C)C)=C(C=C(OC)C=C2)C2=N1 VWOVVZWSGCHNCI-BJKOFHAPSA-N 0.000 description 1
- AKVIZYGPJIWKOS-DTWKUNHWSA-N tert-butyl n-[(1r,2s)-2-aminocyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCCC[C@@H]1N AKVIZYGPJIWKOS-DTWKUNHWSA-N 0.000 description 1
- OBSACSBMTRJNPH-IUCAKERBSA-N tert-butyl n-[(1s,3s)-3-aminocyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CCC[C@H](N)C1 OBSACSBMTRJNPH-IUCAKERBSA-N 0.000 description 1
- SGNKPJPMWHKOJO-UHFFFAOYSA-N tert-butyl n-[4-(hydroxymethyl)cyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(CO)CC1 SGNKPJPMWHKOJO-UHFFFAOYSA-N 0.000 description 1
- ZYSURDPTHWVESU-RBUKOAKNSA-N tert-butyl n-[n'-[(1r,2s)-2-[(2-amino-6-methoxyquinazolin-4-yl)amino]cyclohexyl]-n-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate Chemical compound C12=CC(OC)=CC=C2N=C(N)N=C1N[C@H]1CCCC[C@H]1NC(NC(=O)OC(C)(C)C)=NC(=O)OC(C)(C)C ZYSURDPTHWVESU-RBUKOAKNSA-N 0.000 description 1
- VJTFVESJYZUCHP-LOSJGSFVSA-N tert-butyl n-[n'-[(1r,2s)-2-[[2-[(4-chlorobenzoyl)amino]-6-methoxyquinazolin-4-yl]amino]cyclohexyl]-n-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate Chemical compound N1=C(N[C@@H]2[C@@H](CCCC2)NC(NC(=O)OC(C)(C)C)=NC(=O)OC(C)(C)C)C2=CC(OC)=CC=C2N=C1NC(=O)C1=CC=C(Cl)C=C1 VJTFVESJYZUCHP-LOSJGSFVSA-N 0.000 description 1
- ZIJNPPYJZDDOJX-RRPNLBNLSA-N tert-butyl n-[n'-[(1r,2s)-2-[[6-methoxy-2-[(4-methoxyphenyl)methylamino]quinazolin-4-yl]amino]cyclohexyl]-n-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate Chemical compound C1=CC(OC)=CC=C1CNC1=NC(N[C@@H]2[C@@H](CCCC2)NC(NC(=O)OC(C)(C)C)=NC(=O)OC(C)(C)C)=C(C=C(OC)C=C2)C2=N1 ZIJNPPYJZDDOJX-RRPNLBNLSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
-
- 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
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
-
- 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
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000098874 | 2000-03-31 | ||
| JP2000-98874 | 2000-03-31 | ||
| JP2000-336464 | 2000-11-02 | ||
| JP2000336464 | 2000-11-02 | ||
| PCT/JP2001/002822 WO2001072710A1 (fr) | 2000-03-31 | 2001-03-30 | Dérivés et médicaments hétérocycliques |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2403605A1 true CA2403605A1 (en) | 2002-09-18 |
Family
ID=26589216
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002403605A Abandoned CA2403605A1 (en) | 2000-03-31 | 2001-03-30 | Heterocycle derivatives and drugs |
Country Status (10)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7718663B2 (en) * | 2002-04-26 | 2010-05-18 | Nippon Shinyaku Co., Ltd. | Quinazoline derivatives and medicaments |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004509875A (ja) * | 2000-09-20 | 2004-04-02 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | ４−アミノキナゾリン |
| AU2002212697A1 (en) | 2000-11-02 | 2002-05-15 | Nippon Shinyaku Co. Ltd. | Quinazoline derivatives and drugs |
| JPWO2002074341A1 (ja) * | 2001-03-19 | 2004-10-14 | 日本新薬株式会社 | 鎮痒剤 |
| US6907295B2 (en) * | 2001-08-31 | 2005-06-14 | Biocontrol Medical Ltd. | Electrode assembly for nerve control |
| US7829566B2 (en) * | 2001-09-17 | 2010-11-09 | Werner Mederski | 4-amino-quinazolines |
| JP4805234B2 (ja) * | 2002-12-16 | 2011-11-02 | キッセイ薬品工業株式会社 | 経口固形医薬 |
| US8309562B2 (en) | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | Compounds and therapeutical use thereof |
| CN1984660B (zh) | 2003-07-03 | 2010-12-15 | 美瑞德生物工程公司 | 作为天冬氨酸特异性半胱氨酸蛋白酶活化剂和细胞程序死亡诱导剂的4-芳基氨基-喹唑啉 |
| CA2553969A1 (en) * | 2004-01-23 | 2005-08-04 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| US8258145B2 (en) | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
| CA2592900A1 (en) | 2005-01-03 | 2006-07-13 | Myriad Genetics Inc. | Nitrogen containing bicyclic compounds and therapeutical use thereof |
| PT1944298E (pt) | 2005-10-03 | 2013-02-13 | Nippon Shinyaku Co Ltd | Derivado de quinazolina e fármaco |
| RU2314295C2 (ru) * | 2006-03-01 | 2008-01-10 | Федеральное Государственное Образовательное Учреждение Высшего Профессионального Образования "Южный Федеральный Университет" | 2-гетарилзамещенные 1,3-трополона, способ их получения (варианты) и фармацевтическая композиция антимикробного действия |
| KR20120011093A (ko) * | 2007-05-09 | 2012-02-06 | 화이자 인코포레이티드 | 치환된 헤테로사이클릭 유도체 및 조성물 및 항균제로서의 이의 약학적 용도 |
| EP2017294A1 (de) | 2007-07-16 | 2009-01-21 | Sika Technology AG | Hitzehärtender Schaum |
| ES2554623T3 (es) | 2008-12-30 | 2015-12-22 | Arqule, Inc. | Compuestos de 5,6-dihidro-6-fenilbenzo[f]isoquinolin-2-amina sustituida |
| WO2012027495A1 (en) | 2010-08-27 | 2012-03-01 | University Of The Pacific | Piperazinylpyrimidine analogues as protein kinase inhibitors |
| MY188000A (en) | 2011-12-28 | 2021-11-08 | Fujifilm Corp | Novel nicotinamide derivative or salt thereof |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3753981A (en) * | 1970-07-15 | 1973-08-21 | Squibb & Sons Inc | 4-amino-2-styrylquinazoline compounds |
| PT100905A (pt) | 1991-09-30 | 1994-02-28 | Eisai Co Ltd | Compostos heterociclicos azotados biciclicos contendo aneis de benzeno, ciclo-hexano ou piridina e de pirimidina, piridina ou imidazol substituidos e composicoes farmaceuticas que os contem |
| JP2657760B2 (ja) | 1992-07-15 | 1997-09-24 | 小野薬品工業株式会社 | ４−アミノキナゾリン誘導体およびそれを含有する医薬品 |
| AU7692696A (en) * | 1995-12-01 | 1997-06-27 | Novartis Ag | Heteroaryl derivatives |
| WO1998017267A1 (en) | 1996-10-23 | 1998-04-30 | Zymogenetics, Inc. | Compositions and methods for treating bone deficit conditions |
| CA2226058C (en) * | 1997-01-30 | 2008-01-29 | F. Hoffmann-La Roche Ag | 8-substituted-1,3,8-triaza-spiro[4.5]decan-4-one derivatives |
| AR012634A1 (es) | 1997-05-02 | 2000-11-08 | Sugen Inc | Compuesto basado en quinazolina, composicion famaceutica que lo comprende, metodo para sintetizarlo, su uso, metodos de modulacion de la funcion deserina/treonina proteinaquinasa con dicho compuesto y metodo in vitro para identificar compuestos que modulan dicha funcion |
| WO1998054168A1 (fr) | 1997-05-30 | 1998-12-03 | Banyu Pharmaceutical Co., Ltd. | Derives de 2-0xoimidazole |
| AU8748798A (en) | 1997-08-22 | 1999-03-16 | Kyowa Hakko Kogyo Co. Ltd. | 4-aminoquinazoline derivatives |
| EP1072263A4 (en) * | 1998-03-26 | 2004-03-31 | Japan Tobacco Inc | AMID DERIVATIVES AND NOCICEPTINANT AGONISTS |
| JPWO2002074341A1 (ja) * | 2001-03-19 | 2004-10-14 | 日本新薬株式会社 | 鎮痒剤 |
-
2001
- 2001-03-30 DE DE60140545T patent/DE60140545D1/de not_active Expired - Lifetime
- 2001-03-30 CA CA002403605A patent/CA2403605A1/en not_active Abandoned
- 2001-03-30 WO PCT/JP2001/002822 patent/WO2001072710A1/ja active Application Filing
- 2001-03-30 KR KR1020027012917A patent/KR20020083533A/ko not_active Withdrawn
- 2001-03-30 EP EP01917752A patent/EP1306372B1/en not_active Expired - Lifetime
- 2001-03-30 CN CNB018075347A patent/CN1242993C/zh not_active Expired - Fee Related
- 2001-03-30 RU RU2002129100/04A patent/RU2268260C2/ru not_active IP Right Cessation
- 2001-03-30 AU AU2001244688A patent/AU2001244688A1/en not_active Abandoned
- 2001-03-30 AT AT01917752T patent/ATE449084T1/de not_active IP Right Cessation
- 2001-03-30 US US10/239,750 patent/US6794389B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7718663B2 (en) * | 2002-04-26 | 2010-05-18 | Nippon Shinyaku Co., Ltd. | Quinazoline derivatives and medicaments |
Also Published As
| Publication number | Publication date |
|---|---|
| RU2268260C2 (ru) | 2006-01-20 |
| CN1242993C (zh) | 2006-02-22 |
| ATE449084T1 (de) | 2009-12-15 |
| US20030119855A1 (en) | 2003-06-26 |
| CN1422255A (zh) | 2003-06-04 |
| EP1306372A1 (en) | 2003-05-02 |
| US6794389B2 (en) | 2004-09-21 |
| EP1306372B1 (en) | 2009-11-18 |
| KR20020083533A (ko) | 2002-11-02 |
| DE60140545D1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2009-12-31 |
| EP1306372A4 (en) | 2004-03-17 |
| RU2002129100A (ru) | 2004-02-27 |
| AU2001244688A1 (en) | 2001-10-08 |
| WO2001072710A1 (fr) | 2001-10-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |