KR20050092759A - 신규 화합물 - Google Patents
신규 화합물 Download PDFInfo
- Publication number
- KR20050092759A KR20050092759A KR1020057013124A KR20057013124A KR20050092759A KR 20050092759 A KR20050092759 A KR 20050092759A KR 1020057013124 A KR1020057013124 A KR 1020057013124A KR 20057013124 A KR20057013124 A KR 20057013124A KR 20050092759 A KR20050092759 A KR 20050092759A
- Authority
- KR
- South Korea
- Prior art keywords
- methyl
- formula
- thieno
- compound
- alkyl
- 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
- 150000001875 compounds Chemical class 0.000 title claims description 158
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 67
- 238000000034 method Methods 0.000 claims abstract description 59
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 43
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 42
- 150000003839 salts Chemical class 0.000 claims abstract description 34
- 125000005843 halogen group Chemical group 0.000 claims abstract description 25
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 15
- 125000003118 aryl group Chemical group 0.000 claims abstract description 14
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000001301 oxygen Substances 0.000 claims abstract description 12
- 229910052717 sulfur Chemical group 0.000 claims abstract description 12
- 239000011593 sulfur Chemical group 0.000 claims abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000002619 bicyclic group Chemical group 0.000 claims abstract description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 4
- 239000012453 solvate Substances 0.000 claims abstract description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 3
- -1 cyano, hydroxymethyl Chemical group 0.000 claims description 39
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- ABKXKHLBOFZAII-UHFFFAOYSA-N C(=O)=S1C=CC2=C1C(=NN(C2=O)C)C(C)C Chemical compound C(=O)=S1C=CC2=C1C(=NN(C2=O)C)C(C)C ABKXKHLBOFZAII-UHFFFAOYSA-N 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 125000006413 ring segment Chemical group 0.000 claims description 6
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
- WBJKZNUEBLYOBR-HNNXBMFYSA-N 2-[(3,5-dimethyl-1-pyridin-2-ylpyrazol-4-yl)methyl]-7-ethyl-3-[(4s)-4-hydroxy-1,2-oxazolidine-2-carbonyl]-5-methylthieno[2,3-d]pyridazin-4-one Chemical compound CC1=NN(C=2N=CC=CC=2)C(C)=C1CC=1SC=2C(CC)=NN(C)C(=O)C=2C=1C(=O)N1C[C@H](O)CO1 WBJKZNUEBLYOBR-HNNXBMFYSA-N 0.000 claims description 4
- OIWSCNLIZBUBKU-VWLOTQADSA-N 2-[(3,5-dimethyl-1-pyridin-2-ylpyrazol-4-yl)methyl]-7-ethyl-3-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-5-methylthieno[2,3-d]pyridazin-4-one Chemical compound CC1=NN(C=2N=CC=CC=2)C(C)=C1CC=1SC=2C(CC)=NN(C)C(=O)C=2C=1C(=O)N1C[C@](C)(O)CO1 OIWSCNLIZBUBKU-VWLOTQADSA-N 0.000 claims description 4
- LIGIZFGWSFQIKC-ZDUSSCGKSA-N 2-[(3,5-dimethyl-1h-pyrazol-4-yl)methyl]-3-[(4s)-4-hydroxy-1,2-oxazolidine-2-carbonyl]-5-methyl-7-(2-methylpropyl)thieno[2,3-d]pyridazin-4-one Chemical compound CC1=NNC(C)=C1CC=1SC=2C(CC(C)C)=NN(C)C(=O)C=2C=1C(=O)N1C[C@H](O)CO1 LIGIZFGWSFQIKC-ZDUSSCGKSA-N 0.000 claims description 4
- JDJZBFLLHALONW-QFIPXVFZSA-N 2-[(3,5-dimethyl-1h-pyrazol-4-yl)methyl]-3-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-5-methyl-7-(2-methylpropyl)thieno[2,3-d]pyridazin-4-one Chemical compound CC1=NNC(C)=C1CC=1SC=2C(CC(C)C)=NN(C)C(=O)C=2C=1C(=O)N1C[C@](C)(O)CO1 JDJZBFLLHALONW-QFIPXVFZSA-N 0.000 claims description 4
- GQUIXLOQPRBJNH-NSHDSACASA-N 2-[(3,5-dimethyl-1h-pyrazol-4-yl)methyl]-7-ethyl-3-[(4s)-4-hydroxy-1,2-oxazolidine-2-carbonyl]-5-methylthieno[2,3-d]pyridazin-4-one Chemical compound CC1=NNC(C)=C1CC=1SC=2C(CC)=NN(C)C(=O)C=2C=1C(=O)N1C[C@H](O)CO1 GQUIXLOQPRBJNH-NSHDSACASA-N 0.000 claims description 4
- ZSUQVIZBBAAIIH-AWEZNQCLSA-N 3-[(4s)-4-hydroxy-1,2-oxazolidine-2-carbonyl]-5-methyl-7-(2-methylpropyl)-2-[(1,3,5-trimethylpyrazol-4-yl)methyl]thieno[2,3-d]pyridazin-4-one Chemical compound CC1=NN(C)C(C)=C1CC=1SC=2C(CC(C)C)=NN(C)C(=O)C=2C=1C(=O)N1C[C@H](O)CO1 ZSUQVIZBBAAIIH-AWEZNQCLSA-N 0.000 claims description 4
- JJFADIPQVDQFNB-LBPRGKRZSA-N 7-cyclopropyl-2-[(3,5-dimethyl-1h-pyrazol-4-yl)methyl]-3-[(4s)-4-hydroxy-1,2-oxazolidine-2-carbonyl]-5-methylthieno[2,3-d]pyridazin-4-one Chemical compound CC1=NNC(C)=C1CC1=C(C(=O)N2OC[C@@H](O)C2)C(C(=O)N(C)N=C2C3CC3)=C2S1 JJFADIPQVDQFNB-LBPRGKRZSA-N 0.000 claims description 4
- FILIGAJYNUCMJI-QFIPXVFZSA-N 7-ethyl-3-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-5-methyl-2-(1h-pyrrolo[2,3-b]pyridin-3-ylmethyl)thieno[2,3-d]pyridazin-4-one Chemical compound C=1NC2=NC=CC=C2C=1CC=1SC=2C(CC)=NN(C)C(=O)C=2C=1C(=O)N1C[C@](C)(O)CO1 FILIGAJYNUCMJI-QFIPXVFZSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000003965 isoxazolidinyl group Chemical group 0.000 claims description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 4
- HOIOIQPTCHIVDJ-FQEVSTJZSA-N 2-[(3,5-dimethyl-1h-pyrazol-4-yl)methyl]-7-ethyl-3-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-5-methylthieno[2,3-d]pyridazin-4-one Chemical compound CC1=NNC(C)=C1CC=1SC=2C(CC)=NN(C)C(=O)C=2C=1C(=O)N1C[C@](C)(O)CO1 HOIOIQPTCHIVDJ-FQEVSTJZSA-N 0.000 claims description 3
- FACVQJBQWNITOR-NRFANRHFSA-N 7-cyclopropyl-2-[(3,5-dimethyl-1h-pyrazol-4-yl)methyl]-3-[(4s)-4-hydroxy-4-methyl-1,2-oxazolidine-2-carbonyl]-5-methylthieno[2,3-d]pyridazin-4-one Chemical compound CC1=NNC(C)=C1CC1=C(C(=O)N2OC[C@@](C)(O)C2)C(C(=O)N(C)N=C2C3CC3)=C2S1 FACVQJBQWNITOR-NRFANRHFSA-N 0.000 claims description 3
- FLXIPFUVHRVGHE-ZDUSSCGKSA-N 7-cyclopropyl-2-[(3,5-dimethyl-1h-pyrazol-4-yl)methyl]-5-ethyl-3-[(4s)-4-hydroxy-1,2-oxazolidine-2-carbonyl]thieno[2,3-d]pyridazin-4-one Chemical compound C1=2SC(CC3=C(NN=C3C)C)=C(C(=O)N3OC[C@@H](O)C3)C=2C(=O)N(CC)N=C1C1CC1 FLXIPFUVHRVGHE-ZDUSSCGKSA-N 0.000 claims description 3
- 206010062016 Immunosuppression Diseases 0.000 claims description 3
- 239000007822 coupling agent Substances 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 230000001506 immunosuppresive effect Effects 0.000 claims description 3
- 208000023504 respiratory system disease Diseases 0.000 claims description 3
- ZJCNHWZZXYGYHC-UHFFFAOYSA-N C(=O)=S1C(=CC2=C1C(=NN(C2=O)C)CC(C)C)CC1=CNC2=NC=CC=C21 Chemical compound C(=O)=S1C(=CC2=C1C(=NN(C2=O)C)CC(C)C)CC1=CNC2=NC=CC=C21 ZJCNHWZZXYGYHC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 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 claims description 2
- 230000001012 protector Effects 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 208000023275 Autoimmune disease Diseases 0.000 abstract description 5
- 238000002360 preparation method Methods 0.000 abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 101
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 80
- 239000007787 solid Substances 0.000 description 78
- 239000000047 product Substances 0.000 description 75
- 239000000243 solution Substances 0.000 description 51
- 239000000203 mixture Substances 0.000 description 47
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 38
- 235000019439 ethyl acetate Nutrition 0.000 description 34
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 239000000377 silicon dioxide Substances 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 17
- 239000000284 extract Substances 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 206010039083 rhinitis Diseases 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 238000010992 reflux Methods 0.000 description 7
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000001569 carbon dioxide Substances 0.000 description 6
- 229910002092 carbon dioxide Inorganic materials 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- 208000030507 AIDS Diseases 0.000 description 4
- 201000004624 Dermatitis Diseases 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 125000001246 bromo group Chemical group Br* 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 4
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 description 4
- LLCWGQYEQKYRDO-DFWYDOINSA-N (4s)-1,2-oxazolidin-4-ol;hydrochloride Chemical compound Cl.O[C@H]1CNOC1 LLCWGQYEQKYRDO-DFWYDOINSA-N 0.000 description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
- ZYQVKMMNWSKEAX-UHFFFAOYSA-N 2-bromo-7-ethyl-5-methylthieno[2,3-d]pyridazin-4-one Chemical compound CCC1=NN(C)C(=O)C2=C1SC(Br)=C2 ZYQVKMMNWSKEAX-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- 239000007818 Grignard reagent Substances 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 206010024229 Leprosy Diseases 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 208000010668 atopic eczema Diseases 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 210000004027 cell Anatomy 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
- LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 150000004795 grignard reagents Chemical class 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 210000005259 peripheral blood Anatomy 0.000 description 3
- 239000011886 peripheral blood Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- WBDGGIYZBHZWKO-WCCKRBBISA-N (4s)-4-methyl-1,2-oxazolidin-4-ol;hydrochloride Chemical compound Cl.C[C@]1(O)CNOC1 WBDGGIYZBHZWKO-WCCKRBBISA-N 0.000 description 2
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- NWELCUKYUCBVKK-UHFFFAOYSA-N pyridin-2-ylhydrazine Chemical compound NNC1=CC=CC=N1 NWELCUKYUCBVKK-UHFFFAOYSA-N 0.000 description 1
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Classifications
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Landscapes
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Applications Claiming Priority (2)
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| SE0300120A SE0300120D0 (sv) | 2003-01-17 | 2003-01-17 | Novel compounds |
| SE0300120-3 | 2003-01-17 |
Publications (1)
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| KR20050092759A true KR20050092759A (ko) | 2005-09-22 |
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| KR1020057013124A Abandoned KR20050092759A (ko) | 2003-01-17 | 2004-01-15 | 신규 화합물 |
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| EP (1) | EP1587809B1 (https=) |
| JP (1) | JP4589298B2 (https=) |
| KR (1) | KR20050092759A (https=) |
| CN (1) | CN100358900C (https=) |
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| BR (1) | BRPI0406780A (https=) |
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| ES (1) | ES2293208T3 (https=) |
| IL (1) | IL169363A (https=) |
| IS (1) | IS2503B (https=) |
| MX (1) | MXPA05007494A (https=) |
| NO (1) | NO20053827L (https=) |
| NZ (1) | NZ541216A (https=) |
| PL (1) | PL378223A1 (https=) |
| RU (1) | RU2331646C2 (https=) |
| SE (1) | SE0300120D0 (https=) |
| UA (1) | UA80175C2 (https=) |
| WO (1) | WO2004065393A1 (https=) |
| ZA (1) | ZA200505273B (https=) |
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| GB0117583D0 (en) | 2001-07-19 | 2001-09-12 | Astrazeneca Ab | Novel compounds |
| GB0118479D0 (en) * | 2001-07-28 | 2001-09-19 | Astrazeneca Ab | Novel compounds |
| SE0300120D0 (sv) * | 2003-01-17 | 2003-01-17 | Astrazeneca Ab | Novel compounds |
| MXPA05007495A (es) * | 2003-01-17 | 2005-09-21 | Astrazeneca Ab | Tienopiridazinonas y su uso en la modulacion de enfermedades autoinmunes. |
| SE0300119D0 (sv) | 2003-01-17 | 2003-01-17 | Astrazeneca Ab | Novel compounds |
| CN1925855B (zh) | 2003-12-19 | 2010-06-16 | 普莱希科公司 | 开发Ret调节剂的化合物和方法 |
| US7498342B2 (en) | 2004-06-17 | 2009-03-03 | Plexxikon, Inc. | Compounds modulating c-kit activity |
| US7846941B2 (en) | 2005-05-17 | 2010-12-07 | Plexxikon, Inc. | Compounds modulating c-kit and c-fms activity and uses therefor |
| UA95244C2 (ru) | 2005-06-22 | 2011-07-25 | Плексикон, Инк. | Соединения и способ модулирования активности киназ, и показания для их применения |
| ES2559521T3 (es) * | 2006-10-16 | 2016-02-12 | Thesan Pharmaceuticals, Inc. | Pirazolil tienopiridinas terapéuticas |
| WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
| WO2008079909A1 (en) | 2006-12-21 | 2008-07-03 | Plexxikon, Inc. | Pyrrolo [2,3-b] pyridines as kinase modulators |
| PE20121126A1 (es) | 2006-12-21 | 2012-08-24 | Plexxikon Inc | Compuestos pirrolo [2,3-b] piridinas como moduladores de quinasa |
| JP2010514695A (ja) | 2006-12-21 | 2010-05-06 | プレキシコン，インコーポレーテッド | キナーゼ調節のための化合物および方法およびそのための適応症 |
| WO2009012283A1 (en) | 2007-07-17 | 2009-01-22 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| MY172424A (en) | 2009-04-03 | 2019-11-25 | Hoffmann La Roche | Propane- i-sulfonic acid {3- (4-chloro-phenyl)-1h-pyrrolo [2, 3-b] pyridine-3-carconyl] -2, 4-difluoro-phenyl} -amide compositions and uses thereof |
| US8329724B2 (en) | 2009-08-03 | 2012-12-11 | Hoffmann-La Roche Inc. | Process for the manufacture of pharmaceutically active compounds |
| CN106220623A (zh) | 2009-11-06 | 2016-12-14 | 普莱希科公司 | 用于激酶调节的化合物和方法及其适应症 |
| US9624213B2 (en) | 2011-02-07 | 2017-04-18 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| AR085279A1 (es) | 2011-02-21 | 2013-09-18 | Plexxikon Inc | Formas solidas de {3-[5-(4-cloro-fenil)-1h-pirrolo[2,3-b]piridina-3-carbonil]-2,4-difluor-fenil}-amida del acido propano-1-sulfonico |
| JO3407B1 (ar) | 2012-05-31 | 2019-10-20 | Eisai R&D Man Co Ltd | مركبات رباعي هيدرو بيرازولو بيريميدين |
| US9150570B2 (en) | 2012-05-31 | 2015-10-06 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
| US9200005B2 (en) * | 2013-03-13 | 2015-12-01 | AbbVie Deutschland GmbH & Co. KG | Inhibitor compounds of phosphodiesterase type 10A |
| PL3060562T3 (pl) * | 2013-10-21 | 2022-01-10 | Genosco | Podstawione związki pirymidynowe i ich zastosowanie jako inhibitory syk |
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| DE3620860A1 (de) * | 1986-06-21 | 1987-12-23 | Basf Ag | Substituierte acrylsaeureester und fungizide, die diese verbindungen enthalten |
| WO1999029695A1 (en) * | 1997-12-05 | 1999-06-17 | Astrazeneca Uk Limited | Novel compounds |
| US6469014B1 (en) * | 1997-05-28 | 2002-10-22 | Astrazeneca Ab | Thieno[2,3-d] pyrimidinediones, their preparation and use in therapy |
| SE9702001D0 (sv) * | 1997-05-28 | 1997-05-28 | Astra Pharma Prod | Novel compounds |
| US6232320B1 (en) * | 1998-06-04 | 2001-05-15 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| DE69912618T2 (de) * | 1998-08-28 | 2004-10-28 | Astrazeneca Ab | NEUE THIENO[2,3-d]PYRIMIDINDIONE, VERFAHREN FÜR IHRE HERSTELLUNG UND IHRE VERWENDUNG IN DER THERAPIE |
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| GB0118479D0 (en) * | 2001-07-28 | 2001-09-19 | Astrazeneca Ab | Novel compounds |
| MXPA05007495A (es) * | 2003-01-17 | 2005-09-21 | Astrazeneca Ab | Tienopiridazinonas y su uso en la modulacion de enfermedades autoinmunes. |
| SE0300120D0 (sv) * | 2003-01-17 | 2003-01-17 | Astrazeneca Ab | Novel compounds |
| SE0300119D0 (sv) * | 2003-01-17 | 2003-01-17 | Astrazeneca Ab | Novel compounds |
-
2003
- 2003-01-17 SE SE0300120A patent/SE0300120D0/xx unknown
-
2004
- 2004-01-15 CN CNB2004800071016A patent/CN100358900C/zh not_active Expired - Fee Related
- 2004-01-15 US US10/542,194 patent/US7064126B2/en not_active Expired - Fee Related
- 2004-01-15 PL PL378223A patent/PL378223A1/pl unknown
- 2004-01-15 MX MXPA05007494A patent/MXPA05007494A/es active IP Right Grant
- 2004-01-15 DE DE602004009407T patent/DE602004009407T2/de not_active Expired - Lifetime
- 2004-01-15 JP JP2006500749A patent/JP4589298B2/ja not_active Expired - Fee Related
- 2004-01-15 AU AU2004205617A patent/AU2004205617B2/en not_active Ceased
- 2004-01-15 RU RU2005121493/04A patent/RU2331646C2/ru not_active IP Right Cessation
- 2004-01-15 AT AT04702471T patent/ATE375352T1/de not_active IP Right Cessation
- 2004-01-15 UA UAA200506375A patent/UA80175C2/uk unknown
- 2004-01-15 KR KR1020057013124A patent/KR20050092759A/ko not_active Abandoned
- 2004-01-15 EP EP04702471A patent/EP1587809B1/en not_active Expired - Lifetime
- 2004-01-15 NZ NZ541216A patent/NZ541216A/en not_active IP Right Cessation
- 2004-01-15 WO PCT/SE2004/000051 patent/WO2004065393A1/en not_active Ceased
- 2004-01-15 ES ES04702471T patent/ES2293208T3/es not_active Expired - Lifetime
- 2004-01-15 BR BR0406780-0A patent/BRPI0406780A/pt not_active IP Right Cessation
- 2004-01-15 CA CA002512736A patent/CA2512736A1/en not_active Abandoned
-
2005
- 2005-06-23 IL IL169363A patent/IL169363A/en not_active IP Right Cessation
- 2005-06-29 ZA ZA200505273A patent/ZA200505273B/xx unknown
- 2005-08-15 IS IS7982A patent/IS2503B/is unknown
- 2005-08-15 NO NO20053827A patent/NO20053827L/no not_active Application Discontinuation
-
2006
- 2006-06-06 US US11/447,343 patent/US20060223809A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CN100358900C (zh) | 2008-01-02 |
| WO2004065393A1 (en) | 2004-08-05 |
| JP4589298B2 (ja) | 2010-12-01 |
| IS7982A (is) | 2005-08-15 |
| IL169363A0 (en) | 2007-07-04 |
| IS2503B (is) | 2009-04-15 |
| ATE375352T1 (de) | 2007-10-15 |
| ZA200505273B (en) | 2006-04-26 |
| US20060052380A1 (en) | 2006-03-09 |
| DE602004009407T2 (de) | 2008-07-24 |
| JP2006515373A (ja) | 2006-05-25 |
| SE0300120D0 (sv) | 2003-01-17 |
| MXPA05007494A (es) | 2005-09-21 |
| IL169363A (en) | 2011-02-28 |
| NO20053827D0 (no) | 2005-08-15 |
| BRPI0406780A (pt) | 2006-01-17 |
| DE602004009407D1 (de) | 2007-11-22 |
| NO20053827L (no) | 2005-10-17 |
| US7064126B2 (en) | 2006-06-20 |
| ES2293208T3 (es) | 2008-03-16 |
| RU2005121493A (ru) | 2006-02-20 |
| HK1081958A1 (en) | 2006-05-26 |
| RU2331646C2 (ru) | 2008-08-20 |
| EP1587809B1 (en) | 2007-10-10 |
| EP1587809A1 (en) | 2005-10-26 |
| AU2004205617A1 (en) | 2004-08-05 |
| PL378223A1 (pl) | 2006-03-20 |
| UA80175C2 (en) | 2007-08-27 |
| CN1761670A (zh) | 2006-04-19 |
| NZ541216A (en) | 2008-05-30 |
| AU2004205617B2 (en) | 2007-03-08 |
| US20060223809A1 (en) | 2006-10-05 |
| CA2512736A1 (en) | 2004-08-05 |
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