PT564409E - Derivados de pirimidina e processos para a sua preparacao - Google Patents
Derivados de pirimidina e processos para a sua preparacao Download PDFInfo
- Publication number
- PT564409E PT564409E PT93810219T PT93810219T PT564409E PT 564409 E PT564409 E PT 564409E PT 93810219 T PT93810219 T PT 93810219T PT 93810219 T PT93810219 T PT 93810219T PT 564409 E PT564409 E PT 564409E
- Authority
- PT
- Portugal
- Prior art keywords
- phenyl
- pyridyl
- substituted
- formula
- lower alkyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 46
- 230000008569 process Effects 0.000 title claims description 21
- 238000002360 preparation method Methods 0.000 title claims description 17
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 title description 2
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 2
- -1 4-pyrazinyl Chemical group 0.000 claims abstract description 173
- 150000001875 compounds Chemical class 0.000 claims abstract description 135
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 101
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 63
- 239000001257 hydrogen Substances 0.000 claims abstract description 62
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 37
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 36
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 35
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 30
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 27
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 27
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 26
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 24
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000001301 oxygen Substances 0.000 claims abstract description 23
- 125000003277 amino group Chemical group 0.000 claims abstract description 22
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 19
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 18
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 13
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 13
- 125000002757 morpholinyl group Chemical class 0.000 claims abstract description 10
- 125000003386 piperidinyl group Chemical class 0.000 claims abstract description 10
- 125000000719 pyrrolidinyl group Chemical class 0.000 claims abstract description 10
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 9
- 125000001841 imino group Chemical group [H]N=* 0.000 claims abstract description 9
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims abstract description 8
- 125000005277 alkyl imino group Chemical group 0.000 claims abstract description 7
- 125000001041 indolyl group Chemical group 0.000 claims abstract description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 5
- 150000004046 2-(N-anilino)pyrimidines Chemical class 0.000 claims abstract description 4
- 150000003839 salts Chemical class 0.000 claims description 86
- 239000002253 acid Substances 0.000 claims description 48
- 238000011282 treatment Methods 0.000 claims description 37
- 238000006243 chemical reaction Methods 0.000 claims description 29
- 125000003282 alkyl amino group Chemical group 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 22
- 125000006239 protecting group Chemical group 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 21
- 239000003795 chemical substances by application Substances 0.000 claims description 20
- 125000001153 fluoro group Chemical group F* 0.000 claims description 17
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 15
- 239000011737 fluorine Substances 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 14
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
- 125000004423 acyloxy group Chemical group 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000000524 functional group Chemical group 0.000 claims description 11
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 9
- 241001465754 Metazoa Species 0.000 claims description 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 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 6
- 125000004193 piperazinyl group Chemical group 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
- 239000000460 chlorine Chemical group 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 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 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- HFQHGGZJZTXYKH-UHFFFAOYSA-N n-(3-nitrophenyl)-4-pyridin-3-ylpyrimidin-2-amine Chemical compound [O-][N+](=O)C1=CC=CC(NC=2N=C(C=CN=2)C=2C=NC=CC=2)=C1 HFQHGGZJZTXYKH-UHFFFAOYSA-N 0.000 claims description 4
- 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 description 3
- 238000002512 chemotherapy Methods 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 3
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- LLJRXVHJOJRCSM-UHFFFAOYSA-N 3-pyridin-4-yl-1H-indole Chemical group C=1NC2=CC=CC=C2C=1C1=CC=NC=C1 LLJRXVHJOJRCSM-UHFFFAOYSA-N 0.000 claims description 2
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- CRXFIXDVCCWTEZ-UHFFFAOYSA-N n-(3-methyl-5-nitrophenyl)-4-pyridin-3-ylpyrimidin-2-amine Chemical compound [O-][N+](=O)C1=CC(C)=CC(NC=2N=C(C=CN=2)C=2C=NC=CC=2)=C1 CRXFIXDVCCWTEZ-UHFFFAOYSA-N 0.000 claims description 2
- OAGOHUJDUADUHK-UHFFFAOYSA-N n-[3-nitro-5-(trifluoromethyl)phenyl]-4-pyridin-3-ylpyrimidin-2-amine Chemical compound FC(F)(F)C1=CC([N+](=O)[O-])=CC(NC=2N=C(C=CN=2)C=2C=NC=CC=2)=C1 OAGOHUJDUADUHK-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims 2
- QLBMWQJKAHFYHB-UHFFFAOYSA-N 4-pyridin-3-yl-n-[3-(trifluoromethoxy)phenyl]pyrimidin-2-amine Chemical compound FC(F)(F)OC1=CC=CC(NC=2N=C(C=CN=2)C=2C=NC=CC=2)=C1 QLBMWQJKAHFYHB-UHFFFAOYSA-N 0.000 claims 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 19
- 125000003118 aryl group Chemical group 0.000 abstract description 8
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 7
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 111
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- 150000003254 radicals Chemical class 0.000 description 43
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
- 239000013543 active substance Substances 0.000 description 19
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 239000007858 starting material Substances 0.000 description 18
- 108090000315 Protein Kinase C Proteins 0.000 description 15
- 102000003923 Protein Kinase C Human genes 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 13
- 150000008064 anhydrides Chemical class 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 229920002472 Starch Polymers 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 230000002401 inhibitory effect Effects 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 8
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 8
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 150000001721 carbon Chemical group 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 229940100445 wheat starch Drugs 0.000 description 8
- ZQTRXPRIWRFHRY-UHFFFAOYSA-N 3-n-(4-pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamine Chemical compound NC1=CC=CC(NC=2N=C(C=CN=2)C=2C=NC=CC=2)=C1 ZQTRXPRIWRFHRY-UHFFFAOYSA-N 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 239000000454 talc Substances 0.000 description 7
- 229910052623 talc Inorganic materials 0.000 description 7
- 235000012222 talc Nutrition 0.000 description 7
- MZLRFUCMBQWLNV-UHFFFAOYSA-N 3-(dimethylamino)-1-pyridin-3-ylprop-2-en-1-one Chemical compound CN(C)C=CC(=O)C1=CC=CN=C1 MZLRFUCMBQWLNV-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 108091008606 PDGF receptors Proteins 0.000 description 6
- 108091000080 Phosphotransferase Proteins 0.000 description 6
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 6
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 6
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 6
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 102000020233 phosphotransferase Human genes 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 6
- 235000012239 silicon dioxide Nutrition 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 229910002651 NO3 Inorganic materials 0.000 description 5
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 150000001718 carbodiimides Chemical class 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 239000000825 pharmaceutical preparation Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000001253 Protein Kinase Human genes 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 125000001931 aliphatic group Chemical group 0.000 description 4
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-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
- 230000000694 effects Effects 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- VBYYPCNNGNGURO-UHFFFAOYSA-N nitric acid;2-(3-nitrophenyl)guanidine Chemical compound O[N+]([O-])=O.NC(N)=NC1=CC=CC([N+]([O-])=O)=C1 VBYYPCNNGNGURO-UHFFFAOYSA-N 0.000 description 4
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 4
- 239000004033 plastic Substances 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- 108060006633 protein kinase Proteins 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000003797 solvolysis reaction Methods 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- 229920001567 vinyl ester resin Polymers 0.000 description 4
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 3
- NQUVCRCCRXRJCK-UHFFFAOYSA-N 4-methylbenzoyl chloride Chemical compound CC1=CC=C(C(Cl)=O)C=C1 NQUVCRCCRXRJCK-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-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
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 238000006136 alcoholysis reaction Methods 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 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
- 230000001419 dependent effect Effects 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
- HFAFXVOPGDBAOK-UHFFFAOYSA-M pyridine-2-carboxylate;hydrochloride Chemical compound [Cl-].OC(=O)C1=CC=CC=N1 HFAFXVOPGDBAOK-UHFFFAOYSA-M 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 description 2
- YYDIGPGUISOOIJ-UHFFFAOYSA-N 1-(2h-pyridin-1-yloxy)-2h-pyridine Chemical compound C1C=CC=CN1ON1C=CC=CC1 YYDIGPGUISOOIJ-UHFFFAOYSA-N 0.000 description 2
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- OLRJXMHANKMLTD-UHFFFAOYSA-N silyl Chemical compound [SiH3] OLRJXMHANKMLTD-UHFFFAOYSA-N 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- RZWQDAUIUBVCDD-UHFFFAOYSA-M sodium;benzenethiolate Chemical compound [Na+].[S-]C1=CC=CC=C1 RZWQDAUIUBVCDD-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- QIQITDHWZYEEPA-UHFFFAOYSA-N thiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CS1 QIQITDHWZYEEPA-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 125000005039 triarylmethyl group Chemical group 0.000 description 1
- PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 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
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 239000006200 vaporizer Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D401/14—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 three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Macromonomer-Based Addition Polymer (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Paints Or Removers (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH108392 | 1992-04-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT564409E true PT564409E (pt) | 2000-06-30 |
Family
ID=4202064
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT93810219T PT564409E (pt) | 1992-04-03 | 1993-03-25 | Derivados de pirimidina e processos para a sua preparacao |
Country Status (29)
| Country | Link |
|---|---|
| EP (1) | EP0564409B1 (OSRAM) |
| JP (1) | JP2706682B2 (OSRAM) |
| KR (1) | KR100261366B1 (OSRAM) |
| CN (1) | CN1043531C (OSRAM) |
| AT (1) | ATE188964T1 (OSRAM) |
| AU (1) | AU666709B2 (OSRAM) |
| BR (1) | BR1100739A (OSRAM) |
| CA (1) | CA2093203C (OSRAM) |
| CY (2) | CY2229B1 (OSRAM) |
| CZ (1) | CZ283944B6 (OSRAM) |
| DE (2) | DE10299016I2 (OSRAM) |
| DK (1) | DK0564409T3 (OSRAM) |
| ES (1) | ES2142857T3 (OSRAM) |
| FI (1) | FI109534B (OSRAM) |
| GR (1) | GR3032927T3 (OSRAM) |
| HU (2) | HU226488B1 (OSRAM) |
| IL (1) | IL105264A (OSRAM) |
| LU (1) | LU90908I2 (OSRAM) |
| MX (1) | MX9301929A (OSRAM) |
| NL (1) | NL300086I2 (OSRAM) |
| NO (2) | NO302473B1 (OSRAM) |
| NZ (1) | NZ247299A (OSRAM) |
| PT (1) | PT564409E (OSRAM) |
| RU (1) | RU2125992C1 (OSRAM) |
| SA (1) | SA93140441B1 (OSRAM) |
| SG (1) | SG43859A1 (OSRAM) |
| SK (1) | SK280620B6 (OSRAM) |
| TW (1) | TW225528B (OSRAM) |
| ZA (1) | ZA932397B (OSRAM) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5521184A (en) * | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
| GB9212673D0 (en) * | 1992-06-15 | 1992-07-29 | Celltech Ltd | Chemical compounds |
| US6171786B1 (en) | 1992-09-17 | 2001-01-09 | Board Of Trustees Of University Of Illinois | Methods for preventing multidrug resistance in cancer cells |
| US5972598A (en) * | 1992-09-17 | 1999-10-26 | Board Of Trustess Of The University Of Illinois | Methods for preventing multidrug resistance in cancer cells |
| GB9222253D0 (en) * | 1992-10-23 | 1992-12-09 | Celltech Ltd | Chemical compounds |
| GB9304920D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| GB9304919D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| AU693475B2 (en) * | 1993-10-01 | 1998-07-02 | Novartis Ag | Pyrimidineamine derivatives and processes for the preparation thereof |
| AU691834B2 (en) * | 1993-10-01 | 1998-05-28 | Novartis Ag | Pharmacologically active pyridine derivatives and processes for the preparation thereof |
| EP0672042B1 (en) * | 1993-10-01 | 2006-05-03 | Novartis AG | Pharmacologically active pyrimidineamine derivatives and processes for the preparation thereof |
| US5543520A (en) * | 1993-10-01 | 1996-08-06 | Ciba-Geigy Corporation | Pyrimidine derivatives |
| GB9325217D0 (en) * | 1993-12-09 | 1994-02-09 | Zeneca Ltd | Pyrimidine derivatives |
| GB9326600D0 (en) * | 1993-12-22 | 1994-03-02 | Celltech Ltd | Chemical compounds |
| DE69433594T2 (de) * | 1993-12-22 | 2004-08-05 | Celltech R&D Ltd., Slough | Trisubstituierte phenyl-derivate, verfahren zu deren herstellung und deren verwendung als phosphodiesterase (typ iv) hemmstoffe |
| US5786354A (en) * | 1994-06-21 | 1998-07-28 | Celltech Therapeutics, Limited | Tri-substituted phenyl derivatives and processes for their preparation |
| US6245774B1 (en) | 1994-06-21 | 2001-06-12 | Celltech Therapeutics Limited | Tri-substituted phenyl or pyridine derivatives |
| GB9412571D0 (en) * | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| GB9412573D0 (en) | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| GB9412672D0 (en) * | 1994-06-23 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| US5756527A (en) * | 1995-06-07 | 1998-05-26 | Ontogen Corporation | Imidazole derivatives useful as modulators of multi drug resistances |
| GB9523675D0 (en) * | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9526245D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9526246D0 (en) * | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9608435D0 (en) * | 1996-04-24 | 1996-06-26 | Celltech Therapeutics Ltd | Chemical compounds |
| EP0812830A1 (en) * | 1996-06-14 | 1997-12-17 | Ontogen Corporation | Modulators of multi-drug resistances |
| EP0812829A1 (en) * | 1996-06-14 | 1997-12-17 | Ontogen Corporation | Substituted imidazoles as modulators of multi-drug resistance |
| GB9619284D0 (en) * | 1996-09-16 | 1996-10-30 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9622363D0 (en) * | 1996-10-28 | 1997-01-08 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9625184D0 (en) * | 1996-12-04 | 1997-01-22 | Celltech Therapeutics Ltd | Chemical compounds |
| US6057329A (en) * | 1996-12-23 | 2000-05-02 | Celltech Therapeutics Limited | Fused polycyclic 2-aminopyrimidine derivatives |
| GB9705361D0 (en) * | 1997-03-14 | 1997-04-30 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9713087D0 (en) * | 1997-06-20 | 1997-08-27 | Celltech Therapeutics Ltd | Chemical compounds |
| CO4940418A1 (es) * | 1997-07-18 | 2000-07-24 | Novartis Ag | Modificacion de cristal de un derivado de n-fenil-2- pirimidinamina, procesos para su fabricacion y su uso |
| GB9914258D0 (en) | 1999-06-18 | 1999-08-18 | Celltech Therapeutics Ltd | Chemical compounds |
| CA2383546A1 (en) | 1999-06-30 | 2001-01-04 | William H. Parsons | Src kinase inhibitor compounds |
| US6329380B1 (en) | 1999-06-30 | 2001-12-11 | Merck & Co., Inc. | SRC kinase inhibitor compounds |
| CA2376951A1 (en) | 1999-06-30 | 2001-01-04 | Peter J. Sinclair | Src kinase inhibitor compounds |
| GB9919778D0 (en) | 1999-08-21 | 1999-10-27 | Zeneca Ltd | Chemical compounds |
| WO2001017995A1 (en) | 1999-09-10 | 2001-03-15 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| GB9924862D0 (en) | 1999-10-20 | 1999-12-22 | Celltech Therapeutics Ltd | Chemical compounds |
| CA2400447C (en) * | 2000-02-17 | 2008-04-22 | Amgen Inc. | Kinase inhibitors |
| GB0004888D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004890D0 (en) * | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004886D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004887D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| US7087608B2 (en) * | 2000-03-03 | 2006-08-08 | Robert Charles Atkins | Use of PDGF receptor tyrosine kinase inhibitors for the treatment of diabetic nephropathy |
| GB0007371D0 (en) | 2000-03-28 | 2000-05-17 | Astrazeneca Uk Ltd | Chemical compounds |
| US7030219B2 (en) | 2000-04-28 | 2006-04-18 | Johns Hopkins University | B7-DC, Dendritic cell co-stimulatory molecules |
| PT1315715E (pt) | 2000-08-18 | 2008-10-30 | Millennium Pharm Inc | Derivados de quianazolina utilizados como inibidores de quinase |
| GB0022438D0 (en) * | 2000-09-13 | 2000-11-01 | Novartis Ag | Organic Compounds |
| CN1276754C (zh) * | 2000-10-27 | 2006-09-27 | 诺瓦提斯公司 | 胃肠基质肿瘤的治疗 |
| EP1330444B1 (en) | 2000-11-01 | 2011-03-23 | Millennium Pharmaceuticals, Inc. | Nitrogenous heterocyclic compounds and process for making them |
| GB0103926D0 (en) * | 2001-02-17 | 2001-04-04 | Astrazeneca Ab | Chemical compounds |
| DK2762140T3 (en) | 2001-02-19 | 2017-07-10 | Novartis Ag | Treatment of solid brain tumors with a rapamycin derivative |
| SE0100569D0 (sv) * | 2001-02-20 | 2001-02-20 | Astrazeneca Ab | New compounds |
| CN1511036B (zh) | 2001-02-27 | 2010-05-05 | 诺瓦提斯公司 | 包含信号转导抑制剂和埃坡霉素衍生物的联合形式 |
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| AU2002342878A1 (en) * | 2001-05-16 | 2002-11-25 | Axxima Pharmaceuticals Ag | Pyridylpyrimidine derivatives as effective compounds against prion diseases |
| JP4444651B2 (ja) | 2001-06-14 | 2010-03-31 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Ｓｔｉ−５７１に対する耐性に関連するｂｃｒ−ａｂｌチロシンキナーゼの変異 |
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| WO2003003006A2 (en) * | 2001-06-29 | 2003-01-09 | Ab Science | New potent, selective and non toxic c-kit inhibitors |
| WO2003004006A2 (en) * | 2001-06-29 | 2003-01-16 | Ab Science | Use of potent, selective and non toxic c-kit inhibitors for treating tumor angiogenesis |
| ATE343415T1 (de) | 2001-06-29 | 2006-11-15 | Ab Science | Die verwendung von c-kit hemmer zur behandlung von entzündlichen darmerkrankungen |
| JP2005511596A (ja) * | 2001-09-20 | 2005-04-28 | アブ サイエンス | ヒトの皮膚を白くし、且つメラノサイト機能不全関連疾病を治療するためのチロシンキナーゼ阻害剤の使用方法 |
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| EP2343365A1 (en) | 2001-10-05 | 2011-07-13 | Novartis AG | Mutated Abl kinase domains |
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| GB0202873D0 (en) | 2002-02-07 | 2002-03-27 | Novartis Ag | Organic compounds |
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| JP2005523282A (ja) * | 2002-02-22 | 2005-08-04 | ザ・ガバメント・オブ・ザ・ユナイテッド・ステイツ・ザ・デパートメント・オブ・ベテランズ・アフェアーズ | 精上皮腫を処置するための４−（４−メチルピペラジン−１−イルメチル）−ｎ−［４−メチル−３−（４−ピリジン−３−イル）ピリミジン−２−イルアミノ］フェニル］−ベンズアミドの使用 |
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| DE2814202C2 (de) * | 1977-04-05 | 1985-12-19 | Taiho Pharmaceutical Co., Ltd., Tokio/Tokyo | Verwendung von Uracilderivaten zur Bekämpfung von Krebs oder krebsartigen Erkrankungen |
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