JP2005522438A - ピリミジン化合物 - Google Patents
ピリミジン化合物 Download PDFInfo
- Publication number
- JP2005522438A JP2005522438A JP2003565975A JP2003565975A JP2005522438A JP 2005522438 A JP2005522438 A JP 2005522438A JP 2003565975 A JP2003565975 A JP 2003565975A JP 2003565975 A JP2003565975 A JP 2003565975A JP 2005522438 A JP2005522438 A JP 2005522438A
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- JP
- Japan
- Prior art keywords
- amino
- phenyl
- methyl
- alkyl
- pyrimidin
- 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.)
- Pending
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- 150000003230 pyrimidines Chemical class 0.000 title abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 61
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims abstract description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 38
- 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 claims abstract description 37
- 102100022014 Angiopoietin-1 receptor Human genes 0.000 claims abstract description 36
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims abstract description 34
- BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 claims abstract description 31
- 238000011282 treatment Methods 0.000 claims abstract description 20
- 150000001875 compounds Chemical class 0.000 claims description 140
- 229910052739 hydrogen Inorganic materials 0.000 claims description 126
- 239000001257 hydrogen Substances 0.000 claims description 121
- -1 C 1 -C 4 alkyl Chemical group 0.000 claims description 117
- 150000002431 hydrogen Chemical group 0.000 claims description 113
- 125000000217 alkyl group Chemical group 0.000 claims description 91
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 82
- 125000000623 heterocyclic group Chemical group 0.000 claims description 82
- 125000003118 aryl group Chemical group 0.000 claims description 74
- 150000003839 salts Chemical class 0.000 claims description 73
- 125000003545 alkoxy group Chemical group 0.000 claims description 71
- 125000001072 heteroaryl group Chemical group 0.000 claims description 60
- 239000012453 solvate Substances 0.000 claims description 56
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 55
- 125000004104 aryloxy group Chemical group 0.000 claims description 48
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 42
- 230000000694 effects Effects 0.000 claims description 38
- 229910052736 halogen Inorganic materials 0.000 claims description 35
- 150000002367 halogens Chemical group 0.000 claims description 35
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 31
- 208000035475 disorder Diseases 0.000 claims description 31
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 31
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 230000033115 angiogenesis Effects 0.000 claims description 29
- 239000003814 drug Substances 0.000 claims description 29
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims description 27
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 26
- 125000003282 alkyl amino group Chemical group 0.000 claims description 26
- 206010028980 Neoplasm Diseases 0.000 claims description 25
- 201000011510 cancer Diseases 0.000 claims description 24
- 230000006870 function Effects 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 241000124008 Mammalia Species 0.000 claims description 23
- 125000001769 aryl amino group Chemical group 0.000 claims description 23
- 229940079593 drug Drugs 0.000 claims description 22
- 239000000460 chlorine Substances 0.000 claims description 18
- 239000002246 antineoplastic agent Substances 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
- 102000009465 Growth Factor Receptors Human genes 0.000 claims description 15
- 108010009202 Growth Factor Receptors Proteins 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 14
- 125000001188 haloalkyl group Chemical group 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 13
- 108091008605 VEGF receptors Proteins 0.000 claims description 11
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims description 11
- 229940034982 antineoplastic agent Drugs 0.000 claims description 10
- 125000001475 halogen functional group Chemical group 0.000 claims description 10
- 230000001404 mediated effect Effects 0.000 claims description 10
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 229940124530 sulfonamide Drugs 0.000 claims description 8
- 150000001408 amides Chemical class 0.000 claims description 7
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 6
- DTUXNRWKSVIUOF-UHFFFAOYSA-N 1-[4-[methyl-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]-3-propylurea Chemical compound C1=CC(NC(=O)NCCC)=CC=C1N(C)C1=CC=NC(NC=2C=C(CS(C)(=O)=O)C=CC=2)=N1 DTUXNRWKSVIUOF-UHFFFAOYSA-N 0.000 claims description 6
- 102000001301 EGF receptor Human genes 0.000 claims description 6
- 108060006698 EGF receptor Proteins 0.000 claims description 6
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 claims description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- RJINUSFBYKYLTQ-UHFFFAOYSA-N 1-[4-[methyl-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]-3-phenylthiourea Chemical compound C=1C=NC(NC=2C=C(CS(C)(=O)=O)C=CC=2)=NC=1N(C)C(C=C1)=CC=C1NC(=S)NC1=CC=CC=C1 RJINUSFBYKYLTQ-UHFFFAOYSA-N 0.000 claims description 4
- 108091008606 PDGF receptors Proteins 0.000 claims description 4
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 claims description 4
- 229940091171 VEGFR-2 tyrosine kinase inhibitor Drugs 0.000 claims description 4
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 claims description 4
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 claims description 4
- 239000004202 carbamide Substances 0.000 claims description 4
- SQQWBSBBCSFQGC-JLHYYAGUSA-N ubiquinone-2 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CCC=C(C)C)=C(C)C1=O SQQWBSBBCSFQGC-JLHYYAGUSA-N 0.000 claims description 4
- LZWJEODSCLZMOY-UHFFFAOYSA-N 1-(2,3-dihydro-1h-inden-5-yl)-3-[4-[methyl-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]urea Chemical compound C=1C=C(NC(=O)NC=2C=C3CCCC3=CC=2)C=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=CC(CS(C)(=O)=O)=C1 LZWJEODSCLZMOY-UHFFFAOYSA-N 0.000 claims description 3
- USCPNRWCYGQBGN-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-[4-[[2-(5-ethylsulfonyl-2-methoxyanilino)pyrimidin-4-yl]-methylamino]phenyl]urea Chemical compound CCS(=O)(=O)C1=CC=C(OC)C(NC=2N=C(C=CN=2)N(C)C=2C=CC(NC(=O)NC=3C=C(Cl)C=CC=3)=CC=2)=C1 USCPNRWCYGQBGN-UHFFFAOYSA-N 0.000 claims description 3
- RZFLHAKBZISSBN-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-[4-[[2-[3-(methanesulfonamidomethyl)anilino]pyrimidin-4-yl]-methylamino]phenyl]urea Chemical compound C=1C=NC(NC=2C=C(CNS(C)(=O)=O)C=CC=2)=NC=1N(C)C(C=C1)=CC=C1NC(=O)NC1=CC=CC(Cl)=C1 RZFLHAKBZISSBN-UHFFFAOYSA-N 0.000 claims description 3
- ISIGZINVBPDMCU-UHFFFAOYSA-N 1-(3-fluorophenyl)-3-[4-[methyl-[2-[4-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]urea;hydrochloride Chemical compound Cl.C=1C=NC(NC=2C=CC(CS(C)(=O)=O)=CC=2)=NC=1N(C)C(C=C1)=CC=C1NC(=O)NC1=CC=CC(F)=C1 ISIGZINVBPDMCU-UHFFFAOYSA-N 0.000 claims description 3
- UIIXIQWTXSGBOP-UHFFFAOYSA-N 1-(4-fluorophenyl)-3-[4-[methyl-[2-[4-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]urea Chemical compound C=1C=NC(NC=2C=CC(CS(C)(=O)=O)=CC=2)=NC=1N(C)C(C=C1)=CC=C1NC(=O)NC1=CC=C(F)C=C1 UIIXIQWTXSGBOP-UHFFFAOYSA-N 0.000 claims description 3
- RREMTKSPGOIRHQ-UHFFFAOYSA-N 1-[2-(dimethylamino)ethyl]-3-[4-[methyl-[2-[3-(2-methylsulfonylethyl)anilino]pyrimidin-4-yl]amino]phenyl]urea Chemical compound C1=CC(NC(=O)NCCN(C)C)=CC=C1N(C)C1=CC=NC(NC=2C=C(CCS(C)(=O)=O)C=CC=2)=N1 RREMTKSPGOIRHQ-UHFFFAOYSA-N 0.000 claims description 3
- YBLPVRFSDNONDP-UHFFFAOYSA-N 1-[4-[[2-(5-ethylsulfonyl-2-methoxyanilino)pyrimidin-4-yl]-methylamino]phenyl]-3-(3-fluorophenyl)urea Chemical compound CCS(=O)(=O)C1=CC=C(OC)C(NC=2N=C(C=CN=2)N(C)C=2C=CC(NC(=O)NC=3C=C(F)C=CC=3)=CC=2)=C1 YBLPVRFSDNONDP-UHFFFAOYSA-N 0.000 claims description 3
- RYIZQWVKFLSVHM-UHFFFAOYSA-N 1-[4-[[2-(5-ethylsulfonyl-2-methoxyanilino)pyrimidin-4-yl]-methylamino]phenyl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea Chemical compound CCS(=O)(=O)C1=CC=C(OC)C(NC=2N=C(C=CN=2)N(C)C=2C=CC(NC(=O)NC=3C(=CC=C(C=3)C(F)(F)F)F)=CC=2)=C1 RYIZQWVKFLSVHM-UHFFFAOYSA-N 0.000 claims description 3
- DQXBQPHEQRETIN-UHFFFAOYSA-N 1-[4-[methyl-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]-3-(2-phenylethyl)urea Chemical compound C=1C=NC(NC=2C=C(CS(C)(=O)=O)C=CC=2)=NC=1N(C)C(C=C1)=CC=C1NC(=O)NCCC1=CC=CC=C1 DQXBQPHEQRETIN-UHFFFAOYSA-N 0.000 claims description 3
- ZMDSDIMLVJXMJA-UHFFFAOYSA-N 1-[4-[methyl-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C=1C=NC(NC=2C=C(CS(C)(=O)=O)C=CC=2)=NC=1N(C)C(C=C1)=CC=C1NC(=O)NC1=CC=C(OC(F)(F)F)C=C1 ZMDSDIMLVJXMJA-UHFFFAOYSA-N 0.000 claims description 3
- NJVJUCVNZRPMBF-UHFFFAOYSA-N 1-[4-[methyl-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]-3-phenylurea Chemical compound C=1C=NC(NC=2C=C(CS(C)(=O)=O)C=CC=2)=NC=1N(C)C(C=C1)=CC=C1NC(=O)NC1=CC=CC=C1 NJVJUCVNZRPMBF-UHFFFAOYSA-N 0.000 claims description 3
- GDFXLACGLHMCTE-UHFFFAOYSA-N 1-[4-[methyl-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]-3-propan-2-ylurea Chemical compound C1=CC(NC(=O)NC(C)C)=CC=C1N(C)C1=CC=NC(NC=2C=C(CS(C)(=O)=O)C=CC=2)=N1 GDFXLACGLHMCTE-UHFFFAOYSA-N 0.000 claims description 3
- LVGQTXJDZKXBOC-UHFFFAOYSA-N 1-[4-[methyl-[2-[4-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]-3-(4-phenylmethoxyphenyl)urea Chemical compound C=1C=NC(NC=2C=CC(CS(C)(=O)=O)=CC=2)=NC=1N(C)C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1OCC1=CC=CC=C1 LVGQTXJDZKXBOC-UHFFFAOYSA-N 0.000 claims description 3
- AHDFVTJYNGXCEO-UHFFFAOYSA-N 1-[4-[methyl-[2-[4-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]-3-[4-(4-methylpiperazine-1-carbonyl)phenyl]urea Chemical compound C=1C=NC(NC=2C=CC(CS(C)(=O)=O)=CC=2)=NC=1N(C)C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1C(=O)N1CCN(C)CC1 AHDFVTJYNGXCEO-UHFFFAOYSA-N 0.000 claims description 3
- WUUXQSKAAWHECK-UHFFFAOYSA-N 1-[4-[methyl-[2-[4-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]-3-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]urea Chemical compound C=1C=NC(NC=2C=CC(CS(C)(=O)=O)=CC=2)=NC=1N(C)C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1CN1CCN(C)CC1 WUUXQSKAAWHECK-UHFFFAOYSA-N 0.000 claims description 3
- CCGBGVNOJXOFAR-UHFFFAOYSA-N 1-butyl-3-[4-[methyl-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]urea Chemical compound C1=CC(NC(=O)NCCCC)=CC=C1N(C)C1=CC=NC(NC=2C=C(CS(C)(=O)=O)C=CC=2)=N1 CCGBGVNOJXOFAR-UHFFFAOYSA-N 0.000 claims description 3
- HQILAAKXJCORFA-UHFFFAOYSA-N 1-cyclohexyl-3-[4-[methyl-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]urea Chemical compound C=1C=NC(NC=2C=C(CS(C)(=O)=O)C=CC=2)=NC=1N(C)C(C=C1)=CC=C1NC(=O)NC1CCCCC1 HQILAAKXJCORFA-UHFFFAOYSA-N 0.000 claims description 3
- QCXCNKJISLRDOZ-UHFFFAOYSA-N 1-ethyl-3-[4-[methyl-[2-[4-[2-(methylsulfamoyl)ethyl]anilino]pyrimidin-4-yl]amino]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1N(C)C1=CC=NC(NC=2C=CC(CCS(=O)(=O)NC)=CC=2)=N1 QCXCNKJISLRDOZ-UHFFFAOYSA-N 0.000 claims description 3
- RZBKPAOZLPAYEX-UHFFFAOYSA-N 1-methyl-1-[4-[methyl-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]-3-phenylurea Chemical compound C=1C=C(N(C)C=2N=C(NC=3C=C(CS(C)(=O)=O)C=CC=3)N=CC=2)C=CC=1N(C)C(=O)NC1=CC=CC=C1 RZBKPAOZLPAYEX-UHFFFAOYSA-N 0.000 claims description 3
- VRVGEKJEMKGQCS-UHFFFAOYSA-N 1-tert-butyl-3-[4-[methyl-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]urea Chemical compound C=1C=NC(NC=2C=C(CS(C)(=O)=O)C=CC=2)=NC=1N(C)C1=CC=C(NC(=O)NC(C)(C)C)C=C1 VRVGEKJEMKGQCS-UHFFFAOYSA-N 0.000 claims description 3
- WTTQMMJLQSHYGL-UHFFFAOYSA-N 2-[4-[methyl-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]-1-phenylguanidine Chemical compound C=1C=NC(NC=2C=C(CS(C)(=O)=O)C=CC=2)=NC=1N(C)C(C=C1)=CC=C1N=C(N)NC1=CC=CC=C1 WTTQMMJLQSHYGL-UHFFFAOYSA-N 0.000 claims description 3
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- 102000012753 TIE-2 Receptor Human genes 0.000 claims description 3
- VYWQTJWGWLKBQA-UHFFFAOYSA-N [amino(hydroxy)methylidene]azanium;chloride Chemical compound Cl.NC(N)=O VYWQTJWGWLKBQA-UHFFFAOYSA-N 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- ROIHUUVUCIGOLZ-UHFFFAOYSA-N n-[4-[methyl-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]-1-phenylmethanesulfonamide Chemical compound C=1C=NC(NC=2C=C(CS(C)(=O)=O)C=CC=2)=NC=1N(C)C(C=C1)=CC=C1NS(=O)(=O)CC1=CC=CC=C1 ROIHUUVUCIGOLZ-UHFFFAOYSA-N 0.000 claims description 3
- XGJGNIZVSIGIJT-UHFFFAOYSA-N n-[4-[methyl-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]phenyl]-2-phenylacetamide Chemical compound C=1C=NC(NC=2C=C(CS(C)(=O)=O)C=CC=2)=NC=1N(C)C(C=C1)=CC=C1NC(=O)CC1=CC=CC=C1 XGJGNIZVSIGIJT-UHFFFAOYSA-N 0.000 claims description 3
- BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 claims description 3
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- XIDCNIZERXGXGB-UHFFFAOYSA-N CN(C1=CC=C(C=C1)NC(=O)NC2=C(C=CC(=C2)C(F)(F)F)F)C3=NC(=NC=C3)NC4=CC=CC=C4 Chemical compound CN(C1=CC=C(C=C1)NC(=O)NC2=C(C=CC(=C2)C(F)(F)F)F)C3=NC(=NC=C3)NC4=CC=CC=C4 XIDCNIZERXGXGB-UHFFFAOYSA-N 0.000 claims description 2
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- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- HHJUWIANJFBDHT-KOTLKJBCSA-N vindesine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(N)=O)N4C)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 HHJUWIANJFBDHT-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229930195724 β-lactose Natural products 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
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US35504602P | 2002-02-08 | 2002-02-08 | |
| PCT/US2003/003816 WO2003066601A1 (en) | 2002-02-08 | 2003-02-07 | Pyrimidine compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005522438A true JP2005522438A (ja) | 2005-07-28 |
| JP2005522438A5 JP2005522438A5 (enExample) | 2006-03-23 |
Family
ID=27734457
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003565975A Pending JP2005522438A (ja) | 2002-02-08 | 2003-02-07 | ピリミジン化合物 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7459455B2 (enExample) |
| EP (1) | EP1472233A1 (enExample) |
| JP (1) | JP2005522438A (enExample) |
| AU (1) | AU2003209077A1 (enExample) |
| CA (1) | CA2476281A1 (enExample) |
| MX (1) | MXPA04007637A (enExample) |
| WO (1) | WO2003066601A1 (enExample) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009008371A1 (ja) * | 2007-07-06 | 2009-01-15 | Astellas Pharma Inc. | ジ（アリールアミノ）アリール化合物 |
| JP2009542751A (ja) * | 2006-07-12 | 2009-12-03 | バイエル・シエーリング・ファーマ アクチエンゲゼルシャフト | Ｔｉｅ２阻害剤としての置換スルホキシミンおよびその塩、それを含む医薬組成物、それを調製する方法およびその使用 |
| JP2011502956A (ja) * | 2007-04-24 | 2011-01-27 | インゲニウム ファーマシューティカルズ ジーエムビーエイチ | プロテインキナーゼの阻害剤 |
| JP2012507497A (ja) * | 2008-11-03 | 2012-03-29 | ジェネリクス・（ユーケー）・リミテッド | ボセンタンおよび関連物質のｈｐｌｃ分析方法、ならびに参照スタンダードまたはマーカーとしてのこれら物質の使用 |
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|---|---|---|---|---|
| HRP20031081A2 (en) | 2001-05-29 | 2005-10-31 | Schering Aktiengesellschaft | Cdk inhibiting pyrimidines, production thereof and their use as medicaments |
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| GB0206215D0 (en) | 2002-03-15 | 2002-05-01 | Novartis Ag | Organic compounds |
| RS51752B (sr) | 2002-07-29 | 2011-12-31 | Rigel Pharmaceuticals | Metode tretiranja i prevencije autoimunih oboljenja jedinjenjima 2,4-pirimidindiamina |
| GB0305929D0 (en) | 2003-03-14 | 2003-04-23 | Novartis Ag | Organic compounds |
| ATE368121T1 (de) * | 2003-07-22 | 2007-08-15 | Sungene Gmbh | Expressionskassetten zur bidirektionalen transgenen expression von nukleinsäuren in pflanzen |
| HRP20130602T1 (en) | 2003-07-30 | 2013-07-31 | Rigel Pharmaceuticals, Inc. | 2,4-pyrimidinediamine compounds for use in the treatment or prevention of autoimmune diseases |
| RU2395500C2 (ru) * | 2003-08-15 | 2010-07-27 | Новартис Аг | 2,4-пиримидиндиамины, применяемые в лечении неопластических болезней, воспалительных и иммунных расстройств |
| AU2004272288B2 (en) * | 2003-09-18 | 2008-11-13 | Novartis Ag | 2,4-di (phenylamino) pyrimidines useful in the treatment of proliferative disorders |
| US20070134670A1 (en) * | 2003-12-12 | 2007-06-14 | Bayer Pharmaceuticals Corporation | Methods for prediction and prognosis of cancer, and monitoring cancer therapy |
| TW200626559A (en) * | 2004-10-13 | 2006-08-01 | Wyeth Corp | Anilino-pyrimidine analogs |
| DK1814878T3 (da) | 2004-11-24 | 2012-05-07 | Rigel Pharmaceuticals Inc | Spiro-2, 4-pyrimidindiamin-forbindelser og anvendelser deraf |
| DE602006010979D1 (de) | 2005-01-19 | 2010-01-21 | Rigel Pharmaceuticals Inc | Prodrugs aus 2,4-pyrimidindiamin-verbindungen und ihre verwendungen |
| US20070203161A1 (en) | 2006-02-24 | 2007-08-30 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| CA2608367C (en) | 2005-06-08 | 2014-08-19 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| FR2888239B1 (fr) * | 2005-07-11 | 2008-05-09 | Sanofi Aventis Sa | Nouveaux derives de 2,4-dianilinopyrimidines, leur preparation, a titre de medicaments, compositions pharmaceutiques et notamment comme inhibiteurs de ikk |
| NZ564872A (en) * | 2005-07-11 | 2010-01-29 | Sanofi Aventis | Novel 2,4-dianilinopyrimidine derivatives, the preparation thereof, their use as medicaments, pharmaceutical compositions and, in particular, as ikk inhibitors |
| US7523289B2 (en) | 2005-09-30 | 2009-04-21 | Spectra Logic Corporation | Random access storage system capable of performing storage operations intended for alternative storage devices |
| ES2622493T3 (es) | 2006-02-24 | 2017-07-06 | Rigel Pharmaceuticals, Inc. | Composiciones y métodos para la inhibición de la ruta de JAK |
| EP2258700A1 (en) | 2006-05-09 | 2010-12-08 | Pfizer Products Inc. | Cycloalkylamino acid derivatives and pharmaceutical compositions thereof |
| EP1873159A1 (en) * | 2006-06-21 | 2008-01-02 | Bayer Schering Pharma Aktiengesellschaft | Substituted sulphonamido-macrocycles as Tie2 inhibitors and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
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| KR20100132550A (ko) | 2008-04-16 | 2010-12-17 | 포톨라 파마슈티컬스, 인코포레이티드 | ｓｙｋ 또는 ＪＡＫ 키나제 억제제로서의 ２,６－디아미노-피리미딘－５－일－카르복스아미드 |
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| AU2013227139B2 (en) | 2012-02-28 | 2017-02-16 | Astellas Pharma Inc. | Nitrogen-containing aromatic heterocyclic compound |
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| US9133134B2 (en) * | 2012-05-16 | 2015-09-15 | Pharmacyclics Llc | Inhibitors of bruton's tyrosine kinase |
| EP2903970A4 (en) | 2012-10-08 | 2016-11-30 | Portola Pharm Inc | SUBSTITUTED PYRIMIDINYL KINASE INHIBITORS |
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| US9492471B2 (en) | 2013-08-27 | 2016-11-15 | Celgene Avilomics Research, Inc. | Methods of treating a disease or disorder associated with Bruton'S Tyrosine Kinase |
| US9415049B2 (en) | 2013-12-20 | 2016-08-16 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
| BR112016026544A2 (pt) * | 2014-05-15 | 2017-12-12 | Catalyst Therapeutics Pty Ltd | métodos para inibir a necroptose |
| WO2016025561A1 (en) | 2014-08-13 | 2016-02-18 | Celgene Avilomics Research, Inc. | Forms and compositions of an erk inhibitor |
| CN107531645A (zh) * | 2015-02-10 | 2018-01-02 | 催化剂治疗私人有限公司 | 坏死性凋亡的抑制剂 |
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| ES2208737T3 (es) | 1995-03-10 | 2004-06-16 | Berlex Laboratories, Inc. | Derivados de benzamidina, su preparacion y su utilizacion como anticoagulantes. |
| US5691364A (en) * | 1995-03-10 | 1997-11-25 | Berlex Laboratories, Inc. | Benzamidine derivatives and their use as anti-coagulants |
| GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| AU5438299A (en) * | 1998-08-29 | 2000-03-21 | Astrazeneca Ab | Pyrimidine compounds |
| GB9828511D0 (en) * | 1998-12-24 | 1999-02-17 | Zeneca Ltd | Chemical compounds |
| WO2000076980A1 (en) | 1999-06-10 | 2000-12-21 | Yamanouchi Pharmaceutical Co., Ltd. | Novel nitrogen-contaiing heterocyclic derivatives or salts thereof |
| GB9914258D0 (en) | 1999-06-18 | 1999-08-18 | Celltech Therapeutics Ltd | Chemical compounds |
| JP2003532635A (ja) | 2000-02-17 | 2003-11-05 | アムジエン・インコーポレーテツド | キナーゼ阻害薬 |
| GB0004888D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| TWI329105B (en) * | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
-
2003
- 2003-02-07 AU AU2003209077A patent/AU2003209077A1/en not_active Abandoned
- 2003-02-07 CA CA002476281A patent/CA2476281A1/en not_active Abandoned
- 2003-02-07 JP JP2003565975A patent/JP2005522438A/ja active Pending
- 2003-02-07 EP EP03707805A patent/EP1472233A1/en not_active Withdrawn
- 2003-02-07 US US10/503,874 patent/US7459455B2/en not_active Expired - Fee Related
- 2003-02-07 WO PCT/US2003/003816 patent/WO2003066601A1/en not_active Ceased
- 2003-02-07 MX MXPA04007637A patent/MXPA04007637A/es unknown
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009542751A (ja) * | 2006-07-12 | 2009-12-03 | バイエル・シエーリング・ファーマ アクチエンゲゼルシャフト | Ｔｉｅ２阻害剤としての置換スルホキシミンおよびその塩、それを含む医薬組成物、それを調製する方法およびその使用 |
| JP2011502956A (ja) * | 2007-04-24 | 2011-01-27 | インゲニウム ファーマシューティカルズ ジーエムビーエイチ | プロテインキナーゼの阻害剤 |
| WO2009008371A1 (ja) * | 2007-07-06 | 2009-01-15 | Astellas Pharma Inc. | ジ（アリールアミノ）アリール化合物 |
| US8318702B2 (en) | 2007-07-06 | 2012-11-27 | Astellas Pharma Inc. | Di(arylamino)aryl compounds |
| JP5233996B2 (ja) * | 2007-07-06 | 2013-07-10 | アステラス製薬株式会社 | ジ（アリールアミノ）アリール化合物 |
| KR101323566B1 (ko) | 2007-07-06 | 2013-10-29 | 아스테라스 세이야쿠 가부시키가이샤 | 디(아릴아미노)아릴 화합물 |
| JP2012507497A (ja) * | 2008-11-03 | 2012-03-29 | ジェネリクス・（ユーケー）・リミテッド | ボセンタンおよび関連物質のｈｐｌｃ分析方法、ならびに参照スタンダードまたはマーカーとしてのこれら物質の使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20050085637A1 (en) | 2005-04-21 |
| WO2003066601A1 (en) | 2003-08-14 |
| EP1472233A1 (en) | 2004-11-03 |
| AU2003209077A1 (en) | 2003-09-02 |
| CA2476281A1 (en) | 2003-08-14 |
| US7459455B2 (en) | 2008-12-02 |
| MXPA04007637A (es) | 2004-11-10 |
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