JP2003507342A - 結腸ポリープおよび直腸結腸癌の処置または抑制のためのｎｓａｉｄおよびｅｇｆｒキナーゼインヒビターを含有する組成物 - Google Patents
結腸ポリープおよび直腸結腸癌の処置または抑制のためのｎｓａｉｄおよびｅｇｆｒキナーゼインヒビターを含有する組成物Info
- Publication number
- JP2003507342A JP2003507342A JP2001516570A JP2001516570A JP2003507342A JP 2003507342 A JP2003507342 A JP 2003507342A JP 2001516570 A JP2001516570 A JP 2001516570A JP 2001516570 A JP2001516570 A JP 2001516570A JP 2003507342 A JP2003507342 A JP 2003507342A
- Authority
- JP
- Japan
- Prior art keywords
- carbon atoms
- alkyl
- carbon
- atom
- phenyl
- 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
Links
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 title claims abstract description 73
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 title claims abstract description 73
- 238000011282 treatment Methods 0.000 title claims abstract description 16
- 206010009944 Colon cancer Diseases 0.000 title claims abstract description 13
- 208000001333 Colorectal Neoplasms Diseases 0.000 title claims abstract description 12
- 208000014081 polyp of colon Diseases 0.000 title claims abstract description 12
- 229940043355 kinase inhibitor Drugs 0.000 title claims description 21
- 239000003757 phosphotransferase inhibitor Substances 0.000 title claims description 21
- 230000001629 suppression Effects 0.000 title claims description 6
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 title claims 8
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 title claims 7
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 title claims 3
- 239000000203 mixture Substances 0.000 title description 7
- 229940121647 egfr inhibitor Drugs 0.000 claims abstract description 77
- 241000124008 Mammalia Species 0.000 claims abstract description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 1334
- -1 nitro, carboxy Chemical group 0.000 claims description 325
- 125000000217 alkyl group Chemical group 0.000 claims description 234
- 229910052799 carbon Inorganic materials 0.000 claims description 194
- 229910052757 nitrogen Inorganic materials 0.000 claims description 173
- 150000001721 carbon Chemical group 0.000 claims description 124
- 125000003342 alkenyl group Chemical group 0.000 claims description 100
- 229910052739 hydrogen Inorganic materials 0.000 claims description 100
- 239000001257 hydrogen Substances 0.000 claims description 100
- 125000000304 alkynyl group Chemical group 0.000 claims description 94
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 88
- 150000002431 hydrogen Chemical class 0.000 claims description 81
- 125000003545 alkoxy group Chemical group 0.000 claims description 80
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 78
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 72
- 229910052736 halogen Inorganic materials 0.000 claims description 66
- 150000002367 halogens Chemical class 0.000 claims description 66
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 65
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 63
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 62
- 125000003282 alkyl amino group Chemical group 0.000 claims description 60
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 60
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 60
- 125000004970 halomethyl group Chemical group 0.000 claims description 60
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 60
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 56
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 54
- 125000001424 substituent group Chemical group 0.000 claims description 51
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 50
- 239000000126 substance Substances 0.000 claims description 46
- 125000004414 alkyl thio group Chemical group 0.000 claims description 45
- 150000001875 compounds Chemical class 0.000 claims description 45
- 125000000623 heterocyclic group Chemical group 0.000 claims description 45
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 43
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 42
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 39
- 125000004076 pyridyl group Chemical group 0.000 claims description 39
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 39
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 36
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 35
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 34
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 34
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 32
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 30
- 229960000894 sulindac Drugs 0.000 claims description 30
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 claims description 30
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 28
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 28
- 125000004423 acyloxy group Chemical group 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 27
- 150000001540 azides Chemical class 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 26
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 25
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 25
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 25
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 24
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 24
- 229920006395 saturated elastomer Polymers 0.000 claims description 24
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 22
- 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 22
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 18
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 17
- 229940124530 sulfonamide Drugs 0.000 claims description 17
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 16
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 16
- 125000000033 alkoxyamino group Chemical group 0.000 claims description 15
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 15
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 14
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 13
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 12
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 claims description 12
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 12
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 12
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 12
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 12
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 12
- 229910052794 bromium Inorganic materials 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 239000011737 fluorine Substances 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000004043 oxo group Chemical group O=* 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 150000003536 tetrazoles Chemical class 0.000 claims description 12
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 11
- 229930192474 thiophene Natural products 0.000 claims description 11
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 10
- YHIIJNLSGULWAA-UHFFFAOYSA-N 1,4-thiazinane 1-oxide Chemical compound O=S1CCNCC1 YHIIJNLSGULWAA-UHFFFAOYSA-N 0.000 claims description 10
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 9
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- MITFXPHMIHQXPI-UHFFFAOYSA-N Oraflex Chemical compound N=1C2=CC(C(C(O)=O)C)=CC=C2OC=1C1=CC=C(Cl)C=C1 MITFXPHMIHQXPI-UHFFFAOYSA-N 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 150000003254 radicals Chemical class 0.000 claims description 6
- WVUNYSQLFKLYNI-UHFFFAOYSA-N N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxy-6-quinolinyl]-4-(dimethylamino)-2-butenamide Chemical compound C=12C=C(NC(=O)C=CCN(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC1=CC=C(F)C(Cl)=C1 WVUNYSQLFKLYNI-UHFFFAOYSA-N 0.000 claims description 5
- BTYYWOYVBXILOJ-UHFFFAOYSA-N N-{4-[(3-bromophenyl)amino]quinazolin-6-yl}but-2-ynamide Chemical group C12=CC(NC(=O)C#CC)=CC=C2N=CN=C1NC1=CC=CC(Br)=C1 BTYYWOYVBXILOJ-UHFFFAOYSA-N 0.000 claims description 5
- 229960005293 etodolac Drugs 0.000 claims description 5
- XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 229960002390 flurbiprofen Drugs 0.000 claims description 4
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 claims description 4
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims description 4
- 229960000991 ketoprofen Drugs 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- RJMIEHBSYVWVIN-LLVKDONJSA-N (2r)-2-[4-(3-oxo-1h-isoindol-2-yl)phenyl]propanoic acid Chemical compound C1=CC([C@H](C(O)=O)C)=CC=C1N1C(=O)C2=CC=CC=C2C1 RJMIEHBSYVWVIN-LLVKDONJSA-N 0.000 claims description 3
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 claims description 3
- MDKGKXOCJGEUJW-VIFPVBQESA-N (2s)-2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 MDKGKXOCJGEUJW-VIFPVBQESA-N 0.000 claims description 3
- AIQFOGOHLOICRK-UHFFFAOYSA-N 6-amino-4-(3-chloro-4-fluoroanilino)-7-ethoxyquinoline-3-carbonitrile Chemical compound C=12C=C(N)C(OCC)=CC2=NC=C(C#N)C=1NC1=CC=C(F)C(Cl)=C1 AIQFOGOHLOICRK-UHFFFAOYSA-N 0.000 claims description 3
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 3
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- LCIYFINKFGDAHD-UHFFFAOYSA-N azepane;3-nitrobenzoic acid Chemical compound C1CCCNCC1.OC(=O)C1=CC=CC([N+]([O-])=O)=C1 LCIYFINKFGDAHD-UHFFFAOYSA-N 0.000 claims description 3
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- IVUMCTKHWDRRMH-UHFFFAOYSA-N carprofen Chemical compound C1=CC(Cl)=C[C]2C3=CC=C(C(C(O)=O)C)C=C3N=C21 IVUMCTKHWDRRMH-UHFFFAOYSA-N 0.000 claims description 3
- 229960001419 fenoprofen Drugs 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
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- 229960001680 ibuprofen Drugs 0.000 claims description 3
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- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 claims description 3
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- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 3
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
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- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 claims description 2
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- 239000003937 drug carrier Substances 0.000 claims description 2
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 claims description 2
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- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims 2
- 101150039808 Egfr gene Proteins 0.000 claims 1
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- 230000000144 pharmacologic effect Effects 0.000 description 10
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 230000035772 mutation Effects 0.000 description 9
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 8
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- 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
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- A—HUMAN NECESSITIES
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Landscapes
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- Chemical & Material Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| PCT/US2000/021021 WO2001012227A1 (en) | 1999-08-12 | 2000-08-02 | Nsaid and efgr kinase inhibitor containing composition for the treatment or inhibition of colonic polyps and colorectal cancer |
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| MXPA02008836A (es) * | 2000-03-13 | 2003-02-10 | American Cyanamid Co | Uso de cianoquinolinas para tratar o inhibir los polipos colonicos. |
| US6384051B1 (en) | 2000-03-13 | 2002-05-07 | American Cyanamid Company | Method of treating or inhibiting colonic polyps |
| WO2003000705A1 (en) | 2001-06-21 | 2003-01-03 | Ariad Pharmaceuticals, Inc. | Novel quinolines and uses thereof |
| ATE341545T1 (de) | 2001-07-16 | 2006-10-15 | Astrazeneca Ab | Quinolin-derivate und ihre verwendung als inhibitoren der tyrosine kinase |
| DK1441714T3 (da) * | 2001-10-25 | 2008-03-31 | Novartis Ag | Kombinationer omfattende en selektiv cyclooxygenase-2-inhibitor |
| US6924285B2 (en) | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
| CA2494061C (en) | 2002-07-31 | 2011-06-14 | Wayne R. Danter | Protein tyrosine kinase inhibitors |
| WO2004033446A1 (en) | 2002-10-09 | 2004-04-22 | Danter Wayne R | Protein tyrosine kinase inhibitors |
| JP4606879B2 (ja) * | 2002-11-15 | 2011-01-05 | ジェノミック ヘルス， インコーポレイテッド | Ｅｇｆｒ陽性癌の遺伝子発現プロファイリング |
| CN1984660B (zh) | 2003-07-03 | 2010-12-15 | 美瑞德生物工程公司 | 作为天冬氨酸特异性半胱氨酸蛋白酶活化剂和细胞程序死亡诱导剂的4-芳基氨基-喹唑啉 |
| US8309562B2 (en) | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | Compounds and therapeutical use thereof |
| WO2006074147A2 (en) | 2005-01-03 | 2006-07-13 | Myriad Genetics, Inc. | Nitrogen containing bicyclic compounds and therapeutical use thereof |
| GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
| TW200529846A (en) | 2004-02-20 | 2005-09-16 | Wyeth Corp | 3-quinolinecarbonitrile protein kinase inhibitors |
| AR048518A1 (es) | 2004-04-02 | 2006-05-03 | Osi Pharm Inc | Inhibidores heterobiciclicos de proteina quinasas sustituidos con anillos 6,6 -biciclicos |
| US7456176B2 (en) | 2004-04-08 | 2008-11-25 | Targegen, Inc. | Benzotriazine inhibitors of kinases |
| SI1746999T1 (sl) | 2004-05-06 | 2012-01-31 | Warner Lambert Co | 4-fenilamino-kinazolin-6-il-amidi |
| MXPA06014002A (es) | 2004-06-03 | 2007-02-08 | Hoffmann La Roche | Tratamiento con cisplatina y un inhibidor de cinasa del receptor del factor de crecimiento epidermico (egfr). |
| US8258145B2 (en) | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
| NZ592990A (en) | 2005-11-01 | 2013-01-25 | Targegen Inc | Bi-aryl meta-pyrimidine inhibitors of kinases |
| US8575164B2 (en) | 2005-12-19 | 2013-11-05 | OSI Pharmaceuticals, LLC | Combination cancer therapy |
| EP1921070A1 (de) | 2006-11-10 | 2008-05-14 | Boehringer Ingelheim Pharma GmbH & Co. KG | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstelllung |
| EA200901041A1 (ru) | 2007-02-06 | 2010-02-26 | Бёрингер Ингельхайм Интернациональ Гмбх | Бициклические гетероциклы, содержащие эти соединения лекарственные средства, их применение и способ их получения |
| CA2710039C (en) | 2007-12-26 | 2018-07-03 | Critical Outcome Technologies, Inc. | Semicarbazones, thiosemicarbazones and related compounds and methods for treatment of cancer |
| PL2245026T3 (pl) | 2008-02-07 | 2013-01-31 | Boehringer Ingelheim Int | Spirocykliczne heterocykle, leki zawierające te związki, ich zastosowanie i sposób ich produkcji |
| ES2444128T3 (es) | 2008-05-13 | 2014-02-24 | Astrazeneca Ab | Nueva SAL-554 |
| EP2283020B8 (en) | 2008-05-19 | 2012-12-12 | OSI Pharmaceuticals, LLC | Substituted imidazopyr-and imidazotri-azines |
| WO2010006438A1 (en) | 2008-07-17 | 2010-01-21 | Critical Outcome Technologies Inc. | Thiosemicarbazone inhibitor compounds and cancer treatment methods |
| JP5539351B2 (ja) | 2008-08-08 | 2014-07-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | シクロヘキシルオキシ置換ヘテロ環、これらの化合物を含有する医薬、およびそれらを生成するための方法 |
| PL387312A1 (pl) | 2009-02-19 | 2010-08-30 | Farma-Projekt Spółka Z Ograniczoną Odpowiedzialnością | Zastosowanie sulindaku i/lub jego metabolitu we wspomagającym leczeniu raka jelita grubego u ludzi |
| JP2012520893A (ja) | 2009-03-18 | 2012-09-10 | オーエスアイ・ファーマシューティカルズ，エルエルシー | Ｅｇｆｒ阻害薬及びｉｇｆ−１ｒ阻害剤の投与を含む組み合わせ癌治療 |
| MX2011011025A (es) | 2009-04-20 | 2011-11-02 | Osi Pharmaceuticals Llc | Preparacion de c-piracin-metilaminas. |
| US8987272B2 (en) | 2010-04-01 | 2015-03-24 | Critical Outcome Technologies Inc. | Compounds and method for treatment of HIV |
| WO2012060847A1 (en) | 2010-11-07 | 2012-05-10 | Targegen, Inc. | Compositions and methods for treating myelofibrosis |
| WO2012129145A1 (en) | 2011-03-18 | 2012-09-27 | OSI Pharmaceuticals, LLC | Nscle combination therapy |
| JP6093759B2 (ja) * | 2011-06-01 | 2017-03-08 | ジャナス バイオセラピューティクス，インク． | 新規の免疫系調節剤 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999024037A1 (en) * | 1997-11-06 | 1999-05-20 | American Cyanamid Company | Use of quinazoline derivatives as tyrosine kinase inhibitors for treating colonic polyps |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUP0004150A3 (en) * | 1997-11-04 | 2001-08-28 | Pfizer Prod Inc | Indazole derivatives as tyrosine kinase receptor antagonists and pharmaceutical compositions containing them |
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- 2000-08-02 HK HK02104004.4A patent/HK1042244A1/zh unknown
- 2000-08-02 WO PCT/US2000/021021 patent/WO2001012227A1/en not_active Ceased
- 2000-08-02 EP EP00950930A patent/EP1202746B1/en not_active Expired - Lifetime
- 2000-08-02 AU AU63959/00A patent/AU783116B2/en not_active Ceased
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- 2000-08-02 KR KR1020027001817A patent/KR20020018201A/ko not_active Ceased
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- 2000-08-02 JP JP2001516570A patent/JP2003507342A/ja active Pending
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- 2000-08-02 IL IL14791300A patent/IL147913A0/xx unknown
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999024037A1 (en) * | 1997-11-06 | 1999-05-20 | American Cyanamid Company | Use of quinazoline derivatives as tyrosine kinase inhibitors for treating colonic polyps |
Also Published As
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| DE60031127D1 (de) | 2006-11-16 |
| AU6395900A (en) | 2001-03-13 |
| EA006876B1 (ru) | 2006-04-28 |
| HUP0203162A2 (hu) | 2003-01-28 |
| NZ517120A (en) | 2004-10-29 |
| DE60031127T2 (de) | 2007-02-01 |
| CZ2002474A3 (cs) | 2003-02-12 |
| EA200200246A1 (ru) | 2002-08-29 |
| PL353267A1 (en) | 2003-11-03 |
| WO2001012227A1 (en) | 2001-02-22 |
| CA2380904C (en) | 2009-02-10 |
| HUP0203162A3 (en) | 2006-07-28 |
| ATE341341T1 (de) | 2006-10-15 |
| AU783116B2 (en) | 2005-09-29 |
| CA2380904A1 (en) | 2001-02-22 |
| EP1202746A1 (en) | 2002-05-08 |
| IL147913A0 (en) | 2002-08-14 |
| CN1229142C (zh) | 2005-11-30 |
| EP1202746B1 (en) | 2006-10-04 |
| HK1042244A1 (zh) | 2002-08-09 |
| CN1370080A (zh) | 2002-09-18 |
| BR0013219A (pt) | 2002-04-23 |
| PT1202746E (pt) | 2007-01-31 |
| DK1202746T3 (da) | 2007-01-02 |
| KR20020018201A (ko) | 2002-03-07 |
| AR029763A1 (es) | 2003-07-16 |
| NO20020663L (no) | 2002-04-09 |
| NO20020663D0 (no) | 2002-02-11 |
| ES2272305T3 (es) | 2007-05-01 |
| ZA200201156B (en) | 2003-05-12 |
| MXPA02001448A (es) | 2002-07-02 |
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