ES2272305T3 - Composicion de contine un nsaid y un inhibidor de efgr cinasa para el tratamiento o la inhibicion de los polipos de colon y del cancer colorrectal. - Google Patents
Composicion de contine un nsaid y un inhibidor de efgr cinasa para el tratamiento o la inhibicion de los polipos de colon y del cancer colorrectal. Download PDFInfo
- Publication number
- ES2272305T3 ES2272305T3 ES00950930T ES00950930T ES2272305T3 ES 2272305 T3 ES2272305 T3 ES 2272305T3 ES 00950930 T ES00950930 T ES 00950930T ES 00950930 T ES00950930 T ES 00950930T ES 2272305 T3 ES2272305 T3 ES 2272305T3
- Authority
- ES
- Spain
- Prior art keywords
- carbon atoms
- carbon
- atoms
- alkyl
- 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.)
- Expired - Lifetime
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- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 title claims abstract description 48
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 title claims abstract description 47
- 230000005764 inhibitory process Effects 0.000 title claims abstract description 16
- 239000003112 inhibitor Substances 0.000 title claims description 16
- 206010028980 Neoplasm Diseases 0.000 title description 12
- 201000011510 cancer Diseases 0.000 title description 8
- 239000000203 mixture Substances 0.000 title description 8
- 210000001072 colon Anatomy 0.000 title description 4
- 229940121647 egfr inhibitor Drugs 0.000 claims abstract description 48
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 206010009944 Colon cancer Diseases 0.000 claims abstract description 12
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 10
- 208000014081 polyp of colon Diseases 0.000 claims abstract description 10
- 241000124008 Mammalia Species 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 893
- -1 nitro, carboxy Chemical group 0.000 claims description 270
- 229910052799 carbon Inorganic materials 0.000 claims description 233
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 232
- 125000004429 atom Chemical group 0.000 claims description 163
- 229910052757 nitrogen Inorganic materials 0.000 claims description 138
- 125000000217 alkyl group Chemical group 0.000 claims description 119
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 90
- 150000003254 radicals Chemical class 0.000 claims description 80
- 229910052739 hydrogen Inorganic materials 0.000 claims description 70
- 239000001257 hydrogen Substances 0.000 claims description 70
- 125000000304 alkynyl group Chemical group 0.000 claims description 65
- 125000003342 alkenyl group Chemical group 0.000 claims description 64
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 64
- 125000003545 alkoxy group Chemical group 0.000 claims description 55
- 125000003282 alkyl amino group Chemical group 0.000 claims description 53
- 150000002431 hydrogen Chemical class 0.000 claims description 52
- 150000001875 compounds Chemical class 0.000 claims description 48
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 47
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 47
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 45
- 229910052736 halogen Inorganic materials 0.000 claims description 44
- 150000002367 halogens Chemical class 0.000 claims description 44
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 44
- 125000001424 substituent group Chemical group 0.000 claims description 42
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 40
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 40
- 125000004970 halomethyl group Chemical group 0.000 claims description 40
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 40
- 125000000623 heterocyclic group Chemical group 0.000 claims description 39
- 125000004414 alkyl thio group Chemical group 0.000 claims description 38
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 37
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 36
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 36
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 35
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 34
- 125000001072 heteroaryl group Chemical group 0.000 claims description 31
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 29
- 229920006395 saturated elastomer Polymers 0.000 claims description 29
- 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 29
- 229960000894 sulindac Drugs 0.000 claims description 29
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 28
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 28
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 26
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 25
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 25
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 24
- 125000004076 pyridyl group Chemical group 0.000 claims description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 24
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 23
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 23
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
- 125000004423 acyloxy group Chemical group 0.000 claims description 22
- 125000006323 alkenyl amino group Chemical group 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 20
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 20
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 20
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 19
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 18
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 17
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 16
- 125000002619 bicyclic group Chemical group 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 13
- 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
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 12
- 229910052794 bromium Inorganic materials 0.000 claims description 12
- 150000001721 carbon Chemical group 0.000 claims description 12
- 239000000460 chlorine Substances 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 11
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 10
- 125000000033 alkoxyamino group Chemical group 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 10
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 9
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 8
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 8
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 8
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 125000004043 oxo group Chemical group O=* 0.000 claims description 8
- 229930192474 thiophene Natural products 0.000 claims description 8
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 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
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 6
- 150000003536 tetrazoles Chemical class 0.000 claims description 6
- 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
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- 229960005430 benoxaprofen Drugs 0.000 claims description 3
- 229960003184 carprofen Drugs 0.000 claims description 3
- 229960005293 etodolac Drugs 0.000 claims description 3
- 229960001419 fenoprofen Drugs 0.000 claims description 3
- 229960002390 flurbiprofen Drugs 0.000 claims description 3
- 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 3
- 229960001680 ibuprofen Drugs 0.000 claims description 3
- 229960004187 indoprofen Drugs 0.000 claims description 3
- 229960004752 ketorolac Drugs 0.000 claims description 3
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 claims description 3
- 229960002009 naproxen Drugs 0.000 claims description 3
- 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
- 229960004492 suprofen Drugs 0.000 claims description 3
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 claims description 2
- YHIIJNLSGULWAA-UHFFFAOYSA-N 1,4-thiazinane 1-oxide Chemical compound O=S1CCNCC1 YHIIJNLSGULWAA-UHFFFAOYSA-N 0.000 claims description 2
- 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
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims description 2
- 229960000590 celecoxib Drugs 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 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
- 229960000371 rofecoxib Drugs 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 5
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 5
- 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 2
- 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 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 2
- 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 1
- 102000001301 EGF receptor Human genes 0.000 description 25
- 108060006698 EGF receptor Proteins 0.000 description 25
- 208000037062 Polyps Diseases 0.000 description 24
- 238000000034 method Methods 0.000 description 15
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 12
- CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical class [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 10
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 10
- 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
- 229940043355 kinase inhibitor Drugs 0.000 description 8
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 8
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- 108091000080 Phosphotransferase Proteins 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 208000029664 classic familial adenomatous polyposis Diseases 0.000 description 7
- 230000000144 pharmacologic effect Effects 0.000 description 7
- 102000020233 phosphotransferase Human genes 0.000 description 7
- 239000000758 substrate Substances 0.000 description 7
- 238000010998 test method Methods 0.000 description 7
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 7
- 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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- 239000007788 liquid Substances 0.000 description 6
- 150000003246 quinazolines Chemical class 0.000 description 6
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 6
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 5
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 229940098779 methanesulfonic acid Drugs 0.000 description 5
- 150000007522 mineralic acids Chemical class 0.000 description 5
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- WDXARTMCIRVMAE-UHFFFAOYSA-N quinoline-2-carbonitrile Chemical class C1=CC=CC2=NC(C#N)=CC=C21 WDXARTMCIRVMAE-UHFFFAOYSA-N 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 4
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 4
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 4
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- XGXNTJHZPBRBHJ-UHFFFAOYSA-N n-phenylpyrimidin-2-amine Chemical class N=1C=CC=NC=1NC1=CC=CC=C1 XGXNTJHZPBRBHJ-UHFFFAOYSA-N 0.000 description 1
- AHLKSOXEVRYIRD-UHFFFAOYSA-N n-phenylquinazolin-2-amine Chemical class N=1C=C2C=CC=CC2=NC=1NC1=CC=CC=C1 AHLKSOXEVRYIRD-UHFFFAOYSA-N 0.000 description 1
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- 150000004943 pyrrolo[2,3-d]pyrimidines Chemical class 0.000 description 1
- 150000004944 pyrrolopyrimidines Chemical class 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
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Classifications
-
- 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
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- 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)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37326199A | 1999-08-12 | 1999-08-12 | |
| US373261 | 1999-08-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2272305T3 true ES2272305T3 (es) | 2007-05-01 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| ES00950930T Expired - Lifetime ES2272305T3 (es) | 1999-08-12 | 2000-08-02 | Composicion de contine un nsaid y un inhibidor de efgr cinasa para el tratamiento o la inhibicion de los polipos de colon y del cancer colorrectal. |
Country Status (24)
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|---|---|
| EP (1) | EP1202746B1 (https=) |
| JP (1) | JP2003507342A (https=) |
| KR (1) | KR20020018201A (https=) |
| CN (1) | CN1229142C (https=) |
| AR (1) | AR029763A1 (https=) |
| AT (1) | ATE341341T1 (https=) |
| AU (1) | AU783116B2 (https=) |
| BR (1) | BR0013219A (https=) |
| CA (1) | CA2380904C (https=) |
| CZ (1) | CZ2002474A3 (https=) |
| DE (1) | DE60031127T2 (https=) |
| DK (1) | DK1202746T3 (https=) |
| EA (1) | EA006876B1 (https=) |
| ES (1) | ES2272305T3 (https=) |
| HK (1) | HK1042244A1 (https=) |
| HU (1) | HUP0203162A3 (https=) |
| IL (1) | IL147913A0 (https=) |
| MX (1) | MXPA02001448A (https=) |
| NO (1) | NO20020663L (https=) |
| NZ (1) | NZ517120A (https=) |
| PL (1) | PL353267A1 (https=) |
| PT (1) | PT1202746E (https=) |
| WO (1) | WO2001012227A1 (https=) |
| ZA (1) | ZA200201156B (https=) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040127470A1 (en) * | 1998-12-23 | 2004-07-01 | Pharmacia Corporation | Methods and compositions for the prevention or treatment of neoplasia comprising a Cox-2 inhibitor in combination with an epidermal growth factor receptor antagonist |
| US6384051B1 (en) | 2000-03-13 | 2002-05-07 | American Cyanamid Company | Method of treating or inhibiting colonic polyps |
| CN1190197C (zh) * | 2000-03-13 | 2005-02-23 | 惠氏控股公司 | 氰基喹啉用于制备治疗或抑制结肠息肉药物中的用途 |
| EP1412367A4 (en) | 2001-06-21 | 2006-05-03 | Ariad Pharma Inc | NEW CHINOLINE AND ITS USE |
| WO2003008409A1 (en) | 2001-07-16 | 2003-01-30 | Astrazeneca Ab | Quinoline derivatives and their use as tyrosine kinase inhibitors |
| US20050043409A1 (en) * | 2001-10-25 | 2005-02-24 | Chen Ying-Nan Pan | Combinations comprising a selective 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 |
| DE60313339T2 (de) | 2002-07-31 | 2008-01-03 | Critical Outcome Technologies, Inc. | Protein tyrosin kinase inhibitoren |
| US7629347B2 (en) | 2002-10-09 | 2009-12-08 | Critical Outcome Technologies, Inc. | Protein tyrosine kinase inhibitors |
| WO2004046386A1 (en) * | 2002-11-15 | 2004-06-03 | Genomic Health, Inc. | Gene expression profiling of egfr positive cancer |
| AU2004253967B2 (en) | 2003-07-03 | 2010-02-18 | Cytovia, Inc. | 4-arylamino-quinazolines as activators of caspases and inducers of apoptosis |
| WO2006074147A2 (en) | 2005-01-03 | 2006-07-13 | Myriad Genetics, Inc. | Nitrogen containing bicyclic compounds and therapeutical use thereof |
| US8309562B2 (en) | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | 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 |
| EP2168968B1 (en) | 2004-04-02 | 2017-08-23 | OSI Pharmaceuticals, LLC | 6,6-bicyclic ring substituted heterobicyclic protein kinase inhibitors |
| EP2543376A1 (en) | 2004-04-08 | 2013-01-09 | Targegen, Inc. | Benzotriazine inhibitors of kinases |
| KR20080095915A (ko) | 2004-05-06 | 2008-10-29 | 워너-램버트 캄파니 엘엘씨 | 4-페닐아미노-퀴나졸린-6-일-아미드 |
| RU2006146612A (ru) | 2004-06-03 | 2008-07-20 | Ф.Хоффманн-Ля Рош Аг (Ch) | Лечение цисплатином и ингибитором рецептора эпидермального фактора роста (egfr) |
| US8258145B2 (en) | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
| JP5191391B2 (ja) | 2005-11-01 | 2013-05-08 | ターゲジェン インコーポレーティッド | キナーゼのビ−アリールメタ−ピリミジン阻害剤 |
| 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 |
| AU2008212999A1 (en) | 2007-02-06 | 2008-08-14 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, drugs containing said compounds, use thereof, and method for production thereof |
| CA2710039C (en) | 2007-12-26 | 2018-07-03 | Critical Outcome Technologies, Inc. | Semicarbazones, thiosemicarbazones and related compounds and methods for treatment of cancer |
| US8497369B2 (en) | 2008-02-07 | 2013-07-30 | Boehringer Ingelheim International Gmbh | Spirocyclic heterocycles medicaments containing said compounds, use thereof and method for their production |
| JP5739802B2 (ja) | 2008-05-13 | 2015-06-24 | アストラゼネカ アクチボラグ | ４−（３−クロロ−２−フルオロアニリノ）−７−メトキシ−６−｛［１−（ｎ−メチルカルバモイルメチル）ピペリジン−４−イル］オキシ｝キナゾリンのフマル酸塩 |
| ES2396613T3 (es) | 2008-05-19 | 2013-02-22 | OSI Pharmaceuticals, LLC | Imidazopirazinas e imidazotriazinas sustituidas |
| EP2318406B1 (en) | 2008-07-17 | 2016-01-27 | Critical Outcome Technologies, Inc. | Thiosemicarbazone inhibitor compounds and cancer treatment methods |
| EP2313397B1 (de) | 2008-08-08 | 2016-04-20 | Boehringer Ingelheim International GmbH | Cyclohexyloxy-substituierte heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| 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 |
| EP2408479A1 (en) | 2009-03-18 | 2012-01-25 | OSI Pharmaceuticals, LLC | Combination cancer therapy comprising administration of an egfr inhibitor and an igf-1r inhibitor |
| US8513415B2 (en) | 2009-04-20 | 2013-08-20 | OSI Pharmaceuticals, LLC | Preparation of C-pyrazine-methylamines |
| EP2552915B1 (en) | 2010-04-01 | 2017-07-19 | Critical Outcome Technologies Inc. | Compounds for the treatment of hiv |
| AU2010363329A1 (en) | 2010-11-07 | 2013-05-09 | Targegen, Inc. | Compositions and methods for treating myelofibrosis |
| WO2012129145A1 (en) | 2011-03-18 | 2012-09-27 | OSI Pharmaceuticals, LLC | Nscle combination therapy |
| CA2837227C (en) * | 2011-06-01 | 2022-05-10 | Janus Biotherapeutics, Inc. | Novel immune system modulators |
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| IL135900A0 (en) * | 1997-11-04 | 2001-05-20 | Pfizer Prod Inc | Indazole bioisostere replacement of catechol in therapeuticaly active compounds |
| BR9814116A (pt) * | 1997-11-06 | 2000-10-03 | American Cyanamid Co | Uso de derivados de quinazolina como inibidores de cinase de tirosina para tratamento de pólipo colÈnico |
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2000
- 2000-08-02 HU HU0203162A patent/HUP0203162A3/hu unknown
- 2000-08-02 BR BR0013219-5A patent/BR0013219A/pt not_active IP Right Cessation
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- 2000-08-02 AU AU63959/00A patent/AU783116B2/en not_active Ceased
- 2000-08-02 EA EA200200246A patent/EA006876B1/ru not_active IP Right Cessation
- 2000-08-02 CZ CZ2002474A patent/CZ2002474A3/cs unknown
- 2000-08-02 MX MXPA02001448A patent/MXPA02001448A/es active IP Right Grant
- 2000-08-02 DK DK00950930T patent/DK1202746T3/da active
- 2000-08-02 HK HK02104004.4A patent/HK1042244A1/zh unknown
- 2000-08-02 DE DE60031127T patent/DE60031127T2/de not_active Expired - Lifetime
- 2000-08-02 IL IL14791300A patent/IL147913A0/xx unknown
- 2000-08-02 PT PT00950930T patent/PT1202746E/pt unknown
- 2000-08-02 NZ NZ517120A patent/NZ517120A/en unknown
- 2000-08-02 CN CNB008117977A patent/CN1229142C/zh not_active Expired - Fee Related
- 2000-08-02 KR KR1020027001817A patent/KR20020018201A/ko not_active Ceased
- 2000-08-02 EP EP00950930A patent/EP1202746B1/en not_active Expired - Lifetime
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Also Published As
| Publication number | Publication date |
|---|---|
| DE60031127T2 (de) | 2007-02-01 |
| EP1202746A1 (en) | 2002-05-08 |
| DE60031127D1 (de) | 2006-11-16 |
| HUP0203162A3 (en) | 2006-07-28 |
| EA200200246A1 (ru) | 2002-08-29 |
| MXPA02001448A (es) | 2002-07-02 |
| HK1042244A1 (zh) | 2002-08-09 |
| AR029763A1 (es) | 2003-07-16 |
| HUP0203162A2 (hu) | 2003-01-28 |
| AU783116B2 (en) | 2005-09-29 |
| CA2380904A1 (en) | 2001-02-22 |
| BR0013219A (pt) | 2002-04-23 |
| KR20020018201A (ko) | 2002-03-07 |
| EP1202746B1 (en) | 2006-10-04 |
| NO20020663D0 (no) | 2002-02-11 |
| ZA200201156B (en) | 2003-05-12 |
| CA2380904C (en) | 2009-02-10 |
| DK1202746T3 (da) | 2007-01-02 |
| JP2003507342A (ja) | 2003-02-25 |
| EA006876B1 (ru) | 2006-04-28 |
| PL353267A1 (en) | 2003-11-03 |
| CN1370080A (zh) | 2002-09-18 |
| IL147913A0 (en) | 2002-08-14 |
| PT1202746E (pt) | 2007-01-31 |
| ATE341341T1 (de) | 2006-10-15 |
| WO2001012227A1 (en) | 2001-02-22 |
| AU6395900A (en) | 2001-03-13 |
| NO20020663L (no) | 2002-04-09 |
| NZ517120A (en) | 2004-10-29 |
| CZ2002474A3 (cs) | 2003-02-12 |
| CN1229142C (zh) | 2005-11-30 |
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