NZ532418A - Combinations comprising a selective cyclooxygenase-2 inhibitor and a microtubule interfering agent - Google Patents
Combinations comprising a selective cyclooxygenase-2 inhibitor and a microtubule interfering agentInfo
- Publication number
- NZ532418A NZ532418A NZ532418A NZ53241802A NZ532418A NZ 532418 A NZ532418 A NZ 532418A NZ 532418 A NZ532418 A NZ 532418A NZ 53241802 A NZ53241802 A NZ 53241802A NZ 532418 A NZ532418 A NZ 532418A
- Authority
- NZ
- New Zealand
- Prior art keywords
- fluoro
- pharmaceutically acceptable
- methyl
- inhibitor
- chloro
- Prior art date
Links
- 239000003795 chemical substances by application Substances 0.000 title claims abstract description 24
- 102000029749 Microtubule Human genes 0.000 title claims abstract description 7
- 108091022875 Microtubule Proteins 0.000 title claims abstract description 7
- 210000004688 microtubule Anatomy 0.000 title claims abstract description 7
- 230000002452 interceptive effect Effects 0.000 title claims abstract description 6
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 title claims description 54
- 229940093444 Cyclooxygenase 2 inhibitor Drugs 0.000 title claims description 14
- 150000003839 salts Chemical class 0.000 claims abstract description 64
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 35
- 210000001072 colon Anatomy 0.000 claims abstract description 22
- 208000029742 colonic neoplasm Diseases 0.000 claims abstract description 21
- 230000003902 lesion Effects 0.000 claims abstract description 20
- AADVCYNFEREWOS-UHFFFAOYSA-N (+)-DDM Natural products C=CC=CC(C)C(OC(N)=O)C(C)C(O)C(C)CC(C)=CC(C)C(O)C(C)C=CC(O)CC1OC(=O)C(C)C(O)C1C AADVCYNFEREWOS-UHFFFAOYSA-N 0.000 claims abstract description 19
- 206010009944 Colon cancer Diseases 0.000 claims abstract description 19
- 230000003211 malignant effect Effects 0.000 claims abstract description 19
- HESCAJZNRMSMJG-HGYUPSKWSA-N epothilone A Natural products O=C1[C@H](C)[C@H](O)[C@H](C)CCC[C@H]2O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C HESCAJZNRMSMJG-HGYUPSKWSA-N 0.000 claims abstract description 17
- QXRSDHAAWVKZLJ-OXZHEXMSSA-N Epothilone B Natural products O=C1[C@H](C)[C@H](O)[C@@H](C)CCC[C@@]2(C)O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C QXRSDHAAWVKZLJ-OXZHEXMSSA-N 0.000 claims abstract description 16
- QXRSDHAAWVKZLJ-PVYNADRNSA-N epothilone B Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 QXRSDHAAWVKZLJ-PVYNADRNSA-N 0.000 claims abstract description 16
- AADVCYNFEREWOS-OBRABYBLSA-N Discodermolide Chemical compound C=C\C=C/[C@H](C)[C@H](OC(N)=O)[C@@H](C)[C@H](O)[C@@H](C)C\C(C)=C/[C@H](C)[C@@H](O)[C@@H](C)\C=C/[C@@H](O)C[C@@H]1OC(=O)[C@H](C)[C@@H](O)[C@H]1C AADVCYNFEREWOS-OBRABYBLSA-N 0.000 claims abstract description 15
- 229930012538 Paclitaxel Natural products 0.000 claims abstract description 9
- 229960001592 paclitaxel Drugs 0.000 claims abstract description 9
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims abstract description 9
- 229960005499 (+)-discodermolide Drugs 0.000 claims abstract description 8
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims abstract description 7
- 229960003668 docetaxel Drugs 0.000 claims abstract description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 71
- 238000011282 treatment Methods 0.000 claims description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims description 58
- 239000001257 hydrogen Substances 0.000 claims description 58
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 41
- 229940111134 coxibs Drugs 0.000 claims description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- -1 chloro, methyl Chemical group 0.000 claims description 32
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 28
- 150000002148 esters Chemical class 0.000 claims description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 24
- 239000000651 prodrug Substances 0.000 claims description 22
- 229940002612 prodrug Drugs 0.000 claims description 22
- 125000005907 alkyl ester group Chemical group 0.000 claims description 21
- 230000002265 prevention Effects 0.000 claims description 20
- 201000011510 cancer Diseases 0.000 claims description 18
- 239000002552 dosage form Substances 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 16
- 150000003883 epothilone derivatives Chemical class 0.000 claims description 16
- 239000004480 active ingredient Substances 0.000 claims description 14
- 239000012453 solvate Substances 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 229930013356 epothilone Natural products 0.000 claims description 12
- 230000002062 proliferating effect Effects 0.000 claims description 10
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 9
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 241001465754 Metazoa Species 0.000 claims description 8
- 230000008859 change Effects 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 5
- 229960003424 phenylacetic acid Drugs 0.000 claims description 5
- 239000003279 phenylacetic acid Substances 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 201000001514 prostate carcinoma Diseases 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- MOVASDGQPSQCSB-UHFFFAOYSA-N 2-[2-(2-fluoroanilino)-5-methylphenyl]acetic acid Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=CC=CC=C1F MOVASDGQPSQCSB-UHFFFAOYSA-N 0.000 claims 1
- 229920000136 polysorbate Polymers 0.000 claims 1
- 239000000843 powder Substances 0.000 claims 1
- 230000036210 malignancy Effects 0.000 abstract description 18
- KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 abstract description 11
- 238000002648 combination therapy Methods 0.000 abstract description 8
- 239000003112 inhibitor Substances 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 description 38
- 239000002525 vasculotropin inhibitor Substances 0.000 description 26
- 229940121647 egfr inhibitor Drugs 0.000 description 21
- 238000000034 method Methods 0.000 description 20
- 208000037062 Polyps Diseases 0.000 description 18
- 208000032177 Intestinal Polyps Diseases 0.000 description 12
- 150000002431 hydrogen Chemical group 0.000 description 12
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 11
- 108091008605 VEGF receptors Proteins 0.000 description 11
- YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 8
- XRYJULCDUUATMC-CYBMUJFWSA-N 4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=C(O)C=C1 XRYJULCDUUATMC-CYBMUJFWSA-N 0.000 description 8
- 241000124008 Mammalia Species 0.000 description 8
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 7
- 229940123237 Taxane Drugs 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 7
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 6
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 6
- 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 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 6
- 241001050985 Disco Species 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 229940122803 Vinca alkaloid Drugs 0.000 description 5
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 5
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 4
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 4
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 4
- 229960001338 colchicine Drugs 0.000 description 4
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 4
- HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 4
- 229960001237 podophyllotoxin Drugs 0.000 description 4
- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 229960003048 vinblastine Drugs 0.000 description 4
- WHOWNXIYXLWMGJ-UHFFFAOYSA-N 1-(pyridin-4-ylmethyl)phthalazine Chemical class N=1N=CC2=CC=CC=C2C=1CC1=CC=NC=C1 WHOWNXIYXLWMGJ-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 3
- 108010037464 Cyclooxygenase 1 Proteins 0.000 description 3
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 206010025323 Lymphomas Diseases 0.000 description 3
- 206010029113 Neovascularisation Diseases 0.000 description 3
- 206010033128 Ovarian cancer Diseases 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- 238000000692 Student's t-test Methods 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 210000003679 cervix uteri Anatomy 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 201000010536 head and neck cancer Diseases 0.000 description 3
- 208000014829 head and neck neoplasm Diseases 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 208000015768 polyposis Diseases 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 238000010972 statistical evaluation Methods 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000011269 treatment regimen Methods 0.000 description 3
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 3
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 3
- 210000003932 urinary bladder Anatomy 0.000 description 3
- 210000004291 uterus Anatomy 0.000 description 3
- 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 3
- AQTQHPDCURKLKT-JKDPCDLQSA-N vincristine sulfate Chemical compound OS(O)(=O)=O.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=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 AQTQHPDCURKLKT-JKDPCDLQSA-N 0.000 description 3
- 229960002110 vincristine sulfate Drugs 0.000 description 3
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical class N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 description 2
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 2
- 229960002986 dinoprostone Drugs 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 230000008472 epithelial growth Effects 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 229960005420 etoposide Drugs 0.000 description 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 2
- 231100000304 hepatotoxicity Toxicity 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 150000003951 lactams Chemical class 0.000 description 2
- 230000007056 liver toxicity Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229960001278 teniposide Drugs 0.000 description 2
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine 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-CFWMRBGOSA-N 0.000 description 2
- KDQAABAKXDWYSZ-PNYVAJAMSA-N vinblastine sulfate Chemical compound OS(O)(=O)=O.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 KDQAABAKXDWYSZ-PNYVAJAMSA-N 0.000 description 2
- 229960004982 vinblastine sulfate Drugs 0.000 description 2
- 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 2
- 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 2
- 229960002066 vinorelbine Drugs 0.000 description 2
- DJHIWVKWYUSYKV-UHFFFAOYSA-N 2-[2-(2-chloro-6-fluoroanilino)-4-methylphenyl]acetic acid Chemical compound CC1=CC=C(CC(O)=O)C(NC=2C(=CC=CC=2F)Cl)=C1 DJHIWVKWYUSYKV-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- BEFZAMRWPCMWFJ-JRBBLYSQSA-N Epothilone C Natural products O=C1[C@H](C)[C@@H](O)[C@@H](C)CCC/C=C\C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C BEFZAMRWPCMWFJ-JRBBLYSQSA-N 0.000 description 1
- XOZIUKBZLSUILX-SDMHVBBESA-N Epothilone D Natural products O=C1[C@H](C)[C@@H](O)[C@@H](C)CCC/C(/C)=C/C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C XOZIUKBZLSUILX-SDMHVBBESA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- BEFZAMRWPCMWFJ-UHFFFAOYSA-N desoxyepothilone A Natural products O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC=CCC1C(C)=CC1=CSC(C)=N1 BEFZAMRWPCMWFJ-UHFFFAOYSA-N 0.000 description 1
- XOZIUKBZLSUILX-UHFFFAOYSA-N desoxyepothilone B Natural products O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC(C)=CCC1C(C)=CC1=CSC(C)=N1 XOZIUKBZLSUILX-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical class CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000000773 effect on pain Effects 0.000 description 1
- BEFZAMRWPCMWFJ-QJKGZULSSA-N epothilone C Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C=C/C[C@H]1C(\C)=C\C1=CSC(C)=N1 BEFZAMRWPCMWFJ-QJKGZULSSA-N 0.000 description 1
- XOZIUKBZLSUILX-GIQCAXHBSA-N epothilone D Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C(C)=C/C[C@H]1C(\C)=C\C1=CSC(C)=N1 XOZIUKBZLSUILX-GIQCAXHBSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 229960000752 etoposide phosphate Drugs 0.000 description 1
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 150000002411 histidines Chemical class 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 230000008728 vascular permeability Effects 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
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
-
- 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)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (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)
- Medicines Containing Plant Substances (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34473501P | 2001-10-25 | 2001-10-25 | |
| US34473401P | 2001-10-25 | 2001-10-25 | |
| US33603301P | 2001-11-15 | 2001-11-15 | |
| PCT/EP2002/011924 WO2003035047A2 (en) | 2001-10-25 | 2002-10-24 | Combinations comprising a selective cyclooxygenase-2 inhibitor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ532418A true NZ532418A (en) | 2007-02-23 |
Family
ID=27407094
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ532418A NZ532418A (en) | 2001-10-25 | 2002-10-24 | Combinations comprising a selective cyclooxygenase-2 inhibitor and a microtubule interfering agent |
| NZ552335A NZ552335A (en) | 2001-10-25 | 2002-10-24 | Combinations comprising a selective COX-2 inhibitor and a microtubule interfering agent |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ552335A NZ552335A (en) | 2001-10-25 | 2002-10-24 | Combinations comprising a selective COX-2 inhibitor and a microtubule interfering agent |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US20050043409A1 (enExample) |
| EP (1) | EP1441714B1 (enExample) |
| JP (1) | JP2005506366A (enExample) |
| KR (1) | KR100954625B1 (enExample) |
| CN (1) | CN100506224C (enExample) |
| AT (1) | ATE381930T1 (enExample) |
| AU (2) | AU2006252156A1 (enExample) |
| BR (1) | BR0213486A (enExample) |
| CA (1) | CA2464309C (enExample) |
| CY (1) | CY1108045T1 (enExample) |
| DE (1) | DE60224299T2 (enExample) |
| DK (1) | DK1441714T3 (enExample) |
| ES (1) | ES2295428T3 (enExample) |
| HU (1) | HUP0600235A3 (enExample) |
| IL (1) | IL161462A0 (enExample) |
| MX (1) | MXPA04003878A (enExample) |
| NZ (2) | NZ532418A (enExample) |
| PL (1) | PL369305A1 (enExample) |
| PT (1) | PT1441714E (enExample) |
| RU (1) | RU2333754C2 (enExample) |
| SI (1) | SI1441714T1 (enExample) |
| WO (1) | WO2003035047A2 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0223341D0 (en) * | 2002-10-08 | 2002-11-13 | Groningen Acad Ziekenhuis | Organic compounds |
| WO2005021554A1 (en) | 2003-08-29 | 2005-03-10 | Pfizer Inc. | Thienopyridine-phenylacet amides and their derivatives useful as new anti-angiogenic agents |
| MXPA06003164A (es) * | 2003-09-23 | 2006-06-05 | Novartis Ag | Combinaciones de un inhibidor del receptor de vegf con otros agentes terapeuticos. |
| JP2007505938A (ja) * | 2003-09-23 | 2007-03-15 | ノバルティス アクチエンゲゼルシャフト | Vegf受容体阻害剤と化学療法剤の組み合わせ |
| CA2551508C (en) | 2003-12-23 | 2011-08-09 | Pfizer Inc. | Novel quinoline derivatives |
| JO2596B1 (en) * | 2004-11-30 | 2011-02-27 | نوفارتيس ايه جي | Compositions include epothelones and tyrosine protein kinase inhibitors and their pharmaceutical uses |
| EP1982718A4 (en) * | 2006-02-09 | 2010-05-12 | Daiichi Sankyo Co Ltd | PHARMACEUTICAL COMPOSITION FOR THE PREVENTION OF CANCER |
| EP2065054A1 (en) | 2007-11-29 | 2009-06-03 | Bayer Schering Pharma Aktiengesellschaft | Combinations comprising a prostaglandin and uses thereof |
| AR077975A1 (es) | 2009-08-28 | 2011-10-05 | Irm Llc | Derivados de pirazol pirimidina y composiciones como inhibidores de cinasa de proteina |
| CN103917236A (zh) | 2011-11-11 | 2014-07-09 | 诺华股份有限公司 | 治疗增生性疾病的方法 |
| MD565Z (ro) * | 2012-05-23 | 2013-07-31 | Институт Генетики, Физиологии И Защиты Растений Академии Наук Молдовы | Procedeu de tratare a seminţelor de sfeclă de zahăr |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100558356C (zh) * | 1996-10-15 | 2009-11-11 | G.D.瑟尔公司 | 应用环加氧酶-2抑制剂治疗和预防肿瘤形成的方法 |
| US6380394B1 (en) * | 1996-12-13 | 2002-04-30 | The Scripps Research Institute | Epothilone analogs |
| CO4950519A1 (es) * | 1997-02-13 | 2000-09-01 | Novartis Ag | Ftalazinas, preparaciones farmaceuticas que las comprenden y proceso para su preparacion |
| US6034256A (en) * | 1997-04-21 | 2000-03-07 | G.D. Searle & Co. | Substituted benzopyran derivatives for the treatment of inflammation |
| CO4960662A1 (es) * | 1997-08-28 | 2000-09-25 | Novartis Ag | Ciertos acidos 5-alquil-2-arilaminofenilaceticos y sus derivados |
| US6025353A (en) * | 1997-11-19 | 2000-02-15 | G.D. Searle & Co. | Method of using cyclooxygenase-2 inhibitors as anti-angiogenic agents |
| US6887893B1 (en) * | 1997-12-24 | 2005-05-03 | Sankyo Company, Limited | Methods and compositions for treatment and prevention of tumors, tumor-related disorders and cachexia |
| CA2356462A1 (en) * | 1998-12-23 | 2000-07-06 | G.D. Searle & Co. | Method of using an integrin antagonist and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia |
| IL147913A0 (en) * | 1999-08-12 | 2002-08-14 | American Cyanamid Co | Nsaid and efgr kinase inhibitor containing composition for the treatment or inhibition of colonic polyps and colorectal cancer |
| CA2392931A1 (en) * | 1999-12-03 | 2001-06-07 | Pfizer Products Inc. | Heterocyclo-alkylsulfonyl pyrazole derivatives as anti-inflammatory/analgesic agents |
| ITMI992711A1 (it) * | 1999-12-27 | 2001-06-27 | Novartis Ag | Composti organici |
| WO2001060365A1 (en) * | 2000-02-17 | 2001-08-23 | Merck & Co., Inc. | Treatment or prevention of prostate cancer with a cox-2 selective inhibiting drug |
| EP1259236A4 (en) * | 2000-02-25 | 2004-11-03 | Merck & Co Inc | Tyrosine kinase inhibitors |
| WO2001064669A1 (en) * | 2000-03-03 | 2001-09-07 | Pfizer Products Inc. | Pyrazole ether derivatives as anti-inflammatory/analgesic agents |
| TWI310684B (en) * | 2000-03-27 | 2009-06-11 | Bristol Myers Squibb Co | Synergistic pharmaceutical kits for treating cancer |
-
2002
- 2002-10-24 DE DE60224299T patent/DE60224299T2/de not_active Expired - Lifetime
- 2002-10-24 JP JP2003537614A patent/JP2005506366A/ja active Pending
- 2002-10-24 AT AT02787507T patent/ATE381930T1/de active
- 2002-10-24 EP EP02787507A patent/EP1441714B1/en not_active Expired - Lifetime
- 2002-10-24 PT PT02787507T patent/PT1441714E/pt unknown
- 2002-10-24 RU RU2004116069/15A patent/RU2333754C2/ru not_active IP Right Cessation
- 2002-10-24 KR KR1020047006101A patent/KR100954625B1/ko not_active Expired - Fee Related
- 2002-10-24 CA CA2464309A patent/CA2464309C/en not_active Expired - Fee Related
- 2002-10-24 NZ NZ532418A patent/NZ532418A/en not_active IP Right Cessation
- 2002-10-24 SI SI200230672T patent/SI1441714T1/sl unknown
- 2002-10-24 ES ES02787507T patent/ES2295428T3/es not_active Expired - Lifetime
- 2002-10-24 CN CNB028211375A patent/CN100506224C/zh not_active Expired - Fee Related
- 2002-10-24 HU HU0600235A patent/HUP0600235A3/hu unknown
- 2002-10-24 IL IL16146202A patent/IL161462A0/xx unknown
- 2002-10-24 NZ NZ552335A patent/NZ552335A/en not_active IP Right Cessation
- 2002-10-24 BR BR0213486-1A patent/BR0213486A/pt active Search and Examination
- 2002-10-24 PL PL02369305A patent/PL369305A1/xx not_active Application Discontinuation
- 2002-10-24 MX MXPA04003878A patent/MXPA04003878A/es active IP Right Grant
- 2002-10-24 WO PCT/EP2002/011924 patent/WO2003035047A2/en not_active Ceased
- 2002-10-24 DK DK02787507T patent/DK1441714T3/da active
- 2002-10-24 US US10/493,297 patent/US20050043409A1/en not_active Abandoned
-
2006
- 2006-12-20 AU AU2006252156A patent/AU2006252156A1/en not_active Abandoned
-
2008
- 2008-02-18 CY CY20081100197T patent/CY1108045T1/el unknown
-
2010
- 2010-02-08 AU AU2010200433A patent/AU2010200433A1/en not_active Abandoned
- 2010-11-03 US US12/938,868 patent/US20110046190A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| KR100954625B1 (ko) | 2010-04-27 |
| CA2464309C (en) | 2012-01-03 |
| AU2010200433A1 (en) | 2010-02-25 |
| PL369305A1 (en) | 2005-04-18 |
| CN100506224C (zh) | 2009-07-01 |
| US20050043409A1 (en) | 2005-02-24 |
| WO2003035047A2 (en) | 2003-05-01 |
| DK1441714T3 (da) | 2008-03-31 |
| BR0213486A (pt) | 2005-05-10 |
| NZ552335A (en) | 2008-11-28 |
| ATE381930T1 (de) | 2008-01-15 |
| EP1441714A2 (en) | 2004-08-04 |
| KR20040048992A (ko) | 2004-06-10 |
| SI1441714T1 (sl) | 2008-06-30 |
| JP2005506366A (ja) | 2005-03-03 |
| EP1441714B1 (en) | 2007-12-26 |
| WO2003035047A3 (en) | 2003-10-23 |
| HK1068261A1 (en) | 2005-04-29 |
| HUP0600235A3 (en) | 2008-04-28 |
| RU2333754C2 (ru) | 2008-09-20 |
| DE60224299D1 (de) | 2008-02-07 |
| IL161462A0 (en) | 2004-09-27 |
| RU2004116069A (ru) | 2005-06-10 |
| ES2295428T3 (es) | 2008-04-16 |
| AU2006252156A1 (en) | 2007-01-18 |
| PT1441714E (pt) | 2008-03-10 |
| HUP0600235A2 (en) | 2007-02-28 |
| MXPA04003878A (es) | 2004-07-08 |
| CN1575168A (zh) | 2005-02-02 |
| CY1108045T1 (el) | 2013-09-04 |
| US20110046190A1 (en) | 2011-02-24 |
| CA2464309A1 (en) | 2003-05-01 |
| DE60224299T2 (de) | 2008-12-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20110046190A1 (en) | Combinations comprising a selective cyclooxygenase-2 inhibitor | |
| US20060270665A1 (en) | Combination comprising an agent decreasing VEGF activity and an agent decreasing EGF activity | |
| CN104116738A (zh) | 癌症的治疗 | |
| US7723339B2 (en) | Combination comprising a signal transduction inhibitor and an epothilone derivative | |
| AU2002308218A1 (en) | Combination comprising a signal transduction inhibitor and an epothilone derivative | |
| AU2007247112B2 (en) | Combination comprising an iron chelator and an anti-neoplastic agent and use thereof | |
| AU2002351784A1 (en) | Combinations comprising a selective cyclooxygenase-2 inhibitor | |
| ZA200402939B (en) | Combinations comprising a selective cyclooxygenase-2 inhibitor. | |
| WO2025214358A1 (zh) | 用于治疗胰腺癌的药物及其用途 | |
| HK1068261B (en) | Combinations comprising a selective cyclooxygenase-2 inhibitor | |
| TWI343258B (en) | Combination comprising an active ingredient which decreases the activity of the epidermal growth factor (egf) and an epothilone derivative | |
| HK1062266B (en) | Combination comprising a signal transduction inhibitor and an epothilone derivative | |
| HK1150028A (en) | Combination comprising an iron chelator and an anti-neoplastic agent and use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RENW | Renewal (renewal fees accepted) | ||
| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) | ||
| RENW | Renewal (renewal fees accepted) | ||
| LAPS | Patent lapsed |