ZA200502753B - Use of the quinazoline derivative ZD6747 combined with gemcitabine and optionally ionising radiation in the treatment of diseases associated with angiogenesis and/or increased vascular permeability - Google Patents
Use of the quinazoline derivative ZD6747 combined with gemcitabine and optionally ionising radiation in the treatment of diseases associated with angiogenesis and/or increased vascular permeability Download PDFInfo
- Publication number
- ZA200502753B ZA200502753B ZA200502753A ZA200502753A ZA200502753B ZA 200502753 B ZA200502753 B ZA 200502753B ZA 200502753 A ZA200502753 A ZA 200502753A ZA 200502753 A ZA200502753 A ZA 200502753A ZA 200502753 B ZA200502753 B ZA 200502753B
- Authority
- ZA
- South Africa
- Prior art keywords
- gemcitabine
- composition
- pharmaceutically acceptable
- substance
- acceptable salt
- Prior art date
Links
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 title claims abstract description 115
- 229960005277 gemcitabine Drugs 0.000 title claims abstract description 115
- 238000011282 treatment Methods 0.000 title claims abstract description 51
- 230000005855 radiation Effects 0.000 title claims abstract description 47
- 230000008728 vascular permeability Effects 0.000 title claims abstract description 25
- 201000010099 disease Diseases 0.000 title description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 8
- 230000033115 angiogenesis Effects 0.000 title description 4
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title 1
- UHTHHESEBZOYNR-UHFFFAOYSA-N vandetanib Chemical compound COC1=CC(C(/N=CN2)=N/C=3C(=CC(Br)=CC=3)F)=C2C=C1OCC1CCN(C)CC1 UHTHHESEBZOYNR-UHFFFAOYSA-N 0.000 claims abstract description 115
- 241001465754 Metazoa Species 0.000 claims abstract description 78
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 54
- 238000000034 method Methods 0.000 claims abstract description 49
- 238000004519 manufacturing process Methods 0.000 claims abstract description 43
- 201000011510 cancer Diseases 0.000 claims abstract description 26
- 239000003814 drug Substances 0.000 claims abstract description 20
- 230000001772 anti-angiogenic effect Effects 0.000 claims abstract description 19
- 230000001603 reducing effect Effects 0.000 claims abstract description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims description 53
- 230000000694 effects Effects 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 33
- 239000000126 substance Substances 0.000 claims description 29
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
- 239000003937 drug carrier Substances 0.000 claims description 14
- 230000001093 anti-cancer Effects 0.000 claims description 10
- 230000000259 anti-tumor effect Effects 0.000 claims description 10
- 238000002560 therapeutic procedure Methods 0.000 abstract description 7
- 239000013066 combination product Substances 0.000 abstract description 3
- 229940127555 combination product Drugs 0.000 abstract description 3
- 238000011284 combination treatment Methods 0.000 description 26
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 19
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 19
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 19
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 11
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 11
- 230000004044 response Effects 0.000 description 9
- 239000002552 dosage form Substances 0.000 description 8
- 230000012010 growth Effects 0.000 description 8
- 238000001959 radiotherapy Methods 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 239000002246 antineoplastic agent Substances 0.000 description 7
- 206010061818 Disease progression Diseases 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 229940127089 cytotoxic agent Drugs 0.000 description 6
- 230000005750 disease progression Effects 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 6
- 101800003838 Epidermal growth factor Proteins 0.000 description 5
- 102400001368 Epidermal growth factor Human genes 0.000 description 5
- 229940116977 epidermal growth factor Drugs 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 230000002195 synergetic effect Effects 0.000 description 5
- 230000003442 weekly effect Effects 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 4
- 210000000496 pancreas Anatomy 0.000 description 4
- 230000000306 recurrent effect Effects 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 4
- 208000007766 Kaposi sarcoma Diseases 0.000 description 3
- 208000007433 Lymphatic Metastasis Diseases 0.000 description 3
- 206010027457 Metastases to liver Diseases 0.000 description 3
- 206010027459 Metastases to lymph nodes Diseases 0.000 description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
- 201000002528 pancreatic cancer Diseases 0.000 description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 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 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 2
- 102000016548 Vascular Endothelial Growth Factor Receptor-1 Human genes 0.000 description 2
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 2
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
- -1 alkali metal salt Chemical class 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- OKKDEIYWILRZIA-OSZBKLCCSA-N gemcitabine hydrochloride Chemical compound [H+].[Cl-].O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 OKKDEIYWILRZIA-OSZBKLCCSA-N 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 201000011066 hemangioma Diseases 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 238000003305 oral gavage Methods 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- 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 2
- 229950000578 vatalanib Drugs 0.000 description 2
- 206010051113 Arterial restenosis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 206010013908 Dysfunctional uterine bleeding Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 101150021185 FGF gene Proteins 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 101000993347 Gallus gallus Ciliary neurotrophic factor Proteins 0.000 description 1
- 208000012766 Growth delay Diseases 0.000 description 1
- 206010019695 Hepatic neoplasm Diseases 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
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 206010025282 Lymphoedema Diseases 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 206010027514 Metrorrhagia Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- BKAYIFDRRZZKNF-VIFPVBQESA-N N-acetylcarnosine Chemical compound CC(=O)NCCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BKAYIFDRRZZKNF-VIFPVBQESA-N 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
- 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 1
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 230000003185 calcium uptake Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 229940046044 combinations of antineoplastic agent Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229960001776 edrecolomab Drugs 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- XXUJMEYKYHETBZ-UHFFFAOYSA-N ethyl 4-nitrophenyl ethylphosphonate Chemical compound CCOP(=O)(CC)OC1=CC=C([N+]([O-])=O)C=C1 XXUJMEYKYHETBZ-UHFFFAOYSA-N 0.000 description 1
- 229940020967 gemzar Drugs 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 208000002502 lymphedema Diseases 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical class N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 150000003246 quinazolines Chemical class 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 210000001210 retinal vessel Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 239000004066 vascular targeting agent Substances 0.000 description 1
- 210000003905 vulva Anatomy 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth 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)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Iron Core Of Rotating Electric Machines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0223380.7A GB0223380D0 (en) | 2002-10-09 | 2002-10-09 | Combination therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200502753B true ZA200502753B (en) | 2006-03-29 |
Family
ID=9945538
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200502753A ZA200502753B (en) | 2002-10-09 | 2006-01-17 | Use of the quinazoline derivative ZD6747 combined with gemcitabine and optionally ionising radiation in the treatment of diseases associated with angiogenesis and/or increased vascular permeability |
Country Status (23)
| Country | Link |
|---|---|
| US (2) | US20060009418A1 (zh) |
| EP (1) | EP1551409B1 (zh) |
| JP (2) | JP5416328B2 (zh) |
| KR (1) | KR101098061B1 (zh) |
| CN (1) | CN100363004C (zh) |
| AT (1) | ATE357236T1 (zh) |
| AU (1) | AU2003269253B2 (zh) |
| BR (1) | BR0315088A (zh) |
| CA (1) | CA2501651C (zh) |
| CY (1) | CY1106601T1 (zh) |
| DE (1) | DE60312715T2 (zh) |
| DK (1) | DK1551409T3 (zh) |
| ES (1) | ES2282656T3 (zh) |
| GB (1) | GB0223380D0 (zh) |
| HK (1) | HK1078771A1 (zh) |
| IL (1) | IL167633A (zh) |
| MX (1) | MXPA05003595A (zh) |
| NO (1) | NO330601B1 (zh) |
| NZ (1) | NZ538999A (zh) |
| PT (1) | PT1551409E (zh) |
| SI (1) | SI1551409T1 (zh) |
| WO (1) | WO2004032937A1 (zh) |
| ZA (1) | ZA200502753B (zh) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1244647E (pt) * | 1999-11-05 | 2006-10-31 | Astrazeneca Ab | Derivados de quinazolina como inibidores de vegf |
| GB0008269D0 (en) * | 2000-04-05 | 2000-05-24 | Astrazeneca Ab | Combination chemotherapy |
| KR100600550B1 (ko) | 2000-10-20 | 2006-07-13 | 에자이 가부시키가이샤 | 질소 함유 방향환 유도체 |
| GB0126879D0 (en) * | 2001-11-08 | 2002-01-02 | Astrazeneca Ab | Combination therapy |
| GB0218526D0 (en) * | 2002-08-09 | 2002-09-18 | Astrazeneca Ab | Combination therapy |
| GB0223380D0 (en) * | 2002-10-09 | 2002-11-13 | Astrazeneca Ab | Combination therapy |
| JP4593464B2 (ja) | 2002-11-04 | 2010-12-08 | アストラゼネカ アクチボラグ | Ｓｒｃチロシンキナーゼ阻害剤としてのキナゾリン誘導体 |
| DE602004032310D1 (de) * | 2003-02-13 | 2011-06-01 | Astrazeneca Ab | Kombinationstherapie von zd6474 mit 5-fu oder/und cpt-11 |
| JPWO2004080462A1 (ja) | 2003-03-10 | 2006-06-08 | エーザイ株式会社 | ｃ−Ｋｉｔキナーゼ阻害剤 |
| GB0310401D0 (en) * | 2003-05-07 | 2003-06-11 | Astrazeneca Ab | Therapeutic agent |
| ATE478671T1 (de) * | 2003-07-10 | 2010-09-15 | Astrazeneca Ab | Verwendung des chinazolin-derivats zd6474 in kombination mit platinverbindungen und optional ionisierender strahlung bei der behandlung von erkrankungen im zusammenhang mit angiogenese und/oder erhöhter gefässpermeabilität |
| CN101337930B (zh) | 2003-11-11 | 2010-09-08 | 卫材R&D管理有限公司 | 脲衍生物的制备方法 |
| ATE428421T1 (de) | 2004-09-17 | 2009-05-15 | Eisai R&D Man Co Ltd | Medizinische zusammensetzung mit verbesserter stabilität und reduzierten gelierungseigenschaften |
| JP2008514577A (ja) * | 2004-09-27 | 2008-05-08 | アストラゼネカ アクチボラグ | Ｚｄ６４７４及びイマチニブを含んでなる組合せ |
| GB0424339D0 (en) * | 2004-11-03 | 2004-12-08 | Astrazeneca Ab | Combination therapy |
| EP1901754A2 (en) * | 2005-07-06 | 2008-03-26 | AstraZeneca AB | Combination therapy of cancer with azd2171 and gemcitabine |
| JP2009502960A (ja) * | 2005-07-27 | 2009-01-29 | ザ・ボード・オブ・リージェンツ・オブ・ザ・ユニバーシティ・オブ・テキサス・システム | 膵臓癌の処置のためのゲムシタビンおよびチロシンキナーゼ阻害剤を含む組み合わせ |
| WO2007015578A1 (ja) | 2005-08-02 | 2007-02-08 | Eisai R & D Management Co., Ltd. | 血管新生阻害物質の効果を検定する方法 |
| GB0519879D0 (en) | 2005-09-30 | 2005-11-09 | Astrazeneca Ab | Chemical process |
| WO2007071958A2 (en) * | 2005-12-22 | 2007-06-28 | Astrazeneca Ab | Combination of zd6474 and pemetrexed |
| CN101443009A (zh) | 2006-05-18 | 2009-05-27 | 卫材R&D管理有限公司 | 针对甲状腺癌的抗肿瘤剂 |
| KR101472600B1 (ko) | 2006-08-28 | 2014-12-15 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 미분화형 위암에 대한 항종양제 |
| EP2066353B1 (en) * | 2006-09-29 | 2013-01-02 | AstraZeneca AB | Combination of zd6474 and bevacizumab for cancer therapy |
| AU2008205847A1 (en) | 2007-01-19 | 2008-07-24 | Eisai R & D Management Co., Ltd. | Composition for treatment of pancreatic cancer |
| WO2008093855A1 (ja) | 2007-01-29 | 2008-08-07 | Eisai R & D Management Co., Ltd. | 未分化型胃癌治療用組成物 |
| CA2704000C (en) | 2007-11-09 | 2016-12-13 | Eisai R&D Management Co., Ltd. | Combination of anti-angiogenic substance and anti-tumor platinum complex |
| US20120070368A1 (en) * | 2010-04-16 | 2012-03-22 | Exelixis, Inc. | Methods of Using C-Met Modulators |
| KR101677790B1 (ko) | 2010-06-25 | 2016-11-18 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 키나제 저해 작용을 갖는 화합물의 병용에 의한 항종양제 |
| RU2580609C2 (ru) | 2011-04-18 | 2016-04-10 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Противоопухолевое терапевтическое средство |
| EP3444363B1 (en) | 2011-06-03 | 2020-11-25 | Eisai R&D Management Co., Ltd. | Biomarkers for prediciting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds |
| KR20150098605A (ko) | 2012-12-21 | 2015-08-28 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 퀴놀린 유도체의 비정질 형태 및 그의 제조방법 |
| SG11201509278XA (en) | 2013-05-14 | 2015-12-30 | Eisai R&D Man Co Ltd | Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds |
| SI3524595T1 (sl) | 2014-08-28 | 2022-10-28 | Eisai R&D Management Co., Ltd. | Derivat kinolina visoke čistosti in postopek njegove proizvodnje |
| WO2016136745A1 (ja) | 2015-02-25 | 2016-09-01 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | キノリン誘導体の苦味抑制方法 |
| KR102662228B1 (ko) | 2015-03-04 | 2024-05-02 | 머크 샤프 앤드 돔 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합 |
| CA2988707C (en) | 2015-06-16 | 2023-10-10 | Eisai R&D Management Co., Ltd. | Combination of cbp/catenin inhibitor and immune checkpoint inhibitor for treating cancer |
| CN106619688A (zh) * | 2016-12-27 | 2017-05-10 | 郑州郑先医药科技有限公司 | 一种治疗糖尿病的药物组合物及应用 |
| CN106727657A (zh) * | 2016-12-27 | 2017-05-31 | 郑州郑先医药科技有限公司 | 一种治疗糖尿病的西药组合物及应用 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3587500T2 (de) * | 1984-12-04 | 1993-12-16 | Lilly Co Eli | Tumorbehandlung bei Säugetieren. |
| US7132458B2 (en) * | 1994-08-10 | 2006-11-07 | Chemaphor Inc. | Oxidized carotenoid fractions and ketoaldehyde useful as cell-differentiation inducers, cytostatic agents, and anti-tumor agents |
| GB9718972D0 (en) * | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| PT1244647E (pt) * | 1999-11-05 | 2006-10-31 | Astrazeneca Ab | Derivados de quinazolina como inibidores de vegf |
| TWI310684B (en) * | 2000-03-27 | 2009-06-11 | Bristol Myers Squibb Co | Synergistic pharmaceutical kits for treating cancer |
| GB0008269D0 (en) * | 2000-04-05 | 2000-05-24 | Astrazeneca Ab | Combination chemotherapy |
| US6953679B2 (en) * | 2000-09-19 | 2005-10-11 | Bristol-Myers Squibb Company | Method for the preparation of fused heterocyclic succinimide compounds and analogs thereof |
| GB0126879D0 (en) * | 2001-11-08 | 2002-01-02 | Astrazeneca Ab | Combination therapy |
| CN1313094C (zh) * | 2002-08-09 | 2007-05-02 | 阿斯利康(瑞典)有限公司 | Zd6474在制备在用电离辐射治疗的人体中治疗癌症的药物的用途 |
| GB0218526D0 (en) * | 2002-08-09 | 2002-09-18 | Astrazeneca Ab | Combination therapy |
| GB0223380D0 (en) * | 2002-10-09 | 2002-11-13 | Astrazeneca Ab | Combination therapy |
| GB0226434D0 (en) * | 2002-11-13 | 2002-12-18 | Astrazeneca Ab | Combination product |
| DE602004032310D1 (de) * | 2003-02-13 | 2011-06-01 | Astrazeneca Ab | Kombinationstherapie von zd6474 mit 5-fu oder/und cpt-11 |
| ATE478671T1 (de) * | 2003-07-10 | 2010-09-15 | Astrazeneca Ab | Verwendung des chinazolin-derivats zd6474 in kombination mit platinverbindungen und optional ionisierender strahlung bei der behandlung von erkrankungen im zusammenhang mit angiogenese und/oder erhöhter gefässpermeabilität |
| JP2008514577A (ja) * | 2004-09-27 | 2008-05-08 | アストラゼネカ アクチボラグ | Ｚｄ６４７４及びイマチニブを含んでなる組合せ |
| GB0424339D0 (en) * | 2004-11-03 | 2004-12-08 | Astrazeneca Ab | Combination therapy |
| EP1901754A2 (en) * | 2005-07-06 | 2008-03-26 | AstraZeneca AB | Combination therapy of cancer with azd2171 and gemcitabine |
| WO2007071958A2 (en) * | 2005-12-22 | 2007-06-28 | Astrazeneca Ab | Combination of zd6474 and pemetrexed |
| EP2066353B1 (en) * | 2006-09-29 | 2013-01-02 | AstraZeneca AB | Combination of zd6474 and bevacizumab for cancer therapy |
| US20100212978A1 (en) * | 2009-02-23 | 2010-08-26 | Wen-Hung Huang | Bicycle with two operation molds |
-
2002
- 2002-10-09 GB GBGB0223380.7A patent/GB0223380D0/en not_active Ceased
-
2003
- 2003-10-06 PT PT03751032T patent/PT1551409E/pt unknown
- 2003-10-06 CA CA2501651A patent/CA2501651C/en not_active Expired - Fee Related
- 2003-10-06 JP JP2004542620A patent/JP5416328B2/ja not_active Expired - Fee Related
- 2003-10-06 KR KR1020057005960A patent/KR101098061B1/ko active IP Right Grant
- 2003-10-06 EP EP03751032A patent/EP1551409B1/en not_active Expired - Lifetime
- 2003-10-06 CN CNB2003801011766A patent/CN100363004C/zh not_active Expired - Fee Related
- 2003-10-06 AT AT03751032T patent/ATE357236T1/de active
- 2003-10-06 NZ NZ538999A patent/NZ538999A/en not_active IP Right Cessation
- 2003-10-06 ES ES03751032T patent/ES2282656T3/es not_active Expired - Lifetime
- 2003-10-06 US US10/530,567 patent/US20060009418A1/en not_active Abandoned
- 2003-10-06 SI SI200330784T patent/SI1551409T1/sl unknown
- 2003-10-06 DE DE60312715T patent/DE60312715T2/de not_active Expired - Lifetime
- 2003-10-06 DK DK03751032T patent/DK1551409T3/da active
- 2003-10-06 MX MXPA05003595A patent/MXPA05003595A/es active IP Right Grant
- 2003-10-06 WO PCT/GB2003/004334 patent/WO2004032937A1/en active IP Right Grant
- 2003-10-06 BR BR0315088-7A patent/BR0315088A/pt not_active IP Right Cessation
- 2003-10-06 AU AU2003269253A patent/AU2003269253B2/en not_active Ceased
-
2005
- 2005-03-24 IL IL167633A patent/IL167633A/en active IP Right Grant
- 2005-03-29 NO NO20051575A patent/NO330601B1/no not_active IP Right Cessation
- 2005-11-24 HK HK05110642A patent/HK1078771A1/xx not_active IP Right Cessation
-
2006
- 2006-01-17 ZA ZA200502753A patent/ZA200502753B/en unknown
-
2007
- 2007-05-17 CY CY20071100670T patent/CY1106601T1/el unknown
-
2009
- 2009-08-14 US US12/541,647 patent/US20100120708A1/en not_active Abandoned
-
2010
- 2010-12-24 JP JP2010287659A patent/JP2011088921A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| NO330601B1 (no) | 2011-05-23 |
| GB0223380D0 (en) | 2002-11-13 |
| SI1551409T1 (sl) | 2007-08-31 |
| HK1078771A1 (en) | 2006-03-24 |
| IL167633A (en) | 2013-03-24 |
| CN100363004C (zh) | 2008-01-23 |
| CN1703223A (zh) | 2005-11-30 |
| CY1106601T1 (el) | 2012-01-25 |
| EP1551409A1 (en) | 2005-07-13 |
| NO20051575L (no) | 2005-04-25 |
| CA2501651A1 (en) | 2004-04-22 |
| DK1551409T3 (da) | 2007-06-11 |
| JP2011088921A (ja) | 2011-05-06 |
| KR20050055070A (ko) | 2005-06-10 |
| DE60312715T2 (de) | 2007-12-06 |
| BR0315088A (pt) | 2005-08-16 |
| JP2006504723A (ja) | 2006-02-09 |
| JP5416328B2 (ja) | 2014-02-12 |
| US20100120708A1 (en) | 2010-05-13 |
| NZ538999A (en) | 2008-02-29 |
| ATE357236T1 (de) | 2007-04-15 |
| US20060009418A1 (en) | 2006-01-12 |
| DE60312715D1 (de) | 2007-05-03 |
| MXPA05003595A (es) | 2005-06-03 |
| AU2003269253B2 (en) | 2007-04-05 |
| EP1551409B1 (en) | 2007-03-21 |
| KR101098061B1 (ko) | 2011-12-26 |
| PT1551409E (pt) | 2007-05-31 |
| CA2501651C (en) | 2011-02-15 |
| ES2282656T3 (es) | 2007-10-16 |
| WO2004032937A1 (en) | 2004-04-22 |
| AU2003269253A1 (en) | 2004-05-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2003269253B2 (en) | Use of the quinazoline derivative ZD6474 combined with gemcitabine and optionally ionising radiation in the treatment of diseases associated with angiogenesis and/or increased vascular permeability | |
| CA2531862C (en) | Use of the quinazoline derivative zd6474 combined with platinum compounds and optionally ionising radiation in the treatment of diseases associated with angiogenesis and/or increased vascular permeability | |
| AU2006328189B2 (en) | Combination of ZD6474 and pemetrexed | |
| AU2005225193B2 (en) | Combination therapy | |
| NZ568812A (en) | Combination of AZD2171 and pemetrexed | |
| AU2006264620B2 (en) | Combination therapy of cancer with AZD2171 and gemcitabine | |
| NZ549554A (en) | Combination therapy involving 4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (AZD2171) and a taxane | |
| ZA200600186B (en) | Use of the quinazoline derivative ZD6474 combined with platinum compounds and optionally ionising radiation in the treatment of deseases associated with angiogenesis and/or increased vascular permeability |