NZ512189A - N-[4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4- yl-propoxy)-quinazolin-6-yl]-acrylamide useful as an irreversible inhibitor of tyrosine kinases - Google Patents
N-[4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4- yl-propoxy)-quinazolin-6-yl]-acrylamide useful as an irreversible inhibitor of tyrosine kinasesInfo
- Publication number
- NZ512189A NZ512189A NZ512189A NZ51218999A NZ512189A NZ 512189 A NZ512189 A NZ 512189A NZ 512189 A NZ512189 A NZ 512189A NZ 51218999 A NZ51218999 A NZ 51218999A NZ 512189 A NZ512189 A NZ 512189A
- Authority
- NZ
- New Zealand
- Prior art keywords
- compound
- medicament
- chloro
- egf
- manufacture
- Prior art date
Links
- OMZCMEYTWSXEPZ-UHFFFAOYSA-N canertinib Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCOCC3)=C(NC(=O)C=C)C=C12 OMZCMEYTWSXEPZ-UHFFFAOYSA-N 0.000 title claims abstract description 12
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 title claims description 21
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 title claims description 21
- 239000013038 irreversible inhibitor Substances 0.000 title description 5
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 44
- 201000011510 cancer Diseases 0.000 claims abstract description 26
- 208000037803 restenosis Diseases 0.000 claims abstract description 21
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 12
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 51
- 229940125904 compound 1 Drugs 0.000 claims description 36
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 27
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 22
- 230000028327 secretion Effects 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 18
- 239000004017 serum-free culture medium Substances 0.000 claims description 17
- 230000005764 inhibitory process Effects 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 9
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 9
- 201000009273 Endometriosis Diseases 0.000 claims description 7
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 claims description 7
- 108010009583 Transforming Growth Factors Proteins 0.000 claims description 7
- 102000009618 Transforming Growth Factors Human genes 0.000 claims description 7
- 101800004564 Transforming growth factor alpha Proteins 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 230000026731 phosphorylation Effects 0.000 claims description 6
- 238000006366 phosphorylation reaction Methods 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 5
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 208000029742 colonic neoplasm Diseases 0.000 claims description 3
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical group 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 claims 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 abstract description 6
- 230000002427 irreversible effect Effects 0.000 abstract description 5
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 abstract description 4
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 29
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 27
- -1 EGF Proteins 0.000 description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 23
- 229910001868 water Inorganic materials 0.000 description 20
- 239000000243 solution Substances 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 18
- 102100033237 Pro-epidermal growth factor Human genes 0.000 description 16
- 102000001301 EGF receptor Human genes 0.000 description 15
- 108060006698 EGF receptor Proteins 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- 238000000034 method Methods 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 8
- 230000004614 tumor growth Effects 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 235000011187 glycerol Nutrition 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 206010041823 squamous cell carcinoma Diseases 0.000 description 6
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 102000009465 Growth Factor Receptors Human genes 0.000 description 5
- 108010009202 Growth Factor Receptors Proteins 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000003102 growth factor Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 230000019491 signal transduction Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 108091008794 FGF receptors Proteins 0.000 description 4
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 4
- 208000012766 Growth delay Diseases 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229940116977 epidermal growth factor Drugs 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- NMWKYTGJWUAZPZ-WWHBDHEGSA-N (4S)-4-[[(4R,7S,10S,16S,19S,25S,28S,31R)-31-[[(2S)-2-[[(1R,6R,9S,12S,18S,21S,24S,27S,30S,33S,36S,39S,42R,47R,53S,56S,59S,62S,65S,68S,71S,76S,79S,85S)-47-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-18-(4-aminobutyl)-27,68-bis(3-amino-3-oxopropyl)-36,71,76-tribenzyl-39-(3-carbamimidamidopropyl)-24-(2-carboxyethyl)-21,56-bis(carboxymethyl)-65,85-bis[(1R)-1-hydroxyethyl]-59-(hydroxymethyl)-62,79-bis(1H-imidazol-4-ylmethyl)-9-methyl-33-(2-methylpropyl)-8,11,17,20,23,26,29,32,35,38,41,48,54,57,60,63,66,69,72,74,77,80,83,86-tetracosaoxo-30-propan-2-yl-3,4,44,45-tetrathia-7,10,16,19,22,25,28,31,34,37,40,49,55,58,61,64,67,70,73,75,78,81,84,87-tetracosazatetracyclo[40.31.14.012,16.049,53]heptaoctacontane-6-carbonyl]amino]-3-methylbutanoyl]amino]-7-(3-carbamimidamidopropyl)-25-(hydroxymethyl)-19-[(4-hydroxyphenyl)methyl]-28-(1H-imidazol-4-ylmethyl)-10-methyl-6,9,12,15,18,21,24,27,30-nonaoxo-16-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29-nonazacyclodotriacontane-4-carbonyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](Cc4ccccc4)NC3=O)[C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N3CCC[C@H]3C(=O)N[C@@H](C)C(=O)N2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)C(=O)N[C@@H](C)C(O)=O NMWKYTGJWUAZPZ-WWHBDHEGSA-N 0.000 description 3
- 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 3
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 3
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 102400000058 Neuregulin-1 Human genes 0.000 description 3
- 108090000556 Neuregulin-1 Proteins 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 3
- 208000009956 adenocarcinoma Diseases 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 230000031018 biological processes and functions Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 229940068917 polyethylene glycols Drugs 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000007909 solid dosage form Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 3
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- RPTKRGHYKSBDJL-UHFFFAOYSA-N 6-nitroquinazoline Chemical compound N1=CN=CC2=CC([N+](=O)[O-])=CC=C21 RPTKRGHYKSBDJL-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 241000206672 Gelidium Species 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 2
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 2
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 2
- 108060006706 SRC Proteins 0.000 description 2
- 102000001332 SRC Human genes 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 238000002399 angioplasty Methods 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 230000003305 autocrine Effects 0.000 description 2
- 230000035578 autophosphorylation Effects 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 235000012216 bentonite Nutrition 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 230000001804 emulsifying effect Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000009036 growth inhibition Effects 0.000 description 2
- 230000005917 in vivo anti-tumor Effects 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 210000003800 pharynx Anatomy 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 229960004063 propylene glycol Drugs 0.000 description 2
- 235000013772 propylene glycol Nutrition 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 125000004547 quinazolin-6-yl group Chemical group N1=CN=CC2=CC(=CC=C12)* 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 102000009076 src-Family Kinases Human genes 0.000 description 2
- 108010087686 src-Family Kinases Proteins 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 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 2
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical class CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- FBKSHXJRRCENPH-UHFFFAOYSA-N 2-nitroquinazoline Chemical compound C1=CC=CC2=NC([N+](=O)[O-])=NC=C21 FBKSHXJRRCENPH-UHFFFAOYSA-N 0.000 description 1
- YSEMCVGMNUUNRK-UHFFFAOYSA-N 3-chloro-4-fluoroaniline Chemical compound NC1=CC=C(F)C(Cl)=C1 YSEMCVGMNUUNRK-UHFFFAOYSA-N 0.000 description 1
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
- VZKSLWJLGAGPIU-UHFFFAOYSA-N 3-morpholin-4-ylpropan-1-ol Chemical compound OCCCN1CCOCC1 VZKSLWJLGAGPIU-UHFFFAOYSA-N 0.000 description 1
- AAALVYBICLMAMA-UHFFFAOYSA-N 4,5-dianilinophthalimide Chemical compound C=1C=CC=CC=1NC=1C=C2C(=O)NC(=O)C2=CC=1NC1=CC=CC=C1 AAALVYBICLMAMA-UHFFFAOYSA-N 0.000 description 1
- UYQMNEZWVKRWMS-UHFFFAOYSA-N 4-chloro-7-fluoro-6-nitroquinazoline Chemical compound N1=CN=C2C=C(F)C([N+](=O)[O-])=CC2=C1Cl UYQMNEZWVKRWMS-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000003200 Adenoma Diseases 0.000 description 1
- 206010001233 Adenoma benign Diseases 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 244000056139 Brassica cretica Species 0.000 description 1
- 235000003351 Brassica cretica Nutrition 0.000 description 1
- 235000003343 Brassica rupestris Nutrition 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 108010069682 CSK Tyrosine-Protein Kinase Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 208000010667 Carcinoma of liver and intrahepatic biliary tract Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 102000056372 ErbB-3 Receptor Human genes 0.000 description 1
- 102000044591 ErbB-4 Receptor Human genes 0.000 description 1
- 101150021185 FGF gene Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 206010073069 Hepatic cancer Diseases 0.000 description 1
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- 101000851176 Homo sapiens Pro-epidermal growth factor Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010020772 Hypertension 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
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108010001127 Insulin Receptor Proteins 0.000 description 1
- 102000003746 Insulin Receptor Human genes 0.000 description 1
- 108090000828 Insulysin Proteins 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 206010023347 Keratoacanthoma Diseases 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 208000002454 Nasopharyngeal Carcinoma Diseases 0.000 description 1
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102100031167 Tyrosine-protein kinase CSK Human genes 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 description 1
- 239000003655 absorption accelerator Substances 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000006229 amino acid addition Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000002682 anti-psoriatic effect Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 210000003433 aortic smooth muscle cell Anatomy 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 210000001099 axilla Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
- 201000001531 bladder carcinoma Diseases 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 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
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 229940121647 egfr inhibitor Drugs 0.000 description 1
- 230000032692 embryo implantation Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 201000002222 hemangioblastoma Diseases 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229940045996 isethionic acid Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 208000003849 large cell carcinoma Diseases 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 201000002250 liver carcinoma Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000002625 monoclonal antibody therapy Methods 0.000 description 1
- 235000010460 mustard Nutrition 0.000 description 1
- GIEWYYZWGADAIQ-UHFFFAOYSA-N n-(3-bromophenyl)-7-(3-morpholin-4-ylpropoxy)-6-nitroquinazolin-4-amine Chemical compound N1=CN=C2C=C(OCCCN3CCOCC3)C([N+](=O)[O-])=CC2=C1NC1=CC=CC(Br)=C1 GIEWYYZWGADAIQ-UHFFFAOYSA-N 0.000 description 1
- SPRQBIBULHKTIB-UHFFFAOYSA-N n-(3-bromophenyl)-7-fluoro-6-nitroquinazolin-4-amine Chemical compound N1=CN=C2C=C(F)C([N+](=O)[O-])=CC2=C1NC1=CC=CC(Br)=C1 SPRQBIBULHKTIB-UHFFFAOYSA-N 0.000 description 1
- CJOJDNRJDBWZKM-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine Chemical compound N1=CN=C2C=C(F)C([N+](=O)[O-])=CC2=C1NC1=CC=C(F)C(Cl)=C1 CJOJDNRJDBWZKM-UHFFFAOYSA-N 0.000 description 1
- 125000005487 naphthalate group Chemical group 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 201000011216 nasopharynx carcinoma Diseases 0.000 description 1
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(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](CC=1C=CC(O)=CC=1)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](CCCCN)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)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)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=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 102000027450 oncoproteins Human genes 0.000 description 1
- 108091008819 oncoproteins Proteins 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229940039748 oxalate Drugs 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 201000010198 papillary carcinoma Diseases 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000003566 phosphorylation assay Methods 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- LBKJNHPKYFYCLL-UHFFFAOYSA-N potassium;trimethyl(oxido)silane Chemical compound [K+].C[Si](C)(C)[O-] LBKJNHPKYFYCLL-UHFFFAOYSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- XFGPXURFKAUHQR-UHFFFAOYSA-N quinazolin-6-amine Chemical compound N1=CN=CC2=CC(N)=CC=C21 XFGPXURFKAUHQR-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 230000002885 thrombogenetic effect Effects 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 208000010576 undifferentiated carcinoma Diseases 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 229910000166 zirconium phosphate Inorganic materials 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10906598P | 1998-11-19 | 1998-11-19 | |
| PCT/US1999/022116 WO2000031048A1 (en) | 1998-11-19 | 1999-09-23 | N-[4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide, an irreversible inhibitor of tyrosine kinases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ512189A true NZ512189A (en) | 2003-10-31 |
Family
ID=22325607
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ527718A NZ527718A (en) | 1998-11-19 | 1999-09-23 | N-[4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide, an irreversible inhibitor of tyrosine kinases |
| NZ512189A NZ512189A (en) | 1998-11-19 | 1999-09-23 | N-[4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4- yl-propoxy)-quinazolin-6-yl]-acrylamide useful as an irreversible inhibitor of tyrosine kinases |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ527718A NZ527718A (en) | 1998-11-19 | 1999-09-23 | N-[4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide, an irreversible inhibitor of tyrosine kinases |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US6344455B1 (enExample) |
| EP (1) | EP1131304B1 (enExample) |
| JP (1) | JP3687900B2 (enExample) |
| KR (1) | KR20010080491A (enExample) |
| CN (1) | CN1160338C (enExample) |
| AR (1) | AR023706A1 (enExample) |
| AT (1) | ATE229008T1 (enExample) |
| AU (1) | AU763626B2 (enExample) |
| BG (1) | BG105608A (enExample) |
| BR (1) | BR9915487A (enExample) |
| CA (1) | CA2349721A1 (enExample) |
| CO (1) | CO5150185A1 (enExample) |
| CZ (1) | CZ20011759A3 (enExample) |
| DE (1) | DE69904358T2 (enExample) |
| DK (1) | DK1131304T3 (enExample) |
| EA (1) | EA003786B1 (enExample) |
| EE (1) | EE200100271A (enExample) |
| ES (1) | ES2188254T3 (enExample) |
| GE (1) | GEP20032997B (enExample) |
| HU (1) | HUP0104211A3 (enExample) |
| IL (1) | IL143089A0 (enExample) |
| NO (1) | NO319357B1 (enExample) |
| NZ (2) | NZ527718A (enExample) |
| PE (1) | PE20001242A1 (enExample) |
| PL (1) | PL347717A1 (enExample) |
| PT (1) | PT1131304E (enExample) |
| SK (1) | SK283688B6 (enExample) |
| UY (1) | UY25809A1 (enExample) |
| WO (1) | WO2000031048A1 (enExample) |
| ZA (1) | ZA200103535B (enExample) |
Families Citing this family (234)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6811779B2 (en) | 1994-02-10 | 2004-11-02 | Imclone Systems Incorporated | Methods for reducing tumor growth with VEGF receptor antibody combined with radiation and chemotherapy |
| US6706721B1 (en) | 1998-04-29 | 2004-03-16 | Osi Pharmaceuticals, Inc. | N-(3-ethynylphenylamino)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine mesylate anhydrate and monohydrate |
| US7087613B2 (en) | 1999-11-11 | 2006-08-08 | Osi Pharmaceuticals, Inc. | Treating abnormal cell growth with a stable polymorph of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine hydrochloride |
| UA74803C2 (uk) | 1999-11-11 | 2006-02-15 | Осі Фармасьютікалз, Інк. | Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування |
| GB0002952D0 (en) * | 2000-02-09 | 2000-03-29 | Pharma Mar Sa | Process for producing kahalalide F compounds |
| US7569551B2 (en) | 2000-02-25 | 2009-08-04 | The University Of British Columbia | Chemo- and radiation-sensitization of cancer by antisense TRPM-2 oligodeoxynucleotides |
| UA73993C2 (uk) | 2000-06-06 | 2005-10-17 | Астразенека Аб | Хіназолінові похідні для лікування пухлин та фармацевтична композиція |
| DE10031971A1 (de) * | 2000-06-30 | 2002-01-10 | Goedecke Ag | Polymorphe Formen/Hydrate von N-[4-(3-Chlor-4-fluor-phenylamino)-7-(3-morpholin-4-yl-propoxy)-chinazolin-6-yl]-acrylamid Dihydrochlorid, Verfahren zu ihrer Herstellung sowie die Verwendung derselben zur Herstellung von Medikamenten mit irreversibler Tyrosinkinasehemmwirkung |
| EP1170011A1 (en) * | 2000-07-06 | 2002-01-09 | Boehringer Ingelheim International GmbH | Novel use of inhibitors of the epidermal growth factor receptor |
| AU9500201A (en) * | 2000-08-09 | 2002-02-18 | Imclone Systems Inc | Treatment of hyperproliferative diseases with epidermal growth factor receptor antagonists |
| US6403580B1 (en) | 2000-08-26 | 2002-06-11 | Boehringer Ingelheim Pharma Kg | Quinazolines, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
| DE10042064A1 (de) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma | Chinazoline, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| US20020119148A1 (en) | 2000-09-01 | 2002-08-29 | Gerritsen Mary E. | ErbB4 antagonists |
| MX242553B (es) | 2000-10-20 | 2006-12-06 | Eisai Co Ltd | Derivados aromaticos que contienen nitrogeno. |
| US7776315B2 (en) | 2000-10-31 | 2010-08-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions based on anticholinergics and additional active ingredients |
| US7019012B2 (en) | 2000-12-20 | 2006-03-28 | Boehringer Ingelheim International Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
| NZ516873A (en) * | 2001-02-12 | 2003-11-28 | Warner Lambert Co | Compositions containing retinoids and erb inhibitors and their use in inhibiting retinoid skin damage |
| EP1283053A1 (en) | 2001-08-09 | 2003-02-12 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Inhibitors of HER3 activity |
| CA2469685C (en) | 2002-01-17 | 2013-03-12 | The University Of British Columbia | Bispecific antisense oligonucleotides that inhibit igfbp-2 and igfbp-5 and methods of using same |
| DE10221018A1 (de) | 2002-05-11 | 2003-11-27 | Boehringer Ingelheim Pharma | Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie |
| EP1510221A4 (en) * | 2002-06-03 | 2009-04-29 | Mitsubishi Tanabe Pharma Corp | MEANS FOR THE PREVENTION AND / OR TREATMENT OF PERSONS EXPRESSING OR ACTIVATING HER2 AND / OR EGFR |
| CA2491191C (en) | 2002-07-15 | 2014-02-04 | Exelixis, Inc. | Receptor-type kinase modulators and methods of use |
| GB0304367D0 (en) * | 2003-02-26 | 2003-04-02 | Pharma Mar Sau | Methods for treating psoriasis |
| US7687506B2 (en) | 2003-04-11 | 2010-03-30 | The Regents Of The University Of California | Selective serine/threonine kinase inhibitors |
| EP2348110B1 (en) | 2003-05-30 | 2013-03-27 | OncoTherapy Science, Inc. | Process for screening a drug response in cancer patients |
| JP2007500248A (ja) | 2003-06-09 | 2007-01-11 | ワクサル，サムエル | 細胞外アンタゴニストおよび細胞内アンタゴニストによる受容体チロシンキナーゼの抑制方法 |
| US7501427B2 (en) | 2003-08-14 | 2009-03-10 | Array Biopharma, Inc. | Quinazoline analogs as receptor tyrosine kinase inhibitors |
| KR100953246B1 (ko) | 2003-08-14 | 2010-04-16 | 어레이 바이오파마 인크. | 수용체 티로신 키나아제 억제제로서의 퀴나졸린 유사체 |
| GB0321066D0 (en) * | 2003-09-09 | 2003-10-08 | Pharma Mar Sau | New antitumoral compounds |
| DK1667991T3 (da) * | 2003-09-16 | 2008-08-18 | Astrazeneca Ab | Quinazolinderivater som tyrosinkinaseinhibitorer |
| GB0321620D0 (en) * | 2003-09-16 | 2003-10-15 | Astrazeneca Ab | Quinazoline derivatives |
| CA2744997A1 (en) | 2003-09-26 | 2005-04-07 | Exelixis, Inc. | C-met modulators and method of use |
| US7683172B2 (en) | 2003-11-11 | 2010-03-23 | Eisai R&D Management Co., Ltd. | Urea derivative and process for preparing the same |
| RU2402569C2 (ru) | 2004-03-19 | 2010-10-27 | Имклоун Элэлси | Человеческие антитела к рецептору эпидермального фактора роста |
| EP1740184A1 (en) * | 2004-03-30 | 2007-01-10 | Pfizer Products Incorporated | Combinations of signal transduction inhibitors |
| US8080577B2 (en) | 2004-05-06 | 2011-12-20 | Bioresponse, L.L.C. | Diindolylmethane formulations for the treatment of leiomyomas |
| EP1746999B1 (en) | 2004-05-06 | 2011-11-16 | Warner-Lambert Company LLC | 4-phenylamino-quinazolin-6-yl-amides |
| US20060035893A1 (en) | 2004-08-07 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders |
| WO2006030826A1 (ja) | 2004-09-17 | 2006-03-23 | Eisai R & D Management Co., Ltd. | 医薬組成物 |
| PE20060777A1 (es) | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas |
| WO2006071079A1 (en) * | 2004-12-29 | 2006-07-06 | Hanmi Pharm. Co., Ltd. | Quinazoline derivatives for inhibiting cancer cell growth and method for the preparation thereof |
| CA2593084C (en) | 2004-12-30 | 2014-03-18 | Bioresponse, Llc | Use of diindolylmethane-related indoles for the treatment and prevention of respiratory syncytial virus associated conditions |
| US20060188498A1 (en) * | 2005-02-18 | 2006-08-24 | Genentech, Inc. | Methods of using death receptor agonists and EGFR inhibitors |
| US20090155247A1 (en) * | 2005-02-18 | 2009-06-18 | Ashkenazi Avi J | Methods of Using Death Receptor Agonists and EGFR Inhibitors |
| CN101500597A (zh) | 2005-06-17 | 2009-08-05 | 伊姆克罗尼系统公司 | 治疗转移性骨癌的受体拮抗剂 |
| EP2281901B1 (en) | 2005-08-02 | 2013-11-27 | Eisai R&D Management Co., Ltd. | Anti-tumour pharmaceutical composition with angiogenesis inhibitors |
| EP1917528B1 (en) | 2005-08-24 | 2011-08-17 | Bristol-Myers Squibb Company | Biomarkers and methods for determining sensitivity to epidermal growth factor receptor modulators |
| KR100832593B1 (ko) * | 2005-11-08 | 2008-05-27 | 한미약품 주식회사 | 신호전달 저해제로서의 퀴나졸린 유도체 및 이의 제조방법 |
| JP5688877B2 (ja) | 2005-11-11 | 2015-03-25 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌疾患の治療用キナゾリン誘導体 |
| DE602006009968D1 (de) | 2005-11-15 | 2009-12-03 | Array Biopharma Inc | N4-phenyl-chinazolin-4-aminderivate und verwandte verbindungen als inhibitoren der erbb-typ-i-rezeptortyrosinkinase zur behandlung hyperproliferativer krankheiten |
| AU2007252506C1 (en) | 2006-05-18 | 2012-07-19 | Eisai R & D Management Co., Ltd. | Antitumor agent for thyroid cancer |
| EP2065372B1 (en) | 2006-08-28 | 2012-11-28 | Eisai R&D Management Co., Ltd. | Antitumor agent for undifferentiated gastric cancer |
| EP2845912A1 (en) | 2006-09-12 | 2015-03-11 | Genentech, Inc. | Methods and compositions for the diagnosis and treatment of lung cancer using KIT gene as genetic marker |
| CA2663599A1 (en) | 2006-09-18 | 2008-03-27 | Boehringer Ingelheim International Gmbh | Method for treating cancer harboring egfr mutations |
| BRPI0717753B1 (pt) | 2006-10-27 | 2022-04-12 | Bioresponse, Llc | Uso de uma composição compreendendo 50-250 mg de um ou mais indóis relacionados com dim e um ou mais agentes anti-protozoários, e, composição |
| CN101600694A (zh) | 2007-01-29 | 2009-12-09 | 卫材R&D管理有限公司 | 未分化型胃癌治疗用组合物 |
| US8642067B2 (en) | 2007-04-02 | 2014-02-04 | Allergen, Inc. | Methods and compositions for intraocular administration to treat ocular conditions |
| MX2010004259A (es) * | 2007-10-19 | 2010-08-31 | Pharma Mar Sa | Tratamientos antitumorales mejorados. |
| AU2008325608B2 (en) | 2007-11-09 | 2013-03-14 | Eisai R & D Management Co., Ltd. | Combination of anti-angiogenic substance and anti-tumor platinum complex |
| WO2009067543A2 (en) * | 2007-11-19 | 2009-05-28 | The Regents Of The University Of Colorado | Treatment of histone deacetylase mediated disorders |
| EP2252315A1 (en) * | 2008-01-30 | 2010-11-24 | Pharma Mar, S.A. | Improved antitumoral treatments |
| TWI472339B (zh) | 2008-01-30 | 2015-02-11 | Genentech Inc | 包含結合至ｈｅｒ２結構域ii之抗體及其酸性變異體的組合物 |
| JP2011513370A (ja) * | 2008-03-07 | 2011-04-28 | ファルマ・マール・ソシエダード・アノニマ | 改善された抗腫瘍治療法 |
| CN101544609A (zh) | 2008-03-25 | 2009-09-30 | 上海艾力斯医药科技有限公司 | 4-苯胺喹唑啉衍生物的结晶形式 |
| DK2387563T4 (da) | 2009-01-16 | 2022-07-18 | Exelixis Inc | Malatsalt af n-(4-{ [ 6, 7-bis(methyloxy)quinolin-4-yl]oxy}phenyl-n'-(4-fluorphenyl)cyclopropan-1,1-dicarboxamid, og krystallinske former deraf til behandling af cancer |
| NZ594665A (en) | 2009-03-20 | 2013-08-30 | Genentech Inc | Bispecific anti-her antibodies |
| US8530492B2 (en) | 2009-04-17 | 2013-09-10 | Nektar Therapeutics | Oligomer-protein tyrosine kinase inhibitor conjugates |
| JP5963672B2 (ja) | 2009-07-06 | 2016-08-03 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｂｉｂｗ２９９２、その塩及びこの活性成分を含む固体医薬製剤の乾燥方法 |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| NZ598705A (en) | 2009-09-16 | 2014-06-27 | Celgene Avilomics Res Inc | Protein kinase conjugates and inhibitors |
| US20120220594A1 (en) | 2009-10-30 | 2012-08-30 | Bristol-Meyers Squibb Company | Methods for treating cancer in patients having igf-1r inhibitor resistance |
| EP2498817A2 (en) | 2009-11-12 | 2012-09-19 | F. Hoffmann-La Roche AG | A method of promoting dendritic spine density |
| JP2013516422A (ja) | 2009-12-30 | 2013-05-13 | アビラ セラピューティクス， インコーポレイテッド | タンパク質のリガンド−指向性共有的修飾 |
| EP2523957A1 (en) | 2010-01-12 | 2012-11-21 | F. Hoffmann-La Roche AG | Tricyclic heterocyclic compounds, compositions and methods of use thereof |
| ES2519348T3 (es) | 2010-02-18 | 2014-11-06 | Genentech, Inc. | Antagonistas de neurregulina y uso de los mismos en el tratamiento del cáncer |
| RU2012141536A (ru) | 2010-03-17 | 2014-04-27 | Ф. Хоффманн-Ля Рош Аг | Имидазопиридины, композиции и способы применения |
| CN103038643A (zh) | 2010-04-16 | 2013-04-10 | 基因泰克公司 | 作为pi3k/akt激酶途径抑制剂效能的预测性生物标记的foxo3a |
| KR101677790B1 (ko) | 2010-06-25 | 2016-11-18 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 키나제 저해 작용을 갖는 화합물의 병용에 의한 항종양제 |
| BR112013004673A8 (pt) | 2010-08-31 | 2018-01-02 | Genentech Inc | biomarcadores e métodos de tratamento. |
| CN103209695A (zh) | 2010-09-15 | 2013-07-17 | 弗·哈夫曼-拉罗切有限公司 | 氮杂苯并噻唑化合物、组合物及应用方法 |
| KR20140009259A (ko) | 2010-11-19 | 2014-01-22 | 에프. 호프만-라 로슈 아게 | 피라졸로피리딘 및 tyk2 억제제로서 이의 용도 |
| WO2012085176A1 (en) | 2010-12-23 | 2012-06-28 | F. Hoffmann-La Roche Ag | Tricyclic pyrazinone compounds, compositions and methods of use thereof as janus kinase inhibitors |
| KR101762999B1 (ko) | 2011-04-18 | 2017-07-28 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 종양 치료제 |
| GB201106870D0 (en) | 2011-04-26 | 2011-06-01 | Univ Belfast | Marker |
| US9945862B2 (en) | 2011-06-03 | 2018-04-17 | Eisai R&D Management Co., Ltd. | Biomarkers for predicting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds |
| WO2013007768A1 (en) | 2011-07-13 | 2013-01-17 | F. Hoffmann-La Roche Ag | Tricyclic heterocyclic compounds, compositions and methods of use thereof as jak inhibitors |
| WO2013007765A1 (en) | 2011-07-13 | 2013-01-17 | F. Hoffmann-La Roche Ag | Fused tricyclic compounds for use as inhibitors of janus kinases |
| JP5855253B2 (ja) | 2011-08-12 | 2016-02-09 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | インダゾール化合物、組成物及び使用方法 |
| WO2013025853A1 (en) | 2011-08-17 | 2013-02-21 | Genentech, Inc. | Neuregulin antibodies and uses thereof |
| WO2013041539A1 (en) | 2011-09-20 | 2013-03-28 | F. Hoffmann-La Roche Ag | Imidazopyridine compounds, compositions and methods of use |
| US20140309229A1 (en) | 2011-10-13 | 2014-10-16 | Bristol-Myers Squibb Company | Methods for selecting and treating cancer in patients with igf-1r/ir inhibitors |
| CA2857114A1 (en) | 2011-11-30 | 2013-06-06 | Genentech, Inc. | Erbb3 mutations in cancer |
| EP2831115A1 (en) | 2012-03-27 | 2015-02-04 | F. Hoffmann-La Roche AG | Diagnosis and treatments relating to her3 inhibitors |
| ES2894830T3 (es) | 2012-04-03 | 2022-02-16 | Novartis Ag | Productos combinados con inhibidores de tirosina·cinasa y su uso |
| CA2889866A1 (en) | 2012-12-21 | 2014-06-26 | Eisai R&D Management Co., Ltd. | Amorphous form of quinoline derivative, and method for producing same |
| MX2015010791A (es) | 2013-02-22 | 2015-11-26 | Hoffmann La Roche | Metodos para tratar el cancer y prevenir la resistencia a farmacos. |
| CN105246511A (zh) | 2013-03-06 | 2016-01-13 | 豪夫迈·罗氏有限公司 | 治疗和预防癌症药物抗性的方法 |
| EP2970307B1 (en) | 2013-03-13 | 2020-03-11 | Genentech, Inc. | Pyrazolo compounds and uses thereof |
| SG11201507477XA (en) | 2013-03-14 | 2015-10-29 | Genentech Inc | Combinations of a mek inhibitor compound with an her3/egfr inhibitor compound and methods of use |
| HK1220916A1 (zh) | 2013-03-14 | 2017-05-19 | 基因泰克公司 | 治疗癌症和预防癌症药物抗性的方法 |
| KR20150130451A (ko) | 2013-03-15 | 2015-11-23 | 제넨테크, 인크. | 암 치료 방법 및 항암제 내성 예방을 위한 방법 |
| NZ714049A (en) | 2013-05-14 | 2020-05-29 | Eisai R&D Man Co Ltd | Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds |
| CN103242244B (zh) * | 2013-05-16 | 2015-03-25 | 苏州明锐医药科技有限公司 | 一种卡奈替尼的制备方法 |
| EP3041474B1 (en) | 2013-09-05 | 2020-03-18 | Genentech, Inc. | Antiproliferative compounds |
| CN104513229A (zh) * | 2013-09-28 | 2015-04-15 | 正大天晴药业集团股份有限公司 | 喹唑啉衍生物及其制备方法 |
| WO2015049325A1 (en) | 2013-10-03 | 2015-04-09 | F. Hoffmann-La Roche Ag | Therapeutic inhibitors of cdk8 and uses thereof |
| EP3057615B1 (en) | 2013-10-18 | 2021-02-24 | F.Hoffmann-La Roche Ag | Anti-rspo antibodies and methods of use |
| JP6841656B2 (ja) | 2013-12-17 | 2021-03-10 | ジェネンテック， インコーポレイテッド | Ｐｄ−１軸結合アンタゴニスト及びタキサンを使用する癌の治療方法 |
| BR112016013963A2 (pt) | 2013-12-17 | 2017-10-10 | Genentech Inc | terapia de combinação compreendendo agonistas de ligação de ox40 e antagonistas de ligação do eixo de pd-1 |
| US9242965B2 (en) | 2013-12-31 | 2016-01-26 | Boehringer Ingelheim International Gmbh | Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors |
| EP3122900A1 (en) | 2014-03-24 | 2017-02-01 | F. Hoffmann-La Roche AG | Cancer treatment with c-met antagonists and correlation of the latter with hgf expression |
| HRP20192285T1 (hr) | 2014-03-31 | 2020-03-06 | F. Hoffmann - La Roche Ag | Anti-ox40 protutijela i postupci uporabe |
| CA2943834A1 (en) | 2014-03-31 | 2015-10-08 | Genentech, Inc. | Combination therapy comprising anti-angiogenesis agents and ox40 binding agonists |
| HRP20221047T1 (hr) | 2014-08-28 | 2022-11-11 | Eisai R&D Management Co., Ltd. | Derivat kinolina visoke čistoće i postupak za njegovu proizvodnju |
| CN107074823B (zh) | 2014-09-05 | 2021-05-04 | 基因泰克公司 | 治疗性化合物及其用途 |
| EP3193866A1 (en) | 2014-09-19 | 2017-07-26 | Genentech, Inc. | Use of cbp/ep300 and bet inhibitors for treatment of cancer |
| JP6783230B2 (ja) | 2014-10-10 | 2020-11-11 | ジェネンテック， インコーポレイテッド | ヒストンデメチラーゼのインヒビターとしてのピロリドンアミド化合物 |
| EP3206717B1 (en) | 2014-10-17 | 2020-11-25 | Novartis AG | Combination of ceritinib with an egfr inhibitor |
| BR112017009151A2 (pt) | 2014-11-03 | 2018-03-06 | Genentech, Inc. | ensaios para detectar subgrupos imunológicos de célula t e métodos de uso dos mesmos |
| WO2016073380A1 (en) | 2014-11-03 | 2016-05-12 | Genentech, Inc. | Method and biomarkers for predicting efficacy and evaluation of an ox40 agonist treatment |
| CN107073126A (zh) | 2014-11-06 | 2017-08-18 | 豪夫迈·罗氏有限公司 | 包含ox40结合激动剂和tigit抑制剂的组合疗法 |
| MA40943A (fr) | 2014-11-10 | 2017-09-19 | Constellation Pharmaceuticals Inc | Pyrrolopyridines substituées utilisées en tant qu'inhibiteurs de bromodomaines |
| JP6639497B2 (ja) | 2014-11-10 | 2020-02-05 | ジェネンテック， インコーポレイテッド | ブロモドメインインヒビターおよびその使用 |
| MA40940A (fr) | 2014-11-10 | 2017-09-19 | Constellation Pharmaceuticals Inc | Pyrrolopyridines substituées utilisées en tant qu'inhibiteurs de bromodomaines |
| KR20170096112A (ko) | 2014-11-17 | 2017-08-23 | 제넨테크, 인크. | Ox40 결합 효능제 및 pd-1 축 결합 길항제를 포함하는 조합 요법 |
| WO2016086200A1 (en) | 2014-11-27 | 2016-06-02 | Genentech, Inc. | 4,5,6,7-tetrahydro-1 h-pyrazolo[4,3-c]pyridin-3-amine compounds as cbp and/or ep300 inhibitors |
| CA2968359A1 (en) | 2014-12-23 | 2016-06-30 | Genentech, Inc. | Compositions and methods for treating and diagnosing chemotherapy-resistant cancers |
| WO2016109546A2 (en) | 2014-12-30 | 2016-07-07 | Genentech, Inc. | Methods and compositions for prognosis and treatment of cancers |
| WO2016112284A1 (en) | 2015-01-09 | 2016-07-14 | Genentech, Inc. | (piperidin-3-yl)(naphthalen-2-yl)methanone derivatives and related compounds as inhibitors of the histone demethylase kdm2b for the treatment of cancer |
| CN107406429B (zh) | 2015-01-09 | 2021-07-06 | 基因泰克公司 | 哒嗪酮衍生物及其在治疗癌症中的用途 |
| WO2016112251A1 (en) | 2015-01-09 | 2016-07-14 | Genentech, Inc. | 4,5-dihydroimidazole derivatives and their use as histone demethylase (kdm2b) inhibitors |
| JP6709792B2 (ja) | 2015-01-29 | 2020-06-17 | ジェネンテック， インコーポレイテッド | 治療用化合物およびその使用 |
| JP6636031B2 (ja) | 2015-01-30 | 2020-01-29 | ジェネンテック， インコーポレイテッド | 治療用化合物およびその使用 |
| HUE064614T2 (hu) | 2015-02-25 | 2024-04-28 | Eisai R&D Man Co Ltd | Eljárás egy kinolin-származék keserû ízének elnyomására |
| MA41598A (fr) | 2015-02-25 | 2018-01-02 | Constellation Pharmaceuticals Inc | Composés thérapeutiques de pyridazine et leurs utilisations |
| CA2978226C (en) | 2015-03-04 | 2025-02-18 | Eisai R&D Management Co., Ltd. | COMBINATION OF A PD-1 ANTAGONIST AND A VEGFR/FGFR/RET TYROSINE KINASE INHIBITOR TO TREAT CANCER |
| RU2720810C2 (ru) | 2015-03-20 | 2020-05-13 | Чиа Тай Тяньцин Фармасьютикал Груп Ко., Лтд. | Соли производного хиназолина и способ их получения |
| WO2016164480A1 (en) | 2015-04-07 | 2016-10-13 | Genentech, Inc. | Antigen binding complex having agonistic activity and methods of use |
| PT3294770T (pt) | 2015-05-12 | 2020-12-04 | Hoffmann La Roche | Métodos terapêuticos e diagnósticos para o cancro |
| PL3303632T5 (pl) | 2015-05-29 | 2023-07-03 | F. Hoffmann-La Roche Ag | Terapeutyczne i diagnostyczne sposoby stosowane w nowotworze |
| AU2016274585A1 (en) | 2015-06-08 | 2017-12-14 | Genentech, Inc. | Methods of treating cancer using anti-OX40 antibodies |
| MX2017015937A (es) | 2015-06-08 | 2018-12-11 | Genentech Inc | Métodos de tratamiento del cáncer con anticuerpos anti-ox40 y antagonistas de unión al eje de pd-1. |
| BR112017027227B1 (pt) | 2015-06-16 | 2023-12-12 | Eisai R&D Management Co., Ltd | Agente anti-câncer |
| WO2016205320A1 (en) | 2015-06-17 | 2016-12-22 | Genentech, Inc. | Methods of treating locally advanced or metastatic breast cancers using pd-1 axis binding antagonists and taxanes |
| MX381976B (es) | 2015-08-20 | 2025-03-13 | Eisai R&D Man Co Ltd | Agente terapéutico contra tumores. |
| ES2862727T3 (es) | 2015-08-26 | 2021-10-07 | Fundacion Del Sector Publico Estatal Centro Nac De Investigaciones Oncologicas Carlos Iii F S P Cnio | Compuestos tricíclicos condensados como inhibidores de proteínas quinasas |
| SI3353210T1 (sl) | 2015-09-25 | 2025-03-31 | F. Hoffmann-La Roche Ag | Protitelesa proti TIGIT in postopki uporabe |
| DK3389662T3 (da) | 2015-12-16 | 2022-02-28 | Genentech Inc | Fremgangsmåde til fremstilling af tricykliske PI3K-inhibitorforbindelser og fremgangsmåder til anvendelse af disse til behandling af cancer |
| AU2017205089B2 (en) | 2016-01-08 | 2023-10-05 | F. Hoffmann-La Roche Ag | Methods of treating CEA-positive cancers using PD-1 axis binding antagonists and anti-CEA/anti-CD3 bispecific antibodies |
| CN105732522A (zh) * | 2016-02-01 | 2016-07-06 | 刘平 | 一种治疗牙周炎的药物组合物 |
| CN114395624A (zh) | 2016-02-29 | 2022-04-26 | 基因泰克公司 | 用于癌症的治疗和诊断方法 |
| EP3865511A1 (en) | 2016-04-14 | 2021-08-18 | F. Hoffmann-La Roche AG | Anti-rspo3 antibodies and methods of use |
| CN109072311A (zh) | 2016-04-15 | 2018-12-21 | 豪夫迈·罗氏有限公司 | 用于癌症的诊断和治疗方法 |
| ES2850428T3 (es) | 2016-04-15 | 2021-08-30 | Hoffmann La Roche | Procedimientos de monitorización y tratamiento del cáncer |
| WO2017181079A2 (en) | 2016-04-15 | 2017-10-19 | Genentech, Inc. | Methods for monitoring and treating cancer |
| CN115028617A (zh) | 2016-05-24 | 2022-09-09 | 基因泰克公司 | Cbp/ep300的杂环抑制剂及其在治疗癌症中的用途 |
| JP7014736B2 (ja) | 2016-05-24 | 2022-02-01 | ジェネンテック， インコーポレイテッド | がんの処置のためのピラゾロピリジン誘導体 |
| WO2017214373A1 (en) | 2016-06-08 | 2017-12-14 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| EP3494139B1 (en) | 2016-08-05 | 2022-01-12 | F. Hoffmann-La Roche AG | Multivalent and multiepitopic anitibodies having agonistic activity and methods of use |
| CN109476748B (zh) | 2016-08-08 | 2023-05-23 | 豪夫迈·罗氏有限公司 | 用于癌症的治疗和诊断方法 |
| AU2017339517B2 (en) | 2016-10-06 | 2024-03-14 | Foundation Medicine, Inc. | Therapeutic and diagnostic methods for cancer |
| WO2018078143A1 (en) | 2016-10-28 | 2018-05-03 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Means and methods for determining efficacy of anti-egfr inhibitors in colorectal cancer (crc) therapy |
| JP2019535250A (ja) | 2016-10-29 | 2019-12-12 | ジェネンテック， インコーポレイテッド | 抗ｍｉｃ抗体及び使用方法 |
| KR102539920B1 (ko) | 2017-02-08 | 2023-06-05 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 종양-치료용 약제학적 조성물 |
| WO2018160841A1 (en) | 2017-03-01 | 2018-09-07 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| EP3609537A1 (en) | 2017-04-13 | 2020-02-19 | H. Hoffnabb-La Roche Ag | An interleukin-2 immunoconjugate, a cd40 agonist, and optionally a pd-1 axis binding antagonist for use in methods of treating cancer |
| RU2019134940A (ru) | 2017-05-16 | 2021-06-16 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Лечение гепатоцеллюлярной карциномы |
| CN111492245A (zh) | 2017-07-21 | 2020-08-04 | 基因泰克公司 | 癌症的治疗和诊断方法 |
| JP2020530297A (ja) | 2017-08-11 | 2020-10-22 | ジェネンテック， インコーポレイテッド | 抗ｃｄ８抗体及びその使用 |
| WO2019051296A1 (en) | 2017-09-08 | 2019-03-14 | Genentech, Inc. | DIAGNOSTIC AND THERAPEUTIC METHODS OF CANCER |
| EP3710001B1 (en) | 2017-10-27 | 2025-06-18 | University Of Virginia Patent Foundation | Compounds and methods for regulating, limiting, or inhibiting avil expression |
| WO2019090263A1 (en) | 2017-11-06 | 2019-05-09 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| EP3740756A4 (en) | 2018-01-15 | 2021-10-27 | Epiaxis Therapeutics Pty Ltd | AGENTS AND METHODS FOR PREDICTING THE THERAPEUTIC RESPONSE |
| MX2020008882A (es) | 2018-02-26 | 2021-01-08 | Genentech Inc | Dosificación para tratamiento con anticuerpos antagonistas anti-tigit y anti-pd-l1. |
| EP3797173A2 (en) | 2018-05-21 | 2021-03-31 | Nanostring Technologies, Inc. | Molecular gene signatures and methods of using same |
| MA52968A (fr) | 2018-06-23 | 2021-04-28 | Hoffmann La Roche | Méthodes de traitement du cancer du poumon à l'aide d'un antagoniste de liaison à l'axe pd-1, d'un agent de platine et d'un inhibiteur de la topoisomérase ii |
| KR20210034622A (ko) | 2018-07-18 | 2021-03-30 | 제넨테크, 인크. | Pd-1 축 결합 길항제, 항 대사제, 및 백금 제제를 이용한 폐암 치료 방법 |
| EP3847154A1 (en) | 2018-09-03 | 2021-07-14 | F. Hoffmann-La Roche AG | Carboxamide and sulfonamide derivatives useful as tead modulators |
| MX2021003214A (es) | 2018-09-19 | 2021-05-12 | Genentech Inc | Metodos terapeuticos y de diagnostico para el cancer de vejiga. |
| PL3857230T3 (pl) | 2018-09-21 | 2023-10-16 | F. Hoffmann-La Roche Ag | Sposoby diagnostyczne dla potrójnie ujemnego raka piersi |
| EP3867405A4 (en) | 2018-10-17 | 2022-07-20 | The University of Queensland | Epigenetic biomarker and uses therefor |
| CN113196061A (zh) | 2018-10-18 | 2021-07-30 | 豪夫迈·罗氏有限公司 | 肉瘤样肾癌的诊断和治疗方法 |
| US12180207B2 (en) | 2018-12-19 | 2024-12-31 | Array Biopharma Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as inhibitors of FGFR tyrosine kinases |
| CN113474337A (zh) | 2018-12-19 | 2021-10-01 | 奥瑞生物药品公司 | 作为fgfr抑制剂用于治疗癌症的7-((3，5-二甲氧基苯基)氨基)喹喔啉衍生物 |
| WO2020163589A1 (en) | 2019-02-08 | 2020-08-13 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| AU2020228383A1 (en) | 2019-02-27 | 2021-09-23 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-CD20 or anti-CD38 antibodies |
| EP3931565A4 (en) | 2019-02-27 | 2023-04-12 | Epiaxis Therapeutics Pty Ltd | METHODS AND MEANS OF EVALUATING T-CELL FUNCTION AND PREDICTING RESPONSE TO THERAPY |
| WO2020223233A1 (en) | 2019-04-30 | 2020-11-05 | Genentech, Inc. | Prognostic and therapeutic methods for colorectal cancer |
| JP2022530674A (ja) | 2019-05-03 | 2022-06-30 | ジェネンテック， インコーポレイテッド | 抗ｐｄ－ｌ１抗体を用いたがんの処置方法 |
| CN112300279A (zh) | 2019-07-26 | 2021-02-02 | 上海复宏汉霖生物技术股份有限公司 | 针对抗cd73抗体和变体的方法和组合物 |
| EP4025608A1 (en) | 2019-09-04 | 2022-07-13 | F. Hoffmann-La Roche AG | Cd8 binding agents and uses thereof |
| WO2021062085A1 (en) | 2019-09-27 | 2021-04-01 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
| WO2021083949A1 (en) | 2019-10-29 | 2021-05-06 | F. Hoffmann-La Roche Ag | Bifunctional compounds for the treatment of cancer |
| EP4055388A1 (en) | 2019-11-06 | 2022-09-14 | Genentech, Inc. | Diagnostic and therapeutic methods for treatment of hematologic cancers |
| AU2020381458A1 (en) | 2019-11-13 | 2022-05-12 | Genentech, Inc. | Therapeutic compounds and methods of use |
| CN110963972A (zh) * | 2019-11-21 | 2020-04-07 | 苏州明锐医药科技有限公司 | 一种喹唑啉衍生物及其制备方法与药物用途 |
| US11845799B2 (en) | 2019-12-13 | 2023-12-19 | Genentech, Inc. | Anti-Ly6G6D antibodies and methods of use |
| AU2020408562A1 (en) | 2019-12-20 | 2022-06-23 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
| WO2021194481A1 (en) | 2020-03-24 | 2021-09-30 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
| KR20220133243A (ko) | 2020-01-27 | 2022-10-04 | 제넨테크, 인크. | 항 tigit 길항제 항체를 이용한 암의 치료 방법 |
| WO2021177980A1 (en) | 2020-03-06 | 2021-09-10 | Genentech, Inc. | Combination therapy for cancer comprising pd-1 axis binding antagonist and il6 antagonist |
| CN115698717A (zh) | 2020-04-03 | 2023-02-03 | 基因泰克公司 | 癌症的治疗和诊断方法 |
| JP2023523450A (ja) | 2020-04-28 | 2023-06-05 | ジェネンテック， インコーポレイテッド | 非小細胞肺がん免疫療法のための方法及び組成物 |
| EP4164627A1 (en) | 2020-06-16 | 2023-04-19 | Genentech, Inc. | Methods and compositions for treating triple-negative breast cancer |
| US20210395366A1 (en) | 2020-06-18 | 2021-12-23 | Genentech, Inc. | Treatment with anti-tigit antibodies and pd-1 axis binding antagonists |
| US11787775B2 (en) | 2020-07-24 | 2023-10-17 | Genentech, Inc. | Therapeutic compounds and methods of use |
| CN116568824A (zh) | 2020-08-03 | 2023-08-08 | 基因泰克公司 | 淋巴瘤的诊断和治疗方法 |
| EP4196612A1 (en) | 2020-08-12 | 2023-06-21 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| WO2022066805A1 (en) | 2020-09-23 | 2022-03-31 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
| CA3193952A1 (en) | 2020-10-05 | 2022-04-14 | Bernard Martin Fine | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
| WO2022133345A1 (en) | 2020-12-18 | 2022-06-23 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
| CA3210553A1 (en) | 2021-02-12 | 2022-08-18 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydroazepine derivatives for the treatment of cancer |
| EP4347603A1 (en) | 2021-05-25 | 2024-04-10 | Erasca, Inc. | Sulfur-containing heteroaromatic tricyclic kras inhibitors |
| US20240293558A1 (en) | 2021-06-16 | 2024-09-05 | Erasca, Inc. | Kras inhibitor conjugates |
| TW202321261A (zh) | 2021-08-10 | 2023-06-01 | 美商伊瑞斯卡公司 | 選擇性ｋｒａｓ抑制劑 |
| EP4436969A2 (en) | 2021-11-24 | 2024-10-02 | Genentech, Inc. | Bicyclic therapeutic compounds and methods of use in the treatment of cancer |
| JP2024541508A (ja) | 2021-11-24 | 2024-11-08 | ジェネンテック， インコーポレイテッド | 治療用インダゾール化合物およびがんの治療における使用方法 |
| CN114634453B (zh) * | 2022-03-15 | 2023-10-10 | 沈阳工业大学 | 喹唑啉衍生物制备方法及其应用 |
| EP4504780A1 (en) | 2022-04-01 | 2025-02-12 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
| WO2023219613A1 (en) | 2022-05-11 | 2023-11-16 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
| KR20250022049A (ko) | 2022-06-07 | 2025-02-14 | 제넨테크, 인크. | 항-pd-l1 길항제 및 항-tigit 길항제 항체를 포함하는, 폐암 치료의 효율을 결정하는 방법 |
| EP4554978A1 (en) | 2022-07-13 | 2025-05-21 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
| JP2025523845A (ja) | 2022-07-19 | 2025-07-25 | ジェネンテック， インコーポレイテッド | 抗ｆｃｒｈ５／抗ｃｄ３二重特異性抗体による処置のための投薬 |
| TW202417001A (zh) | 2022-08-11 | 2024-05-01 | 瑞士商赫孚孟拉羅股份公司 | 雙環四氫吖呯衍生物 |
| CN119677733A (zh) | 2022-08-11 | 2025-03-21 | 豪夫迈·罗氏有限公司 | 双环四氢硫氮杂䓬衍生物 |
| AR130169A1 (es) | 2022-08-11 | 2024-11-13 | Hoffmann La Roche | Derivados de tetrahidrotiazepina bicíclicos |
| CR20250042A (es) | 2022-08-11 | 2025-03-25 | Hoffmann La Roche | Derivados de tetrahidrotiazepina bicíclicos |
| JP2025538859A (ja) | 2022-10-21 | 2025-12-02 | 公益財団法人川崎市産業振興財団 | 非吸着性またはスーパーステルス小胞 |
| AU2023367741A1 (en) | 2022-10-25 | 2025-05-01 | Genentech, Inc. | Therapeutic and diagnostic methods for multiple myeloma |
| WO2024173842A1 (en) | 2023-02-17 | 2024-08-22 | Erasca, Inc. | Kras inhibitors |
| AU2024270495A1 (en) | 2023-05-05 | 2025-10-09 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
| TW202504641A (zh) | 2023-06-08 | 2025-02-01 | 美商建南德克公司 | 用於淋巴瘤之診斷及治療方法的巨噬細胞特徵 |
| WO2025024257A1 (en) | 2023-07-21 | 2025-01-30 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| TW202515614A (zh) | 2023-08-25 | 2025-04-16 | 美商建南德克公司 | 治療非小細胞肺癌之方法及組成物 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RO121900B1 (ro) * | 1996-04-12 | 2008-07-30 | Warner-Lambert Company | Compuşi inhibitori, ireversibili, ai tirozin kinazelor, compoziţie farmaceutică care îi conţine şi utilizarea acestora |
-
1999
- 1999-09-23 EP EP99949821A patent/EP1131304B1/en not_active Expired - Lifetime
- 1999-09-23 NZ NZ527718A patent/NZ527718A/en unknown
- 1999-09-23 CA CA002349721A patent/CA2349721A1/en not_active Abandoned
- 1999-09-23 DK DK99949821T patent/DK1131304T3/da active
- 1999-09-23 PL PL99347717A patent/PL347717A1/xx not_active IP Right Cessation
- 1999-09-23 KR KR1020017006276A patent/KR20010080491A/ko not_active Ceased
- 1999-09-23 GE GEAP19995950A patent/GEP20032997B/en unknown
- 1999-09-23 DE DE69904358T patent/DE69904358T2/de not_active Expired - Fee Related
- 1999-09-23 NZ NZ512189A patent/NZ512189A/en unknown
- 1999-09-23 WO PCT/US1999/022116 patent/WO2000031048A1/en not_active Ceased
- 1999-09-23 AT AT99949821T patent/ATE229008T1/de not_active IP Right Cessation
- 1999-09-23 BR BR9915487-0A patent/BR9915487A/pt not_active IP Right Cessation
- 1999-09-23 IL IL14308999A patent/IL143089A0/xx unknown
- 1999-09-23 PT PT99949821T patent/PT1131304E/pt unknown
- 1999-09-23 US US09/831,991 patent/US6344455B1/en not_active Expired - Fee Related
- 1999-09-23 ES ES99949821T patent/ES2188254T3/es not_active Expired - Lifetime
- 1999-09-23 CN CNB998146358A patent/CN1160338C/zh not_active Expired - Fee Related
- 1999-09-23 CZ CZ20011759A patent/CZ20011759A3/cs unknown
- 1999-09-23 EA EA200100546A patent/EA003786B1/ru not_active IP Right Cessation
- 1999-09-23 AU AU62612/99A patent/AU763626B2/en not_active Ceased
- 1999-09-23 JP JP2000583876A patent/JP3687900B2/ja not_active Expired - Fee Related
- 1999-09-23 SK SK657-2001A patent/SK283688B6/sk unknown
- 1999-09-23 EE EEP200100271A patent/EE200100271A/xx unknown
- 1999-09-23 HU HU0104211A patent/HUP0104211A3/hu unknown
- 1999-11-18 CO CO99072597A patent/CO5150185A1/es unknown
- 1999-11-18 PE PE1999001167A patent/PE20001242A1/es not_active Application Discontinuation
- 1999-11-18 AR ARP990105858A patent/AR023706A1/es unknown
- 1999-11-18 UY UY25809A patent/UY25809A1/es unknown
-
2001
- 2001-05-02 ZA ZA200103535A patent/ZA200103535B/en unknown
- 2001-05-18 NO NO20012465A patent/NO319357B1/no unknown
- 2001-06-15 BG BG105608A patent/BG105608A/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1131304B1 (en) | N- 4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide, an irreversible inhibitor of tyrosine kinases | |
| US6127374A (en) | Irreversible inhibitors of tyrosine kinases | |
| US6153617A (en) | Irreversible bicyclic inhibitors of tyrosine kinases | |
| US6602863B1 (en) | Irreversible inhibitors of tyrosine kinases | |
| MXPA00010610A (es) | Mesilato de n-(e-etinilfenilamino)-6,7-bis (2-metoxietoxi)-4-quinazolinamina, anhidro y monohidratado. | |
| HK1041695B (en) | N-[4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide, an irreversible inhibitor of tyrosine kinases | |
| HK1064675B (en) | Irreversible inhibitors of tyrosine kinases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RENW | Renewal (renewal fees accepted) | ||
| PSEA | Patent sealed |