AU2011282973B2 - 6-(1-methyl-1H-pyrazol-4-yl)-3-(2-methyl-2H-indazol -5-ylthio)-[1,2,4] triazolo [4,3-b]pyridazine as a c-Met inhibitor - Google Patents
6-(1-methyl-1H-pyrazol-4-yl)-3-(2-methyl-2H-indazol -5-ylthio)-[1,2,4] triazolo [4,3-b]pyridazine as a c-Met inhibitor Download PDFInfo
- Publication number
- AU2011282973B2 AU2011282973B2 AU2011282973A AU2011282973A AU2011282973B2 AU 2011282973 B2 AU2011282973 B2 AU 2011282973B2 AU 2011282973 A AU2011282973 A AU 2011282973A AU 2011282973 A AU2011282973 A AU 2011282973A AU 2011282973 B2 AU2011282973 B2 AU 2011282973B2
- Authority
- AU
- Australia
- Prior art keywords
- compound
- cancer
- methyl
- met
- salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000003112 inhibitor Substances 0.000 title abstract description 10
- JYXHZDNTBJUJNH-UHFFFAOYSA-N 3-(2-methylindazol-5-yl)sulfanyl-6-(1-methylpyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C1=NN(C)C=C1C1=NN2C(SC3=CC4=CN(C)N=C4C=C3)=NN=C2C=C1 JYXHZDNTBJUJNH-UHFFFAOYSA-N 0.000 title 1
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 41
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 201000011510 cancer Diseases 0.000 claims abstract description 21
- 150000001875 compounds Chemical class 0.000 claims description 137
- 238000000034 method Methods 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 13
- 230000002496 gastric effect Effects 0.000 claims description 11
- 208000005017 glioblastoma Diseases 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 210000000481 breast Anatomy 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 5
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 5
- 206010017758 gastric cancer Diseases 0.000 claims description 5
- 201000011549 stomach cancer Diseases 0.000 claims description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical class OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 8
- 230000001404 mediated effect Effects 0.000 abstract description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- 210000004027 cell Anatomy 0.000 description 23
- 239000000243 solution Substances 0.000 description 21
- 239000000203 mixture Substances 0.000 description 18
- 238000003556 assay Methods 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 230000005764 inhibitory process Effects 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 230000003285 pharmacodynamic effect Effects 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 239000007787 solid Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 8
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 8
- 230000002459 sustained effect Effects 0.000 description 8
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 8
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 229960001484 edetic acid Drugs 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 239000007983 Tris buffer Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 230000004614 tumor growth Effects 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 239000011534 wash buffer Substances 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- 241000220479 Acacia Species 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 239000006166 lysate Substances 0.000 description 4
- 238000002552 multiple reaction monitoring Methods 0.000 description 4
- 230000026731 phosphorylation Effects 0.000 description 4
- 238000006366 phosphorylation reaction Methods 0.000 description 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000011550 stock solution Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- FIQGETDPEXQPPK-UHFFFAOYSA-N 5-iodo-2-methylindazole Chemical compound C1=C(I)C=CC2=NN(C)C=C21 FIQGETDPEXQPPK-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000005921 Phosmet Substances 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000008482 dysregulation Effects 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- LMNZTLDVJIUSHT-UHFFFAOYSA-N phosmet Chemical compound C1=CC=C2C(=O)N(CSP(=S)(OC)OC)C(=O)C2=C1 LMNZTLDVJIUSHT-UHFFFAOYSA-N 0.000 description 3
- 230000036470 plasma concentration Effects 0.000 description 3
- 230000006920 protein precipitation Effects 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
- 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 2
- XBTOSRUBOXQWBO-UHFFFAOYSA-N 1h-indazol-5-amine Chemical compound NC1=CC=C2NN=CC2=C1 XBTOSRUBOXQWBO-UHFFFAOYSA-N 0.000 description 2
- 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 2
- LIRXMNGKIROHGY-UHFFFAOYSA-N 3-chloro-6-(1-methylpyrazol-4-yl)pyridazine Chemical compound C1=NN(C)C=C1C1=CC=C(Cl)N=N1 LIRXMNGKIROHGY-UHFFFAOYSA-N 0.000 description 2
- CGCHCLICSHIAAM-UHFFFAOYSA-N 5-iodo-1h-indazole Chemical compound IC1=CC=C2NN=CC2=C1 CGCHCLICSHIAAM-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 108010090804 Streptavidin Proteins 0.000 description 2
- MTPVKCALSWHVLT-UHFFFAOYSA-N [6-(1-methylpyrazol-4-yl)pyridazin-3-yl]hydrazine Chemical compound C1=NN(C)C=C1C1=CC=C(NN)N=N1 MTPVKCALSWHVLT-UHFFFAOYSA-N 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000000622 liquid--liquid extraction Methods 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 208000037819 metastatic cancer Diseases 0.000 description 2
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 2
- 210000003739 neck Anatomy 0.000 description 2
- 238000003305 oral gavage Methods 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000012134 supernatant fraction Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- -1 trimethyloxonium tetrafluoroborate Chemical compound 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- QQQZEFAUOMUXLS-UHFFFAOYSA-N (1-diphenylphosphanyl-9,9-dimethylxanthen-2-yl)-diphenylphosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C1=C2C(C)(C)C3=CC=CC=C3OC2=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QQQZEFAUOMUXLS-UHFFFAOYSA-N 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- BJMSXWLXFYZHIU-UHFFFAOYSA-N 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound CN1C=CC(B2OC(C)(C)C(C)(C)O2)=N1 BJMSXWLXFYZHIU-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- GUSWJGOYDXFJSI-UHFFFAOYSA-N 3,6-dichloropyridazine Chemical compound ClC1=CC=C(Cl)N=N1 GUSWJGOYDXFJSI-UHFFFAOYSA-N 0.000 description 1
- WSGURAYTCUVDQL-UHFFFAOYSA-N 5-nitro-1h-indazole Chemical compound [O-][N+](=O)C1=CC=C2NN=CC2=C1 WSGURAYTCUVDQL-UHFFFAOYSA-N 0.000 description 1
- ZFDDTPYVXBYWLZ-UHFFFAOYSA-N 6-(1-methylpyrazol-4-yl)-2h-[1,2,4]triazolo[4,3-b]pyridazine-3-thione Chemical compound C1=NN(C)C=C1C1=NN2C(S)=NN=C2C=C1 ZFDDTPYVXBYWLZ-UHFFFAOYSA-N 0.000 description 1
- 108091023020 Aldehyde Oxidase Proteins 0.000 description 1
- 102000048262 Aldehyde oxidases Human genes 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 101710178035 Chorismate synthase 2 Proteins 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 101710152694 Cysteine synthase 2 Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000027927 Hereditary papillary renal cell carcinoma Diseases 0.000 description 1
- 101000898034 Homo sapiens Hepatocyte growth factor Proteins 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- SIOXPEMLGUPBBT-UHFFFAOYSA-N Picolinic acid Natural products OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 239000012083 RIPA buffer Substances 0.000 description 1
- BCZUAADEACICHN-UHFFFAOYSA-N SGX-523 Chemical compound C1=NN(C)C=C1C1=NN2C(SC=3C=C4C=CC=NC4=CC=3)=NN=C2C=C1 BCZUAADEACICHN-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 239000013024 dilution buffer Substances 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 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
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 102000057308 human HGF Human genes 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- RZSCFTDHFNHMOR-UHFFFAOYSA-N n-(2,4-difluorophenyl)-2-[3-(trifluoromethyl)phenoxy]pyridine-3-carboxamide;1,1-dimethyl-3-(4-propan-2-ylphenyl)urea Chemical compound CC(C)C1=CC=C(NC(=O)N(C)C)C=C1.FC1=CC(F)=CC=C1NC(=O)C1=CC=CN=C1OC1=CC=CC(C(F)(F)F)=C1 RZSCFTDHFNHMOR-UHFFFAOYSA-N 0.000 description 1
- 238000004848 nephelometry Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 201000002689 pediatric hepatocellular carcinoma Diseases 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 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
- 230000002265 prevention Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 108091006082 receptor inhibitors Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- VXKWYPOMXBVZSJ-UHFFFAOYSA-N tetramethyltin Chemical compound C[Sn](C)(C)C VXKWYPOMXBVZSJ-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 230000005751 tumor progression Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36933510P | 2010-07-30 | 2010-07-30 | |
| US61/369,335 | 2010-07-30 | ||
| PCT/US2011/044926 WO2012015677A1 (en) | 2010-07-30 | 2011-07-22 | 6- (1-methyl-1h-pyrazol-4-yl)-3-(2-methyl-2h-indazol-5- |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2011282973A1 AU2011282973A1 (en) | 2013-01-10 |
| AU2011282973B2 true AU2011282973B2 (en) | 2014-03-20 |
Family
ID=44513148
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2011282973A Expired - Fee Related AU2011282973B2 (en) | 2010-07-30 | 2011-07-22 | 6-(1-methyl-1H-pyrazol-4-yl)-3-(2-methyl-2H-indazol -5-ylthio)-[1,2,4] triazolo [4,3-b]pyridazine as a c-Met inhibitor |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US8268836B2 (enExample) |
| EP (1) | EP2598144B1 (enExample) |
| JP (1) | JP5738412B2 (enExample) |
| KR (1) | KR20130052740A (enExample) |
| CN (1) | CN103002898A (enExample) |
| AR (1) | AR085183A1 (enExample) |
| AU (1) | AU2011282973B2 (enExample) |
| BR (1) | BR112013002211A2 (enExample) |
| CA (1) | CA2805494A1 (enExample) |
| EA (1) | EA201270818A1 (enExample) |
| ES (1) | ES2516940T3 (enExample) |
| IN (1) | IN2012MN02924A (enExample) |
| MX (1) | MX2013001247A (enExample) |
| TW (1) | TWI431008B (enExample) |
| WO (1) | WO2012015677A1 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6129956B2 (ja) * | 2012-05-09 | 2017-05-17 | イーライ リリー アンド カンパニー | 抗ｃ−Ｍｅｔ抗体 |
| CN103122000B (zh) * | 2012-09-03 | 2013-12-25 | 中美冠科生物技术（太仓）有限公司 | 用作抗肿瘤药物的高选择性的c-Met激酶抑制剂 |
| TWI667233B (zh) | 2013-12-19 | 2019-08-01 | 德商拜耳製藥公司 | 新穎吲唑羧醯胺，其製備方法、含彼等之醫藥製劑及其製造醫藥之用途 |
| US10386376B2 (en) | 2015-11-09 | 2019-08-20 | Jeimei, Llc | Sample container with integrated test strip |
| CN106924260B (zh) * | 2015-12-31 | 2018-05-25 | 北京浦润奥生物科技有限责任公司 | 化合物在制备用于治疗脑胶质瘤的药物中的用途 |
| BR112021018168B1 (pt) | 2019-03-21 | 2023-11-28 | Onxeo | Composição farmacêutica, combinação e kit compreendendo uma molécula dbait e um inibidor de quinase para o tratamento de câncer |
| US20220401436A1 (en) | 2019-11-08 | 2022-12-22 | INSERM (Institute National de la Santé et de la Recherche Médicale) | Methods for the treatment of cancers that have acquired resistance to kinase inhibitors |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| WO2024206858A1 (en) | 2023-03-30 | 2024-10-03 | Revolution Medicines, Inc. | Compositions for inducing ras gtp hydrolysis and uses thereof |
| WO2024229406A1 (en) | 2023-05-04 | 2024-11-07 | Revolution Medicines, Inc. | Combination therapy for a ras related disease or disorder |
| US20250049810A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| WO2025080946A2 (en) | 2023-10-12 | 2025-04-17 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
| US20250375445A1 (en) | 2024-06-07 | 2025-12-11 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| WO2025265060A1 (en) | 2024-06-21 | 2025-12-26 | Revolution Medicines, Inc. | Therapeutic compositions and methods for managing treatment-related effects |
| WO2026006747A1 (en) | 2024-06-28 | 2026-01-02 | Revolution Medicines, Inc. | Ras inhibitors |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008051808A2 (en) * | 2006-10-23 | 2008-05-02 | Sgx Pharmaceuticals, Inc. | Bicyclic triazoles as protein kinase modulators |
| WO2009056692A2 (fr) * | 2007-08-09 | 2009-05-07 | Sanofi-Aventis | Nouveaux derives de 6-triazolopyridazine-sulfanyl benzothiazole et benzimidazole, leur procede de preparation, leur application a titre de medicaments, compositions pharmaceutiques et nouvelle utilisation notamment comme inhibiteurs de met |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0619252A2 (pt) * | 2005-11-30 | 2011-09-20 | Vertex Pharma | inibidores de c-met e seus usos |
| US8217177B2 (en) | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| PE20121506A1 (es) | 2006-07-14 | 2012-11-26 | Amgen Inc | Compuestos triazolopiridinas como inhibidores de c-met |
| KR101083177B1 (ko) | 2006-10-23 | 2011-11-11 | 에스지엑스 파마슈티컬스, 인코포레이티드 | 트리아졸로-피리다진 단백질 키나제 조정제 |
| CN101558070A (zh) * | 2006-10-23 | 2009-10-14 | Sgx药品公司 | 三唑并哒嗪蛋白激酶调节剂 |
| CN102015716B (zh) | 2008-02-28 | 2014-09-17 | 诺华股份有限公司 | 用于治疗C-Met酪氨酸激酶介导的疾病的咪唑并[1,2-b]哒嗪衍生物 |
-
2011
- 2011-07-20 AR ARP110102632A patent/AR085183A1/es unknown
- 2011-07-22 KR KR1020137002382A patent/KR20130052740A/ko not_active Ceased
- 2011-07-22 BR BR112013002211A patent/BR112013002211A2/pt not_active IP Right Cessation
- 2011-07-22 JP JP2013521838A patent/JP5738412B2/ja not_active Expired - Fee Related
- 2011-07-22 US US13/188,496 patent/US8268836B2/en not_active Expired - Fee Related
- 2011-07-22 EP EP11741372.4A patent/EP2598144B1/en not_active Not-in-force
- 2011-07-22 WO PCT/US2011/044926 patent/WO2012015677A1/en not_active Ceased
- 2011-07-22 CN CN2011800371928A patent/CN103002898A/zh active Pending
- 2011-07-22 ES ES11741372.4T patent/ES2516940T3/es active Active
- 2011-07-22 CA CA2805494A patent/CA2805494A1/en not_active Abandoned
- 2011-07-22 TW TW100126076A patent/TWI431008B/zh not_active IP Right Cessation
- 2011-07-22 MX MX2013001247A patent/MX2013001247A/es not_active Application Discontinuation
- 2011-07-22 EA EA201270818A patent/EA201270818A1/ru unknown
- 2011-07-22 AU AU2011282973A patent/AU2011282973B2/en not_active Expired - Fee Related
-
2012
- 2012-12-31 IN IN2924MUN2012 patent/IN2012MN02924A/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008051808A2 (en) * | 2006-10-23 | 2008-05-02 | Sgx Pharmaceuticals, Inc. | Bicyclic triazoles as protein kinase modulators |
| WO2009056692A2 (fr) * | 2007-08-09 | 2009-05-07 | Sanofi-Aventis | Nouveaux derives de 6-triazolopyridazine-sulfanyl benzothiazole et benzimidazole, leur procede de preparation, leur application a titre de medicaments, compositions pharmaceutiques et nouvelle utilisation notamment comme inhibiteurs de met |
Also Published As
| Publication number | Publication date |
|---|---|
| MX2013001247A (es) | 2013-03-18 |
| ES2516940T3 (es) | 2014-10-31 |
| IN2012MN02924A (enExample) | 2015-06-12 |
| EA201270818A1 (ru) | 2013-05-30 |
| WO2012015677A1 (en) | 2012-02-02 |
| AU2011282973A1 (en) | 2013-01-10 |
| KR20130052740A (ko) | 2013-05-23 |
| CA2805494A1 (en) | 2012-02-02 |
| JP2013532687A (ja) | 2013-08-19 |
| EP2598144B1 (en) | 2014-08-13 |
| EP2598144A1 (en) | 2013-06-05 |
| TW201219393A (en) | 2012-05-16 |
| AR085183A1 (es) | 2013-09-18 |
| BR112013002211A2 (pt) | 2016-05-24 |
| WO2012015677A9 (en) | 2012-12-13 |
| CN103002898A (zh) | 2013-03-27 |
| US8268836B2 (en) | 2012-09-18 |
| JP5738412B2 (ja) | 2015-06-24 |
| TWI431008B (zh) | 2014-03-21 |
| US20120028984A1 (en) | 2012-02-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2011282973B2 (en) | 6-(1-methyl-1H-pyrazol-4-yl)-3-(2-methyl-2H-indazol -5-ylthio)-[1,2,4] triazolo [4,3-b]pyridazine as a c-Met inhibitor | |
| KR101546493B1 (ko) | 이미다조[1,2-ｂ]피리다진 및 피라졸로[1,5-ａ]피리미딘 유도체 및 단백질 키나제 억제제로서의 이의 용도 | |
| EP1560829B1 (en) | Pyrimido compounds having antiproliferative activity (ii) | |
| EP2850082B1 (en) | 1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido(2,3-d)pyrimidin-6-yl)phenyl)urea as Raf kinase inhibitor for the treatment of cancer | |
| EP2931722B1 (en) | Substituted 1h-pyrrolo [2,3-b]pyridine and 1h-pyrazolo [3, 4-b]pyridine derivatives as salt inducible kinase 2 (sik2) inhibitors | |
| WO2018017983A1 (en) | Compounds useful for treating disorders related to ret | |
| EP3294742B1 (en) | New (5,8-dimethyl-9-phenyl-5,8-dihydro-6h-pyrazolo[3,4-h)quinazolin-2-yl)-(1h-pyrazol-5-yl)-amines and theri derivatives as igf-1r/1r inhibitors. | |
| CN109689641B (zh) | 一种取代的2-氢-吡唑衍生物的晶型、盐型及其制备方法 | |
| CN107922354A (zh) | 作为idh2抑制剂的杂环化合物 | |
| EP4116302B1 (en) | Compound and preparation method thereof and application thereof in preparation of therapeutic anti-cancer drug | |
| WO2014135028A1 (zh) | 吡啶并嘧啶或嘧啶并嘧啶类化合物、其制备方法、药物组合物及其用途 | |
| EP3154547B1 (en) | Pyrimidine compounds and methods using the same | |
| WO2019029629A1 (en) | SUBSTITUTED PYRAZOLOPYRIMIDINES FOR USE AS KINASE INHIBITORS | |
| Zhao et al. | Discovery of thieno [3, 2-c] pyridin-4-amines as novel Bruton’s tyrosine kinase (BTK) inhibitors | |
| CN109400613B (zh) | 喹啉类化合物富马酸盐的晶型、制备方法、组合物与应用 | |
| Jin et al. | Pyrrolo [2, 3-b] pyridine-3-one derivatives as novel fibroblast growth factor receptor 4 inhibitors for the treatment of hepatocellular carcinoma | |
| EP3661936B1 (en) | [1,2,4]triazolo[4,3-a]pyrazin-6(5h)-one derivatives | |
| US20250074908A1 (en) | Salt of rock inhibitor, crystal form of salt, composition, and pharmaceutical use | |
| KR100714370B1 (ko) | 항종양 활성을 갖는〔1,2,4〕―트리아졸로〔4,3―ｃ〕퀴나졸린 유도체 | |
| CN116490507A (zh) | 用于治疗癌症的杂环包缩合cdc7激酶抑制剂 | |
| HK1249145A1 (zh) | 用於ttk抑制剂化疗的预後生物标记 | |
| HK1249145B (en) | Prognostic biomarkers for ttk inhibitor chemotherapy | |
| HK1175778A1 (en) | Process for preparing a 5h-pyrimido[5,4-d][2]benzazepine | |
| HK1175778B (en) | Process for preparing a 5h-pyrimido[5,4-d][2]benzazepine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK25 | Application lapsed reg. 22.2i(2) - failure to pay acceptance fee |