CA2572331A1 - C-met modulators and method of use - Google Patents
C-met modulators and method of use Download PDFInfo
- Publication number
- CA2572331A1 CA2572331A1 CA002572331A CA2572331A CA2572331A1 CA 2572331 A1 CA2572331 A1 CA 2572331A1 CA 002572331 A CA002572331 A CA 002572331A CA 2572331 A CA2572331 A CA 2572331A CA 2572331 A1 CA2572331 A1 CA 2572331A1
- Authority
- CA
- Canada
- Prior art keywords
- optionally substituted
- compound according
- 6alkyl
- mmol
- ring system
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 57
- 150000001875 compounds Chemical class 0.000 claims abstract description 212
- 239000000203 mixture Substances 0.000 claims abstract description 107
- 230000000694 effects Effects 0.000 claims abstract description 60
- 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 50
- 102000020233 phosphotransferase Human genes 0.000 claims abstract description 50
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 claims abstract description 41
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 40
- 201000010099 disease Diseases 0.000 claims abstract description 37
- 102000001253 Protein Kinase Human genes 0.000 claims abstract description 20
- 108060006633 protein kinase Proteins 0.000 claims abstract description 20
- 230000001413 cellular effect Effects 0.000 claims abstract description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 62
- 125000004122 cyclic group Chemical group 0.000 claims description 61
- 229920006395 saturated elastomer Polymers 0.000 claims description 58
- 125000000623 heterocyclic group Chemical group 0.000 claims description 50
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 45
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 125000003107 substituted aryl group Chemical group 0.000 claims description 32
- 229910052757 nitrogen Inorganic materials 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 23
- 125000005842 heteroatom Chemical group 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- 125000004429 atom Chemical group 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 19
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 230000005764 inhibitory process Effects 0.000 claims description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 230000002159 abnormal effect Effects 0.000 claims description 9
- 125000001118 alkylidene group Chemical group 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 9
- 238000006467 substitution reaction Methods 0.000 claims description 9
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- 238000012216 screening Methods 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 238000001727 in vivo Methods 0.000 claims description 7
- 239000002207 metabolite Substances 0.000 claims description 7
- 239000000651 prodrug Substances 0.000 claims description 7
- 229940002612 prodrug Drugs 0.000 claims description 7
- 125000002723 alicyclic group Chemical group 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 229910052698 phosphorus Inorganic materials 0.000 claims description 5
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 claims description 4
- YHIIJNLSGULWAA-UHFFFAOYSA-N 1,4-thiazinane 1-oxide Chemical compound O=S1CCNCC1 YHIIJNLSGULWAA-UHFFFAOYSA-N 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims description 4
- ZQHJAAMMKABEBS-UHFFFAOYSA-N morpholin-2-one Chemical compound O=C1CNCCO1 ZQHJAAMMKABEBS-UHFFFAOYSA-N 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 4
- 125000000732 arylene group Chemical group 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000005549 heteroarylene group Chemical group 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 3
- 230000002062 proliferating effect Effects 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
- 239000003937 drug carrier Substances 0.000 claims 1
- 108020003175 receptors Proteins 0.000 abstract description 17
- 230000035755 proliferation Effects 0.000 abstract description 7
- 125000002619 bicyclic group Chemical group 0.000 abstract description 6
- 230000002255 enzymatic effect Effects 0.000 abstract description 6
- 238000013508 migration Methods 0.000 abstract description 6
- 230000019491 signal transduction Effects 0.000 abstract description 6
- 230000012292 cell migration Effects 0.000 abstract description 5
- 230000001419 dependent effect Effects 0.000 abstract description 5
- 238000003782 apoptosis assay Methods 0.000 abstract description 3
- 230000004069 differentiation Effects 0.000 abstract description 3
- 230000005522 programmed cell death Effects 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 197
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- -1 CSFIR Proteins 0.000 description 84
- 239000000243 solution Substances 0.000 description 70
- 235000019439 ethyl acetate Nutrition 0.000 description 66
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
- 239000007787 solid Substances 0.000 description 53
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 43
- 238000005481 NMR spectroscopy Methods 0.000 description 43
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 42
- 239000011541 reaction mixture Substances 0.000 description 42
- 238000003756 stirring Methods 0.000 description 42
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 41
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 40
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
- 230000027455 binding Effects 0.000 description 32
- 101150041968 CDC13 gene Proteins 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- 238000006243 chemical reaction Methods 0.000 description 28
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 239000012267 brine Substances 0.000 description 23
- 229910052938 sodium sulfate Inorganic materials 0.000 description 23
- 235000011152 sodium sulphate Nutrition 0.000 description 23
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 22
- 206010028980 Neoplasm Diseases 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 21
- 238000003556 assay Methods 0.000 description 20
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 20
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- 235000017557 sodium bicarbonate Nutrition 0.000 description 19
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 19
- 239000002904 solvent Substances 0.000 description 19
- 229940086542 triethylamine Drugs 0.000 description 19
- 102000004169 proteins and genes Human genes 0.000 description 18
- 108090000623 proteins and genes Proteins 0.000 description 18
- 150000003254 radicals Chemical class 0.000 description 18
- 235000018102 proteins Nutrition 0.000 description 17
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 102000005962 receptors Human genes 0.000 description 16
- 102000004190 Enzymes Human genes 0.000 description 15
- 108090000790 Enzymes Proteins 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 235000019441 ethanol Nutrition 0.000 description 14
- 239000003446 ligand Substances 0.000 description 14
- 239000003921 oil Substances 0.000 description 14
- 235000019198 oils Nutrition 0.000 description 14
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 13
- 230000004663 cell proliferation Effects 0.000 description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 12
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 11
- 201000011510 cancer Diseases 0.000 description 11
- 239000001257 hydrogen Substances 0.000 description 11
- 229910052739 hydrogen Inorganic materials 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 10
- 239000012230 colorless oil Substances 0.000 description 10
- 230000000875 corresponding effect Effects 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 9
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 102000050554 Eph Family Receptors Human genes 0.000 description 8
- 108091008815 Eph receptors Proteins 0.000 description 8
- 206010025323 Lymphomas Diseases 0.000 description 8
- 239000007832 Na2SO4 Substances 0.000 description 8
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 8
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
- 230000004614 tumor growth Effects 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- 239000007821 HATU Substances 0.000 description 7
- 206010039491 Sarcoma Diseases 0.000 description 7
- 208000009956 adenocarcinoma Diseases 0.000 description 7
- 125000003710 aryl alkyl group Chemical group 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 125000004043 oxo group Chemical group O=* 0.000 description 7
- 229920001223 polyethylene glycol Polymers 0.000 description 7
- 125000005415 substituted alkoxy group Chemical group 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- PFMAFXYUHZDKPY-UHFFFAOYSA-N 1-[(4-fluorophenyl)carbamoyl]cyclopropane-1-carboxylic acid Chemical compound C=1C=C(F)C=CC=1NC(=O)C1(C(=O)O)CC1 PFMAFXYUHZDKPY-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 229920004890 Triton X-100 Polymers 0.000 description 6
- 239000013504 Triton X-100 Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 108060002566 ephrin Proteins 0.000 description 6
- 102000012803 ephrin Human genes 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 108020001756 ligand binding domains Proteins 0.000 description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 206010041823 squamous cell carcinoma Diseases 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- CMTHQKQPGXHACS-UHFFFAOYSA-N 3-fluoro-4-(7h-pyrrolo[2,3-d]pyrimidin-4-yloxy)aniline Chemical compound FC1=CC(N)=CC=C1OC1=NC=NC2=C1C=CN2 CMTHQKQPGXHACS-UHFFFAOYSA-N 0.000 description 5
- 201000009030 Carcinoma Diseases 0.000 description 5
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 5
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
- 201000004681 Psoriasis Diseases 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 229940024606 amino acid Drugs 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 239000006071 cream Substances 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- FEHLGOYZDFFMND-UHFFFAOYSA-N cyclopropane-1,1-dicarboxamide Chemical compound NC(=O)C1(C(N)=O)CC1 FEHLGOYZDFFMND-UHFFFAOYSA-N 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- TXKSDFSJPIWKQO-UHFFFAOYSA-N ethyl 4-chloro-7-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-d]pyrimidine-6-carboxylate Chemical compound N1=CN=C2N(COCC[Si](C)(C)C)C(C(=O)OCC)=CC2=C1Cl TXKSDFSJPIWKQO-UHFFFAOYSA-N 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 5
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 4
- PZYVZLVSUWOROY-UHFFFAOYSA-N 4-[1-(oxan-2-yl)pyrazolo[3,4-d]pyrimidin-4-yl]oxyaniline Chemical compound C1=CC(N)=CC=C1OC1=NC=NC2=C1C=NN2C1OCCCC1 PZYVZLVSUWOROY-UHFFFAOYSA-N 0.000 description 4
- MFYVNLJMAFHQEU-UHFFFAOYSA-N 4-[9-(oxan-2-yl)purin-6-yl]oxyaniline Chemical compound C1=CC(N)=CC=C1OC1=NC=NC2=C1N=CN2C1OCCCC1 MFYVNLJMAFHQEU-UHFFFAOYSA-N 0.000 description 4
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 206010024612 Lipoma Diseases 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 230000033115 angiogenesis Effects 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 238000005094 computer simulation Methods 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 201000011066 hemangioma Diseases 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000009545 invasion Effects 0.000 description 4
- 238000000021 kinase assay Methods 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 235000006408 oxalic acid Nutrition 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 229960002920 sorbitol Drugs 0.000 description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
- 239000003656 tris buffered saline Substances 0.000 description 4
- 229960004441 tyrosine Drugs 0.000 description 4
- UCDANKIMQBZXSO-JGVFFNPUSA-N (3s,8as)-3-(chloromethyl)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[2,1-c][1,4]oxazine Chemical compound C1O[C@H](CCl)CN2CCC[C@H]21 UCDANKIMQBZXSO-JGVFFNPUSA-N 0.000 description 3
- YJYHAHZIQBZRCN-UHFFFAOYSA-N 2,3,4,6,7,8,9,9a-octahydro-1h-quinolizin-3-ylmethanol Chemical compound C1CCCN2CC(CO)CCC21 YJYHAHZIQBZRCN-UHFFFAOYSA-N 0.000 description 3
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 3
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 3
- 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 3
- ZFJOLNZPELDZNC-UHFFFAOYSA-N 2-phenylacetyl isothiocyanate Chemical compound S=C=NC(=O)CC1=CC=CC=C1 ZFJOLNZPELDZNC-UHFFFAOYSA-N 0.000 description 3
- YHFNYEAHTNIHHJ-UHFFFAOYSA-N 4-(2-fluoro-4-nitrophenoxy)-7h-pyrrolo[2,3-d]pyrimidine Chemical compound FC1=CC([N+](=O)[O-])=CC=C1OC1=NC=NC2=C1C=CN2 YHFNYEAHTNIHHJ-UHFFFAOYSA-N 0.000 description 3
- HDOALQVIGYWUQP-UHFFFAOYSA-N 4-[2-fluoro-4-[[1-[(4-fluorophenyl)carbamoyl]cyclopropanecarbonyl]amino]phenoxy]-7-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-d]pyrimidine-6-carboxylic acid Chemical compound N1=CN=C2N(COCC[Si](C)(C)C)C(C(O)=O)=CC2=C1OC(C(=C1)F)=CC=C1NC(=O)C1(C(=O)NC=2C=CC(F)=CC=2)CC1 HDOALQVIGYWUQP-UHFFFAOYSA-N 0.000 description 3
- JVPZYGIDOLOTSM-UHFFFAOYSA-N 4-chloro-1-(oxan-2-yl)pyrazolo[3,4-d]pyrimidine Chemical compound N1=CC=2C(Cl)=NC=NC=2N1C1CCCCO1 JVPZYGIDOLOTSM-UHFFFAOYSA-N 0.000 description 3
- MJAMOZPOSSCWFV-UHFFFAOYSA-N 6-(4-nitrophenoxy)-9-(oxan-2-yl)purine Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1=NC=NC2=C1N=CN2C1OCCCC1 MJAMOZPOSSCWFV-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 3
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 3
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
- 201000008808 Fibrosarcoma Diseases 0.000 description 3
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 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 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 3
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 3
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 206010043276 Teratoma Diseases 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000036983 biotransformation Effects 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 230000004709 cell invasion Effects 0.000 description 3
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 3
- 239000005516 coenzyme A Substances 0.000 description 3
- 229940093530 coenzyme a Drugs 0.000 description 3
- 238000004590 computer program Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 3
- YEWDOWIBJZTOCM-UHFFFAOYSA-N diethyl 5-amino-1h-pyrrole-2,4-dicarboxylate Chemical compound CCOC(=O)C1=CC(C(=O)OCC)=C(N)N1 YEWDOWIBJZTOCM-UHFFFAOYSA-N 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 229940000406 drug candidate Drugs 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- GFXVSDKTQFNDES-UHFFFAOYSA-N ethyl 4-[2-fluoro-4-[[1-[(4-fluorophenyl)carbamoyl]cyclopropanecarbonyl]amino]phenoxy]-7-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-d]pyrimidine-6-carboxylate Chemical compound N1=CN=C2N(COCC[Si](C)(C)C)C(C(=O)OCC)=CC2=C1OC(C(=C1)F)=CC=C1NC(=O)C1(C(=O)NC=2C=CC(F)=CC=2)CC1 GFXVSDKTQFNDES-UHFFFAOYSA-N 0.000 description 3
- BMVGJDTURCUCNP-UHFFFAOYSA-N ethyl 4-chloro-7h-pyrrolo[2,3-d]pyrimidine-6-carboxylate Chemical compound N1=CN=C2NC(C(=O)OCC)=CC2=C1Cl BMVGJDTURCUCNP-UHFFFAOYSA-N 0.000 description 3
- RSJUPDUDZRGVRW-UHFFFAOYSA-N ethyl 4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidine-6-carboxylate Chemical compound N1C=NC(=O)C2=C1NC(C(=O)OCC)=C2 RSJUPDUDZRGVRW-UHFFFAOYSA-N 0.000 description 3
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 206010016629 fibroma Diseases 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 208000005017 glioblastoma Diseases 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 3
- 229910052740 iodine Chemical group 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- 230000005012 migration Effects 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 239000012038 nucleophile Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 3
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 241000701447 unidentified baculovirus Species 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 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 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-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
- VKPHHMBMJQKPRP-YUMQZZPRSA-N (3r,9as)-3-(chloromethyl)-3,4,6,7,9,9a-hexahydro-1h-[1,4]oxazino[3,4-c][1,4]oxazine Chemical compound C1COC[C@H]2CO[C@@H](CCl)CN21 VKPHHMBMJQKPRP-YUMQZZPRSA-N 0.000 description 2
- YFQSZFRZMNFZGB-BQBZGAKWSA-N (3s,8as)-3-(hydroxymethyl)-3,4,6,7,8,8a-hexahydro-2h-pyrrolo[1,2-a]pyrazin-1-one Chemical compound O=C1N[C@H](CO)CN2CCC[C@H]21 YFQSZFRZMNFZGB-BQBZGAKWSA-N 0.000 description 2
- SSMNLBMTCPCHEW-RYUDHWBXSA-N (3s,8as)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-3,4,6,7,8,8a-hexahydro-2h-pyrrolo[1,2-a]pyrazin-1-one Chemical compound O=C1N[C@H](CO[Si](C)(C)C(C)(C)C)CN2CCC[C@H]21 SSMNLBMTCPCHEW-RYUDHWBXSA-N 0.000 description 2
- PTSFHCVPJIAAAR-ULUSZKPHSA-N (8ar)-6-(chloromethyl)-1,3,5,6,8,8a-hexahydro-[1,3]thiazolo[4,3-c][1,4]oxazine Chemical compound C1OC(CCl)CN2CSC[C@H]21 PTSFHCVPJIAAAR-ULUSZKPHSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- ZIPURTBBOFIUNR-UHFFFAOYSA-N 1-(benzylcarbamoyl)cyclopropane-1-carboxylic acid Chemical compound C=1C=CC=CC=1CNC(=O)C1(C(=O)O)CC1 ZIPURTBBOFIUNR-UHFFFAOYSA-N 0.000 description 2
- KDXROTVXLGAFGW-UHFFFAOYSA-N 1-(phenylcarbamoyl)cyclopropane-1-carboxylic acid Chemical compound C=1C=CC=CC=1NC(=O)C1(C(=O)O)CC1 KDXROTVXLGAFGW-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- VFVHFJYRAAWDCK-UHFFFAOYSA-N 1-n'-(4-fluorophenyl)-1-n-[4-(1h-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl]cyclopropane-1,1-dicarboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1(C(=O)NC=2C=CC(OC=3C=4C=NNC=4N=CN=3)=CC=2)CC1 VFVHFJYRAAWDCK-UHFFFAOYSA-N 0.000 description 2
- MTLQUWLYBNOXML-UHFFFAOYSA-N 1-n'-(4-fluorophenyl)-1-n-[4-(7h-purin-6-yloxy)phenyl]cyclopropane-1,1-dicarboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1(C(=O)NC=2C=CC(OC=3C=4N=CNC=4N=CN=3)=CC=2)CC1 MTLQUWLYBNOXML-UHFFFAOYSA-N 0.000 description 2
- BLGYQUBVPNVYHY-UHFFFAOYSA-N 1-n'-[3-fluoro-4-[6-(2-morpholin-4-ylethylcarbamoyl)-7-(2-trimethylsilylethoxymethyl)pyrrolo[2,3-d]pyrimidin-4-yl]oxyphenyl]-1-n-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide Chemical compound N1=CN=C2N(COCC[Si](C)(C)C)C(C(=O)NCCN3CCOCC3)=CC2=C1OC(C(=C1)F)=CC=C1NC(=O)C1(C(=O)NC=2C=CC(F)=CC=2)CC1 BLGYQUBVPNVYHY-UHFFFAOYSA-N 0.000 description 2
- WGLLSSPDPJPLOR-UHFFFAOYSA-N 2,3-dimethylbut-2-ene Chemical compound CC(C)=C(C)C WGLLSSPDPJPLOR-UHFFFAOYSA-N 0.000 description 2
- BMPSUPGXDFHRFS-UHFFFAOYSA-N 2-phenyl-n-[[4-(1h-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl]carbamothioyl]acetamide Chemical compound C=1C=C(OC=2C=3C=NNC=3N=CN=2)C=CC=1NC(=S)NC(=O)CC1=CC=CC=C1 BMPSUPGXDFHRFS-UHFFFAOYSA-N 0.000 description 2
- FVBOXLDZEZKGHW-UHFFFAOYSA-N 2-phenyl-n-[[4-(7h-purin-6-yloxy)phenyl]carbamothioyl]acetamide Chemical compound C=1C=C(OC=2C=3N=CNC=3N=CN=2)C=CC=1NC(=S)NC(=O)CC1=CC=CC=C1 FVBOXLDZEZKGHW-UHFFFAOYSA-N 0.000 description 2
- BMCUERANXGNXQY-UHFFFAOYSA-N 3,4,6,7,9,9a-hexahydro-1h-[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl acetate Chemical compound C1COCC2COC(COC(=O)C)CN21 BMCUERANXGNXQY-UHFFFAOYSA-N 0.000 description 2
- VKPHHMBMJQKPRP-UHFFFAOYSA-N 3-(chloromethyl)-3,4,6,7,9,9a-hexahydro-1h-[1,4]oxazino[3,4-c][1,4]oxazine Chemical compound C1COCC2COC(CCl)CN21 VKPHHMBMJQKPRP-UHFFFAOYSA-N 0.000 description 2
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 201000003076 Angiosarcoma Diseases 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- 206010003571 Astrocytoma Diseases 0.000 description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-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
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 241000206672 Gelidium Species 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- 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 2
- 239000004471 Glycine Substances 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 208000001258 Hemangiosarcoma Diseases 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 2
- 208000018142 Leiomyosarcoma Diseases 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- 102000047918 Myelin Basic Human genes 0.000 description 2
- 101710107068 Myelin basic protein Proteins 0.000 description 2
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 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
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
- SNDFBMZJYGYZDQ-YUMQZZPRSA-N [(3s,8as)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[2,1-c][1,4]oxazin-3-yl]methanol Chemical compound C1O[C@H](CO)CN2CCC[C@H]21 SNDFBMZJYGYZDQ-YUMQZZPRSA-N 0.000 description 2
- USFGZYHXXXYUIA-UWVGGRQHSA-N [(3s,8as)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[2,1-c][1,4]oxazin-3-yl]methyl acetate Chemical compound C1O[C@H](COC(=O)C)CN2CCC[C@H]21 USFGZYHXXXYUIA-UWVGGRQHSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 229960003121 arginine Drugs 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 230000035578 autophosphorylation Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000008901 benefit 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
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 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 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 2
- 229960001948 caffeine Drugs 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 208000002458 carcinoid tumor Diseases 0.000 description 2
- 230000033077 cellular process Effects 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- FDKLLWKMYAMLIF-UHFFFAOYSA-N cyclopropane-1,1-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CC1 FDKLLWKMYAMLIF-UHFFFAOYSA-N 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000002532 enzyme inhibitor Substances 0.000 description 2
- 229940125532 enzyme inhibitor Drugs 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 125000001207 fluorophenyl group Chemical group 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000002496 gastric effect 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
- 229940080856 gleevec Drugs 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 229960002885 histidine Drugs 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 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
- 230000003993 interaction Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- 201000010260 leiomyoma Diseases 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 235000018977 lysine Nutrition 0.000 description 2
- 208000002780 macular degeneration Diseases 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- WRIRWRKPLXCTFD-UHFFFAOYSA-N malonamide Chemical compound NC(=O)CC(N)=O WRIRWRKPLXCTFD-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 206010027191 meningioma Diseases 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- PUQXMHMLGKCVRB-GJZGRUSLSA-N methyl (2s)-1-[(2s)-3-hydroxy-2-(phenylmethoxycarbonylamino)propyl]pyrrolidine-2-carboxylate Chemical compound COC(=O)[C@@H]1CCCN1C[C@@H](CO)NC(=O)OCC1=CC=CC=C1 PUQXMHMLGKCVRB-GJZGRUSLSA-N 0.000 description 2
- 208000025113 myeloid leukemia Diseases 0.000 description 2
- ZJRRFXJRPBXEHJ-UHFFFAOYSA-N n-(4-fluorophenyl)-n'-[3-fluoro-4-(7h-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl]propanediamide Chemical compound C1=CC(F)=CC=C1NC(=O)CC(=O)NC(C=C1F)=CC=C1OC1=NC=NC2=C1C=CN2 ZJRRFXJRPBXEHJ-UHFFFAOYSA-N 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 230000000771 oncological effect Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 239000011574 phosphorus Chemical group 0.000 description 2
- 229940068917 polyethylene glycols Drugs 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 235000011056 potassium acetate Nutrition 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 229960004063 propylene glycol Drugs 0.000 description 2
- 235000013772 propylene glycol Nutrition 0.000 description 2
- 125000004542 purin-6-yl group Chemical group N1=CN=C2N=CNC2=C1* 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 2
- 125000005551 pyridylene group Chemical group 0.000 description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 2
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000007423 screening assay Methods 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 229940126586 small molecule drug Drugs 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000005556 structure-activity relationship Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- HJWIRJGCSNBOJJ-ZACCUICWSA-N tert-butyl (3ar,6as)-5-methylsulfonyloxy-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrole-2-carboxylate Chemical compound C1C(OS(C)(=O)=O)C[C@@H]2CN(C(=O)OC(C)(C)C)C[C@@H]21 HJWIRJGCSNBOJJ-ZACCUICWSA-N 0.000 description 2
- XRNJMGKDWQLIJX-FGWVZKOKSA-N tert-butyl (3as,6ar)-5-(hydroxymethyl)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrole-2-carboxylate Chemical compound C1C(CO)C[C@@H]2CN(C(=O)OC(C)(C)C)C[C@@H]21 XRNJMGKDWQLIJX-FGWVZKOKSA-N 0.000 description 2
- DIDQRACXWWEPDZ-ULKQDVFKSA-N tert-butyl (3as,6ar)-5-hydroxy-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrole-2-carboxylate Chemical compound C1C(O)C[C@@H]2CN(C(=O)OC(C)(C)C)C[C@@H]21 DIDQRACXWWEPDZ-ULKQDVFKSA-N 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 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
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- UCDANKIMQBZXSO-SFYZADRCSA-N (3r,8ar)-3-(chloromethyl)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[2,1-c][1,4]oxazine Chemical compound C1O[C@@H](CCl)CN2CCC[C@@H]21 UCDANKIMQBZXSO-SFYZADRCSA-N 0.000 description 1
- UCDANKIMQBZXSO-YUMQZZPRSA-N (3r,8as)-3-(chloromethyl)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[2,1-c][1,4]oxazine Chemical compound C1O[C@@H](CCl)CN2CCC[C@H]21 UCDANKIMQBZXSO-YUMQZZPRSA-N 0.000 description 1
- UCDANKIMQBZXSO-HTQZYQBOSA-N (3s,8ar)-3-(chloromethyl)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[2,1-c][1,4]oxazine Chemical compound C1O[C@H](CCl)CN2CCC[C@@H]21 UCDANKIMQBZXSO-HTQZYQBOSA-N 0.000 description 1
- CZARQGWAPJFVJH-YUMQZZPRSA-N (3s,8as)-3-(hydroxymethyl)-2-methyl-3,4,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-1-one Chemical compound O=C1N(C)[C@H](CO)CN2CCC[C@H]21 CZARQGWAPJFVJH-YUMQZZPRSA-N 0.000 description 1
- KRNLDGREVSUHFN-STQMWFEESA-N (3s,8as)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-2-methyl-3,4,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-1-one Chemical compound O=C1N(C)[C@H](CO[Si](C)(C)C(C)(C)C)CN2CCC[C@H]21 KRNLDGREVSUHFN-STQMWFEESA-N 0.000 description 1
- VKPHHMBMJQKPRP-JGVFFNPUSA-N (3s,9as)-3-(chloromethyl)-3,4,6,7,9,9a-hexahydro-1h-[1,4]oxazino[3,4-c][1,4]oxazine Chemical compound C1COC[C@H]2CO[C@H](CCl)CN21 VKPHHMBMJQKPRP-JGVFFNPUSA-N 0.000 description 1
- ICLYJLBTOGPLMC-KVVVOXFISA-N (z)-octadec-9-enoate;tris(2-hydroxyethyl)azanium Chemical compound OCCN(CCO)CCO.CCCCCCCC\C=C/CCCCCCCC(O)=O ICLYJLBTOGPLMC-KVVVOXFISA-N 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- XLOVPKCQAPHUKK-UHFFFAOYSA-N 1,2,3,4,4a,5,8,8a-octahydronaphthalene Chemical compound C1C=CCC2CCCCC21 XLOVPKCQAPHUKK-UHFFFAOYSA-N 0.000 description 1
- SCZNXLWKYFICFV-UHFFFAOYSA-N 1,2,3,4,5,7,8,9-octahydropyrido[1,2-b]diazepine Chemical compound C1CCCNN2CCCC=C21 SCZNXLWKYFICFV-UHFFFAOYSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- WEERVPDNCOGWJF-UHFFFAOYSA-N 1,4-bis(ethenyl)benzene Chemical compound C=CC1=CC=C(C=C)C=C1 WEERVPDNCOGWJF-UHFFFAOYSA-N 0.000 description 1
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
- MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 1
- KPYPZGHLRKVTHJ-UHFFFAOYSA-N 1-n'-(4-fluorophenyl)-1-n-[4-[1-(oxan-2-yl)pyrazolo[3,4-d]pyrimidin-4-yl]oxyphenyl]cyclopropane-1,1-dicarboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1(C(=O)NC=2C=CC(OC=3C=4C=NN(C=4N=CN=3)C3OCCCC3)=CC=2)CC1 KPYPZGHLRKVTHJ-UHFFFAOYSA-N 0.000 description 1
- HVHQELNLBVVJJG-UHFFFAOYSA-N 1-n'-(4-fluorophenyl)-1-n-[4-[9-(oxan-2-yl)purin-6-yl]oxyphenyl]cyclopropane-1,1-dicarboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1(C(=O)NC=2C=CC(OC=3C=4N=CN(C=4N=CN=3)C3OCCCC3)=CC=2)CC1 HVHQELNLBVVJJG-UHFFFAOYSA-N 0.000 description 1
- QPMULYMBRFIZTH-UHFFFAOYSA-N 1-n-(4-fluorophenyl)-1-n'-[3-fluoro-4-(7h-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl]cyclopropane-1,1-dicarboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1(C(=O)NC=2C=C(F)C(OC=3C=4C=CNC=4N=CN=3)=CC=2)CC1 QPMULYMBRFIZTH-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
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 1
- UZURTQHPMXADGG-UHFFFAOYSA-N 2,3,3a,4,7,7a-hexahydro-1h-indene Chemical compound C1C=CCC2CCCC21 UZURTQHPMXADGG-UHFFFAOYSA-N 0.000 description 1
- PHXGAJLBHUUAKB-UHFFFAOYSA-N 2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound O1CCC2OCCC21 PHXGAJLBHUUAKB-UHFFFAOYSA-N 0.000 description 1
- XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 1
- XTGOWLIKIQLYRG-UHFFFAOYSA-N 2,3,4,5,6-pentafluoropyridine Chemical compound FC1=NC(F)=C(F)C(F)=C1F XTGOWLIKIQLYRG-UHFFFAOYSA-N 0.000 description 1
- FWUJIDULGWIBPD-UHFFFAOYSA-N 2-(1-phenylhex-5-en-1-yn-3-yl)naphthalene Chemical compound C=1C=C2C=CC=CC2=CC=1C(CC=C)C#CC1=CC=CC=C1 FWUJIDULGWIBPD-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
- WRFPVMFCRNYQNR-UHFFFAOYSA-N 2-hydroxyphenylalanine Chemical compound OC(=O)C(N)CC1=CC=CC=C1O WRFPVMFCRNYQNR-UHFFFAOYSA-N 0.000 description 1
- BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical group CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 1
- 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
- 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- FNWRXXFQHUUCJN-UHFFFAOYSA-N 2H-1,4-oxazin-3-ylmethyl methanesulfonate Chemical compound CS(=O)(=O)OCC=1COC=CN1 FNWRXXFQHUUCJN-UHFFFAOYSA-N 0.000 description 1
- LGCYVLDNGBSOOW-UHFFFAOYSA-N 2H-benzotriazol-4-ol 1-hydroxybenzotriazole Chemical compound OC1=CC=CC2=C1N=NN2.C1=CC=C2N(O)N=NC2=C1 LGCYVLDNGBSOOW-UHFFFAOYSA-N 0.000 description 1
- KWPQTFXULUUCGD-UHFFFAOYSA-N 3,4,5,7,8,9,10,10a-octahydropyrido[1,2-a][1,4]diazepine Chemical compound C1CCN=CC2CCCCN21 KWPQTFXULUUCGD-UHFFFAOYSA-N 0.000 description 1
- JBIHMFNMKHDTEE-UHFFFAOYSA-N 3,4,6,7,8,8a-hexahydro-2h-pyrrolo[1,2-a]pyrazin-1-one Chemical compound O=C1NCCN2CCCC12 JBIHMFNMKHDTEE-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- QMAHVAFURJBOFV-UHFFFAOYSA-N 4-(bromomethyl)-3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C(CBr)C([N+]([O-])=O)=C1 QMAHVAFURJBOFV-UHFFFAOYSA-N 0.000 description 1
- KWXVDUACPKJCCN-UHFFFAOYSA-N 4-[(3,4-diethoxyphenyl)methylamino]benzenecarboximidamide Chemical compound C1=C(OCC)C(OCC)=CC=C1CNC1=CC=C(C(N)=N)C=C1 KWXVDUACPKJCCN-UHFFFAOYSA-N 0.000 description 1
- YMXQUFUYCADCFL-UHFFFAOYSA-N 4-chloro-1h-pyrazolo[3,4-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=NN2 YMXQUFUYCADCFL-UHFFFAOYSA-N 0.000 description 1
- BPTCCCTWWAUJRK-UHFFFAOYSA-N 4-chloro-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=CN2 BPTCCCTWWAUJRK-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
- 125000005986 4-piperidonyl group Chemical group 0.000 description 1
- ORPHLVJBJOCHBR-UHFFFAOYSA-N 403-19-0 Chemical compound OC1=CC=C([N+]([O-])=O)C=C1F ORPHLVJBJOCHBR-UHFFFAOYSA-N 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- QSTASPNCKDPSAH-UHFFFAOYSA-N 6-chloro-9-(oxan-2-yl)purine Chemical compound C1=NC=2C(Cl)=NC=NC=2N1C1CCCCO1 QSTASPNCKDPSAH-UHFFFAOYSA-N 0.000 description 1
- SNZSSCZJMVIOCR-UHFFFAOYSA-N 7-azabicyclo[2.2.1]heptane Chemical compound C1CC2CCC1N2 SNZSSCZJMVIOCR-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 206010001233 Adenoma benign Diseases 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 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 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 102000007299 Amphiregulin Human genes 0.000 description 1
- 108010033760 Amphiregulin Proteins 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- 229930091051 Arenine Natural products 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
- 102400001242 Betacellulin Human genes 0.000 description 1
- 101800001382 Betacellulin Proteins 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 206010073106 Bone giant cell tumour malignant Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 208000009458 Carcinoma in Situ Diseases 0.000 description 1
- 206010008263 Cervical dysplasia Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 201000005262 Chondroma Diseases 0.000 description 1
- 208000005243 Chondrosarcoma Diseases 0.000 description 1
- 201000009047 Chordoma Diseases 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 206010048832 Colon adenoma Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 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
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 208000007033 Dysgerminoma Diseases 0.000 description 1
- 208000000471 Dysplastic Nevus Syndrome Diseases 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 201000009051 Embryonal Carcinoma Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- 206010014967 Ependymoma Diseases 0.000 description 1
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 208000007659 Fibroadenoma Diseases 0.000 description 1
- 206010053717 Fibrous histiocytoma Diseases 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 208000000527 Germinoma Diseases 0.000 description 1
- 208000007569 Giant Cell Tumors Diseases 0.000 description 1
- 201000005409 Gliomatosis cerebri Diseases 0.000 description 1
- 206010018404 Glucagonoma Diseases 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
- 206010018691 Granuloma Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 208000002927 Hamartoma Diseases 0.000 description 1
- 101800001649 Heparin-binding EGF-like growth factor Proteins 0.000 description 1
- 102400001369 Heparin-binding EGF-like growth factor Human genes 0.000 description 1
- 206010019629 Hepatic adenoma Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001005128 Homo sapiens LIM domain kinase 1 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 208000005045 Interdigitating dendritic cell sarcoma Diseases 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- JTTHKOPSMAVJFE-VIFPVBQESA-N L-homophenylalanine Chemical compound OC(=O)[C@@H](N)CCC1=CC=CC=C1 JTTHKOPSMAVJFE-VIFPVBQESA-N 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- JZKXXXDKRQWDET-QMMMGPOBSA-N L-m-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC(O)=C1 JZKXXXDKRQWDET-QMMMGPOBSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- 102100026023 LIM domain kinase 1 Human genes 0.000 description 1
- 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 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000002404 Liver Cell Adenoma Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000006644 Malignant Fibrous Histiocytoma Diseases 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
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- 208000014767 Myeloproliferative disease Diseases 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 125000000815 N-oxide group Chemical group 0.000 description 1
- 101150020251 NR13 gene Proteins 0.000 description 1
- 102400000058 Neuregulin-1 Human genes 0.000 description 1
- 108090000556 Neuregulin-1 Proteins 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 201000004404 Neurofibroma Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 201000010133 Oligodendroglioma Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 206010031149 Osteitis Diseases 0.000 description 1
- 208000000035 Osteochondroma Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 101100272976 Panax ginseng CYP716A53v2 gene Proteins 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 108010067902 Peptide Library Proteins 0.000 description 1
- 108010077495 Peptide oostatic hormone Proteins 0.000 description 1
- 208000007641 Pinealoma Diseases 0.000 description 1
- 102000001393 Platelet-Derived Growth Factor alpha Receptor Human genes 0.000 description 1
- 108010068588 Platelet-Derived Growth Factor alpha Receptor Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 101710098940 Pro-epidermal growth factor Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000008022 Proto-Oncogene Proteins c-met Human genes 0.000 description 1
- 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 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
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 208000005678 Rhabdomyoma Diseases 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- 208000000097 Sertoli-Leydig cell tumor Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102400001320 Transforming growth factor alpha Human genes 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
- 208000009311 VIPoma Diseases 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 1
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Chemical group 0.000 description 1
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 206010048214 Xanthoma Diseases 0.000 description 1
- 206010048215 Xanthomatosis Diseases 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
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 description 1
- HVVNJUAVDAZWCB-YFKPBYRVSA-N [(2s)-pyrrolidin-2-yl]methanol Chemical compound OC[C@@H]1CCCN1 HVVNJUAVDAZWCB-YFKPBYRVSA-N 0.000 description 1
- UCDFBOLUCCNTDQ-RXMQYKEDSA-N [(3r)-morpholin-3-yl]methanol Chemical compound OC[C@@H]1COCCN1 UCDFBOLUCCNTDQ-RXMQYKEDSA-N 0.000 description 1
- BMCUERANXGNXQY-VHSXEESVSA-N [(3r,9as)-3,4,6,7,9,9a-hexahydro-1h-[1,4]oxazino[3,4-c][1,4]oxazin-3-yl]methyl acetate Chemical compound C1COC[C@H]2CO[C@@H](COC(=O)C)CN21 BMCUERANXGNXQY-VHSXEESVSA-N 0.000 description 1
- VTDJDXOAGJTAKU-IUCAKERBSA-N [(3s,8as)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[2,1-c][1,4]oxazin-3-yl]methyl methanesulfonate Chemical compound C1O[C@H](COS(=O)(=O)C)CN2CCC[C@H]21 VTDJDXOAGJTAKU-IUCAKERBSA-N 0.000 description 1
- BMCUERANXGNXQY-UWVGGRQHSA-N [(3s,9as)-3,4,6,7,9,9a-hexahydro-1h-[1,4]oxazino[3,4-c][1,4]oxazin-3-yl]methyl acetate Chemical compound C1COC[C@H]2CO[C@H](COC(=O)C)CN21 BMCUERANXGNXQY-UWVGGRQHSA-N 0.000 description 1
- PNWWDRJAZASPST-SCSAIBSYSA-N [(4r)-1,3-thiazolidin-4-yl]methanol Chemical compound OC[C@@H]1CSCN1 PNWWDRJAZASPST-SCSAIBSYSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- CTCBPRXHVPZNHB-VQFZJOCSSA-N [[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate;(2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O.C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O CTCBPRXHVPZNHB-VQFZJOCSSA-N 0.000 description 1
- 239000003655 absorption accelerator Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012042 active reagent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 208000002718 adenomatoid tumor Diseases 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 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
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000005530 alkylenedioxy group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 238000011122 anti-angiogenic therapy Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000007080 aromatic substitution reaction Methods 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- AAMATCKFMHVIDO-UHFFFAOYSA-N azane;1h-pyrrole Chemical compound N.C=1C=CNC=1 AAMATCKFMHVIDO-UHFFFAOYSA-N 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
- 208000001119 benign fibrous histiocytoma Diseases 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 229960004217 benzyl alcohol Drugs 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 239000012867 bioactive agent Substances 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 208000018339 bone inflammation disease Diseases 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 201000009480 botryoid rhabdomyosarcoma Diseases 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 201000003149 breast fibroadenoma Diseases 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
- 201000002143 bronchus adenoma Diseases 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 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
- 238000004422 calculation algorithm Methods 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 125000005518 carboxamido group Chemical group 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 239000000460 chlorine Chemical group 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 201000005217 chondroblastoma Diseases 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 208000009060 clear cell adenocarcinoma Diseases 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
- 210000001072 colon Anatomy 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 201000010305 cutaneous fibrous histiocytoma Diseases 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 125000005507 decahydroisoquinolyl group Chemical group 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 239000012973 diazabicyclooctane Substances 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
- 230000029087 digestion Effects 0.000 description 1
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
- 229960005156 digoxin Drugs 0.000 description 1
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
- 125000004982 dihaloalkyl group Chemical group 0.000 description 1
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- XNMQEEKYCVKGBD-UHFFFAOYSA-N dimethylacetylene Natural products CC#CC XNMQEEKYCVKGBD-UHFFFAOYSA-N 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 238000002337 electrophoretic mobility shift assay Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 201000009409 embryonal rhabdomyosarcoma Diseases 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 201000003914 endometrial carcinoma Diseases 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 230000008472 epithelial growth Effects 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- JYGHNNMPKVPTKF-UHFFFAOYSA-N ethyl 3-amino-3-ethoxyprop-2-enoate;hydrochloride Chemical compound [Cl-].CCOC([NH3+])=CC(=O)OCC JYGHNNMPKVPTKF-UHFFFAOYSA-N 0.000 description 1
- VICYTAYPKBLQFB-UHFFFAOYSA-N ethyl 3-bromo-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CBr VICYTAYPKBLQFB-UHFFFAOYSA-N 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 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
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 108091071773 flk family Proteins 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 108010003374 fms-Like Tyrosine Kinase 3 Proteins 0.000 description 1
- 102000004632 fms-Like Tyrosine Kinase 3 Human genes 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 108010074605 gamma-Globulins Proteins 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 238000001030 gas--liquid chromatography Methods 0.000 description 1
- 208000015419 gastrin-producing neuroendocrine tumor Diseases 0.000 description 1
- 201000000052 gastrinoma Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 201000003115 germ cell cancer Diseases 0.000 description 1
- 229960002442 glucosamine Drugs 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
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960002743 glutamine Drugs 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
- 239000008187 granular material Substances 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000003106 haloaryl group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 208000006359 hepatoblastoma Diseases 0.000 description 1
- 201000002735 hepatocellular adenoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 125000005844 heterocyclyloxy group Chemical group 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 102000055590 human KDR Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000005113 hydroxyalkoxy group Chemical group 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 229960003685 imatinib mesylate Drugs 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 201000004933 in situ carcinoma Diseases 0.000 description 1
- 238000012750 in vivo screening Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000008611 intercellular interaction Effects 0.000 description 1
- 210000002570 interstitial cell Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 201000010985 invasive ductal carcinoma Diseases 0.000 description 1
- 239000011630 iodine Chemical group 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 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
- 210000001117 keloid Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000008101 lactose Substances 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
- 230000000670 limiting effect Effects 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000006249 magnetic particle Substances 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
- 239000011976 maleic acid Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 201000004593 malignant giant cell tumor Diseases 0.000 description 1
- 201000000289 malignant teratoma Diseases 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- JZKXXXDKRQWDET-UHFFFAOYSA-N meta-tyrosine Natural products OC(=O)C(N)CC1=CC=CC(O)=C1 JZKXXXDKRQWDET-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- HQEIPVHJHZTMDP-JEDNCBNOSA-N methyl (2s)-pyrrolidine-2-carboxylate;hydrochloride Chemical compound Cl.COC(=O)[C@@H]1CCCN1 HQEIPVHJHZTMDP-JEDNCBNOSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 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
- 230000001617 migratory effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 208000010492 mucinous cystadenocarcinoma Diseases 0.000 description 1
- 238000007040 multi-step synthesis reaction Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 208000009091 myxoma Diseases 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- SAFBOMGDPFJMQM-UHFFFAOYSA-N n-[[3-fluoro-4-(7h-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl]carbamothioyl]-2-phenylacetamide Chemical compound C=1C=C(OC=2C=3C=CNC=3N=CN=2)C(F)=CC=1NC(=S)NC(=O)CC1=CC=CC=C1 SAFBOMGDPFJMQM-UHFFFAOYSA-N 0.000 description 1
- FXFQHCBXCIWKNA-UHFFFAOYSA-N n-[[4-[1-(oxan-2-yl)pyrazolo[3,4-d]pyrimidin-4-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound C=1C=C(OC=2C=3C=NN(C=3N=CN=2)C2OCCCC2)C=CC=1NC(=S)NC(=O)CC1=CC=CC=C1 FXFQHCBXCIWKNA-UHFFFAOYSA-N 0.000 description 1
- VQCKOLREBPCHRL-UHFFFAOYSA-N n-[[4-[9-(oxan-2-yl)purin-6-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound C=1C=C(OC=2C=3N=CN(C=3N=CN=2)C2OCCCC2)C=CC=1NC(=S)NC(=O)CC1=CC=CC=C1 VQCKOLREBPCHRL-UHFFFAOYSA-N 0.000 description 1
- RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000007538 neurilemmoma Diseases 0.000 description 1
- 201000004662 neurofibroma of spinal cord Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 208000004649 neutrophil actin dysfunction Diseases 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 150000007523 nucleic acids Chemical group 0.000 description 1
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
- 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
- 125000005061 octahydroisoindolyl group Chemical group C1(NCC2CCCCC12)* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 208000003388 osteoid osteoma Diseases 0.000 description 1
- 208000008798 osteoma Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 210000003101 oviduct Anatomy 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 150000002916 oxazoles Chemical class 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000005968 oxazolinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 208000003154 papilloma Diseases 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 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
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000003566 phosphorylation assay Methods 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 208000024724 pineal body neoplasm Diseases 0.000 description 1
- 201000004123 pineal gland cancer Diseases 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 108010040003 polyglutamine Proteins 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- IAHIMVFWYADCJJ-UHFFFAOYSA-N prop-1-enylcyclohexane Chemical group CC=CC1CCCCC1 IAHIMVFWYADCJJ-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 150000003219 pyrazolines Chemical class 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 208000029922 reticulum cell sarcoma Diseases 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 206010039667 schwannoma Diseases 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 208000004548 serous cystadenocarcinoma Diseases 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
- VFWRGKJLLYDFBY-UHFFFAOYSA-N silver;hydrate Chemical compound O.[Ag].[Ag] VFWRGKJLLYDFBY-UHFFFAOYSA-N 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 239000002002 slurry Substances 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
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 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
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 208000001608 teratocarcinoma Diseases 0.000 description 1
- PEPVPLRKPVJCCP-YOGCLGLASA-N tert-butyl (3ar,6as)-5-(methylsulfonyloxymethyl)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrole-2-carboxylate Chemical compound C1C(COS(C)(=O)=O)C[C@@H]2CN(C(=O)OC(C)(C)C)C[C@@H]21 PEPVPLRKPVJCCP-YOGCLGLASA-N 0.000 description 1
- QCJGDXIONIXKEH-PHIMTYICSA-N tert-butyl (3as,6ar)-5-methylidene-1,3,3a,4,6,6a-hexahydrocyclopenta[c]pyrrole-2-carboxylate Chemical compound C1C(=C)C[C@H]2CN(C(=O)OC(C)(C)C)C[C@H]21 QCJGDXIONIXKEH-PHIMTYICSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 150000004867 thiadiazoles Chemical class 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000006090 thiamorpholinyl sulfone group Chemical group 0.000 description 1
- 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000011200 topical administration Methods 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
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 206010044412 transitional cell carcinoma Diseases 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 229940117013 triethanolamine oleate Drugs 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Substances CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 1
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 1
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Substances COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- 208000022271 tubular adenoma Diseases 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 229910052720 vanadium Inorganic materials 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
- 208000009540 villous adenoma Diseases 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 210000003905 vulva Anatomy 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/28—Oxygen atom
- C07D473/30—Oxygen atom attached in position 6, e.g. hypoxanthine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/20—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Neurosurgery (AREA)
- Communicable Diseases (AREA)
- Urology & Nephrology (AREA)
- Neurology (AREA)
- Heart & Thoracic Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Gastroenterology & Hepatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Vascular Medicine (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 |
|---|---|---|---|
| US58497704P | 2004-07-02 | 2004-07-02 | |
| US60/584,977 | 2004-07-02 | ||
| PCT/US2005/023364 WO2006014325A2 (en) | 2004-07-02 | 2005-07-01 | C-met modulators and method of use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2572331A1 true CA2572331A1 (en) | 2006-02-09 |
Family
ID=35787565
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002572331A Abandoned CA2572331A1 (en) | 2004-07-02 | 2005-07-01 | C-met modulators and method of use |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US7977345B2 (enExample) |
| EP (1) | EP1773826A4 (enExample) |
| JP (1) | JP5368701B2 (enExample) |
| AU (1) | AU2005270068B2 (enExample) |
| CA (1) | CA2572331A1 (enExample) |
| WO (1) | WO2006014325A2 (enExample) |
Families Citing this family (116)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2744997A1 (en) * | 2003-09-26 | 2005-04-07 | Exelixis, Inc. | C-met modulators and method of use |
| EP1719762B1 (en) | 2004-02-27 | 2012-06-27 | Eisai R&D Management Co., Ltd. | Novel pyridine derivative and pyrimidine derivative (1) |
| CA2573538C (en) * | 2004-07-30 | 2014-11-25 | Methylgene Inc. | Inhibitors of vegf receptor and hgf receptor signaling |
| ES2473341T3 (es) | 2005-05-20 | 2014-07-04 | Methylgene Inc | Inhibidores de la se�alizaci�n del receptor del VEGF y del receptor del HGF |
| JP5148499B2 (ja) * | 2005-05-20 | 2013-02-20 | メチルジーン インコーポレイテッド | Ｖｅｇｆ受容体およびｈｇｆ受容体シグナル伝達の阻害剤 |
| KR20080026562A (ko) * | 2005-06-02 | 2008-03-25 | 갤럭시 바이오테크, 엘엘씨 | 항체를 이용한 뇌종양 치료 방법 |
| PL1889836T3 (pl) | 2005-08-24 | 2013-10-31 | Eisai R&D Man Co Ltd | Nowa pochodna pirydyny i pochodna pirymidyny (3) |
| AU2006309171A1 (en) * | 2005-10-28 | 2007-05-10 | Irm Llc | Compounds and compositions as protein kinase inhibitors |
| NL2000291C2 (nl) | 2005-11-10 | 2009-02-17 | Pfizer Prod Inc | 1-(1-(2-ethoxyethyl)-3-ethyl-7-(4-methylpyridin-2-ylamino)-1H- pyrazool(4,3-d)pyrimidine-5-yl)piperidine-4-carbonzuur en zouten daarvan. |
| AR059246A1 (es) | 2006-01-30 | 2008-03-19 | Array Biopharma Inc | Compuestos heterobiciclicos de tiofeno y metodos de uso |
| MX2008011220A (es) | 2006-03-07 | 2008-09-11 | Array Biopharma Inc | Compuestos de pirazol heterobiciclicos y metodos de uso. |
| AR059922A1 (es) * | 2006-04-01 | 2008-05-07 | Galaxy Biotech Llc | Anticuerpos monoclonales humanizados para el factor de crecimiento de hepatocitos |
| JP5302883B2 (ja) | 2006-04-07 | 2013-10-02 | 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 | 医薬組成物用のｍｎｋ１／ｍｎｋ２阻害活性を有するチエノピリミジン |
| US20110053931A1 (en) * | 2006-06-08 | 2011-03-03 | John Gaudino | Quinoline compounds and methods of use |
| EP1889847A1 (en) | 2006-07-10 | 2008-02-20 | DeveloGen Aktiengesellschaft | Pyrrolopyrimidines for pharmaceutical compositions |
| JP2010500365A (ja) | 2006-08-07 | 2010-01-07 | インサイト・コーポレイション | キナーゼ阻害剤としてのトリアゾロトリアジン |
| CN101454311B (zh) | 2006-08-23 | 2013-03-27 | 卫材R&D管理有限公司 | 苯氧基吡啶衍生物的盐和其结晶及其制备方法 |
| US7790885B2 (en) | 2006-08-31 | 2010-09-07 | Eisai R&D Management Co., Ltd. | Process for preparing phenoxypyridine derivatives |
| WO2008049855A2 (en) * | 2006-10-27 | 2008-05-02 | Glaxo Group Limited | 7-azaindole derivatives as c-met kinase inhibitors |
| ES2560435T3 (es) | 2006-11-22 | 2016-02-19 | Incyte Holdings Corporation | Imidazotriazinas e imidazopirimidinas como inhibidores de la quinasa |
| BRPI0722383A2 (pt) | 2006-12-08 | 2012-06-05 | Irm Llc | compostos inibidores de proteìna quinase, composições contendo os mesmos bem como seus usos |
| DE102007026341A1 (de) | 2007-06-06 | 2008-12-11 | Merck Patent Gmbh | Benzoxazolonderivate |
| CN101918403A (zh) * | 2007-09-06 | 2010-12-15 | 阵列生物制药公司 | 作为酪氨酸激酶抑制剂的吡唑并吡啶类化合物 |
| JP2009132660A (ja) | 2007-11-30 | 2009-06-18 | Eisai R & D Management Co Ltd | 食道癌治療用組成物 |
| WO2009109035A1 (en) | 2008-03-05 | 2009-09-11 | Methylgene Inc. | Inhibitors of protein tyrosine kinase activity |
| MX393622B (es) | 2008-05-21 | 2025-03-24 | Incyte Corp | Sales de 2-fluoro-n-metil-4-[7-(quinolin-6-il-metil)-imidazo[1,2-b][1,2,4]triazin-2-il]benzamida y procesos relacionados con la preparacion de las mismas. |
| HRP20140395T1 (hr) * | 2008-08-20 | 2014-06-06 | Zoetis Llc | SPOJEVI PIROLO[2,3-d]PIRIMIDINA |
| KR20110045019A (ko) | 2008-08-26 | 2011-05-03 | 베링거 인겔하임 인터내셔날 게엠베하 | 약제학적 조성물을 위한 티에노피리미딘 |
| CA2740746A1 (en) * | 2008-10-14 | 2010-04-22 | Ning Xi | Compounds comprising a spiro-ring and and methods of use |
| DE102009003975A1 (de) | 2009-01-07 | 2010-07-08 | Merck Patent Gmbh | Benzothiazolonderivate |
| EA038195B1 (ru) | 2009-01-16 | 2021-07-22 | Экселиксис, Инк. | Малатная соль n-(4-{[6,7-бис-(метилокси)хинолин-4-ил]окси}фенил)-n'-(4-фторфенил)циклопропан-1,1-дикарбоксамида и ее применение для лечения рака почек и печени |
| EP2408300B1 (en) * | 2009-03-21 | 2016-05-11 | Sunshine Lake Pharma Co., Ltd. | Amino ester derivatives, salts thereof and methods of use |
| EP2245936A1 (en) | 2009-04-27 | 2010-11-03 | Bayer CropScience AG | Use of 4-aza indole derivatives for the reduction of mycotoxin contamination |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| IN2012DN02577A (enExample) * | 2009-10-15 | 2015-08-28 | Pfizer | |
| DE102009056886A1 (de) | 2009-12-03 | 2011-06-09 | Bayer Schering Pharma Aktiengesellschaft | cMet-Inhibitoren zur Behandlung der Endometriose |
| JP5714030B2 (ja) | 2010-02-03 | 2015-05-07 | インサイト コーポレーションＩｎｃｙｔｅ Ｃｏｒｐｏｒａｔｉｏｎ | Ｃ−Ｍｅｔ阻害剤としてのイミダゾ［１，２−ｂ］［１，２，４］トリアジン |
| AR080328A1 (es) | 2010-02-26 | 2012-03-28 | Boehringer Ingelheim Int | Tienopirimidinas que contienen un grupo alquilo sustituido inhibidoras de quinasas mnk1 y/o mnk2, composiciones farmaceuticas que las contienen y uso de las mismas para el tratamiento de trastornos metabolicos tales como diabetes y obesidad, y trastornos hiperproliferativos, entre otros |
| UY33241A (es) | 2010-02-26 | 2011-09-30 | Boehringer Ingelheim Int | ?Tienopirimidinas que contienen heterocicloalquilo para composiciones farmacéuticas?. |
| EA201201191A1 (ru) | 2010-02-26 | 2013-04-30 | Бёрингер Ингельхайм Интернациональ Гмбх | 4-[циклоалкилокси(гетеро)ариламино]тиено[2,3-d]пиримидины, обладающие ингибирующей активностью по отношению к mnkl/mnk2, предназначенные для фармацевтических композиций |
| EP3450432A1 (en) | 2010-05-17 | 2019-03-06 | Incozen Therapeutics Pvt. Ltd. | Novel 3,5-disubstitued-3h-imidazo[4,5-b]pyridine and 3,5- disubstitued - 3h-[1,2,3]triazolo[4,5-b] pyridine compounds as modulators of protein kinases |
| WO2011146287A1 (en) | 2010-05-20 | 2011-11-24 | Takeda Pharmaceutical Company Limited | Pyrazolo[4,3-b]pyridine-7-amine inhibitors of alk5 |
| CA2802644C (en) | 2010-06-25 | 2017-02-21 | Eisai R & D Management Co., Ltd. | Antitumor agent using compounds having kinase inhibitory effect in combination |
| WO2012009722A1 (en) | 2010-07-16 | 2012-01-19 | Exelixis, Inc. | C-met modulator pharmaceutical compositions |
| DK2621481T4 (da) | 2010-09-27 | 2023-01-09 | Exelixis Inc | Dobbelte inhibitorer af MET og VEGF til behandling af kastrationsresistent prostatacancer og osteoblastiske knoglemetastaser |
| US9309322B2 (en) | 2010-11-12 | 2016-04-12 | Scott & White Healthcare (Swh) | Antibodies to tumor endothelial marker 8 |
| TWI640509B (zh) | 2011-02-10 | 2018-11-11 | 艾克塞里克斯公司 | 製造喹啉化合物之方法及包含該化合物之醫藥組合物 |
| US20120252840A1 (en) | 2011-04-04 | 2012-10-04 | Exelixis, Inc. | Method of Treating Cancer |
| TWI610918B (zh) | 2011-05-02 | 2018-01-11 | 艾克塞里克斯公司 | 治療癌症及骨癌疼痛之方法 |
| TW201311679A (zh) | 2011-08-04 | 2013-03-16 | Takeda Pharmaceutical | 含氮雜環化合物 |
| ES2575710T3 (es) | 2011-09-22 | 2016-06-30 | Pfizer Inc | Derivados de pirrolopirimidina y purina |
| GEP201606523B (en) | 2011-09-22 | 2016-08-10 | Exelixis Inc | Method for treating osteoporosis |
| EP2768796B1 (en) * | 2011-10-20 | 2019-11-20 | Exelixis, Inc. | Process for preparing quinoline derivatives |
| US9586965B2 (en) | 2012-01-13 | 2017-03-07 | Acea Biosciences Inc. | Pyrrolo[2,3-d]pyrimidine compounds as inhibitors of protein kinases |
| AU2013207712B2 (en) | 2012-01-13 | 2017-08-31 | Acea Biosciences Inc. | Heterocyclic compounds and uses as anticancer agents. |
| US9464089B2 (en) | 2012-01-13 | 2016-10-11 | Acea Biosciences Inc. | Heterocyclic compounds and uses thereof |
| US9034885B2 (en) | 2012-01-13 | 2015-05-19 | Acea Biosciences Inc. | EGFR modulators and uses thereof |
| AP3908A (en) | 2012-03-30 | 2016-11-24 | Rhizen Pharmaceuticals Sa | Novel 3,5-disubstituted-3H-imidazo[4,5-B]pyridine and 3,5-disubstituted-3H-[1,2,3]triazolo [4,5-B] pyridine compounds as modulators of C-met protein kinases |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| WO2013166296A1 (en) | 2012-05-02 | 2013-11-07 | Exelixis, Inc. | A dual met - vegf modulator for treating osteolytic bone metastases |
| TWI520962B (zh) | 2012-06-29 | 2016-02-11 | As the c-Met tyrosine kinase inhibitors novel fused pyridine derivatives | |
| CN104507930B (zh) * | 2012-06-29 | 2017-10-10 | 贝达药业股份有限公司 | 作为c‑Met酪氨酸激酶抑制剂的新型稠合吡啶衍生物 |
| CN103570723B (zh) * | 2012-07-27 | 2016-07-13 | 广西梧州制药（集团）股份有限公司 | 吡唑并嘧啶衍生物及其制备方法和在药物制备中的用途 |
| EP2917216B1 (en) | 2012-11-08 | 2017-10-18 | Pfizer Inc | Heteroaromatic compounds as dopamine d1 ligands |
| CN102964308B (zh) * | 2012-11-30 | 2015-03-18 | 中国药科大学 | 新型嘧啶类化合物、其制备方法、包含此类化合物的药物组合物及其用途 |
| AU2013364953A1 (en) | 2012-12-21 | 2015-04-30 | Eisai R&D Management Co., Ltd. | Amorphous form of quinoline derivative, and method for producing same |
| CA2907334C (en) | 2013-03-15 | 2021-12-07 | Exelixis, Inc. | Metabolites of n-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-n'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide |
| US11564915B2 (en) | 2013-04-04 | 2023-01-31 | Exelixis, Inc. | Cabozantinib dosage form and use in the treatment of cancer |
| KR20150138268A (ko) * | 2013-04-04 | 2015-12-09 | 엑셀리시스, 인코포레이티드 | 암을 치료하기 위한 약물 병용요법 |
| CN105264380B (zh) | 2013-05-14 | 2017-09-05 | 卫材R&D管理有限公司 | 用于预测和评价子宫内膜癌受试者对乐伐替尼化合物响应性的生物标志 |
| KR102173433B1 (ko) | 2013-07-11 | 2020-11-04 | 에이시아 바이오사이언시스 인코포레이티드. | 키나아제 억제제로써의 피리미딘 유도체 |
| AU2015218236B2 (en) | 2014-02-14 | 2019-06-13 | Exelixis, Inc. | Crystalline solid forms of N-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl) cyclopropane-1, 1-dicarboxamide, processes for making, and methods of use |
| MX2016012285A (es) | 2014-03-24 | 2017-01-23 | Genentech Inc | Tratamiento de cáncer con antagonista de c-met y correlación de estos con la expresión de hgf. |
| WO2015162515A1 (en) | 2014-04-25 | 2015-10-29 | Pfizer Inc. | Heteroaromatic compounds and their use as dopamine d1 ligands |
| WO2015162518A1 (en) | 2014-04-25 | 2015-10-29 | Pfizer Inc. | Heteroaromatic compounds and their use as dopamine d1 ligands |
| CN106715397B (zh) | 2014-07-31 | 2021-07-23 | 埃克塞里艾克西斯公司 | 制备氟-18标记的卡博替尼及其类似物的方法 |
| BR112017002318A2 (pt) | 2014-08-05 | 2018-07-17 | Exelixis, Inc. | combinações de fármacos para tratar mieloma múltiplo. |
| CA2957005C (en) | 2014-08-28 | 2021-10-12 | Eisai R&D Management Co., Ltd. | High-purity quinoline derivative and method for manufacturing same |
| SG11201706630UA (en) | 2015-02-25 | 2017-09-28 | Eisai R&D Man Co Ltd | Method for suppressing bitterness of quinoline derivative |
| WO2016140717A1 (en) | 2015-03-04 | 2016-09-09 | Merck Sharp & Dohme Corp. | Combination of a pd-1 antagonist and a vegfr/fgfr/ret tyrosine kinase inhibitor for treating cancer |
| BR112017027227B1 (pt) | 2015-06-16 | 2023-12-12 | Eisai R&D Management Co., Ltd | Agente anti-câncer |
| JP6721617B2 (ja) * | 2015-07-20 | 2020-07-15 | ベータ ファーマシューティカルズ カンパニー リミテッド | 縮合ピリジン誘導体のマレエートの結晶形態およびその使用 |
| EP3325473A4 (en) | 2015-07-22 | 2019-06-26 | The Royal Institution for the Advancement of Learning / McGill University | Compounds and uses thereof in the treatment of cancer and other medical disorders |
| JP6553726B2 (ja) | 2015-08-20 | 2019-07-31 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 腫瘍治療剤 |
| WO2017059702A1 (en) | 2015-10-09 | 2017-04-13 | Acea Biosciences, Inc | Pharmaceutical salts, physical forms, and compositions of pyrrolopyrimidine kinase inhibitors, and methods of making same |
| GB201520500D0 (en) | 2015-11-20 | 2016-01-06 | Medical Res Council Technology | Compounds |
| GB201520499D0 (en) | 2015-11-20 | 2016-01-06 | Medical Res Council Technology | Compounds |
| CN109069499A (zh) | 2016-04-15 | 2018-12-21 | 埃克塞里艾克西斯公司 | 使用 n-(4-(6,7-二甲氧基喹啉-4-基氧基)苯基)-n’-(4-氟苯基)环丙烷-1,1-二甲酰胺,(2s)-羟基丁二酸盐治疗肾细胞癌的方法 |
| CN106496232B (zh) * | 2016-09-22 | 2018-11-09 | 南方医科大学 | 一种具有抗肿瘤活性的1-(2-四氢吡喃)-1H-吡唑并[3,4-d]嘧啶类化合物及其制备方法 |
| US12303505B2 (en) | 2017-02-08 | 2025-05-20 | Eisai R&D Management Co., Ltd. | Tumor-treating pharmaceutical composition |
| US11498922B2 (en) | 2017-04-07 | 2022-11-15 | ACEA Therapeutics, Inc. | Pharmaceutical composition comprising N-(3-((2-((3-fluoro-4-(4-methylpiperazin-1-yl phenyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)phenylacrylamide |
| BR112019023064A2 (pt) | 2017-05-16 | 2020-06-09 | Eisai R&D Man Co Ltd | tratamento de carcinoma hepatocelular |
| WO2018228923A1 (en) | 2017-06-13 | 2018-12-20 | Bayer Pharma Aktiengesellschaft | Substituted pyrrolopyridine-derivatives as map4k1 modulators for the treatment of cancer diseases |
| WO2018228925A1 (en) | 2017-06-13 | 2018-12-20 | Bayer Pharma Aktiengesellschaft | Substituted pyrrolopyridine-derivatives |
| CA3066859A1 (en) | 2017-06-13 | 2018-12-20 | Bayer Pharma Aktiengesellschaft | Substituted pyrrolopyridine-derivatives |
| US11427578B1 (en) | 2017-07-18 | 2022-08-30 | Bayer Pharma Aktiengesellschaft | Substituted pyrrolopyridine-derivatives |
| AU2019216351B2 (en) | 2018-01-31 | 2024-07-25 | Deciphera Pharmaceuticals, Llc | Combination therapy for the treatment of mastocytosis |
| EP3746059B1 (en) | 2018-01-31 | 2026-03-04 | Deciphera Pharmaceuticals, LLC | Combination therapy for the treatment of gastrointestinal stromal tumors |
| CN120305263A (zh) | 2018-06-15 | 2025-07-15 | 汉达癌症医药责任有限公司 | 卡博替尼的盐类于制备治疗癌症的剂型的用途 |
| UY38349A (es) | 2018-08-30 | 2020-03-31 | Array Biopharma Inc | Compuestos de pirazolo[3,4-b]piridina como inhibidores de cinasas tam y met |
| US20220047603A1 (en) | 2018-12-11 | 2022-02-17 | Bayer Aktiengesellschaft | Substituted pyrrolopyridine-derivatives |
| ES2974634T3 (es) | 2018-12-21 | 2024-06-28 | Celgene Corp | Inhibidores de tienopiridinas de RIPK2 |
| NL2022471B1 (en) | 2019-01-29 | 2020-08-18 | Vationpharma B V | Solid state forms of oclacitinib |
| WO2020185812A1 (en) | 2019-03-11 | 2020-09-17 | Teva Pharmaceuticals International Gmbh | Solid state forms of ripretinib |
| KR20220054286A (ko) * | 2019-06-25 | 2022-05-02 | 시놉세 테라페우틱스 | 눈 장애의 치료를 위한 화합물 |
| FI4013412T3 (fi) | 2019-08-12 | 2026-03-24 | Deciphera Pharmaceuticals Llc | Ripretinibi ruoansulatuskanavan stroomakasvaimien hoitoon |
| TWI878335B (zh) | 2019-08-12 | 2025-04-01 | 美商迪賽孚爾製藥有限公司 | 治療胃腸道基質瘤方法 |
| PL4084779T3 (pl) | 2019-12-30 | 2025-02-24 | Deciphera Pharmaceuticals, Llc | Kompozycje 1-(4-bromo-5-(1-etylo-7-(metyloamino)-2-okso-1,2-dihydro-1,6-naftyrydyn-3-ylo)-2-fluorofenylo)-3-fenylomocznika |
| AU2020419197B2 (en) | 2019-12-30 | 2023-08-31 | Deciphera Pharmaceuticals, Llc | Amorphous kinase inhibitor formulations and methods of use thereof |
| WO2021249913A1 (en) | 2020-06-09 | 2021-12-16 | Bayer Aktiengesellschaft | 2'-(quinolin-3-yl)-5',6'-dihydrospiro[azetidine-3,4'-pyrrolo[1,2-b]pyrazole]-1-carboxylate derivatives and related compounds as map4k1 (hpk1) inhibitors for the treatment of cancer |
| US20240174683A1 (en) | 2021-02-05 | 2024-05-30 | Bayer Aktiengesellschaft | Map4k1 inhibitors |
| CN116836176B (zh) * | 2022-03-23 | 2026-02-24 | 中国科学院上海药物研究所 | 青蒿素类化合物、其制备方法和应用 |
| CN115160340B (zh) * | 2022-06-07 | 2023-07-21 | 四川大学华西医院 | 一种具有ack1抑制活性的小分子化合物及其应用 |
| US11779572B1 (en) | 2022-09-02 | 2023-10-10 | Deciphera Pharmaceuticals, Llc | Methods of treating gastrointestinal stromal tumors |
| EP4622961A1 (en) * | 2022-11-25 | 2025-10-01 | Synthon B.V. | A process for preparation of cabozantinib or tivozanib |
| AU2024215796A1 (en) | 2023-01-31 | 2025-05-15 | Handa Oncology, Llc | Improved cabozantinib compositions and methods of use |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3149111A (en) * | 1961-09-29 | 1964-09-15 | Burroughs Wellcome Co | Dinitrophenylmercaptopurines |
| IL112249A (en) * | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
| GB9604361D0 (en) * | 1996-02-29 | 1996-05-01 | Pharmacia Spa | 4-Substituted pyrrolopyrimidine compounds as tyrosine kinase inhibitors |
| US6107300A (en) * | 1996-03-27 | 2000-08-22 | Dupont Pharmaceuticals | Arylamino fused pyrimidines |
| JP2004509059A (ja) * | 1999-06-03 | 2004-03-25 | アボット・ラボラトリーズ | 細胞接着抑制性抗炎症化合物 |
| US7135466B2 (en) * | 1999-12-24 | 2006-11-14 | Kirin Beer Kabushiki Kaisha | Quinoline and quinazoline derivatives and drugs containing the same |
| EP1415987B1 (en) * | 2000-10-20 | 2007-02-28 | Eisai R&D Management Co., Ltd. | Nitrogenous aromatic ring compounds as anti cancer agents |
| CA2454538A1 (en) * | 2001-06-22 | 2003-01-03 | Kirin Beer Kabushiki Kaisha | Quinoline derivatives and quinazoline derivatives capable of inhibiting autophosphorylation of hepatocyte growth factor receptors, and pharmaceutical composition comprising the same |
| JP4224979B2 (ja) * | 2002-04-09 | 2009-02-18 | 大正製薬株式会社 | インターロイキン１２抑制剤 |
| US7271179B2 (en) * | 2002-05-06 | 2007-09-18 | Vertex Pharmaceuticals Incorporated | Inhibitors of JAK protein kinase |
| GB0219746D0 (en) * | 2002-08-23 | 2002-10-02 | Inst Of Ex Botany Ascr | Azapurine derivatives |
| US20070213374A1 (en) * | 2003-07-07 | 2007-09-13 | Merck Patent Gmbh | Malonamide Derivatives |
| US7439246B2 (en) * | 2004-06-28 | 2008-10-21 | Bristol-Myers Squibb Company | Fused heterocyclic kinase inhibitors |
| US20050288290A1 (en) * | 2004-06-28 | 2005-12-29 | Borzilleri Robert M | Fused heterocyclic kinase inhibitors |
-
2005
- 2005-07-01 WO PCT/US2005/023364 patent/WO2006014325A2/en not_active Ceased
- 2005-07-01 US US11/571,140 patent/US7977345B2/en not_active Expired - Fee Related
- 2005-07-01 JP JP2007520386A patent/JP5368701B2/ja not_active Expired - Fee Related
- 2005-07-01 CA CA002572331A patent/CA2572331A1/en not_active Abandoned
- 2005-07-01 EP EP05763620A patent/EP1773826A4/en not_active Withdrawn
- 2005-07-01 AU AU2005270068A patent/AU2005270068B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| AU2005270068A1 (en) | 2006-02-09 |
| US20070179130A1 (en) | 2007-08-02 |
| JP2008505181A (ja) | 2008-02-21 |
| WO2006014325A2 (en) | 2006-02-09 |
| EP1773826A4 (en) | 2009-06-03 |
| WO2006014325A3 (en) | 2007-03-01 |
| JP5368701B2 (ja) | 2013-12-18 |
| AU2005270068B2 (en) | 2012-04-19 |
| US7977345B2 (en) | 2011-07-12 |
| EP1773826A2 (en) | 2007-04-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2005270068B2 (en) | C-Met modulators and method of use | |
| EP1521747B1 (en) | Receptor-type kinase modulators and methods of use | |
| US7872014B2 (en) | Anaplastic lymphoma kinase modulators and methods of use | |
| US20080161305A1 (en) | C-Met Modulators and Methods of Use | |
| CA2506546A1 (en) | Kinase modulators | |
| AU2011202643B2 (en) | Anaplastic lymphoma kinase modulators and methods of use | |
| HK1148277A (en) | Process for preparing receptor-type kinase modulators | |
| HK1147484A (en) | Compounds, pharmaceutical compositions thereof and their use in treating cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20150702 |