NO321696B1 - Kinolinderivater som inhibitorer av MEK-enzymer, fremgangsmate for fremstilling og anvendelse derav, samt farmasoytisk preparat. - Google Patents
Kinolinderivater som inhibitorer av MEK-enzymer, fremgangsmate for fremstilling og anvendelse derav, samt farmasoytisk preparat. Download PDFInfo
- Publication number
- NO321696B1 NO321696B1 NO20015448A NO20015448A NO321696B1 NO 321696 B1 NO321696 B1 NO 321696B1 NO 20015448 A NO20015448 A NO 20015448A NO 20015448 A NO20015448 A NO 20015448A NO 321696 B1 NO321696 B1 NO 321696B1
- Authority
- NO
- Norway
- Prior art keywords
- carbon atoms
- alkyl
- formula
- optionally substituted
- group
- Prior art date
Links
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 title claims abstract description 22
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims description 24
- 238000000034 method Methods 0.000 title claims description 16
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 7
- 239000003112 inhibitor Substances 0.000 title description 9
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 3
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 88
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 62
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 30
- -1 pyimidinyl Chemical group 0.000 claims abstract description 29
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 239000001257 hydrogen Substances 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 14
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 13
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 6
- 230000005764 inhibitory process Effects 0.000 claims abstract description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 239000002243 precursor Substances 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 4
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 4
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 230000009466 transformation Effects 0.000 claims description 4
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000006319 alkynyl amino group Chemical group 0.000 claims description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000004970 halomethyl group Chemical group 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
- 125000003566 oxetanyl group Chemical group 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims 1
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims 1
- 125000004949 alkyl amino carbonyl amino group Chemical group 0.000 claims 1
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 1
- 125000000466 oxiranyl group Chemical group 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 14
- 150000001204 N-oxides Chemical class 0.000 abstract 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract 1
- 125000000962 organic group Chemical group 0.000 abstract 1
- 125000003107 substituted aryl group Chemical group 0.000 abstract 1
- 238000001819 mass spectrum Methods 0.000 description 24
- 239000000203 mixture Substances 0.000 description 21
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 17
- 239000000543 intermediate Substances 0.000 description 16
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 16
- 239000004480 active ingredient Substances 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 13
- 108091054455 MAP kinase family Proteins 0.000 description 12
- 102000043136 MAP kinase family Human genes 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 12
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 206010028980 Neoplasm Diseases 0.000 description 9
- 102000016914 ras Proteins Human genes 0.000 description 9
- 108010014186 ras Proteins Proteins 0.000 description 9
- 239000000843 powder Substances 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 239000007859 condensation product Substances 0.000 description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 6
- 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 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 6
- 229940124647 MEK inhibitor Drugs 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 235000003599 food sweetener Nutrition 0.000 description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 description 6
- 239000003755 preservative agent Substances 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- XKMLYUALXHKNFT-UUOKFMHZSA-N Guanosine-5'-triphosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XKMLYUALXHKNFT-UUOKFMHZSA-N 0.000 description 5
- 102000047918 Myelin Basic Human genes 0.000 description 5
- 101710107068 Myelin basic protein Proteins 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 230000036961 partial effect Effects 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 4
- 102000001253 Protein Kinase Human genes 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- 108060006633 protein kinase Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000000375 suspending agent Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 3
- 101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 3
- 102100023266 Dual specificity mitogen-activated protein kinase kinase 2 Human genes 0.000 description 3
- 101710146529 Dual specificity mitogen-activated protein kinase kinase 2 Proteins 0.000 description 3
- QGWNDRXFNXRZMB-UUOKFMHZSA-N GDP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O QGWNDRXFNXRZMB-UUOKFMHZSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 239000007900 aqueous suspension Substances 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- QGWNDRXFNXRZMB-UHFFFAOYSA-N guanidine diphosphate Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O QGWNDRXFNXRZMB-UHFFFAOYSA-N 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000002390 rotary evaporation Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- OFUFXTHGZWIDDB-UHFFFAOYSA-N 2-chloroquinoline Chemical compound C1=CC=CC2=NC(Cl)=CC=C21 OFUFXTHGZWIDDB-UHFFFAOYSA-N 0.000 description 2
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 235000006491 Acacia senegal Nutrition 0.000 description 2
- 235000003911 Arachis Nutrition 0.000 description 2
- 244000105624 Arachis hypogaea Species 0.000 description 2
- 108010011485 Aspartame Proteins 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 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 2
- 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 2
- 101000876610 Dictyostelium discoideum Extracellular signal-regulated kinase 2 Proteins 0.000 description 2
- 101100342473 Drosophila melanogaster Raf gene Proteins 0.000 description 2
- 102000005720 Glutathione transferase Human genes 0.000 description 2
- 108010070675 Glutathione transferase Proteins 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 101001052493 Homo sapiens Mitogen-activated protein kinase 1 Proteins 0.000 description 2
- 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 2
- 108040008097 MAP kinase activity proteins Proteins 0.000 description 2
- 102000019149 MAP kinase activity proteins Human genes 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 2
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 2
- 102000001788 Proto-Oncogene Proteins c-raf Human genes 0.000 description 2
- 108010029869 Proto-Oncogene Proteins c-raf Proteins 0.000 description 2
- 101100523543 Rattus norvegicus Raf1 gene Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 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
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 101100523549 Xenopus laevis raf1 gene Proteins 0.000 description 2
- 101150037250 Zhx2 gene Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 2
- 125000005422 alkyl sulfonamido group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000000605 aspartame Substances 0.000 description 2
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 2
- 235000010357 aspartame Nutrition 0.000 description 2
- 229960003438 aspartame Drugs 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 230000010307 cell transformation Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 150000003248 quinolines Chemical class 0.000 description 2
- 108700042226 ras Genes Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 102000034285 signal transducing proteins Human genes 0.000 description 2
- 108091006024 signal transducing proteins Proteins 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000007916 tablet composition Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000005490 tosylate group Chemical group 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
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 238000005406 washing Methods 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 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- MAQLAURHIDSERO-UHFFFAOYSA-N 2-(3-chloropropoxy)quinoline Chemical compound C1=CC=CC2=NC(OCCCCl)=CC=C21 MAQLAURHIDSERO-UHFFFAOYSA-N 0.000 description 1
- VOHILFSOWRNVJJ-UHFFFAOYSA-N 2-(bromomethyl)oxolane Chemical compound BrCC1CCCO1 VOHILFSOWRNVJJ-UHFFFAOYSA-N 0.000 description 1
- QTMAZYGAVHCKKX-UHFFFAOYSA-N 2-[(4-amino-5-bromopyrrolo[2,3-d]pyrimidin-7-yl)methoxy]propane-1,3-diol Chemical compound NC1=NC=NC2=C1C(Br)=CN2COC(CO)CO QTMAZYGAVHCKKX-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- XFOFRBMGVDBINH-UHFFFAOYSA-N 4-(2-methoxyphenoxy)aniline Chemical compound COC1=CC=CC=C1OC1=CC=C(N)C=C1 XFOFRBMGVDBINH-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical group N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- HMLOMVBFQJAMCN-UHFFFAOYSA-N 4-chloro-6,7-dimethoxyquinoline-3-carbonitrile Chemical compound C1=C(C#N)C(Cl)=C2C=C(OC)C(OC)=CC2=N1 HMLOMVBFQJAMCN-UHFFFAOYSA-N 0.000 description 1
- JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 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
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 102000034286 G proteins Human genes 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 1
- 102100029974 GTPase HRas Human genes 0.000 description 1
- 101710091881 GTPase HRas Proteins 0.000 description 1
- 108091006109 GTPases Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-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
- 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 1
- 108010075654 MAP Kinase Kinase Kinase 1 Proteins 0.000 description 1
- 108060006687 MAP kinase kinase kinase Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102100033115 Mitogen-activated protein kinase kinase kinase 1 Human genes 0.000 description 1
- 101001058457 Mus musculus Glycosylation-dependent cell adhesion molecule 1 Proteins 0.000 description 1
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 description 1
- 241001181114 Neta Species 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 102100027584 Protein c-Fos Human genes 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 1
- 102000007568 Proto-Oncogene Proteins c-fos Human genes 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 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
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 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
- 239000013543 active substance Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000005133 alkynyloxy group Chemical group 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229960001701 chloroform Drugs 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
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 230000006552 constitutive activation Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- UVCJGUGAGLDPAA-UHFFFAOYSA-N ensulizole Chemical compound N1C2=CC(S(=O)(=O)O)=CC=C2N=C1C1=CC=CC=C1 UVCJGUGAGLDPAA-UHFFFAOYSA-N 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical group O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000008263 liquid aerosol Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 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
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 230000008747 mitogenic response Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 230000006740 morphological transformation Effects 0.000 description 1
- 230000035772 mutation Effects 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- PSACHCMMPFMFAJ-UHFFFAOYSA-N nmm n-methylmorpholine Chemical compound CN1CCOCC1.CN1CCOCC1 PSACHCMMPFMFAJ-UHFFFAOYSA-N 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000009701 normal cell proliferation Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000012071 phase Substances 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
- 239000006187 pill Substances 0.000 description 1
- 229920009537 polybutylene succinate adipate Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- QZZYYBQGTSGDPP-UHFFFAOYSA-N quinoline-3-carbonitrile Chemical class C1=CC=CC2=CC(C#N)=CN=C21 QZZYYBQGTSGDPP-UHFFFAOYSA-N 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 239000012588 trypsin Substances 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
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 230000009750 upstream signaling Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Quinoline Compounds (AREA)
- Saccharide Compounds (AREA)
- Luminescent Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9910577.7A GB9910577D0 (en) | 1999-05-08 | 1999-05-08 | Chemical compounds |
| PCT/GB2000/001697 WO2000068201A1 (en) | 1999-05-08 | 2000-05-03 | Quinoline derivatives as inhibitors of mek enzymes |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20015448D0 NO20015448D0 (no) | 2001-11-07 |
| NO20015448L NO20015448L (no) | 2002-01-07 |
| NO321696B1 true NO321696B1 (no) | 2006-06-26 |
Family
ID=10852987
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20015448A NO321696B1 (no) | 1999-05-08 | 2001-11-07 | Kinolinderivater som inhibitorer av MEK-enzymer, fremgangsmate for fremstilling og anvendelse derav, samt farmasoytisk preparat. |
Country Status (26)
| Country | Link |
|---|---|
| EP (2) | EP1584619A1 (cs) |
| JP (1) | JP2002544196A (cs) |
| KR (1) | KR100667719B1 (cs) |
| CN (1) | CN1219768C (cs) |
| AT (1) | ATE319688T1 (cs) |
| AU (1) | AU772846B2 (cs) |
| BG (1) | BG106073A (cs) |
| BR (1) | BR0010391A (cs) |
| CA (1) | CA2372663A1 (cs) |
| CZ (1) | CZ20013997A3 (cs) |
| DE (1) | DE60026509T2 (cs) |
| DK (1) | DK1178967T3 (cs) |
| EE (1) | EE200100589A (cs) |
| ES (1) | ES2258455T3 (cs) |
| GB (2) | GB9910577D0 (cs) |
| HU (1) | HUP0201219A3 (cs) |
| IL (1) | IL146317A0 (cs) |
| IS (1) | IS6138A (cs) |
| NO (1) | NO321696B1 (cs) |
| NZ (1) | NZ514980A (cs) |
| PL (1) | PL352413A1 (cs) |
| PT (1) | PT1178967E (cs) |
| SK (1) | SK16102001A3 (cs) |
| TR (1) | TR200103186T2 (cs) |
| WO (1) | WO2000068201A1 (cs) |
| ZA (1) | ZA200108971B (cs) |
Families Citing this family (82)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020054869A1 (en) | 2000-09-01 | 2002-05-09 | Han-Mo Koo | Inhibition of mitogen-activated protein kinase (MAPK) pathway: a selective therapeutic strategy against melanoma |
| US7253184B2 (en) | 2000-11-02 | 2007-08-07 | Astrazeneca Ab | 4-Substituted quinolines as antitumor agents |
| US7067532B2 (en) | 2000-11-02 | 2006-06-27 | Astrazeneca | Substituted quinolines as antitumor agents |
| MXPA03005855A (es) | 2000-12-29 | 2003-09-10 | Wyeth Corp | Metodo para preparacion regioselectiva de benzo[g]quinolin-3-carbonitrilos sustituidos y benzo[g]quinazolinas sustituidas. |
| WO2002076496A1 (en) * | 2001-03-22 | 2002-10-03 | Van Andel Institute | Anthrax lethal factor inhibits tumor growth and angiogenesis |
| GB0112834D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| US6706699B2 (en) | 2001-06-21 | 2004-03-16 | Ariad Pharmaceuticals, Inc. | Quinolines and uses thereof |
| JP4326328B2 (ja) | 2001-07-16 | 2009-09-02 | アストラゼネカ アクチボラグ | キノリン誘導体及びそれらのチロシンキナーゼ阻害薬としての使用 |
| KR20050044599A (ko) * | 2001-11-27 | 2005-05-12 | 와이어쓰 홀딩스 코포레이션 | Ｅｇｆ-ｒ 및 ｈｅｒ2 키나아제의 억제제로서의3-시아노퀴놀린 |
| WO2003047582A1 (en) * | 2001-12-05 | 2003-06-12 | Astrazeneca Ab | Quinoline derivatives as antitumour agents |
| WO2003047584A1 (en) * | 2001-12-05 | 2003-06-12 | Astrazeneca Ab | Quinoline derivatives |
| WO2003048159A1 (en) * | 2001-12-05 | 2003-06-12 | Astrazeneca Ab | Quinoline derivatives |
| PL401637A1 (pl) | 2002-03-13 | 2013-05-27 | Array Biopharma Inc. | N3 alkilowane pochodne benzimidazolu jako inhibitory MEK |
| US7235537B2 (en) | 2002-03-13 | 2007-06-26 | Array Biopharma, Inc. | N3 alkylated benzimidazole derivatives as MEK inhibitors |
| IL164167A0 (en) * | 2002-03-30 | 2005-12-18 | Boehringer Ingelheim Pharma | 4-(N-phenylamino)-quinazolines/ quinolines as tyrosine kinase inhibitors |
| US6924285B2 (en) | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
| GB0215823D0 (en) | 2002-07-09 | 2002-08-14 | Astrazeneca Ab | Quinazoline derivatives |
| EP1521747B1 (en) | 2002-07-15 | 2018-09-05 | Symphony Evolution, Inc. | Receptor-type kinase modulators and methods of use |
| GB0225579D0 (en) * | 2002-11-02 | 2002-12-11 | Astrazeneca Ab | Chemical compounds |
| WO2004069249A1 (en) * | 2003-02-03 | 2004-08-19 | Astrazeneca Ab | 3-cyano-quinoline derivatives as non-receptor tyrosine kinase inhibitors |
| WO2004069250A1 (en) * | 2003-02-03 | 2004-08-19 | Astrazeneca Ab | 3-cyano-quinoline derivatives as non-receptor tyrosine kinase inhibitors |
| WO2004106308A1 (en) * | 2003-05-27 | 2004-12-09 | Pfizer Products Inc. | Quinazolines and pyrido [3,4-d] pyrimidines as receptor tyrosine kinase inhibitors |
| US7538120B2 (en) | 2003-09-03 | 2009-05-26 | Array Biopharma Inc. | Method of treating inflammatory diseases |
| US7144907B2 (en) | 2003-09-03 | 2006-12-05 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| ATE517091T1 (de) | 2003-09-26 | 2011-08-15 | Exelixis Inc | C-met-modulatoren und verwendungsverfahren |
| US7517994B2 (en) | 2003-11-19 | 2009-04-14 | Array Biopharma Inc. | Heterocyclic inhibitors of MEK and methods of use thereof |
| WO2005051302A2 (en) | 2003-11-19 | 2005-06-09 | Array Biopharma Inc. | Bicyclic inhibitors of mek and methods of use thereof |
| US7732616B2 (en) | 2003-11-19 | 2010-06-08 | Array Biopharma Inc. | Dihydropyridine and dihydropyridazine derivatives as inhibitors of MEK and methods of use thereof |
| CN1882347A (zh) | 2003-11-21 | 2006-12-20 | 阿雷生物药品公司 | Akt蛋白激酶抑制剂 |
| GT200500008A (es) * | 2004-01-16 | 2005-08-16 | Intermediarios de quinolina como inhibidores de receptores de tirosina quinasas y la sintesis de los mismos | |
| TW200529846A (en) | 2004-02-20 | 2005-09-16 | Wyeth Corp | 3-quinolinecarbonitrile protein kinase inhibitors |
| SI1802579T1 (sl) | 2004-10-20 | 2014-03-31 | Merck Serono Sa | Derivati 3-arilaminopiridina |
| FR2884516B1 (fr) * | 2005-04-15 | 2007-06-22 | Cerep Sa | Antagonistes npy, preparation et utilisations |
| EP1967516B1 (en) | 2005-05-18 | 2009-11-04 | Array Biopharma, Inc. | 4-(phenylamino)-6-oxo-1,6-dihydropyridazine-3-carboxamide derivatives as MEK inhibitors for the treatment of hyperproliferative diseases |
| AR057455A1 (es) * | 2005-07-22 | 2007-12-05 | Merck & Co Inc | Inhibidores de la transcriptasa reversa de vih y composicion farmaceutica |
| US8648087B2 (en) * | 2005-11-15 | 2014-02-11 | Array Biopharma, Inc. | N4-phenyl-quinazoline-4-amine derivatives and related compounds as ErbB type I receptor tyrosine kinase inhibitors for the treatment of hyperproliferative diseases |
| WO2007132867A1 (ja) | 2006-05-15 | 2007-11-22 | Takeda Pharmaceutical Company Limited | 癌の予防及び治療剤 |
| US8063050B2 (en) | 2006-07-06 | 2011-11-22 | Array Biopharma Inc. | Hydroxylated and methoxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
| EP2054418B1 (en) | 2006-07-06 | 2011-11-09 | Array Biopharma Inc. | Dihydrothieno pyrimidines as akt protein kinase inhibitors |
| US8329701B2 (en) | 2006-07-06 | 2012-12-11 | Array Biopharma Inc. | Dihydrofuro pyrimidines as AKT protein kinase inhibitors |
| BRPI0713555A2 (pt) | 2006-07-06 | 2012-03-20 | Array Biopharma, Inc. | ciclopenta [d] pirimidinas como inibidores de akt protéina cinase |
| EP1921070A1 (de) | 2006-11-10 | 2008-05-14 | Boehringer Ingelheim Pharma GmbH & Co. KG | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstelllung |
| KR20090116782A (ko) | 2007-02-06 | 2009-11-11 | 베링거 인겔하임 인터내셔날 게엠베하 | 바이사이클릭 헤테로사이클, 당해 화합물을 함유하는 약물, 이의 용도 및 이의 제조방법 |
| EP1969932A1 (de) * | 2007-03-12 | 2008-09-17 | Bayer CropScience AG | Phenoxyphenylamidine und deren Verwendung als Fungizide |
| JP2010520900A (ja) | 2007-03-12 | 2010-06-17 | バイエル・クロツプサイエンス・アクチエンゲゼルシヤフト | フェノキシ置換されたフェニルアミジン誘導体及び殺真菌剤としてのその使用 |
| AU2008272830B8 (en) | 2007-07-05 | 2013-12-12 | Array Biopharma Inc. | Pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
| CA2692506C (en) | 2007-07-05 | 2015-11-24 | Array Biopharma Inc. | Pyrimidyl cyclopentanes as akt protein kinase inhibitors |
| US9409886B2 (en) | 2007-07-05 | 2016-08-09 | Array Biopharma Inc. | Pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
| US8846683B2 (en) | 2007-07-05 | 2014-09-30 | Array Biopharma, Inc. | Pyrimidyl cyclopentanes as Akt protein kinase inhibitors |
| HUE025421T2 (en) * | 2007-11-15 | 2016-02-29 | Clanotech Ab | Quinoline derivatives, pharmaceutical compositions containing them, and their use |
| RU2010125220A (ru) | 2007-11-20 | 2011-12-27 | Мерк Шарп Энд Домэ Корп. (Us) | Ненуклеозидные ингибиторы обратной транскриптазы |
| MX2010007546A (es) | 2008-01-09 | 2010-09-30 | Array Biopharma Inc | Pirimidil ciclopentanos hidroxilados en forma de inhibidores de akt proteína quinasa. |
| NZ586346A (en) | 2008-01-09 | 2012-02-24 | Array Biopharma Inc | Hydroxylated pyrimidyl cyclopentanes as akt protein kinase inhibitors |
| KR20100111291A (ko) | 2008-02-07 | 2010-10-14 | 베링거 인겔하임 인터내셔날 게엠베하 | 스피로사이클릭 헤테로사이클, 상기 화합물을 함유하는 약제, 이의 용도 및 이의 제조 방법 |
| CA2732828C (en) | 2008-08-04 | 2017-06-13 | Merck Patent Gmbh | Phenylamino isonicotinamide compounds |
| US8648191B2 (en) | 2008-08-08 | 2014-02-11 | Boehringer Ingelheim International Gmbh | Cyclohexyloxy substituted heterocycles, pharmaceutical compositions containing these compounds and processes for preparing them |
| WO2010051933A2 (en) | 2008-11-10 | 2010-05-14 | Bayer Schering Pharma Aktiengesellschaft | Substituted sulphonamido phenoxybenzamides |
| KR102187034B1 (ko) | 2009-01-16 | 2020-12-04 | 엑셀리시스, 인코포레이티드 | 암 치료용 ｎ-（４-｛〔６，７-비스（메틸옥시）퀴놀린-4-일〕옥시｝페닐）-ｎ＇-（４-플루오로페닐）사이클로프로판-1,1-디카르복사미드의 말산염 및 그 결정형 |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| JP2013508318A (ja) | 2009-10-21 | 2013-03-07 | バイエル・ファルマ・アクチェンゲゼルシャフト | 置換されたベンゾスルホンアミド誘導体 |
| CA2777430A1 (en) | 2009-10-21 | 2011-04-28 | Bayer Pharma Aktiengesellschaft | Substituted benzosulphonamides |
| WO2011047796A1 (en) | 2009-10-21 | 2011-04-28 | Bayer Schering Pharma Aktiengesellschaft | Substituted halophenoxybenzamide derivatives |
| ES2575215T3 (es) * | 2009-12-11 | 2016-06-27 | Autifony Therapeutics Limited | Derivados de imidazolidindiona |
| ES2639407T3 (es) * | 2010-06-09 | 2017-10-26 | Tianjin Hemay Oncology Pharmaceutical Co., Ltd. | Derivados de cianoquinolina |
| WO2012055953A1 (en) | 2010-10-29 | 2012-05-03 | Bayer Pharma Aktiengesellschaft | Substituted phenoxypyridines |
| CN102020651B (zh) | 2010-11-02 | 2012-07-18 | 北京赛林泰医药技术有限公司 | 6-芳基氨基吡啶酮甲酰胺mek抑制剂 |
| HUE036513T2 (hu) | 2011-04-01 | 2018-07-30 | Genentech Inc | AKT inhibitor vegyület és abirateron kombinációja terápiás kezelésekben való alkalmazásra |
| CN103841976A (zh) | 2011-04-01 | 2014-06-04 | 基因泰克公司 | Akt和mek抑制剂化合物的组合及其使用方法 |
| ES2597052T3 (es) | 2011-05-25 | 2017-01-13 | Université Paris Descartes | Inhibidores de ERK para su uso en el tratamiento de atrofia muscular espinal |
| CN103204822B (zh) | 2012-01-17 | 2014-12-03 | 上海科州药物研发有限公司 | 作为蛋白激酶抑制剂的苯并噁唑化合物及其制备方法和用途 |
| WO2015038704A1 (en) | 2013-09-11 | 2015-03-19 | The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone | Compositions for preparing cardiomyocytes |
| EP3094736A4 (en) | 2014-01-14 | 2017-10-25 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for identification, assessment, prevention, and treatment of melanoma using pd-l1 isoforms |
| US20170248603A1 (en) | 2014-10-06 | 2017-08-31 | Dana-Farber Cancer Institute, Inc. | Angiopoiten-2 biomarkers predictive of anti-immune checkpoint response |
| MA41866A (fr) | 2015-03-31 | 2018-02-06 | Massachusetts Gen Hospital | Molécules à auto-assemblage pour l'administration ciblée de médicaments |
| US11124483B2 (en) * | 2015-09-02 | 2021-09-21 | The Regents Of The University Of California | HER3 ligands and uses thereof |
| BR112018006873A2 (pt) | 2015-10-05 | 2018-11-06 | The Trustees Of Columbia University In The City Of New York | ativadores do fluxo autofágico e fosfolipase d e depuração de agregados de proteína incluindo tau e tratamento de proteinopatias |
| JP7333313B2 (ja) * | 2017-09-01 | 2023-08-24 | シャンハイ ファーマシューティカルズ ホールディング カンパニー，リミティド | 窒素含有複素環化合物、製造方法、中間体、組成物および使用 |
| BR112020026148A2 (pt) * | 2018-06-21 | 2021-03-16 | Cellestia Biotech Ag | Processo para fabricar éteres amino diarílicos e sais de cloridratos de éteres amino diarílicos |
| EP3942045A1 (en) | 2019-03-21 | 2022-01-26 | Onxeo | A dbait molecule in combination with kinase inhibitor for the treatment of cancer |
| EP4054579A1 (en) | 2019-11-08 | 2022-09-14 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods for the treatment of cancers that have acquired resistance to kinase inhibitors |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| TW202342018A (zh) | 2022-03-04 | 2023-11-01 | 美商奇奈特生物製藥公司 | Mek激酶抑制劑 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6809097B1 (en) * | 1996-09-25 | 2004-10-26 | Zeneca Limited | Quinoline derivatives inhibiting the effect of growth factors such as VEGF |
| UA73073C2 (uk) * | 1997-04-03 | 2005-06-15 | Уайт Холдінгз Корпорейшн | Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція |
| HUP0003731A3 (en) * | 1997-07-01 | 2002-11-28 | Warner Lambert Co | 4-bromo or 4-iodo phenylamino benzhydroxamic acid derivatives and their use as mek inhibitors |
| SI2253620T1 (sl) * | 1998-09-29 | 2014-06-30 | Wyeth Holdings Llc | Substituirani 3-cianokinolini kot inhibitorji protein tirozin-kinaz |
| UA72749C2 (en) * | 1998-09-29 | 2005-04-15 | White Holdings Corp | Substituted 3-cyanoquinolines, a method for the preparation thereof (variants), pharmaceutical composition based thereon, a method for the treatment, inhibiting the growth or elimination of neoplasms and a method for the treatment, inhibiting progressing or elimination of polycystic kidney disease using them |
-
1999
- 1999-05-08 GB GBGB9910577.7A patent/GB9910577D0/en not_active Ceased
-
2000
- 2000-04-19 GB GBGB0009532.3A patent/GB0009532D0/en not_active Ceased
- 2000-05-03 CZ CZ20013997A patent/CZ20013997A3/cs unknown
- 2000-05-03 PT PT00927491T patent/PT1178967E/pt unknown
- 2000-05-03 EP EP05013587A patent/EP1584619A1/en not_active Withdrawn
- 2000-05-03 SK SK1610-2001A patent/SK16102001A3/sk unknown
- 2000-05-03 EP EP00927491A patent/EP1178967B1/en not_active Expired - Lifetime
- 2000-05-03 CA CA002372663A patent/CA2372663A1/en not_active Abandoned
- 2000-05-03 TR TR2001/03186T patent/TR200103186T2/xx unknown
- 2000-05-03 NZ NZ514980A patent/NZ514980A/en unknown
- 2000-05-03 JP JP2000617181A patent/JP2002544196A/ja active Pending
- 2000-05-03 AT AT00927491T patent/ATE319688T1/de not_active IP Right Cessation
- 2000-05-03 ES ES00927491T patent/ES2258455T3/es not_active Expired - Lifetime
- 2000-05-03 PL PL00352413A patent/PL352413A1/xx not_active Application Discontinuation
- 2000-05-03 KR KR1020017014244A patent/KR100667719B1/ko not_active IP Right Cessation
- 2000-05-03 CN CNB008099596A patent/CN1219768C/zh not_active Expired - Fee Related
- 2000-05-03 DK DK00927491T patent/DK1178967T3/da active
- 2000-05-03 EE EEP200100589A patent/EE200100589A/xx unknown
- 2000-05-03 HU HU0201219A patent/HUP0201219A3/hu unknown
- 2000-05-03 IL IL14631700A patent/IL146317A0/xx unknown
- 2000-05-03 BR BR0010391-8A patent/BR0010391A/pt not_active Application Discontinuation
- 2000-05-03 DE DE60026509T patent/DE60026509T2/de not_active Expired - Fee Related
- 2000-05-03 AU AU45891/00A patent/AU772846B2/en not_active Ceased
- 2000-05-03 WO PCT/GB2000/001697 patent/WO2000068201A1/en active IP Right Grant
-
2001
- 2001-10-30 ZA ZA200108971A patent/ZA200108971B/en unknown
- 2001-10-30 IS IS6138A patent/IS6138A/is unknown
- 2001-11-01 BG BG106073A patent/BG106073A/xx unknown
- 2001-11-07 NO NO20015448A patent/NO321696B1/no unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO321696B1 (no) | Kinolinderivater som inhibitorer av MEK-enzymer, fremgangsmate for fremstilling og anvendelse derav, samt farmasoytisk preparat. | |
| EP1178965B1 (en) | Quinoline derivatives as inhibitors of mek enzymes | |
| US6809106B1 (en) | Quinoline derivatives as inhibitors of MEK enzymes | |
| WO2018035072A1 (en) | 4-substituted aminoisoquinoline derivatives | |
| KR101028952B1 (ko) | 수용체 티로신 키나아제 억제제로서의 퀴나졸린 유사체 | |
| EP2552888B1 (en) | Trpv1 vanilloid receptor antagonists with a bicyclic portion | |
| US12030896B2 (en) | PIKfyve inhibitors | |
| AU2018226922B2 (en) | Urea-substituted aromatic ring-linked dioxane-quinazoline and -linked dioxane-quinoline compounds, preparation method therefor and use thereof | |
| US20050101630A1 (en) | 4-Substituted quinolines as antitumor agents | |
| JPH11513398A (ja) | タンパク質チロシンキナーゼ阻害剤としての二環式複素芳香族化合物 | |
| MXPA02009440A (es) | Inhibidores de proteina cinasa triciclica. | |
| US11548900B2 (en) | Oxazino-quinazoline and oxazino-quinoline type compound, preparation method and uses thereof | |
| WO2018157730A1 (zh) | 脲取代的芳环连二噁烷并喹唑啉与连二噁烷并喹啉类化合物及其制备方法与应用 | |
| CN112794851B (zh) | 3-(吡啶-3基)-7-氮杂吲哚衍生物PI3Kδ抑制剂及其制备方法与应用 | |
| JP2024528251A (ja) | Ｈｄａｃとｎａｄ合成を標的とする多標的阻害剤及びその用途 | |
| MXPA01011360A (en) | Quinoline derivatives asinhibitors of mek enzymes | |
| MXPA01011361A (en) | Quinoline derivatives as inhibitors of mek enzymes | |
| CA2458399A1 (en) | Cyclic indole and heteroindole derivatives, the production and use thereof as medicaments |