JP4386967B2 - プロテインチロシンキナーゼ阻害剤としての縮合複素環式化合物 - Google Patents
プロテインチロシンキナーゼ阻害剤としての縮合複素環式化合物 Download PDFInfo
- Publication number
- JP4386967B2 JP4386967B2 JP50559698A JP50559698A JP4386967B2 JP 4386967 B2 JP4386967 B2 JP 4386967B2 JP 50559698 A JP50559698 A JP 50559698A JP 50559698 A JP50559698 A JP 50559698A JP 4386967 B2 JP4386967 B2 JP 4386967B2
- Authority
- JP
- Japan
- Prior art keywords
- quinazolin
- methyl
- benzyloxy
- amine
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 2
- 239000005483 tyrosine kinase inhibitor Substances 0.000 title 1
- -1 methylsulfonylethylamino, methylsulfinylethylamino, methylsulfonylethyl Chemical group 0.000 claims description 245
- 150000001875 compounds Chemical class 0.000 claims description 206
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- 239000001257 hydrogen Substances 0.000 claims description 60
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 54
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 52
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 44
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 40
- 125000000217 alkyl group Chemical group 0.000 claims description 40
- 239000012453 solvate Substances 0.000 claims description 36
- 238000011282 treatment Methods 0.000 claims description 26
- 125000005843 halogen group Chemical group 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 150000003852 triazoles Chemical class 0.000 claims description 16
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 14
- 125000004175 fluorobenzyl group Chemical group 0.000 claims description 12
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 11
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000006287 difluorobenzyl group Chemical group 0.000 claims description 9
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 9
- 201000011510 cancer Diseases 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- WUJYYMGQHNKEGQ-UHFFFAOYSA-N 6-[5-[[methyl(2-methylsulfonylethyl)amino]methyl]furan-2-yl]-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound O1C(CN(CCS(C)(=O)=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 WUJYYMGQHNKEGQ-UHFFFAOYSA-N 0.000 claims description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 4
- 125000005955 1H-indazolyl group Chemical group 0.000 claims description 3
- CAIJGAFHVSALOJ-UHFFFAOYSA-N 2-[[5-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-yl]methylamino]ethanesulfonamide Chemical compound O1C(CNCCS(=O)(=O)N)=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 CAIJGAFHVSALOJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- MGRNWJPWIAFGQE-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-[5-[(2-methylsulfonylethylamino)methyl]-1,2,4-oxadiazol-3-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=NC(C=2C=C3C(NC=4C=C5C=NN(CC=6C=CC=CC=6)C5=CC=4)=NC=NC3=CC=2)=N1 MGRNWJPWIAFGQE-UHFFFAOYSA-N 0.000 claims description 3
- NIWCLOVPIUBQEZ-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=CC=CC=5)C4=CC=3)C2=C1 NIWCLOVPIUBQEZ-UHFFFAOYSA-N 0.000 claims description 3
- PGUXMZHODKGDJQ-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-7-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(C(NC=2C=C3C=NN(CC=4C=CC=CC=4)C3=CC=2)=NC=N2)C2=C1 PGUXMZHODKGDJQ-UHFFFAOYSA-N 0.000 claims description 3
- JFYXRFGHVISHRB-UHFFFAOYSA-N n-[2-[[5-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-yl]methylamino]ethyl]methanesulfonamide Chemical compound O1C(CNCCNS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 JFYXRFGHVISHRB-UHFFFAOYSA-N 0.000 claims description 3
- GPURBJOXKSEHNK-UHFFFAOYSA-N n-methyl-2-[[5-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-yl]methylamino]ethanesulfonamide Chemical compound O1C(CNCCS(=O)(=O)NC)=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 GPURBJOXKSEHNK-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 239000004471 Glycine Substances 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 2
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 claims description 2
- PEGMJAWCBJOPAD-UHFFFAOYSA-N n-(2-methylsulfonylethyl)-5-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-carboxamide Chemical compound O1C(C(=O)NCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 PEGMJAWCBJOPAD-UHFFFAOYSA-N 0.000 claims description 2
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 202
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 159
- 239000000203 mixture Substances 0.000 description 123
- 239000007787 solid Substances 0.000 description 99
- 238000000034 method Methods 0.000 description 88
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 83
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 71
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 70
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 60
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 60
- 229910052757 nitrogen Inorganic materials 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
- 235000019439 ethyl acetate Nutrition 0.000 description 57
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 238000006243 chemical reaction Methods 0.000 description 51
- 239000000243 solution Substances 0.000 description 47
- 239000000047 product Substances 0.000 description 43
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
- 238000010992 reflux Methods 0.000 description 41
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 29
- 125000000623 heterocyclic group Chemical group 0.000 description 27
- 239000000377 silicon dioxide Substances 0.000 description 27
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 25
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 25
- 238000001914 filtration Methods 0.000 description 25
- 230000000694 effects Effects 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 20
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 20
- 229910052760 oxygen Inorganic materials 0.000 description 19
- 125000001424 substituent group Chemical group 0.000 description 19
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 18
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 18
- 239000003153 chemical reaction reagent Substances 0.000 description 17
- 239000002253 acid Substances 0.000 description 15
- 239000003054 catalyst Substances 0.000 description 14
- 201000010099 disease Diseases 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 239000012299 nitrogen atmosphere Substances 0.000 description 14
- 238000010898 silica gel chromatography Methods 0.000 description 14
- 238000006467 substitution reaction Methods 0.000 description 14
- 229910052717 sulfur Inorganic materials 0.000 description 14
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 13
- 150000001412 amines Chemical class 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 12
- 125000003118 aryl group Chemical group 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 12
- 239000003921 oil Substances 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 10
- 108060006698 EGF receptor Proteins 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 239000006071 cream Substances 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- 238000001665 trituration Methods 0.000 description 10
- AYBKEGIZSWJSIZ-UHFFFAOYSA-N 2-(4-chloroquinazolin-6-yl)-5-(trifluoromethyl)-1,3,4-oxadiazole Chemical compound O1C(C(F)(F)F)=NN=C1C1=CC=C(N=CN=C2Cl)C2=C1 AYBKEGIZSWJSIZ-UHFFFAOYSA-N 0.000 description 9
- YNQNAOZPEQKXJY-UHFFFAOYSA-N 2-(4-chloroquinazolin-6-yl)-5-methyl-1,3,4-oxadiazole Chemical compound O1C(C)=NN=C1C1=CC=C(N=CN=C2Cl)C2=C1 YNQNAOZPEQKXJY-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 9
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 150000003536 tetrazoles Chemical class 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- 229930192474 thiophene Natural products 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 125000002837 carbocyclic group Chemical group 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 7
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- 239000006196 drop Substances 0.000 description 7
- 125000001041 indolyl group Chemical group 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- JQXJBXVWVPVTOO-UHFFFAOYSA-L 4-diphenylphosphanylbutyl(diphenyl)phosphane;palladium(2+);dichloride Chemical compound Cl[Pd]Cl.C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 JQXJBXVWVPVTOO-UHFFFAOYSA-L 0.000 description 6
- XFTUDEYATQLWOU-UHFFFAOYSA-N 6-bromo-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound C12=CC(Br)=CC=C2N=CN=C1NC(C=C1)=CC=C1OCC1=CC=CC=C1 XFTUDEYATQLWOU-UHFFFAOYSA-N 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 6
- 201000004681 Psoriasis Diseases 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 125000005879 dioxolanyl group Chemical group 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 125000004076 pyridyl group Chemical group 0.000 description 6
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 5
- BQUSMTPKYUILPD-UHFFFAOYSA-N 1-benzylindazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC=C1 BQUSMTPKYUILPD-UHFFFAOYSA-N 0.000 description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
- 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 compound 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 5
- FIIDVVUUWRJXLF-UHFFFAOYSA-N 4-phenylmethoxyaniline Chemical compound C1=CC(N)=CC=C1OCC1=CC=CC=C1 FIIDVVUUWRJXLF-UHFFFAOYSA-N 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- 206010006187 Breast cancer Diseases 0.000 description 5
- 208000026310 Breast neoplasm Diseases 0.000 description 5
- VLJNHYLEOZPXFW-BYPYZUCNSA-N L-prolinamide Chemical compound NC(=O)[C@@H]1CCCN1 VLJNHYLEOZPXFW-BYPYZUCNSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 125000004122 cyclic group Chemical group 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 5
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- UYDNPZLYDODKKA-UHFFFAOYSA-N 1-benzylindol-5-amine Chemical compound C1=CC2=CC(N)=CC=C2N1CC1=CC=CC=C1 UYDNPZLYDODKKA-UHFFFAOYSA-N 0.000 description 4
- WCTNNANEJFKYCG-UHFFFAOYSA-N 5-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-carbaldehyde;hydrochloride Chemical compound Cl.O1C(C=O)=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 WCTNNANEJFKYCG-UHFFFAOYSA-N 0.000 description 4
- HOCGWOOAFSKFHG-UHFFFAOYSA-N 5-[4-[(1-benzylindazol-5-yl)amino]quinazolin-6-yl]furan-2-carbaldehyde Chemical compound O1C(C=O)=CC=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=CC=CC=5)C4=CC=3)C2=C1 HOCGWOOAFSKFHG-UHFFFAOYSA-N 0.000 description 4
- VIYRBOKXYWEHRC-UHFFFAOYSA-N 5-[4-[(1-benzylindazol-5-yl)amino]quinazolin-7-yl]furan-2-carbaldehyde Chemical compound O1C(C=O)=CC=C1C1=CC=C(C(NC=2C=C3C=NN(CC=4C=CC=CC=4)C3=CC=2)=NC=N2)C2=C1 VIYRBOKXYWEHRC-UHFFFAOYSA-N 0.000 description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 4
- 101150093908 PDGFRB gene Proteins 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 102000001332 SRC Human genes 0.000 description 4
- 108060006706 SRC Proteins 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000036210 malignancy Effects 0.000 description 4
- 125000001624 naphthyl group Chemical group 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 239000011574 phosphorus Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- MLTAABXMDQKTIZ-LJAQVGFWSA-N (2s)-1-[[5-[4-[(1-benzylindazol-5-yl)amino]quinazolin-6-yl]furan-2-yl]methyl]pyrrolidine-2-carboxamide Chemical compound NC(=O)[C@@H]1CCCN1CC1=CC=C(C=2C=C3C(NC=4C=C5C=NN(CC=6C=CC=CC=6)C5=CC=4)=NC=NC3=CC=2)O1 MLTAABXMDQKTIZ-LJAQVGFWSA-N 0.000 description 3
- NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 3
- HNAXFSKDGWBXFI-UHFFFAOYSA-N 1-[(2-fluorophenyl)methyl]indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC=C1F HNAXFSKDGWBXFI-UHFFFAOYSA-N 0.000 description 3
- BTNPJMNKYNWUPD-UHFFFAOYSA-N 1-[(3-fluorophenyl)methyl]indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC(F)=C1 BTNPJMNKYNWUPD-UHFFFAOYSA-N 0.000 description 3
- FBALMZOHSLGBHL-UHFFFAOYSA-N 1-[[3-[4-[(1-benzylindazol-5-yl)amino]quinazolin-6-yl]-1,2,4-oxadiazol-5-yl]methyl]piperidin-4-one Chemical compound C1CC(=O)CCN1CC1=NC(C=2C=C3C(NC=4C=C5C=NN(CC=6C=CC=CC=6)C5=CC=4)=NC=NC3=CC=2)=NO1 FBALMZOHSLGBHL-UHFFFAOYSA-N 0.000 description 3
- LONPVIGEVNTHTN-UHFFFAOYSA-N 1-benzyl-5-nitroindole Chemical compound C1=CC2=CC([N+](=O)[O-])=CC=C2N1CC1=CC=CC=C1 LONPVIGEVNTHTN-UHFFFAOYSA-N 0.000 description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 3
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 3
- HQNZNIJPAYTWJK-UHFFFAOYSA-N 2-amino-5-cyanobenzoic acid Chemical compound NC1=CC=C(C#N)C=C1C(O)=O HQNZNIJPAYTWJK-UHFFFAOYSA-N 0.000 description 3
- RJRCBHTXQMHLQP-UHFFFAOYSA-N 3-methyl-2-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]imidazole-4-carbaldehyde Chemical compound CN1C(C=O)=CN=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 RJRCBHTXQMHLQP-UHFFFAOYSA-N 0.000 description 3
- ULWXPLHRGWSTAP-UHFFFAOYSA-N 3-methylsulfanyl-2-oxoindole-5-carbonitrile Chemical compound C1=C(C#N)C=CC2=NC(=O)C(SC)=C21 ULWXPLHRGWSTAP-UHFFFAOYSA-N 0.000 description 3
- ARKQSUYCILKUKZ-UHFFFAOYSA-N 4-[(2-fluorophenyl)methoxy]aniline Chemical compound C1=CC(N)=CC=C1OCC1=CC=CC=C1F ARKQSUYCILKUKZ-UHFFFAOYSA-N 0.000 description 3
- LMKDKHDGVBPEKI-UHFFFAOYSA-N 4-[(3-fluorophenyl)methoxy]aniline Chemical compound C1=CC(N)=CC=C1OCC1=CC=CC(F)=C1 LMKDKHDGVBPEKI-UHFFFAOYSA-N 0.000 description 3
- WKJLZHPOOMPGPI-UHFFFAOYSA-N 4-[(4-fluorophenyl)methoxy]aniline Chemical compound C1=CC(N)=CC=C1OCC1=CC=C(F)C=C1 WKJLZHPOOMPGPI-UHFFFAOYSA-N 0.000 description 3
- BIJFAHQDVZZUBO-UHFFFAOYSA-N 5-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-carbaldehyde Chemical compound O1C(C=O)=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 BIJFAHQDVZZUBO-UHFFFAOYSA-N 0.000 description 3
- DIIQEKYPVNCRHF-UHFFFAOYSA-N 6-(3-methylimidazol-4-yl)-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound CN1C=NC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 DIIQEKYPVNCRHF-UHFFFAOYSA-N 0.000 description 3
- IXCKNOPBMIVAMZ-UHFFFAOYSA-N 6-(5-methyl-1,2,4-oxadiazol-3-yl)-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound O1C(C)=NC(C=2C=C3C(NC=4C=CC(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)=N1 IXCKNOPBMIVAMZ-UHFFFAOYSA-N 0.000 description 3
- CJQVGTFFDYKCRG-UHFFFAOYSA-N 6-(furan-2-yl)-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound C=1C=CC=CC=1COC(C=C1)=CC=C1NC(C1=C2)=NC=NC1=CC=C2C1=CC=CO1 CJQVGTFFDYKCRG-UHFFFAOYSA-N 0.000 description 3
- KEAHPTLEJWSJLB-UHFFFAOYSA-N 6-[5-(1,3-dioxolan-2-yl)-1-methylimidazol-2-yl]-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound CN1C(C2OCCO2)=CN=C1C(C=C12)=CC=C1N=CN=C2NC(C=C1)=CC=C1OCC1=CC=CC=C1 KEAHPTLEJWSJLB-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 101150028321 Lck gene Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical group C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000000000 cycloalkoxy group Chemical group 0.000 description 3
- 125000004989 dicarbonyl group Chemical group 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 239000002808 molecular sieve Substances 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- RLJDFBACKBVWIS-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-(5-methyl-1h-1,2,4-triazol-3-yl)quinazolin-4-amine Chemical compound N1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=CC=CC=5)C4=CC=3)C2=C1 RLJDFBACKBVWIS-UHFFFAOYSA-N 0.000 description 3
- OPQBTPSBHMCKCF-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-7-iodoquinazolin-4-amine;hydrochloride Chemical compound Cl.N=1C=NC2=CC(I)=CC=C2C=1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 OPQBTPSBHMCKCF-UHFFFAOYSA-N 0.000 description 3
- IPSWMRTYUZOQMS-UHFFFAOYSA-N n-(4-phenylmethoxyphenyl)-6-pyridin-2-ylquinazolin-4-amine Chemical compound C=1C=CC=CC=1COC(C=C1)=CC=C1NC(C1=C2)=NC=NC1=CC=C2C1=CC=CC=N1 IPSWMRTYUZOQMS-UHFFFAOYSA-N 0.000 description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 230000020477 pH reduction Effects 0.000 description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 229940124617 receptor tyrosine kinase inhibitor Drugs 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- SANWDQJIWZEKOD-UHFFFAOYSA-N tributyl(furan-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CO1 SANWDQJIWZEKOD-UHFFFAOYSA-N 0.000 description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
- FWVJXNJMIWTFLH-NDEPHWFRSA-N (2s)-1-[[3-methyl-2-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]imidazol-4-yl]methyl]pyrrolidine-2-carboxamide Chemical compound C=1N=C(C=2C=C3C(NC=4C=CC(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)N(C)C=1CN1CCC[C@H]1C(N)=O FWVJXNJMIWTFLH-NDEPHWFRSA-N 0.000 description 2
- RZBXGNUKPJTWLR-NDEPHWFRSA-N (2s)-1-[[5-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-yl]methyl]pyrrolidine-2-carboxamide Chemical compound NC(=O)[C@@H]1CCCN1CC1=CC=C(C=2C=C3C(NC=4C=CC(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)O1 RZBXGNUKPJTWLR-NDEPHWFRSA-N 0.000 description 2
- WSKCNVNSSBXCFL-LJAQVGFWSA-N (2s)-1-[[5-[4-[(1-benzylindazol-5-yl)amino]quinazolin-7-yl]furan-2-yl]methyl]pyrrolidine-2-carboxamide Chemical compound NC(=O)[C@@H]1CCCN1CC1=CC=C(C=2C=C3N=CN=C(NC=4C=C5C=NN(CC=6C=CC=CC=6)C5=CC=4)C3=CC=2)O1 WSKCNVNSSBXCFL-LJAQVGFWSA-N 0.000 description 2
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 description 2
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 description 2
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 2
- DDCMQWDHBVDKHH-UHFFFAOYSA-N 1-[(2,3-difluorophenyl)methyl]indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC(F)=C1F DDCMQWDHBVDKHH-UHFFFAOYSA-N 0.000 description 2
- ZEGHCBNPNZAANE-UHFFFAOYSA-N 1-[(3,5-difluorophenyl)methyl]indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC(F)=CC(F)=C1 ZEGHCBNPNZAANE-UHFFFAOYSA-N 0.000 description 2
- VHWVWFPJTDRKIK-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=C(F)C=C1 VHWVWFPJTDRKIK-UHFFFAOYSA-N 0.000 description 2
- HDSSTYCOTGKUGV-UHFFFAOYSA-N 1-[[3-[4-[(1-benzylindazol-5-yl)amino]quinazolin-6-yl]-1,2,4-oxadiazol-5-yl]methyl]pyrrolidin-2-one Chemical compound O=C1CCCN1CC1=NC(C=2C=C3C(NC=4C=C5C=NN(CC=6C=CC=CC=6)C5=CC=4)=NC=NC3=CC=2)=NO1 HDSSTYCOTGKUGV-UHFFFAOYSA-N 0.000 description 2
- MACVPLPBEJHWHK-UHFFFAOYSA-N 1-benzyl-3-methyl-5-nitroindazole Chemical compound C12=CC=C([N+]([O-])=O)C=C2C(C)=NN1CC1=CC=CC=C1 MACVPLPBEJHWHK-UHFFFAOYSA-N 0.000 description 2
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical compound C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 description 2
- KWGRIJKRXDHHEU-UHFFFAOYSA-N 2-(4-chloroquinazolin-7-yl)-5-methyl-1,3,4-oxadiazole Chemical compound O1C(C)=NN=C1C1=CC=C(C(Cl)=NC=N2)C2=C1 KWGRIJKRXDHHEU-UHFFFAOYSA-N 0.000 description 2
- WUHRHZZYEXHURO-UHFFFAOYSA-N 2-[[5-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-yl]methylamino]acetic acid Chemical compound O1C(CNCC(=O)O)=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 WUHRHZZYEXHURO-UHFFFAOYSA-N 0.000 description 2
- DGUVEYAZTOUCEJ-UHFFFAOYSA-N 2-aminoethanesulfonamide;hydron;chloride Chemical compound Cl.NCCS(N)(=O)=O DGUVEYAZTOUCEJ-UHFFFAOYSA-N 0.000 description 2
- UMWIVOZCYNITGG-UHFFFAOYSA-N 2-benzyl-6-nitro-1h-benzimidazole Chemical compound N1C2=CC([N+](=O)[O-])=CC=C2N=C1CC1=CC=CC=C1 UMWIVOZCYNITGG-UHFFFAOYSA-N 0.000 description 2
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 2
- BYNLDHAAXNNWBC-UHFFFAOYSA-N 2-oxo-1h-quinazoline-6-carbonitrile Chemical compound N#CC1=CC=C2NC(=O)N=CC2=C1 BYNLDHAAXNNWBC-UHFFFAOYSA-N 0.000 description 2
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
- XFGRSRQUIAXQNB-UHFFFAOYSA-N 3-chloro-4-[(2-fluorophenyl)methoxy]aniline Chemical compound ClC1=CC(N)=CC=C1OCC1=CC=CC=C1F XFGRSRQUIAXQNB-UHFFFAOYSA-N 0.000 description 2
- AYPFEYDGZDPAPE-UHFFFAOYSA-N 3-chloro-4-[(3-fluorophenyl)methoxy]aniline Chemical compound ClC1=CC(N)=CC=C1OCC1=CC=CC(F)=C1 AYPFEYDGZDPAPE-UHFFFAOYSA-N 0.000 description 2
- GDLMZHDQNPWKOL-UHFFFAOYSA-N 4-(4-phenylmethoxyanilino)quinazoline-6-carbonitrile Chemical compound C12=CC(C#N)=CC=C2N=CN=C1NC(C=C1)=CC=C1OCC1=CC=CC=C1 GDLMZHDQNPWKOL-UHFFFAOYSA-N 0.000 description 2
- GDYFDXDATVPPDR-UHFFFAOYSA-N 4-(benzenesulfonyl)aniline Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=CC=C1 GDYFDXDATVPPDR-UHFFFAOYSA-N 0.000 description 2
- ZSYZKJLWLQAKDV-UHFFFAOYSA-N 4-[(1-benzylindazol-5-yl)amino]quinazoline-6-carbonitrile Chemical compound C12=CC(C#N)=CC=C2N=CN=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 ZSYZKJLWLQAKDV-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 2
- BDXIOIHBIAVXQO-UHFFFAOYSA-N 5-[4-(1-benzylindazol-5-yl)quinazolin-6-yl]-1-methylpyrrole-2-carbaldehyde Chemical compound CN1C(C=O)=CC=C1C1=CC=C(N=CN=C2C=3C=C4C=NN(CC=5C=CC=CC=5)C4=CC=3)C2=C1 BDXIOIHBIAVXQO-UHFFFAOYSA-N 0.000 description 2
- XQLSVKIYPIABLH-UHFFFAOYSA-N 5-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-carboxylic acid Chemical compound O1C(C(=O)O)=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 XQLSVKIYPIABLH-UHFFFAOYSA-N 0.000 description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 2
- QLSXZUNIIAEFJH-UHFFFAOYSA-N 6-(3-methyltriazol-4-yl)-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound CN1N=NC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 QLSXZUNIIAEFJH-UHFFFAOYSA-N 0.000 description 2
- DDFVSQBKLRYMHH-UHFFFAOYSA-N 6-[1-[(dimethylamino)methyl]imidazol-2-yl]-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound CN(C)CN1C=CN=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 DDFVSQBKLRYMHH-UHFFFAOYSA-N 0.000 description 2
- XRNSDKKFYAHDMQ-UHFFFAOYSA-N 6-[1-methyl-5-[(4-methylpiperazin-1-yl)methyl]imidazol-2-yl]-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound C1CN(C)CCN1CC(N1C)=CN=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 XRNSDKKFYAHDMQ-UHFFFAOYSA-N 0.000 description 2
- DDLRBFNQXTZNCO-UHFFFAOYSA-N 6-[5-[(4-methylpiperazin-1-yl)methyl]-1h-imidazol-2-yl]-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound C1CN(C)CCN1CC1=CN=C(C=2C=C3C(NC=4C=CC(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)N1 DDLRBFNQXTZNCO-UHFFFAOYSA-N 0.000 description 2
- ZBPYXLDIAWFMKL-UHFFFAOYSA-N 6-[5-[(4-methylpiperazin-1-yl)methyl]furan-2-yl]-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound C1CN(C)CCN1CC1=CC=C(C=2C=C3C(NC=4C=CC(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)O1 ZBPYXLDIAWFMKL-UHFFFAOYSA-N 0.000 description 2
- QGOVBHYIEBVSTR-UHFFFAOYSA-N 6-[5-[(dimethylamino)methyl]-1,2,4-oxadiazol-3-yl]-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound O1C(CN(C)C)=NC(C=2C=C3C(NC=4C=CC(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)=N1 QGOVBHYIEBVSTR-UHFFFAOYSA-N 0.000 description 2
- VNLDHUMQCKXLGR-UHFFFAOYSA-N 6-[5-[(dimethylamino)methyl]-1-methylimidazol-2-yl]-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound CN1C(CN(C)C)=CN=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 VNLDHUMQCKXLGR-UHFFFAOYSA-N 0.000 description 2
- HISLGIGZZWEZHL-UHFFFAOYSA-N 6-[5-[(dimethylamino)methyl]-1h-imidazol-2-yl]-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound N1C(CN(C)C)=CN=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 HISLGIGZZWEZHL-UHFFFAOYSA-N 0.000 description 2
- AKMJYFOLYCJXDQ-UHFFFAOYSA-N 6-[5-[2-(dimethylamino)ethyl]-1,2,4-oxadiazol-3-yl]-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound O1C(CCN(C)C)=NC(C=2C=C3C(NC=4C=CC(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)=N1 AKMJYFOLYCJXDQ-UHFFFAOYSA-N 0.000 description 2
- JFJNDMNYNYLFLJ-UHFFFAOYSA-N 6-bromo-4-chloroquinazoline Chemical compound C1=C(Br)C=C2C(Cl)=NC=NC2=C1 JFJNDMNYNYLFLJ-UHFFFAOYSA-N 0.000 description 2
- XCIBDBIJADQFFZ-UHFFFAOYSA-N 6-iodo-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound C12=CC(I)=CC=C2N=CN=C1NC(C=C1)=CC=C1OCC1=CC=CC=C1 XCIBDBIJADQFFZ-UHFFFAOYSA-N 0.000 description 2
- AKPILYPROGZDMQ-UHFFFAOYSA-N 7-(5-methyl-1,3,4-oxadiazol-2-yl)-1h-quinazolin-4-one Chemical compound O1C(C)=NN=C1C1=CC=C2C(=O)NC=NC2=C1 AKPILYPROGZDMQ-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 101100503636 Danio rerio fyna gene Proteins 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 101150018272 FYN gene Proteins 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
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 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 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- 206010052779 Transplant rejections Diseases 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 125000005236 alkanoylamino group Chemical group 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 238000001516 cell proliferation assay Methods 0.000 description 2
- 229910052681 coesite Inorganic materials 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 229910052906 cristobalite Inorganic materials 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 2
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- ZFUNPOYWDQHPLK-UHFFFAOYSA-N methyl 5-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-carboxylate Chemical compound O1C(C(=O)OC)=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 ZFUNPOYWDQHPLK-UHFFFAOYSA-N 0.000 description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- FKZACOSGHSJDAI-UHFFFAOYSA-N n'-ethyl-n,n-dimethyl-n'-[[5-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-yl]methyl]ethane-1,2-diamine Chemical class O1C(CN(CCN(C)C)CC)=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 FKZACOSGHSJDAI-UHFFFAOYSA-N 0.000 description 2
- SVNTXNQQSYEWQG-UHFFFAOYSA-N n-(1-benzylindazol-3-yl)-6-iodoquinazolin-4-amine Chemical compound C12=CC(I)=CC=C2N=CN=C1NC(C1=CC=CC=C11)=NN1CC1=CC=CC=C1 SVNTXNQQSYEWQG-UHFFFAOYSA-N 0.000 description 2
- JFOLVNRQZDWUNB-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-[5-(methylsulfonylmethyl)-1,2,4-oxadiazol-3-yl]quinazolin-4-amine Chemical compound O1C(CS(=O)(=O)C)=NC(C=2C=C3C(NC=4C=C5C=NN(CC=6C=CC=CC=6)C5=CC=4)=NC=NC3=CC=2)=N1 JFOLVNRQZDWUNB-UHFFFAOYSA-N 0.000 description 2
- GTVOEOSRZRDGLE-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-[5-(methylsulfonylmethyl)-1,3,4-oxadiazol-2-yl]quinazolin-4-amine Chemical compound O1C(CS(=O)(=O)C)=NN=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=CC=CC=5)C4=CC=3)C2=C1 GTVOEOSRZRDGLE-UHFFFAOYSA-N 0.000 description 2
- FSYWDYHHKVHORW-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-iodoquinazolin-4-amine Chemical compound C12=CC(I)=CC=C2N=CN=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 FSYWDYHHKVHORW-UHFFFAOYSA-N 0.000 description 2
- IXMUQOIKBGOACV-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-7-(3-methylimidazol-4-yl)quinazolin-4-amine Chemical compound CN1C=NC=C1C1=CC=C(C(NC=2C=C3C=NN(CC=4C=CC=CC=4)C3=CC=2)=NC=N2)C2=C1 IXMUQOIKBGOACV-UHFFFAOYSA-N 0.000 description 2
- SYMRMSYWORLBPS-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-7-[5-(1,3-dioxolan-2-yl)furan-2-yl]quinazolin-4-amine;hydrochloride Chemical compound Cl.N1=CC2=CC(NC=3C4=CC=C(C=C4N=CN=3)C=3OC(=CC=3)C3OCCO3)=CC=C2N1CC1=CC=CC=C1 SYMRMSYWORLBPS-UHFFFAOYSA-N 0.000 description 2
- GVYJOLVOGBCHMT-UHFFFAOYSA-N n-(4-phenylmethoxyphenyl)-6-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]quinazolin-4-amine Chemical compound O1C(C(F)(F)F)=NN=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 GVYJOLVOGBCHMT-UHFFFAOYSA-N 0.000 description 2
- YAEOWNWJTHWOJU-UHFFFAOYSA-N n-[1-[(3-fluorophenyl)methyl]indazol-5-yl]-6-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]quinazolin-4-amine Chemical compound FC1=CC=CC(CN2C3=CC=C(NC=4C5=CC(=CC=C5N=CN=4)C=4OC(=NN=4)C(F)(F)F)C=C3C=N2)=C1 YAEOWNWJTHWOJU-UHFFFAOYSA-N 0.000 description 2
- ACETYMWHGHNBOF-UHFFFAOYSA-N n-[1-[(4-fluorophenyl)methyl]indazol-5-yl]-6-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]quinazolin-4-amine Chemical compound C1=CC(F)=CC=C1CN1C2=CC=C(NC=3C4=CC(=CC=C4N=CN=3)C=3OC(=NN=3)C(F)(F)F)C=C2C=N1 ACETYMWHGHNBOF-UHFFFAOYSA-N 0.000 description 2
- UHHLGPSFDKTYSK-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine Chemical compound O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC(F)=CC=4)=CC=3)C2=C1 UHHLGPSFDKTYSK-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- YUSMWODGNWPEBC-UHFFFAOYSA-N n-morpholin-4-ylacetamide Chemical group CC(=O)NN1CCOCC1 YUSMWODGNWPEBC-UHFFFAOYSA-N 0.000 description 2
- PDUSWJORWQPNRP-UHFFFAOYSA-N n-propan-2-ylacetamide Chemical compound CC(C)NC(C)=O PDUSWJORWQPNRP-UHFFFAOYSA-N 0.000 description 2
- 150000002828 nitro derivatives Chemical class 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 238000003566 phosphorylation assay Methods 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000006268 reductive amination reaction Methods 0.000 description 2
- 230000021014 regulation of cell growth Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 125000003638 stannyl group Chemical group [H][Sn]([H])([H])* 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 229910052682 stishovite Inorganic materials 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- MIQQFNUHWRYYFY-UHFFFAOYSA-N tributyl-[5-(1,3-dioxolan-2-yl)furan-2-yl]stannane Chemical compound O1C([Sn](CCCC)(CCCC)CCCC)=CC=C1C1OCCO1 MIQQFNUHWRYYFY-UHFFFAOYSA-N 0.000 description 2
- GMYAQHAKWKXYHG-UHFFFAOYSA-N tributylstannylformonitrile Chemical compound CCCC[Sn](CCCC)(CCCC)C#N GMYAQHAKWKXYHG-UHFFFAOYSA-N 0.000 description 2
- 229910052905 tridymite Inorganic materials 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 231100000588 tumorigenic Toxicity 0.000 description 2
- 230000000381 tumorigenic effect Effects 0.000 description 2
- 229910052721 tungsten Inorganic materials 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 229910052720 vanadium Inorganic materials 0.000 description 2
- MLLMAIJXIZOSFS-LURJTMIESA-N (2s)-n,n-dimethylpyrrolidine-2-carboxamide Chemical group CN(C)C(=O)[C@@H]1CCCN1 MLLMAIJXIZOSFS-LURJTMIESA-N 0.000 description 1
- NLQMSBJFLQPLIJ-UHFFFAOYSA-N (3-methyloxetan-3-yl)methanol Chemical compound OCC1(C)COC1 NLQMSBJFLQPLIJ-UHFFFAOYSA-N 0.000 description 1
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 description 1
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 1
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 description 1
- GJFNRSDCSTVPCJ-UHFFFAOYSA-N 1,8-bis(dimethylamino)naphthalene Chemical compound C1=CC(N(C)C)=C2C(N(C)C)=CC=CC2=C1 GJFNRSDCSTVPCJ-UHFFFAOYSA-N 0.000 description 1
- BCXOSCQTHVTUET-UHFFFAOYSA-N 1-(2-fluoro-5-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC([N+]([O-])=O)=CC=C1F BCXOSCQTHVTUET-UHFFFAOYSA-N 0.000 description 1
- BHOSCKKNURHTND-UHFFFAOYSA-N 1-(benzenesulfonyl)indol-5-amine Chemical compound C1=CC2=CC(N)=CC=C2N1S(=O)(=O)C1=CC=CC=C1 BHOSCKKNURHTND-UHFFFAOYSA-N 0.000 description 1
- LXFNLRHJSUSBFL-UHFFFAOYSA-N 1-(pyridin-2-ylmethyl)indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC=N1 LXFNLRHJSUSBFL-UHFFFAOYSA-N 0.000 description 1
- ZSFTXNIYPDDDSG-UHFFFAOYSA-N 1-(pyridin-3-ylmethyl)indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CN=C1 ZSFTXNIYPDDDSG-UHFFFAOYSA-N 0.000 description 1
- JXYVDGXOCFQXTF-UHFFFAOYSA-N 1-(pyridin-4-ylmethyl)indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=NC=C1 JXYVDGXOCFQXTF-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 description 1
- QRBOICRSKLIRGU-UHFFFAOYSA-N 1-benzyl-3-methylindazol-5-amine;1-benzyl-3-methyl-5-nitroindazole Chemical compound C12=CC=C(N)C=C2C(C)=NN1CC1=CC=CC=C1.C12=CC=C([N+]([O-])=O)C=C2C(C)=NN1CC1=CC=CC=C1 QRBOICRSKLIRGU-UHFFFAOYSA-N 0.000 description 1
- KACWEIWGSHNESJ-UHFFFAOYSA-N 1-benzyl-5-nitroindazole Chemical compound N1=CC2=CC([N+](=O)[O-])=CC=C2N1CC1=CC=CC=C1 KACWEIWGSHNESJ-UHFFFAOYSA-N 0.000 description 1
- MXUBFGQYIZXEOV-UHFFFAOYSA-N 1-benzylindazol-5-amine;1-benzyl-5-nitroindazole Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC=C1.N1=CC2=CC([N+](=O)[O-])=CC=C2N1CC1=CC=CC=C1 MXUBFGQYIZXEOV-UHFFFAOYSA-N 0.000 description 1
- CKZUIHNIFQRRNE-UHFFFAOYSA-N 1-methyl-5-tributylstannylpyrrole-2-carbaldehyde Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=C(C=O)N1C CKZUIHNIFQRRNE-UHFFFAOYSA-N 0.000 description 1
- CCOYVBNBUMGEAZ-UHFFFAOYSA-N 1-methylsulfonylethene;hydrochloride Chemical compound Cl.CS(=O)(=O)C=C CCOYVBNBUMGEAZ-UHFFFAOYSA-N 0.000 description 1
- XYPYBPCIYDQYKP-UHFFFAOYSA-N 1-n,1-n-dimethyl-2-n-[[5-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-yl]methyl]propane-1,2-diamine Chemical compound O1C(CNC(CN(C)C)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 XYPYBPCIYDQYKP-UHFFFAOYSA-N 0.000 description 1
- RRQHLOZQFPWDCA-UHFFFAOYSA-N 1-n,1-n-dimethylpropane-1,2-diamine Chemical compound CC(N)CN(C)C RRQHLOZQFPWDCA-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- YDTDKKULPWTHRV-UHFFFAOYSA-N 1H-indazol-3-amine Chemical compound C1=CC=C2C(N)=NNC2=C1 YDTDKKULPWTHRV-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical class C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- ZTNUCKSQJANOAC-UHFFFAOYSA-N 2,2,2-trifluoro-n-(2-methylsulfanylethyl)acetamide Chemical compound CSCCNC(=O)C(F)(F)F ZTNUCKSQJANOAC-UHFFFAOYSA-N 0.000 description 1
- LHVCSRDYAQDDSF-UHFFFAOYSA-N 2,2,2-trifluoro-n-(2-methylsulfonylethyl)acetamide Chemical compound CS(=O)(=O)CCNC(=O)C(F)(F)F LHVCSRDYAQDDSF-UHFFFAOYSA-N 0.000 description 1
- BBUPBICWUURTNP-UHFFFAOYSA-N 2,4-dimethyl-1-nitrobenzene Chemical group CC1=CC=C([N+]([O-])=O)C(C)=C1 BBUPBICWUURTNP-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- 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 1
- MQTBODNTRQAUSK-UHFFFAOYSA-N 2-benzyl-3h-benzimidazol-5-amine Chemical compound N1C2=CC(N)=CC=C2N=C1CC1=CC=CC=C1 MQTBODNTRQAUSK-UHFFFAOYSA-N 0.000 description 1
- WOBMUXLADQPSBY-UHFFFAOYSA-N 2-benzyl-5-nitro-1,3-dihydroindazole Chemical compound C1C2=CC([N+](=O)[O-])=CC=C2NN1CC1=CC=CC=C1 WOBMUXLADQPSBY-UHFFFAOYSA-N 0.000 description 1
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
- IKMGEAMKZUENRW-UHFFFAOYSA-N 2-methylsulfanylbutanoic acid Chemical compound CCC(SC)C(O)=O IKMGEAMKZUENRW-UHFFFAOYSA-N 0.000 description 1
- CYWGSFFHHMQKET-UHFFFAOYSA-N 2-methylsulfanylethanamine Chemical compound CSCCN CYWGSFFHHMQKET-UHFFFAOYSA-N 0.000 description 1
- NYEHUAQIJXERLP-UHFFFAOYSA-N 2-methylsulfonylacetic acid Chemical compound CS(=O)(=O)CC(O)=O NYEHUAQIJXERLP-UHFFFAOYSA-N 0.000 description 1
- SDNXQWUJWNTDCC-UHFFFAOYSA-N 2-methylsulfonylethanamine Chemical compound CS(=O)(=O)CCN SDNXQWUJWNTDCC-UHFFFAOYSA-N 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- 125000001698 2H-pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- QGKGASXQTBQINX-UHFFFAOYSA-N 3,4-dihydro-1h-pyrimidin-2-one Chemical compound O=C1NCC=CN1 QGKGASXQTBQINX-UHFFFAOYSA-N 0.000 description 1
- HGYOGEUJBFVPFC-UHFFFAOYSA-N 3-[[3-[4-[(1-benzylindazol-5-yl)amino]quinazolin-6-yl]-1,2,4-oxadiazol-5-yl]methyl]imidazolidine-2,4-dione Chemical compound O=C1CNC(=O)N1CC1=NC(C=2C=C3C(NC=4C=C5C=NN(CC=6C=CC=CC=6)C5=CC=4)=NC=NC3=CC=2)=NO1 HGYOGEUJBFVPFC-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
- VQCZIZIHGIJMII-UHFFFAOYSA-N 3-chloro-4-[(4-fluorophenyl)methoxy]aniline Chemical compound ClC1=CC(N)=CC=C1OCC1=CC=C(F)C=C1 VQCZIZIHGIJMII-UHFFFAOYSA-N 0.000 description 1
- DKTRZBWXGOPYIX-UHFFFAOYSA-N 3-chloro-4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C(Cl)=C1 DKTRZBWXGOPYIX-UHFFFAOYSA-N 0.000 description 1
- WOWKZTBVWKKGJV-UHFFFAOYSA-N 3-chloro-4-phenylmethoxyaniline Chemical compound ClC1=CC(N)=CC=C1OCC1=CC=CC=C1 WOWKZTBVWKKGJV-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- NDXVNFXIIDXXNL-UHFFFAOYSA-N 4-(5-ethylfuran-2-yl)-2-methoxyphenol Chemical compound O1C(CC)=CC=C1C1=CC=C(O)C(OC)=C1 NDXVNFXIIDXXNL-UHFFFAOYSA-N 0.000 description 1
- OCELZBJNNVNSDE-UHFFFAOYSA-N 4-(pyridin-3-ylmethoxy)aniline Chemical compound C1=CC(N)=CC=C1OCC1=CC=CN=C1 OCELZBJNNVNSDE-UHFFFAOYSA-N 0.000 description 1
- MSDIPDIUEFTOFP-UHFFFAOYSA-N 4-[(1-benzylindazol-5-yl)amino]quinazoline-6-carboxylic acid Chemical compound C12=CC(C(=O)O)=CC=C2N=CN=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 MSDIPDIUEFTOFP-UHFFFAOYSA-N 0.000 description 1
- YBAZINRZQSAIAY-UHFFFAOYSA-N 4-aminobenzonitrile Chemical compound NC1=CC=C(C#N)C=C1 YBAZINRZQSAIAY-UHFFFAOYSA-N 0.000 description 1
- BDAIUOPDSRAOKI-UHFFFAOYSA-N 4-chloro-6-iodoquinazoline Chemical compound C1=C(I)C=C2C(Cl)=NC=NC2=C1 BDAIUOPDSRAOKI-UHFFFAOYSA-N 0.000 description 1
- HUPMXDXBIIKREP-UHFFFAOYSA-N 4-chloro-6-iodoquinazoline;6-iodo-n-(4-phenylmethoxyphenyl)quinazolin-4-amine;hydrochloride Chemical compound Cl.C1=C(I)C=C2C(Cl)=NC=NC2=C1.C12=CC(I)=CC=C2N=CN=C1NC(C=C1)=CC=C1OCC1=CC=CC=C1 HUPMXDXBIIKREP-UHFFFAOYSA-N 0.000 description 1
- BOAIUOKCWDUAKA-UHFFFAOYSA-N 4-chloro-7-iodoquinazoline 7-iodo-3H-quinazolin-4-one Chemical compound IC1=CC=C2C(Cl)=NC=NC2=C1.N1C=NC(=O)C=2C1=CC(I)=CC=2 BOAIUOKCWDUAKA-UHFFFAOYSA-N 0.000 description 1
- RAUWPNXIALNKQM-UHFFFAOYSA-N 4-nitro-1,2-phenylenediamine Chemical compound NC1=CC=C([N+]([O-])=O)C=C1N RAUWPNXIALNKQM-UHFFFAOYSA-N 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
- WARFZQDQEUGANF-UHFFFAOYSA-N 4-oxo-1h-quinazoline-6-carboxylic acid Chemical compound N1C=NC(=O)C2=CC(C(=O)O)=CC=C21 WARFZQDQEUGANF-UHFFFAOYSA-N 0.000 description 1
- ICASWNVSUDFGRH-UHFFFAOYSA-N 4-oxo-1h-quinazoline-7-carboxylic acid Chemical compound N1C=NC(=O)C=2C1=CC(C(=O)O)=CC=2 ICASWNVSUDFGRH-UHFFFAOYSA-N 0.000 description 1
- WOYZXEVUWXQVNV-UHFFFAOYSA-N 4-phenoxyaniline Chemical compound C1=CC(N)=CC=C1OC1=CC=CC=C1 WOYZXEVUWXQVNV-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- FPZYEKYQKDCXQS-UHFFFAOYSA-N 5-(1,3-dioxolan-2-yl)-1-methylimidazole Chemical compound CN1C=NC=C1C1OCCO1 FPZYEKYQKDCXQS-UHFFFAOYSA-N 0.000 description 1
- WEEOMBCRESPONB-UHFFFAOYSA-N 5-(1,3-dioxolan-2-yl)-1-methylimidazole 3-methylimidazole-4-carbaldehyde Chemical compound CN1C=NC=C1C=O.CN1C=NC=C1C1OCCO1 WEEOMBCRESPONB-UHFFFAOYSA-N 0.000 description 1
- FKEJGSNMBSSIBL-UHFFFAOYSA-N 5-[4-(1-benzylindazol-5-yl)quinazolin-7-yl]furan-2-carbaldehyde Chemical compound O1C(C=O)=CC=C1C1=CC=C(C(=NC=N2)C=3C=C4C=NN(CC=5C=CC=CC=5)C4=CC=3)C2=C1 FKEJGSNMBSSIBL-UHFFFAOYSA-N 0.000 description 1
- WSGURAYTCUVDQL-UHFFFAOYSA-N 5-nitro-1h-indazole Chemical compound [O-][N+](=O)C1=CC=C2NN=CC2=C1 WSGURAYTCUVDQL-UHFFFAOYSA-N 0.000 description 1
- OZFPSOBLQZPIAV-UHFFFAOYSA-N 5-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2NC=CC2=C1 OZFPSOBLQZPIAV-UHFFFAOYSA-N 0.000 description 1
- HQYVSCBOKHTQHU-UHFFFAOYSA-O 6-(1-methylpyridin-1-ium-2-yl)-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound C[N+]1=CC=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 HQYVSCBOKHTQHU-UHFFFAOYSA-O 0.000 description 1
- PLLFLDVJQAWGFY-UHFFFAOYSA-N 6-(1h-imidazol-2-yl)-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound C=1C=CC=CC=1COC(C=C1)=CC=C1NC(C1=C2)=NC=NC1=CC=C2C1=NC=CN1 PLLFLDVJQAWGFY-UHFFFAOYSA-N 0.000 description 1
- NPBSQINABLCDFF-UHFFFAOYSA-N 6-(2,3-dihydrofuran-5-yl)-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound C=1C=CC=CC=1COC(C=C1)=CC=C1NC(C1=C2)=NC=NC1=CC=C2C1=CCCO1 NPBSQINABLCDFF-UHFFFAOYSA-N 0.000 description 1
- SIDVCHIGGCUYSZ-UHFFFAOYSA-N 6-(2,3-dimethylimidazol-4-yl)-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound CN1C(C)=NC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 SIDVCHIGGCUYSZ-UHFFFAOYSA-N 0.000 description 1
- FCWRXQVKYNDHHI-UHFFFAOYSA-N 6-(2h-tetrazol-5-yl)-1h-quinazolin-4-one;6-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]-1h-quinazolin-4-one Chemical compound C1=C2C(=O)NC=NC2=CC=C1C1=NN=NN1.O1C(C(F)(F)F)=NN=C1C1=CC=C(N=CNC2=O)C2=C1 FCWRXQVKYNDHHI-UHFFFAOYSA-N 0.000 description 1
- RFZUTZXXKUSJFO-UHFFFAOYSA-N 6-(3-methyl-1,2-oxazol-4-yl)-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound CC1=NOC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 RFZUTZXXKUSJFO-UHFFFAOYSA-N 0.000 description 1
- UJUQXXAYHBXBPU-UHFFFAOYSA-N 6-(3-methyl-1,2-oxazol-5-yl)-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound O1N=C(C)C=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 UJUQXXAYHBXBPU-UHFFFAOYSA-N 0.000 description 1
- OBSYEAJYCVVIOV-UHFFFAOYSA-N 6-(5-methyl-1,3,4-oxadiazol-2-yl)-1h-quinazolin-4-one Chemical compound O1C(C)=NN=C1C1=CC=C(N=CNC2=O)C2=C1 OBSYEAJYCVVIOV-UHFFFAOYSA-N 0.000 description 1
- KJSQNQPWULHTBH-UHFFFAOYSA-N 6-(5-methyl-1,3,4-oxadiazol-2-yl)-n-(4-phenoxyphenyl)quinazolin-4-amine Chemical compound O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=CC(OC=4C=CC=CC=4)=CC=3)C2=C1 KJSQNQPWULHTBH-UHFFFAOYSA-N 0.000 description 1
- NKNRVGIFCBEBNV-UHFFFAOYSA-N 6-(5-methyl-1,3,4-oxadiazol-2-yl)-n-(4-phenoxyphenyl)quinazolin-4-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=CC(OC=4C=CC=CC=4)=CC=3)C2=C1 NKNRVGIFCBEBNV-UHFFFAOYSA-N 0.000 description 1
- NZVJGHZEWMDZBN-UHFFFAOYSA-N 6-(5-methyl-1,3,4-oxadiazol-2-yl)-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 NZVJGHZEWMDZBN-UHFFFAOYSA-N 0.000 description 1
- CZWIJQWLJOIHMG-UHFFFAOYSA-N 6-(5-methyl-1,3,4-oxadiazol-2-yl)-n-(4-phenylmethoxyphenyl)quinazolin-4-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 CZWIJQWLJOIHMG-UHFFFAOYSA-N 0.000 description 1
- NWHLKMUARSJBKQ-UHFFFAOYSA-N 6-[1-[(4-methylpiperazin-1-yl)methyl]imidazol-2-yl]-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound C1CN(C)CCN1CN1C(C=2C=C3C(NC=4C=CC(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)=NC=C1 NWHLKMUARSJBKQ-UHFFFAOYSA-N 0.000 description 1
- LYNQZHMQTTYLQG-UHFFFAOYSA-N 6-[5-(1,3-dioxolan-2-yl)furan-2-yl]-4-N'-(4-phenylmethoxyphenyl)-1H-quinazoline-4,4-diamine 5-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-carbaldehyde hydrochloride Chemical compound C(C1=CC=CC=C1)OC1=CC=C(C=C1)NC1(NC=NC2=CC=C(C=C12)C=1OC(=CC1)C1OCCO1)N.Cl.C(C1=CC=CC=C1)OC1=CC=C(C=C1)NC1=NC=NC2=CC=C(C=C12)C1=CC=C(O1)C=O LYNQZHMQTTYLQG-UHFFFAOYSA-N 0.000 description 1
- IYAVQEWPVOAEAD-UHFFFAOYSA-N 6-[5-[(oxolan-2-ylmethylamino)methyl]furan-2-yl]-n-(4-phenylmethoxyphenyl)quinazolin-4-amine Chemical compound C1CCOC1CNCC(O1)=CC=C1C(C=C12)=CC=C1N=CN=C2NC(C=C1)=CC=C1OCC1=CC=CC=C1 IYAVQEWPVOAEAD-UHFFFAOYSA-N 0.000 description 1
- YAPMNNSFLAQFBM-UHFFFAOYSA-N 6-[5-[(oxolan-2-ylmethylamino)methyl]furan-2-yl]-n-(4-phenylmethoxyphenyl)quinazolin-4-amine;hydrochloride Chemical compound Cl.C1CCOC1CNCC(O1)=CC=C1C(C=C12)=CC=C1N=CN=C2NC(C=C1)=CC=C1OCC1=CC=CC=C1 YAPMNNSFLAQFBM-UHFFFAOYSA-N 0.000 description 1
- VRQJVYBCVCWCTJ-UHFFFAOYSA-N 6-bromo-4-chloroquinazoline;6-bromo-n-(4-phenylmethoxyphenyl)quinazolin-4-amine;hydrochloride Chemical compound Cl.C1=C(Br)C=C2C(Cl)=NC=NC2=C1.C12=CC(Br)=CC=C2N=CN=C1NC(C=C1)=CC=C1OCC1=CC=CC=C1 VRQJVYBCVCWCTJ-UHFFFAOYSA-N 0.000 description 1
- HGNPSLRFAICFIH-UHFFFAOYSA-N 6-iodo-3H-quinazolin-4-one 4-oxo-3H-quinazoline-6-carbonitrile Chemical compound N1C=NC(=O)C2=CC(I)=CC=C21.C1=C(C#N)C=C2C(=O)N=CNC2=C1 HGNPSLRFAICFIH-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- HIDYBUANPLOXCP-UHFFFAOYSA-N C(C)(=O)NCCN.CS(=O)(=O)NCCNC(C)=O Chemical compound C(C)(=O)NCCN.CS(=O)(=O)NCCNC(C)=O HIDYBUANPLOXCP-UHFFFAOYSA-N 0.000 description 1
- MOTNGKGJCGZDIT-UHFFFAOYSA-N C(C1=CC=CC=C1)N1N=CC2=CC(=CC=C12)NC1=NC=NC2=CC=C(C=C12)Br.C(C1=CC=CC=C1)N1N=CC2=CC(=CC=C12)NC1=NC=NC2=CC=C(C=C12)C=1OC(=CC1)C1OCCO1 Chemical compound C(C1=CC=CC=C1)N1N=CC2=CC(=CC=C12)NC1=NC=NC2=CC=C(C=C12)Br.C(C1=CC=CC=C1)N1N=CC2=CC(=CC=C12)NC1=NC=NC2=CC=C(C=C12)C=1OC(=CC1)C1OCCO1 MOTNGKGJCGZDIT-UHFFFAOYSA-N 0.000 description 1
- NBFLKRCWTGDJBJ-UHFFFAOYSA-N C1(=CC=CC=C1)S(=O)(=O)C1=CNC2=CC(=CC=C12)[N+](=O)[O-].C1(=CC=CC=C1)S(=O)(=O)C1=CNC2=CC(=CC=C12)N Chemical compound C1(=CC=CC=C1)S(=O)(=O)C1=CNC2=CC(=CC=C12)[N+](=O)[O-].C1(=CC=CC=C1)S(=O)(=O)C1=CNC2=CC(=CC=C12)N NBFLKRCWTGDJBJ-UHFFFAOYSA-N 0.000 description 1
- ZOLPEBMNABWXPR-UHFFFAOYSA-N C1=CC=C(C=C1)COC2=CC=C(C=C2)C3=NC=C4C=C(C=CC4=N3)I Chemical compound C1=CC=C(C=C1)COC2=CC=C(C=C2)C3=NC=C4C=C(C=CC4=N3)I ZOLPEBMNABWXPR-UHFFFAOYSA-N 0.000 description 1
- SKVMZGKIOYYDGI-UHFFFAOYSA-N C1CCN(C(=O)C1)CC2=NC(=NO2)C3=CC4=C(C=C3)N=CN=C4NC5=CC6=C(C=C5)N(N=C6)CC7=CC=CC=C7 Chemical compound C1CCN(C(=O)C1)CC2=NC(=NO2)C3=CC4=C(C=C3)N=CN=C4NC5=CC6=C(C=C5)N(N=C6)CC7=CC=CC=C7 SKVMZGKIOYYDGI-UHFFFAOYSA-N 0.000 description 1
- RZNWEGIMFKVIIU-UHFFFAOYSA-N CC1C2=C(C=CC=C2N=N1)C3=CC4=C(C=C3)N=CN=C4NC5=CC6=C(C=C5)N(N=C6)CC7=CC=CC=C7 Chemical compound CC1C2=C(C=CC=C2N=N1)C3=CC4=C(C=C3)N=CN=C4NC5=CC6=C(C=C5)N(N=C6)CC7=CC=CC=C7 RZNWEGIMFKVIIU-UHFFFAOYSA-N 0.000 description 1
- YTYMHRQHNDLKFS-UHFFFAOYSA-N CN1C2=CC=CC=C2CN1C3=CC4=C(C=C3)N=CN=C4NC5=CC6=C(C=C5)N(N=C6)CC7=CC=CC=C7 Chemical compound CN1C2=CC=CC=C2CN1C3=CC4=C(C=C3)N=CN=C4NC5=CC6=C(C=C5)N(N=C6)CC7=CC=CC=C7 YTYMHRQHNDLKFS-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-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
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-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
- 241000792859 Enema Species 0.000 description 1
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 1
- 241000400611 Eucalyptus deanei Species 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- CXFATHMTBJEEIF-UHFFFAOYSA-N FC(C(=O)OC(C(F)(F)F)=O)(F)F.CSCCNC(C(F)(F)F)=O Chemical compound FC(C(=O)OC(C(F)(F)F)=O)(F)F.CSCCNC(C(F)(F)F)=O CXFATHMTBJEEIF-UHFFFAOYSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 1
- 101710150918 Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- UZEHAKLHBUVTHN-UHFFFAOYSA-N N-(1-benzylindazol-5-yl)-6-(3-methyl-1,2,4-oxadiazol-5-yl)quinazolin-4-amine 4-(1-benzylindazol-5-yl)quinazoline-6-carboxylic acid hydrochloride Chemical compound C(C1=CC=CC=C1)N1N=CC2=CC(=CC=C12)C1=NC=NC2=CC=C(C=C12)C(=O)O.Cl.C(C1=CC=CC=C1)N1N=CC2=CC(=CC=C12)NC1=NC=NC2=CC=C(C=C12)C1=NC(=NO1)C UZEHAKLHBUVTHN-UHFFFAOYSA-N 0.000 description 1
- JYGBIGTZIINWIT-UHFFFAOYSA-N N-(1-benzylindazol-5-yl)-7-iodoquinazolin-4-amine 4-chloro-7-iodoquinazoline hydrochloride Chemical compound ClC1=NC=NC2=CC(=CC=C12)I.Cl.C(C1=CC=CC=C1)N1N=CC2=CC(=CC=C12)NC1=NC=NC2=CC(=CC=C12)I JYGBIGTZIINWIT-UHFFFAOYSA-N 0.000 description 1
- OYBJCMINOGIUIS-UHFFFAOYSA-N N-(2-aminoethyl)methanesulfonamide N-[2-(methanesulfonamido)ethyl]acetamide hydrochloride Chemical compound CS(=O)(=O)NCCNC(C)=O.Cl.CS(=O)(=O)NCCN OYBJCMINOGIUIS-UHFFFAOYSA-N 0.000 description 1
- JLPDRFTUDWZBFT-UHFFFAOYSA-N N1C=NC=C1.CN(C)CCCN1C=NC=C1 Chemical compound N1C=NC=C1.CN(C)CCCN1C=NC=C1 JLPDRFTUDWZBFT-UHFFFAOYSA-N 0.000 description 1
- PJNABMZMQOMVLD-UHFFFAOYSA-N NC1=CC=C2C(NC=NC2=C1)=O.IC1=CC=C2C(NC=NC2=C1)=O Chemical compound NC1=CC=C2C(NC=NC2=C1)=O.IC1=CC=C2C(NC=NC2=C1)=O PJNABMZMQOMVLD-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000012425 OXONE® Substances 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- 108091008606 PDGF receptors Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 108091005682 Receptor kinases Proteins 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000004280 Sodium formate Substances 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 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
- 208000007536 Thrombosis Diseases 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- YCFQZBVUTQXHCS-UHFFFAOYSA-N [6-(methylamino)pyridin-3-yl]boronic acid Chemical compound CNC1=CC=C(B(O)O)C=N1 YCFQZBVUTQXHCS-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- PMZXXNPJQYDFJX-UHFFFAOYSA-N acetonitrile;2,2,2-trifluoroacetic acid Chemical compound CC#N.OC(=O)C(F)(F)F PMZXXNPJQYDFJX-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000001994 activation Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical group 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000000320 amidine group Chemical group 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 125000003705 anilinocarbonyl group Chemical group O=C([*])N([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 238000011394 anticancer treatment Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000005418 aryl aryl group Chemical group 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 125000005135 aryl sulfinyl group Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 125000005110 aryl thio group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- KHBQMWCZKVMBLN-IDEBNGHGSA-N benzenesulfonamide Chemical group NS(=O)(=O)[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 KHBQMWCZKVMBLN-IDEBNGHGSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=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
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- MSJHOJKVMMEMNX-UHFFFAOYSA-N benzylhydrazine;hydron;dichloride Chemical compound Cl.Cl.NNCC1=CC=CC=C1 MSJHOJKVMMEMNX-UHFFFAOYSA-N 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 201000011263 bladder neck cancer Diseases 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 210000000069 breast epithelial cell Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- FAOSYNUKPVJLNZ-UHFFFAOYSA-N butylstannane Chemical compound CCCC[SnH3] FAOSYNUKPVJLNZ-UHFFFAOYSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- XEVRDFDBXJMZFG-UHFFFAOYSA-N carbonyl dihydrazine Chemical compound NNC(=O)NN XEVRDFDBXJMZFG-UHFFFAOYSA-N 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000062 cyclohexylmethoxy group Chemical group [H]C([H])(O*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 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
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- SCTURDALIRIMLW-UHFFFAOYSA-N furan-2-carboxylic acid methyl furan-2-carboxylate Chemical compound COC(=O)C1=CC=CO1.C1=COC(=C1)C(=O)O SCTURDALIRIMLW-UHFFFAOYSA-N 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002390 heteroarenes Chemical class 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008308 lipophilic cream Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- LRZFEBJUJIQVDQ-UHFFFAOYSA-N methyl 2-(dimethylamino)acetate Chemical compound COC(=O)CN(C)C LRZFEBJUJIQVDQ-UHFFFAOYSA-N 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N methylimidazole Natural products CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- TTYMURDBXAIXQT-UHFFFAOYSA-N n'-(1,3-dichlorohexyl)methanediimine Chemical compound CCCC(Cl)CC(Cl)N=C=N TTYMURDBXAIXQT-UHFFFAOYSA-N 0.000 description 1
- AEXITZJSLGALNH-UHFFFAOYSA-N n'-hydroxyethanimidamide Chemical compound CC(N)=NO AEXITZJSLGALNH-UHFFFAOYSA-N 0.000 description 1
- HWKMMJWNGVLBLE-UHFFFAOYSA-N n,n-dimethyl-3-(2-tributylstannylimidazol-1-yl)propan-1-amine Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CN1CCCN(C)C HWKMMJWNGVLBLE-UHFFFAOYSA-N 0.000 description 1
- KCQLFQFWEGMJOR-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-(1-methylimidazol-2-yl)quinazolin-4-amine Chemical compound CN1C=CN=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=CC=CC=5)C4=CC=3)C2=C1 KCQLFQFWEGMJOR-UHFFFAOYSA-N 0.000 description 1
- CDAIHZYEQRRBOQ-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-(1-methylpyrrol-2-yl)quinazolin-4-amine Chemical compound CN1C=CC=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=CC=CC=5)C4=CC=3)C2=C1 CDAIHZYEQRRBOQ-UHFFFAOYSA-N 0.000 description 1
- JHUFGOTUDFPRRZ-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-(3-methyl-1,2,4-oxadiazol-5-yl)quinazolin-4-amine Chemical compound CC1=NOC(C=2C=C3C(NC=4C=C5C=NN(CC=6C=CC=CC=6)C5=CC=4)=NC=NC3=CC=2)=N1 JHUFGOTUDFPRRZ-UHFFFAOYSA-N 0.000 description 1
- WEVYGRGHPNEVKY-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-(3-methylimidazol-4-yl)quinazolin-4-amine Chemical compound CN1C=NC=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=CC=CC=5)C4=CC=3)C2=C1 WEVYGRGHPNEVKY-UHFFFAOYSA-N 0.000 description 1
- YFDZYYZUHAJGIY-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=CC=CC=5)C4=CC=3)C2=C1 YFDZYYZUHAJGIY-UHFFFAOYSA-N 0.000 description 1
- UGAONAODKSPHBU-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-[1-methyl-5-[(2-methylsulfonylethylamino)methyl]pyrrol-2-yl]quinazolin-4-amine Chemical compound CN1C(CNCCS(C)(=O)=O)=CC=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=CC=CC=5)C4=CC=3)C2=C1 UGAONAODKSPHBU-UHFFFAOYSA-N 0.000 description 1
- PPSPNYYHBDGVGY-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-[5-(1,3-dioxolan-2-yl)furan-2-yl]quinazolin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC(=CC=C4N=CN=3)C=3OC(=CC=3)C3OCCO3)=CC=C2N1CC1=CC=CC=C1 PPSPNYYHBDGVGY-UHFFFAOYSA-N 0.000 description 1
- JPZWLOBWXBNLHW-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]quinazolin-4-amine;hydrochloride Chemical compound Cl.O1C(C(F)(F)F)=NN=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=CC=CC=5)C4=CC=3)C2=C1 JPZWLOBWXBNLHW-UHFFFAOYSA-N 0.000 description 1
- FOZDJUHVXCDQEL-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-bromoquinazolin-4-amine Chemical compound C12=CC(Br)=CC=C2N=CN=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 FOZDJUHVXCDQEL-UHFFFAOYSA-N 0.000 description 1
- ZTCMPWIRTIDASY-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-iodoquinazolin-2-amine Chemical compound N1=CC2=CC(I)=CC=C2N=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 ZTCMPWIRTIDASY-UHFFFAOYSA-N 0.000 description 1
- QSMRESHHDSKFHK-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-iodoquinazolin-4-amine;4-chloro-6-iodoquinazoline;hydrochloride Chemical compound Cl.C1=C(I)C=C2C(Cl)=NC=NC2=C1.C12=CC(I)=CC=C2N=CN=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 QSMRESHHDSKFHK-UHFFFAOYSA-N 0.000 description 1
- OJMVLWOLSOWVGJ-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-iodoquinazolin-4-amine;hydrochloride Chemical compound Cl.C12=CC(I)=CC=C2N=CN=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 OJMVLWOLSOWVGJ-UHFFFAOYSA-N 0.000 description 1
- PQRCJDVGGRKFLG-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-7-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine Chemical compound O1C(C)=NN=C1C1=CC=C(C(NC=2C=C3C=NN(CC=4C=CC=CC=4)C3=CC=2)=NC=N2)C2=C1 PQRCJDVGGRKFLG-UHFFFAOYSA-N 0.000 description 1
- OSDSHQGTZNROGS-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-7-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C1=CC=C(C(NC=2C=C3C=NN(CC=4C=CC=CC=4)C3=CC=2)=NC=N2)C2=C1 OSDSHQGTZNROGS-UHFFFAOYSA-N 0.000 description 1
- WGCYCBPIMSRVPN-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-7-(furan-2-yl)quinazolin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC=C(C=C4N=CN=3)C=3OC=CC=3)=CC=C2N1CC1=CC=CC=C1 WGCYCBPIMSRVPN-UHFFFAOYSA-N 0.000 description 1
- TUNBYJPNCLOFPC-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-7-(furan-2-yl)quinazolin-4-amine;hydrochloride Chemical compound Cl.N1=CC2=CC(NC=3C4=CC=C(C=C4N=CN=3)C=3OC=CC=3)=CC=C2N1CC1=CC=CC=C1 TUNBYJPNCLOFPC-UHFFFAOYSA-N 0.000 description 1
- ZMHFJXUKMNQWAN-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-7-[5-(1,3-dioxolan-2-yl)furan-2-yl]quinazolin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC=C(C=C4N=CN=3)C=3OC(=CC=3)C3OCCO3)=CC=C2N1CC1=CC=CC=C1 ZMHFJXUKMNQWAN-UHFFFAOYSA-N 0.000 description 1
- GCDZDXVTDCMNMN-UHFFFAOYSA-N n-(2-aminoethyl)methanesulfonamide Chemical compound CS(=O)(=O)NCCN GCDZDXVTDCMNMN-UHFFFAOYSA-N 0.000 description 1
- DBFSVVANBGKWKF-UHFFFAOYSA-N n-(4-phenylmethoxyphenyl)-6-(2h-tetrazol-5-yl)quinazolin-4-amine Chemical compound C=1C=CC=CC=1COC(C=C1)=CC=C1NC(C1=C2)=NC=NC1=CC=C2C1=NN=NN1 DBFSVVANBGKWKF-UHFFFAOYSA-N 0.000 description 1
- TZFSZJMIDVRYOJ-UHFFFAOYSA-N n-(4-phenylmethoxyphenyl)-6-[5-[(pyridin-3-ylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound C=1C=C(C=2C=C3C(NC=4C=CC(OCC=5C=CC=CC=5)=CC=4)=NC=NC3=CC=2)OC=1CNC1=CC=CN=C1 TZFSZJMIDVRYOJ-UHFFFAOYSA-N 0.000 description 1
- PVZCCKSERTXAKQ-UHFFFAOYSA-N n-(4-phenylmethoxyphenyl)-6-pyrimidin-2-ylquinazolin-4-amine Chemical compound C=1C=CC=CC=1COC(C=C1)=CC=C1NC(C1=C2)=NC=NC1=CC=C2C1=NC=CC=N1 PVZCCKSERTXAKQ-UHFFFAOYSA-N 0.000 description 1
- KKRQERULMYDVGZ-UHFFFAOYSA-N n-(4-phenylmethoxyphenyl)-6-thiophen-2-ylquinazolin-4-amine Chemical compound C=1C=CC=CC=1COC(C=C1)=CC=C1NC(C1=C2)=NC=NC1=CC=C2C1=CC=CS1 KKRQERULMYDVGZ-UHFFFAOYSA-N 0.000 description 1
- CJURBDHIEJXZMJ-UHFFFAOYSA-N n-(pyridin-2-ylmethyl)-1h-indazol-5-amine Chemical compound C=1C=C2NN=CC2=CC=1NCC1=CC=CC=N1 CJURBDHIEJXZMJ-UHFFFAOYSA-N 0.000 description 1
- MWCWRTFQNLPBDY-UHFFFAOYSA-N n-[1-[(2,3-difluorophenyl)methyl]indazol-5-yl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine Chemical compound O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C(=C(F)C=CC=5)F)C4=CC=3)C2=C1 MWCWRTFQNLPBDY-UHFFFAOYSA-N 0.000 description 1
- MDOSZXNBRUVZQG-UHFFFAOYSA-N n-[1-[(2,3-difluorophenyl)methyl]indazol-5-yl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C(=C(F)C=CC=5)F)C4=CC=3)C2=C1 MDOSZXNBRUVZQG-UHFFFAOYSA-N 0.000 description 1
- WFJPLZFMJHYRRM-UHFFFAOYSA-N n-[1-[(2-fluorophenyl)methyl]indazol-5-yl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine Chemical compound O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C(=CC=CC=5)F)C4=CC=3)C2=C1 WFJPLZFMJHYRRM-UHFFFAOYSA-N 0.000 description 1
- UEXCDLWNYRWLST-UHFFFAOYSA-N n-[1-[(2-fluorophenyl)methyl]indazol-5-yl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C(=CC=CC=5)F)C4=CC=3)C2=C1 UEXCDLWNYRWLST-UHFFFAOYSA-N 0.000 description 1
- ZNSVEDPKHAETCN-UHFFFAOYSA-N n-[1-[(2-fluorophenyl)methyl]indazol-5-yl]-6-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]quinazolin-4-amine Chemical compound FC1=CC=CC=C1CN1C2=CC=C(NC=3C4=CC(=CC=C4N=CN=3)C=3OC(=NN=3)C(F)(F)F)C=C2C=N1 ZNSVEDPKHAETCN-UHFFFAOYSA-N 0.000 description 1
- GWXXIHBMDKDMPT-UHFFFAOYSA-N n-[1-[(3,5-difluorophenyl)methyl]indazol-5-yl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine Chemical compound O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=C(F)C=C(F)C=5)C4=CC=3)C2=C1 GWXXIHBMDKDMPT-UHFFFAOYSA-N 0.000 description 1
- MKZUFJLLGXMNOU-UHFFFAOYSA-N n-[1-[(3,5-difluorophenyl)methyl]indazol-5-yl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=C(F)C=C(F)C=5)C4=CC=3)C2=C1 MKZUFJLLGXMNOU-UHFFFAOYSA-N 0.000 description 1
- VPYZZXWNFFEZIF-UHFFFAOYSA-N n-[1-[(3-fluorophenyl)methyl]indazol-5-yl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine Chemical compound O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=C(F)C=CC=5)C4=CC=3)C2=C1 VPYZZXWNFFEZIF-UHFFFAOYSA-N 0.000 description 1
- DFLSFLRZSOUVIW-UHFFFAOYSA-N n-[1-[(3-fluorophenyl)methyl]indazol-5-yl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=C(F)C=CC=5)C4=CC=3)C2=C1 DFLSFLRZSOUVIW-UHFFFAOYSA-N 0.000 description 1
- VAIQLDVGHBJTAH-UHFFFAOYSA-N n-[2-[[5-[4-(4-phenylmethoxyanilino)quinazolin-6-yl]furan-2-yl]methylamino]ethyl]methanesulfonamide;dihydrochloride Chemical compound Cl.Cl.O1C(CNCCNS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C2=C1 VAIQLDVGHBJTAH-UHFFFAOYSA-N 0.000 description 1
- VIAOULYUINHJCZ-UHFFFAOYSA-N n-[3-chloro-4-[(2-fluorophenyl)methoxy]phenyl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine Chemical compound O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C(=CC=CC=4)F)=CC=3)C2=C1 VIAOULYUINHJCZ-UHFFFAOYSA-N 0.000 description 1
- UTYCNNPDHFZHKQ-UHFFFAOYSA-N n-[3-chloro-4-[(2-fluorophenyl)methoxy]phenyl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C(=CC=CC=4)F)=CC=3)C2=C1 UTYCNNPDHFZHKQ-UHFFFAOYSA-N 0.000 description 1
- TZUCHZCPRXTKLK-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine Chemical compound O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 TZUCHZCPRXTKLK-UHFFFAOYSA-N 0.000 description 1
- KQYFIRXZBLKSMV-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 KQYFIRXZBLKSMV-UHFFFAOYSA-N 0.000 description 1
- UIJYOZSATWLPDL-UHFFFAOYSA-N n-[4-(benzenesulfonyl)phenyl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine Chemical compound O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=CC(=CC=3)S(=O)(=O)C=3C=CC=CC=3)C2=C1 UIJYOZSATWLPDL-UHFFFAOYSA-N 0.000 description 1
- OSHXOGHQLLZYDD-UHFFFAOYSA-N n-[4-(benzenesulfonyl)phenyl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=CC(=CC=3)S(=O)(=O)C=3C=CC=CC=3)C2=C1 OSHXOGHQLLZYDD-UHFFFAOYSA-N 0.000 description 1
- SQBOBKVRRIYNHE-UHFFFAOYSA-N n-[4-[(2-fluorophenyl)methoxy]phenyl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine Chemical compound O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C(=CC=CC=4)F)=CC=3)C2=C1 SQBOBKVRRIYNHE-UHFFFAOYSA-N 0.000 description 1
- OUBPSLQCJGLXAE-UHFFFAOYSA-N n-[4-[(2-fluorophenyl)methoxy]phenyl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C(=CC=CC=4)F)=CC=3)C2=C1 OUBPSLQCJGLXAE-UHFFFAOYSA-N 0.000 description 1
- DCFHFHQEHGKRCN-UHFFFAOYSA-N n-[4-[(2-fluorophenyl)methoxy]phenyl]-6-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]quinazolin-4-amine Chemical compound FC1=CC=CC=C1COC(C=C1)=CC=C1NC1=NC=NC2=CC=C(C=3OC(=NN=3)C(F)(F)F)C=C12 DCFHFHQEHGKRCN-UHFFFAOYSA-N 0.000 description 1
- ZQGWUGPWPIFDRB-UHFFFAOYSA-N n-[4-[(2-fluorophenyl)methoxy]phenyl]-6-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]quinazolin-4-amine;hydrochloride Chemical compound Cl.FC1=CC=CC=C1COC(C=C1)=CC=C1NC1=NC=NC2=CC=C(C=3OC(=NN=3)C(F)(F)F)C=C12 ZQGWUGPWPIFDRB-UHFFFAOYSA-N 0.000 description 1
- UFNRKCUKVMWEGG-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]phenyl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-2-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C1=CC=C(N=C(NC=2C=CC(OCC=3C=C(F)C=CC=3)=CC=2)N=C2)C2=C1 UFNRKCUKVMWEGG-UHFFFAOYSA-N 0.000 description 1
- DVSRUYJNNLWIAT-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]quinazolin-4-amine Chemical compound FC1=CC=CC(COC=2C=CC(NC=3C4=CC(=CC=C4N=CN=3)C=3OC(=NN=3)C(F)(F)F)=CC=2)=C1 DVSRUYJNNLWIAT-UHFFFAOYSA-N 0.000 description 1
- AGZKJDNVWDKCQO-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]quinazolin-4-amine;hydrochloride Chemical compound Cl.FC1=CC=CC(COC=2C=CC(NC=3C4=CC(=CC=C4N=CN=3)C=3OC(=NN=3)C(F)(F)F)=CC=2)=C1 AGZKJDNVWDKCQO-UHFFFAOYSA-N 0.000 description 1
- DMMPESWLQXBVBY-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)quinazolin-4-amine;hydrochloride Chemical compound Cl.O1C(C)=NN=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=CC(F)=CC=4)=CC=3)C2=C1 DMMPESWLQXBVBY-UHFFFAOYSA-N 0.000 description 1
- PRQYVPZTRJFDHX-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-6-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]quinazolin-4-amine Chemical compound C1=CC(F)=CC=C1COC(C=C1)=CC=C1NC1=NC=NC2=CC=C(C=3OC(=NN=3)C(F)(F)F)C=C12 PRQYVPZTRJFDHX-UHFFFAOYSA-N 0.000 description 1
- UGXCGCLUZOLGKT-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-6-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]quinazolin-4-amine;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1COC(C=C1)=CC=C1NC1=NC=NC2=CC=C(C=3OC(=NN=3)C(F)(F)F)C=C12 UGXCGCLUZOLGKT-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- WLNSKTSWPYTNLY-UHFFFAOYSA-N n-ethyl-n',n'-dimethylethane-1,2-diamine Chemical compound CCNCCN(C)C WLNSKTSWPYTNLY-UHFFFAOYSA-N 0.000 description 1
- PZVFQOBASICMME-UHFFFAOYSA-N n-ethylmethanesulfonamide Chemical compound CCNS(C)(=O)=O PZVFQOBASICMME-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 150000005054 naphthyridines Chemical class 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 150000001451 organic peroxides Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- JPILDORBIJCDHE-UHFFFAOYSA-N oxadiazolidin-4-one Chemical group O=C1CONN1 JPILDORBIJCDHE-UHFFFAOYSA-N 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003585 oxepinyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 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
- 235000015927 pasta Nutrition 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 125000000286 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
- FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- XIMLAVRHZBUYBE-UHFFFAOYSA-N piperidin-2-one;hydrate;hydrochloride Chemical compound O.Cl.O=C1CCCCN1 XIMLAVRHZBUYBE-UHFFFAOYSA-N 0.000 description 1
- 125000004928 piperidonyl group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical compound N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 description 1
- 125000005554 pyridyloxy group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- JOZPEVMCAKXSEY-UHFFFAOYSA-N pyrimido[5,4-d]pyrimidine Chemical class N1=CN=CC2=NC=NC=C21 JOZPEVMCAKXSEY-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 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
- 230000009703 regulation of cell differentiation Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 229940043230 sarcosine Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- VFWRGKJLLYDFBY-UHFFFAOYSA-N silver;hydrate Chemical compound O.[Ag].[Ag] VFWRGKJLLYDFBY-UHFFFAOYSA-N 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
- 235000019254 sodium formate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical class [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000005306 thianaphthenyl group Chemical group 0.000 description 1
- 125000003777 thiepinyl group Chemical group 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- QTYBKWIPVOTUQI-UHFFFAOYSA-N tributyl(2,3-dihydrofuran-5-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CCCO1 QTYBKWIPVOTUQI-UHFFFAOYSA-N 0.000 description 1
- GYUURHMITDQTRU-UHFFFAOYSA-N tributyl(pyridin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CC=N1 GYUURHMITDQTRU-UHFFFAOYSA-N 0.000 description 1
- WTFFOOAJSDVASL-UHFFFAOYSA-N tributyl(pyrimidin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CC=N1 WTFFOOAJSDVASL-UHFFFAOYSA-N 0.000 description 1
- UKTDFYOZPFNQOQ-UHFFFAOYSA-N tributyl(thiophen-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CS1 UKTDFYOZPFNQOQ-UHFFFAOYSA-N 0.000 description 1
- KFWFYOPKNSYTMV-UHFFFAOYSA-N tributyl-(1-methylimidazol-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CN1C KFWFYOPKNSYTMV-UHFFFAOYSA-N 0.000 description 1
- CWAPIHCLJCNFTN-UHFFFAOYSA-N tributyl-(2,3-dimethylimidazol-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CN=C(C)N1C CWAPIHCLJCNFTN-UHFFFAOYSA-N 0.000 description 1
- FFSUQKBGKWNUQW-UHFFFAOYSA-N tributyl-(3-methyl-1,2-oxazol-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CON=C1C FFSUQKBGKWNUQW-UHFFFAOYSA-N 0.000 description 1
- OGYWKJKAIAEDQX-UHFFFAOYSA-N tributyl-(3-methylimidazol-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CN=CN1C OGYWKJKAIAEDQX-UHFFFAOYSA-N 0.000 description 1
- DPCBHPVSSFQHLW-UHFFFAOYSA-N tributyl-(3-methyltriazol-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CN=NN1C DPCBHPVSSFQHLW-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 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
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 229940120293 vaginal suppository Drugs 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D405/14—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 three or more hetero rings
-
- 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
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9614755.8 | 1996-07-13 | ||
| GBGB9614755.8A GB9614755D0 (en) | 1996-07-13 | 1996-07-13 | Heterocyclic compounds |
| GB9625458.6 | 1996-12-07 | ||
| GBGB9625458.6A GB9625458D0 (en) | 1996-12-07 | 1996-12-07 | Heterocyclic compounds |
| PCT/EP1997/003672 WO1998002434A1 (en) | 1996-07-13 | 1997-07-11 | Fused heterocyclic compounds as protein tyrosine kinase inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2000514806A JP2000514806A (ja) | 2000-11-07 |
| JP2000514806A5 JP2000514806A5 (enExample) | 2005-03-10 |
| JP4386967B2 true JP4386967B2 (ja) | 2009-12-16 |
Family
ID=26309690
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP50559698A Expired - Lifetime JP4386967B2 (ja) | 1996-07-13 | 1997-07-11 | プロテインチロシンキナーゼ阻害剤としての縮合複素環式化合物 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US6391874B1 (enExample) |
| EP (1) | EP0912559B1 (enExample) |
| JP (1) | JP4386967B2 (enExample) |
| AR (1) | AR007857A1 (enExample) |
| AT (1) | ATE227283T1 (enExample) |
| AU (1) | AU3766897A (enExample) |
| CY (1) | CY2451B1 (enExample) |
| DE (1) | DE69716916T2 (enExample) |
| DK (1) | DK0912559T3 (enExample) |
| ES (1) | ES2186908T3 (enExample) |
| ID (1) | ID19609A (enExample) |
| PT (1) | PT912559E (enExample) |
| WO (1) | WO1998002434A1 (enExample) |
Families Citing this family (507)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR9707495A (pt) | 1996-02-13 | 1999-07-27 | Zeneca Ltd | Derivado de quinazolina processo para a preparação do mesmo composição farmacêutica e processo para a produç o de um efeito antiangiogênico e/ou de redução de permeabilidade vascular em um animal de sangue quente |
| GB9603095D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
| JP4464466B2 (ja) | 1996-03-05 | 2010-05-19 | アストラゼネカ・ユーケイ・リミテッド | 4―アニリノキナゾリン誘導体 |
| GB9707800D0 (en) | 1996-05-06 | 1997-06-04 | Zeneca Ltd | Chemical compounds |
| HRP970371A2 (en) | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| JP2001500890A (ja) | 1996-09-25 | 2001-01-23 | ゼネカ リミテッド | Vegfのような成長因子の作用を阻害するキノリン誘導体 |
| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| US6294532B1 (en) | 1997-08-22 | 2001-09-25 | Zeneca Limited | Oxindolylquinazoline derivatives as angiogenesis inhibitors |
| RS49779B (sr) * | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
| US6297258B1 (en) | 1998-09-29 | 2001-10-02 | American Cyanamid Company | Substituted 3-cyanoquinolines |
| US6288082B1 (en) | 1998-09-29 | 2001-09-11 | American Cyanamid Company | Substituted 3-cyanoquinolines |
| KR100736502B1 (ko) | 1998-09-29 | 2007-07-06 | 와이어쓰 홀딩스 코포레이션 | 단백질 티로신 키나제 억제제로서 치환된 3-시아노퀴놀린 |
| ATE294796T1 (de) * | 1998-10-08 | 2005-05-15 | Astrazeneca Ab | Chinazolin derivate |
| UA71945C2 (en) | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
| JP3270834B2 (ja) * | 1999-01-27 | 2002-04-02 | ファイザー・プロダクツ・インク | 抗がん剤として有用なヘテロ芳香族二環式誘導体 |
| PL199802B1 (pl) | 1999-02-10 | 2008-10-31 | Astrazeneca Ab | Pochodne chinazoliny, sposoby ich wytwarzania, ich kompozycje farmaceutyczne i ich zastosowania |
| GB9904103D0 (en) | 1999-02-24 | 1999-04-14 | Zeneca Ltd | Quinoline derivatives |
| GB9910580D0 (en) | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
| GB9910579D0 (en) | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
| JP2003503354A (ja) | 1999-06-30 | 2003-01-28 | メルク エンド カムパニー インコーポレーテッド | Srcキナーゼ阻害剤化合物 |
| CA2376957A1 (en) | 1999-06-30 | 2001-01-04 | Merck & Co., Inc. | Src kinase inhibitor compounds |
| DE60006541D1 (de) | 1999-06-30 | 2003-12-18 | Merck & Co Inc | Src-kinase hemmende verbindungen |
| US6933299B1 (en) * | 1999-07-09 | 2005-08-23 | Smithkline Beecham Corporation | Anilinoquinazolines as protein tyrosine kinase inhibitors |
| AU5783300A (en) | 1999-07-09 | 2001-01-30 | Glaxo Group Limited | Anilinoquinazolines as protein tyrosine kinase inhibitors |
| US6432979B1 (en) | 1999-08-12 | 2002-08-13 | American Cyanamid Company | Method of treating or inhibiting colonic polyps and colorectal cancer |
| EP1676845B1 (en) | 1999-11-05 | 2008-06-11 | AstraZeneca AB | New quinazoline derivatives |
| UA74803C2 (uk) | 1999-11-11 | 2006-02-15 | Осі Фармасьютікалз, Інк. | Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування |
| UA75055C2 (uk) * | 1999-11-30 | 2006-03-15 | Пфайзер Продактс Інк. | Похідні бензоімідазолу, що використовуються як антипроліферативний засіб, фармацевтична композиція на їх основі |
| US6638929B2 (en) | 1999-12-29 | 2003-10-28 | Wyeth | Tricyclic protein kinase inhibitors |
| GB0002952D0 (en) * | 2000-02-09 | 2000-03-29 | Pharma Mar Sa | Process for producing kahalalide F compounds |
| EP1274692B1 (en) | 2000-04-07 | 2006-08-02 | AstraZeneca AB | Quinazoline compounds |
| UA73993C2 (uk) | 2000-06-06 | 2005-10-17 | Астразенека Аб | Хіназолінові похідні для лікування пухлин та фармацевтична композиція |
| KR100815681B1 (ko) * | 2000-06-30 | 2008-03-20 | 글락소 그룹 리미티드 | 퀴나졸린 디토실레이트 염 화합물 |
| BR0113056A (pt) | 2000-08-09 | 2003-07-08 | Astrazeneca Ab | Composto, processo papa a preparação do mesmo, composição farmacêutica, e, método para produzir um efeito antiangiogênico e/ou redutor da permeabilidade vascular em um animal de sangue quente, e, uso de um composto |
| CZ2003486A3 (cs) | 2000-08-21 | 2003-05-14 | Astrazeneca Ab | Chinazolinové deriváty, způsob jejich přípravy a farmaceutický prostředek, který je obsahuje |
| US6638926B2 (en) * | 2000-09-15 | 2003-10-28 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| US6660731B2 (en) | 2000-09-15 | 2003-12-09 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| US7473691B2 (en) | 2000-09-15 | 2009-01-06 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| WO2002024667A1 (en) * | 2000-09-20 | 2002-03-28 | Merck Patent Gmbh | 4-amino-quinazolines |
| BR0114021A (pt) * | 2000-09-20 | 2003-08-19 | Merck Patent Gmbh | 4-amino-quinazolinas |
| IL154993A0 (en) * | 2000-09-29 | 2003-10-31 | Neurogen Corp | High affinity small molecule c5a receptor modulators |
| AU2001292137A1 (en) | 2000-10-13 | 2002-04-22 | Astrazeneca Ab | Quinazoline derivatives |
| JP2004511479A (ja) | 2000-10-13 | 2004-04-15 | アストラゼネカ アクチボラグ | キナゾリン誘導体 |
| HU230302B1 (hu) | 2000-10-20 | 2015-12-28 | Eisai R&D Management Co., Ltd. | Nitrogéntartalmú aromás származékok és ezeket tartalmazó gyógyászati készítmények |
| AU2001295791A1 (en) | 2000-11-02 | 2002-05-15 | Astrazeneca Ab | 4-substituted quinolines as antitumor agents |
| WO2002044166A1 (en) | 2000-11-02 | 2002-06-06 | Astrazeneca Ab | Substituted quinolines as antitumor agents |
| CA2432799C (en) | 2000-12-21 | 2008-08-19 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| SV2007000775A (es) | 2001-01-05 | 2007-03-15 | Pfizer | Anticuerpos contra el receptor del factor de crecimiento similar a insulina |
| ATE290882T1 (de) | 2001-01-16 | 2005-04-15 | Glaxo Group Ltd | Pharmazeutische mischung gegen krebs, die ein 4- chinazolinamin in kombination mit paclitaxel, carboplatin or vinorelbine enthält |
| JP4329003B2 (ja) * | 2001-03-23 | 2009-09-09 | バイエル コーポレイション | Rhoキナーゼ阻害剤 |
| ES2280517T3 (es) * | 2001-03-23 | 2007-09-16 | Bayer Pharmaceuticals Corporation | Inhibidor de rho-cinasa. |
| US7141577B2 (en) | 2001-04-19 | 2006-11-28 | Astrazeneca Ab | Quinazoline derivatives |
| GB0112834D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| GB0112836D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| US6995171B2 (en) | 2001-06-21 | 2006-02-07 | Agouron Pharmaceuticals, Inc. | Bicyclic pyrimidine and pyrimidine derivatives useful as anticancer agents |
| US7829566B2 (en) * | 2001-09-17 | 2010-11-09 | Werner Mederski | 4-amino-quinazolines |
| GB0126433D0 (en) * | 2001-11-03 | 2002-01-02 | Astrazeneca Ab | Compounds |
| ATE423104T1 (de) * | 2001-11-03 | 2009-03-15 | Astrazeneca Ab | Quinazolin derivate als antitumor-mittel |
| AR039067A1 (es) | 2001-11-09 | 2005-02-09 | Pfizer Prod Inc | Anticuerpos para cd40 |
| JP4202926B2 (ja) * | 2001-12-12 | 2008-12-24 | ファイザー・プロダクツ・インク | E−2−メトキシ−n−(3−(4−(3−メチル−ピリジン−3−イロキシ)−フェニルアミノ)−キナゾリン−6−イル)−アリル)−アセトアミドの塩形態、その製造および癌に対するその使用 |
| US20030187026A1 (en) | 2001-12-13 | 2003-10-02 | Qun Li | Kinase inhibitors |
| US6797825B2 (en) | 2001-12-13 | 2004-09-28 | Abbott Laboratories | Protein kinase inhibitors |
| ES2305435T3 (es) * | 2002-01-10 | 2008-11-01 | Bayer Healthcare Ag | Inhibidores de la rho-quinasa. |
| RS63204A (sr) * | 2002-01-17 | 2006-10-27 | Neurogen Corporation | Supstituisani analozi hinazolin-4-ilamina kao modulatori kapsaicina |
| CA2473510A1 (en) * | 2002-01-23 | 2003-07-31 | Bayer Pharmaceuticals Corporation | Pyrimidine derivatives as rho-kinase inhibitors |
| DE60318177T2 (de) * | 2002-01-23 | 2008-10-09 | Bayer Pharmaceuticals Corp., West Haven | Rho-kinase inhibitoren |
| NZ534171A (en) | 2002-02-01 | 2007-06-29 | Astrazeneca Ab | Quinazoline compounds for the treatment of diseases associated with angiogenesis and/or increased vascular permeability |
| US7645878B2 (en) | 2002-03-22 | 2010-01-12 | Bayer Healthcare Llc | Process for preparing quinazoline Rho-kinase inhibitors and intermediates thereof |
| 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 |
| JP2005534623A (ja) * | 2002-04-08 | 2005-11-17 | スミスクライン ビーチャム コーポレーション | Erbファミリーの阻害剤並びにraf及び/又はras阻害剤を投与することを含む癌の治療法 |
| UA77303C2 (en) | 2002-06-14 | 2006-11-15 | Pfizer | Derivatives of thienopyridines substituted by benzocondensed heteroarylamide useful as therapeutic agents, pharmaceutical compositions and methods for their use |
| MY141867A (en) | 2002-06-20 | 2010-07-16 | Vertex Pharma | Substituted pyrimidines useful as protein kinase inhibitors |
| GB0215823D0 (en) | 2002-07-09 | 2002-08-14 | Astrazeneca Ab | Quinazoline derivatives |
| WO2004004732A1 (en) | 2002-07-09 | 2004-01-15 | Astrazeneca Ab | Quinazoline derivatives for use in the treatment of cancer |
| EP1521747B1 (en) * | 2002-07-15 | 2018-09-05 | Symphony Evolution, Inc. | Receptor-type kinase modulators and methods of use |
| WO2004011456A1 (en) * | 2002-07-31 | 2004-02-05 | Danter Wayne R | Protein tyrosine kinase inhibitors |
| PT1532145E (pt) | 2002-08-02 | 2007-01-31 | Vertex Pharma | Composiçoes de pirazole úteis como inibidores de gsk-3 |
| WO2004033446A1 (en) * | 2002-10-09 | 2004-04-22 | Danter Wayne R | Protein tyrosine kinase inhibitors |
| GB0304367D0 (en) * | 2003-02-26 | 2003-04-02 | Pharma Mar Sau | Methods for treating psoriasis |
| GB0225579D0 (en) * | 2002-11-02 | 2002-12-11 | Astrazeneca Ab | Chemical compounds |
| NZ539408A (en) | 2002-11-04 | 2007-09-28 | Astrazeneca Ab | Quinazoline derivatives as SRC tyrosine kinase inhibitors for treating solid tumours |
| US7488823B2 (en) * | 2003-11-10 | 2009-02-10 | Array Biopharma, Inc. | Cyanoguanidines and cyanoamidines as ErbB2 and EGFR inhibitors |
| CA2509239A1 (en) * | 2002-12-13 | 2004-07-01 | Neurogen Corporation | Carboxylic acid, phosphate or phosphonate substituted quinazolin-4-ylamine analogues as capsaicin receptor modulators |
| DK1585743T3 (da) | 2002-12-19 | 2007-09-17 | Pfizer | 2-(H-indazol-6-ylamino)-benzamid forbindelser som protein kinase inhibitorer, nyttige til behandling opthalmiske sygdomme |
| OA13309A (en) | 2002-12-20 | 2007-04-13 | Pfizer Prod Inc | Pyrimidine derivatives for the treatment of abnormal cell growth. |
| AU2004215428B2 (en) | 2003-02-26 | 2009-08-27 | Sugen LLC | Aminoheteroaryl compounds as protein kinase inhibitors |
| AU2004221812B2 (en) * | 2003-03-19 | 2010-02-18 | Exelixis Inc. | Tie-2 modulators and methods of use |
| GB0309850D0 (en) | 2003-04-30 | 2003-06-04 | Astrazeneca Ab | Quinazoline derivatives |
| TWI328009B (en) | 2003-05-21 | 2010-08-01 | Glaxo Group Ltd | Quinoline derivatives as phosphodiesterase inhibitors |
| WO2005003100A2 (en) * | 2003-07-03 | 2005-01-13 | Myriad Genetics, Inc. | 4-arylamino-quinazolines as activators of caspases and inducers of apoptosis |
| US8309562B2 (en) * | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | Compounds and therapeutical use thereof |
| WO2006074147A2 (en) | 2005-01-03 | 2006-07-13 | Myriad Genetics, Inc. | Nitrogen containing bicyclic compounds and therapeutical use thereof |
| AR045037A1 (es) | 2003-07-10 | 2005-10-12 | Aventis Pharma Sa | Tetrahidro-1h-pirazolo [3,4-c] piridinas sustituidas, composiciones que las contienen y su utilizacion. |
| TW200510373A (en) * | 2003-07-14 | 2005-03-16 | Neurogen Corp | Substituted quinolin-4-ylamine analogues |
| US7329664B2 (en) * | 2003-07-16 | 2008-02-12 | Neurogen Corporation | Substituted (7-pyridyl-4-phenylamino-quinazolin-2-yl)-methanol analogues |
| WO2005011607A2 (en) * | 2003-08-01 | 2005-02-10 | Smithkline Beecham Corporation | Treatment of cancers expressing p95 erbb2 |
| HN2004000285A (es) | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
| NZ545459A (en) * | 2003-08-14 | 2009-12-24 | Array Biopharma Inc | Quinazoline analogs as receptor tyrosine kinase inhibitors |
| US7501427B2 (en) | 2003-08-14 | 2009-03-10 | Array Biopharma, Inc. | Quinazoline analogs as receptor tyrosine kinase inhibitors |
| MXPA06002296A (es) | 2003-08-29 | 2006-05-22 | Pfizer | Tienopiridina-fenilacetamidas y sus derivados utiles como nuevos agentes antiangiogenicos. |
| GB0321066D0 (en) * | 2003-09-09 | 2003-10-08 | Pharma Mar Sau | New antitumoral compounds |
| EP1678173A2 (en) * | 2003-09-09 | 2006-07-12 | Neurogen Corporation | 4-heterobicyclylamino-substituted quinazolines and analogues thereof as capsaicin-antagonists |
| AR045563A1 (es) | 2003-09-10 | 2005-11-02 | Warner Lambert Co | Anticuerpos dirigidos a m-csf |
| AU2004272348B2 (en) | 2003-09-16 | 2008-09-04 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
| GB0322409D0 (en) | 2003-09-25 | 2003-10-29 | Astrazeneca Ab | Quinazoline derivatives |
| ES2436888T3 (es) | 2003-09-26 | 2014-01-07 | Exelixis, Inc | Moduladores c-Met y métodos de uso |
| CN101337930B (zh) | 2003-11-11 | 2010-09-08 | 卫材R&D管理有限公司 | 脲衍生物的制备方法 |
| US7511065B2 (en) * | 2003-11-12 | 2009-03-31 | Eli Lilly And Company | Mixed lineage kinase modulators |
| GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
| JP4864719B2 (ja) * | 2003-11-26 | 2012-02-01 | ファイザー・プロダクツ・インク | Gsk−3インヒビターとしてのアミノピラゾール誘導体 |
| GB0330002D0 (en) | 2003-12-24 | 2004-01-28 | Astrazeneca Ab | Quinazoline derivatives |
| EP1713781B1 (en) | 2004-02-03 | 2008-11-05 | AstraZeneca AB | Quinazoline derivatives |
| PT1746999E (pt) | 2004-05-06 | 2012-01-11 | Warner Lambert Co | 4-fenilamino-quinazolin-6-il-amidas |
| EP1781293A1 (en) | 2004-06-04 | 2007-05-09 | Amphora Discovery Corporation | Quinoline- and isoquinoline-based compounds exhibiting atp-utilizing enzyme inhibitory activity, and compositions, and uses thereof |
| JP2008506681A (ja) | 2004-07-16 | 2008-03-06 | ファイザー・プロダクツ・インク | 抗igf−1r抗体を用いる非血液性の悪性腫瘍の併用療法 |
| MX2007002312A (es) | 2004-08-26 | 2007-04-16 | Pfizer | Compuestos de aminoheteroarilo enantiomericamente puros como inhibidores de proteina quinasa. |
| WO2006031929A2 (en) | 2004-09-15 | 2006-03-23 | Janssen Pharmaceutica, N.V. | Thiazolopyridine kinase inhibitors |
| EP1797881B1 (en) | 2004-09-17 | 2009-04-15 | Eisai R&D Management Co., Ltd. | Medicinal composition with improved stability and reduced gelation properties |
| US20070054916A1 (en) * | 2004-10-01 | 2007-03-08 | Amgen Inc. | Aryl nitrogen-containing bicyclic compounds and methods of use |
| TW200621251A (en) | 2004-10-12 | 2006-07-01 | Neurogen Corp | Substituted biaryl quinolin-4-ylamine analogues |
| JP4881875B2 (ja) | 2004-12-14 | 2012-02-22 | アストラゼネカ アクチボラグ | 抗腫瘍剤としてのピラゾロピリミジン化合物 |
| US8258145B2 (en) | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
| US20090155247A1 (en) * | 2005-02-18 | 2009-06-18 | Ashkenazi Avi J | Methods of Using Death Receptor Agonists and EGFR Inhibitors |
| US20060188498A1 (en) * | 2005-02-18 | 2006-08-24 | Genentech, Inc. | Methods of using death receptor agonists and EGFR inhibitors |
| WO2006090717A1 (ja) | 2005-02-23 | 2006-08-31 | Shionogi & Co., Ltd. | チロシンキナーゼ阻害作用を有するキナゾリン誘導体 |
| RU2413735C2 (ru) | 2005-03-31 | 2011-03-10 | Эдженсис, Инк. | Антитела и родственные молекулы, связывающиеся с белками 161p2f10b |
| MX2007013304A (es) | 2005-04-26 | 2007-12-13 | Pfizer | Anticuerpos de p-caderina. |
| GB0508715D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
| WO2006118749A1 (en) | 2005-05-04 | 2006-11-09 | Janssen Pharmaceutica, N.V. | Thia-tetraazaacenaphthylene kinase inhibitors |
| EP1910296B1 (en) * | 2005-07-27 | 2010-04-21 | F.Hoffmann-La Roche Ag | 4-aryloxy quinoline derivatives as 5-ht6 modulators |
| WO2007015578A1 (ja) | 2005-08-02 | 2007-02-08 | Eisai R & D Management Co., Ltd. | 血管新生阻害物質の効果を検定する方法 |
| PL2447283T3 (pl) | 2005-09-07 | 2015-12-31 | Amgen Fremont Inc | Ludzkie przeciwciała monoklonalne przeciwko kinazie podobnej do receptora aktywiny-1 (ALK-1) |
| WO2007033196A1 (en) * | 2005-09-14 | 2007-03-22 | Bristol-Myers Squibb Company | Met kinase inhibitors |
| ES2354457T3 (es) | 2005-09-20 | 2011-03-15 | Astrazeneca Ab | Compuestos de 4-(1h-indazol-5-il-amino)-quinazolina como inhibidores del receptor erbb de la tirosina quinasa para el tratamiento del cáncer. |
| US8062838B2 (en) | 2005-09-20 | 2011-11-22 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| GB0520475D0 (en) * | 2005-10-07 | 2005-11-16 | Arrow Therapeutics Ltd | Chemical compounds |
| WO2007056163A2 (en) | 2005-11-03 | 2007-05-18 | Vertex Pharmaceuticals Incorporated | Aminopyrimidines useful as kinase inhibitors |
| DE602006009968D1 (de) * | 2005-11-15 | 2009-12-03 | Array Biopharma Inc | N4-phenyl-chinazolin-4-aminderivate und verwandte verbindungen als inhibitoren der erbb-typ-i-rezeptortyrosinkinase zur behandlung hyperproliferativer krankheiten |
| ATE508125T1 (de) * | 2006-01-11 | 2011-05-15 | Arrow Therapeutics Ltd | Triazoloanilinopyrimidinderivate zur verwendung als antivirale mittel |
| DE102006012251A1 (de) * | 2006-03-15 | 2007-11-08 | Grünenthal GmbH | Substituierte 4-Amino-chinazolin-Derivate und ihre Verwendung zur Herstellung von Arzneimitteln |
| EA200802058A1 (ru) | 2006-05-09 | 2009-06-30 | Пфайзер Продактс Инк. | Производные циклоалкиламинокислот и их фармацевтические композиции |
| NL2000613C2 (nl) | 2006-05-11 | 2007-11-20 | Pfizer Prod Inc | Triazoolpyrazinederivaten. |
| ES2556173T3 (es) | 2006-05-18 | 2016-01-13 | Eisai R&D Management Co., Ltd. | Agente antitumoral para un cáncer de tiroides |
| WO2008016123A1 (en) * | 2006-08-03 | 2008-02-07 | Takeda Pharmaceutical Company Limited | GSK-3β INHIBITOR |
| US20110053964A1 (en) * | 2006-08-22 | 2011-03-03 | Roger Tung | 4-aminoquinazoline derivatives and methods of use thereof |
| CN101594870A (zh) * | 2006-08-22 | 2009-12-02 | 康塞特医药品有限公司 | 4-氨基喹唑啉衍生物及其使用方法 |
| CN101511793B (zh) | 2006-08-28 | 2011-08-03 | 卫材R&D管理有限公司 | 针对未分化型胃癌的抗肿瘤剂 |
| WO2008033782A2 (en) | 2006-09-12 | 2008-03-20 | Genentech, Inc. | Methods and compositions for the diagnosis and treatment of lung cancer using pdgfra, kit or kdr gene as genetic marker |
| EP2079739A2 (en) * | 2006-10-04 | 2009-07-22 | Pfizer Products Inc. | Pyrido[4,3-d]pyrimidin-4(3h)-one derivatives as calcium receptor antagonists |
| US7750007B2 (en) | 2006-11-06 | 2010-07-06 | Supergen, Inc. | Imidazo[1,2-beta]pyridazine and pyrazolo[1,5-alpha]pyrimidine derivatives and their use as protein kinase inhibitors |
| 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 |
| US8138191B2 (en) | 2007-01-11 | 2012-03-20 | Critical Outcome Technologies Inc. | Inhibitor compounds and cancer treatment methods |
| CA2673683C (en) | 2007-01-11 | 2014-07-29 | Critical Outcome Technologies, Inc. | Compounds and method for treatment of cancer |
| KR101445892B1 (ko) | 2007-01-29 | 2014-09-29 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 미분화형 위암 치료용 조성물 |
| CA2677336A1 (en) | 2007-02-06 | 2008-08-14 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, the use thereof and processes for the preparation thereof |
| JP5516397B2 (ja) | 2007-04-05 | 2014-06-11 | アムジエン・インコーポレーテツド | オーロラキナーゼ調節物質及び使用方法 |
| WO2008127710A2 (en) | 2007-04-13 | 2008-10-23 | Dana Farber Cancer Institute | Methods for treating cancer resistant to erbb therapeutics |
| DK2146779T3 (en) | 2007-04-18 | 2016-11-28 | Pfizer Prod Inc | Sulfonylamid derivatives to treat abnormal cell growth. |
| JP5389785B2 (ja) | 2007-05-02 | 2014-01-15 | バーテックス ファーマシューティカルズ インコーポレイテッド | キナーゼ阻害剤として有用なチアゾールおよびピラゾール |
| WO2009012647A1 (fr) * | 2007-07-20 | 2009-01-29 | Shanghai Hengrui Pharmaceutical Co., Ltd. | Procédés de préparation de dérivés de quinazoline et leurs utilisations pharmaceutiques |
| CN101367794B (zh) * | 2007-07-20 | 2013-07-10 | 上海恒瑞医药有限公司 | 喹唑啉类衍生物的制备方法及其在医药上的应用 |
| AU2008282156B2 (en) | 2007-07-31 | 2014-07-17 | Vertex Pharmaceuticals Incorporated | Process for preparing 5-fluoro-1H-pyrazolo [3, 4-b] pyridin-3-amine and derivatives thereof |
| SG10201500328QA (en) | 2007-08-21 | 2015-03-30 | Amgen Inc | Human c-fms antigen binding proteins |
| PL2185574T3 (pl) | 2007-09-07 | 2013-09-30 | Agensys Inc | Przeciwciała i powiązane cząsteczki, które wiążą się do białek 24P4C12 |
| AU2008312400A1 (en) * | 2007-10-19 | 2009-04-23 | Albert Einstein College Of Medicine Of Yeshiva University | Improved antitumoral treatments |
| KR20100087185A (ko) | 2007-10-29 | 2010-08-03 | 낫코 파마 리미티드 | 항암제로서의 신규한 4-(테트라졸-5-일)-퀴나졸린 유도체 |
| CN101848895B (zh) | 2007-11-09 | 2013-10-23 | 卫材R&D管理有限公司 | 血管新生抑制物质和抗肿瘤性铂络合物的组合使用 |
| US20110053991A1 (en) * | 2007-11-19 | 2011-03-03 | Gore Lia | Treatment of Histone Deacetylase Mediated Disorders |
| US8466151B2 (en) * | 2007-12-26 | 2013-06-18 | Critical Outcome Technologies, Inc. | Compounds and method for treatment of cancer |
| TWI472339B (zh) | 2008-01-30 | 2015-02-11 | Genentech Inc | 包含結合至her2結構域ii之抗體及其酸性變異體的組合物 |
| EP2252315A1 (en) * | 2008-01-30 | 2010-11-24 | Pharma Mar, S.A. | Improved antitumoral treatments |
| PT2245026E (pt) | 2008-02-07 | 2012-10-15 | Boehringer Ingelheim Int | Heterociclos espirocíclicos, produtos farmacêuticos contendo estes compostos, sua utilização e processo para a sua preparação |
| EP2262522A1 (en) * | 2008-03-07 | 2010-12-22 | Pharma Mar, S.A. | Improved antitumoral treatments |
| ES2413806T3 (es) | 2008-03-20 | 2013-07-17 | Amgen Inc. | Moduladores de la aurora cinasa y método de uso |
| CA2725390C (en) * | 2008-04-08 | 2014-09-23 | Syndax Pharmaceuticals, Inc. | Use of a hdac inhibitor and a her-2 inhibitor in the treatment of breast cancer |
| US8252805B2 (en) * | 2008-05-07 | 2012-08-28 | Teva Pharmaceutical Industries Ltd. | Forms of lapatinib ditosylate and processes for preparation thereof |
| US8088782B2 (en) | 2008-05-13 | 2012-01-03 | Astrazeneca Ab | Crystalline 4-(3-chloro-2-fluoroanilino)-7 methoxy-6-{[1-(N-methylcarbamoylmethyl)piperidin-4-yl]oxy}quinazoline difumarate form A |
| CN101584696A (zh) * | 2008-05-21 | 2009-11-25 | 上海艾力斯医药科技有限公司 | 包含喹唑啉衍生物的组合物及制备方法、用途 |
| US20100197915A1 (en) * | 2008-08-06 | 2010-08-05 | Leonid Metsger | Lapatinib intermediates |
| WO2010015522A1 (de) | 2008-08-08 | 2010-02-11 | Boehringer Ingelheim International Gmbh | Cyclohexyloxy-substituierte heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| US9126935B2 (en) | 2008-08-14 | 2015-09-08 | Amgen Inc. | Aurora kinase modulators and methods of use |
| WO2010027848A2 (en) * | 2008-08-26 | 2010-03-11 | Teva Pharmaceutical Industries Ltd. | Forms of lapatinib compounds and processes for the preparation thereof |
| US8735424B2 (en) * | 2008-09-02 | 2014-05-27 | Novartis Ag | Bicyclic kinase inhibitors |
| CN102215816A (zh) | 2008-09-03 | 2011-10-12 | 沃泰克斯药物股份有限公司 | 共晶和包含所述共晶的药物制剂 |
| TW201014860A (en) | 2008-09-08 | 2010-04-16 | Boehringer Ingelheim Int | New chemical compounds |
| EP2334701A4 (en) | 2008-10-16 | 2014-01-08 | Univ Pittsburgh | FULLY HUMAN ANTIBODIES AGAINST ANTIGENES ASSOCIATED WITH MELANOMA OF HIGH MOLECULAR WEIGHT AND USES THEREOF |
| US8710104B2 (en) | 2008-11-07 | 2014-04-29 | Triact Therapeutics, Inc. | Catecholic butanes and use thereof for cancer therapy |
| CA2995880C (en) | 2009-01-16 | 2021-01-05 | Exelixis, Inc. | Processes for preparing n-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-n'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide |
| CN101787017A (zh) * | 2009-01-23 | 2010-07-28 | 岑均达 | 光学纯喹唑啉类化合物 |
| TW201041892A (en) | 2009-02-09 | 2010-12-01 | Supergen Inc | Pyrrolopyrimidinyl Axl kinase inhibitors |
| EP2400985A2 (en) | 2009-02-25 | 2012-01-04 | OSI Pharmaceuticals, LLC | Combination of an either an anti-igf-1r antibody or an igf binding protein and a small molecule igf-1r kinase inhibitor |
| US20110171124A1 (en) | 2009-02-26 | 2011-07-14 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the EMT status of tumor cells in vivo |
| US8465912B2 (en) | 2009-02-27 | 2013-06-18 | OSI Pharmaceuticals, LLC | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| EP2401614A1 (en) | 2009-02-27 | 2012-01-04 | OSI Pharmaceuticals, LLC | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| US20100222381A1 (en) | 2009-02-27 | 2010-09-02 | Hariprasad Vankayalapati | Cyclopentathiophene/cyclohexathiophene DNA methyltransferase inhibitors |
| EP2408479A1 (en) | 2009-03-18 | 2012-01-25 | OSI Pharmaceuticals, LLC | Combination cancer therapy comprising administration of an egfr inhibitor and an igf-1r inhibitor |
| JP5624114B2 (ja) | 2009-03-20 | 2014-11-12 | ジェネンテック, インコーポレイテッド | 抗her抗体 |
| EP2270002A1 (en) | 2009-06-18 | 2011-01-05 | Vereniging voor Christelijk Hoger Onderwijs, Wetenschappelijk Onderzoek en Patiëntenzorg | Quinazoline derivatives as histamine H4-receptor inhibitors for use in the treatment of inflammatory disorders |
| AR077292A1 (es) | 2009-06-29 | 2011-08-17 | Agios Pharmaceuticals Inc | Derivados de piperazin - quinolin sulfonamidas y composiciones farmaceuticas |
| AU2010266725A1 (en) | 2009-07-02 | 2012-02-23 | Newgen Therapeutics, Inc. | Phosphorus containing quinazoline compounds and methods of use |
| UA108618C2 (uk) | 2009-08-07 | 2015-05-25 | Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку | |
| CN102770140B (zh) | 2009-08-21 | 2017-06-23 | 诺瓦蒂斯公司 | 治疗癌症的方法 |
| JP2013503846A (ja) | 2009-09-01 | 2013-02-04 | ファイザー・インク | ベンズイミダゾール誘導体 |
| PT3575288T (pt) | 2009-09-03 | 2021-12-09 | Bristol Myers Squibb Co | Quinazolinas como inibidores dos canais iónicos de potássio |
| KR101648787B1 (ko) * | 2009-09-28 | 2016-08-17 | 치루 파머수티컬 컴퍼니 리미티드 | 타이로신 키나제 억제제로서 유용한 4-(치환된 아닐리노)-퀴나졸린 유도체 |
| BR112012009997A2 (pt) | 2009-11-12 | 2019-09-24 | Genentech Inc | ''método para aumentar a densidade de espinhas dentriticas nos neurônios de um paciente com um distúrbios cognitivo ou psiquiatrico,método de manutenção da cognição em um sujeito durante o processo de envelhecimento,uso de um antagonista de dr6 na preparação de um medicamento para uso em um paciente com um disturbio cognitivo uo psiquíatrico e uso de um antagonista de p75 na preparação de um medicamento para uso em um paciente com um distúrbio cognitivo ou psiquiátrico'' |
| WO2011058164A1 (en) | 2009-11-13 | 2011-05-19 | Pangaea Biotech, S.A. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
| US20110207736A1 (en) | 2009-12-23 | 2011-08-25 | Gatekeeper Pharmaceuticals, Inc. | Compounds that modulate egfr activity and methods for treating or preventing conditions therewith |
| CN102108079B (zh) * | 2009-12-25 | 2014-10-01 | 齐鲁制药有限公司 | 作为酪氨酸激酶抑制剂的4-(取代苯胺基)喹唑啉衍生物 |
| CN102712640A (zh) | 2010-01-12 | 2012-10-03 | 弗·哈夫曼-拉罗切有限公司 | 三环杂环化合物、其组合物和应用方法 |
| CN102153544B (zh) * | 2010-02-12 | 2015-04-29 | 上海阳帆医药科技有限公司 | 一类酪氨酸激酶抑制剂的制备及用途 |
| JP5745283B2 (ja) | 2010-02-12 | 2015-07-08 | ファイザー・インク | 8−フルオロ−2−{4−[(メチルアミノ)メチル]フェニル}−1,3,4,5−テトラヒドロ−6H−アゼピノ[5,4,3−cd]インドール−6−オンの塩および多形体 |
| RU2587619C2 (ru) | 2010-02-18 | 2016-06-20 | Дженентек, Инк. | Антагонисты неурегулина и применение их в лечении злокачественного новообразования |
| EP2519826A2 (en) | 2010-03-03 | 2012-11-07 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| US20110217309A1 (en) | 2010-03-03 | 2011-09-08 | Buck Elizabeth A | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors |
| WO2011113802A2 (en) | 2010-03-17 | 2011-09-22 | F. Hoffmann-La Roche Ag | Imidazopyridine compounds, compositions and methods of use |
| EP2550269B1 (en) | 2010-03-23 | 2016-03-23 | Scinopharm Taiwan Ltd. | Process and intermediates for preparing lapatinib |
| EP3235818A3 (en) | 2010-04-01 | 2018-03-14 | Critical Outcome Technologies, Inc. | Compounds for the treatment of hiv |
| BR112012026470A2 (pt) | 2010-04-16 | 2016-08-09 | Genentech Inc | método para prever a sensibilidade de crescimento de células tumorais e para tratar um tumor em um paciente |
| WO2011159835A1 (en) | 2010-06-16 | 2011-12-22 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Antibodies to endoplasmin and their use |
| CA2802644C (en) | 2010-06-25 | 2017-02-21 | Eisai R & D Management Co., Ltd. | Antitumor agent using compounds having kinase inhibitory effect in combination |
| DK2612151T3 (en) | 2010-08-31 | 2017-10-02 | Genentech Inc | BIOMARKETS AND METHODS OF TREATMENT |
| BR112013006016A2 (pt) | 2010-09-15 | 2016-06-07 | Hoffmann La Roche | compostos de azabenzotiazol, composições e métodos de uso |
| WO2012052948A1 (en) | 2010-10-20 | 2012-04-26 | Pfizer Inc. | Pyridine- 2- derivatives as smoothened receptor modulators |
| KR20140009259A (ko) | 2010-11-19 | 2014-01-22 | 에프. 호프만-라 로슈 아게 | 피라졸로피리딘 및 tyk2 억제제로서 이의 용도 |
| CN102552271B (zh) * | 2010-12-09 | 2014-08-06 | 中国科学院上海药物研究所 | 一类喹唑啉类化合物在制备抗黄病毒科病毒的药物中的用途 |
| EP2468883A1 (en) | 2010-12-22 | 2012-06-27 | Pangaea Biotech S.L. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
| WO2012085176A1 (en) | 2010-12-23 | 2012-06-28 | F. Hoffmann-La Roche Ag | Tricyclic pyrazinone compounds, compositions and methods of use thereof as janus kinase inhibitors |
| US9134297B2 (en) | 2011-01-11 | 2015-09-15 | Icahn School Of Medicine At Mount Sinai | Method and compositions for treating cancer and related methods |
| WO2012116040A1 (en) | 2011-02-22 | 2012-08-30 | OSI Pharmaceuticals, LLC | Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma |
| EP2492688A1 (en) | 2011-02-23 | 2012-08-29 | Pangaea Biotech, S.A. | Molecular biomarkers for predicting response to antitumor treatment in lung cancer |
| SG193291A1 (en) | 2011-03-04 | 2013-10-30 | Newgen Therapeutics Inc | Alkyne substituted quinazoline compound and methods of use |
| SG192769A1 (en) | 2011-03-04 | 2013-09-30 | Glaxosmithkline Ip No 2 Ltd | Amino-quinolines as kinase inhibitors |
| EP3597761B1 (en) | 2011-03-09 | 2025-05-07 | Richard G. Pestell | Prostate cancer cell lines, gene signatures and uses thereof |
| US9295676B2 (en) | 2011-03-17 | 2016-03-29 | The Trustees Of The University Of Pennsylvania | Mutation mimicking compounds that bind to the kinase domain of EGFR |
| EP2685980B1 (en) | 2011-03-17 | 2017-12-06 | The Trustees Of The University Of Pennsylvania | Methods and use of bifunctional enzyme-building clamp-shaped molecules |
| WO2012129145A1 (en) | 2011-03-18 | 2012-09-27 | OSI Pharmaceuticals, LLC | Nscle combination therapy |
| WO2012142164A1 (en) | 2011-04-12 | 2012-10-18 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Human monoclonal antibodies that bind insulin-like growth factor (igf) i and ii |
| RU2580609C2 (ru) | 2011-04-18 | 2016-04-10 | Эйсай Ар Энд Ди Менеджмент Ко., Лтд. | Противоопухолевое терапевтическое средство |
| EP3536708A1 (en) | 2011-04-19 | 2019-09-11 | Pfizer Inc | Combinations of anti-4-1bb antibodies and adcc-inducing antibodies for the treatment of cancer |
| EP2702173A1 (en) | 2011-04-25 | 2014-03-05 | OSI Pharmaceuticals, LLC | Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment |
| CN102918029B (zh) | 2011-05-17 | 2015-06-17 | 江苏康缘药业股份有限公司 | 4-苯胺-6-丁烯酰胺-7-烷醚喹唑啉衍生物及其制备方法和用途 |
| EP3444363B1 (en) | 2011-06-03 | 2020-11-25 | Eisai R&D Management Co., Ltd. | Biomarkers for prediciting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds |
| WO2013007768A1 (en) | 2011-07-13 | 2013-01-17 | F. Hoffmann-La Roche Ag | Tricyclic heterocyclic compounds, compositions and methods of use thereof as jak inhibitors |
| WO2013007765A1 (en) | 2011-07-13 | 2013-01-17 | F. Hoffmann-La Roche Ag | Fused tricyclic compounds for use as inhibitors of janus kinases |
| ES2834093T3 (es) | 2011-07-21 | 2021-06-16 | Sumitomo Dainippon Pharma Oncology Inc | Inhibidores de proteína quinasa heterocíclicos |
| RU2014105624A (ru) | 2011-08-12 | 2015-09-20 | Ф. Хоффманн-Ля Рош Аг | Соединения индазола, способ их применения и фармацевтическая композиция |
| KR20140057326A (ko) | 2011-08-17 | 2014-05-12 | 제넨테크, 인크. | 뉴레귤린 항체 및 그의 용도 |
| TWI547494B (zh) | 2011-08-18 | 2016-09-01 | 葛蘭素史克智慧財產發展有限公司 | 作為激酶抑制劑之胺基喹唑啉類 |
| RU2614254C2 (ru) | 2011-08-31 | 2017-03-24 | Дженентек, Инк. | Диагностические маркеры |
| HK1198365A1 (en) | 2011-09-20 | 2015-04-10 | F. Hoffmann-La Roche Ag | Imidazopyridine compounds, compositions and methods of use |
| AU2012311184A1 (en) | 2011-09-22 | 2014-03-06 | Pfizer Inc. | Pyrrolopyrimidine and purine derivatives |
| MX2014003698A (es) | 2011-09-30 | 2014-07-28 | Genentech Inc | Marcadores de diagnostico. |
| CA2848842C (en) | 2011-10-04 | 2020-09-29 | King's College London | Ige anti -hmw-maa antibody |
| WO2013060881A1 (en) | 2011-10-27 | 2013-05-02 | Vereniging Voor Christelijk Hoger Onderwijs, Wetenschappelijk Onderzoek En Patientenzorg | Pyridopyrimidines and their therapeutic use |
| IN2014CN04183A (enExample) | 2011-11-08 | 2015-07-17 | Pfizer | |
| CA2857114A1 (en) | 2011-11-30 | 2013-06-06 | Genentech, Inc. | Erbb3 mutations in cancer |
| CN103172641B (zh) | 2011-12-20 | 2014-06-11 | 钱卫 | 杂环胺基烷氧基取代的喹唑啉衍生物及其用途 |
| CA2863287A1 (en) | 2012-01-31 | 2013-08-08 | Smithkline Beecham (Cork) Limited | Method of treating cancer |
| AR090263A1 (es) | 2012-03-08 | 2014-10-29 | Hoffmann La Roche | Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma |
| BR112014024017A8 (pt) | 2012-03-27 | 2017-07-25 | Genentech Inc | Métodos de tratamento de um tipo de câncer, de tratamento do carcinoma, para selecionar uma terapia e para quantificação e inibidor de her3 |
| KR102115047B1 (ko) | 2012-04-03 | 2020-05-26 | 노파르티스 아게 | 티로신 키나제 억제제들을 갖는 조합 제품 및 그의 용도 |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| EP2861302A4 (en) | 2012-05-14 | 2016-08-24 | Prostagene Llc | USE OF CCR5 MODULATORS IN THE TREATMENT OF CANCER |
| WO2013190089A1 (en) | 2012-06-21 | 2013-12-27 | Pangaea Biotech, S.L. | Molecular biomarkers for predicting outcome in lung cancer |
| TWI592417B (zh) | 2012-09-13 | 2017-07-21 | 葛蘭素史克智慧財產發展有限公司 | 胺基喹唑啉激酶抑制劑之前藥 |
| AR092530A1 (es) | 2012-09-13 | 2015-04-22 | Glaxosmithkline Llc | Compuesto de amino-quinolina, composicion farmaceutica que lo comprende y uso de dicho compuesto para la preparacion de un medicamento |
| DK2909181T3 (da) | 2012-10-16 | 2017-11-20 | Tolero Pharmaceuticals Inc | PKM2-modulatorer og fremgangsmåder til anvendelse deraf |
| US9260426B2 (en) | 2012-12-14 | 2016-02-16 | Arrien Pharmaceuticals Llc | Substituted 1H-pyrrolo [2, 3-b] pyridine and 1H-pyrazolo [3, 4-b] pyridine derivatives as salt inducible kinase 2 (SIK2) inhibitors |
| AU2013364953A1 (en) | 2012-12-21 | 2015-04-30 | Eisai R&D Management Co., Ltd. | Amorphous form of quinoline derivative, and method for producing same |
| JP6301374B2 (ja) | 2013-02-21 | 2018-03-28 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | キナーゼ阻害剤としてのキナゾリン類 |
| KR20150118159A (ko) | 2013-02-22 | 2015-10-21 | 에프. 호프만-라 로슈 아게 | 암의 치료 방법 및 약물 내성의 예방 방법 |
| US9834575B2 (en) | 2013-02-26 | 2017-12-05 | Triact Therapeutics, Inc. | Cancer therapy |
| US9468681B2 (en) | 2013-03-01 | 2016-10-18 | California Institute Of Technology | Targeted nanoparticles |
| RU2015137610A (ru) | 2013-03-06 | 2017-04-10 | Дженентек, Инк. | Способы лечения и профилактики лекарственной резистентности злокачественных опухолей |
| CN105980386B (zh) | 2013-03-13 | 2021-08-13 | 基因泰克公司 | 吡唑并化合物及其用途 |
| HK1220916A1 (zh) | 2013-03-14 | 2017-05-19 | 基因泰克公司 | 治疗癌症和预防癌症药物抗性的方法 |
| AU2014236820B2 (en) | 2013-03-14 | 2018-08-02 | Sumitomo Pharma Oncology, Inc. | JAK2 and ALK2 inhibitors and methods for their use |
| SG11201507477XA (en) | 2013-03-14 | 2015-10-29 | Genentech Inc | Combinations of a mek inhibitor compound with an her3/egfr inhibitor compound and methods of use |
| MX2015011899A (es) | 2013-03-15 | 2016-05-05 | Genentech Inc | Metodos para el tratamiento de cáncer y prevención de resistencia a los fármacos para el cáncer. |
| EP2976085A1 (en) | 2013-03-21 | 2016-01-27 | INSERM - Institut National de la Santé et de la Recherche Médicale | Method and pharmaceutical composition for use in the treatment of chronic liver diseases associated with a low hepcidin expression |
| US9206188B2 (en) | 2013-04-18 | 2015-12-08 | Arrien Pharmaceuticals Llc | Substituted pyrrolo[2,3-b]pyridines as ITK and JAK inhibitors |
| WO2014185540A1 (en) | 2013-05-14 | 2014-11-20 | Eisai R&D Management Co., Ltd. | Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds |
| TW201605896A (zh) | 2013-08-30 | 2016-02-16 | 安美基股份有限公司 | Gitr抗原結合蛋白 |
| US9505767B2 (en) | 2013-09-05 | 2016-11-29 | Genentech, Inc. | Pyrazolo[1,5-A]pyrimidin-7(4H)-onehistone demethylase inhibitors |
| EP3044593A4 (en) | 2013-09-09 | 2017-05-17 | Triact Therapeutics, Inc. | Cancer therapy |
| TW201605857A (zh) | 2013-10-03 | 2016-02-16 | 赫孚孟拉羅股份公司 | Cdk8之醫療性抑制劑及其用途 |
| US20150104392A1 (en) | 2013-10-04 | 2015-04-16 | Aptose Biosciences Inc. | Compositions, biomarkers and their use in the treatment of cancer |
| BR112016008477A2 (pt) | 2013-10-18 | 2017-10-03 | Genentech Inc | Corpos, ácido nucleico, célula hospedeira, método de produção de um anticorpo, imunoconjugado, formulação farmacêutica e usos do anticorpo |
| CN103554091B (zh) * | 2013-11-05 | 2016-05-18 | 沈阳工业大学 | 喹唑啉衍生物及其制备方法和用途 |
| UA115388C2 (uk) | 2013-11-21 | 2017-10-25 | Пфайзер Інк. | 2,6-заміщені пуринові похідні та їх застосування в лікуванні проліферативних захворювань |
| US9815797B2 (en) * | 2013-12-09 | 2017-11-14 | Ucb Biopharma Sprl | Fused bicyclic heteroaromatic derivatives as modulators of TNF activity |
| US20150190506A1 (en) | 2013-12-17 | 2015-07-09 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
| EP3647324A1 (en) | 2013-12-17 | 2020-05-06 | F. Hoffmann-La Roche AG | Methods of treating cancers using pd-1 axis binding antagonists and taxanes |
| RU2016141385A (ru) | 2014-03-24 | 2018-04-28 | Дженентек, Инк. | Лечение рака антагонистами с-мет и их корреляция с экспрессией hgf |
| JP6637439B2 (ja) | 2014-03-31 | 2020-01-29 | ジェネンテック, インコーポレイテッド | 抗ox40抗体及び使用方法 |
| AU2015241038A1 (en) | 2014-03-31 | 2016-10-13 | Genentech, Inc. | Combination therapy comprising anti-angiogenesis agents and OX40 binding agonists |
| WO2015155624A1 (en) | 2014-04-10 | 2015-10-15 | Pfizer Inc. | Dihydropyrrolopyrimidine derivatives |
| US20170027940A1 (en) | 2014-04-10 | 2017-02-02 | Stichting Het Nederlands Kanker Instituut | Method for treating cancer |
| US20170050958A1 (en) | 2014-04-30 | 2017-02-23 | Pfizer Inc. | Cycloalkyl-Linked Diheterocycle Derivatives |
| WO2016001789A1 (en) | 2014-06-30 | 2016-01-07 | Pfizer Inc. | Pyrimidine derivatives as pi3k inhibitors for use in the treatment of cancer |
| JP6811706B2 (ja) | 2014-07-31 | 2021-01-13 | ザ ホンコン ユニヴァーシティ オブ サイエンス アンド テクノロジー | Epha4に対するヒトモノクローナル抗体及びそれらの使用 |
| KR102329681B1 (ko) | 2014-08-28 | 2021-11-23 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 고순도의 퀴놀린 유도체 및 이를 제조하는 방법 |
| JP6814730B2 (ja) | 2014-09-05 | 2021-01-20 | ジェネンテック, インコーポレイテッド | 治療用化合物およびその使用 |
| JP2017529358A (ja) | 2014-09-19 | 2017-10-05 | ジェネンテック, インコーポレイテッド | がんの処置のためのcbp/ep300阻害剤およびbet阻害剤の使用 |
| JP6783230B2 (ja) | 2014-10-10 | 2020-11-11 | ジェネンテック, インコーポレイテッド | ヒストンデメチラーゼのインヒビターとしてのピロリドンアミド化合物 |
| US20170252335A1 (en) | 2014-10-17 | 2017-09-07 | Novartis Ag | Combination of Ceritinib with an EGFR Inhibitor |
| KR20170086540A (ko) | 2014-11-03 | 2017-07-26 | 제넨테크, 인크. | T 세포 면역 하위세트를 검출하기 위한 검정 및 그의 사용 방법 |
| KR20170074246A (ko) | 2014-11-03 | 2017-06-29 | 제넨테크, 인크. | Ox40 효능제 치료의 효능 예측 및 평가용 방법 및 바이오마커 |
| CN107073126A (zh) | 2014-11-06 | 2017-08-18 | 豪夫迈·罗氏有限公司 | 包含ox40结合激动剂和tigit抑制剂的组合疗法 |
| JP6639497B2 (ja) | 2014-11-10 | 2020-02-05 | ジェネンテック, インコーポレイテッド | ブロモドメインインヒビターおよびその使用 |
| MA40943A (fr) | 2014-11-10 | 2017-09-19 | Constellation Pharmaceuticals Inc | Pyrrolopyridines substituées utilisées en tant qu'inhibiteurs de bromodomaines |
| MA40940A (fr) | 2014-11-10 | 2017-09-19 | Constellation Pharmaceuticals Inc | Pyrrolopyridines substituées utilisées en tant qu'inhibiteurs de bromodomaines |
| KR20170096112A (ko) | 2014-11-17 | 2017-08-23 | 제넨테크, 인크. | Ox40 결합 효능제 및 pd-1 축 결합 길항제를 포함하는 조합 요법 |
| US9763922B2 (en) | 2014-11-27 | 2017-09-19 | Genentech, Inc. | Therapeutic compounds and uses thereof |
| KR20200091954A (ko) | 2014-12-15 | 2020-07-31 | 더 리젠츠 오브 더 유니버시티 오브 미시간 | Egfr 및 pi3k의 소분자 억제제 |
| WO2016097918A1 (en) | 2014-12-18 | 2016-06-23 | Pfizer Inc. | Pyrimidine and triazine derivatives and their use as axl inhibitors |
| MX2017006864A (es) | 2014-12-23 | 2017-08-28 | Genentech Inc | Composiciones y métodos para tratar y diagnosticar cánceres resistentes a la quimioterapia. |
| CA2969830A1 (en) | 2014-12-24 | 2016-06-30 | Genentech, Inc. | Therapeutic, diagnostic and prognostic methods for cancer of the bladder |
| EP3240908A2 (en) | 2014-12-30 | 2017-11-08 | F. Hoffmann-La Roche AG | Methods and compositions for prognosis and treatment of cancers |
| WO2016112251A1 (en) | 2015-01-09 | 2016-07-14 | Genentech, Inc. | 4,5-dihydroimidazole derivatives and their use as histone demethylase (kdm2b) inhibitors |
| EP3242874B1 (en) | 2015-01-09 | 2018-10-31 | Genentech, Inc. | Pyridazinone derivatives and their use in the treatment of cancer |
| WO2016112284A1 (en) | 2015-01-09 | 2016-07-14 | Genentech, Inc. | (piperidin-3-yl)(naphthalen-2-yl)methanone derivatives and related compounds as inhibitors of the histone demethylase kdm2b for the treatment of cancer |
| CN107531692B (zh) | 2015-01-29 | 2020-12-25 | 基因泰克公司 | 治疗化合物及其用途 |
| EP3250552B1 (en) | 2015-01-30 | 2019-03-27 | Genentech, Inc. | Therapeutic compounds and uses thereof |
| KR20250024102A (ko) | 2015-02-25 | 2025-02-18 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 퀴놀린 유도체의 고미 억제 방법 |
| MA41598A (fr) | 2015-02-25 | 2018-01-02 | Constellation Pharmaceuticals Inc | Composés thérapeutiques de pyridazine et leurs utilisations |
| AU2015384801B2 (en) | 2015-03-04 | 2022-01-06 | Eisai R&D Management Co., Ltd. | Combination of a PD-1 antagonist and a VEGFR/FGFR/RET tyrosine kinase inhibitor for treating cancer |
| EP3280736A1 (en) | 2015-04-07 | 2018-02-14 | F. Hoffmann-La Roche AG | Antigen binding complex having agonistic activity and methods of use |
| EP3611506B1 (en) | 2015-04-20 | 2021-11-17 | Sumitomo Dainippon Pharma Oncology, Inc. | Predicting response to alvocidib by mitochondrial profiling |
| WO2016178876A2 (en) | 2015-05-01 | 2016-11-10 | Cocrystal Pharma, Inc. | Nucleoside analogs for treatment of the flaviviridae family of viruses and cancer |
| CN107667119A (zh) | 2015-05-12 | 2018-02-06 | 豪夫迈·罗氏有限公司 | 用于癌症的治疗和诊断方法 |
| ES2921350T3 (es) | 2015-05-18 | 2022-08-24 | Sumitomo Pharma Oncology Inc | Profármacos de alvocidib que tienen biodisponibilidad aumentada |
| KR20250151554A (ko) | 2015-05-29 | 2025-10-21 | 제넨테크, 인크. | 암에 대한 치료 및 진단 방법 |
| HK1252272A1 (zh) | 2015-06-08 | 2019-05-24 | 豪夫迈‧罗氏有限公司 | 使用抗ox40抗体治疗癌症的方法 |
| KR20180025888A (ko) | 2015-06-08 | 2018-03-09 | 제넨테크, 인크. | 항-ox40 항체 및 pd-1 축 결합 길항제를 사용하여 암을 치료하는 방법 |
| ES2886107T3 (es) | 2015-06-16 | 2021-12-16 | Prism Biolab Co Ltd | Antineoplásico |
| JP6896650B2 (ja) | 2015-06-17 | 2021-06-30 | ジェネンテック, インコーポレイテッド | Pd−1軸結合アンタゴニスト及びタキサンを使用した局所進行性または転移性乳癌の治療方法 |
| CN111643479B (zh) | 2015-07-01 | 2023-10-27 | 加州理工学院 | 基于阳离子粘酸聚合物的递送系统 |
| WO2017009751A1 (en) | 2015-07-15 | 2017-01-19 | Pfizer Inc. | Pyrimidine derivatives |
| BR112018002427A8 (pt) | 2015-08-03 | 2022-10-18 | Tolero Pharmaceuticals Inc | Uso de alvocidib e de azacitidina ou decitabina para tratar câncer e kit e composição farmacêutica contendo as ditas substâncias |
| SG11201801083UA (en) | 2015-08-20 | 2018-03-28 | Eisai R&D Man Co Ltd | Tumor therapeutic agent |
| DK3341376T3 (da) | 2015-08-26 | 2021-03-29 | Fundacion Del Sector Publico Estatal Centro Nac De Investigaciones Oncologicas Carlos Iii F S P Cnio | Kondenserede tricykliske forbindelser som proteinkinase-inhibitorer |
| SMT202500003T1 (it) | 2015-09-25 | 2025-03-12 | Hoffmann La Roche | Anticorpi anti-tigit e procedimenti di utilizzo |
| MX2018004109A (es) | 2015-10-05 | 2018-09-27 | Univ Columbia | Activadores de flujo autofágico y fosfolipasa d y depuración de acumulaciones de proteína que incluyen tau y tratamiento de proteinopatías. |
| EP3383375A1 (en) | 2015-12-03 | 2018-10-10 | Agios Pharmaceuticals, Inc. | Mat2a inhibitors for treating mtap null cancer |
| ES2907574T3 (es) | 2015-12-16 | 2022-04-25 | Genentech Inc | Proceso para la preparación de compuestos inhibidores de pi3k triciclicos y métodos para su utilización para el tratamiento del cáncer. |
| CN108368179B (zh) | 2016-01-08 | 2022-08-23 | 豪夫迈·罗氏有限公司 | 使用pd-1轴结合拮抗剂和抗cea/抗cd3双特异性抗体治疗cea阳性癌症的方法 |
| EP3423596B1 (en) | 2016-02-29 | 2022-09-28 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
| CN107141293B (zh) | 2016-03-01 | 2022-09-23 | 上海医药集团股份有限公司 | 一种含氮杂环化合物、制备方法、中间体、组合物和应用 |
| UA126115C2 (uk) | 2016-03-08 | 2022-08-17 | Янссен Байотек, Інк. | Антитіло до gitr |
| EP3443004A1 (en) | 2016-04-14 | 2019-02-20 | H. Hoffnabb-La Roche Ag | Anti-rspo3 antibodies and methods of use |
| WO2017181111A2 (en) | 2016-04-15 | 2017-10-19 | Genentech, Inc. | Methods for monitoring and treating cancer |
| KR20180134347A (ko) | 2016-04-15 | 2018-12-18 | 제넨테크, 인크. | 암의 진단 및 치료 방법 |
| JP2019515670A (ja) | 2016-04-15 | 2019-06-13 | ジェネンテック, インコーポレイテッド | がんをモニタリングし治療するための方法 |
| WO2017205536A2 (en) | 2016-05-24 | 2017-11-30 | Genentech, Inc. | Therapeutic compounds and uses thereof |
| EP3464286B1 (en) | 2016-05-24 | 2021-08-18 | Genentech, Inc. | Pyrazolopyridine derivatives for the treatment of cancer |
| CN109312407A (zh) | 2016-06-08 | 2019-02-05 | 豪夫迈·罗氏有限公司 | 用于癌症的诊断和治疗方法 |
| IL264161B2 (en) | 2016-07-14 | 2025-06-01 | Scholar Rock Inc | Tgfb antibodies, methods, and uses |
| US11046776B2 (en) | 2016-08-05 | 2021-06-29 | Genentech, Inc. | Multivalent and multiepitopic antibodies having agonistic activity and methods of use |
| WO2018029124A1 (en) | 2016-08-08 | 2018-02-15 | F. Hoffmann-La Roche Ag | Therapeutic and diagnostic methods for cancer |
| AU2017339517B2 (en) | 2016-10-06 | 2024-03-14 | Foundation Medicine, Inc. | Therapeutic and diagnostic methods for cancer |
| EP3532091A2 (en) | 2016-10-29 | 2019-09-04 | H. Hoffnabb-La Roche Ag | Anti-mic antibidies and methods of use |
| WO2018094275A1 (en) | 2016-11-18 | 2018-05-24 | Tolero Pharmaceuticals, Inc. | Alvocidib prodrugs and their use as protein kinase inhibitors |
| JP6619519B2 (ja) | 2016-12-19 | 2019-12-11 | トレロ ファーマシューティカルズ, インコーポレイテッド | プロファイリングペプチドおよび感受性プロファイリングのための方法 |
| MY196830A (en) | 2016-12-22 | 2023-05-03 | Amgen Inc | Kras g12c inhibitors and methods of using the same |
| US12303505B2 (en) | 2017-02-08 | 2025-05-20 | Eisai R&D Management Co., Ltd. | Tumor-treating pharmaceutical composition |
| JP7256127B2 (ja) | 2017-03-01 | 2023-04-11 | ジェネンテック, インコーポレイテッド | がんのための診断及び治療方法 |
| CN110505883A (zh) | 2017-04-13 | 2019-11-26 | 豪夫迈·罗氏有限公司 | 供治疗癌症的方法中使用的白介素-2免疫缀合物,cd40激动剂,和任选地pd-1轴结合拮抗剂 |
| US20200197384A1 (en) | 2017-05-16 | 2020-06-25 | Eisai R&D Management Co., Ltd. | Treatment of hepatocellular carcinoma |
| JOP20190272A1 (ar) | 2017-05-22 | 2019-11-21 | Amgen Inc | مثبطات kras g12c وطرق لاستخدامها |
| CN111492245A (zh) | 2017-07-21 | 2020-08-04 | 基因泰克公司 | 癌症的治疗和诊断方法 |
| WO2019033043A2 (en) | 2017-08-11 | 2019-02-14 | Genentech, Inc. | ANTI-CD8 ANTIBODIES AND USES THEREOF |
| EP3677583A4 (en) | 2017-09-01 | 2021-07-21 | Shanghai Pharmaceuticals Holding Co., Ltd. | NITROGENOUS HETEROCYCLIC COMPOUND, METHOD OF PREPARATION, INTERMEDIATE, COMPOSITION AND APPLICATION |
| US11859252B2 (en) | 2017-09-08 | 2024-01-02 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| AR112797A1 (es) | 2017-09-08 | 2019-12-11 | Amgen Inc | Inhibidores de kras g12c y métodos para utilizarlos |
| JP7196160B2 (ja) | 2017-09-12 | 2022-12-26 | スミトモ ファーマ オンコロジー, インコーポレイテッド | Mcl-1阻害剤アルボシジブを用いた、bcl-2阻害剤に対して非感受性である癌の治療レジメン |
| WO2019075367A1 (en) | 2017-10-13 | 2019-04-18 | Tolero Pharmaceuticals, Inc. | PKM2 ACTIVATORS IN COMBINATION WITH OXYGEN REACTIVE SPECIES FOR THE TREATMENT OF CANCER |
| WO2019084395A1 (en) | 2017-10-27 | 2019-05-02 | University Of Virginia Patent Foundation | COMPOUNDS AND METHODS FOR REGULATING, LIMITING OR INHIBITING AVIL EXPRESSION |
| MX2020004567A (es) | 2017-11-06 | 2020-08-13 | Genentech Inc | Metodos diagnosticos y terapeuticos para el cancer. |
| JP2021506974A (ja) | 2017-12-18 | 2021-02-22 | スターングリーン、インク. | チロシンキナーゼ阻害剤として有用なピリミジン化合物 |
| AU2019207535B2 (en) | 2018-01-15 | 2021-12-23 | Epiaxis Therapeutics Pty Ltd | Agents and methods for predicting response to therapy |
| MX2020008882A (es) | 2018-02-26 | 2021-01-08 | Genentech Inc | Dosificación para tratamiento con anticuerpos antagonistas anti-tigit y anti-pd-l1. |
| AU2019262599B2 (en) | 2018-05-04 | 2023-10-12 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
| WO2019213516A1 (en) | 2018-05-04 | 2019-11-07 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| ES2986917T3 (es) | 2018-05-10 | 2024-11-13 | Amgen Inc | Inhibidores de KRAS G12C para el tratamiento del cáncer |
| EP3797173A2 (en) | 2018-05-21 | 2021-03-31 | Nanostring Technologies, Inc. | Molecular gene signatures and methods of using same |
| CA3098885A1 (en) | 2018-06-01 | 2019-12-05 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| US20190375749A1 (en) | 2018-06-11 | 2019-12-12 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| JP7369719B2 (ja) | 2018-06-12 | 2023-10-26 | アムジエン・インコーポレーテツド | KRas G12C阻害剤及びそれを使用する方法 |
| WO2019241327A1 (en) | 2018-06-13 | 2019-12-19 | California Institute Of Technology | Nanoparticles for crossing the blood brain barrier and methods of treatment using the same |
| MY205645A (en) | 2018-06-23 | 2024-11-02 | Genentech Inc | Methods of treating lung cancer with a pd-1 axis binding antagonist, a platinum agent, and a topoisomerase ii inhibitor |
| TW202011991A (zh) | 2018-07-18 | 2020-04-01 | 美商建南德克公司 | 用pd-1軸結合拮抗劑、抗代謝劑及鉑劑治療肺癌之方法 |
| CN112512597A (zh) | 2018-07-26 | 2021-03-16 | 大日本住友制药肿瘤公司 | 用于治疗与acvr1表达异常相关的疾病的方法以及用于此的acvr1抑制剂 |
| EP3847154A1 (en) | 2018-09-03 | 2021-07-14 | F. Hoffmann-La Roche AG | Carboxamide and sulfonamide derivatives useful as tead modulators |
| MX2021003214A (es) | 2018-09-19 | 2021-05-12 | Genentech Inc | Metodos terapeuticos y de diagnostico para el cancer de vejiga. |
| JP7475336B2 (ja) | 2018-09-21 | 2024-04-26 | ジェネンテック, インコーポレイテッド | トリプルネガティブ乳癌のための診断方法 |
| BR112021006407A8 (pt) | 2018-10-04 | 2022-12-06 | Inst Nat Sante Rech Med | uso de inibidores do egfr para ceratodermas |
| EP3867405A4 (en) | 2018-10-17 | 2022-07-20 | The University of Queensland | Epigenetic biomarker and uses therefor |
| WO2020081767A1 (en) | 2018-10-18 | 2020-04-23 | Genentech, Inc. | Diagnostic and therapeutic methods for sarcomatoid kidney cancer |
| JP7516029B2 (ja) | 2018-11-16 | 2024-07-16 | アムジエン・インコーポレーテツド | Kras g12c阻害剤化合物の重要な中間体の改良合成法 |
| US11053226B2 (en) | 2018-11-19 | 2021-07-06 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
| JP7377679B2 (ja) | 2018-11-19 | 2023-11-10 | アムジエン・インコーポレーテツド | がん治療のためのkrasg12c阻害剤及び1種以上の薬学的に活性な追加の薬剤を含む併用療法 |
| JP2022511029A (ja) | 2018-12-04 | 2022-01-28 | スミトモ ダイニッポン ファーマ オンコロジー, インコーポレイテッド | がんの処置のための薬剤としての使用のためのcdk9インヒビターおよびその多形 |
| CN113490666A (zh) | 2018-12-19 | 2021-10-08 | 奥瑞生物药品公司 | 作为fgfr酪氨酸激酶的抑制剂的取代的吡唑并[1,5-a]吡啶化合物 |
| EP3898615A1 (en) | 2018-12-19 | 2021-10-27 | Array Biopharma, Inc. | 7-((3,5-dimethoxyphenyl)amino)quinoxaline derivatives as fgfr inhibitors for treating cancer |
| CA3123044A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Heteroaryl amides useful as kif18a inhibitors |
| WO2020132651A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Kif18a inhibitors |
| CA3123227A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Heteroaryl amides useful as kif18a inhibitors |
| TWI844602B (zh) | 2018-12-20 | 2024-06-11 | 美商安進公司 | Kif18a抑制劑 |
| WO2020163589A1 (en) | 2019-02-08 | 2020-08-13 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| HUE072069T2 (hu) | 2019-02-12 | 2025-10-28 | Sumitomo Pharma America Inc | 2-((1R,4R)-4-((3-(3-(trifluormetil)fenil)imidazo[1,2- b]piridazin-6-il)amino)ciklohexil)propán-2-ol sósavas sójának kristályos formája |
| WO2020172712A1 (en) | 2019-02-27 | 2020-09-03 | Epiaxis Therapeutics Pty Ltd | Methods and agents for assessing t-cell function and predicting response to therapy |
| CN113710706A (zh) | 2019-02-27 | 2021-11-26 | 豪夫迈·罗氏有限公司 | 用于抗tigit抗体和抗cd20抗体或抗cd38抗体治疗的给药 |
| US20230148450A9 (en) | 2019-03-01 | 2023-05-11 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
| US20230096028A1 (en) | 2019-03-01 | 2023-03-30 | Revolution Medicines, Inc. | Bicyclic heterocyclyl compounds and uses thereof |
| US11793802B2 (en) | 2019-03-20 | 2023-10-24 | Sumitomo Pharma Oncology, Inc. | Treatment of acute myeloid leukemia (AML) with venetoclax failure |
| EP3941463A1 (en) | 2019-03-22 | 2022-01-26 | Sumitomo Dainippon Pharma Oncology, Inc. | Compositions comprising pkm2 modulators and methods of treatment using the same |
| WO2020223233A1 (en) | 2019-04-30 | 2020-11-05 | Genentech, Inc. | Prognostic and therapeutic methods for colorectal cancer |
| JP2022530674A (ja) | 2019-05-03 | 2022-06-30 | ジェネンテック, インコーポレイテッド | 抗pd-l1抗体を用いたがんの処置方法 |
| EP3738593A1 (en) | 2019-05-14 | 2020-11-18 | Amgen, Inc | Dosing of kras inhibitor for treatment of cancers |
| CA3225293A1 (en) | 2019-05-21 | 2020-11-26 | Amgen Inc. | Solid state forms |
| CN112300279A (zh) | 2019-07-26 | 2021-02-02 | 上海复宏汉霖生物技术股份有限公司 | 针对抗cd73抗体和变体的方法和组合物 |
| US20220372018A1 (en) | 2019-08-02 | 2022-11-24 | Amgen Inc. | Kif18a inhibitors |
| AU2020326627A1 (en) | 2019-08-02 | 2022-03-17 | Amgen Inc. | KIF18A inhibitors |
| WO2021026101A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
| MX2022001296A (es) | 2019-08-02 | 2022-02-22 | Amgen Inc | Inhibidores de kif18a. |
| MX2022002738A (es) | 2019-09-04 | 2022-06-27 | Genentech Inc | Agentes de union a cd8 y uso de los mismos. |
| EP4048693A1 (en) | 2019-09-27 | 2022-08-31 | F. Hoffmann-La Roche AG | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
| EP4048671A1 (en) | 2019-10-24 | 2022-08-31 | Amgen Inc. | Pyridopyrimidine derivatives useful as kras g12c and kras g12d inhibitors in the treatment of cancer |
| JP2023511472A (ja) | 2019-10-29 | 2023-03-20 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | がんの治療のための二官能性化合物 |
| CN115894606A (zh) | 2019-11-04 | 2023-04-04 | 锐新医药公司 | Ras抑制剂 |
| CA3160142A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2021091967A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
| AU2020378330A1 (en) | 2019-11-06 | 2022-05-12 | F. Hoffmann-La Roche Ag | Diagnostic and therapeutic methods for treatment of hematologic cancers |
| KR20220100903A (ko) | 2019-11-08 | 2022-07-18 | 레볼루션 메디슨즈, 인크. | 이환식 헤테로아릴 화합물 및 이의 용도 |
| CN112778217B (zh) * | 2019-11-08 | 2024-01-26 | 沈阳化工研究院有限公司 | 一种喹唑啉类化合物及其应用 |
| AU2020381458A1 (en) | 2019-11-13 | 2022-05-12 | Genentech, Inc. | Therapeutic compounds and methods of use |
| US12473281B2 (en) | 2019-11-14 | 2025-11-18 | Amgen Inc. | Synthesis of KRAS G12C inhibitor compound |
| EP4058453A1 (en) | 2019-11-14 | 2022-09-21 | Amgen Inc. | Improved synthesis of kras g12c inhibitor compound |
| EP4065231A1 (en) | 2019-11-27 | 2022-10-05 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| CR20220330A (es) | 2019-12-13 | 2022-08-04 | Genentech Inc | Anticuerpos anti-ly6g6d y métodos de uso. |
| AU2020408562A1 (en) | 2019-12-20 | 2022-06-23 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
| MX2022008305A (es) | 2020-01-07 | 2022-08-08 | Revolution Medicines Inc | Dosificacion de inhibidores de shp2 y metodos de tratamiento del cancer. |
| WO2021194481A1 (en) | 2020-03-24 | 2021-09-30 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
| JP2023511595A (ja) | 2020-01-27 | 2023-03-20 | ジェネンテック, インコーポレイテッド | 抗tigitアンタゴニスト抗体を用いたがんを処置するための方法 |
| WO2021155006A1 (en) | 2020-01-31 | 2021-08-05 | Les Laboratoires Servier Sas | Inhibitors of cyclin-dependent kinases and uses thereof |
| WO2021177980A1 (en) | 2020-03-06 | 2021-09-10 | Genentech, Inc. | Combination therapy for cancer comprising pd-1 axis binding antagonist and il6 antagonist |
| EP4127724A1 (en) | 2020-04-03 | 2023-02-08 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
| JP2023523450A (ja) | 2020-04-28 | 2023-06-05 | ジェネンテック, インコーポレイテッド | 非小細胞肺がん免疫療法のための方法及び組成物 |
| MX2022015877A (es) | 2020-06-16 | 2023-01-24 | Genentech Inc | Metodos y composiciones para tratar cancer de mama triple negativo. |
| JP2023530351A (ja) | 2020-06-18 | 2023-07-14 | レヴォリューション・メディスンズ,インコーポレイテッド | Ras阻害剤への獲得耐性を遅延させる、防止する、及び、治療する方法 |
| US20210395366A1 (en) | 2020-06-18 | 2021-12-23 | Genentech, Inc. | Treatment with anti-tigit antibodies and pd-1 axis binding antagonists |
| US11787775B2 (en) | 2020-07-24 | 2023-10-17 | Genentech, Inc. | Therapeutic compounds and methods of use |
| CN116568824A (zh) | 2020-08-03 | 2023-08-08 | 基因泰克公司 | 淋巴瘤的诊断和治疗方法 |
| EP4196612A1 (en) | 2020-08-12 | 2023-06-21 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| KR20230081726A (ko) | 2020-09-03 | 2023-06-07 | 레볼루션 메디슨즈, 인크. | Shp2 돌연변이가 있는 악성 종양을 치료하기 위한 sos1 억제제의 용도 |
| KR20230067635A (ko) | 2020-09-15 | 2023-05-16 | 레볼루션 메디슨즈, 인크. | 암의 치료에서 ras 억제제로서 인돌 유도체 |
| KR20230094198A (ko) | 2020-09-23 | 2023-06-27 | 에라스카, 아이엔씨. | 3환식 피리돈 및 피리미돈 |
| WO2022076462A1 (en) | 2020-10-05 | 2022-04-14 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
| US20230107642A1 (en) | 2020-12-18 | 2023-04-06 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
| WO2022140427A1 (en) | 2020-12-22 | 2022-06-30 | Qilu Regor Therapeutics Inc. | Sos1 inhibitors and uses thereof |
| US20240239764A1 (en) | 2020-12-22 | 2024-07-18 | Mekanistic Therapeutics | Substituted aminobenzyl heteroaryl compounds as egfr and/or pi3k inhibitors |
| AU2022221124A1 (en) | 2021-02-12 | 2023-08-03 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydroazepine derivatives for the treatment of cancer |
| CN118852330A (zh) | 2021-05-05 | 2024-10-29 | 锐新医药公司 | 用于治疗癌症的ras抑制剂 |
| CA3217393A1 (en) | 2021-05-05 | 2022-11-10 | Elena S. Koltun | Ras inhibitors |
| WO2022235866A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| WO2022251296A1 (en) | 2021-05-25 | 2022-12-01 | Erasca, Inc. | Sulfur-containing heteroaromatic tricyclic kras inhibitors |
| WO2022266206A1 (en) | 2021-06-16 | 2022-12-22 | Erasca, Inc. | Kras inhibitor conjugates |
| WO2023018699A1 (en) | 2021-08-10 | 2023-02-16 | Erasca, Inc. | Selective kras inhibitors |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| JP2024543912A (ja) | 2021-11-24 | 2024-11-26 | ジェネンテック, インコーポレイテッド | 二環式治療用化合物及びがんの処置における使用方法 |
| JP2024541508A (ja) | 2021-11-24 | 2024-11-08 | ジェネンテック, インコーポレイテッド | 治療用インダゾール化合物およびがんの治療における使用方法 |
| TW202340214A (zh) | 2021-12-17 | 2023-10-16 | 美商健臻公司 | 做為shp2抑制劑之吡唑并吡𠯤化合物 |
| EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
| MX2024010828A (es) | 2022-03-07 | 2024-09-17 | Amgen Inc | Procedimiento para preparar 4-metil-2-propan-2-il-piridin-3-carbon itrilo. |
| JP2025510572A (ja) | 2022-03-08 | 2025-04-15 | レボリューション メディシンズ インコーポレイテッド | 免疫不応性肺癌を治療するための方法 |
| JP2025512824A (ja) | 2022-04-01 | 2025-04-22 | ジェネンテック, インコーポレイテッド | 抗fcrh5/抗cd3二重特異性抗体による処置のための投与 |
| EP4522653A1 (en) | 2022-05-11 | 2025-03-19 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
| AU2023284422A1 (en) | 2022-06-07 | 2024-12-19 | Genentech, Inc. | Method for determining the efficacy of a lung cancer treatment comprising an anti-pd-l1 antagonist and an anti-tigit antagonist antibody |
| AU2023285116A1 (en) | 2022-06-10 | 2024-12-19 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| AU2023305619A1 (en) | 2022-07-13 | 2025-01-23 | F. Hoffmann-La Roche Ag | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
| JP2025523845A (ja) | 2022-07-19 | 2025-07-25 | ジェネンテック, インコーポレイテッド | 抗fcrh5/抗cd3二重特異性抗体による処置のための投薬 |
| TW202417439A (zh) | 2022-08-11 | 2024-05-01 | 瑞士商赫孚孟拉羅股份公司 | 雙環四氫噻吖呯衍生物 |
| WO2024033458A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydroazepine derivatives |
| MA71728A (fr) | 2022-08-11 | 2025-05-30 | F. Hoffmann-La Roche Ag | Dérivés bicycliques de tétrahydrothiazépine |
| JP2025526727A (ja) | 2022-08-11 | 2025-08-15 | エフ・ホフマン-ラ・ロシュ・アクチェンゲゼルシャフト | 二環式テトラヒドロチアゼピン誘導体 |
| EP4601644A1 (en) | 2022-10-14 | 2025-08-20 | Black Diamond Therapeutics, Inc. | Methods of treating cancers using isoquinoline or 6-aza-quinoline derivatives |
| WO2024085242A2 (en) | 2022-10-21 | 2024-04-25 | Kawasaki Institute Of Industrial Promotion | Non-fouling or super stealth vesicle |
| AU2023367741A1 (en) | 2022-10-25 | 2025-05-01 | Genentech, Inc. | Therapeutic and diagnostic methods for multiple myeloma |
| WO2024173842A1 (en) | 2023-02-17 | 2024-08-22 | Erasca, Inc. | Kras inhibitors |
| AU2024241633A1 (en) | 2023-03-30 | 2025-11-06 | Revolution Medicines, Inc. | Compositions for inducing ras gtp hydrolysis and uses thereof |
| WO2024211663A1 (en) | 2023-04-07 | 2024-10-10 | Revolution Medicines, Inc. | Condensed macrocyclic compounds as ras inhibitors |
| WO2024211712A1 (en) | 2023-04-07 | 2024-10-10 | Revolution Medicines, Inc. | Condensed macrocyclic compounds as ras inhibitors |
| AU2024252105A1 (en) | 2023-04-14 | 2025-10-16 | Revolution Medicines, Inc. | Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof |
| TW202446388A (zh) | 2023-04-14 | 2024-12-01 | 美商銳新醫藥公司 | Ras抑制劑之結晶形式、含有其之組合物及其使用方法 |
| TW202508595A (zh) | 2023-05-04 | 2025-03-01 | 美商銳新醫藥公司 | 用於ras相關疾病或病症之組合療法 |
| WO2024233341A1 (en) | 2023-05-05 | 2024-11-14 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
| AU2024283865A1 (en) | 2023-06-08 | 2025-11-27 | Genentech, Inc. | Macrophage signatures for diagnostic and therapeutic methods for lymphoma |
| WO2025024257A1 (en) | 2023-07-21 | 2025-01-30 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
| WO2025034702A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Rmc-6291 for use in the treatment of ras protein-related disease or disorder |
| TW202515614A (zh) | 2023-08-25 | 2025-04-16 | 美商建南德克公司 | 治療非小細胞肺癌之方法及組成物 |
| WO2025080946A2 (en) | 2023-10-12 | 2025-04-17 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025137507A1 (en) | 2023-12-22 | 2025-06-26 | Regor Pharmaceuticals, Inc. | Sos1 inhibitors and uses thereof |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5710158A (en) | 1991-05-10 | 1998-01-20 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| US5480883A (en) | 1991-05-10 | 1996-01-02 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| AU661533B2 (en) | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
| GB9314884D0 (en) | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Tricyclic derivatives |
| 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 |
| TW414798B (en) | 1994-09-07 | 2000-12-11 | Thomae Gmbh Dr K | Pyrimido (5,4-d) pyrimidines, medicaments comprising these compounds, their use and processes for their preparation |
| GB9510757D0 (en) * | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
| TW321649B (enExample) * | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
| AU711426B2 (en) | 1994-11-14 | 1999-10-14 | Warner-Lambert Company | 6-aryl pyrido(2,3-d)pyrimidines and naphthyridines for inhibiting protein tyrosine kinase mediated cellular proliferation |
| GB9424233D0 (en) * | 1994-11-30 | 1995-01-18 | Zeneca Ltd | Quinazoline derivatives |
| GB9514265D0 (en) | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
| GB9603095D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
-
1997
- 1997-07-11 AR ARP970103103A patent/AR007857A1/es unknown
- 1997-07-11 ES ES97934458T patent/ES2186908T3/es not_active Expired - Lifetime
- 1997-07-11 US US09/214,267 patent/US6391874B1/en not_active Expired - Lifetime
- 1997-07-11 ID IDP972414A patent/ID19609A/id unknown
- 1997-07-11 DK DK97934458T patent/DK0912559T3/da active
- 1997-07-11 AT AT97934458T patent/ATE227283T1/de active
- 1997-07-11 DE DE69716916T patent/DE69716916T2/de not_active Expired - Lifetime
- 1997-07-11 EP EP97934458A patent/EP0912559B1/en not_active Expired - Lifetime
- 1997-07-11 JP JP50559698A patent/JP4386967B2/ja not_active Expired - Lifetime
- 1997-07-11 PT PT97934458T patent/PT912559E/pt unknown
- 1997-07-11 AU AU37668/97A patent/AU3766897A/en not_active Abandoned
- 1997-07-11 WO PCT/EP1997/003672 patent/WO1998002434A1/en not_active Ceased
-
2002
- 2002-01-31 US US10/062,647 patent/US6828320B2/en not_active Expired - Lifetime
-
2004
- 2004-04-29 CY CY0400034A patent/CY2451B1/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AR007857A1 (es) | 1999-11-24 |
| EP0912559A1 (en) | 1999-05-06 |
| CY2451B1 (en) | 2005-06-03 |
| ID19609A (id) | 1998-07-23 |
| PT912559E (pt) | 2003-03-31 |
| US6391874B1 (en) | 2002-05-21 |
| DE69716916T2 (de) | 2003-07-03 |
| DE69716916D1 (de) | 2002-12-12 |
| ES2186908T3 (es) | 2003-05-16 |
| AU3766897A (en) | 1998-02-09 |
| ATE227283T1 (de) | 2002-11-15 |
| DK0912559T3 (da) | 2003-03-10 |
| JP2000514806A (ja) | 2000-11-07 |
| US6828320B2 (en) | 2004-12-07 |
| WO1998002434A1 (en) | 1998-01-22 |
| US20020147214A1 (en) | 2002-10-10 |
| EP0912559B1 (en) | 2002-11-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4386967B2 (ja) | プロテインチロシンキナーゼ阻害剤としての縮合複素環式化合物 | |
| ES2206729T3 (es) | Compuestos heteroaromaticos biciclicos como inhibidores de la proteina tirosina quinasa. | |
| CN107295799B (zh) | Parg抑制化合物 | |
| KR102010611B1 (ko) | 인다졸-3-카르복사미드 및 WNT/β-카테닌 신호생성 경로 저해제들로써의 이들 용도 | |
| JP6355648B2 (ja) | Wntシグナル伝達経路の3−(ベンゾイミダゾール−2−イル)−インダゾール阻害剤およびそれらの治療的使用 | |
| CN102741256B (zh) | 对于蛋白激酶具有抑制活性的双环杂芳基衍生物 | |
| EP0912572B1 (en) | Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors | |
| RU2260007C2 (ru) | Производные амида, способ их получения (варианты), фармацевтическая композиция, способ ингибирования | |
| CN100357278C (zh) | 作为激酶抑制剂的取代的三唑二胺衍生物 | |
| JP5302884B2 (ja) | Vr1のベンゾイミダゾール系モジュレーター | |
| JP5366349B2 (ja) | ホスホジエステラーゼ阻害剤として有効な置換ピロロピリジノン誘導体 | |
| TW200914443A (en) | Process for preparing substituted quinazolinyl furanaldehyde | |
| WO1999035132A1 (en) | Heterocyclic compounds | |
| EP0843671A1 (en) | Heterocyclic compounds and pharmaceutical compositions containing them | |
| KR20070038531A (ko) | 치환된 환식 우레아 유도체, 그의 제조 방법 및 그의키나아제 억제제로서의 제약학적 용도 | |
| CN107438598A (zh) | 喹唑啉和喹啉化合物及其用途 | |
| TW200400965A (en) | Antiviral compounds | |
| WO2020156283A1 (zh) | 炔基嘧啶或炔基吡啶类化合物、及其组合物与应用 | |
| CN110407839B (zh) | 含杂芳基酰胺结构的三唑并杂环类化合物的制备及应用 | |
| CN101115752A (zh) | 作为周期素依赖激酶抑制剂的4-(4-(咪唑-4-基)嘧啶-2-基氨基)苯甲酰胺 | |
| HK1245253B (zh) | Parg抑制化合物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20040712 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040712 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20080401 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080630 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080811 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080728 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20080728 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20081104 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090130 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20090514 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090529 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090727 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20090904 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20090930 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121009 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121009 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20131009 Year of fee payment: 4 |
|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| R360 | Written notification for declining of transfer of rights |
Free format text: JAPANESE INTERMEDIATE CODE: R360 |
|
| R360 | Written notification for declining of transfer of rights |
Free format text: JAPANESE INTERMEDIATE CODE: R360 |
|
| R371 | Transfer withdrawn |
Free format text: JAPANESE INTERMEDIATE CODE: R371 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R360 | Written notification for declining of transfer of rights |
Free format text: JAPANESE INTERMEDIATE CODE: R360 |
|
| R360 | Written notification for declining of transfer of rights |
Free format text: JAPANESE INTERMEDIATE CODE: R360 |
|
| R371 | Transfer withdrawn |
Free format text: JAPANESE INTERMEDIATE CODE: R371 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |