CA2703767A1 - Novel 4-(tetrazol-5-yl)-quinazoline derivatives as anti cancer agents - Google Patents
Novel 4-(tetrazol-5-yl)-quinazoline derivatives as anti cancer agents Download PDFInfo
- Publication number
- CA2703767A1 CA2703767A1 CA2703767A CA2703767A CA2703767A1 CA 2703767 A1 CA2703767 A1 CA 2703767A1 CA 2703767 A CA2703767 A CA 2703767A CA 2703767 A CA2703767 A CA 2703767A CA 2703767 A1 CA2703767 A1 CA 2703767A1
- Authority
- CA
- Canada
- Prior art keywords
- formula
- quinazoline
- tetrazol
- compound
- substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- AOTAXPQFHSKSIZ-UHFFFAOYSA-N 4-(2h-tetrazol-5-yl)quinazoline Chemical class N=1C=NC2=CC=CC=C2C=1C1=NN=NN1 AOTAXPQFHSKSIZ-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 239000002246 antineoplastic agent Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 110
- 238000000034 method Methods 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 230000008569 process Effects 0.000 claims abstract description 12
- 238000011282 treatment Methods 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 75
- -1 hydroxy, amino, hydroxylamino, carboxy, nitro, guanidino, ureido Chemical group 0.000 claims description 63
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 46
- 239000002904 solvent Substances 0.000 claims description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- 150000003246 quinazolines Chemical class 0.000 claims description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- 206010028980 Neoplasm Diseases 0.000 claims description 21
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 20
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 16
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 16
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 12
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 229910052751 metal Inorganic materials 0.000 claims description 12
- 239000002184 metal Substances 0.000 claims description 12
- 239000008096 xylene Substances 0.000 claims description 12
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 11
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 10
- 150000001336 alkenes Chemical class 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052698 phosphorus Inorganic materials 0.000 claims description 10
- 239000011574 phosphorus Substances 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 8
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 229910052744 lithium Inorganic materials 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 7
- 230000002140 halogenating effect Effects 0.000 claims description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- 150000004679 hydroxides Chemical class 0.000 claims description 7
- 239000000543 intermediate Substances 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- 150000004703 alkoxides Chemical class 0.000 claims description 6
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 6
- 229910052987 metal hydride Inorganic materials 0.000 claims description 6
- 150000004681 metal hydrides Chemical class 0.000 claims description 6
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 claims description 5
- 125000001475 halogen functional group Chemical group 0.000 claims description 5
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 claims description 5
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 claims description 5
- 125000005270 trialkylamine group Chemical group 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- FCEBCZMVZSJVCA-UHFFFAOYSA-N 3-[[5-(6,7-dimethoxyquinazolin-4-yl)tetrazol-1-yl]methyl]aniline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1C1=NN=NN1CC1=CC=CC(N)=C1 FCEBCZMVZSJVCA-UHFFFAOYSA-N 0.000 claims description 4
- TVKKJQLSHMSYNN-UHFFFAOYSA-N 6,7-dimethoxy-4-[1-[(3-nitrophenyl)methyl]tetrazol-5-yl]quinazoline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1C1=NN=NN1CC1=CC=CC([N+]([O-])=O)=C1 TVKKJQLSHMSYNN-UHFFFAOYSA-N 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 4
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 239000002168 alkylating agent Substances 0.000 claims description 4
- 229940100198 alkylating agent Drugs 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 4
- LNENVNGQOUBOIX-UHFFFAOYSA-N azidosilane Chemical compound [SiH3]N=[N+]=[N-] LNENVNGQOUBOIX-UHFFFAOYSA-N 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 4
- DRYRBWIFRVMRPV-UHFFFAOYSA-N quinazolin-4-amine Chemical class C1=CC=C2C(N)=NC=NC2=C1 DRYRBWIFRVMRPV-UHFFFAOYSA-N 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- APGGSERFJKEWFG-UHFFFAOYSA-N 1-(chloromethyl)-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(CCl)=C1 APGGSERFJKEWFG-UHFFFAOYSA-N 0.000 claims description 3
- JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-UHFFFAOYSA-N 0.000 claims description 3
- RYUBYXNEIODQQO-UHFFFAOYSA-N 6,7-dimethoxy-4-[1-(pyridin-2-ylmethyl)tetrazol-5-yl]quinazoline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1C1=NN=NN1CC1=CC=CC=N1 RYUBYXNEIODQQO-UHFFFAOYSA-N 0.000 claims description 3
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 230000002496 gastric effect Effects 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 210000004072 lung Anatomy 0.000 claims description 3
- 238000004237 preparative chromatography Methods 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 2
- 125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims description 2
- MFUAVVKXXPSZRT-UHFFFAOYSA-N 3-[[5-(6,7-dimethoxyquinazolin-4-yl)tetrazol-1-yl]methyl]aniline;hydrochloride Chemical compound Cl.C=12C=C(OC)C(OC)=CC2=NC=NC=1C1=NN=NN1CC1=CC=CC(N)=C1 MFUAVVKXXPSZRT-UHFFFAOYSA-N 0.000 claims description 2
- HGMQPDNSSYTATF-UHFFFAOYSA-N 4-chloro-6,7-diethoxyquinazoline Chemical compound C1=NC(Cl)=C2C=C(OCC)C(OCC)=CC2=N1 HGMQPDNSSYTATF-UHFFFAOYSA-N 0.000 claims description 2
- USQGNYNAUSUQGV-UHFFFAOYSA-N 4-chloro-6,7-dipropoxyquinazoline Chemical compound C1=NC(Cl)=C2C=C(OCCC)C(OCCC)=CC2=N1 USQGNYNAUSUQGV-UHFFFAOYSA-N 0.000 claims description 2
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 claims description 2
- DSHFCNBUHWTUCC-UHFFFAOYSA-N 6,7-dimethoxy-4-[1-[(1-methylimidazol-2-yl)methyl]tetrazol-5-yl]quinazoline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1C1=NN=NN1CC1=NC=CN1C DSHFCNBUHWTUCC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 claims description 2
- 210000000481 breast Anatomy 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 238000005984 hydrogenation reaction Methods 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- 201000002510 thyroid cancer Diseases 0.000 claims description 2
- 230000003463 hyperproliferative effect Effects 0.000 claims 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 3
- 241000124008 Mammalia Species 0.000 claims 3
- 238000000746 purification Methods 0.000 claims 3
- NVVMERNNEDXKSI-UHFFFAOYSA-M (6,7-diethoxyquinazolin-4-yl)-trimethylazanium;chloride Chemical compound [Cl-].C1=NC([N+](C)(C)C)=C2C=C(OCC)C(OCC)=CC2=N1 NVVMERNNEDXKSI-UHFFFAOYSA-M 0.000 claims 1
- RHQWNPQWJJOIDM-UHFFFAOYSA-M (6,7-dimethoxyquinazolin-4-yl)-trimethylazanium;chloride Chemical compound [Cl-].C1=NC([N+](C)(C)C)=C2C=C(OC)C(OC)=CC2=N1 RHQWNPQWJJOIDM-UHFFFAOYSA-M 0.000 claims 1
- LSSZDYKTTANUSZ-UHFFFAOYSA-M (6,7-dipropoxyquinazolin-4-yl)-trimethylazanium;chloride Chemical compound [Cl-].C1=NC([N+](C)(C)C)=C2C=C(OCCC)C(OCCC)=CC2=N1 LSSZDYKTTANUSZ-UHFFFAOYSA-M 0.000 claims 1
- VYEGAEUUQMJXTM-UHFFFAOYSA-N 2-(chloromethyl)-1-methylimidazole Chemical compound CN1C=CN=C1CCl VYEGAEUUQMJXTM-UHFFFAOYSA-N 0.000 claims 1
- AMIQEOQFLOLPCM-UHFFFAOYSA-N 3-[[5-(6,7-diethoxyquinazolin-4-yl)tetrazol-1-yl]methyl]aniline Chemical compound C=12C=C(OCC)C(OCC)=CC2=NC=NC=1C1=NN=NN1CC1=CC=CC(N)=C1 AMIQEOQFLOLPCM-UHFFFAOYSA-N 0.000 claims 1
- IPYQQBIXKCGQRG-UHFFFAOYSA-N 3-[[5-(6,7-dipropoxyquinazolin-4-yl)tetrazol-1-yl]methyl]aniline Chemical compound C=12C=C(OCCC)C(OCCC)=CC2=NC=NC=1C1=NN=NN1CC1=CC=CC(N)=C1 IPYQQBIXKCGQRG-UHFFFAOYSA-N 0.000 claims 1
- VBCAGHWIYIAYBZ-UHFFFAOYSA-N 4-[1-[(1-methylimidazol-2-yl)methyl]tetrazol-5-yl]-6,7-dipropoxyquinazoline Chemical compound C=12C=C(OCCC)C(OCCC)=CC2=NC=NC=1C1=NN=NN1CC1=NC=CN1C VBCAGHWIYIAYBZ-UHFFFAOYSA-N 0.000 claims 1
- PCSGLFRAWWPYIT-UHFFFAOYSA-N 4-[1-[(3-nitrophenyl)methyl]tetrazol-5-yl]-6,7-dipropoxyquinazoline Chemical compound C=12C=C(OCCC)C(OCCC)=CC2=NC=NC=1C1=NN=NN1CC1=CC=CC([N+]([O-])=O)=C1 PCSGLFRAWWPYIT-UHFFFAOYSA-N 0.000 claims 1
- MVMQVSVKQHUUTK-UHFFFAOYSA-N 6,7-diethoxy-4-(2h-tetrazol-5-yl)quinazoline Chemical compound C=12C=C(OCC)C(OCC)=CC2=NC=NC=1C1=NN=NN1 MVMQVSVKQHUUTK-UHFFFAOYSA-N 0.000 claims 1
- MWVSXBJZXARZAY-UHFFFAOYSA-N 6,7-diethoxy-4-[1-(pyridin-2-ylmethyl)tetrazol-5-yl]quinazoline Chemical compound C=12C=C(OCC)C(OCC)=CC2=NC=NC=1C1=NN=NN1CC1=CC=CC=N1 MWVSXBJZXARZAY-UHFFFAOYSA-N 0.000 claims 1
- STDRKXRGIRDSEQ-UHFFFAOYSA-N 6,7-diethoxy-4-[1-[(1-methylimidazol-2-yl)methyl]tetrazol-5-yl]quinazoline Chemical compound C=12C=C(OCC)C(OCC)=CC2=NC=NC=1C1=NN=NN1CC1=NC=CN1C STDRKXRGIRDSEQ-UHFFFAOYSA-N 0.000 claims 1
- HFJTUQHJGULTMR-UHFFFAOYSA-N 6,7-diethoxy-4-[1-[(3-nitrophenyl)methyl]tetrazol-5-yl]quinazoline Chemical compound C=12C=C(OCC)C(OCC)=CC2=NC=NC=1C1=NN=NN1CC1=CC=CC([N+]([O-])=O)=C1 HFJTUQHJGULTMR-UHFFFAOYSA-N 0.000 claims 1
- AYRXTXKTUVFHRG-UHFFFAOYSA-N 6,7-diethoxyquinazoline-4-carbonitrile Chemical compound C1=NC(C#N)=C2C=C(OCC)C(OCC)=CC2=N1 AYRXTXKTUVFHRG-UHFFFAOYSA-N 0.000 claims 1
- GWFNVEQLVWAGRU-UHFFFAOYSA-N 6,7-dimethoxy-3,4-dihydro-1h-quinazolin-2-one Chemical compound C1NC(=O)NC2=C1C=C(OC)C(OC)=C2 GWFNVEQLVWAGRU-UHFFFAOYSA-N 0.000 claims 1
- XOMDVXLRDJPCHY-UHFFFAOYSA-N 6,7-dipropoxy-4-(2h-tetrazol-5-yl)quinazoline Chemical compound C=12C=C(OCCC)C(OCCC)=CC2=NC=NC=1C1=NN=NN1 XOMDVXLRDJPCHY-UHFFFAOYSA-N 0.000 claims 1
- JSKBQKOIPQQMJI-UHFFFAOYSA-N 6,7-dipropoxy-4-[1-(pyridin-2-ylmethyl)tetrazol-5-yl]quinazoline Chemical compound C=12C=C(OCCC)C(OCCC)=CC2=NC=NC=1C1=NN=NN1CC1=CC=CC=N1 JSKBQKOIPQQMJI-UHFFFAOYSA-N 0.000 claims 1
- FOXAFHAHHYHHHP-UHFFFAOYSA-N 6,7-dipropoxyquinazoline-4-carbonitrile Chemical compound C1=NC(C#N)=C2C=C(OCCC)C(OCCC)=CC2=N1 FOXAFHAHHYHHHP-UHFFFAOYSA-N 0.000 claims 1
- 239000007868 Raney catalyst Substances 0.000 claims 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims 1
- 229910000564 Raney nickel Inorganic materials 0.000 claims 1
- 238000007796 conventional method Methods 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000009901 transfer hydrogenation reaction Methods 0.000 claims 1
- 230000001028 anti-proliverative effect Effects 0.000 abstract description 8
- 239000003814 drug Substances 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 7
- 241001465754 Metazoa Species 0.000 abstract description 4
- 230000001093 anti-cancer Effects 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 32
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 25
- 102000001301 EGF receptor Human genes 0.000 description 24
- 108060006698 EGF receptor Proteins 0.000 description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 15
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 15
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- 230000003595 spectral effect Effects 0.000 description 13
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 13
- 101800003838 Epidermal growth factor Proteins 0.000 description 12
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 12
- 229940116977 epidermal growth factor Drugs 0.000 description 12
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 12
- 239000003112 inhibitor Substances 0.000 description 12
- 239000012299 nitrogen atmosphere Substances 0.000 description 12
- 229960001433 erlotinib Drugs 0.000 description 11
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 10
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 10
- 102400001368 Epidermal growth factor Human genes 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 229940113088 dimethylacetamide Drugs 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 229940093499 ethyl acetate Drugs 0.000 description 8
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 7
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 7
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 108700020796 Oncogene Proteins 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 229960002584 gefitinib Drugs 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 6
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- MZXIRYYIJGUPAK-UHFFFAOYSA-N n-(1h-indazol-5-yl)quinazolin-4-amine Chemical class C1=CC=C2C(NC=3C=C4C=NNC4=CC=3)=NC=NC2=C1 MZXIRYYIJGUPAK-UHFFFAOYSA-N 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- RPRDVGQSWALPFM-UHFFFAOYSA-N 6,7-dimethoxy-4-(2h-tetrazol-5-yl)quinazoline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1C1=NN=NN1 RPRDVGQSWALPFM-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 4
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 230000009545 invasion Effects 0.000 description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- MTSNDBYBIZSILH-UHFFFAOYSA-N n-phenylquinazolin-4-amine Chemical class N=1C=NC2=CC=CC=C2C=1NC1=CC=CC=C1 MTSNDBYBIZSILH-UHFFFAOYSA-N 0.000 description 4
- 201000002528 pancreatic cancer Diseases 0.000 description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 description 4
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 4
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 4
- MPNXSZJPSVBLHP-UHFFFAOYSA-N 2-chloro-n-phenylpyridine-3-carboxamide Chemical compound ClC1=NC=CC=C1C(=O)NC1=CC=CC=C1 MPNXSZJPSVBLHP-UHFFFAOYSA-N 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- 108091000080 Phosphotransferase Proteins 0.000 description 3
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 3
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000001516 cell proliferation assay Methods 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 229940121647 egfr inhibitor Drugs 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 238000011580 nude mouse model Methods 0.000 description 3
- 238000011275 oncology therapy Methods 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 102000020233 phosphotransferase Human genes 0.000 description 3
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 229940086542 triethylamine Drugs 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical class C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 description 2
- LLLHRNQLGUOJHP-UHFFFAOYSA-N 4-chloro-6,7-dimethoxyquinazoline Chemical compound C1=NC(Cl)=C2C=C(OC)C(OC)=CC2=N1 LLLHRNQLGUOJHP-UHFFFAOYSA-N 0.000 description 2
- ISOWFPIROGHRSO-UHFFFAOYSA-N 6,7-dimethoxyquinazoline-4-carbonitrile Chemical compound C1=NC(C#N)=C2C=C(OC)C(OC)=CC2=N1 ISOWFPIROGHRSO-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 230000006820 DNA synthesis Effects 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000020897 Formins Human genes 0.000 description 2
- 108091022623 Formins Proteins 0.000 description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 description 2
- 102100034535 Histone H3.1 Human genes 0.000 description 2
- 101001067844 Homo sapiens Histone H3.1 Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 238000007807 Matrigel invasion assay Methods 0.000 description 2
- 208000003445 Mouth Neoplasms Diseases 0.000 description 2
- 102000043276 Oncogene Human genes 0.000 description 2
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 206010043515 Throat cancer Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 230000002491 angiogenic effect Effects 0.000 description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 2
- 108010082117 matrigel Proteins 0.000 description 2
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000004017 serum-free culture medium Substances 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 150000003440 styrenes Chemical class 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- QIVUCLWGARAQIO-OLIXTKCUSA-N (3s)-n-[(3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1h-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide Chemical compound C1([C@H]2[C@H](N(C(=O)[C@@H](NC(=O)C=3C=C4C[C@]5(CC4=NC=3)C3=CC=CN=C3NC5=O)C2)CC(F)(F)F)C)=C(F)C=CC(F)=C1F QIVUCLWGARAQIO-OLIXTKCUSA-N 0.000 description 1
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- XGZYNVJJLOWFDO-UHFFFAOYSA-N 2-propoxyquinazoline Chemical compound C1=CC=CC2=NC(OCCC)=NC=C21 XGZYNVJJLOWFDO-UHFFFAOYSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 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
- QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- HIHOEGPXVVKJPP-JTQLQIEISA-N 5-fluoro-2-[[(1s)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyridine-3-carbonitrile Chemical compound N([C@@H](C)C=1N=CC(F)=CC=1)C(C(=CC=1F)C#N)=NC=1NC=1C=C(C)NN=1 HIHOEGPXVVKJPP-JTQLQIEISA-N 0.000 description 1
- DMSRMHGCZUXCMJ-UHFFFAOYSA-N 6,7-dimethoxy-1h-quinazolin-4-one Chemical compound C1=NC(O)=C2C=C(OC)C(OC)=CC2=N1 DMSRMHGCZUXCMJ-UHFFFAOYSA-N 0.000 description 1
- 102100038778 Amphiregulin Human genes 0.000 description 1
- 108010033760 Amphiregulin Proteins 0.000 description 1
- 101100005765 Arabidopsis thaliana CDF1 gene Proteins 0.000 description 1
- 101100007579 Arabidopsis thaliana CPP1 gene Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 101800001382 Betacellulin Proteins 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 238000007809 Boyden Chamber assay Methods 0.000 description 1
- 101100123850 Caenorhabditis elegans her-1 gene Proteins 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 101710137199 Class II receptor tyrosine kinase Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 229940122558 EGFR antagonist Drugs 0.000 description 1
- 101800000155 Epiregulin Proteins 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
- 101001047090 Homo sapiens Potassium voltage-gated channel subfamily H member 2 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 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
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000018658 Myotonin-Protein Kinase Human genes 0.000 description 1
- 108010052185 Myotonin-Protein Kinase Proteins 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 102000014413 Neuregulin Human genes 0.000 description 1
- 108050003475 Neuregulin Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 238000010934 O-alkylation reaction Methods 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- LSPANGZZENHZNJ-UHFFFAOYSA-N PD-153035 Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC(Br)=C1 LSPANGZZENHZNJ-UHFFFAOYSA-N 0.000 description 1
- 108010055723 PDGF receptor tyrosine kinase Proteins 0.000 description 1
- 101150057744 PDGFA gene Proteins 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 102000038030 PI3Ks Human genes 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 102100022807 Potassium voltage-gated channel subfamily H member 2 Human genes 0.000 description 1
- 102100029837 Probetacellulin Human genes 0.000 description 1
- 102100025498 Proepiregulin Human genes 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 108091008611 Protein Kinase B Proteins 0.000 description 1
- 102000007131 Proto-Oncogene Proteins c-fyn Human genes 0.000 description 1
- 108010072960 Proto-Oncogene Proteins c-fyn Proteins 0.000 description 1
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 1
- 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 102000001332 SRC Human genes 0.000 description 1
- 108060006706 SRC Proteins 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 101150109894 TGFA gene Proteins 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 101100429091 Xiphophorus maculatus xmrk gene Proteins 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000006909 anti-apoptosis Effects 0.000 description 1
- 239000002839 antibiotic anticancer agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 238000011717 athymic nude mouse Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 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
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000017455 cell-cell adhesion Effects 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 230000008406 drug-drug interaction Effects 0.000 description 1
- 229940082789 erbitux Drugs 0.000 description 1
- SIHZWGODIRRSRA-ONEGZZNKSA-N erbstatin Chemical compound OC1=CC=C(O)C(\C=C\NC=O)=C1 SIHZWGODIRRSRA-ONEGZZNKSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 230000002962 histologic effect Effects 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- AKPUJVVHYUHGKY-UHFFFAOYSA-N hydron;propan-2-ol;chloride Chemical compound Cl.CC(C)O AKPUJVVHYUHGKY-UHFFFAOYSA-N 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 229910003480 inorganic solid Inorganic materials 0.000 description 1
- 229940084651 iressa Drugs 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 238000013332 literature search Methods 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- VOVZXURTCKPRDQ-CQSZACIVSA-N n-[4-[chloro(difluoro)methoxy]phenyl]-6-[(3r)-3-hydroxypyrrolidin-1-yl]-5-(1h-pyrazol-5-yl)pyridine-3-carboxamide Chemical compound C1[C@H](O)CCN1C1=NC=C(C(=O)NC=2C=CC(OC(F)(F)Cl)=CC=2)C=C1C1=CC=NN1 VOVZXURTCKPRDQ-CQSZACIVSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- TZLVRPLSVNESQC-UHFFFAOYSA-N potassium azide Chemical compound [K+].[N-]=[N+]=[N-] TZLVRPLSVNESQC-UHFFFAOYSA-N 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- VBCVBVXRDBPFIL-UHFFFAOYSA-N quinazoline-4-carbonitrile Chemical class C1=CC=C2C(C#N)=NC=NC2=C1 VBCVBVXRDBPFIL-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 229940124617 receptor tyrosine kinase inhibitor Drugs 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 208000017572 squamous cell neoplasm Diseases 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940120982 tarceva Drugs 0.000 description 1
- 125000004523 tetrazol-1-yl group Chemical group N1(N=NN=C1)* 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
Classifications
-
- 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
-
- 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
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
-
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN2445CH2007 | 2007-10-29 | ||
| IN2445/CHE/2007 | 2007-10-29 | ||
| PCT/IN2008/000708 WO2009057139A2 (en) | 2007-10-29 | 2008-10-28 | Novel 4-(tetrazol-5-yl)-quinazoline derivatives as anti cancer agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2703767A1 true CA2703767A1 (en) | 2009-05-07 |
Family
ID=40433677
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2703767A Abandoned CA2703767A1 (en) | 2007-10-29 | 2008-10-28 | Novel 4-(tetrazol-5-yl)-quinazoline derivatives as anti cancer agents |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US8080558B2 (enExample) |
| EP (1) | EP2220054A2 (enExample) |
| JP (1) | JP2011502141A (enExample) |
| KR (1) | KR20100087185A (enExample) |
| CN (1) | CN101878203A (enExample) |
| AU (1) | AU2008320342B2 (enExample) |
| CA (1) | CA2703767A1 (enExample) |
| EA (1) | EA018716B1 (enExample) |
| GE (1) | GEP20125603B (enExample) |
| MX (1) | MX2010004625A (enExample) |
| MY (1) | MY150054A (enExample) |
| NZ (1) | NZ585357A (enExample) |
| UA (1) | UA101168C2 (enExample) |
| WO (1) | WO2009057139A2 (enExample) |
| ZA (1) | ZA201002807B (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103130729B (zh) * | 2011-12-05 | 2015-07-15 | 齐鲁制药有限公司 | 一种4-氯代-7-甲氧基喹唑啉-6-醇乙酸酯的制备方法 |
| WO2014039714A2 (en) * | 2012-09-06 | 2014-03-13 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| CN102993114B (zh) * | 2012-10-11 | 2015-08-12 | 南通市华峰化工有限责任公司 | 一种1h-四唑-5-乙酸的生产方法 |
| CN103204817B (zh) * | 2013-04-16 | 2018-03-27 | 江西师范大学 | 4‑氰基喹唑啉衍生物的制备方法 |
| DE102013008118A1 (de) * | 2013-05-11 | 2014-11-13 | Merck Patent Gmbh | Arylchinazoline |
| JP6704422B2 (ja) | 2015-03-20 | 2020-06-03 | チア タイ ティエンチン ファーマシューティカル グループ カンパニー リミテッドChia Tai Tianqing Pharmaceutical Group Co., Ltd. | キナゾリン誘導体の塩およびその製造方法 |
| CN114787151B (zh) * | 2019-11-01 | 2024-04-16 | 正大天晴药业集团股份有限公司 | 喹唑啉衍生物或其盐、或其药物组合物的用途 |
| JP2023549973A (ja) * | 2020-11-23 | 2023-11-29 | エフ． ホフマン－ラ ロシュ アーゲー | テトラゾール誘導体の製造のための新規方法 |
| CN114437041B (zh) * | 2022-02-25 | 2023-11-10 | 湖北科技学院 | 一类具有抗肿瘤活性的4-四唑基取代-3，4-二氢喹唑啉衍生物及其制备方法和应用 |
Family Cites Families (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3800039A (en) * | 1970-10-21 | 1974-03-26 | Mead Johnson & Co | Antithrombogenic process employing substituted 6,7-dialkoxyquinazolines |
| JPH078851B2 (ja) | 1985-07-29 | 1995-02-01 | 鐘淵化学工業株式会社 | ３−フエニルチオメチルスチレン誘導体 |
| DE3874257T2 (de) | 1987-03-11 | 1993-02-11 | Kanegafuchi Chemical Ind | Hydroxystyren-derivate. |
| AU632992B2 (en) | 1987-12-24 | 1993-01-21 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Pharmaceutical compositions comprising benzylidene- and cinnamylidene-malononitrile derivatives for the inhibition of proliferative processes in mammalian cells, certain such novel compounds and their preparation |
| DE3917982A1 (de) | 1989-06-02 | 1990-12-06 | Behringwerke Ag | Verwendung von xylanpolyhydrogensulfaten zur therapie von zellproliferations-bedingten erkrankungen |
| AU658646B2 (en) | 1991-05-10 | 1995-04-27 | Rhone-Poulenc Rorer International (Holdings) Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| NZ243082A (en) | 1991-06-28 | 1995-02-24 | Ici Plc | 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof |
| PT100905A (pt) * | 1991-09-30 | 1994-02-28 | Eisai Co Ltd | Compostos heterociclicos azotados biciclicos contendo aneis de benzeno, ciclo-hexano ou piridina e de pirimidina, piridina ou imidazol substituidos e composicoes farmaceuticas que os contem |
| GB9300059D0 (en) | 1992-01-20 | 1993-03-03 | Zeneca Ltd | Quinazoline derivatives |
| GB9323290D0 (en) | 1992-12-10 | 1994-01-05 | Zeneca Ltd | Quinazoline derivatives |
| GB9314893D0 (en) * | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Quinazoline derivatives |
| GB9510757D0 (en) | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
| TW321649B (enExample) | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
| GB9424233D0 (en) | 1994-11-30 | 1995-01-18 | Zeneca Ltd | Quinazoline derivatives |
| DE69536015D1 (de) | 1995-03-30 | 2009-12-10 | Pfizer Prod Inc | Chinazolinone Derivate |
| WO1996033977A1 (en) | 1995-04-27 | 1996-10-31 | Zeneca Limited | Quinazoline derivatives |
| GB9508537D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| GB9508535D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivative |
| GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| GB9508565D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quiazoline derivative |
| US5747498A (en) | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
| GB9514265D0 (en) | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
| AR004010A1 (es) | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | Compuestos heterociclicos |
| WO1997030035A1 (en) | 1996-02-13 | 1997-08-21 | Zeneca Limited | Quinazoline derivatives as vegf inhibitors |
| GB9603095D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
| SK284073B6 (sk) | 1996-04-12 | 2004-09-08 | Warner-Lambert Company | Polycyklické zlúčeniny, ich použitie a farmaceutické kompozície na ich báze |
| EP0912559B1 (en) | 1996-07-13 | 2002-11-06 | Glaxo Group Limited | Fused heterocyclic compounds as protein tyrosine kinase inhibitors |
| HRP970371A2 (en) | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| DE69718472T2 (de) | 1996-07-13 | 2003-11-06 | Glaxo Group Ltd., Greenford | Bicyclische heteroaromatische verbindungen als protein tyrosine kinase inhibitoren |
| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| GB9800569D0 (en) | 1998-01-12 | 1998-03-11 | Glaxo Group Ltd | Heterocyclic compounds |
| GB9800575D0 (en) | 1998-01-12 | 1998-03-11 | Glaxo Group Ltd | Heterocyclic compounds |
| CZ20021009A3 (cs) | 1999-09-21 | 2002-06-12 | Astrazeneca Ab | Deriváty chinazolinu, způsob jejich přípravy a jejich pouľití jako léčiv |
| GB0002040D0 (en) | 2000-01-28 | 2000-03-22 | Zeneca Ltd | Chemical compounds |
| UA73993C2 (uk) | 2000-06-06 | 2005-10-17 | Астразенека Аб | Хіназолінові похідні для лікування пухлин та фармацевтична композиція |
| DE10042059A1 (de) | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| EP1382603B1 (en) * | 2001-04-26 | 2008-07-23 | Eisai R&D Management Co., Ltd. | Nitrogenous fused-ring compound having pyrazolyl group as substituent and medicinal composition thereof |
| JP2005515176A (ja) | 2001-11-03 | 2005-05-26 | アストラゼネカ アクチボラグ | 抗腫瘍剤としてのキナゾリン誘導体 |
| GB0126433D0 (en) | 2001-11-03 | 2002-01-02 | Astrazeneca Ab | Compounds |
| PL371587A1 (en) * | 2002-01-17 | 2005-06-27 | Neurogen Corporation | Substituted quinazolin-4-ylamine analogues as modulators of capsaicin receptors |
| 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 |
| JP4611745B2 (ja) | 2002-11-20 | 2011-01-12 | アレイ バイオファーマ、インコーポレイテッド | ＥｒｂＢ２及びＥＧＦＲ阻害剤としてのシアノグアニジン及びシアノアミジン |
| GB0309009D0 (en) | 2003-04-22 | 2003-05-28 | Astrazeneca Ab | Quinazoline derivatives |
| GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
| MX2008002363A (es) * | 2005-08-17 | 2008-03-18 | Schering Corp | Ligandos novedosos de cinasa basados en quinolina de alta afinidad. |
| CN101490016A (zh) * | 2006-07-28 | 2009-07-22 | 诺瓦提斯公司 | 作为脂激酶抑制剂的2,4-取代的喹唑啉 |
-
2008
- 2008-10-28 NZ NZ585357A patent/NZ585357A/en not_active IP Right Cessation
- 2008-10-28 CN CN200880118458XA patent/CN101878203A/zh active Pending
- 2008-10-28 UA UAA201006435A patent/UA101168C2/ru unknown
- 2008-10-28 AU AU2008320342A patent/AU2008320342B2/en not_active Ceased
- 2008-10-28 MY MYPI2010001916A patent/MY150054A/en unknown
- 2008-10-28 GE GEAP200811821A patent/GEP20125603B/en unknown
- 2008-10-28 US US12/740,527 patent/US8080558B2/en not_active Expired - Fee Related
- 2008-10-28 EP EP08844368A patent/EP2220054A2/en not_active Withdrawn
- 2008-10-28 WO PCT/IN2008/000708 patent/WO2009057139A2/en not_active Ceased
- 2008-10-28 KR KR1020107011577A patent/KR20100087185A/ko not_active Withdrawn
- 2008-10-28 CA CA2703767A patent/CA2703767A1/en not_active Abandoned
- 2008-10-28 EA EA201070543A patent/EA018716B1/ru not_active IP Right Cessation
- 2008-10-28 MX MX2010004625A patent/MX2010004625A/es unknown
- 2008-10-28 JP JP2010531646A patent/JP2011502141A/ja active Pending
-
2010
- 2010-04-21 ZA ZA2010/02807A patent/ZA201002807B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2008320342A1 (en) | 2009-05-07 |
| KR20100087185A (ko) | 2010-08-03 |
| US20100261740A1 (en) | 2010-10-14 |
| UA101168C2 (ru) | 2013-03-11 |
| CN101878203A (zh) | 2010-11-03 |
| EA201070543A1 (ru) | 2010-12-30 |
| EP2220054A2 (en) | 2010-08-25 |
| NZ585357A (en) | 2012-02-24 |
| AU2008320342B2 (en) | 2012-07-26 |
| JP2011502141A (ja) | 2011-01-20 |
| MX2010004625A (es) | 2010-05-20 |
| MY150054A (en) | 2013-11-29 |
| EA018716B1 (ru) | 2013-10-30 |
| WO2009057139A2 (en) | 2009-05-07 |
| WO2009057139A3 (en) | 2009-09-24 |
| ZA201002807B (en) | 2011-07-27 |
| US8080558B2 (en) | 2011-12-20 |
| AU2008320342A2 (en) | 2010-09-02 |
| GEP20125603B (en) | 2012-08-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2008320342B2 (en) | Novel 4-(tetrazol-5-yl)-quinazoline derivatives as anti cancer agents | |
| AP735A (en) | Quinazoline derivatives. | |
| USRE49851E1 (en) | Pyridinylaminopyrimidine derivatives, preparation process and use thereof | |
| AU2008260772B2 (en) | Novel amide derivative for inhibiting the growth of cancer cells | |
| ZA200403200B (en) | Quinazoline derivatives as antitumor agents. | |
| TW200301121A (en) | Small molecules for the treatment of abnormal cell growth | |
| EP0837063A1 (en) | 4-Aminoquinazoline derivatives | |
| RS46404A (sr) | Oblici soli e-2-metoksi-n-(3-(4-(3-metil-piridin-3-iloksi)- fenilamino)hinazolin-6-il)alil)-acetamida, postupci njihovog dobijanja i njihova primena protiv raka | |
| JP2014521613A (ja) | キナゾリン誘導体、その製造方法、中間体、組成物及びその適用 | |
| CN110372666A (zh) | 喹唑啉类化合物作为egfr三突变抑制剂及其应用 | |
| CN102627632B (zh) | 一种胺基喹唑啉衍生物及其制备方法和用途 | |
| WO2013159698A1 (zh) | 稠环喹唑啉羟肟酸类化合物及其作为抗肿瘤药物的应用 | |
| US20120172380A1 (en) | Novel 4-(tetrazol-5-yl)-quinazoline derivatives as anti cancer agent | |
| CN104163815B (zh) | 含吲哚的喹唑啉类化合物及其在治疗egfr依赖性肿瘤疾病中的用途 | |
| CN118221696A (zh) | 含有n-甲基哌嗪结构的嘧啶杂环类化合物及其制备方法和应用 | |
| HK1231045A1 (en) | Quinazoline derivatives | |
| HK1141804A (en) | Quinazoline derivatives | |
| HK1042083A (en) | Quinazoline derivatives | |
| HK1038740B (en) | Quinazoline derivatives | |
| AU7939101A (en) | Intermediates for the preparation of 4-(substituted phenylamino)quinazoline derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |
Effective date: 20141028 |