NZ245662A

NZ245662A - Quinazoline derivatives, preparation and pharmaceutical compositions thereof

Quinazoline derivatives, preparation and pharmaceutical compositions thereof

Info

Publication number: NZ245662A
Authority: NZ; New Zealand
Prior art keywords: alkyl; alkoxy; amino; alkylamino; quinazoline
Prior art date: 1992-01-20

Application number

NZ245662A

Other languages

English (en)

Inventor

Andrew John Barker

Original Assignee

Zeneca Ltd

Priority date

1992-01-20

Filing date

1993-01-12

Publication date

1995-09-26

1992-01-20 Priority claimed from GB929201095A external-priority patent/GB9201095D0/en

1992-06-26 Priority claimed from GB929213572A external-priority patent/GB9213572D0/en

1992-11-12 Priority claimed from GB929223735A external-priority patent/GB9223735D0/en

1993-01-12 Application filed by Zeneca Ltd filed Critical Zeneca Ltd

1995-09-26 Publication of NZ245662A publication Critical patent/NZ245662A/en

Links

238000002360 preparation method Methods 0.000 title claims abstract description 16
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title abstract description 5
-1 hydroxy, amino, carboxy, carbamoyl Chemical group 0.000 claims abstract description 338
125000000217 alkyl group Chemical group 0.000 claims abstract description 267
125000003545 alkoxy group Chemical group 0.000 claims abstract description 150
150000001875 compounds Chemical class 0.000 claims abstract description 93
238000000034 method Methods 0.000 claims abstract description 63
150000003839 salts Chemical class 0.000 claims abstract description 55
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 34
239000001257 hydrogen Substances 0.000 claims abstract description 26
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 26
125000005843 halogen group Chemical group 0.000 claims abstract description 25
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 23
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 21
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 15
125000005530 alkylenedioxy group Chemical group 0.000 claims abstract description 14
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 13
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 9
230000008569 process Effects 0.000 claims abstract description 9
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims abstract description 7
125000005115 alkyl carbamoyl group Chemical group 0.000 claims abstract description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 5
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 5
125000000033 alkoxyamino group Chemical group 0.000 claims abstract description 4
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims abstract description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 5
125000003282 alkyl amino group Chemical group 0.000 claims description 102
150000003246 quinazolines Chemical class 0.000 claims description 85
125000005236 alkanoylamino group Chemical group 0.000 claims description 80
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 36
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 claims description 28
238000004519 manufacturing process Methods 0.000 claims description 24
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 22
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 18
125000004414 alkyl thio group Chemical group 0.000 claims description 18
238000006243 chemical reaction Methods 0.000 claims description 18
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 16
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 15
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 14
VKOGLNSKGDTRGH-UHFFFAOYSA-N 4-[(6-methoxyquinazolin-4-yl)amino]phenol Chemical compound C12=CC(OC)=CC=C2N=CN=C1NC1=CC=C(O)C=C1 VKOGLNSKGDTRGH-UHFFFAOYSA-N 0.000 claims description 13
GBJXFMREUNFKRX-UHFFFAOYSA-N 4-n-(4-aminophenyl)quinazoline-4,6-diamine Chemical compound C1=CC(N)=CC=C1NC1=NC=NC2=CC=C(N)C=C12 GBJXFMREUNFKRX-UHFFFAOYSA-N 0.000 claims description 13
JFDWMFYUKLPRSP-UHFFFAOYSA-N 6-methyl-n-phenylquinazolin-4-amine Chemical compound C12=CC(C)=CC=C2N=CN=C1NC1=CC=CC=C1 JFDWMFYUKLPRSP-UHFFFAOYSA-N 0.000 claims description 13
230000001093 anti-cancer Effects 0.000 claims description 13
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
CRZPVSMPJCPEPP-UHFFFAOYSA-N 4-([1,3]dioxolo[4,5-g]quinazolin-8-ylamino)phenol Chemical compound C1=CC(O)=CC=C1NC(C1=C2)=NC=NC1=CC1=C2OCO1 CRZPVSMPJCPEPP-UHFFFAOYSA-N 0.000 claims description 12
MJKCGAHOCZLYDG-UHFFFAOYSA-N 6,7-dimethoxy-n-phenylquinazolin-4-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC=C1 MJKCGAHOCZLYDG-UHFFFAOYSA-N 0.000 claims description 12
241001465754 Metazoa Species 0.000 claims description 12
239000000126 substance Substances 0.000 claims description 12
125000001424 substituent group Chemical group 0.000 claims description 12
YPBYGBLLRMWZAF-UHFFFAOYSA-N 4-[(6,7,8-trimethoxyquinazolin-4-yl)amino]phenol Chemical compound N1=CN=C2C(OC)=C(OC)C(OC)=CC2=C1NC1=CC=C(O)C=C1 YPBYGBLLRMWZAF-UHFFFAOYSA-N 0.000 claims description 11
125000004423 acyloxy group Chemical group 0.000 claims description 10
BYBQXGBBLHNCIR-UHFFFAOYSA-N 4-(4-chloroanilino)quinazolin-8-ol Chemical compound N1=CN=C2C(O)=CC=CC2=C1NC1=CC=C(Cl)C=C1 BYBQXGBBLHNCIR-UHFFFAOYSA-N 0.000 claims description 8
ZFSSJGZFLIOOKN-UHFFFAOYSA-N 4-(4-methoxyanilino)quinazolin-8-ol Chemical compound C1=CC(OC)=CC=C1NC1=NC=NC2=C(O)C=CC=C12 ZFSSJGZFLIOOKN-UHFFFAOYSA-N 0.000 claims description 8
URJYCHBAPFKHRE-UHFFFAOYSA-N 8-methoxy-n-(4-methoxyphenyl)quinazolin-4-amine Chemical compound C1=CC(OC)=CC=C1NC1=NC=NC2=C(OC)C=CC=C12 URJYCHBAPFKHRE-UHFFFAOYSA-N 0.000 claims description 7
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 7
239000003795 chemical substances by application Substances 0.000 claims description 7
MPIHIJBPYYKLEA-UHFFFAOYSA-N n-(4-chlorophenyl)-8-methoxyquinazolin-4-amine Chemical compound N1=CN=C2C(OC)=CC=CC2=C1NC1=CC=C(Cl)C=C1 MPIHIJBPYYKLEA-UHFFFAOYSA-N 0.000 claims description 7
239000002253 acid Substances 0.000 claims description 6
125000001246 bromo group Chemical group Br* 0.000 claims description 6
125000001309 chloro group Chemical group Cl* 0.000 claims description 6
125000001153 fluoro group Chemical group F* 0.000 claims description 6
230000003647 oxidation Effects 0.000 claims description 6
238000007254 oxidation reaction Methods 0.000 claims description 6
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 5
230000009467 reduction Effects 0.000 claims description 5
230000010933 acylation Effects 0.000 claims description 4
238000005917 acylation reaction Methods 0.000 claims description 4
230000029936 alkylation Effects 0.000 claims description 4
238000005804 alkylation reaction Methods 0.000 claims description 4
125000001589 carboacyl group Chemical group 0.000 claims description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
238000003776 cleavage reaction Methods 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
BCZUPYLJRTXVOY-UHFFFAOYSA-N 6,7-diethoxy-n-(3-methylphenyl)quinazolin-4-amine Chemical compound C=12C=C(OCC)C(OCC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 BCZUPYLJRTXVOY-UHFFFAOYSA-N 0.000 claims description 3
YMQNMNWEDFTMTJ-UHFFFAOYSA-N 6-n,6-n-dimethyl-4-n-(3-methylphenyl)quinazoline-4,6-diamine Chemical compound C12=CC(N(C)C)=CC=C2N=CN=C1NC1=CC=CC(C)=C1 YMQNMNWEDFTMTJ-UHFFFAOYSA-N 0.000 claims description 3
BWENYVDMLAZGTP-UHFFFAOYSA-N 7-methoxy-4-n-(3-methylphenyl)quinazoline-4,6-diamine Chemical compound C=12C=C(N)C(OC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 BWENYVDMLAZGTP-UHFFFAOYSA-N 0.000 claims description 3
WLGDTJBSQGRVRX-UHFFFAOYSA-N [4-(3-methylanilino)quinazolin-6-yl]urea Chemical compound CC1=CC=CC(NC=2C3=CC(NC(N)=O)=CC=C3N=CN=2)=C1 WLGDTJBSQGRVRX-UHFFFAOYSA-N 0.000 claims description 3
150000001412 amines Chemical class 0.000 claims description 3
230000007062 hydrolysis Effects 0.000 claims description 3
238000006460 hydrolysis reaction Methods 0.000 claims description 3
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 claims description 3
BIGXXKQBMRKUJG-UHFFFAOYSA-N n-(3-methylphenyl)-7,8-dihydro-[1,4]dioxino[2,3-g]quinazolin-4-amine Chemical compound CC1=CC=CC(NC=2C3=CC=4OCCOC=4C=C3N=CN=2)=C1 BIGXXKQBMRKUJG-UHFFFAOYSA-N 0.000 claims description 3
VQIWZLBIZSXBLT-UHFFFAOYSA-N n-[4-(3-methylanilino)quinazolin-6-yl]benzamide Chemical compound CC1=CC=CC(NC=2C3=CC(NC(=O)C=4C=CC=CC=4)=CC=C3N=CN=2)=C1 VQIWZLBIZSXBLT-UHFFFAOYSA-N 0.000 claims description 3
QYXLGBIMSTYMHA-UHFFFAOYSA-N 6,7-dimethoxy-n-(3-nitrophenyl)quinazolin-4-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC([N+]([O-])=O)=C1 QYXLGBIMSTYMHA-UHFFFAOYSA-N 0.000 claims description 2
ULUILBSHRZPHGK-UHFFFAOYSA-N 6-(2-methoxyethoxymethyl)-n-(3-methylphenyl)quinazolin-4-amine Chemical compound C12=CC(COCCOC)=CC=C2N=CN=C1NC1=CC=CC(C)=C1 ULUILBSHRZPHGK-UHFFFAOYSA-N 0.000 claims description 2
ZJCCYDYNZMGIHC-UHFFFAOYSA-N 6-methoxy-n-(3-methylphenyl)quinazolin-4-amine Chemical compound C12=CC(OC)=CC=C2N=CN=C1NC1=CC=CC(C)=C1 ZJCCYDYNZMGIHC-UHFFFAOYSA-N 0.000 claims description 2
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 2
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 2
NZHRGFLNIISRAV-UHFFFAOYSA-N n-(3,4-dichlorophenyl)-6,7-dimethoxyquinazolin-4-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=C(Cl)C(Cl)=C1 NZHRGFLNIISRAV-UHFFFAOYSA-N 0.000 claims description 2
JDEKFVYZUIPHET-UHFFFAOYSA-N n-(3-chlorophenyl)-6-methoxyquinazolin-4-amine Chemical compound C12=CC(OC)=CC=C2N=CN=C1NC1=CC=CC(Cl)=C1 JDEKFVYZUIPHET-UHFFFAOYSA-N 0.000 claims description 2
230000007017 scission Effects 0.000 claims description 2
ACCVTKJXKFSAAH-UHFFFAOYSA-N 5-methoxyquinazoline Chemical compound C1=NC=C2C(OC)=CC=CC2=N1 ACCVTKJXKFSAAH-UHFFFAOYSA-N 0.000 claims 1
MCBABIOGLXZCHP-UHFFFAOYSA-N 6,7-dimethoxy-n-phenylquinazolin-2-amine Chemical compound N1=C2C=C(OC)C(OC)=CC2=CN=C1NC1=CC=CC=C1 MCBABIOGLXZCHP-UHFFFAOYSA-N 0.000 claims 1
UWSJFQYJMQTBQA-UHFFFAOYSA-N 6-methyl-N-phenylquinazolin-2-amine Chemical compound N1=CC2=CC(C)=CC=C2N=C1NC1=CC=CC=C1 UWSJFQYJMQTBQA-UHFFFAOYSA-N 0.000 claims 1
125000003396 thiol group Chemical class [H]S* 0.000 claims 1
206010028980 Neoplasm Diseases 0.000 abstract description 17
102000027426 receptor tyrosine kinases Human genes 0.000 abstract description 16
108091008598 receptor tyrosine kinases Proteins 0.000 abstract description 16
238000011282 treatment Methods 0.000 abstract description 13
201000011510 cancer Diseases 0.000 abstract description 9
230000002401 inhibitory effect Effects 0.000 abstract description 8
239000000203 mixture Substances 0.000 description 299
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 201
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 138
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 114
238000000921 elemental analysis Methods 0.000 description 85
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 84
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 68
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
239000000243 solution Substances 0.000 description 57
238000004440 column chromatography Methods 0.000 description 56
239000003480 eluent Substances 0.000 description 56
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 49
239000007858 starting material Substances 0.000 description 44
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 43
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
238000010992 reflux Methods 0.000 description 36
239000000047 product Substances 0.000 description 32
238000012360 testing method Methods 0.000 description 32
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 27
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
239000002244 precipitate Substances 0.000 description 26
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 25
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
JJYPMNFTHPTTDI-UHFFFAOYSA-N 3-methylaniline Chemical compound CC1=CC=CC(N)=C1 JJYPMNFTHPTTDI-UHFFFAOYSA-N 0.000 description 20
239000012074 organic phase Substances 0.000 description 20
239000012258 stirred mixture Substances 0.000 description 20
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
239000000463 material Substances 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
210000004027 cell Anatomy 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 16
239000007787 solid Substances 0.000 description 16
NFBCSWGEYDCCDW-UHFFFAOYSA-N 4-n-(3-methylphenyl)quinazoline-4,6-diamine Chemical compound CC1=CC=CC(NC=2C3=CC(N)=CC=C3N=CN=2)=C1 NFBCSWGEYDCCDW-UHFFFAOYSA-N 0.000 description 15
241000282414 Homo sapiens Species 0.000 description 13
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 12
PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 12
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 12
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
229910000027 potassium carbonate Inorganic materials 0.000 description 11
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 10
125000004356 hydroxy functional group Chemical group O* 0.000 description 10
239000012071 phase Substances 0.000 description 10
CMYBAHRLNADCKS-UHFFFAOYSA-N 6-(bromomethyl)-n-(3-methylphenyl)quinazolin-4-amine Chemical compound CC1=CC=CC(NC=2C3=CC(CBr)=CC=C3N=CN=2)=C1 CMYBAHRLNADCKS-UHFFFAOYSA-N 0.000 description 9
239000002585 base Substances 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
239000003921 oil Substances 0.000 description 9
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 8
KPHNOFBKQHPSGB-UHFFFAOYSA-N 6-methoxy-4-(3-methylanilino)quinazolin-7-ol Chemical compound N1=CN=C2C=C(O)C(OC)=CC2=C1NC1=CC=CC(C)=C1 KPHNOFBKQHPSGB-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
239000012458 free base Substances 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
230000002829 reductive effect Effects 0.000 description 8
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 8
102400001368 Epidermal growth factor Human genes 0.000 description 7
101800003838 Epidermal growth factor Proteins 0.000 description 7
229960000583 acetic acid Drugs 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
229940116977 epidermal growth factor Drugs 0.000 description 7
230000012010 growth Effects 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
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