CZ282038B6

CZ282038B6 - Chinazolinové deriváty, způsob jejich přípravy a farmaceutické kompozice tyto deriváty obsahující

Chinazolinové deriváty, způsob jejich přípravy a farmaceutické kompozice tyto deriváty obsahující Download PDF

Info

Publication number: CZ282038B6
Authority: CZ; Czechia
Prior art keywords: carbon atoms; group; radical contains; alkyl; alkyl radical
Prior art date: 1992-01-20

Application number

CZ9343A

Other languages

Czech (cs)

English (en)

Other versions

CZ4393A3 (en

Inventor

Andrew John Barker

Original Assignee

Zeneca Limited

Priority date

1992-01-20

Filing date

1993-01-18

Publication date

1997-04-16

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

1993-01-18 Application filed by Zeneca Limited filed Critical Zeneca Limited

1993-10-13 Publication of CZ4393A3 publication Critical patent/CZ4393A3/cs

1997-04-16 Publication of CZ282038B6 publication Critical patent/CZ282038B6/cs

Links

238000000034 method Methods 0.000 title claims abstract description 62
238000002360 preparation method Methods 0.000 title claims abstract description 23
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 8
230000008569 process Effects 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 amino, carboxyl Chemical group 0.000 claims abstract description 974
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 787
125000000217 alkyl group Chemical group 0.000 claims abstract description 119
150000001875 compounds Chemical class 0.000 claims abstract description 107
125000003545 alkoxy group Chemical group 0.000 claims abstract description 53
150000003839 salts Chemical class 0.000 claims abstract description 50
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 22
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 22
125000003277 amino group Chemical group 0.000 claims abstract description 20
125000005843 halogen group Chemical group 0.000 claims abstract description 16
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 15
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 14
125000005530 alkylenedioxy group Chemical group 0.000 claims abstract description 13
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 13
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims abstract description 9
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 9
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 8
125000005118 N-alkylcarbamoyl 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
150000003246 quinazolines Chemical class 0.000 claims description 87
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 54
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 36
150000003254 radicals Chemical class 0.000 claims description 32
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical group NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 26
125000001424 substituent group Chemical group 0.000 claims description 25
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 24
239000002253 acid Substances 0.000 claims description 20
229910052739 hydrogen Inorganic materials 0.000 claims description 20
125000004414 alkyl thio group Chemical group 0.000 claims description 19
125000003282 alkyl amino group Chemical group 0.000 claims description 18
239000001257 hydrogen Substances 0.000 claims description 18
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 15
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 15
241001465754 Metazoa Species 0.000 claims description 14
125000005236 alkanoylamino group Chemical group 0.000 claims description 14
230000001093 anti-cancer Effects 0.000 claims description 14
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
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 12
125000004663 dialkyl amino group Chemical group 0.000 claims description 12
125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 11
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 10
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 10
KHBQMWCZKVMBLN-IDEBNGHGSA-N benzenesulfonamide Chemical group NS(=O)(=O)[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 KHBQMWCZKVMBLN-IDEBNGHGSA-N 0.000 claims description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
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 9
125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 9
125000006524 alkoxy alkyl amino group Chemical group 0.000 claims description 8
125000005085 alkoxycarbonylalkoxy group Chemical group 0.000 claims description 8
125000004984 dialkylaminoalkoxy group Chemical group 0.000 claims description 8
125000001188 haloalkyl group Chemical group 0.000 claims description 8
125000005191 hydroxyalkylamino group Chemical group 0.000 claims description 8
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-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 7
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 7
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
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 7
125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 7
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
125000002768 hydroxyalkyl group Chemical group 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
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
125000006016 2-bromoethoxy group Chemical group 0.000 claims description 6
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 6
125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 6
125000004103 aminoalkyl group Chemical group 0.000 claims description 6
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 6
125000004438 haloalkoxy group Chemical group 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
229940080818 propionamide Drugs 0.000 claims description 6
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
125000005041 acyloxyalkyl group Chemical group 0.000 claims description 5
125000005084 alkoxyalkylaminoalkyl group Chemical group 0.000 claims description 5
125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 5
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 5
125000005122 aminoalkylamino group Chemical group 0.000 claims description 5
125000005111 carboxyalkoxy group Chemical group 0.000 claims description 5
125000001309 chloro group Chemical group Cl* 0.000 claims description 5
125000004966 cyanoalkyl group Chemical group 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
125000004992 haloalkylamino group Chemical group 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
125000005181 hydroxyalkylaminoalkyl group Chemical group 0.000 claims description 5
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 5
230000009467 reduction Effects 0.000 claims description 5
OAAKFAXUEYTMHF-UHFFFAOYSA-N 2-ethoxyacetamide Chemical compound CCOCC(N)=O OAAKFAXUEYTMHF-UHFFFAOYSA-N 0.000 claims description 4
MTEZLAATISORQK-UHFFFAOYSA-N 2-methoxyacetamide Chemical compound COCC(N)=O MTEZLAATISORQK-UHFFFAOYSA-N 0.000 claims description 4
125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 4
125000003418 alkyl amino alkoxy group Chemical group 0.000 claims description 4
125000005242 carbamoyl alkyl group Chemical group 0.000 claims description 4
125000001589 carboacyl group Chemical group 0.000 claims description 4
125000004181 carboxyalkyl group Chemical group 0.000 claims description 4
238000003776 cleavage reaction Methods 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 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
125000002071 phenylalkoxy group Chemical group 0.000 claims description 4
TZGPACAKMCUCKX-UHFFFAOYSA-N 2-hydroxyacetamide Chemical compound NC(=O)CO TZGPACAKMCUCKX-UHFFFAOYSA-N 0.000 claims description 3
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 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
125000002431 aminoalkoxy group Chemical group 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
125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([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
125000005359 phenoxyalkyl group Chemical group 0.000 claims description 3
230000007017 scission Effects 0.000 claims description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
UFQQKRSIOKGSIU-UHFFFAOYSA-N 6,7-bis(2-methoxyethoxy)-n-(3-methylphenyl)quinazolin-4-amine Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 UFQQKRSIOKGSIU-UHFFFAOYSA-N 0.000 claims description 2
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 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
230000029936 alkylation Effects 0.000 claims description 2
238000005804 alkylation reaction Methods 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
VOPNWXZDJKCCRE-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 VOPNWXZDJKCCRE-UHFFFAOYSA-N 0.000 claims description 2
230000001590 oxidative effect Effects 0.000 claims description 2
125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims 1
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 1
FAUYSBITBLFUOX-UHFFFAOYSA-N 10,12-dioxa-8,13-diazatricyclo[7.3.1.02,7]trideca-1(13),2,4,6,8-pentaene Chemical compound C1=CC=CC2=NC(OCO3)=NC3=C21 FAUYSBITBLFUOX-UHFFFAOYSA-N 0.000 claims 1
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical group NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims 1
OCXSVYSGSKIORX-UHFFFAOYSA-N C1(=CC=CC=C1)NC(NC(C(=O)N)Cl)=O Chemical compound C1(=CC=CC=C1)NC(NC(C(=O)N)Cl)=O OCXSVYSGSKIORX-UHFFFAOYSA-N 0.000 claims 1
101100348017 Drosophila melanogaster Nazo gene Proteins 0.000 claims 1
KMBHYOPMKJLNMX-UHFFFAOYSA-N N-(4-chlorophenyl)-8-methoxyquinazolin-2-amine Chemical compound ClC1=CC=C(NC2=NC3=C(C=CC=C3C=N2)OC)C=C1 KMBHYOPMKJLNMX-UHFFFAOYSA-N 0.000 claims 1
ZVMHFEYAUBCJDQ-UHFFFAOYSA-N OC=1C=CC=C2C(=CC=NC=12)NC1=CC=C(C=C1)Cl Chemical compound OC=1C=CC=C2C(=CC=NC=12)NC1=CC=C(C=C1)Cl ZVMHFEYAUBCJDQ-UHFFFAOYSA-N 0.000 claims 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 claims 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 1
125000001246 bromo group Chemical group Br* 0.000 claims 1
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 1
125000003386 piperidinyl group Chemical group 0.000 claims 1
XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 claims 1
125000003396 thiol group Chemical class [H]S* 0.000 claims 1
239000003112 inhibitor Substances 0.000 abstract description 4
239000000203 mixture Substances 0.000 description 225
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 210
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 135
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 121
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 92
238000000921 elemental analysis Methods 0.000 description 86
239000011541 reaction mixture Substances 0.000 description 81
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 73
230000008018 melting Effects 0.000 description 67
238000002844 melting Methods 0.000 description 67
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 67
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 56
239000000243 solution Substances 0.000 description 55
238000004440 column chromatography Methods 0.000 description 54
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
239000000047 product Substances 0.000 description 47
239000007858 starting material Substances 0.000 description 44
235000019439 ethyl acetate Nutrition 0.000 description 41
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
238000012360 testing method Methods 0.000 description 33
238000010992 reflux Methods 0.000 description 29
229910052943 magnesium sulfate Inorganic materials 0.000 description 28
235000019341 magnesium sulphate Nutrition 0.000 description 28
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 27
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 26
239000002244 precipitate Substances 0.000 description 26
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 25
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
239000012258 stirred mixture Substances 0.000 description 21
JJYPMNFTHPTTDI-UHFFFAOYSA-N 3-methylaniline Chemical compound CC1=CC=CC(N)=C1 JJYPMNFTHPTTDI-UHFFFAOYSA-N 0.000 description 20
206010028980 Neoplasm Diseases 0.000 description 19
238000004458 analytical method Methods 0.000 description 19
239000012074 organic phase Substances 0.000 description 19
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 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
210000004027 cell Anatomy 0.000 description 15
239000007787 solid Substances 0.000 description 15
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
238000006243 chemical reaction Methods 0.000 description 14
238000003756 stirring Methods 0.000 description 14
102000027426 receptor tyrosine kinases Human genes 0.000 description 13
108091008598 receptor tyrosine kinases Proteins 0.000 description 13
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 12
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
201000011510 cancer Diseases 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
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
229910000041 hydrogen chloride Inorganic materials 0.000 description 11
230000002401 inhibitory effect Effects 0.000 description 11
229910000027 potassium carbonate Inorganic materials 0.000 description 11
239000003480 eluent Substances 0.000 description 10
239000012071 phase Substances 0.000 description 10
230000002441 reversible effect Effects 0.000 description 10
239000000126 substance Substances 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 8
239000003054 catalyst Substances 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
229960000583 acetic acid Drugs 0.000 description 7
150000002431 hydrogen Chemical class 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
230000002829 reductive effect Effects 0.000 description 7
238000011282 treatment Methods 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
102400001368 Epidermal growth factor Human genes 0.000 description 6
101800003838 Epidermal growth factor Proteins 0.000 description 6
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 6
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 6
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
229910052783 alkali metal Inorganic materials 0.000 description 6
229910052801 chlorine Inorganic materials 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
230000000694 effects Effects 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
239000003701 inert diluent Substances 0.000 description 6
239000012442 inert solvent Substances 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
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 6
AHGSPAKNJWCSRF-UHFFFAOYSA-N 4-n-(3-methylphenyl)quinazoline-4,7-diamine Chemical compound CC1=CC=CC(NC=2C3=CC=C(N)C=C3N=CN=2)=C1 AHGSPAKNJWCSRF-UHFFFAOYSA-N 0.000 description 5
RSVNNWQHWIOIOC-UHFFFAOYSA-N 6,7-dimethoxy-n-(3-methylphenyl)quinazolin-4-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 RSVNNWQHWIOIOC-UHFFFAOYSA-N 0.000 description 5
FUWFVMHHNPEPHD-UHFFFAOYSA-N 6-(bromomethyl)-4-chloroquinazoline Chemical compound C1=C(CBr)C=C2C(Cl)=NC=NC2=C1 FUWFVMHHNPEPHD-UHFFFAOYSA-N 0.000 description 5
BUYIXGTWVMBDLP-UHFFFAOYSA-N 7-chloro-n-(3-methylphenyl)-6-nitroquinazolin-4-amine Chemical compound CC1=CC=CC(NC=2C3=CC(=C(Cl)C=C3N=CN=2)[N+]([O-])=O)=C1 BUYIXGTWVMBDLP-UHFFFAOYSA-N 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
108700020796 Oncogene Proteins 0.000 description 5
239000000908 ammonium hydroxide Substances 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
229940116977 epidermal growth factor Drugs 0.000 description 5
229910052731 fluorine Inorganic materials 0.000 description 5
239000012362 glacial acetic acid Substances 0.000 description 5
230000012010 growth Effects 0.000 description 5
238000000746 purification Methods 0.000 description 5
QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 5
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
ZFXHOCBCURBSDT-UHFFFAOYSA-N 2-[6-methoxy-4-(3-methylanilino)quinazolin-7-yl]oxyethanol Chemical compound N1=CN=C2C=C(OCCO)C(OC)=CC2=C1NC1=CC=CC(C)=C1 ZFXHOCBCURBSDT-UHFFFAOYSA-N 0.000 description 4
JJKWHOSQTYYFAE-UHFFFAOYSA-N 2-methoxyacetyl chloride Chemical compound COCC(Cl)=O JJKWHOSQTYYFAE-UHFFFAOYSA-N 0.000 description 4
MBEQLZLCWSXTPD-UHFFFAOYSA-N 4-(3-methylanilino)quinazoline-6,7-diol Chemical compound CC1=CC=CC(NC=2C3=CC(O)=C(O)C=C3N=CN=2)=C1 MBEQLZLCWSXTPD-UHFFFAOYSA-N 0.000 description 4
XNILKVADCMYCQT-UHFFFAOYSA-N 4-chloro-6-methylquinazoline Chemical compound N1=CN=C(Cl)C2=CC(C)=CC=C21 XNILKVADCMYCQT-UHFFFAOYSA-N 0.000 description 4
LZOSFEDULGODDH-UHFFFAOYSA-N 4-chloro-6-nitroquinazoline Chemical compound N1=CN=C(Cl)C2=CC([N+](=O)[O-])=CC=C21 LZOSFEDULGODDH-UHFFFAOYSA-N 0.000 description 4
GVRRXASZZAKBMN-UHFFFAOYSA-N 4-chloroquinazoline Chemical class C1=CC=C2C(Cl)=NC=NC2=C1 GVRRXASZZAKBMN-UHFFFAOYSA-N 0.000 description 4
AWAYNEMCHILZCF-UHFFFAOYSA-N 4-n-(3-chlorophenyl)quinazoline-4,6-diamine Chemical compound C12=CC(N)=CC=C2N=CN=C1NC1=CC=CC(Cl)=C1 AWAYNEMCHILZCF-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
108091003079 Bovine Serum Albumin Proteins 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
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 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
229920004890 Triton X-100 Polymers 0.000 description 4
150000008064 anhydrides Chemical class 0.000 description 4
239000002246 antineoplastic agent Substances 0.000 description 4
239000012298 atmosphere Substances 0.000 description 4
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 4
239000012267 brine Substances 0.000 description 4
239000002775 capsule Substances 0.000 description 4
230000010261 cell growth Effects 0.000 description 4
229940088598 enzyme Drugs 0.000 description 4
239000003102 growth factor Substances 0.000 description 4
150000003840 hydrochlorides Chemical class 0.000 description 4
238000005984 hydrogenation reaction Methods 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000008101 lactose Substances 0.000 description 4
210000004185 liver Anatomy 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
239000012047 saturated solution Substances 0.000 description 4
239000011734 sodium Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 3
238000005160 1H NMR spectroscopy Methods 0.000 description 3
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
UMKSAURFQFUULT-UHFFFAOYSA-N 2-Amino-5-methoxybenzoic acid Chemical compound COC1=CC=C(N)C(C(O)=O)=C1 UMKSAURFQFUULT-UHFFFAOYSA-N 0.000 description 3
LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 3
ZKUYSJHXBFFGPU-UHFFFAOYSA-N 2516-95-2 Chemical compound OC(=O)C1=CC(Cl)=CC=C1[N+]([O-])=O ZKUYSJHXBFFGPU-UHFFFAOYSA-N 0.000 description 3
MJLHSJRIMKQIFP-UHFFFAOYSA-N 3-n-(6,7-dimethoxyquinazolin-4-yl)benzene-1,3-diamine;hydrochloride Chemical compound Cl.C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC(N)=C1 MJLHSJRIMKQIFP-UHFFFAOYSA-N 0.000 description 3
YIEFGGZKSXIYFW-UHFFFAOYSA-N 4-(3-methylanilino)quinazoline-7-carboxylic acid Chemical compound CC1=CC=CC(NC=2C3=CC=C(C=C3N=CN=2)C(O)=O)=C1 YIEFGGZKSXIYFW-UHFFFAOYSA-N 0.000 description 3
ATRZVHJSCCURLJ-UHFFFAOYSA-N 4-(4-chloroquinazolin-6-yl)morpholine Chemical compound C1=C2C(Cl)=NC=NC2=CC=C1N1CCOCC1 ATRZVHJSCCURLJ-UHFFFAOYSA-N 0.000 description 3
ASLFKOTWRWCLSK-UHFFFAOYSA-N 4-chloro-6-piperidin-1-ylquinazoline Chemical compound C1=C2C(Cl)=NC=NC2=CC=C1N1CCCCC1 ASLFKOTWRWCLSK-UHFFFAOYSA-N 0.000 description 3
WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 3
JHWXBNQNSFQNPY-UHFFFAOYSA-N 7-(2-bromoethoxy)-6-methoxy-n-(3-methylphenyl)quinazolin-4-amine Chemical compound N1=CN=C2C=C(OCCBr)C(OC)=CC2=C1NC1=CC=CC(C)=C1 JHWXBNQNSFQNPY-UHFFFAOYSA-N 0.000 description 3
PMLONMIODRHERC-UHFFFAOYSA-N 7-chloro-1h-quinazolin-4-one Chemical compound N1C=NC(=O)C=2C1=CC(Cl)=CC=2 PMLONMIODRHERC-UHFFFAOYSA-N 0.000 description 3
WZLMWRBGVYVLDZ-UHFFFAOYSA-N 7-methoxy-n-(3-methylphenyl)-6-nitroquinazolin-4-amine Chemical compound C=12C=C([N+]([O-])=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 WZLMWRBGVYVLDZ-UHFFFAOYSA-N 0.000 description 3
HQQMBKAUTNDSQY-UHFFFAOYSA-N 7-n-[3-(dimethylamino)propyl]-4-n-(3-methylphenyl)-6-nitroquinazoline-4,7-diamine Chemical compound C=12C=C([N+]([O-])=O)C(NCCCN(C)C)=CC2=NC=NC=1NC1=CC=CC(C)=C1 HQQMBKAUTNDSQY-UHFFFAOYSA-N 0.000 description 3
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
201000009030 Carcinoma Diseases 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
108091000080 Phosphotransferase Proteins 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 3
239000013504 Triton X-100 Substances 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
230000004663 cell proliferation Effects 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
239000008120 corn starch Substances 0.000 description 3
229940099112 cornstarch Drugs 0.000 description 3
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 3
239000012894 fetal calf serum Substances 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
210000003494 hepatocyte Anatomy 0.000 description 3
208000032839 leukemia Diseases 0.000 description 3
229910052751 metal Inorganic materials 0.000 description 3
239000002184 metal Substances 0.000 description 3
DNZMCCLHPQTXJQ-UHFFFAOYSA-N methyl 4-(3-methylanilino)quinazoline-7-carboxylate Chemical compound N=1C=NC2=CC(C(=O)OC)=CC=C2C=1NC1=CC=CC(C)=C1 DNZMCCLHPQTXJQ-UHFFFAOYSA-N 0.000 description 3
CSOBGYJJXIKZGA-UHFFFAOYSA-N n-(3-methylphenyl)-6-nitroquinazolin-4-amine Chemical compound CC1=CC=CC(NC=2C3=CC(=CC=C3N=CN=2)[N+]([O-])=O)=C1 CSOBGYJJXIKZGA-UHFFFAOYSA-N 0.000 description 3
IVUMMNZRJFAFQP-UHFFFAOYSA-N n-(3-methylphenyl)-7-methylsulfanyl-6-nitroquinazolin-4-amine Chemical compound C=12C=C([N+]([O-])=O)C(SC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 IVUMMNZRJFAFQP-UHFFFAOYSA-N 0.000 description 3
HGIWILAPVIDGKH-UHFFFAOYSA-N n-(3-methylphenyl)-7-nitroquinazolin-4-amine Chemical compound CC1=CC=CC(NC=2C3=CC=C(C=C3N=CN=2)[N+]([O-])=O)=C1 HGIWILAPVIDGKH-UHFFFAOYSA-N 0.000 description 3
ZNHMGZYTJLEROX-UHFFFAOYSA-N n-[4-(3-methylanilino)quinazolin-6-yl]acetamide Chemical compound C12=CC(NC(=O)C)=CC=C2N=CN=C1NC1=CC=CC(C)=C1 ZNHMGZYTJLEROX-UHFFFAOYSA-N 0.000 description 3
239000007800 oxidant agent Substances 0.000 description 3
102000020233 phosphotransferase Human genes 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
102000005962 receptors Human genes 0.000 description 3
108020003175 receptors Proteins 0.000 description 3
238000010898 silica gel chromatography Methods 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
239000002904 solvent Substances 0.000 description 3
239000006228 supernatant Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
230000009466 transformation Effects 0.000 description 3
239000008215 water for injection Substances 0.000 description 3
LSBGXLOBLBWVEN-UHFFFAOYSA-N (4-chloroquinazolin-6-yl) acetate Chemical compound N1=CN=C(Cl)C2=CC(OC(=O)C)=CC=C21 LSBGXLOBLBWVEN-UHFFFAOYSA-N 0.000 description 2
HJVAVGOPTDJYOJ-UHFFFAOYSA-N 2-amino-4,5-dimethoxybenzoic acid Chemical compound COC1=CC(N)=C(C(O)=O)C=C1OC HJVAVGOPTDJYOJ-UHFFFAOYSA-N 0.000 description 2
JYYLQSCZISREGY-UHFFFAOYSA-N 2-amino-4-chlorobenzoic acid Chemical compound NC1=CC(Cl)=CC=C1C(O)=O JYYLQSCZISREGY-UHFFFAOYSA-N 0.000 description 2
RUYCUDHAVDCXIX-UHFFFAOYSA-N 2-chloro-n-[4-(3-methylanilino)quinazolin-6-yl]acetamide Chemical compound CC1=CC=CC(NC=2C3=CC(NC(=O)CCl)=CC=C3N=CN=2)=C1 RUYCUDHAVDCXIX-UHFFFAOYSA-N 0.000 description 2
KUOMDAPBHJIEKP-UHFFFAOYSA-N 2-methoxy-n-[4-(3-methylanilino)quinazolin-7-yl]acetamide Chemical compound N=1C=NC2=CC(NC(=O)COC)=CC=C2C=1NC1=CC=CC(C)=C1 KUOMDAPBHJIEKP-UHFFFAOYSA-N 0.000 description 2
ZQIWRIWTTKXCIO-UHFFFAOYSA-N 4-(3-methylanilino)quinazolin-7-ol Chemical compound CC1=CC=CC(NC=2C3=CC=C(O)C=C3N=CN=2)=C1 ZQIWRIWTTKXCIO-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
QNLKPXGXCBGDDC-UHFFFAOYSA-N 4-chloro-6-(dibromomethyl)quinazoline Chemical compound C1=C(C(Br)Br)C=C2C(Cl)=NC=NC2=C1 QNLKPXGXCBGDDC-UHFFFAOYSA-N 0.000 description 2
CCCGYXZEVXWXAU-UHFFFAOYSA-N 4-chloro-7-nitroquinazoline Chemical compound ClC1=NC=NC2=CC([N+](=O)[O-])=CC=C21 CCCGYXZEVXWXAU-UHFFFAOYSA-N 0.000 description 2
SBGUQHNSYZGPLX-UHFFFAOYSA-N 4-n-(3-methylphenyl)-7-morpholin-4-ylquinazoline-4,6-diamine Chemical compound CC1=CC=CC(NC=2C3=CC(N)=C(N4CCOCC4)C=C3N=CN=2)=C1 SBGUQHNSYZGPLX-UHFFFAOYSA-N 0.000 description 2
DLVMGJPGJHCIJW-UHFFFAOYSA-N 4-n-[3-(trifluoromethyl)phenyl]quinazoline-4,6-diamine Chemical compound C12=CC(N)=CC=C2N=CN=C1NC1=CC=CC(C(F)(F)F)=C1 DLVMGJPGJHCIJW-UHFFFAOYSA-N 0.000 description 2
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 2
HDXUENATWBWIRX-UHFFFAOYSA-N 6,7-dimethoxy-n-(3-methylphenyl)-5-nitroquinazolin-4-amine Chemical compound C=12C([N+]([O-])=O)=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 HDXUENATWBWIRX-UHFFFAOYSA-N 0.000 description 2
TWDBGKCEJPCGEK-UHFFFAOYSA-N 6-(2-bromoethoxy)-n-(3-methylphenyl)quinazolin-4-amine Chemical compound CC1=CC=CC(NC=2C3=CC(OCCBr)=CC=C3N=CN=2)=C1 TWDBGKCEJPCGEK-UHFFFAOYSA-N 0.000 description 2
VVNQBWHRGUXZNH-UHFFFAOYSA-N 6-methoxy-7-(2-methoxyethoxy)-n-(3-methylphenyl)quinazolin-4-amine Chemical compound C=12C=C(OC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 VVNQBWHRGUXZNH-UHFFFAOYSA-N 0.000 description 2
JUCDXPIFJIVICL-UHFFFAOYSA-N 6-methyl-1h-quinazolin-4-one Chemical compound N1C=NC(=O)C2=CC(C)=CC=C21 JUCDXPIFJIVICL-UHFFFAOYSA-N 0.000 description 2
AHEHMDXRXAAMGF-UHFFFAOYSA-N 6-methyl-n-(3-methylphenyl)quinazolin-4-amine Chemical compound CC1=CC=CC(NC=2C3=CC(C)=CC=C3N=CN=2)=C1 AHEHMDXRXAAMGF-UHFFFAOYSA-N 0.000 description 2
KHYGXPXJZPATPD-UHFFFAOYSA-N 6-n-(2-methoxyethyl)-4-n-(3-methylphenyl)quinazoline-4,6-diamine Chemical compound C12=CC(NCCOC)=CC=C2N=CN=C1NC1=CC=CC(C)=C1 KHYGXPXJZPATPD-UHFFFAOYSA-N 0.000 description 2
MOBNCKURXDGQCB-UHFFFAOYSA-N 6-nitro-1h-quinazolin-4-one Chemical compound N1C=NC(=O)C2=CC([N+](=O)[O-])=CC=C21 MOBNCKURXDGQCB-UHFFFAOYSA-N 0.000 description 2
FKOOZPWZRRDRTK-UHFFFAOYSA-N 6-nitro-n-[3-(trifluoromethyl)phenyl]quinazolin-4-amine Chemical compound C12=CC([N+](=O)[O-])=CC=C2N=CN=C1NC1=CC=CC(C(F)(F)F)=C1 FKOOZPWZRRDRTK-UHFFFAOYSA-N 0.000 description 2
KCLLIYLLKJSXGQ-UHFFFAOYSA-N 7-methoxy-4-(3-methylanilino)quinazolin-6-ol Chemical compound C=12C=C(O)C(OC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 KCLLIYLLKJSXGQ-UHFFFAOYSA-N 0.000 description 2
GHEITLVPLGZZQI-UHFFFAOYSA-N 7-methoxy-n-(3-methylphenyl)quinazolin-4-amine Chemical compound N=1C=NC2=CC(OC)=CC=C2C=1NC1=CC=CC(C)=C1 GHEITLVPLGZZQI-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
206010006187 Breast cancer Diseases 0.000 description 2
208000026310 Breast neoplasm Diseases 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
230000006820 DNA synthesis Effects 0.000 description 2
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
102000001301 EGF receptor Human genes 0.000 description 2
108060006698 EGF receptor Proteins 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
238000004566 IR spectroscopy Methods 0.000 description 2
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 2
LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
102000043276 Oncogene Human genes 0.000 description 2
206010061902 Pancreatic neoplasm Diseases 0.000 description 2
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
208000024770 Thyroid neoplasm Diseases 0.000 description 2
102000006747 Transforming Growth Factor alpha Human genes 0.000 description 2
101800004564 Transforming growth factor alpha Proteins 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
125000004423 acyloxy group Chemical group 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
150000001347 alkyl bromides Chemical class 0.000 description 2
150000001351 alkyl iodides Chemical class 0.000 description 2
239000002168 alkylating agent Substances 0.000 description 2
229940100198 alkylating agent Drugs 0.000 description 2
230000002152 alkylating effect Effects 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
238000003556 assay Methods 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
238000009835 boiling Methods 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
230000003182 bronchodilatating effect Effects 0.000 description 2
229940124630 bronchodilator Drugs 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
210000001072 colon Anatomy 0.000 description 2
238000002648 combination therapy Methods 0.000 description 2
XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 2
125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 2
USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
201000010099 disease Diseases 0.000 description 2
239000012153 distilled water Substances 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
229940079593 drug Drugs 0.000 description 2
WGDFCNRIGUMPIC-UHFFFAOYSA-N ethyl 2-[6-methoxy-4-(3-methylanilino)quinazolin-7-yl]oxyacetate Chemical compound C=12C=C(OC)C(OCC(=O)OCC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 WGDFCNRIGUMPIC-UHFFFAOYSA-N 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
230000002440 hepatic effect Effects 0.000 description 2
230000001077 hypotensive effect Effects 0.000 description 2
238000000099 in vitro assay Methods 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
230000001939 inductive effect Effects 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
239000010410 layer Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
229910001629 magnesium chloride Inorganic materials 0.000 description 2
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
239000000463 material Substances 0.000 description 2
BYHDRGRVVXBJIP-UHFFFAOYSA-N methyl 4-chloroquinazoline-7-carboxylate Chemical compound ClC1=NC=NC2=CC(C(=O)OC)=CC=C21 BYHDRGRVVXBJIP-UHFFFAOYSA-N 0.000 description 2
QNNZNPUJXPQPJI-UHFFFAOYSA-N n-(3-methylphenyl)-7-morpholin-4-yl-6-nitroquinazolin-4-amine Chemical compound CC1=CC=CC(NC=2C3=CC(=C(N4CCOCC4)C=C3N=CN=2)[N+]([O-])=O)=C1 QNNZNPUJXPQPJI-UHFFFAOYSA-N 0.000 description 2
150000002828 nitro derivatives Chemical class 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
201000002528 pancreatic cancer Diseases 0.000 description 2
208000008443 pancreatic carcinoma Diseases 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 2
238000006366 phosphorylation reaction Methods 0.000 description 2
229910052697 platinum Inorganic materials 0.000 description 2
229940068918 polyethylene glycol 400 Drugs 0.000 description 2
229950008882 polysorbate Drugs 0.000 description 2
229920000136 polysorbate Polymers 0.000 description 2
108090000765 processed proteins & peptides Proteins 0.000 description 2
125000006308 propyl amino group Chemical group 0.000 description 2
210000002307 prostate Anatomy 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
238000011160 research Methods 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 2
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
239000001488 sodium phosphate Substances 0.000 description 2
229910000162 sodium phosphate Inorganic materials 0.000 description 2
238000004611 spectroscopical analysis Methods 0.000 description 2
230000000638 stimulation Effects 0.000 description 2
150000003440 styrenes Chemical class 0.000 description 2
125000000547 substituted alkyl group Chemical group 0.000 description 2
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 2
IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 2
239000012414 tert-butyl nitrite Substances 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
231100000331 toxic Toxicity 0.000 description 2
230000002588 toxic effect Effects 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
210000004881 tumor cell Anatomy 0.000 description 2
229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
239000005483 tyrosine kinase inhibitor Substances 0.000 description 2
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
QHSILJZBWLFQGR-UHFFFAOYSA-N (4-oxo-1h-quinazolin-6-yl) acetate Chemical compound N1=CNC(=O)C2=CC(OC(=O)C)=CC=C21 QHSILJZBWLFQGR-UHFFFAOYSA-N 0.000 description 1
ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
SCZNXLWKYFICFV-UHFFFAOYSA-N 1,2,3,4,5,7,8,9-octahydropyrido[1,2-b]diazepine Chemical compound C1CCCNN2CCCC=C21 SCZNXLWKYFICFV-UHFFFAOYSA-N 0.000 description 1
GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 1
WZCQRUWWHSTZEM-UHFFFAOYSA-N 1,3-phenylenediamine Chemical compound NC1=CC=CC(N)=C1 WZCQRUWWHSTZEM-UHFFFAOYSA-N 0.000 description 1
CBCKQZAAMUWICA-UHFFFAOYSA-N 1,4-phenylenediamine Chemical compound NC1=CC=C(N)C=C1 CBCKQZAAMUWICA-UHFFFAOYSA-N 0.000 description 1
ZQRROVFSALJMMI-UHFFFAOYSA-N 1-[4-(3-methylanilino)quinazolin-6-yl]-3-phenylurea Chemical compound CC1=CC=CC(NC=2C3=CC(NC(=O)NC=4C=CC=CC=4)=CC=C3N=CN=2)=C1 ZQRROVFSALJMMI-UHFFFAOYSA-N 0.000 description 1
UDJDCUHZIBKBJL-UHFFFAOYSA-N 1-[4-(3-methylanilino)quinazolin-6-yl]pyrrolidin-2-one Chemical compound CC1=CC=CC(NC=2C3=CC(=CC=C3N=CN=2)N2C(CCC2)=O)=C1 UDJDCUHZIBKBJL-UHFFFAOYSA-N 0.000 description 1
LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 description 1
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
LDKSCZJUIURGMW-UHFFFAOYSA-N 1-isothiocyanato-3-methylsulfanylpropane Chemical group CSCCCN=C=S LDKSCZJUIURGMW-UHFFFAOYSA-N 0.000 description 1
JQCSUVJDBHJKNG-UHFFFAOYSA-N 1-methoxy-ethyl Chemical group C[CH]OC JQCSUVJDBHJKNG-UHFFFAOYSA-N 0.000 description 1
125000000586 2-(4-morpholinyl)ethoxy group Chemical group [H]C([H])(O*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 1
PPQDYOBQQWPTIS-UHFFFAOYSA-N 2-(diethylamino)acetamide Chemical compound CCN(CC)CC(N)=O PPQDYOBQQWPTIS-UHFFFAOYSA-N 0.000 description 1
YGRTYMUFCRBWIK-UHFFFAOYSA-N 2-(dimethylamino)-n-[4-(3-methylanilino)quinazolin-6-yl]acetamide Chemical compound C12=CC(NC(=O)CN(C)C)=CC=C2N=CN=C1NC1=CC=CC(C)=C1 YGRTYMUFCRBWIK-UHFFFAOYSA-N 0.000 description 1
WKJOQYHMXRVQDK-UHFFFAOYSA-N 2-(dimethylamino)acetamide Chemical compound CN(C)CC(N)=O WKJOQYHMXRVQDK-UHFFFAOYSA-N 0.000 description 1
SNFFHBJWQFQMBC-UHFFFAOYSA-N 2-(ethylamino)acetamide Chemical compound CCNCC(N)=O SNFFHBJWQFQMBC-UHFFFAOYSA-N 0.000 description 1
CBBFWSMELCDMPZ-UHFFFAOYSA-N 2-(methylamino)acetamide Chemical compound CNCC(N)=O CBBFWSMELCDMPZ-UHFFFAOYSA-N 0.000 description 1
LKZRYXDGZQOPNA-UHFFFAOYSA-N 2-(propylamino)acetamide Chemical compound CCCNCC(N)=O LKZRYXDGZQOPNA-UHFFFAOYSA-N 0.000 description 1
HYNQTSZBTIOFKH-UHFFFAOYSA-N 2-Amino-5-hydroxybenzoic acid Chemical compound NC1=CC=C(O)C=C1C(O)=O HYNQTSZBTIOFKH-UHFFFAOYSA-N 0.000 description 1
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
JXSIKEXWVFQUAR-UHFFFAOYSA-N 2-[4-(3-methylanilino)quinazolin-6-yl]acetonitrile Chemical compound CC1=CC=CC(NC=2C3=CC(CC#N)=CC=C3N=CN=2)=C1 JXSIKEXWVFQUAR-UHFFFAOYSA-N 0.000 description 1
JJRIZRKUNDUATE-UHFFFAOYSA-N 2-[6-methoxy-4-(3-methylanilino)quinazolin-7-yl]oxyacetic acid Chemical compound N1=CN=C2C=C(OCC(O)=O)C(OC)=CC2=C1NC1=CC=CC(C)=C1 JJRIZRKUNDUATE-UHFFFAOYSA-N 0.000 description 1
HVOXXLLDKLJFND-UHFFFAOYSA-N 2-[7-(2-hydroxyethoxy)-4-(3-methylanilino)quinazolin-6-yl]oxyethanol Chemical compound CC1=CC=CC(NC=2C3=CC(OCCO)=C(OCCO)C=C3N=CN=2)=C1 HVOXXLLDKLJFND-UHFFFAOYSA-N 0.000 description 1
KBCHMLUJHCFUST-UHFFFAOYSA-N 2-[[4-(3-methylanilino)quinazolin-7-yl]amino]ethanol Chemical compound CC1=CC=CC(NC=2C3=CC=C(NCCO)C=C3N=CN=2)=C1 KBCHMLUJHCFUST-UHFFFAOYSA-N 0.000 description 1
REBBDMHTSKPGCO-UHFFFAOYSA-N 2-amino-4,5-dimethylbenzoic acid Chemical compound CC1=CC(N)=C(C(O)=O)C=C1C REBBDMHTSKPGCO-UHFFFAOYSA-N 0.000 description 1
HHNWXQCVWVVVQZ-UHFFFAOYSA-N 2-amino-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C(N)=C1 HHNWXQCVWVVVQZ-UHFFFAOYSA-N 0.000 description 1
UXNGDCBPIGOZFO-UHFFFAOYSA-N 2-amino-5-(trifluoromethoxy)benzoic acid Chemical compound NC1=CC=C(OC(F)(F)F)C=C1C(O)=O UXNGDCBPIGOZFO-UHFFFAOYSA-N 0.000 description 1
HFHMPAKMODSNJN-UHFFFAOYSA-N 2-amino-5-morpholin-4-ylbenzoic acid Chemical compound C1=C(C(O)=O)C(N)=CC=C1N1CCOCC1 HFHMPAKMODSNJN-UHFFFAOYSA-N 0.000 description 1
DNABDRZWPKYYTH-UHFFFAOYSA-N 2-amino-5-piperidin-1-ylbenzoic acid Chemical compound C1=C(C(O)=O)C(N)=CC=C1N1CCCCC1 DNABDRZWPKYYTH-UHFFFAOYSA-N 0.000 description 1
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
GPNNOCMCNFXRAO-UHFFFAOYSA-N 2-aminoterephthalic acid Chemical compound NC1=CC(C(O)=O)=CC=C1C(O)=O GPNNOCMCNFXRAO-UHFFFAOYSA-N 0.000 description 1
JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical group NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 1
125000005999 2-bromoethyl group Chemical group 0.000 description 1
NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 1
VXIVSQZSERGHQP-HQMMCQRPSA-N 2-chloroacetamide Chemical group N[14C](=O)CCl VXIVSQZSERGHQP-HQMMCQRPSA-N 0.000 description 1
125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
125000003635 2-dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 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
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
JDTUPLBMGDDPJS-UHFFFAOYSA-N 2-methoxy-2-phenylethanol Chemical compound COC(CO)C1=CC=CC=C1 JDTUPLBMGDDPJS-UHFFFAOYSA-N 0.000 description 1
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
FMTHDYACPOHXSC-UHFFFAOYSA-N 2-n-(6,7-dimethoxyquinazolin-4-yl)benzene-1,2-diamine;hydrochloride Chemical compound Cl.C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC=C1N FMTHDYACPOHXSC-UHFFFAOYSA-N 0.000 description 1
RPNHCXPJSUGRAB-UHFFFAOYSA-N 2-nitro-5-(piperidin-1-yl)benzoic acid Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(N2CCCCC2)=C1 RPNHCXPJSUGRAB-UHFFFAOYSA-N 0.000 description 1
JWDAQACFBLXJBZ-UHFFFAOYSA-N 2-propoxyacetamide Chemical compound CCCOCC(N)=O JWDAQACFBLXJBZ-UHFFFAOYSA-N 0.000 description 1
SDYWXFYBZPNOFX-UHFFFAOYSA-N 3,4-dichloroaniline Chemical compound NC1=CC=C(Cl)C(Cl)=C1 SDYWXFYBZPNOFX-UHFFFAOYSA-N 0.000 description 1
FTZIQBGFCYJWKA-UHFFFAOYSA-N 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Chemical compound S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 FTZIQBGFCYJWKA-UHFFFAOYSA-N 0.000 description 1
NIXQLMVKRBUSPF-UHFFFAOYSA-N 3-(dimethylamino)propanamide Chemical compound CN(C)CCC(N)=O NIXQLMVKRBUSPF-UHFFFAOYSA-N 0.000 description 1
PPUXNQHLNOVQRG-UHFFFAOYSA-N 3-(ethylamino)propanamide Chemical compound CCNCCC(N)=O PPUXNQHLNOVQRG-UHFFFAOYSA-N 0.000 description 1
FFJLSBFLTYYWII-UHFFFAOYSA-N 3-(methylamino)propanamide Chemical compound CNCCC(N)=O FFJLSBFLTYYWII-UHFFFAOYSA-N 0.000 description 1
VIUDTWATMPPKEL-UHFFFAOYSA-N 3-(trifluoromethyl)aniline Chemical compound NC1=CC=CC(C(F)(F)F)=C1 VIUDTWATMPPKEL-UHFFFAOYSA-N 0.000 description 1
CWLKGDAVCFYWJK-UHFFFAOYSA-N 3-aminophenol Chemical compound NC1=CC=CC(O)=C1 CWLKGDAVCFYWJK-UHFFFAOYSA-N 0.000 description 1
229940018563 3-aminophenol Drugs 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
DBIVLAVBOICUQX-UHFFFAOYSA-N 3-bromopropanamide Chemical group NC(=O)CCBr DBIVLAVBOICUQX-UHFFFAOYSA-N 0.000 description 1
PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
JQDXZJYAUSVHDH-UHFFFAOYSA-N 3-chloropropanamide Chemical group NC(=O)CCCl JQDXZJYAUSVHDH-UHFFFAOYSA-N 0.000 description 1
229940105325 3-dimethylaminopropylamine Drugs 0.000 description 1
SOYBEXQHNURCGE-UHFFFAOYSA-N 3-ethoxypropan-1-amine Chemical compound CCOCCCN SOYBEXQHNURCGE-UHFFFAOYSA-N 0.000 description 1
WGVNJQHQQWPGJL-UHFFFAOYSA-N 3-ethoxypropanamide Chemical compound CCOCCC(N)=O WGVNJQHQQWPGJL-UHFFFAOYSA-N 0.000 description 1
SMGLHFBQMBVRCP-UHFFFAOYSA-N 3-hydroxypropanamide Chemical group NC(=O)CCO SMGLHFBQMBVRCP-UHFFFAOYSA-N 0.000 description 1
125000001137 3-hydroxypropoxy group Chemical group [H]OC([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
FAXDZWQIWUSWJH-UHFFFAOYSA-N 3-methoxypropan-1-amine Chemical compound COCCCN FAXDZWQIWUSWJH-UHFFFAOYSA-N 0.000 description 1
BPXCLLWXDHBFRH-UHFFFAOYSA-N 3-methoxypropanamide Chemical compound COCCC(N)=O BPXCLLWXDHBFRH-UHFFFAOYSA-N 0.000 description 1
125000005977 3-phenylpropyloxy group Chemical group 0.000 description 1
BTBVSLMBNRBDIR-UHFFFAOYSA-N 4-(3-chloroanilino)quinazoline-6,7-diol Chemical compound C=12C=C(O)C(O)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1 BTBVSLMBNRBDIR-UHFFFAOYSA-N 0.000 description 1
ZLNPUJYIVLCGAY-UHFFFAOYSA-N 4-(3-methylanilino)quinazolin-6-ol Chemical compound CC1=CC=CC(NC=2C3=CC(O)=CC=C3N=CN=2)=C1 ZLNPUJYIVLCGAY-UHFFFAOYSA-N 0.000 description 1
YGTHBVOCTPFJHQ-UHFFFAOYSA-N 4-(dimethylamino)butanamide Chemical compound CN(C)CCCC(N)=O YGTHBVOCTPFJHQ-UHFFFAOYSA-N 0.000 description 1
COTFQUPGWBMXMW-UHFFFAOYSA-N 4-(methylamino)butanamide Chemical compound CNCCCC(N)=O COTFQUPGWBMXMW-UHFFFAOYSA-N 0.000 description 1
RWLYIYZYVWCDJW-UHFFFAOYSA-N 4-(quinazolin-4-ylamino)phenol Chemical class C1=CC(O)=CC=C1NC1=NC=NC2=CC=CC=C12 RWLYIYZYVWCDJW-UHFFFAOYSA-N 0.000 description 1
BNDYIYYKEIXHNK-UHFFFAOYSA-N 4-[3-hydroxyanilino]-6,7-dimethoxyquinazoline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC(O)=C1 BNDYIYYKEIXHNK-UHFFFAOYSA-N 0.000 description 1
WCVPFJVXEXJFLB-UHFFFAOYSA-N 4-aminobutanamide Chemical group NCCCC(N)=O WCVPFJVXEXJFLB-UHFFFAOYSA-N 0.000 description 1
WIKQNBCDJYNKED-UHFFFAOYSA-N 4-chloro-6,7-dimethylquinazoline Chemical compound C1=NC(Cl)=C2C=C(C)C(C)=CC2=N1 WIKQNBCDJYNKED-UHFFFAOYSA-N 0.000 description 1
ZGIDAXLBBURWOL-UHFFFAOYSA-N 4-chloro-6-(trifluoromethoxy)quinazoline Chemical compound N1=CN=C(Cl)C2=CC(OC(F)(F)F)=CC=C21 ZGIDAXLBBURWOL-UHFFFAOYSA-N 0.000 description 1
MREJJMASIQVOTH-UHFFFAOYSA-N 4-chloro-6-methoxyquinazoline Chemical compound N1=CN=C(Cl)C2=CC(OC)=CC=C21 MREJJMASIQVOTH-UHFFFAOYSA-N 0.000 description 1
GUQZHZBMDPEBQG-UHFFFAOYSA-N 4-chloro-7-methoxyquinazoline Chemical compound ClC1=NC=NC2=CC(OC)=CC=C21 GUQZHZBMDPEBQG-UHFFFAOYSA-N 0.000 description 1
LOESDOAIWSCMKM-UHFFFAOYSA-N 4-hydroxybutanamide Chemical group NC(=O)CCCO LOESDOAIWSCMKM-UHFFFAOYSA-N 0.000 description 1
XJXBWJFUCWOLSY-UHFFFAOYSA-N 4-methoxybutanamide Chemical compound COCCCC(N)=O XJXBWJFUCWOLSY-UHFFFAOYSA-N 0.000 description 1
125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
SQSSULVYIBYQSG-UHFFFAOYSA-N 4-n-(3-methylphenyl)-7-methylsulfanylquinazoline-4,6-diamine Chemical compound C=12C=C(N)C(SC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 SQSSULVYIBYQSG-UHFFFAOYSA-N 0.000 description 1
WIEWJZVAKXFUTG-UHFFFAOYSA-N 4-n-(6,7-dimethoxyquinazolin-4-yl)benzene-1,4-diamine;hydrochloride Chemical compound Cl.C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=C(N)C=C1 WIEWJZVAKXFUTG-UHFFFAOYSA-N 0.000 description 1
UEALKTCRMBVTFN-UHFFFAOYSA-N 4-nitroanthranilic acid Chemical compound NC1=CC([N+]([O-])=O)=CC=C1C(O)=O UEALKTCRMBVTFN-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
AGQATLDTZCPZJT-UHFFFAOYSA-N 4-quinazolin-6-ylmorpholine Chemical compound C1COCCN1C1=CC=C(N=CN=C2)C2=C1 AGQATLDTZCPZJT-UHFFFAOYSA-N 0.000 description 1
YLZSNFZNVCUXMM-UHFFFAOYSA-N 5-morpholin-4-yl-2-nitrobenzoic acid Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(N2CCOCC2)=C1 YLZSNFZNVCUXMM-UHFFFAOYSA-N 0.000 description 1
RUCHWTKMOWXHLU-UHFFFAOYSA-N 5-nitroanthranilic acid Chemical compound NC1=CC=C([N+]([O-])=O)C=C1C(O)=O RUCHWTKMOWXHLU-UHFFFAOYSA-N 0.000 description 1
RHISQWTXRCBOBJ-UHFFFAOYSA-N 6,7,8-trimethoxyquinazoline Chemical class N1=CN=C2C(OC)=C(OC)C(OC)=CC2=C1 RHISQWTXRCBOBJ-UHFFFAOYSA-N 0.000 description 1
GQZJIWRQFUXHGZ-UHFFFAOYSA-N 6,7-bis(2-methoxyethoxy)-n-(3-methylphenyl)quinazolin-4-amine;hydrochloride Chemical compound Cl.C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 GQZJIWRQFUXHGZ-UHFFFAOYSA-N 0.000 description 1
NJPNKDPGKPSJPR-UHFFFAOYSA-N 6,7-dimethoxy-4-n-(3-methylphenyl)quinazoline-4,5-diamine Chemical compound C=12C(N)=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 NJPNKDPGKPSJPR-UHFFFAOYSA-N 0.000 description 1
JBTUFBGGRVLCFF-UHFFFAOYSA-N 6,7-dimethoxy-5-nitro-1h-quinazolin-4-one Chemical compound N1=CNC(=O)C2=C1C=C(OC)C(OC)=C2[N+]([O-])=O JBTUFBGGRVLCFF-UHFFFAOYSA-N 0.000 description 1
PBHYWXWANPMYSG-UHFFFAOYSA-N 6,7-dimethoxy-n-(3-methylphenyl)quinazolin-4-amine;hydrochloride Chemical compound Cl.C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 PBHYWXWANPMYSG-UHFFFAOYSA-N 0.000 description 1
KEQCEKUDWPXRRQ-UHFFFAOYSA-N 6,7-dimethoxy-n-[3-(trifluoromethyl)phenyl]quinazolin-4-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC(C(F)(F)F)=C1 KEQCEKUDWPXRRQ-UHFFFAOYSA-N 0.000 description 1
JRDRXNJUOHNEAQ-UHFFFAOYSA-N 6,7-dimethoxy-n-phenylquinazolin-4-amine;hydrochloride Chemical compound Cl.C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC=C1 JRDRXNJUOHNEAQ-UHFFFAOYSA-N 0.000 description 1
FYMQPWWNOCENRN-UHFFFAOYSA-N 6,7-dimethoxyquinazoline Chemical compound N1=CN=C2C=C(OC)C(OC)=CC2=C1 FYMQPWWNOCENRN-UHFFFAOYSA-N 0.000 description 1
POXXGTPTPULVDC-UHFFFAOYSA-N 6-(2-methoxyethoxy)-n-(3-methylphenyl)quinazolin-4-amine Chemical compound C12=CC(OCCOC)=CC=C2N=CN=C1NC1=CC=CC(C)=C1 POXXGTPTPULVDC-UHFFFAOYSA-N 0.000 description 1
YIWFXXWSEKDDJR-UHFFFAOYSA-N 6-(anilinomethyl)-n-(3-methylphenyl)quinazolin-4-amine Chemical compound CC1=CC=CC(NC=2C3=CC(CNC=4C=CC=CC=4)=CC=C3N=CN=2)=C1 YIWFXXWSEKDDJR-UHFFFAOYSA-N 0.000 description 1
OCAWACKWBYEOSN-UHFFFAOYSA-N 6-(methoxymethyl)-n-(3-methylphenyl)quinazolin-4-amine Chemical compound C12=CC(COC)=CC=C2N=CN=C1NC1=CC=CC(C)=C1 OCAWACKWBYEOSN-UHFFFAOYSA-N 0.000 description 1
JNYLMODTPLSLIF-UHFFFAOYSA-N 6-(trifluoromethyl)pyridine-3-carboxylic acid Chemical group OC(=O)C1=CC=C(C(F)(F)F)N=C1 JNYLMODTPLSLIF-UHFFFAOYSA-N 0.000 description 1
MBWSFACVGYJPPE-UHFFFAOYSA-N 6-[(dimethylamino)methyl]-n-(3-methylphenyl)quinazolin-4-amine Chemical compound C12=CC(CN(C)C)=CC=C2N=CN=C1NC1=CC=CC(C)=C1 MBWSFACVGYJPPE-UHFFFAOYSA-N 0.000 description 1
TVHKDIOQVKDWQQ-UHFFFAOYSA-N 6-[2-(dimethylamino)ethoxy]-n-(3-methylphenyl)quinazolin-4-amine;hydrobromide Chemical compound Br.C12=CC(OCCN(C)C)=CC=C2N=CN=C1NC1=CC=CC(C)=C1 TVHKDIOQVKDWQQ-UHFFFAOYSA-N 0.000 description 1
OJTOAMSTANUUMJ-UHFFFAOYSA-N 6-amino-1,3-benzodioxole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C(N)=CC2=C1OCO2 OJTOAMSTANUUMJ-UHFFFAOYSA-N 0.000 description 1
WWSGQFXMLMGYJK-UHFFFAOYSA-N 6-chloro-n-phenylquinazolin-4-amine Chemical class C12=CC(Cl)=CC=C2N=CN=C1NC1=CC=CC=C1 WWSGQFXMLMGYJK-UHFFFAOYSA-N 0.000 description 1
QJRNXXLTDWMENM-UHFFFAOYSA-N 6-hydroxy-1h-quinazolin-4-one Chemical compound N1C=NC(=O)C2=CC(O)=CC=C21 QJRNXXLTDWMENM-UHFFFAOYSA-N 0.000 description 1
KKAHSVDGWDURSJ-UHFFFAOYSA-N 6-methoxy-n-(3-methylphenyl)-7-(2-morpholin-4-ylethoxy)quinazolin-4-amine Chemical compound N1=CN=C2C=C(OCCN3CCOCC3)C(OC)=CC2=C1NC1=CC=CC(C)=C1 KKAHSVDGWDURSJ-UHFFFAOYSA-N 0.000 description 1
PWWZQDDEXXYYHZ-UHFFFAOYSA-N 6-methoxy-n-(3-methylphenyl)-7-propan-2-yloxyquinazolin-4-amine Chemical compound N1=CN=C2C=C(OC(C)C)C(OC)=CC2=C1NC1=CC=CC(C)=C1 PWWZQDDEXXYYHZ-UHFFFAOYSA-N 0.000 description 1
LNUACJNTNFFFCF-UHFFFAOYSA-N 6-morpholin-4-yl-1h-quinazolin-4-one Chemical compound C1=C2C(=O)NC=NC2=CC=C1N1CCOCC1 LNUACJNTNFFFCF-UHFFFAOYSA-N 0.000 description 1
IWBVCRRXSCJLQC-UHFFFAOYSA-N 6-n-methyl-4-n-(3-methylphenyl)quinazoline-4,6-diamine Chemical compound C12=CC(NC)=CC=C2N=CN=C1NC1=CC=CC(C)=C1 IWBVCRRXSCJLQC-UHFFFAOYSA-N 0.000 description 1
SVFHMJGZJXLEIF-UHFFFAOYSA-N 6-piperidin-1-yl-1h-quinazolin-4-one Chemical compound C1=C2C(=O)NC=NC2=CC=C1N1CCCCC1 SVFHMJGZJXLEIF-UHFFFAOYSA-N 0.000 description 1
ITFLBRGWNXCRFJ-UHFFFAOYSA-N 6-piperidin-1-ylquinazoline Chemical compound C1CCCCN1C1=CC=C(N=CN=C2)C2=C1 ITFLBRGWNXCRFJ-UHFFFAOYSA-N 0.000 description 1
NKLHAODPKDGWMZ-UHFFFAOYSA-N 7-(2-anilinoethoxy)-6-methoxy-n-(3-methylphenyl)quinazolin-4-amine Chemical compound N1=CN=C2C=C(OCCNC=3C=CC=CC=3)C(OC)=CC2=C1NC1=CC=CC(C)=C1 NKLHAODPKDGWMZ-UHFFFAOYSA-N 0.000 description 1
CZUUUCCKUDTMKH-UHFFFAOYSA-N 7-[2-(dimethylamino)ethoxy]-6-methoxy-n-(3-methylphenyl)quinazolin-4-amine Chemical compound N1=CN=C2C=C(OCCN(C)C)C(OC)=CC2=C1NC1=CC=CC(C)=C1 CZUUUCCKUDTMKH-UHFFFAOYSA-N 0.000 description 1
URDYTQYZXZKBQT-UHFFFAOYSA-N 7-chloro-6-nitro-1h-quinazolin-4-one Chemical compound N1C=NC(=O)C2=C1C=C(Cl)C([N+](=O)[O-])=C2 URDYTQYZXZKBQT-UHFFFAOYSA-N 0.000 description 1
NBVNEDHQRFJKCG-UHFFFAOYSA-N 7-n-methyl-4-n-(3-methylphenyl)-6-nitroquinazoline-4,7-diamine Chemical compound C=12C=C([N+]([O-])=O)C(NC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 NBVNEDHQRFJKCG-UHFFFAOYSA-N 0.000 description 1
DYEVXLNQIXWWDH-UHFFFAOYSA-N 7-n-methyl-4-n-(3-methylphenyl)quinazoline-4,6,7-triamine Chemical compound C=12C=C(N)C(NC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 DYEVXLNQIXWWDH-UHFFFAOYSA-N 0.000 description 1
RZCJSVRGPHXBSM-UHFFFAOYSA-N 8-chloro-[1,3]dioxolo[4,5-g]quinazoline Chemical compound C1=C2C(Cl)=NC=NC2=CC2=C1OCO2 RZCJSVRGPHXBSM-UHFFFAOYSA-N 0.000 description 1
MAORQWZHGHOAOK-UHFFFAOYSA-N 8-methoxyquinazoline Chemical class N1=CN=C2C(OC)=CC=CC2=C1 MAORQWZHGHOAOK-UHFFFAOYSA-N 0.000 description 1
RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
102000015790 Asparaginase Human genes 0.000 description 1
108010024976 Asparaginase Proteins 0.000 description 1
WOVKYSAHUYNSMH-UHFFFAOYSA-N BROMODEOXYURIDINE Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-UHFFFAOYSA-N 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
108010006654 Bleomycin Proteins 0.000 description 1
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
208000003174 Brain Neoplasms Diseases 0.000 description 1
238000010599 BrdU assay Methods 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
KZHSNCMVWMKZLU-UHFFFAOYSA-N CN(CCNNC(C(NCCCN(CC)CC)(NCCCN(C)C)NCCN(CC)CC)=O)C Chemical compound CN(CCNNC(C(NCCCN(CC)CC)(NCCCN(C)C)NCCN(CC)CC)=O)C KZHSNCMVWMKZLU-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
208000003495 Coccidiosis Diseases 0.000 description 1
206010009944 Colon cancer Diseases 0.000 description 1
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-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
208000009849 Female Genital Neoplasms Diseases 0.000 description 1
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
102000009465 Growth Factor Receptors Human genes 0.000 description 1
108010009202 Growth Factor Receptors Proteins 0.000 description 1
VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
102000014150 Interferons Human genes 0.000 description 1
108010050904 Interferons Proteins 0.000 description 1
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
206010023076 Isosporiasis Diseases 0.000 description 1
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
241000699660 Mus musculus Species 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 1
208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
239000012425 OXONE® Substances 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 1
208000015634 Rectal Neoplasms Diseases 0.000 description 1
KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 description 1
206010039491 Sarcoma Diseases 0.000 description 1
229940124639 Selective inhibitor Drugs 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
208000005718 Stomach Neoplasms Diseases 0.000 description 1
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
208000002495 Uterine Neoplasms Diseases 0.000 description 1
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
NYWDTNWEQNOENK-UHFFFAOYSA-N [1,3]dioxolo[4,5-h]quinazoline Chemical compound C1=NC=NC2=C(OCO3)C3=CC=C21 NYWDTNWEQNOENK-UHFFFAOYSA-N 0.000 description 1
AGIOYQIKFISKCK-UHFFFAOYSA-N [4-(3-methylanilino)quinazolin-7-yl]methanol Chemical compound CC1=CC=CC(NC=2C3=CC=C(CO)C=C3N=CN=2)=C1 AGIOYQIKFISKCK-UHFFFAOYSA-N 0.000 description 1
OECAAUNBQHKSFL-UHFFFAOYSA-N [6-methoxy-4-(3-methylanilino)quinazolin-7-yl] 2-methoxyacetate Chemical compound C=12C=C(OC)C(OC(=O)COC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 OECAAUNBQHKSFL-UHFFFAOYSA-N 0.000 description 1
230000003187 abdominal effect Effects 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000009471 action Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
150000001266 acyl halides Chemical class 0.000 description 1
125000004442 acylamino group Chemical group 0.000 description 1
229940009456 adriamycin Drugs 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
150000001348 alkyl chlorides Chemical class 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
GRKUXCWELVWVMZ-UHFFFAOYSA-N amino acetate Chemical group CC(=O)ON GRKUXCWELVWVMZ-UHFFFAOYSA-N 0.000 description 1
SDBCCDNTZKHGBJ-UHFFFAOYSA-N amino butanoate Chemical group CCCC(=O)ON SDBCCDNTZKHGBJ-UHFFFAOYSA-N 0.000 description 1
KTYVHLCLTPLSGC-UHFFFAOYSA-N amino propanoate Chemical group CCC(=O)ON KTYVHLCLTPLSGC-UHFFFAOYSA-N 0.000 description 1
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
230000000202 analgesic effect Effects 0.000 description 1
HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
230000003288 anthiarrhythmic effect Effects 0.000 description 1
230000002280 anti-androgenic effect Effects 0.000 description 1
230000003388 anti-hormonal effect Effects 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
230000000078 anti-malarial effect Effects 0.000 description 1
230000000340 anti-metabolite Effects 0.000 description 1
230000001775 anti-pathogenic effect Effects 0.000 description 1
239000000051 antiandrogen Substances 0.000 description 1
229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
238000011394 anticancer treatment Methods 0.000 description 1
229940100197 antimetabolite Drugs 0.000 description 1
239000002256 antimetabolite Substances 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
108010060350 arginyl-arginyl-leucyl-isoleucyl-glutamyl-aspartyl-alanyl-glutamyl-tyrosyl-alanyl-alanyl-arginyl-glycine Proteins 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
239000003849 aromatic solvent Substances 0.000 description 1
125000004104 aryloxy group Chemical group 0.000 description 1
229960003272 asparaginase Drugs 0.000 description 1
DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 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
VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
230000008901 benefit Effects 0.000 description 1
PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
125000005605 benzo group Chemical group 0.000 description 1
AQIHMSVIAGNIDM-UHFFFAOYSA-N benzoyl bromide Chemical compound BrC(=O)C1=CC=CC=C1 AQIHMSVIAGNIDM-UHFFFAOYSA-N 0.000 description 1
235000019400 benzoyl peroxide Nutrition 0.000 description 1
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
229940073608 benzyl chloride Drugs 0.000 description 1
RSDOASZYYCOXIB-UHFFFAOYSA-N beta-alaninamide Chemical group NCCC(N)=O RSDOASZYYCOXIB-UHFFFAOYSA-N 0.000 description 1
230000005540 biological transmission Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
229960001561 bleomycin Drugs 0.000 description 1
OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
210000000481 breast Anatomy 0.000 description 1
125000005997 bromomethyl group Chemical group 0.000 description 1
229950004398 broxuridine Drugs 0.000 description 1
239000000872 buffer Substances 0.000 description 1
244000309464 bull Species 0.000 description 1
DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 1
SNCZNSNPXMPCGN-UHFFFAOYSA-N butanediamide Chemical group NC(=O)CCC(N)=O SNCZNSNPXMPCGN-UHFFFAOYSA-N 0.000 description 1
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
229960004562 carboplatin Drugs 0.000 description 1
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
229940097647 casodex Drugs 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
230000008859 change Effects 0.000 description 1
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 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
229910052804 chromium Inorganic materials 0.000 description 1
239000011651 chromium Substances 0.000 description 1
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
229960004316 cisplatin Drugs 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
208000029742 colonic neoplasm Diseases 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000006071 cream Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000009109 curative therapy Methods 0.000 description 1
XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
239000002274 desiccant Substances 0.000 description 1
125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
239000000839 emulsion Substances 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
125000006627 ethoxycarbonylamino group Chemical group 0.000 description 1
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
UVSPVEYCSVXYBB-UHFFFAOYSA-N ethyl 3-amino-3-oxopropanoate Chemical compound CCOC(=O)CC(N)=O UVSPVEYCSVXYBB-UHFFFAOYSA-N 0.000 description 1
AJZOXCVIKHPZEU-UHFFFAOYSA-N ethyl 4-amino-4-oxobutanoate Chemical compound CCOC(=O)CCC(N)=O AJZOXCVIKHPZEU-UHFFFAOYSA-N 0.000 description 1
125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
125000006125 ethylsulfonyl group Chemical group 0.000 description 1
125000006351 ethylthiomethyl group Chemical group [H]C([H])([H])C([H])([H])SC([H])([H])* 0.000 description 1
VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
229960005420 etoposide Drugs 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
229960002949 fluorouracil Drugs 0.000 description 1
238000009472 formulation Methods 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000007789 gas Substances 0.000 description 1
206010017758 gastric cancer Diseases 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
230000014509 gene expression Effects 0.000 description 1
GTFMAONWNTUZEW-UHFFFAOYSA-N glutaramic acid Chemical group NC(=O)CCCC(O)=O GTFMAONWNTUZEW-UHFFFAOYSA-N 0.000 description 1
BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical group NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
229960001330 hydroxycarbamide Drugs 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
230000002055 immunohistochemical effect Effects 0.000 description 1
239000000367 immunologic factor Substances 0.000 description 1
238000011534 incubation Methods 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000012444 intercalating antibiotic Substances 0.000 description 1
229940079322 interferon Drugs 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
239000011630 iodine Substances 0.000 description 1
PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
150000002505 iron Chemical class 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-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
210000003734 kidney Anatomy 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
210000005265 lung cell Anatomy 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
230000036210 malignancy Effects 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
CGJMROBVSBIBKP-UHFFFAOYSA-N malonamic acid Chemical group NC(=O)CC(O)=O CGJMROBVSBIBKP-UHFFFAOYSA-N 0.000 description 1
WRIRWRKPLXCTFD-UHFFFAOYSA-N malonamide Chemical group NC(=O)CC(N)=O WRIRWRKPLXCTFD-UHFFFAOYSA-N 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000006626 methoxycarbonylamino group Chemical group 0.000 description 1
MOVBJUGHBJJKOW-UHFFFAOYSA-N methyl 2-amino-5-methoxybenzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1N MOVBJUGHBJJKOW-UHFFFAOYSA-N 0.000 description 1
LSNSJCKGQREPDW-UHFFFAOYSA-N methyl 3-amino-3-oxopropanoate Chemical compound COC(=O)CC(N)=O LSNSJCKGQREPDW-UHFFFAOYSA-N 0.000 description 1
MTLGWFNVNBMOFC-UHFFFAOYSA-N methyl 4-[[4-(3-methylanilino)quinazolin-6-yl]amino]-4-oxobutanoate Chemical compound C12=CC(NC(=O)CCC(=O)OC)=CC=C2N=CN=C1NC1=CC=CC(C)=C1 MTLGWFNVNBMOFC-UHFFFAOYSA-N 0.000 description 1
MQQJAAAEIQKHAG-UHFFFAOYSA-N methyl 4-[[4-(3-methylanilino)quinazolin-6-yl]amino]butanoate Chemical compound C12=CC(NCCCC(=O)OC)=CC=C2N=CN=C1NC1=CC=CC(C)=C1 MQQJAAAEIQKHAG-UHFFFAOYSA-N 0.000 description 1
HURZMSZDVGMYKJ-UHFFFAOYSA-N methyl 4-amino-4-oxobutanoate Chemical compound COC(=O)CCC(N)=O HURZMSZDVGMYKJ-UHFFFAOYSA-N 0.000 description 1
ZZUYIRISBMWFMV-UHFFFAOYSA-N methyl 4-chlorobutanoate Chemical compound COC(=O)CCCCl ZZUYIRISBMWFMV-UHFFFAOYSA-N 0.000 description 1
RUSVJCCYUALGPZ-UHFFFAOYSA-N methyl 4-oxo-1h-quinazoline-7-carboxylate Chemical compound N1C=NC(=O)C=2C1=CC(C(=O)OC)=CC=2 RUSVJCCYUALGPZ-UHFFFAOYSA-N 0.000 description 1
UAPJKEJWOPOJJY-UHFFFAOYSA-N methyl 5-methoxy-2-nitrobenzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1[N+]([O-])=O UAPJKEJWOPOJJY-UHFFFAOYSA-N 0.000 description 1
125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000000394 mitotic effect Effects 0.000 description 1
238000002703 mutagenesis Methods 0.000 description 1
231100000350 mutagenesis Toxicity 0.000 description 1
VFWKRMDOKBGBLF-UHFFFAOYSA-N n,n-dimethyl-4-(3-methylanilino)quinazoline-7-carboxamide Chemical compound N=1C=NC2=CC(C(=O)N(C)C)=CC=C2C=1NC1=CC=CC(C)=C1 VFWKRMDOKBGBLF-UHFFFAOYSA-N 0.000 description 1
XXVNQHJAVBZSFX-UHFFFAOYSA-N n-(3,4-dichlorophenyl)-6-piperidin-1-ylquinazolin-4-amine;hydrochloride Chemical compound Cl.C1=C(Cl)C(Cl)=CC=C1NC1=NC=NC2=CC=C(N3CCCCC3)C=C12 XXVNQHJAVBZSFX-UHFFFAOYSA-N 0.000 description 1
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 description 1
USAMIYATKINXLP-UHFFFAOYSA-N n-(3-chlorophenyl)-6-nitroquinazolin-4-amine Chemical compound C12=CC([N+](=O)[O-])=CC=C2N=CN=C1NC1=CC=CC(Cl)=C1 USAMIYATKINXLP-UHFFFAOYSA-N 0.000 description 1
MKLLQFMZATXPIU-UHFFFAOYSA-N n-(3-methylphenyl)-6-(methylsulfanylmethyl)quinazolin-4-amine Chemical compound C12=CC(CSC)=CC=C2N=CN=C1NC1=CC=CC(C)=C1 MKLLQFMZATXPIU-UHFFFAOYSA-N 0.000 description 1
LBRNXYNVMWRILO-UHFFFAOYSA-N n-(3-methylphenyl)-6-(morpholin-4-ylmethyl)quinazolin-4-amine Chemical compound CC1=CC=CC(NC=2C3=CC(CN4CCOCC4)=CC=C3N=CN=2)=C1 LBRNXYNVMWRILO-UHFFFAOYSA-N 0.000 description 1
QUQRGGIZFWJIKA-UHFFFAOYSA-N n-(3-methylphenyl)-6-(phenylsulfanylmethyl)quinazolin-4-amine Chemical compound CC1=CC=CC(NC=2C3=CC(CSC=4C=CC=CC=4)=CC=C3N=CN=2)=C1 QUQRGGIZFWJIKA-UHFFFAOYSA-N 0.000 description 1
YZOKGFVFCZZKBP-UHFFFAOYSA-N n-(3-methylphenyl)-6-(piperazin-1-ylmethyl)quinazolin-4-amine Chemical compound CC1=CC=CC(NC=2C3=CC(CN4CCNCC4)=CC=C3N=CN=2)=C1 YZOKGFVFCZZKBP-UHFFFAOYSA-N 0.000 description 1
USXLZROFUIENBM-UHFFFAOYSA-N n-(3-methylphenyl)-6-morpholin-4-ylquinazolin-4-amine;hydrochloride Chemical compound Cl.CC1=CC=CC(NC=2C3=CC(=CC=C3N=CN=2)N2CCOCC2)=C1 USXLZROFUIENBM-UHFFFAOYSA-N 0.000 description 1
JCKRUPOZHCVXTD-UHFFFAOYSA-N n-[3-[(6,7-dimethoxyquinazolin-4-yl)amino]phenyl]acetamide Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC(NC(C)=O)=C1 JCKRUPOZHCVXTD-UHFFFAOYSA-N 0.000 description 1
OWZVFFZPZXVPLM-UHFFFAOYSA-N n-[4-(3-chloroanilino)quinazolin-6-yl]acetamide Chemical compound C12=CC(NC(=O)C)=CC=C2N=CN=C1NC1=CC=CC(Cl)=C1 OWZVFFZPZXVPLM-UHFFFAOYSA-N 0.000 description 1
XMNDQZSHZWDRLT-UHFFFAOYSA-N n-[4-(3-methylanilino)quinazolin-7-yl]benzenesulfonamide Chemical compound CC1=CC=CC(NC=2C3=CC=C(NS(=O)(=O)C=4C=CC=CC=4)C=C3N=CN=2)=C1 XMNDQZSHZWDRLT-UHFFFAOYSA-N 0.000 description 1
JEZKOONZDJHDBD-UHFFFAOYSA-N n-[4-[3-(trifluoromethyl)anilino]quinazolin-6-yl]acetamide Chemical compound C12=CC(NC(=O)C)=CC=C2N=CN=C1NC1=CC=CC(C(F)(F)F)=C1 JEZKOONZDJHDBD-UHFFFAOYSA-N 0.000 description 1
SILYXJFZBRKOIH-UHFFFAOYSA-N n-[7-methoxy-4-(3-methylanilino)quinazolin-6-yl]hydroxylamine Chemical compound C=12C=C(NO)C(OC)=CC2=NC=NC=1NC1=CC=CC(C)=C1 SILYXJFZBRKOIH-UHFFFAOYSA-N 0.000 description 1
ANFDQKXMPFOSGL-UHFFFAOYSA-N n-methyl-n-phenylquinazolin-2-amine Chemical compound N=1C=C2C=CC=CC2=NC=1N(C)C1=CC=CC=C1 ANFDQKXMPFOSGL-UHFFFAOYSA-N 0.000 description 1
VCLXUEIYTZFLMO-UHFFFAOYSA-N n-methyl-n-phenylquinazolin-4-amine Chemical compound N=1C=NC2=CC=CC=C2C=1N(C)C1=CC=CC=C1 VCLXUEIYTZFLMO-UHFFFAOYSA-N 0.000 description 1
MTSNDBYBIZSILH-UHFFFAOYSA-N n-phenylquinazolin-4-amine Chemical compound N=1C=NC2=CC=CC=C2C=1NC1=CC=CC=C1 MTSNDBYBIZSILH-UHFFFAOYSA-N 0.000 description 1
229940085033 nolvadex Drugs 0.000 description 1
238000011580 nude mouse model Methods 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
229940127084 other anti-cancer agent Drugs 0.000 description 1
229940127075 other antimetabolite Drugs 0.000 description 1
230000002611 ovarian Effects 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000008188 pellet Substances 0.000 description 1
RCCYSVYHULFYHE-UHFFFAOYSA-N pentanediamide Chemical group NC(=O)CCCC(N)=O RCCYSVYHULFYHE-UHFFFAOYSA-N 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
229940080469 phosphocellulose Drugs 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
FJVZDOGVDJCCCR-UHFFFAOYSA-M potassium periodate Chemical compound [K+].[O-]I(=O)(=O)=O FJVZDOGVDJCCCR-UHFFFAOYSA-M 0.000 description 1
OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
238000012545 processing Methods 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000006628 propoxycarbonylamino group Chemical group 0.000 description 1
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
DRYRBWIFRVMRPV-UHFFFAOYSA-N quinazolin-4-amine Chemical class C1=CC=C2C(N)=NC=NC2=C1 DRYRBWIFRVMRPV-UHFFFAOYSA-N 0.000 description 1
BBPMVEXRMOAIKQ-UHFFFAOYSA-N quinazolin-6-ol Chemical compound N1=CN=CC2=CC(O)=CC=C21 BBPMVEXRMOAIKQ-UHFFFAOYSA-N 0.000 description 1
LNNRQIKKDKDFRV-UHFFFAOYSA-N quinazolin-8-ol Chemical class N1=CN=C2C(O)=CC=CC2=C1 LNNRQIKKDKDFRV-UHFFFAOYSA-N 0.000 description 1
ADYNJDNYIVZXNK-UHFFFAOYSA-N quinazoline;dihydrochloride Chemical compound Cl.Cl.N1=CN=CC2=CC=CC=C21 ADYNJDNYIVZXNK-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
229940124617 receptor tyrosine kinase inhibitor Drugs 0.000 description 1
206010038038 rectal cancer Diseases 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
201000001275 rectum cancer Diseases 0.000 description 1
230000010076 replication Effects 0.000 description 1
238000012502 risk assessment Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000013049 sediment Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
LHQPVHQIMISDRO-UHFFFAOYSA-N sodium;2-sulfanylethanol Chemical compound [Na].OCCS LHQPVHQIMISDRO-UHFFFAOYSA-N 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
206010041823 squamous cell carcinoma Diseases 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
201000011549 stomach cancer Diseases 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000005415 substituted alkoxy group Chemical group 0.000 description 1
JDVPQXZIJDEHAN-UHFFFAOYSA-N succinamic acid Chemical group NC(=O)CCC(O)=O JDVPQXZIJDEHAN-UHFFFAOYSA-N 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
239000000829 suppository Substances 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
229960001603 tamoxifen Drugs 0.000 description 1
238000003419 tautomerization reaction Methods 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000004149 thio group Chemical group *S* 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
201000002510 thyroid cancer Diseases 0.000 description 1
210000001685 thyroid gland Anatomy 0.000 description 1
208000013076 thyroid tumor Diseases 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
229940044693 topoisomerase inhibitor Drugs 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
KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 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
GFNNBHLJANVSQV-UHFFFAOYSA-N tyrphostin AG 1478 Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1 GFNNBHLJANVSQV-UHFFFAOYSA-N 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
206010046766 uterine cancer Diseases 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
238000005406 washing Methods 0.000 description 1