DK166621B1 - 4-oxo-6-aminomethyl-quinazolinderivater, fremgangsmaade til fremstilling heraf, farmaceutisk middel omfattende dem og anvendelse af dem til fremstilling af laegemidler til behandling af tumorer - Google Patents

4-oxo-6-aminomethyl-quinazolinderivater, fremgangsmaade til fremstilling heraf, farmaceutisk middel omfattende dem og anvendelse af dem til fremstilling af laegemidler til behandling af tumorer Download PDF

Info

Publication number: DK166621B1
Authority: DK; Denmark
Prior art keywords: amino; methyl; dihydro; hydroxy; group
Prior art date: 1986-03-27

Application number

DK155087A

Other languages

Danish (da)

English (en)

Other versions

DK155087D0 (da

DK155087A (da

Inventor

Leslie Richard Hughes

Original Assignee

Ici Plc

Nat Res Dev

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1986-03-27

Filing date

1987-03-26

Publication date

1993-06-21

1987-03-26 Application filed by Ici Plc, Nat Res Dev filed Critical Ici Plc

1987-03-26 Publication of DK155087D0 publication Critical patent/DK155087D0/da

1987-09-28 Publication of DK155087A publication Critical patent/DK155087A/da

1993-06-21 Application granted granted Critical

1993-06-21 Publication of DK166621B1 publication Critical patent/DK166621B1/da

Links

238000000034 method Methods 0.000 title claims description 84
206010028980 Neoplasm Diseases 0.000 title claims description 8
238000004519 manufacturing process Methods 0.000 title claims description 3
GXIWDAZXYHOCMK-UHFFFAOYSA-N 6-(aminomethyl)-1h-quinazolin-4-one Chemical class N1C=NC(=O)C2=CC(CN)=CC=C21 GXIWDAZXYHOCMK-UHFFFAOYSA-N 0.000 title description 3
239000008194 pharmaceutical composition Substances 0.000 title description 2
-1 hydroxy, mercapto Chemical class 0.000 claims description 268
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 67
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 56
150000001875 compounds Chemical class 0.000 claims description 54
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 46
125000006239 protecting group Chemical group 0.000 claims description 45
229960002989 glutamic acid Drugs 0.000 claims description 35
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 34
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 33
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 29
LPJXPACOXRZCCP-VIFPVBQESA-N (2s)-2-benzamidopentanedioic acid Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)C1=CC=CC=C1 LPJXPACOXRZCCP-VIFPVBQESA-N 0.000 claims description 26
125000004432 carbon atom Chemical group C* 0.000 claims description 26
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 24
238000002360 preparation method Methods 0.000 claims description 24
238000006243 chemical reaction Methods 0.000 claims description 23
239000002253 acid Substances 0.000 claims description 22
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 22
125000003545 alkoxy group Chemical group 0.000 claims description 20
125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 17
239000001257 hydrogen Substances 0.000 claims description 16
229910052739 hydrogen Inorganic materials 0.000 claims description 16
150000002148 esters Chemical class 0.000 claims description 15
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 14
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 13
125000004103 aminoalkyl group Chemical group 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 11
125000004414 alkyl thio group Chemical group 0.000 claims description 11
125000004181 carboxyalkyl group Chemical group 0.000 claims description 11
150000002367 halogens Chemical class 0.000 claims description 11
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 10
230000007062 hydrolysis Effects 0.000 claims description 10
238000006460 hydrolysis reaction Methods 0.000 claims description 10
150000003246 quinazolines Chemical class 0.000 claims description 10
150000003839 salts Chemical class 0.000 claims description 10
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 8
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 8
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 7
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 6
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 6
AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims description 6
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229960005261 aspartic acid Drugs 0.000 claims description 6
125000003709 fluoroalkyl group Chemical group 0.000 claims description 6
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 6
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 5
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125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 claims description 5
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 5
239000011737 fluorine Substances 0.000 claims description 5
229910052731 fluorine Inorganic materials 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
239000004471 Glycine Substances 0.000 claims description 4
241001465754 Metazoa Species 0.000 claims description 4
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
125000005236 alkanoylamino group Chemical group 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 4
125000000304 alkynyl group Chemical group 0.000 claims description 4
229940024606 amino acid Drugs 0.000 claims description 4
150000001413 amino acids Chemical class 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 4
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
229960003104 ornithine Drugs 0.000 claims description 4
239000008177 pharmaceutical agent Substances 0.000 claims description 4
229960001153 serine Drugs 0.000 claims description 4
QDGAVODICPCDMU-UHFFFAOYSA-N 2-amino-3-[3-[bis(2-chloroethyl)amino]phenyl]propanoic acid Chemical compound OC(=O)C(N)CC1=CC=CC(N(CCCl)CCCl)=C1 QDGAVODICPCDMU-UHFFFAOYSA-N 0.000 claims description 3
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 claims description 3
QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 3
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 3
AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims description 3
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 3
229960003767 alanine Drugs 0.000 claims description 3
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
125000003277 amino group Chemical group 0.000 claims description 3
125000005242 carbamoyl alkyl group Chemical group 0.000 claims description 3
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
125000004966 cyanoalkyl group Chemical group 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
229960002449 glycine Drugs 0.000 claims description 3
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 claims description 2
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
150000001350 alkyl halides Chemical class 0.000 claims description 2
125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 2
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 2
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 6
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 3
125000005449 2-fluoro-1,4-phenylene group Chemical group [H]C1=C([*:2])C([H])=C(F)C([*:1])=C1[H] 0.000 claims 1
125000001931 aliphatic group Chemical group 0.000 claims 1
125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 claims 1
PJPOCNJHYFUPCE-UHFFFAOYSA-N picen-1-ol Chemical compound C1=CC=CC2=C(C=CC=3C4=CC=C5C=CC=C(C=35)O)C4=CC=C21 PJPOCNJHYFUPCE-UHFFFAOYSA-N 0.000 claims 1
238000007789 sealing Methods 0.000 claims 1
239000000203 mixture Substances 0.000 description 188
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 168
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 144
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 94
229910001868 water Inorganic materials 0.000 description 86
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 81
239000000243 solution Substances 0.000 description 69
239000007858 starting material Substances 0.000 description 62
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 58
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 54
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 45
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 43
239000000047 product Substances 0.000 description 43
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
230000008018 melting Effects 0.000 description 40
238000002844 melting Methods 0.000 description 40
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
238000004587 chromatography analysis Methods 0.000 description 38
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 37
239000000741 silica gel Substances 0.000 description 37
229910002027 silica gel Inorganic materials 0.000 description 37
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 36
239000003480 eluent Substances 0.000 description 36
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
229910052943 magnesium sulfate Inorganic materials 0.000 description 27
235000019341 magnesium sulphate Nutrition 0.000 description 27
239000000284 extract Substances 0.000 description 26
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
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UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
238000000921 elemental analysis Methods 0.000 description 16
YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 16
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YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
125000003118 aryl group Chemical group 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 14
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 14
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 12
YAHALGNQKDVJLJ-UHFFFAOYSA-N 6-(bromomethyl)-2-methyl-1h-quinazolin-4-one Chemical compound BrCC1=CC=C2NC(C)=NC(=O)C2=C1 YAHALGNQKDVJLJ-UHFFFAOYSA-N 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
239000011780 sodium chloride Substances 0.000 description 12
HERPVHLYIHBEFW-ZETCQYMHSA-N diethyl (2s)-2-aminopentanedioate Chemical compound CCOC(=O)CC[C@H](N)C(=O)OCC HERPVHLYIHBEFW-ZETCQYMHSA-N 0.000 description 11
239000002585 base Substances 0.000 description 10
WSEQLMQNPBNMSL-FJXQXJEOSA-N diethyl (2s)-2-aminopentanedioate;hydron;chloride Chemical compound Cl.CCOC(=O)CC[C@H](N)C(=O)OCC WSEQLMQNPBNMSL-FJXQXJEOSA-N 0.000 description 10
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 10
150000002500 ions Chemical class 0.000 description 10
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
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239000012300 argon atmosphere Substances 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
229910052938 sodium sulfate Inorganic materials 0.000 description 9
235000011152 sodium sulphate Nutrition 0.000 description 9
238000004949 mass spectrometry Methods 0.000 description 8
238000001819 mass spectrum Methods 0.000 description 8
150000004682 monohydrates Chemical class 0.000 description 8
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 8
238000000746 purification Methods 0.000 description 8
238000010992 reflux Methods 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
LTKHPMDRMUCUEB-IBGZPJMESA-N CB3717 Chemical compound C=1C=C2NC(N)=NC(=O)C2=CC=1CN(CC#C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 LTKHPMDRMUCUEB-IBGZPJMESA-N 0.000 description 7
229910000019 calcium carbonate Inorganic materials 0.000 description 7
239000003921 oil Substances 0.000 description 7
239000000126 substance Substances 0.000 description 7
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AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical compound C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 description 6
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
239000000460 chlorine Substances 0.000 description 6
229940049906 glutamate Drugs 0.000 description 6
230000002401 inhibitory effect Effects 0.000 description 6
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SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
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201000011510 cancer Diseases 0.000 description 5
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 5
150000002431 hydrogen Chemical class 0.000 description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
VZDVVLXYAOVNRW-UHFFFAOYSA-N 2,4-dichloro-6-methylquinazoline Chemical compound N1=C(Cl)N=C(Cl)C2=CC(C)=CC=C21 VZDVVLXYAOVNRW-UHFFFAOYSA-N 0.000 description 4
BPCKZQCTLCTDST-UHFFFAOYSA-N 4-nitro-2-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1C(F)(F)F BPCKZQCTLCTDST-UHFFFAOYSA-N 0.000 description 4
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ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
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FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
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235000019400 benzoyl peroxide Nutrition 0.000 description 4
238000005119 centrifugation Methods 0.000 description 4
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230000000694 effects Effects 0.000 description 4
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125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 4
150000007524 organic acids Chemical class 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
239000000725 suspension Substances 0.000 description 4
125000003396 thiol group Chemical group [H]S* 0.000 description 4
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DFLNOERYMJLPGK-UHFFFAOYSA-N n-[(6-methyl-4-oxo-1h-quinazolin-2-yl)methyl]acetamide Chemical compound C1=C(C)C=C2C(=O)NC(CNC(=O)C)=NC2=C1 DFLNOERYMJLPGK-UHFFFAOYSA-N 0.000 description 1
RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
239000002674 ointment Substances 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
229940127075 other antimetabolite Drugs 0.000 description 1
WYMSBXTXOHUIGT-UHFFFAOYSA-N paraoxon Chemical compound CCOP(=O)(OCC)OC1=CC=C([N+]([O-])=O)C=C1 WYMSBXTXOHUIGT-UHFFFAOYSA-N 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
229940081066 picolinic acid Drugs 0.000 description 1
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920002643 polyglutamic acid Polymers 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
229940080818 propionamide Drugs 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000012265 solid product Substances 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
125000005415 substituted alkoxy group Chemical group 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
239000000829 suppository Substances 0.000 description 1
KZDKDSWGCFVJCE-ZETCQYMHSA-N tert-butyl (2s)-2,5-diaminopentanoate Chemical compound CC(C)(C)OC(=O)[C@@H](N)CCCN KZDKDSWGCFVJCE-ZETCQYMHSA-N 0.000 description 1
LCZVKKUAUWQDPX-UHFFFAOYSA-N tert-butyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]ethyl]amino]acetate Chemical compound CC(=O)OC1=CC=CC=C1CN(CC(=O)OC(C)(C)C)CCN(CC(=O)OC(C)(C)C)CC1=CC=CC=C1OC(C)=O LCZVKKUAUWQDPX-UHFFFAOYSA-N 0.000 description 1
KJHXSOOIOVLNPZ-UHFFFAOYSA-N tert-butyl thiophene-2-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CC=CS1 KJHXSOOIOVLNPZ-UHFFFAOYSA-N 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
VCZQFJFZMMALHB-UHFFFAOYSA-N tetraethylsilane Chemical compound CC[Si](CC)(CC)CC VCZQFJFZMMALHB-UHFFFAOYSA-N 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
229940044693 topoisomerase inhibitor Drugs 0.000 description 1
229960004295 valine Drugs 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
229910052724 xenon Inorganic materials 0.000 description 1
FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/90—Oxygen atoms with acyclic radicals attached in position 2 or 3
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
- C07D239/96—Two oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

DK155087A 1986-03-27 1987-03-26 4-oxo-6-aminomethyl-quinazolinderivater, fremgangsmaade til fremstilling heraf, farmaceutisk middel omfattende dem og anvendelse af dem til fremstilling af laegemidler til behandling af tumorer DK166621B1 (da)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB868607683A GB8607683D0 (en)	1986-03-27	1986-03-27	Anti-tumor agents
GB8607683		1986-03-27

Publications (3)

Publication Number	Publication Date
DK155087D0 DK155087D0 (da)	1987-03-26
DK155087A DK155087A (da)	1987-09-28
DK166621B1 true DK166621B1 (da)	1993-06-21

Family

ID=10595358

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK155087A DK166621B1 (da)	1986-03-27	1987-03-26	4-oxo-6-aminomethyl-quinazolinderivater, fremgangsmaade til fremstilling heraf, farmaceutisk middel omfattende dem og anvendelse af dem til fremstilling af laegemidler til behandling af tumorer

Country Status (22)

Country	Link
US (2)	US4992550A (fr)
EP (1)	EP0239362B1 (fr)
JP (1)	JPH0657699B2 (fr)
AR (1)	AR244213A1 (fr)
AT (1)	ATE70057T1 (fr)
AU (1)	AU592628B2 (fr)
CA (1)	CA1285943C (fr)
DE (1)	DE3774909D1 (fr)
DK (1)	DK166621B1 (fr)
ES (1)	ES2038170T3 (fr)
FI (1)	FI89912C (fr)
GB (2)	GB8607683D0 (fr)
GR (1)	GR3003282T3 (fr)
HK (1)	HK8594A (fr)
HU (1)	HU197317B (fr)
IE (1)	IE60302B1 (fr)
IL (1)	IL81924A (fr)
LU (1)	LU88797I2 (fr)
NL (1)	NL970024I2 (fr)
NO (2)	NO173545C (fr)
PT (1)	PT84571B (fr)
ZA (1)	ZA871998B (fr)

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1986
- 1986-03-27 GB GB868607683A patent/GB8607683D0/en active Pending
1987
- 1987-03-16 FI FI871139A patent/FI89912C/fi not_active IP Right Cessation
- 1987-03-16 IE IE69987A patent/IE60302B1/en not_active IP Right Cessation
- 1987-03-18 ZA ZA871998A patent/ZA871998B/xx unknown
- 1987-03-18 IL IL81924A patent/IL81924A/xx not_active IP Right Cessation
- 1987-03-20 AU AU70472/87A patent/AU592628B2/en not_active Expired
- 1987-03-24 GB GB8706948A patent/GB2188319B/en not_active Expired
- 1987-03-24 AT AT87302525T patent/ATE70057T1/de active
- 1987-03-24 LU LU88797C patent/LU88797I2/fr unknown
- 1987-03-24 DE DE8787302525T patent/DE3774909D1/de not_active Expired - Lifetime
- 1987-03-24 ES ES198787302525T patent/ES2038170T3/es not_active Expired - Lifetime
- 1987-03-24 EP EP87302525A patent/EP0239362B1/fr not_active Expired - Lifetime
- 1987-03-26 DK DK155087A patent/DK166621B1/da not_active IP Right Cessation
- 1987-03-26 NO NO871266A patent/NO173545C/no unknown
- 1987-03-26 CA CA000533035A patent/CA1285943C/fr not_active Expired - Lifetime
- 1987-03-26 PT PT84571A patent/PT84571B/pt unknown
- 1987-03-27 AR AR87307137A patent/AR244213A1/es active
- 1987-03-27 JP JP62071960A patent/JPH0657699B2/ja not_active Expired - Lifetime
- 1987-03-27 HU HU871343A patent/HU197317B/hu unknown
1989
- 1989-04-06 US US07/334,748 patent/US4992550A/en not_active Expired - Lifetime
1990
- 1990-09-05 US US07/577,579 patent/US5081124A/en not_active Expired - Lifetime
1991
- 1991-12-05 GR GR91401138T patent/GR3003282T3/el unknown
1994
- 1994-01-21 HK HK85/94A patent/HK8594A/en not_active IP Right Cessation
1997
- 1997-07-07 NL NL970024C patent/NL970024I2/nl unknown
1998
- 1998-09-08 NO NO1998020C patent/NO1998020I1/no unknown

Also Published As

Publication number	Publication date
GB2188319B (en)	1989-12-13
FI89912B (fi)	1993-08-31
DE3774909D1 (de)	1992-01-16
NO1998020I1 (no)	1998-09-28
DK155087D0 (da)	1987-03-26
EP0239362A2 (fr)	1987-09-30
NO173545C (no)	1993-12-29
NL970024I2 (nl)	1997-10-01
CA1285943C (fr)	1991-07-09
LU88797I2 (fr)	1996-11-05
ES2038170T3 (es)	1993-07-16
DK155087A (da)	1987-09-28
HU197317B (en)	1989-03-28
NO173545B (no)	1993-09-20
JPH01125373A (ja)	1989-05-17
IE60302B1 (en)	1994-06-29
ZA871998B (en)	1987-11-25
NO871266D0 (no)	1987-03-26
PT84571B (pt)	1989-11-30
FI871139A0 (fi)	1987-03-16
NL970024I1 (nl)	1997-09-01
FI89912C (fi)	1993-12-10
HUT43835A (en)	1987-12-28
GB8706948D0 (en)	1987-04-29
GB8607683D0 (en)	1986-04-30
EP0239362B1 (fr)	1991-12-04
GB2188319A (en)	1987-09-30
AR244213A1 (es)	1993-10-29
FI871139A7 (fi)	1987-09-28
JPH0657699B2 (ja)	1994-08-03
IE870699L (en)	1987-09-27
US5081124A (en)	1992-01-14
ATE70057T1 (de)	1991-12-15
NO871266L (no)	1987-09-28
GR3003282T3 (en)	1993-02-17
US4992550A (en)	1991-02-12
AU592628B2 (en)	1990-01-18
PT84571A (en)	1987-04-01
AU7047287A (en)	1987-10-01
EP0239362A3 (en)	1989-07-05
IL81924A (en)	1991-07-18
HK8594A (en)	1994-02-04

Legal Events

Date	Code	Title
1993-06-21	B1	Patent granted (law 1993)
2001-06-25	PUP	Patent expired
2007-04-10	PUP	Patent expired

Publication	Publication Date	Title
DK166621B1 (da)	1993-06-21	4-oxo-6-aminomethyl-quinazolinderivater, fremgangsmaade til fremstilling heraf, farmaceutisk middel omfattende dem og anvendelse af dem til fremstilling af laegemidler til behandling af tumorer
US5187167A (en)	1993-02-16	Pharmaceutical compositions comprising quinazolin-4-one derivatives
DK167013B1 (da)	1993-08-16	4-oxo-6-aminomethyl-quinazolinderivater,fremgangsmaade til fremstilling deraf, farmaceutiske midler indeholdende disse samt anvendelse af disse til fremstilling af laegemidler til behandling af tumorer
KR100226114B1 (ko)	1999-10-15	항증식 작용을 가진 퀴나졸린 화합물
JP3160111B2 (ja)	2001-04-23	キナゾリン誘導体、その製造法および該化合物を含有する、温血動物中に抗腫瘍作用を生じさせるための医薬調剤
EP0318225B1 (fr)	1994-03-16	Dérivés de la 6-arylaminométhylquinoléine et leur utilisation comme agents antitumoraux
JP6090801B2 (ja)	2017-03-08	キナーゼ阻害剤としてのアミノキナゾリン
IE61566B1 (en)	1994-11-16	Anti-tumour 4-oxoquinazoline derivatives
TW200806667A (en)	2008-02-01	New compounds
ES2905985T3 (es)	2022-04-12	Compuesto de oxazino-quinazolina y de tipo oxazino-quinazolina, método de preparación y usos de los mismos
AU2022475622A1 (en)	2024-11-14	5-pyridine-1h-indazole compound, pharmaceutical composition, and use
ITMI20082336A1 (it)	2010-06-30	Composti inibitori irreversibili di egfr con attivita' antiproliferativa
EP0365763A1 (fr)	1990-05-02	Composés cycliques antiproléfératifs
US5395838A (en)	1995-03-07	6-substituted quinazolines processing anti-tumor activity
CN117567473B (zh)	2025-07-04	一种靶向同源二聚体的抑制剂及其制备方法与应用
WO1994003439A1 (fr)	1994-02-17	Composes tricycliques a activite antiproliferatrice
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