CS186391A3 - Pharmaceuticals - Google Patents

Info

Publication number

CS186391A3

CS186391A3 CS911863A CS186391A CS186391A3 CS 186391 A3 CS186391 A3 CS 186391A3 CS 911863 A CS911863 A CS 911863A CS 186391 A CS186391 A CS 186391A CS 186391 A3 CS186391 A3 CS 186391A3

Authority

CS

Czechoslovakia

Prior art keywords

methyl

group

amino

quinazolin

compound

Prior art date

1990-06-19

Links

• Espacenet
• Global Dossier
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• 239000003814 drug Substances 0.000 title description 7
• -1 wherein R 8 Chemical compound 0.000 claims description 311
• 150000001875 compounds Chemical class 0.000 claims description 248
• 238000000034 method Methods 0.000 claims description 131
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 127
• 238000002360 preparation method Methods 0.000 claims description 113
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 106
• 229910052757 nitrogen Inorganic materials 0.000 claims description 103
• 229910052739 hydrogen Inorganic materials 0.000 claims description 97
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 89
• 229910052799 carbon Inorganic materials 0.000 claims description 76
• UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 59
• 125000004432 carbon atom Chemical group C* 0.000 claims description 55
• 150000002148 esters Chemical class 0.000 claims description 49
• 239000001257 hydrogen Substances 0.000 claims description 47
• 239000002253 acid Substances 0.000 claims description 42
• 125000000217 alkyl group Chemical group 0.000 claims description 35
• 150000003839 salts Chemical class 0.000 claims description 35
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 33
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
• 229910052717 sulfur Inorganic materials 0.000 claims description 26
• 125000001424 substituent group Chemical group 0.000 claims description 25
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 23
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
• 125000005843 halogen group Chemical group 0.000 claims description 22
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
• 125000003118 aryl group Chemical group 0.000 claims description 21
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 19
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
• 125000001931 aliphatic group Chemical group 0.000 claims description 17
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
• 239000008194 pharmaceutical composition Substances 0.000 claims description 15
• 125000005605 benzo group Chemical group 0.000 claims description 14
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 11
• 206010028980 Neoplasm Diseases 0.000 claims description 11
• 125000003545 alkoxy group Chemical group 0.000 claims description 11
• 125000003277 amino group Chemical group 0.000 claims description 11
• 150000002431 hydrogen Chemical class 0.000 claims description 11
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
• 229910052736 halogen Inorganic materials 0.000 claims description 10
• 150000002367 halogens Chemical group 0.000 claims description 9
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
• DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 claims description 7
• 125000004429 atom Chemical group 0.000 claims description 7
• 125000000623 heterocyclic group Chemical group 0.000 claims description 6
• 229910052760 oxygen Inorganic materials 0.000 claims description 6
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 6
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 5
• 125000000539 amino acid group Chemical group 0.000 claims description 5
• ALDMAQRTQWQNEM-UHFFFAOYSA-N 4h-benzo[f]quinazolin-1-one Chemical compound C1=CC=CC2=C3C(=O)NC=NC3=CC=C21 ALDMAQRTQWQNEM-UHFFFAOYSA-N 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• 239000004471 Glycine Substances 0.000 claims description 3
• 150000001413 amino acids Chemical class 0.000 claims description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 125000002560 nitrile group Chemical group 0.000 claims description 3
• 239000002243 precursor Substances 0.000 claims description 3
• 125000002947 alkylene group Chemical group 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
• 125000006239 protecting group Chemical group 0.000 claims description 2
• 125000002252 acyl group Chemical group 0.000 claims 2
• 125000001302 tertiary amino group Chemical group 0.000 claims 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
• UIUJIQZEACWQSV-UHFFFAOYSA-M 4-oxobutanoate Chemical compound [O-]C(=O)CCC=O UIUJIQZEACWQSV-UHFFFAOYSA-M 0.000 claims 1
• 125000000837 carbohydrate group Chemical group 0.000 claims 1
• 125000005243 carbonyl alkyl group Chemical group 0.000 claims 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims 1
• 125000000547 substituted alkyl group Chemical group 0.000 claims 1
• 239000000243 solution Substances 0.000 description 256
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 219
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 186
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 178
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 177
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 156
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 139
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 132
• 239000007787 solid Substances 0.000 description 129
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 129
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 125
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 124
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 117
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 107
• 239000000203 mixture Substances 0.000 description 99
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 96
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 86
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 75
• 239000011541 reaction mixture Substances 0.000 description 74
• 239000000741 silica gel Substances 0.000 description 74
• 229910002027 silica gel Inorganic materials 0.000 description 74
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 54
• 239000000725 suspension Substances 0.000 description 54
• 229960002989 glutamic acid Drugs 0.000 description 51
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 49
• 238000004519 manufacturing process Methods 0.000 description 49
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 47
• 238000001819 mass spectrum Methods 0.000 description 46
• 238000010992 reflux Methods 0.000 description 42
• 229960000583 acetic acid Drugs 0.000 description 40
• 238000004587 chromatography analysis Methods 0.000 description 34
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 33
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 32
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
• 238000006243 chemical reaction Methods 0.000 description 30
• 238000003756 stirring Methods 0.000 description 27
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 25
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
• 239000002244 precipitate Substances 0.000 description 25
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 24
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
• 238000004458 analytical method Methods 0.000 description 21
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 21
• 238000001816 cooling Methods 0.000 description 19
• 239000012299 nitrogen atmosphere Substances 0.000 description 19
• 239000003921 oil Substances 0.000 description 19
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
• 239000000706 filtrate Substances 0.000 description 18
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 18
• 238000002844 melting Methods 0.000 description 17
• 230000008018 melting Effects 0.000 description 17
• 238000001914 filtration Methods 0.000 description 16
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 16
• 125000001246 bromo group Chemical group Br* 0.000 description 15
• 238000004113 cell culture Methods 0.000 description 15
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
• 235000019341 magnesium sulphate Nutrition 0.000 description 15
• 238000005481 NMR spectroscopy Methods 0.000 description 14
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
• 231100000135 cytotoxicity Toxicity 0.000 description 14
• 230000003013 cytotoxicity Effects 0.000 description 14
• 239000012298 atmosphere Substances 0.000 description 13
• 229910000027 potassium carbonate Inorganic materials 0.000 description 13
• 235000011181 potassium carbonates Nutrition 0.000 description 13
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
• 210000004881 tumor cell Anatomy 0.000 description 13
• 239000002904 solvent Substances 0.000 description 12
• 238000000921 elemental analysis Methods 0.000 description 11
• 239000010410 layer Substances 0.000 description 11
• 238000000746 purification Methods 0.000 description 11
• 229920002554 vinyl polymer Polymers 0.000 description 11
• PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 description 10
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 10
• 239000005711 Benzoic acid Substances 0.000 description 10
• 102000004190 Enzymes Human genes 0.000 description 10
• 108090000790 Enzymes Proteins 0.000 description 10
• 239000012043 crude product Substances 0.000 description 10
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 10
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 235000010233 benzoic acid Nutrition 0.000 description 9
• 238000009835 boiling Methods 0.000 description 9
• 239000000460 chlorine Substances 0.000 description 9
• 125000001309 chloro group Chemical group Cl* 0.000 description 9
• 239000000543 intermediate Substances 0.000 description 9
• 229940124530 sulfonamide Drugs 0.000 description 9
• 241000124008 Mammalia Species 0.000 description 8
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
• 239000002585 base Substances 0.000 description 8
• 229910052794 bromium Inorganic materials 0.000 description 8
• 210000004027 cell Anatomy 0.000 description 8
• 150000005690 diesters Chemical class 0.000 description 8
• SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 8
• 238000001704 evaporation Methods 0.000 description 8
• 230000007062 hydrolysis Effects 0.000 description 8
• 238000006460 hydrolysis reaction Methods 0.000 description 8
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
• JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 7
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
• 239000004220 glutamic acid Substances 0.000 description 7
• 239000000047 product Substances 0.000 description 7
• 239000012312 sodium hydride Substances 0.000 description 7
• 229910000104 sodium hydride Inorganic materials 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 7
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 6
• GTKPIWUKWQTDQU-UHFFFAOYSA-N 9-(bromomethyl)-3-methyl-4h-benzo[f]quinazolin-1-one Chemical compound C1=CC(CBr)=CC2=C(C(=O)NC(C)=N3)C3=CC=C21 GTKPIWUKWQTDQU-UHFFFAOYSA-N 0.000 description 6
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
• 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 6
• 241001465754 Metazoa Species 0.000 description 6
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
• 239000004480 active ingredient Substances 0.000 description 6
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 6
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 6
• 239000003054 catalyst Substances 0.000 description 6
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 6
• 230000008020 evaporation Effects 0.000 description 6
• 229910052731 fluorine Inorganic materials 0.000 description 6
• 239000012362 glacial acetic acid Substances 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 239000002609 medium Substances 0.000 description 6
• 238000010898 silica gel chromatography Methods 0.000 description 6
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
• 238000001228 spectrum Methods 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 5
• YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 5
• KCKZIWSINLBROE-UHFFFAOYSA-N 3,4-dihydro-1h-naphthalen-2-one Chemical class C1=CC=C2CC(=O)CCC2=C1 KCKZIWSINLBROE-UHFFFAOYSA-N 0.000 description 5
• GTCLUWHIGIAUGO-UHFFFAOYSA-N 3-amino-9-bromo-4h-benzo[f]quinazolin-1-one Chemical compound C1=CC(Br)=CC2=C(C(=O)NC(N)=N3)C3=CC=C21 GTCLUWHIGIAUGO-UHFFFAOYSA-N 0.000 description 5
• SGFQSLFNJLMDQX-UHFFFAOYSA-N 3-methyl-1-oxo-5,6-dihydro-4h-benzo[f]quinazoline-9-sulfonyl chloride Chemical compound C1CC2=CC=C(S(Cl)(=O)=O)C=C2C2=C1N=C(C)NC2=O SGFQSLFNJLMDQX-UHFFFAOYSA-N 0.000 description 5
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 5
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
• 108010022394 Threonine synthase Proteins 0.000 description 5
• 102000005497 Thymidylate Synthase Human genes 0.000 description 5
• 230000002378 acidificating effect Effects 0.000 description 5
• PQIUGRLKNKSKTC-UHFFFAOYSA-N benzo[h]quinazoline Chemical compound N1=CN=C2C3=CC=CC=C3C=CC2=C1 PQIUGRLKNKSKTC-UHFFFAOYSA-N 0.000 description 5
• 229910052801 chlorine Inorganic materials 0.000 description 5
• XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 5
• 238000001035 drying Methods 0.000 description 5
• 210000002950 fibroblast Anatomy 0.000 description 5
• 239000007789 gas Substances 0.000 description 5
• 238000010438 heat treatment Methods 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 229910052740 iodine Inorganic materials 0.000 description 5
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 5
• 239000011734 sodium Substances 0.000 description 5
• 229910052708 sodium Inorganic materials 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• AKYCOAMUNLESIH-UHFFFAOYSA-N 2-(3-methylsulfanylphenyl)acetic acid Chemical compound CSC1=CC=CC(CC(O)=O)=C1 AKYCOAMUNLESIH-UHFFFAOYSA-N 0.000 description 4
• VLQLJPWPRYUYMK-UHFFFAOYSA-N 2-(3-phenylphenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(C=2C=CC=CC=2)=C1 VLQLJPWPRYUYMK-UHFFFAOYSA-N 0.000 description 4
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
• KLZFQYOHEQUBIA-UHFFFAOYSA-N 3,9-dimethyl-4h-benzo[f]quinazolin-1-one Chemical compound N1=C(C)NC(=O)C2=C1C=CC1=CC=C(C)C=C12 KLZFQYOHEQUBIA-UHFFFAOYSA-N 0.000 description 4
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