CS186391A3 - Pharmaceuticals - Google Patents

Pharmaceuticals Download PDF

Info

Publication number: CS186391A3
Authority: CS; Czechoslovakia
Prior art keywords: methyl; group; amino; quinazolin; compound
Prior art date: 1990-06-19

Application number

CS911863A

Other languages

Czech (cs)

English (en)

Inventor

William Pendergast

Scott Howard Dickerson

Julius Vass Johnson

Robert Ferone

Original Assignee

Wellcome Found

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.)

1990-06-19

Filing date

1991-06-18

Publication date

1992-04-15

1991-06-18 Application filed by Wellcome Found filed Critical Wellcome Found

1992-04-15 Publication of CS186391A3 publication Critical patent/CS186391A3/cs

Links

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
VQHCXCBRGLBXBR-UHFFFAOYSA-N 3-amino-9-bromo-10-nitro-4h-benzo[f]quinazolin-1-one Chemical compound C1=C(Br)C([N+]([O-])=O)=C2C3=C(O)N=C(N)N=C3C=CC2=C1 VQHCXCBRGLBXBR-UHFFFAOYSA-N 0.000 description 4
MSPDOIDTGBVYAT-UHFFFAOYSA-N 3-amino-9-ethynyl-4h-benzo[f]quinazolin-1-one Chemical compound C1=CC(C#C)=CC2=C(C(=O)NC(N)=N3)C3=CC=C21 MSPDOIDTGBVYAT-UHFFFAOYSA-N 0.000 description 4
VSYKXHCYXBLHGV-UHFFFAOYSA-N 7-ethynyl-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1=C(C#C)C=C2CC(=O)CCC2=C1 VSYKXHCYXBLHGV-UHFFFAOYSA-N 0.000 description 4
WCQXCXDTQWDBHZ-UHFFFAOYSA-N 9-bromo-3-methyl-4h-benzo[f]quinazolin-1-one Chemical compound C1=CC(Br)=CC2=C(C(=O)NC(C)=N3)C3=CC=C21 WCQXCXDTQWDBHZ-UHFFFAOYSA-N 0.000 description 4
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
108010020346 Polyglutamic Acid Proteins 0.000 description 4
239000000908 ammonium hydroxide Substances 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
210000002798 bone marrow cell Anatomy 0.000 description 4
244000309464 bull Species 0.000 description 4
201000011510 cancer Diseases 0.000 description 4
150000001721 carbon Chemical group 0.000 description 4
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
150000004985 diamines Chemical class 0.000 description 4
RJXFBLRRPYBPTM-ZDUSSCGKSA-N diethyl (2s)-2-[(4-aminobenzoyl)amino]pentanedioate Chemical compound CCOC(=O)CC[C@@H](C(=O)OCC)NC(=O)C1=CC=C(N)C=C1 RJXFBLRRPYBPTM-ZDUSSCGKSA-N 0.000 description 4
239000000284 extract Substances 0.000 description 4
229940049906 glutamate Drugs 0.000 description 4
235000013922 glutamic acid Nutrition 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
239000011630 iodine Substances 0.000 description 4
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 4
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 4
229920002643 polyglutamic acid Polymers 0.000 description 4
239000000843 powder Substances 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
238000010183 spectrum analysis Methods 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
238000001665 trituration Methods 0.000 description 4
239000008215 water for injection Substances 0.000 description 4
KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical compound C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 description 3
OZAIFHULBGXAKX-UHFFFAOYSA-N 2,2'-azo-bis-isobutyronitrile Substances N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 3
HRFLULLBPLPBSW-UHFFFAOYSA-N 2-(3-ethoxyphenyl)acetic acid Chemical compound CCOC1=CC=CC(CC(O)=O)=C1 HRFLULLBPLPBSW-UHFFFAOYSA-N 0.000 description 3
YCNSIAMNVFIXRR-UHFFFAOYSA-N 2-(3-ethylsulfanylphenyl)acetic acid Chemical compound CCSC1=CC=CC(CC(O)=O)=C1 YCNSIAMNVFIXRR-UHFFFAOYSA-N 0.000 description 3
XEOQLLOHKNZVQZ-UHFFFAOYSA-N 3,10-diamino-9-bromo-4h-benzo[f]quinazolin-1-one Chemical compound C1=C(Br)C(N)=C2C3=C(O)N=C(N)N=C3C=CC2=C1 XEOQLLOHKNZVQZ-UHFFFAOYSA-N 0.000 description 3
ARIQVZAPFSKYSS-UHFFFAOYSA-N 3,9-diamino-4h-benzo[f]quinazolin-1-one Chemical compound N1=C(N)NC(=O)C2=C1C=CC1=CC=C(N)C=C12 ARIQVZAPFSKYSS-UHFFFAOYSA-N 0.000 description 3
AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 3
ULWBVFPOHRVIHQ-UHFFFAOYSA-N 3-amino-1-oxo-5,6-dihydro-4h-benzo[f]quinazoline-8-sulfonyl chloride Chemical compound C1CC2=CC(S(Cl)(=O)=O)=CC=C2C2=C1N=C(N)NC2=O ULWBVFPOHRVIHQ-UHFFFAOYSA-N 0.000 description 3
OGNDZLUHWUEELW-UHFFFAOYSA-N 3-amino-8-bromo-1-oxo-5,6-dihydro-4h-benzo[f]quinazoline-9-sulfonyl chloride Chemical compound C1CC2=CC(Br)=C(S(Cl)(=O)=O)C=C2C2=C1N=C(N)NC2=O OGNDZLUHWUEELW-UHFFFAOYSA-N 0.000 description 3
NRQYRGFHKMDBDL-UHFFFAOYSA-N 3-amino-8-bromo-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical compound C1CC2=CC(Br)=CC=C2C2=C1N=C(N)NC2=O NRQYRGFHKMDBDL-UHFFFAOYSA-N 0.000 description 3
ZFJLMIDDCRGFBM-UHFFFAOYSA-N 3-amino-8-bromo-n,n-diethyl-1-oxo-5,6-dihydro-4h-benzo[f]quinazoline-9-sulfonamide Chemical compound N1=C(N)NC(=O)C2=C1CCC1=C2C=C(S(=O)(=O)N(CC)CC)C(Br)=C1 ZFJLMIDDCRGFBM-UHFFFAOYSA-N 0.000 description 3
JJPNUYHDMXFJIO-UHFFFAOYSA-N 3-amino-9-bromo-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical compound C1CC2=CC=C(Br)C=C2C2=C1N=C(N)NC2=O JJPNUYHDMXFJIO-UHFFFAOYSA-N 0.000 description 3
LCNYCXOULVZWQU-UHFFFAOYSA-N 3-amino-9-ethenyl-4h-benzo[f]quinazolin-1-one Chemical compound C1=CC(C=C)=CC2=C(C(=O)NC(N)=N3)C3=CC=C21 LCNYCXOULVZWQU-UHFFFAOYSA-N 0.000 description 3
GKUPFLWKPATNMY-UHFFFAOYSA-N 3-amino-9-methoxy-4h-benzo[f]quinazolin-1-one Chemical compound N1=C(N)NC(=O)C2=C1C=CC1=CC=C(OC)C=C12 GKUPFLWKPATNMY-UHFFFAOYSA-N 0.000 description 3
KGGJFPIBKACXRX-UHFFFAOYSA-N 3-amino-n,n-diethyl-1-oxo-4h-benzo[f]quinazoline-9-sulfonamide Chemical compound N1=C(N)NC(=O)C2=C1C=CC1=CC=C(S(=O)(=O)N(CC)CC)C=C12 KGGJFPIBKACXRX-UHFFFAOYSA-N 0.000 description 3
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
JDZQATQJCMKPDN-UHFFFAOYSA-N 4-[(3-methyl-1-oxo-4h-benzo[f]quinazolin-9-yl)oxy]benzonitrile Chemical compound C=1C2=C3C(=O)NC(C)=NC3=CC=C2C=CC=1OC1=CC=C(C#N)C=C1 JDZQATQJCMKPDN-UHFFFAOYSA-N 0.000 description 3
ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical group NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 3
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 3
NCTYMQMYDHAKCE-UHFFFAOYSA-N 7-bromo-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=CC(Br)=CC=C21 NCTYMQMYDHAKCE-UHFFFAOYSA-N 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
206010006187 Breast cancer Diseases 0.000 description 3
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
239000005977 Ethylene Substances 0.000 description 3
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 3
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 3
206010058467 Lung neoplasm malignant Diseases 0.000 description 3
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
AZFNGPAYDKGCRB-XCPIVNJJSA-M [(1s,2s)-2-amino-1,2-diphenylethyl]-(4-methylphenyl)sulfonylazanide;chlororuthenium(1+);1-methyl-4-propan-2-ylbenzene Chemical compound [Ru+]Cl.CC(C)C1=CC=C(C)C=C1.C1=CC(C)=CC=C1S(=O)(=O)[N-][C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 AZFNGPAYDKGCRB-XCPIVNJJSA-M 0.000 description 3
150000008065 acid anhydrides Chemical class 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
239000000443 aerosol Substances 0.000 description 3
125000003342 alkenyl group Chemical group 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
229940024606 amino acid Drugs 0.000 description 3
235000001014 amino acid Nutrition 0.000 description 3
230000000118 anti-neoplastic effect Effects 0.000 description 3
230000037396 body weight Effects 0.000 description 3
230000031709 bromination Effects 0.000 description 3
238000005893 bromination reaction Methods 0.000 description 3
125000005997 bromomethyl group Chemical group 0.000 description 3
239000002775 capsule Substances 0.000 description 3
229910002092 carbon dioxide Inorganic materials 0.000 description 3
210000001072 colon Anatomy 0.000 description 3
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
239000013078 crystal Substances 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
238000002784 cytotoxicity assay Methods 0.000 description 3
231100000263 cytotoxicity test Toxicity 0.000 description 3
238000006356 dehydrogenation reaction Methods 0.000 description 3
239000003480 eluent Substances 0.000 description 3
238000010828 elution Methods 0.000 description 3
239000011737 fluorine Chemical group 0.000 description 3
125000001153 fluoro group Chemical group F* 0.000 description 3
235000019256 formaldehyde Nutrition 0.000 description 3
229930195712 glutamate Natural products 0.000 description 3
239000008187 granular material Substances 0.000 description 3
239000012456 homogeneous solution Substances 0.000 description 3
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
239000003112 inhibitor Substances 0.000 description 3
239000008101 lactose Substances 0.000 description 3
201000005202 lung cancer Diseases 0.000 description 3
208000020816 lung neoplasm Diseases 0.000 description 3
229910052751 metal Inorganic materials 0.000 description 3
239000002184 metal Substances 0.000 description 3
QGYXFRVODXAEPB-UHFFFAOYSA-N methyl 2-(3-ethoxyphenyl)acetate Chemical compound CCOC1=CC=CC(CC(=O)OC)=C1 QGYXFRVODXAEPB-UHFFFAOYSA-N 0.000 description 3
GNWBJFNIQJZLKP-UHFFFAOYSA-N methyl 2-hydroxy-3,4-dihydronaphthalene-1-carboxylate Chemical class C1=CC=C2C(C(=O)OC)=C(O)CCC2=C1 GNWBJFNIQJZLKP-UHFFFAOYSA-N 0.000 description 3
NEIKKQSVQVEWOC-UHFFFAOYSA-N methyl 7-bromo-2-hydroxy-3,4-dihydronaphthalene-1-carboxylate Chemical compound C1=C(Br)C=C2C(C(=O)OC)=C(O)CCC2=C1 NEIKKQSVQVEWOC-UHFFFAOYSA-N 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
VZKNWUMSJBIMMC-UHFFFAOYSA-N phenanthro[9,10-d]pyrimidine-2,4-diamine Chemical compound C1=CC=C2C3=NC(N)=NC(N)=C3C3=CC=CC=C3C2=C1 VZKNWUMSJBIMMC-UHFFFAOYSA-N 0.000 description 3
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
229920000053 polysorbate 80 Polymers 0.000 description 3
239000004304 potassium nitrite Substances 0.000 description 3
235000010289 potassium nitrite Nutrition 0.000 description 3
150000003254 radicals Chemical class 0.000 description 3
BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
235000010288 sodium nitrite Nutrition 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
239000007858 starting material Substances 0.000 description 3
229940124597 therapeutic agent Drugs 0.000 description 3
NJPOCNLEBZBVTF-UHFFFAOYSA-N triethyl 5-(4-nitrophenyl)-5-oxopentane-1,3,3-tricarboxylate Chemical compound CCOC(=O)CCC(C(=O)OCC)(C(=O)OCC)CC(=O)C1=CC=C([N+]([O-])=O)C=C1 NJPOCNLEBZBVTF-UHFFFAOYSA-N 0.000 description 3
239000003643 water by type Substances 0.000 description 3
SOYHTRIVKATKIK-FJXQXJEOSA-N (2s)-2-(diethylamino)pentanedioic acid;hydrochloride Chemical compound Cl.CCN(CC)[C@H](C(O)=O)CCC(O)=O SOYHTRIVKATKIK-FJXQXJEOSA-N 0.000 description 2
GGYBAFVBOIILIZ-IBGZPJMESA-N (2s)-2-[[4-[(3-amino-1-oxo-4h-benzo[f]quinazolin-9-yl)methylamino]benzoyl]amino]pentanedioic acid Chemical compound C=1C2=C3C(=O)NC(N)=NC3=CC=C2C=CC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 GGYBAFVBOIILIZ-IBGZPJMESA-N 0.000 description 2
SVDMCNNCRPTKSP-FQEVSTJZSA-N (2s)-2-[[4-[(3-methyl-1-oxo-4h-benzo[f]quinazolin-9-yl)sulfonylamino]benzoyl]amino]pentanedioic acid Chemical compound N=1C(C)=NC(O)=C(C2=C3)C=1C=CC2=CC=C3S(=O)(=O)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 SVDMCNNCRPTKSP-FQEVSTJZSA-N 0.000 description 2
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 description 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 2
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 2
238000005160 1H NMR spectroscopy Methods 0.000 description 2
NOPMBRCHCNZTDW-UHFFFAOYSA-N 2-(3-phenylphenyl)ethanol Chemical compound OCCC1=CC=CC(C=2C=CC=CC=2)=C1 NOPMBRCHCNZTDW-UHFFFAOYSA-N 0.000 description 2
VQVBNWUUKLBHGI-UHFFFAOYSA-N 2-(4-bromophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=C(Br)C=C1 VQVBNWUUKLBHGI-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
CLMGXDZZMPGEDF-UHFFFAOYSA-N 2-[3-(4-cyanophenoxy)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OC=2C=CC(=CC=2)C#N)=C1 CLMGXDZZMPGEDF-UHFFFAOYSA-N 0.000 description 2
QQAJSDNLHNNYMM-UHFFFAOYSA-N 3,8-diamino-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical compound N1=C(N)NC(=O)C2=C1CCC1=CC(N)=CC=C21 QQAJSDNLHNNYMM-UHFFFAOYSA-N 0.000 description 2
JFDKEPQCKTUVRK-UHFFFAOYSA-N 3-(benzylamino)-7-bromo-4h-benzo[f]quinazolin-1-one Chemical compound BrC1=CC=CC(C=2C(=O)N3)=C1C=CC=2N=C3NCC1=CC=CC=C1 JFDKEPQCKTUVRK-UHFFFAOYSA-N 0.000 description 2
QMJPVUCPZIBSGS-UHFFFAOYSA-N 3-(methylamino)-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical compound C1CC2=CC=CC=C2C2=C1N=C(NC)NC2=O QMJPVUCPZIBSGS-UHFFFAOYSA-N 0.000 description 2
ZMIUJNZPUYHCIH-UHFFFAOYSA-N 3-amino-4h-benzo[f]quinazolin-1-one Chemical compound C1=CC=C2C(C(=O)N=C(N3)N)=C3C=CC2=C1 ZMIUJNZPUYHCIH-UHFFFAOYSA-N 0.000 description 2
OSVPVMWWUHZUBK-UHFFFAOYSA-N 3-amino-6-(methoxymethyl)-4h-benzo[f]quinazolin-1-one Chemical compound C12=CC=CC=C2C(COC)=CC2=C1C(=O)NC(N)=N2 OSVPVMWWUHZUBK-UHFFFAOYSA-N 0.000 description 2
VLRQZZCQFUBRDA-UHFFFAOYSA-N 3-amino-7,9-dimethyl-4h-benzo[f]quinazolin-1-one Chemical compound N1=C(N)NC(=O)C2=C1C=CC1=C(C)C=C(C)C=C12 VLRQZZCQFUBRDA-UHFFFAOYSA-N 0.000 description 2
FEQIANAJHPBQDL-UHFFFAOYSA-N 3-amino-8-bromo-4h-benzo[f]quinazolin-1-one Chemical compound C1=C(Br)C=CC2=C(C(=O)NC(N)=N3)C3=CC=C21 FEQIANAJHPBQDL-UHFFFAOYSA-N 0.000 description 2
NRIRWLRWSGDYBN-UHFFFAOYSA-N 3-amino-8-bromo-9-nitro-4h-benzo[f]quinazolin-1-one Chemical compound C1=C(Br)C([N+]([O-])=O)=CC2=C(C(=O)NC(N)=N3)C3=CC=C21 NRIRWLRWSGDYBN-UHFFFAOYSA-N 0.000 description 2
IZQIBAIYWWSYMS-UHFFFAOYSA-N 3-amino-8-bromo-n,n-diethyl-1-oxo-4h-benzo[f]quinazoline-9-sulfonamide Chemical compound N1=C(N)NC(=O)C2=C1C=CC1=C2C=C(S(=O)(=O)N(CC)CC)C(Br)=C1 IZQIBAIYWWSYMS-UHFFFAOYSA-N 0.000 description 2
HNYGYCAECLFPNE-UHFFFAOYSA-N 3-amino-9-[(4-fluoroanilino)methyl]-4h-benzo[f]quinazolin-1-one Chemical compound C=1C2=C3C(=O)NC(N)=NC3=CC=C2C=CC=1CNC1=CC=C(F)C=C1 HNYGYCAECLFPNE-UHFFFAOYSA-N 0.000 description 2
CXATXNKZINHFEL-UHFFFAOYSA-N 3-amino-9-ethyl-4h-benzo[f]quinazolin-1-one Chemical compound N1=C(N)NC(=O)C2=C1C=CC1=CC=C(CC)C=C12 CXATXNKZINHFEL-UHFFFAOYSA-N 0.000 description 2
WPKWPICWYRCHKM-UHFFFAOYSA-N 3-amino-9-hydroxy-4h-benzo[f]quinazolin-1-one Chemical compound C1=CC(O)=CC2=C(C(=O)NC(N)=N3)C3=CC=C21 WPKWPICWYRCHKM-UHFFFAOYSA-N 0.000 description 2
APJAEXGNDLFGPD-AWCRTANDSA-N 3-amino-n-{4-[2-(2,6-dimethyl-phenoxy)-acetylamino]-3-hydroxy-1-isobutyl-5-phenyl-pentyl}-benzamide Chemical compound C([C@@H]([C@@H](O)C[C@H](CC(C)C)NC(=O)C=1C=CC(N)=CC=1)NC(=O)COC=1C(=CC=CC=1C)C)C1=CC=CC=C1 APJAEXGNDLFGPD-AWCRTANDSA-N 0.000 description 2
LYJJWZCHXZYACH-UHFFFAOYSA-N 3-methyl-1-oxo-5,6-dihydro-4h-benzo[f]quinazoline-9-sulfonamide Chemical compound C1CC2=CC=C(S(N)(=O)=O)C=C2C2=C1N=C(C)NC2=O LYJJWZCHXZYACH-UHFFFAOYSA-N 0.000 description 2
GMTQTFKXSONTDW-UHFFFAOYSA-N 3-methyl-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical class C1CC2=CC=CC=C2C2=C1N=C(C)NC2=O GMTQTFKXSONTDW-UHFFFAOYSA-N 0.000 description 2
CWXUCOIJSLPOCZ-UHFFFAOYSA-N 4,4-dimethyl-1,3-dihydronaphthalen-2-one Chemical compound C1=CC=C2C(C)(C)CC(=O)CC2=C1 CWXUCOIJSLPOCZ-UHFFFAOYSA-N 0.000 description 2
MEFVOBKOEJGUQI-UHFFFAOYSA-N 4,4-dimethyl-2,3-dihydro-1h-naphthalen-1-ol Chemical compound C1=CC=C2C(C)(C)CCC(O)C2=C1 MEFVOBKOEJGUQI-UHFFFAOYSA-N 0.000 description 2
NVQAKPKZYJWBTP-UHFFFAOYSA-N 4-(4-nitrophenyl)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)C1=CC=C([N+]([O-])=O)C=C1 NVQAKPKZYJWBTP-UHFFFAOYSA-N 0.000 description 2
KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 2
AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 2
OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 description 2
LVGPUDKBSXRFFI-UHFFFAOYSA-N 5,6-dihydrobenzo[h]quinazoline Chemical compound C1=CC=C2CCC3=CN=CN=C3C2=C1 LVGPUDKBSXRFFI-UHFFFAOYSA-N 0.000 description 2
BYHKDUFPSJWJDI-UHFFFAOYSA-N 6-bromo-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=CC(Br)=CC=C21 BYHKDUFPSJWJDI-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 2
KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
241000588724 Escherichia coli Species 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
241000282412 Homo Species 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
CRZQGDNQQAALAY-UHFFFAOYSA-N Methyl benzeneacetate Chemical compound COC(=O)CC1=CC=CC=C1 CRZQGDNQQAALAY-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
GADGMZDHLQLZRI-VIFPVBQESA-N N-(4-aminobenzoyl)-L-glutamic acid Chemical group NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 GADGMZDHLQLZRI-VIFPVBQESA-N 0.000 description 2
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 2
IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
125000000304 alkynyl group Chemical group 0.000 description 2
125000003275 alpha amino acid group Chemical group 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
239000003708 ampul Substances 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
125000000129 anionic group Chemical group 0.000 description 2
230000000259 anti-tumor effect Effects 0.000 description 2
150000004982 aromatic amines Chemical class 0.000 description 2
238000003556 assay Methods 0.000 description 2
BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
210000000481 breast Anatomy 0.000 description 2
239000001569 carbon dioxide Substances 0.000 description 2
125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
239000012954 diazonium Substances 0.000 description 2
150000001989 diazonium salts Chemical class 0.000 description 2
ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 2
QLFHNYHWNXXKBF-ZDUSSCGKSA-N diethyl (2s)-2-(5-nitro-1,3-dioxoisoindol-2-yl)pentanedioate Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N([C@@H](CCC(=O)OCC)C(=O)OCC)C(=O)C2=C1 QLFHNYHWNXXKBF-ZDUSSCGKSA-N 0.000 description 2
NTZVLSWXZVDNLA-AWEZNQCLSA-N diethyl (2s)-2-(6-amino-3-oxo-1h-isoindol-2-yl)pentanedioate Chemical compound NC1=CC=C2C(=O)N([C@@H](CCC(=O)OCC)C(=O)OCC)CC2=C1 NTZVLSWXZVDNLA-AWEZNQCLSA-N 0.000 description 2
HFVFBGSLNPUCED-LBPRGKRZSA-N diethyl (2s)-2-(6-nitro-3-oxo-1,2-benzothiazol-2-yl)pentanedioate Chemical compound [O-][N+](=O)C1=CC=C2C(=O)N([C@H](C(=O)OCC)CCC(=O)OCC)SC2=C1 HFVFBGSLNPUCED-LBPRGKRZSA-N 0.000 description 2
HERPVHLYIHBEFW-ZETCQYMHSA-N diethyl (2s)-2-aminopentanedioate Chemical group CCOC(=O)CC[C@H](N)C(=O)OCC HERPVHLYIHBEFW-ZETCQYMHSA-N 0.000 description 2
YYRUABYDPMPYCB-UHFFFAOYSA-N diethyl 2-[2-(4-nitrophenyl)-2-oxoethyl]pentanedioate Chemical compound CCOC(=O)CCC(C(=O)OCC)CC(=O)C1=CC=C([N+]([O-])=O)C=C1 YYRUABYDPMPYCB-UHFFFAOYSA-N 0.000 description 2
OLEICLKZWZMZEK-UHFFFAOYSA-N diethyl 2-[2-(4-nitrophenyl)-2-oxoethyl]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)CC(=O)C1=CC=C([N+]([O-])=O)C=C1 OLEICLKZWZMZEK-UHFFFAOYSA-N 0.000 description 2
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 description 2
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 2
VNCWXNMRUXUEBC-UHFFFAOYSA-N dodecyl 4-(4-nitrophenyl)-4-oxobutanoate Chemical compound CCCCCCCCCCCCOC(=O)CCC(=O)C1=CC=C([N+]([O-])=O)C=C1 VNCWXNMRUXUEBC-UHFFFAOYSA-N 0.000 description 2
239000006196 drop Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
239000012259 ether extract Substances 0.000 description 2
XSMWHIUJJBBMJS-UHFFFAOYSA-N ethyl 2-[3-(4-cyanophenoxy)phenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC(OC=2C=CC(=CC=2)C#N)=C1 XSMWHIUJJBBMJS-UHFFFAOYSA-N 0.000 description 2
MDVKJHZAEHJTJV-UHFFFAOYSA-N ethyl 2-hydroxy-3,4-dihydronaphthalene-1-carboxylate Chemical compound C1=CC=C2C(C(=O)OCC)=C(O)CCC2=C1 MDVKJHZAEHJTJV-UHFFFAOYSA-N 0.000 description 2
VXQOHLGYAHDYBT-UHFFFAOYSA-N ethyl 4-(4-nitrophenyl)-4-oxobutanoate Chemical compound CCOC(=O)CCC(=O)C1=CC=C([N+]([O-])=O)C=C1 VXQOHLGYAHDYBT-UHFFFAOYSA-N 0.000 description 2
HGGGQXBRWMWYSL-UHFFFAOYSA-N ethyl 4-[[2-(methoxymethyl)-3-methyl-1-oxobenzo[f]quinazolin-9-yl]methoxy]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1OCC1=CC=C(C=CC2=C3C(=O)N(COC)C(C)=N2)C3=C1 HGGGQXBRWMWYSL-UHFFFAOYSA-N 0.000 description 2
229940014144 folate Drugs 0.000 description 2
OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
235000019152 folic acid Nutrition 0.000 description 2
239000011724 folic acid Substances 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
239000011521 glass Substances 0.000 description 2
229960004198 guanidine Drugs 0.000 description 2
229960000789 guanidine hydrochloride Drugs 0.000 description 2
PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
238000011065 in-situ storage Methods 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
229910052742 iron Inorganic materials 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
208000032839 leukemia Diseases 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000000155 melt Substances 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
BVKGNQRDVFGNIW-UHFFFAOYSA-N methyl 2-(3-aminophenyl)acetate Chemical compound COC(=O)CC1=CC=CC(N)=C1 BVKGNQRDVFGNIW-UHFFFAOYSA-N 0.000 description 2
YOWNZOXGHKFUQW-UHFFFAOYSA-N methyl 5-(4-cyano-n-(2,2,2-trifluoroacetyl)anilino)-2-hydroxy-3,4-dihydronaphthalene-1-carboxylate Chemical compound C1=CC=C2C(C(=O)OC)=C(O)CCC2=C1N(C(=O)C(F)(F)F)C1=CC=C(C#N)C=C1 YOWNZOXGHKFUQW-UHFFFAOYSA-N 0.000 description 2
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
239000011707 mineral Substances 0.000 description 2
238000000465 moulding Methods 0.000 description 2
YHOPSRTVUHECDR-UHFFFAOYSA-N n-(4-cyanophenyl)-2,2,2-trifluoro-n-(5,6,7,8-tetrahydronaphthalen-1-yl)acetamide Chemical compound C=1C=CC=2CCCCC=2C=1N(C(=O)C(F)(F)F)C1=CC=C(C#N)C=C1 YHOPSRTVUHECDR-UHFFFAOYSA-N 0.000 description 2
BSMNRTQALNMUOH-UHFFFAOYSA-N n-(4-cyanophenyl)-2,2,2-trifluoro-n-(6-oxo-7,8-dihydro-5h-naphthalen-1-yl)acetamide Chemical compound C=1C=CC=2CC(=O)CCC=2C=1N(C(=O)C(F)(F)F)C1=CC=C(C#N)C=C1 BSMNRTQALNMUOH-UHFFFAOYSA-N 0.000 description 2
VQFRLSNLAXXSIN-UHFFFAOYSA-N n-(4-cyanophenyl)-n-(7,8-dihydronaphthalen-1-yl)-2,2,2-trifluoroacetamide Chemical compound C=1C=CC=2C=CCCC=2C=1N(C(=O)C(F)(F)F)C1=CC=C(C#N)C=C1 VQFRLSNLAXXSIN-UHFFFAOYSA-N 0.000 description 2
NAJYMWNQSHRCGP-UHFFFAOYSA-N n-(5,6,7,8-tetrahydronaphthalen-1-yl)acetamide Chemical compound C1CCCC2=C1C=CC=C2NC(=O)C NAJYMWNQSHRCGP-UHFFFAOYSA-N 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
150000002825 nitriles Chemical class 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
239000007800 oxidant agent Substances 0.000 description 2
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
239000012071 phase Substances 0.000 description 2
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
239000008227 sterile water for injection Substances 0.000 description 2
239000012258 stirred mixture Substances 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
150000003456 sulfonamides Chemical class 0.000 description 2
125000004434 sulfur atom Chemical group 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
229910052723 transition metal Inorganic materials 0.000 description 2
150000003624 transition metals Chemical class 0.000 description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
239000011701 zinc Substances 0.000 description 2
TXTWXQXDMWILOF-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl)azanium;chloride Chemical compound [Cl-].CCOC(=O)C[NH3+] TXTWXQXDMWILOF-UHFFFAOYSA-N 0.000 description 1
NXWYAHLLQFLYDY-ZETCQYMHSA-N (2s)-2-(diethylamino)pentanedioic acid Chemical compound CCN(CC)[C@H](C(O)=O)CCC(O)=O NXWYAHLLQFLYDY-ZETCQYMHSA-N 0.000 description 1
BYMZVHOVULHHSA-FQEVSTJZSA-N (2s)-2-[6-[(3-methyl-1-oxo-4h-benzo[f]quinazolin-9-yl)methylamino]-3-oxo-1,2-benzothiazol-2-yl]pentanedioic acid Chemical compound C1=C2C(=O)N([C@@H](CCC(O)=O)C(O)=O)SC2=CC(NCC=2C=CC3=CC=C4N=C(NC(=O)C4=C3C=2)C)=C1 BYMZVHOVULHHSA-FQEVSTJZSA-N 0.000 description 1
DRCAJGUBGOLYTB-IBGZPJMESA-N (2s)-2-[[4-[(3-methyl-1-oxo-4h-benzo[f]quinazolin-7-yl)sulfonylamino]benzoyl]amino]pentanedioic acid Chemical compound N=1C(C)=NC(O)=C(C2=CC=C3)C=1C=CC2=C3S(=O)(=O)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 DRCAJGUBGOLYTB-IBGZPJMESA-N 0.000 description 1
ZNCGZGIDONZDAI-FQEVSTJZSA-N (2s)-2-[[4-[(3-methyl-1-oxo-5,6-dihydro-4h-benzo[f]quinazolin-9-yl)sulfonylamino]benzoyl]amino]pentanedioic acid Chemical compound N=1C(C)=NC(O)=C(C2=C3)C=1CCC2=CC=C3S(=O)(=O)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 ZNCGZGIDONZDAI-FQEVSTJZSA-N 0.000 description 1
RPAJSBKBKSSMLJ-DFWYDOINSA-N (2s)-2-aminopentanedioic acid;hydrochloride Chemical compound Cl.OC(=O)[C@@H](N)CCC(O)=O RPAJSBKBKSSMLJ-DFWYDOINSA-N 0.000 description 1
PFTNRHTVAQAQHE-VIFPVBQESA-N (4s)-4-amino-5-(4-aminobenzoyl)oxy-5-oxopentanoic acid Chemical compound OC(=O)CC[C@H](N)C(=O)OC(=O)C1=CC=C(N)C=C1 PFTNRHTVAQAQHE-VIFPVBQESA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
NLZXHRIIPLQJIX-UHFFFAOYSA-N 1,1-dimethyl-2h-naphthalene Chemical compound C1=CC=C2C(C)(C)CC=CC2=C1 NLZXHRIIPLQJIX-UHFFFAOYSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
229940005561 1,4-benzoquinone Drugs 0.000 description 1
GPRYKVSEZCQIHD-UHFFFAOYSA-N 1-(4-aminophenyl)ethanone Chemical compound CC(=O)C1=CC=C(N)C=C1 GPRYKVSEZCQIHD-UHFFFAOYSA-N 0.000 description 1
USYQKCQEVBFJRP-UHFFFAOYSA-N 1-bromo-3-phenylbenzene Chemical group BrC1=CC=CC(C=2C=CC=CC=2)=C1 USYQKCQEVBFJRP-UHFFFAOYSA-N 0.000 description 1
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical class C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 1
LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
XNTNPKXCRBTDTR-UHFFFAOYSA-N 2,2-dimethyl-3,4-dihydronaphthalen-1-one Chemical compound C1=CC=C2C(=O)C(C)(C)CCC2=C1 XNTNPKXCRBTDTR-UHFFFAOYSA-N 0.000 description 1
AVBFLDWZBMRUGQ-UHFFFAOYSA-N 2,2-dimethyl-n-[1-oxo-9-(2-trimethylsilylethynyl)-4h-benzo[f]quinazolin-3-yl]propanamide Chemical compound C1=CC(C#C[Si](C)(C)C)=CC2=C(C(=O)NC(NC(=O)C(C)(C)C)=N3)C3=CC=C21 AVBFLDWZBMRUGQ-UHFFFAOYSA-N 0.000 description 1
ILRYTEWLYUECKK-UHFFFAOYSA-N 2,4-dimethylbenzo[h]quinazoline Chemical compound C1=CC=C2C3=NC(C)=NC(C)=C3C=CC2=C1 ILRYTEWLYUECKK-UHFFFAOYSA-N 0.000 description 1
YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 description 1
GXXXUZIRGXYDFP-UHFFFAOYSA-N 2-(4-methylphenyl)acetic acid Chemical compound CC1=CC=C(CC(O)=O)C=C1 GXXXUZIRGXYDFP-UHFFFAOYSA-N 0.000 description 1
XCIBTOJMNCXUTO-UHFFFAOYSA-N 2-(methoxymethyl)-3,9-dimethylbenzo[f]quinazolin-1-one Chemical compound C1=CC(C)=CC2=C(C(N(COC)C(C)=N3)=O)C3=CC=C21 XCIBTOJMNCXUTO-UHFFFAOYSA-N 0.000 description 1
QTMAZYGAVHCKKX-UHFFFAOYSA-N 2-[(4-amino-5-bromopyrrolo[2,3-d]pyrimidin-7-yl)methoxy]propane-1,3-diol Chemical compound NC1=NC=NC2=C1C(Br)=CN2COC(CO)CO QTMAZYGAVHCKKX-UHFFFAOYSA-N 0.000 description 1
VIYJWTSKSLYKMI-UHFFFAOYSA-N 2-amino-1h-phenanthro[9,10-d]pyrimidin-4-one Chemical compound C1=CC=CC2=C(C(=O)NC(N)=N3)C3=C(C=CC=C3)C3=C21 VIYJWTSKSLYKMI-UHFFFAOYSA-N 0.000 description 1
SQFRICUZRIGZEP-UHFFFAOYSA-N 2-amino-9-bromobenzo[f]quinazolin-1-one Chemical compound C1=CC(Br)=CC2=C(C(N(N)C=N3)=O)C3=CC=C21 SQFRICUZRIGZEP-UHFFFAOYSA-N 0.000 description 1
MBUPVGIGAMCMBT-UHFFFAOYSA-N 2-bromo-1-(4-nitrophenyl)ethanone Chemical compound [O-][N+](=O)C1=CC=C(C(=O)CBr)C=C1 MBUPVGIGAMCMBT-UHFFFAOYSA-N 0.000 description 1
FTZQXOJYPFINKJ-UHFFFAOYSA-N 2-fluoroaniline Chemical compound NC1=CC=CC=C1F FTZQXOJYPFINKJ-UHFFFAOYSA-N 0.000 description 1
XKJUWRGDFCRVPF-UHFFFAOYSA-N 2-hydroxy-3,4-dihydronaphthalene-1-carboxylic acid Chemical class C1=CC=C2C(C(=O)O)=C(O)CCC2=C1 XKJUWRGDFCRVPF-UHFFFAOYSA-N 0.000 description 1
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
AXNUZKSSQHTNPZ-UHFFFAOYSA-N 3,4-difluoroaniline Chemical compound NC1=CC=C(F)C(F)=C1 AXNUZKSSQHTNPZ-UHFFFAOYSA-N 0.000 description 1
SFGQODWSGDEDEQ-UHFFFAOYSA-N 3,7-diamino-8-bromo-4h-benzo[f]quinazolin-1-one Chemical compound NC1=C(Br)C=CC2=C(C(=O)NC(N)=N3)C3=CC=C21 SFGQODWSGDEDEQ-UHFFFAOYSA-N 0.000 description 1
BZNNWQUXERUGID-UHFFFAOYSA-N 3,8-diamino-7,9-dibromo-4h-benzo[f]quinazolin-1-one Chemical compound BrC1=C(N)C(Br)=CC2=C(C(=O)NC(N)=N3)C3=CC=C21 BZNNWQUXERUGID-UHFFFAOYSA-N 0.000 description 1
FRDQZSYEMGCGNR-UHFFFAOYSA-N 3,8-dimethyl-4h-benzo[f]quinazolin-1-one Chemical compound N1=C(C)NC(=O)C2=C1C=CC1=CC(C)=CC=C21 FRDQZSYEMGCGNR-UHFFFAOYSA-N 0.000 description 1
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
KQMJPJJSRFEPJN-UHFFFAOYSA-N 3-amino-1-oxo-5,6-dihydro-4h-benzo[f]quinazoline-8-sulfonamide Chemical compound C1CC2=CC(S(N)(=O)=O)=CC=C2C2=C1N=C(N)NC2=O KQMJPJJSRFEPJN-UHFFFAOYSA-N 0.000 description 1
KQTGGFXRDJELJZ-UHFFFAOYSA-N 3-amino-10-nitro-4h-benzo[f]quinazolin-1-one Chemical compound C1=CC([N+]([O-])=O)=C2C3=C(O)N=C(N)N=C3C=CC2=C1 KQTGGFXRDJELJZ-UHFFFAOYSA-N 0.000 description 1
VXKOVZZJDGUSEF-UHFFFAOYSA-N 3-amino-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical compound C1CC2=CC=CC=C2C2=C1N=C(N)NC2=O VXKOVZZJDGUSEF-UHFFFAOYSA-N 0.000 description 1
NUZGTHRCAKDJOX-UHFFFAOYSA-N 3-amino-6-(hydroxymethyl)-4h-benzo[f]quinazolin-1-one Chemical compound C1=CC=CC2=C(C(=O)NC(N)=N3)C3=CC(CO)=C21 NUZGTHRCAKDJOX-UHFFFAOYSA-N 0.000 description 1
HJJJDQRODGIFQB-UHFFFAOYSA-N 3-amino-6-methyl-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical compound C12=CC=CC=C2C(C)CC2=C1C(=O)NC(N)=N2 HJJJDQRODGIFQB-UHFFFAOYSA-N 0.000 description 1
NFQSGQYZCZHRHW-UHFFFAOYSA-N 3-amino-7,9-dimethyl-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical compound N1=C(N)NC(=O)C2=C1CCC1=C(C)C=C(C)C=C12 NFQSGQYZCZHRHW-UHFFFAOYSA-N 0.000 description 1
WODRQTQVTDATPH-UHFFFAOYSA-N 3-amino-7-methoxy-5,6-dihydro-4h-benzo[f]quinazolin-1-one;hydrochloride Chemical compound Cl.N1=C(N)NC(=O)C2=C1CCC1=C2C=CC=C1OC WODRQTQVTDATPH-UHFFFAOYSA-N 0.000 description 1
XQEAEEXVHTXAJZ-UHFFFAOYSA-N 3-amino-8-chloro-6-methyl-4h-benzo[f]quinazolin-1-one Chemical compound C12=CC=C(Cl)C=C2C(C)=CC2=C1C(=O)NC(N)=N2 XQEAEEXVHTXAJZ-UHFFFAOYSA-N 0.000 description 1
HSJJRFUIZALZAY-UHFFFAOYSA-N 3-amino-8-fluoro-10-nitro-4h-benzo[f]quinazolin-1-one Chemical compound FC1=CC([N+]([O-])=O)=C2C3=C(O)N=C(N)N=C3C=CC2=C1 HSJJRFUIZALZAY-UHFFFAOYSA-N 0.000 description 1
PFBWYCJMPAFZLU-UHFFFAOYSA-N 3-amino-8-fluoro-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical compound C1CC2=CC(F)=CC=C2C2=C1N=C(N)NC2=O PFBWYCJMPAFZLU-UHFFFAOYSA-N 0.000 description 1
LOZFBBUDSDZQQF-UHFFFAOYSA-N 3-amino-8-methoxy-5,6-dihydro-4h-benzo[f]quinazolin-1-one;hydrochloride Chemical compound Cl.N1=C(N)NC(=O)C2=C1CCC1=CC(OC)=CC=C21 LOZFBBUDSDZQQF-UHFFFAOYSA-N 0.000 description 1
XMOBLAUADVCLMS-UHFFFAOYSA-N 3-amino-8-nitro-5,6-dihydro-4h-benzo[f]quinazolin-1-one;sulfuric acid;hydrate Chemical compound O.OS(O)(=O)=O.[O-][N+](=O)C1=CC=C2C(C(=O)N=C(N3)N)=C3CCC2=C1 XMOBLAUADVCLMS-UHFFFAOYSA-N 0.000 description 1
DENFZDSWBRRYIV-UHFFFAOYSA-N 3-amino-9-[(4-nitroanilino)methyl]-4h-benzo[f]quinazolin-1-one Chemical compound C=1C2=C3C(=O)NC(N)=NC3=CC=C2C=CC=1CNC1=CC=C([N+]([O-])=O)C=C1 DENFZDSWBRRYIV-UHFFFAOYSA-N 0.000 description 1
LBIMNOKJPOYBJC-UHFFFAOYSA-N 3-amino-9-chloro-5,6-dihydro-4h-benzo[f]quinazolin-1-one;hydrochloride Chemical compound Cl.C1CC2=CC=C(Cl)C=C2C2=C1N=C(N)NC2=O LBIMNOKJPOYBJC-UHFFFAOYSA-N 0.000 description 1
KDMWCHIEXCZAPJ-UHFFFAOYSA-N 3-amino-9-ethynyl-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical compound C1CC2=CC=C(C#C)C=C2C2=C1N=C(N)NC2=O KDMWCHIEXCZAPJ-UHFFFAOYSA-N 0.000 description 1
SAYXODQHEIVWAX-UHFFFAOYSA-N 3-amino-9-hydroxy-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical compound C1CC2=CC=C(O)C=C2C2=C1N=C(N)NC2=O SAYXODQHEIVWAX-UHFFFAOYSA-N 0.000 description 1
QJKXSJVNMHELDM-UHFFFAOYSA-N 3-amino-9-methoxy-5,6-dihydro-4h-benzo[f]quinazolin-1-one;hydrochloride Chemical compound Cl.N1=C(N)NC(=O)C2=C1CCC1=CC=C(OC)C=C12 QJKXSJVNMHELDM-UHFFFAOYSA-N 0.000 description 1
LPISJPHJGWSBRI-UHFFFAOYSA-N 3-amino-n,n-diethyl-1-oxo-5,6-dihydro-4h-benzo[f]quinazoline-8-sulfonamide Chemical compound N1=C(N)NC(=O)C2=C1CCC1=CC(S(=O)(=O)N(CC)CC)=CC=C21 LPISJPHJGWSBRI-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
MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
KBNVCOJFMUTFLT-UHFFFAOYSA-N 3-methyl-1-oxo-4h-benzo[f]quinazoline-9-carbonitrile Chemical compound C1=CC(C#N)=CC2=C(C(=O)NC(C)=N3)C3=CC=C21 KBNVCOJFMUTFLT-UHFFFAOYSA-N 0.000 description 1
HVULCQPSGYYROI-UHFFFAOYSA-N 3-methyl-4h-benzo[f]quinazolin-1-one Chemical compound C1=CC=CC2=C(C(=O)NC(C)=N3)C3=CC=C21 HVULCQPSGYYROI-UHFFFAOYSA-N 0.000 description 1
NZYPYGOACINRJG-UHFFFAOYSA-N 3-methyl-8-nitro-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical compound C1CC2=CC([N+]([O-])=O)=CC=C2C2=C1N=C(C)NC2=O NZYPYGOACINRJG-UHFFFAOYSA-N 0.000 description 1
ACLLWSAIOROEGV-UHFFFAOYSA-N 3-methyl-9-[(4-nitroanilino)methyl]-4h-benzo[f]quinazolin-1-one Chemical compound C=1C2=C3C(=O)NC(C)=NC3=CC=C2C=CC=1CNC1=CC=C([N+]([O-])=O)C=C1 ACLLWSAIOROEGV-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
QOWSWEBLNVACCL-UHFFFAOYSA-N 4-Bromophenyl acetate Chemical compound OC(=O)CC1=CC=C(Br)C=C1 QOWSWEBLNVACCL-UHFFFAOYSA-N 0.000 description 1
IQSDWLCUPOLHKM-UHFFFAOYSA-N 4-[(3-amino-1-oxo-4h-benzo[f]quinazolin-7-yl)amino]benzoic acid Chemical compound C=1C=CC2=C3C(=O)NC(N)=NC3=CC=C2C=1NC1=CC=C(C(O)=O)C=C1 IQSDWLCUPOLHKM-UHFFFAOYSA-N 0.000 description 1
DJWUPXSZWCFNAU-UHFFFAOYSA-N 4-[(3-methyl-1-oxo-4h-benzo[f]quinazolin-9-yl)methoxy]benzoic acid Chemical compound C=1C2=C3C(=O)NC(C)=NC3=CC=C2C=CC=1COC1=CC=C(C(O)=O)C=C1 DJWUPXSZWCFNAU-UHFFFAOYSA-N 0.000 description 1
JVEWPQCUBOXCFO-UHFFFAOYSA-N 4-[(3-methyl-1-oxo-4h-benzo[f]quinazolin-9-yl)methylamino]benzoic acid Chemical compound C=1C2=C3C(=O)NC(C)=NC3=CC=C2C=CC=1CNC1=CC=C(C(O)=O)C=C1 JVEWPQCUBOXCFO-UHFFFAOYSA-N 0.000 description 1
OWPKIRFZYYBAQA-UHFFFAOYSA-N 4-[(3-methyl-1-oxo-4h-benzo[f]quinazolin-9-yl)methylamino]benzonitrile Chemical compound C=1C2=C3C(=O)NC(C)=NC3=CC=C2C=CC=1CNC1=CC=C(C#N)C=C1 OWPKIRFZYYBAQA-UHFFFAOYSA-N 0.000 description 1
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
ALYNCZNDIQEVRV-PZFLKRBQSA-N 4-amino-3,5-ditritiobenzoic acid Chemical compound [3H]c1cc(cc([3H])c1N)C(O)=O ALYNCZNDIQEVRV-PZFLKRBQSA-N 0.000 description 1
YECHMIOBPCMIGF-UHFFFAOYSA-N 4-amino-n-(2-hydroxyethyl)benzamide Chemical compound NC1=CC=C(C(=O)NCCO)C=C1 YECHMIOBPCMIGF-UHFFFAOYSA-N 0.000 description 1
YBAZINRZQSAIAY-UHFFFAOYSA-N 4-aminobenzonitrile Chemical compound NC1=CC=C(C#N)C=C1 YBAZINRZQSAIAY-UHFFFAOYSA-N 0.000 description 1
IRQWEODKXLDORP-UHFFFAOYSA-N 4-ethenylbenzoic acid Chemical compound OC(=O)C1=CC=C(C=C)C=C1 IRQWEODKXLDORP-UHFFFAOYSA-N 0.000 description 1
TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 1
CQOHASUGAQTTJX-UHFFFAOYSA-N 5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical class C1CC2=CC=CC=C2C2=C1N=CNC2=O CQOHASUGAQTTJX-UHFFFAOYSA-N 0.000 description 1
XLLBOUOFVRYIQZ-UHFFFAOYSA-N 5,7-dimethyl-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=CC(C)=CC(C)=C21 XLLBOUOFVRYIQZ-UHFFFAOYSA-N 0.000 description 1
HODOSJNSRPXYBH-UHFFFAOYSA-N 5-amino-2,3-dihydroinden-1-one Chemical compound NC1=CC=C2C(=O)CCC2=C1 HODOSJNSRPXYBH-UHFFFAOYSA-N 0.000 description 1
DDVQSZNNPLLKCW-UHFFFAOYSA-N 5-bromo-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=C1C=CC=C2Br DDVQSZNNPLLKCW-UHFFFAOYSA-N 0.000 description 1
AWOCGXZKCTYRCP-UHFFFAOYSA-N 5-chloro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=C1C=CC=C2Cl AWOCGXZKCTYRCP-UHFFFAOYSA-N 0.000 description 1
DAHDFURQTOLYBB-UHFFFAOYSA-N 5-fluoro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=C1C=CC=C2F DAHDFURQTOLYBB-UHFFFAOYSA-N 0.000 description 1
MDAIAXRTLTVEOU-UHFFFAOYSA-N 5-methoxy-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=C1C=CC=C2OC MDAIAXRTLTVEOU-UHFFFAOYSA-N 0.000 description 1
ISBHQRSVUQBOMI-UHFFFAOYSA-N 5-methyl-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=C1C=CC=C2C ISBHQRSVUQBOMI-UHFFFAOYSA-N 0.000 description 1
MMVIDXVHQANYAE-UHFFFAOYSA-N 5-nitro-2-benzofuran-1,3-dione Chemical compound [O-][N+](=O)C1=CC=C2C(=O)OC(=O)C2=C1 MMVIDXVHQANYAE-UHFFFAOYSA-N 0.000 description 1
GCGWMNQPZFQYCQ-UHFFFAOYSA-N 5-phenyl-3,4-dihydro-1H-naphthalen-2-one Chemical compound C1(=CC=CC=C1)C1=C2CCC(CC2=CC=C1)=O GCGWMNQPZFQYCQ-UHFFFAOYSA-N 0.000 description 1
125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
BEZIJCXXAGNMFX-UHFFFAOYSA-N 6,7-dichloro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=C1C=C(Cl)C(Cl)=C2 BEZIJCXXAGNMFX-UHFFFAOYSA-N 0.000 description 1
KJPMWVKPVCVZNK-UHFFFAOYSA-N 6,7-dimethoxy-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=C1C=C(OC)C(OC)=C2 KJPMWVKPVCVZNK-UHFFFAOYSA-N 0.000 description 1
QQSYTUUAEZUAKL-UHFFFAOYSA-N 6-chloro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=CC(Cl)=CC=C21 QQSYTUUAEZUAKL-UHFFFAOYSA-N 0.000 description 1
QMXOEISLPMFMBQ-UHFFFAOYSA-N 6-fluoro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=CC(F)=CC=C21 QMXOEISLPMFMBQ-UHFFFAOYSA-N 0.000 description 1
RMRKDYNVZWKAFP-UHFFFAOYSA-N 6-methoxy-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1C(=O)CCC2=CC(OC)=CC=C21 RMRKDYNVZWKAFP-UHFFFAOYSA-N 0.000 description 1
CSIHHNSBJNDXNO-UHFFFAOYSA-N 7-chloro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=CC(Cl)=CC=C21 CSIHHNSBJNDXNO-UHFFFAOYSA-N 0.000 description 1
PGDHHCIZOPWTJZ-UHFFFAOYSA-N 7-chloro-4-methyl-3,4-dihydro-1h-naphthalen-2-one Chemical compound ClC1=CC=C2C(C)CC(=O)CC2=C1 PGDHHCIZOPWTJZ-UHFFFAOYSA-N 0.000 description 1
UMGOZJYVLSYDDY-UHFFFAOYSA-N 7-iodo-3-methyl-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical compound C1CC2=C(I)C=CC=C2C2=C1N=C(C)NC2=O UMGOZJYVLSYDDY-UHFFFAOYSA-N 0.000 description 1
XEAPZXNZOJGVCZ-UHFFFAOYSA-N 7-methoxy-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=CC(OC)=CC=C21 XEAPZXNZOJGVCZ-UHFFFAOYSA-N 0.000 description 1
QVEPTNHEDDSLNI-UHFFFAOYSA-N 7-methyl-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=CC(C)=CC=C21 QVEPTNHEDDSLNI-UHFFFAOYSA-N 0.000 description 1
KJTOLWAJITXXAJ-UHFFFAOYSA-N 7-methyl-3,4-dihydro-1h-naphthalene-2-thione Chemical compound C1CC(=S)CC2=CC(C)=CC=C21 KJTOLWAJITXXAJ-UHFFFAOYSA-N 0.000 description 1
WAIHJRHXIDWTNK-UHFFFAOYSA-N 8-bromo-5,6-dihydrobenzo[f]quinazoline-1,3-diamine Chemical compound BrC1=CC=C2C3=C(N)N=C(N)N=C3CCC2=C1 WAIHJRHXIDWTNK-UHFFFAOYSA-N 0.000 description 1
ZBLPUKDWONQIMX-UHFFFAOYSA-N 8-chloro-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1CC(=O)CC2=C1C=CC=C2Cl ZBLPUKDWONQIMX-UHFFFAOYSA-N 0.000 description 1
OGEXWZSNJVKZBR-UHFFFAOYSA-N 9-(bromomethyl)-2-(methoxymethyl)-3-methylbenzo[f]quinazolin-1-one Chemical compound C1=CC(CBr)=CC2=C(C(N(COC)C(C)=N3)=O)C3=CC=C21 OGEXWZSNJVKZBR-UHFFFAOYSA-N 0.000 description 1
YTSIRJWMNLSRBJ-UHFFFAOYSA-N 9-(bromomethyl)benzo[h]quinazoline Chemical compound N1=CN=C2C3=CC(CBr)=CC=C3C=CC2=C1 YTSIRJWMNLSRBJ-UHFFFAOYSA-N 0.000 description 1
XTOAUVKTWZWDGB-UHFFFAOYSA-N 9-[(2-fluoroanilino)methyl]-3-methyl-4h-benzo[f]quinazolin-1-one Chemical compound C=1C2=C3C(=O)NC(C)=NC3=CC=C2C=CC=1CNC1=CC=CC=C1F XTOAUVKTWZWDGB-UHFFFAOYSA-N 0.000 description 1
VYQREOGLXJJOQM-UHFFFAOYSA-N 9-[(3,4-difluoroanilino)methyl]-3-methyl-4h-benzo[f]quinazolin-1-one Chemical compound C=1C2=C3C(=O)NC(C)=NC3=CC=C2C=CC=1CNC1=CC=C(F)C(F)=C1 VYQREOGLXJJOQM-UHFFFAOYSA-N 0.000 description 1
LLDVUBMJCWMVQE-UHFFFAOYSA-N 9-[(3-chloroanilino)methyl]-3-methyl-4h-benzo[f]quinazolin-1-one Chemical compound C=1C2=C3C(=O)NC(C)=NC3=CC=C2C=CC=1CNC1=CC=CC(Cl)=C1 LLDVUBMJCWMVQE-UHFFFAOYSA-N 0.000 description 1
LIGWERNJABDYOL-UHFFFAOYSA-N 9-[(4-acetylanilino)methyl]-3-amino-4h-benzo[f]quinazolin-1-one Chemical compound C1=CC(C(=O)C)=CC=C1NCC1=CC=C(C=CC2=C3C(=O)NC(N)=N2)C3=C1 LIGWERNJABDYOL-UHFFFAOYSA-N 0.000 description 1
WIEGWUSMDMEQBM-UHFFFAOYSA-N 9-[(4-acetylanilino)methyl]-3-methyl-4h-benzo[f]quinazolin-1-one Chemical compound C1=CC(C(=O)C)=CC=C1NCC1=CC=C(C=CC2=C3C(=O)NC(C)=N2)C3=C1 WIEGWUSMDMEQBM-UHFFFAOYSA-N 0.000 description 1
UBPLUIYIFVAKJQ-UHFFFAOYSA-N 9-[(4-methoxyanilino)methyl]-3-methyl-4h-benzo[f]quinazolin-1-one Chemical compound C1=CC(OC)=CC=C1NCC1=CC=C(C=CC2=C3C(=O)NC(C)=N2)C3=C1 UBPLUIYIFVAKJQ-UHFFFAOYSA-N 0.000 description 1
ANTGTJFDKIMDSI-UHFFFAOYSA-N 9-bromo-3-methyl-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical compound C1CC2=CC=C(Br)C=C2C2=C1N=C(C)NC2=O ANTGTJFDKIMDSI-UHFFFAOYSA-N 0.000 description 1
UVGQQPTVMPIEFR-UHFFFAOYSA-N 9-fluoro-3-methyl-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical compound C1CC2=CC=C(F)C=C2C2=C1N=C(C)NC2=O UVGQQPTVMPIEFR-UHFFFAOYSA-N 0.000 description 1
WTEBMUFFEUNBER-UHFFFAOYSA-N 9-iodo-3-methyl-4h-benzo[f]quinazolin-1-one Chemical compound C1=CC(I)=CC2=C(C(=O)NC(C)=N3)C3=CC=C21 WTEBMUFFEUNBER-UHFFFAOYSA-N 0.000 description 1
SJOMEDACMXHFNB-UHFFFAOYSA-N 9-iodo-3-methyl-5,6-dihydro-4h-benzo[f]quinazolin-1-one Chemical compound C1CC2=CC=C(I)C=C2C2=C1N=C(C)NC2=O SJOMEDACMXHFNB-UHFFFAOYSA-N 0.000 description 1
101150108397 Abcd2 gene Proteins 0.000 description 1
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
208000035143 Bacterial infection Diseases 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
DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 1
241000167854 Bourreria succulenta Species 0.000 description 1
208000026310 Breast neoplasm Diseases 0.000 description 1
RSUOYNFEFHPREF-UHFFFAOYSA-N C(=O)N(C)C.C[O-].[Na+] Chemical compound C(=O)N(C)C.C[O-].[Na+] RSUOYNFEFHPREF-UHFFFAOYSA-N 0.000 description 1
FCEAUOYNOAFNOK-UHFFFAOYSA-N C1CC2=CC=C(Cl)C=C2C2=C1N=C(C)NC2=O.N1=C(N)NC(=O)C2=C1C=CC1=CC=C(S(=O)(=O)N(C)C)C=C12 Chemical compound C1CC2=CC=C(Cl)C=C2C2=C1N=C(C)NC2=O.N1=C(N)NC(=O)C2=C1C=CC1=CC=C(S(=O)(=O)N(C)C)C=C12 FCEAUOYNOAFNOK-UHFFFAOYSA-N 0.000 description 1
LMFVJPKLJHBEMG-UHFFFAOYSA-N CC1=NC=2C=CC3=C(C2C(N1)=O)C=C(C=C3)CNC3=CC=CC=C3.C(C3=CC=CC=C3)(=O)O Chemical compound CC1=NC=2C=CC3=C(C2C(N1)=O)C=C(C=C3)CNC3=CC=CC=C3.C(C3=CC=CC=C3)(=O)O LMFVJPKLJHBEMG-UHFFFAOYSA-N 0.000 description 1
241000222122 Candida albicans Species 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
230000006820 DNA synthesis Effects 0.000 description 1
OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
239000004593 Epoxy Substances 0.000 description 1
JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
241000400611 Eucalyptus deanei Species 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
238000005727 Friedel-Crafts reaction Methods 0.000 description 1
206010017533 Fungal infection Diseases 0.000 description 1
201000003741 Gastrointestinal carcinoma Diseases 0.000 description 1
229920001503 Glucan Polymers 0.000 description 1
XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
208000005016 Intestinal Neoplasms Diseases 0.000 description 1
229930195714 L-glutamate Natural products 0.000 description 1
102000003960 Ligases Human genes 0.000 description 1
108090000364 Ligases Proteins 0.000 description 1
UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
208000031888 Mycoses Diseases 0.000 description 1
SGSSKEDGVONRGC-UHFFFAOYSA-N N(2)-methylguanine Chemical compound O=C1NC(NC)=NC2=C1N=CN2 SGSSKEDGVONRGC-UHFFFAOYSA-N 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
BZORFPDSXLZWJF-UHFFFAOYSA-N N,N-dimethyl-1,4-phenylenediamine Chemical compound CN(C)C1=CC=C(N)C=C1 BZORFPDSXLZWJF-UHFFFAOYSA-N 0.000 description 1
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
RGBJLKTYCLOSFE-UHFFFAOYSA-N NC1=NC=2C=CC3=C(C2C(N1)=O)C=C(C=C3)SCC.NC3=NC=1C=CC2=C(C1C(N3)=O)C=CC=C2Cl.NC2=NC=3C=CC1=C(C3C(N2)=O)C=C(C(=C1Br)N)Br Chemical compound NC1=NC=2C=CC3=C(C2C(N1)=O)C=C(C=C3)SCC.NC3=NC=1C=CC2=C(C1C(N3)=O)C=CC=C2Cl.NC2=NC=3C=CC1=C(C3C(N2)=O)C=C(C(=C1Br)N)Br RGBJLKTYCLOSFE-UHFFFAOYSA-N 0.000 description 1
CKFNIKIEJGVVCL-UHFFFAOYSA-N NC1=NC=2C=CC3=C(C2C(N1)=O)C=CC(=C3)N.NC3=NC=1C=CC2=C(C1C(N3)=O)C=C(C=C2)OC.NC2=NC=3C=CC1=C(C3C(N2)=O)C=CC=C1Br.NC1=NC=2C=C(C3=C(C2C(N1)=O)C=CC=C3)C Chemical compound NC1=NC=2C=CC3=C(C2C(N1)=O)C=CC(=C3)N.NC3=NC=1C=CC2=C(C1C(N3)=O)C=C(C=C2)OC.NC2=NC=3C=CC1=C(C3C(N2)=O)C=CC=C1Br.NC1=NC=2C=C(C3=C(C2C(N1)=O)C=CC=C3)C CKFNIKIEJGVVCL-UHFFFAOYSA-N 0.000 description 1
WHTHRYLWADCWRD-UHFFFAOYSA-N NC1=NC=2CCC3=C(C2C(N1)=O)C=C(C=C3)I.NC3=NC=1CC(C2=C(C1C(N3)=O)C=C(C=C2)Cl)C.NC2=NC=3CCC1=C(C3C(N2)=O)C=C(C=C1)C Chemical compound NC1=NC=2CCC3=C(C2C(N1)=O)C=C(C=C3)I.NC3=NC=1CC(C2=C(C1C(N3)=O)C=C(C=C2)Cl)C.NC2=NC=3CCC1=C(C3C(N2)=O)C=C(C=C1)C WHTHRYLWADCWRD-UHFFFAOYSA-N 0.000 description 1
101100109871 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) aro-8 gene Proteins 0.000 description 1
CYPRMUMKDSHJER-UHFFFAOYSA-N O.O.O.O.O.O.O.O.O.[Na] Chemical compound O.O.O.O.O.O.O.O.O.[Na] CYPRMUMKDSHJER-UHFFFAOYSA-N 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
RZKYEQDPDZUERB-UHFFFAOYSA-N Pindone Chemical group C1=CC=C2C(=O)C(C(=O)C(C)(C)C)C(=O)C2=C1 RZKYEQDPDZUERB-UHFFFAOYSA-N 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
239000012980 RPMI-1640 medium Substances 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
101100073357 Streptomyces halstedii sch2 gene Proteins 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
229940127327 Thymidylate Synthetase Inhibitors Drugs 0.000 description 1
YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
238000001042 affinity chromatography Methods 0.000 description 1
238000013019 agitation Methods 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
125000005083 alkoxyalkoxy group Chemical group 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
125000005103 alkyl silyl group Chemical group 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 description 1
229960004050 aminobenzoic acid Drugs 0.000 description 1
239000000538 analytical sample Substances 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
230000001093 anti-cancer Effects 0.000 description 1
230000000840 anti-viral effect Effects 0.000 description 1
239000000729 antidote Substances 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
230000001580 bacterial effect Effects 0.000 description 1
208000022362 bacterial infectious disease Diseases 0.000 description 1
230000003385 bacteriostatic effect Effects 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
235000013405 beer Nutrition 0.000 description 1
WTFASAWZXCAUHE-UHFFFAOYSA-N benzene;1-bromopyrrolidine-2,5-dione Chemical compound C1=CC=CC=C1.BrN1C(=O)CCC1=O WTFASAWZXCAUHE-UHFFFAOYSA-N 0.000 description 1
XMMHEFXLOOKEJO-UHFFFAOYSA-N benzo[h]quinazoline-9-sulfonyl chloride Chemical compound N1=CN=C2C3=CC(S(=O)(=O)Cl)=CC=C3C=CC2=C1 XMMHEFXLOOKEJO-UHFFFAOYSA-N 0.000 description 1
RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
235000019400 benzoyl peroxide Nutrition 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
210000000941 bile Anatomy 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
201000008274 breast adenocarcinoma Diseases 0.000 description 1
239000012267 brine Substances 0.000 description 1
150000001649 bromium compounds Chemical class 0.000 description 1
JAMFGQBENKSWOF-UHFFFAOYSA-N bromo(methoxy)methane Chemical compound COCBr JAMFGQBENKSWOF-UHFFFAOYSA-N 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
239000000872 buffer Substances 0.000 description 1
KVUAALJSMIVURS-ZEDZUCNESA-L calcium folinate Chemical compound [Ca+2].C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)C=C1 KVUAALJSMIVURS-ZEDZUCNESA-L 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
244000309466 calf Species 0.000 description 1
229940095731 candida albicans Drugs 0.000 description 1
125000001589 carboacyl group Chemical group 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
238000005266 casting Methods 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
125000002091 cationic group Chemical class 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
230000010261 cell growth Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
235000019693 cherries Nutrition 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
229940117975 chromium trioxide Drugs 0.000 description 1
WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Substances OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
238000010367 cloning Methods 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
201000010897 colon adenocarcinoma Diseases 0.000 description 1
208000029742 colonic neoplasm Diseases 0.000 description 1
238000004040 coloring Methods 0.000 description 1
238000004891 communication Methods 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
239000006071 cream Substances 0.000 description 1
239000013058 crude material Substances 0.000 description 1
UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 1
GYOZYWVXFNDGLU-XLPZGREQSA-N dTMP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 GYOZYWVXFNDGLU-XLPZGREQSA-N 0.000 description 1
238000007256 debromination reaction Methods 0.000 description 1
238000007269 dehydrobromination reaction Methods 0.000 description 1
239000002274 desiccant Substances 0.000 description 1
QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical compound NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 description 1
NIKHDNKTUVZBSF-LBPRGKRZSA-N diethyl (2s)-2-(6-amino-3-oxo-1,2-benzothiazol-2-yl)pentanedioate Chemical compound NC1=CC=C2C(=O)N([C@H](C(=O)OCC)CCC(=O)OCC)SC2=C1 NIKHDNKTUVZBSF-LBPRGKRZSA-N 0.000 description 1
GJSWUDZFAUEVEP-HNNXBMFYSA-N diethyl (2s)-2-[6-(methylamino)-3-oxo-1h-isoindol-2-yl]pentanedioate Chemical compound CNC1=CC=C2C(=O)N([C@@H](CCC(=O)OCC)C(=O)OCC)CC2=C1 GJSWUDZFAUEVEP-HNNXBMFYSA-N 0.000 description 1
VEVINTQROMAHBD-UHFFFAOYSA-N diethyl 2-[2-(4-aminophenyl)-2-oxoethyl]pentanedioate Chemical compound CCOC(=O)CCC(C(=O)OCC)CC(=O)C1=CC=C(N)C=C1 VEVINTQROMAHBD-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
LRRNLUXASMUQDU-UHFFFAOYSA-N dodecyl 4-(4-aminophenyl)-4-oxobutanoate Chemical compound CCCCCCCCCCCCOC(=O)CCC(=O)C1=CC=C(N)C=C1 LRRNLUXASMUQDU-UHFFFAOYSA-N 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
NSQBADKMIYCCSC-UHFFFAOYSA-N ethyl 2-(3-hydroxyphenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC(O)=C1 NSQBADKMIYCCSC-UHFFFAOYSA-N 0.000 description 1
YRQRUHBXPRQHHA-UHFFFAOYSA-N ethyl 2-[(2-fluoro-4-nitrobenzoyl)amino]acetate Chemical compound CCOC(=O)CNC(=O)C1=CC=C([N+]([O-])=O)C=C1F YRQRUHBXPRQHHA-UHFFFAOYSA-N 0.000 description 1
ZFHSICJRFPJEIS-UHFFFAOYSA-N ethyl 4-(4-aminophenyl)-4-oxobutanoate Chemical compound CCOC(=O)CCC(=O)C1=CC=C(N)C=C1 ZFHSICJRFPJEIS-UHFFFAOYSA-N 0.000 description 1
FJSMYPGIVBGQGK-UHFFFAOYSA-N ethyl 4-[(3-methyl-1-oxo-4h-benzo[f]quinazolin-9-yl)methylamino]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1NCC1=CC=C(C=CC2=C3C(=O)NC(C)=N2)C3=C1 FJSMYPGIVBGQGK-UHFFFAOYSA-N 0.000 description 1
DORJXVMKCKUMFL-UHFFFAOYSA-N ethyl 6-bromo-2-hydroxy-3,4-dihydronaphthalene-1-carboxylate Chemical compound BrC1=CC=C2C(C(=O)OCC)=C(O)CCC2=C1 DORJXVMKCKUMFL-UHFFFAOYSA-N 0.000 description 1
CELDLBYOSDAIEZ-UHFFFAOYSA-N ethyl 7-chloro-2-hydroxy-4-methyl-3,4-dihydronaphthalene-1-carboxylate Chemical compound C1=C(Cl)C=C2C(C(=O)OCC)=C(O)CC(C)C2=C1 CELDLBYOSDAIEZ-UHFFFAOYSA-N 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000006260 foam Substances 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
FATAVLOOLIRUNA-UHFFFAOYSA-N formylmethyl Chemical group [CH2]C=O FATAVLOOLIRUNA-UHFFFAOYSA-N 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 1
150000002306 glutamic acid derivatives Chemical class 0.000 description 1
125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
150000002332 glycine derivatives Chemical class 0.000 description 1
230000005484 gravity Effects 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
125000001188 haloalkyl group Chemical group 0.000 description 1
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
210000005260 human cell Anatomy 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
125000002768 hydroxyalkyl group Chemical group 0.000 description 1
239000005457 ice water Substances 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
201000009019 intestinal benign neoplasm Diseases 0.000 description 1
201000002313 intestinal cancer Diseases 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
RUTXIHLAWFEWGM-UHFFFAOYSA-H iron(3+) sulfate Chemical compound [Fe+3].[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RUTXIHLAWFEWGM-UHFFFAOYSA-H 0.000 description 1
229910000360 iron(III) sulfate Inorganic materials 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000011981 lindlar catalyst Substances 0.000 description 1
XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
229910052808 lithium carbonate Inorganic materials 0.000 description 1
UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
235000001055 magnesium Nutrition 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
201000001441 melanoma Diseases 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
HOLHLHZHUMWDMS-UHFFFAOYSA-N methyl 2-(3-ethylsulfanylphenyl)acetate Chemical compound CCSC1=CC=CC(CC(=O)OC)=C1 HOLHLHZHUMWDMS-UHFFFAOYSA-N 0.000 description 1
AMDDOQIUPAINLH-UHFFFAOYSA-N methyl 2-(3-hydroxyphenyl)acetate Chemical compound COC(=O)CC1=CC=CC(O)=C1 AMDDOQIUPAINLH-UHFFFAOYSA-N 0.000 description 1
YGBZFWWWQTWCOV-UHFFFAOYSA-N methyl 4-[(3-amino-1-oxo-4h-benzo[f]quinazolin-9-yl)sulfamoyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1S(=O)(=O)NC1=CC=C(C=CC2=C3C(=O)NC(N)=N2)C3=C1 YGBZFWWWQTWCOV-UHFFFAOYSA-N 0.000 description 1
CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 description 1
OBWFJXLKRAFEDI-UHFFFAOYSA-N methyl cyanoformate Chemical compound COC(=O)C#N OBWFJXLKRAFEDI-UHFFFAOYSA-N 0.000 description 1
ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000007932 molded tablet Substances 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 1
VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
RMJVYERUERZQRV-UHFFFAOYSA-N n,n,3-trimethyl-1,4,5,6-tetrahydrobenzo[f]quinazoline-9-sulfonamide Chemical compound C12=CC(S(=O)(=O)N(C)C)=CC=C2CCC2=C1CNC(C)=N2 RMJVYERUERZQRV-UHFFFAOYSA-N 0.000 description 1
GLFGGZDSFDCNNW-UHFFFAOYSA-N n-(4-cyanophenyl)-n-(5,6,7,8-tetrahydronaphthalen-1-yl)acetamide Chemical compound C=1C=CC=2CCCCC=2C=1N(C(=O)C)C1=CC=C(C#N)C=C1 GLFGGZDSFDCNNW-UHFFFAOYSA-N 0.000 description 1
YYJRXIPLSQTGRP-UHFFFAOYSA-N n-(9-bromo-1-oxo-4h-benzo[f]quinazolin-3-yl)formamide Chemical compound N1=C(NC=O)NC(=O)C2=C1C=CC1=CC=C(Br)C=C12 YYJRXIPLSQTGRP-UHFFFAOYSA-N 0.000 description 1
DILPZWHEDXJWHU-UHFFFAOYSA-N n-(9-ethenyl-1-oxo-4h-benzo[f]quinazolin-3-yl)-2,2-dimethylpropanamide Chemical compound C1=CC(C=C)=CC2=C(C(=O)NC(NC(=O)C(C)(C)C)=N3)C3=CC=C21 DILPZWHEDXJWHU-UHFFFAOYSA-N 0.000 description 1
239000007923 nasal drop Substances 0.000 description 1
229940100662 nasal drops Drugs 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
229910000069 nitrogen hydride Inorganic materials 0.000 description 1
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
239000007764 o/w emulsion Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
229940100692 oral suspension Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
LWHYKTAISUZRAD-UHFFFAOYSA-L palladium(2+);carbonate Chemical compound [Pd+2].[O-]C([O-])=O LWHYKTAISUZRAD-UHFFFAOYSA-L 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
KIHQWOBUUIPWAN-UHFFFAOYSA-N phenanthren-9-amine Chemical compound C1=CC=C2C(N)=CC3=CC=CC=C3C2=C1 KIHQWOBUUIPWAN-UHFFFAOYSA-N 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
QXTLQADUMJZAKD-UHFFFAOYSA-N phenyl 4-oxobutanoate Chemical compound O=CCCC(=O)OC1=CC=CC=C1 QXTLQADUMJZAKD-UHFFFAOYSA-N 0.000 description 1
229960003424 phenylacetic acid Drugs 0.000 description 1
239000003279 phenylacetic acid Substances 0.000 description 1
XIPFMBOWZXULIA-UHFFFAOYSA-N pivalamide Chemical compound CC(C)(C)C(N)=O XIPFMBOWZXULIA-UHFFFAOYSA-N 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 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
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910052939 potassium sulfate Inorganic materials 0.000 description 1
239000001120 potassium sulphate Substances 0.000 description 1
235000011151 potassium sulphates Nutrition 0.000 description 1
ZPFBCFAPICAMJZ-UHFFFAOYSA-M potassium;ethanethiolate Chemical compound [K+].CC[S-] ZPFBCFAPICAMJZ-UHFFFAOYSA-M 0.000 description 1
BEBPTRYPELOERP-UHFFFAOYSA-M potassium;methanethiolate Chemical compound [K+].[S-]C BEBPTRYPELOERP-UHFFFAOYSA-M 0.000 description 1
229940069328 povidone Drugs 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
238000012545 processing Methods 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
239000002718 pyrimidine nucleoside Substances 0.000 description 1
WDPKGGDLSJZCOO-UHFFFAOYSA-N quinazoline-8-sulfonamide Chemical compound N1=CN=CC2=CC=CC(=C12)S(=O)(=O)N WDPKGGDLSJZCOO-UHFFFAOYSA-N 0.000 description 1
239000002994 raw material Substances 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
230000000630 rising effect Effects 0.000 description 1
238000007789 sealing Methods 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
235000015424 sodium Nutrition 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
229940080313 sodium starch Drugs 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
IXBPPZBJIFNGJJ-UHFFFAOYSA-N sodium;cyanoiminomethylideneazanide Chemical compound [Na+].N#C[N-]C#N IXBPPZBJIFNGJJ-UHFFFAOYSA-N 0.000 description 1
239000012265 solid product Substances 0.000 description 1
230000003381 solubilizing effect Effects 0.000 description 1
125000003003 spiro group Chemical group 0.000 description 1
239000007921 spray Substances 0.000 description 1
229940032147 starch Drugs 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
150000003512 tertiary amines Chemical group 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
238000009210 therapy by ultrasound Methods 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
229940104230 thymidine Drugs 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000000699 topical effect Effects 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
125000004665 trialkylsilyl group Chemical group 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
229910052722 tritium Inorganic materials 0.000 description 1
230000004565 tumor cell growth Effects 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/60—Three or more oxygen or sulfur atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
- 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
- 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
- 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)
Chemical Kinetics & Catalysis (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Hematology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CS911863A 1990-06-19 1991-06-18 Pharmaceuticals CS186391A3 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB909013615A GB9013615D0 (en)	1990-06-19	1990-06-19	Pharmaceutical compounds

Publications (1)

Publication Number	Publication Date
CS186391A3 true CS186391A3 (en)	1992-04-15

Family

ID=10677828

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS911863A CS186391A3 (en)	1990-06-19	1991-06-18	Pharmaceuticals

Country Status (26)

Country	Link
US (4)	US6090941A (es)
EP (2)	EP0535034B1 (es)
JP (1)	JP2966929B2 (es)
KR (1)	KR0183042B1 (es)
CN (1)	CN1049215C (es)
AP (1)	AP218A (es)
AT (2)	ATE222243T1 (es)
AU (1)	AU639815B2 (es)
CA (1)	CA2085589C (es)
CS (1)	CS186391A3 (es)
DE (2)	DE69133371T2 (es)
DK (2)	DK0535034T3 (es)
ES (2)	ES2178632T3 (es)
FI (1)	FI925778A0 (es)
GB (1)	GB9013615D0 (es)
HU (2)	HUT62273A (es)
IE (1)	IE912073A1 (es)
IL (1)	IL98542A (es)
MC (1)	MC2290A1 (es)
MY (1)	MY107001A (es)
NO (1)	NO924929D0 (es)
NZ (1)	NZ238582A (es)
PL (1)	PL169927B1 (es)
PT (1)	PT98021B (es)
WO (1)	WO1991019700A1 (es)
ZA (1)	ZA914676B (es)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9013615D0 (en) *	1990-06-19	1990-08-08	Wellcome Found	Pharmaceutical compounds
US6762188B1 (en)	1990-06-19	2004-07-13	Smithkline Beecham Corporation	Pharmaceutically active benzoquinazoline compounds
GB9223352D0 (en) *	1992-11-06	1992-12-23	Ici Plc	Tricyclic compounds
GB9226842D0 (en)	1992-12-23	1993-02-17	Wellcome Found	Pharmaceutical compounds
GB9408936D0 (en) *	1994-05-05	1994-06-22	Cancer Res Inst	Anti-cancer compounds
US6531454B1 (en)	1999-03-16	2003-03-11	The Regents Of The University Of California	Glycosylated polyamines and methods of use therefor
US6420344B1 (en)	1999-03-16	2002-07-16	The Regents Of The University Of California	Glycosylated polyamines
CN1446080A (zh) *	2000-06-09	2003-10-01	Osi药物公司	脂质体苯并喹唑啉胸苷酸合成酶抑制剂制剂
BR0212829A (pt) *	2001-09-26	2004-08-03	Bayer Pharmaceuticals Corp	Derivados de 1,8-naftiridina e seu uso para tratar diabetes e distúrbios relacionados
CN100434425C (zh) *	2005-03-09	2008-11-19	首都师范大学	4-喹唑啉酮衍生物及其在抗肿瘤药物中的应用
EP1754484A1 (en)	2005-08-17	2007-02-21	Dan Stoicescu	Condensed pyrimidine derivatives as inhibitors of foic acid-dependent enzymes
JP5237821B2 (ja)	2005-12-05	2013-07-17	日東電工株式会社	ポリグルタミン酸−アミノ酸結合体および方法
GB0525069D0 (en) *	2005-12-08	2006-01-18	Novartis Ag	Organic compounds
CA2663436A1 (en)	2006-10-04	2008-04-10	Pfizer Products Inc.	Pyrido[4,3-d]pyrimidin-4(3h)-one derivatives as calcium receptor antagonists
EP1958632A1 (en)	2007-02-14	2008-08-20	Dan Stoicescu	Use of condensed pyrimidine derivatives for the treatment of autoimmune and inflammatory diseases
JP2010528122A (ja) *	2007-05-09	2010-08-19	日東電工株式会社	白金薬剤と結合されたポリマー
EP2155253A2 (en) *	2007-05-09	2010-02-24	Nitto Denko Corporation	Polyglutamate conjugates and polyglutamate-amino acid conjugates having a plurality of drugs
DK2155255T3 (da) *	2007-05-09	2013-09-02	Nitto Denko Corp	Sammensætninger der omfatter en hydrofob forbindelse og et polyaminosyrekonjugat
US8146622B2 (en)	2007-08-20	2012-04-03	Ford Global Technologies, Llc	Switch and hose-valve connection arrangement for vehicle temporary mobility kit
US8517760B2 (en)	2007-08-20	2013-08-27	Ford Global Technologies, Llc	Cord wrap and power plug receptacle arrangement for inflator
US8501242B2 (en)	2009-05-29	2013-08-06	University Of Florida Research Foundation	Methods and compositions for treating neoplasia
CN101580501B (zh) *	2009-06-01	2011-03-09	南京卡文迪许生物工程技术有限公司	3-(取代二氢异吲哚酮-2-基)-2,6-哌啶二酮的合成方法及其中间体
WO2011078226A1 (ja) *	2009-12-22	2011-06-30	協和発酵キリン株式会社	三環系化合物
CA3195150A1 (en)	2020-10-08	2022-04-14	Sven Weiler	Benzo[h]quinazolin-4-amine and thieno[3,2-h]quinazolin-4-amine derivatives for the treatment of cancer
CN116547280A (zh) *	2020-10-08	2023-08-04	雷多纳治疗公司	用于治疗癌症的苯并[h]喹唑啉-4-胺和噻吩并[3,2-h]喹唑啉-4-胺衍生物

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
UST862021I4 (en) *	1969-01-27	1969-05-27		Defensive publication
DE2202847A1 (de) *	1971-02-05	1972-08-17	Apaw Sa	Speiseeismaschine,insbesondere fuer Familiengebrauch,Kleinbetriebe od.dgl.
EP0031237B1 (en) *	1979-12-19	1984-10-17	National Research Development Corporation	Quinazoline derivatives, processes for their preparation, compositions containing them and their use as anti-cancer agents
US4814335A (en) *	1982-12-30	1989-03-21	Biomeasure, Incorporated	Antiviral compounds
GB8513754D0 (en) *	1985-05-31	1985-07-03	Jones T R	Anti-cancer quinazoline derivatives
US4603186A (en)	1985-10-21	1986-07-29	The Standard Oil Company	Tetrapolymers containing indene
GB8607683D0 (en) *	1986-03-27	1986-04-30	Ici Plc	Anti-tumor agents
US4818819A (en) *	1986-10-20	1989-04-04	The Trustees Of Princeton University	Process for the preparation of fused pyridine compounds
GB8707053D0 (en) *	1987-03-25	1987-04-29	Ici Plc	Anti-tumour agents
US4857530A (en) *	1987-11-03	1989-08-15	Warner-Lambert Company	Substituted quinazolinones as anticancer agents
US4902624A (en) *	1987-11-23	1990-02-20	Eastman Kodak Company	Temperature cycling cuvette
GB8727737D0 (en) *	1987-11-26	1987-12-31	Ici Plc	Antitumour agents
GB8829296D0 (en) *	1988-12-15	1989-01-25	Ici Plc	Anti-tumour compounds
US5405851A (en) *	1990-06-19	1995-04-11	Burroughs Wellcome Co.	Pharmaceutical compounds
GB9013615D0 (en) *	1990-06-19	1990-08-08	Wellcome Found	Pharmaceutical compounds

1990
- 1990-06-19 GB GB909013615A patent/GB9013615D0/en active Pending
1991
- 1991-06-18 AU AU80943/91A patent/AU639815B2/en not_active Ceased
- 1991-06-18 DK DK91910823T patent/DK0535034T3/da active
- 1991-06-18 ZA ZA914676A patent/ZA914676B/xx unknown
- 1991-06-18 AT AT91910823T patent/ATE222243T1/de not_active IP Right Cessation
- 1991-06-18 IL IL9854291A patent/IL98542A/en not_active IP Right Cessation
- 1991-06-18 PL PL91297195A patent/PL169927B1/pl unknown
- 1991-06-18 MC MC91@@D patent/MC2290A1/xx unknown
- 1991-06-18 NZ NZ238582A patent/NZ238582A/en unknown
- 1991-06-18 PT PT98021A patent/PT98021B/pt not_active IP Right Cessation
- 1991-06-18 MY MYPI91001094A patent/MY107001A/en unknown
- 1991-06-18 WO PCT/GB1991/000977 patent/WO1991019700A1/en not_active Ceased
- 1991-06-18 ES ES91910823T patent/ES2178632T3/es not_active Expired - Lifetime
- 1991-06-18 HU HU924011A patent/HUT62273A/hu unknown
- 1991-06-18 IE IE207391A patent/IE912073A1/en unknown
- 1991-06-18 EP EP91910823A patent/EP0535034B1/en not_active Expired - Lifetime
- 1991-06-18 CA CA002085589A patent/CA2085589C/en not_active Expired - Lifetime
- 1991-06-18 KR KR1019920703287A patent/KR0183042B1/ko not_active Expired - Fee Related
- 1991-06-18 CN CN91105021A patent/CN1049215C/zh not_active Expired - Fee Related
- 1991-06-18 DK DK02075192T patent/DK1199307T3/da active
- 1991-06-18 ES ES02075192T patent/ES2211851T3/es not_active Expired - Lifetime
- 1991-06-18 AP APAP/P/1991/000283A patent/AP218A/en active
- 1991-06-18 AT AT02075192T patent/ATE260262T1/de not_active IP Right Cessation
- 1991-06-18 JP JP3510950A patent/JP2966929B2/ja not_active Expired - Fee Related
- 1991-06-18 EP EP02075192A patent/EP1199307B1/en not_active Expired - Lifetime
- 1991-06-18 DE DE69133371T patent/DE69133371T2/de not_active Expired - Fee Related
- 1991-06-18 DE DE69133088T patent/DE69133088T2/de not_active Expired - Fee Related
- 1991-06-18 CS CS911863A patent/CS186391A3/cs unknown
1992
- 1992-12-18 FI FI925778A patent/FI925778A0/fi not_active Application Discontinuation
- 1992-12-18 NO NO924929A patent/NO924929D0/no unknown
1993
- 1993-01-13 US US07/956,018 patent/US6090941A/en not_active Expired - Fee Related
1995
- 1995-05-12 HU HU95P/P00133P patent/HU211265A9/hu unknown
- 1995-05-25 US US08/449,959 patent/US5663337A/en not_active Expired - Lifetime
- 1995-05-26 US US08/452,337 patent/US5661155A/en not_active Expired - Lifetime
2000
- 2000-06-06 US US09/588,790 patent/US6306865B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
US5661155A (en)	1997-08-26
IL98542A0 (en)	1992-07-15
DK0535034T3 (da)	2002-12-09
PT98021B (pt)	1998-11-30
HU211265A9 (en)	1995-11-28
FI925778A7 (fi)	1992-12-18
US6090941A (en)	2000-07-18
NZ238582A (en)	1993-12-23
FI925778A0 (fi)	1992-12-18
ES2211851T3 (es)	2004-07-16
HU9204011D0 (en)	1993-03-29
JPH05507704A (ja)	1993-11-04
CA2085589C (en)	2001-12-18
EP1199307B1 (en)	2004-02-25
KR930701415A (ko)	1993-06-11
DE69133088T2 (de)	2003-03-20
US6306865B1 (en)	2001-10-23
KR0183042B1 (ko)	1999-05-01
DE69133371D1 (de)	2004-04-01
MY107001A (en)	1995-08-30
IE912073A1 (en)	1992-01-01
DE69133088D1 (de)	2002-09-19
EP0535034A1 (en)	1993-04-07
JP2966929B2 (ja)	1999-10-25
CA2085589A1 (en)	1991-12-20
CN1049215C (zh)	2000-02-09
AU639815B2 (en)	1993-08-05
GB9013615D0 (en)	1990-08-08
HUT62273A (en)	1993-04-28
NO924929L (no)	1992-12-18
DE69133371T2 (de)	2005-01-27
AP218A (en)	1992-09-27
MC2290A1 (fr)	1993-07-14
ES2178632T3 (es)	2003-01-01
AU8094391A (en)	1992-01-07
PL169927B1 (pl)	1996-09-30
EP1199307A1 (en)	2002-04-24
DK1199307T3 (da)	2004-06-14
WO1991019700A1 (en)	1991-12-26
IL98542A (en)	1995-05-26
ZA914676B (en)	1993-02-24
EP0535034B1 (en)	2002-08-14
ATE222243T1 (de)	2002-08-15
CN1058208A (zh)	1992-01-29
PT98021A (pt)	1992-04-30
AP9100283A0 (en)	1991-07-31
ATE260262T1 (de)	2004-03-15
US5663337A (en)	1997-09-02
NO924929D0 (no)	1992-12-18

Publication	Publication Date	Title
US6090941A (en)	2000-07-18	Pharmaceutically active benzoquinazoline compounds
US20050171101A1 (en)	2005-08-04	Phenanthridinones as parp inhibitors
EP0831829B1 (en)	2003-08-20	Heterocyclic ring-fused pyrimidine derivatives
FI113765B (fi)	2004-06-15	Menetelmä uusien antiproliferatiivisten 5-substituoitujen kinatsoliiniyhdisteiden valmistamiseksi
JP7157764B2 (ja)	2022-10-20	新規なピペリジン－２，６－ジオン誘導体及びその用途
ES2262087T3 (es)	2006-11-16	Compuestos heteroaromiticos biciclicos como inhibidores de proteina tirosina cinasa.
JP2000508657A (ja)	2000-07-11	チロシンキナーゼの不可逆的阻害剤
US6407116B1 (en)	2002-06-18	Nitrogenous fused-ring compounds, process for the preparation of the same, and drugs
BR112013004750B1 (pt)	2021-06-15	Derivados de quinolina e quinoxalina como inibidores da cinase
HK1246294A1 (zh)	2018-09-07	稠环或三环芳基嘧啶化合物用作激酶抑制剂
SK283952B6 (sk)	2004-06-08	Pyrido [2,3-D]pyrimidíny a farmaceutické kompozície na ich báze
WO2016022460A1 (en)	2016-02-11	Potent dual brd4-kinase inhibitors as cancer therapeutics
AU2006271297B2 (en)	2012-02-02	Novel heterocyclidene acetamide derivative
CA3093323A1 (en)	2019-09-12	Oxazino-quinazoline and oxazino-quinoline type compound, preparation method and uses thereof
US5405851A (en)	1995-04-11	Pharmaceutical compounds
US6762188B1 (en)	2004-07-13	Pharmaceutically active benzoquinazoline compounds
AU680431B2 (en)	1997-07-31	2,5-disubstituted isoquindazole-6-(2H)-ones
CN104860890A (zh)	2015-08-26	T790m突变型egfr的抑制剂及其在制备抗肿瘤药物中的应用
KR870000279B1 (ko)	1987-02-23	피리도 [1,4] 벤조디아제핀 및 [2-[(니트로피리디닐) 아미노]페닐] 아릴메타논의 제조방법
CN117285527A (zh)	2023-12-26	一种噌啉类par4拮抗剂及其医药应用