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
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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)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Public Health (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 (de)
EP (2)	EP0535034B1 (de)
JP (1)	JP2966929B2 (de)
KR (1)	KR0183042B1 (de)
CN (1)	CN1049215C (de)
AP (1)	AP218A (de)
AT (2)	ATE260262T1 (de)
AU (1)	AU639815B2 (de)
CA (1)	CA2085589C (de)
CS (1)	CS186391A3 (de)
DE (2)	DE69133371T2 (de)
DK (2)	DK1199307T3 (de)
ES (2)	ES2178632T3 (de)
FI (1)	FI925778A0 (de)
GB (1)	GB9013615D0 (de)
HU (2)	HUT62273A (de)
IE (1)	IE912073A1 (de)
IL (1)	IL98542A (de)
MC (1)	MC2290A1 (de)
MY (1)	MY107001A (de)
NO (1)	NO924929L (de)
NZ (1)	NZ238582A (de)
PL (1)	PL169927B1 (de)
PT (1)	PT98021B (de)
WO (1)	WO1991019700A1 (de)
ZA (1)	ZA914676B (de)

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
AU3883600A (en)	1999-03-16	2000-10-04	Regents Of The University Of California, The	Glycosylated polyamines
US6531454B1 (en)	1999-03-16	2003-03-11	The Regents Of The University Of California	Glycosylated polyamines and methods of use therefor
US6689381B2 (en)	2000-06-09	2004-02-10	Osi Pharmaceuticals, Inc.	Liposomal benzoquinazoline thymidylate synthase inhibitor formulations
RU2004112787A (ru) *	2001-09-26	2005-10-10	Байер Фармасьютикалс Корпорейшн (US)	Производные 1,6-нафтиридина как противодиабетические средства
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 (de)	2005-08-17	2007-02-21	Dan Stoicescu	Kondensierte Pyrimidinderivative als Inhibitoren der Folsäure-abhängiger Enzyme
EP2077290B1 (de)	2005-12-05	2010-04-21	Nitto Denko Corporation	Polyglutamat-Aminosäure-Konjugate und Verfahren
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 (de)	2007-02-14	2008-08-20	Dan Stoicescu	Kondensierte Pyrimidinderivaten zur Behandlung von Entzündungserkrankungen und Autoimmunerkrankungen
ES2430380T3 (es) *	2007-05-09	2013-11-20	Nitto Denko Corporation	Composiciones que incluyen un compuesto hidrófobo y un conjugado de poliaminoácido
CN101730549B (zh) *	2007-05-09	2015-12-09	日东电工株式会社	与铂类药物结合的聚合物
EP2155253A2 (de) *	2007-05-09	2010-02-24	Nitto Denko Corporation	Polyglutamatkonjugate und polyglutamat-aminosäure-konjugate mit mehreren wirkstoffen
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1990
- 1990-06-19 GB GB909013615A patent/GB9013615D0/en active Pending
1991
- 1991-06-18 CS CS911863A patent/CS186391A3/cs unknown
- 1991-06-18 CN CN91105021A patent/CN1049215C/zh not_active Expired - Fee Related
- 1991-06-18 CA CA002085589A patent/CA2085589C/en not_active Expired - Lifetime
- 1991-06-18 ES ES91910823T patent/ES2178632T3/es not_active Expired - Lifetime
- 1991-06-18 EP EP91910823A patent/EP0535034B1/de 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 DK DK02075192T patent/DK1199307T3/da active
- 1991-06-18 JP JP3510950A patent/JP2966929B2/ja not_active Expired - Fee Related
- 1991-06-18 HU HU924011A patent/HUT62273A/hu 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 DE DE69133371T patent/DE69133371T2/de not_active Expired - Fee Related
- 1991-06-18 WO PCT/GB1991/000977 patent/WO1991019700A1/en not_active Ceased
- 1991-06-18 DK DK91910823T patent/DK0535034T3/da active
- 1991-06-18 NZ NZ238582A patent/NZ238582A/en unknown
- 1991-06-18 ES ES02075192T patent/ES2211851T3/es not_active Expired - Lifetime
- 1991-06-18 IE IE207391A patent/IE912073A1/en unknown
- 1991-06-18 KR KR1019920703287A patent/KR0183042B1/ko not_active Expired - Fee Related
- 1991-06-18 MC MC91@@D patent/MC2290A1/xx unknown
- 1991-06-18 IL IL9854291A patent/IL98542A/en not_active IP Right Cessation
- 1991-06-18 DE DE69133088T patent/DE69133088T2/de not_active Expired - Fee Related
- 1991-06-18 AT AT91910823T patent/ATE222243T1/de not_active IP Right Cessation
- 1991-06-18 EP EP02075192A patent/EP1199307B1/de not_active Expired - Lifetime
- 1991-06-18 ZA ZA914676A patent/ZA914676B/xx unknown
- 1991-06-18 AU AU80943/91A patent/AU639815B2/en not_active Ceased
- 1991-06-18 PL PL91297195A patent/PL169927B1/pl unknown
1992
- 1992-12-18 FI FI925778A patent/FI925778A0/fi not_active Application Discontinuation
- 1992-12-18 NO NO92924929A patent/NO924929L/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
ES2211851T3 (es)	2004-07-16
PT98021B (pt)	1998-11-30
AU8094391A (en)	1992-01-07
DE69133088D1 (de)	2002-09-19
AU639815B2 (en)	1993-08-05
EP0535034B1 (de)	2002-08-14
DK1199307T3 (da)	2004-06-14
US5661155A (en)	1997-08-26
WO1991019700A1 (en)	1991-12-26
CA2085589A1 (en)	1991-12-20
CA2085589C (en)	2001-12-18
NO924929D0 (no)	1992-12-18
IL98542A0 (en)	1992-07-15
MC2290A1 (fr)	1993-07-14
PT98021A (pt)	1992-04-30
US6090941A (en)	2000-07-18
AP218A (en)	1992-09-27
MY107001A (en)	1995-08-30
IL98542A (en)	1995-05-26
US6306865B1 (en)	2001-10-23
EP1199307B1 (de)	2004-02-25
FI925778A7 (fi)	1992-12-18
ATE222243T1 (de)	2002-08-15
KR930701415A (ko)	1993-06-11
AP9100283A0 (en)	1991-07-31
ATE260262T1 (de)	2004-03-15
JPH05507704A (ja)	1993-11-04
CN1058208A (zh)	1992-01-29
PL169927B1 (pl)	1996-09-30
DE69133371D1 (de)	2004-04-01
HU211265A9 (en)	1995-11-28
NZ238582A (en)	1993-12-23
FI925778A0 (fi)	1992-12-18
EP1199307A1 (de)	2002-04-24
HUT62273A (en)	1993-04-28
DK0535034T3 (da)	2002-12-09
HU9204011D0 (en)	1993-03-29
ES2178632T3 (es)	2003-01-01
GB9013615D0 (en)	1990-08-08
EP0535034A1 (de)	1993-04-07
KR0183042B1 (ko)	1999-05-01
DE69133088T2 (de)	2003-03-20
CN1049215C (zh)	2000-02-09
ZA914676B (en)	1993-02-24
DE69133371T2 (de)	2005-01-27
IE912073A1 (en)	1992-01-01
US5663337A (en)	1997-09-02
JP2966929B2 (ja)	1999-10-25
NO924929L (no)	1992-12-18

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