AP218A - Benzoquinazole derivatives and pharmaceutical compounds thereof. - Google Patents

Benzoquinazole derivatives and pharmaceutical compounds thereof. Download PDF

Info

Publication number: AP218A
Authority: AP; ARIPO
Prior art keywords: group; amino; methyl; compound; hydrogen
Prior art date: 1990-06-19

Application number

APAP/P/1991/000283A

Other languages

English (en)

Other versions

AP9100283A0 (en

Inventor

William Pendergast

Howard Dickerson

Julius Vass Johnson

Robert Ferone

Original Assignee

The Wellcome Foundation Ltd

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

1992-09-27

1991-06-18 Application filed by The Wellcome Foundation Ltd filed Critical The Wellcome Foundation Ltd

1991-07-31 Publication of AP9100283A0 publication Critical patent/AP9100283A0/xx

1992-09-27 Application granted granted Critical

1992-09-27 Publication of AP218A publication Critical patent/AP218A/en

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 166
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 79
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 77
239000001257 hydrogen Substances 0.000 claims abstract description 77
125000000217 alkyl group Chemical group 0.000 claims abstract description 65
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 48
150000003839 salts Chemical class 0.000 claims abstract description 45
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 21
150000002431 hydrogen Chemical class 0.000 claims abstract description 16
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 5
125000001589 carboacyl group Chemical group 0.000 claims abstract description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 216
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 69
239000002253 acid Substances 0.000 claims description 64
150000002148 esters Chemical group 0.000 claims description 55
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 55
229910052757 nitrogen Inorganic materials 0.000 claims description 50
238000006243 chemical reaction Methods 0.000 claims description 48
229960002989 glutamic acid Drugs 0.000 claims description 42
125000005843 halogen group Chemical group 0.000 claims description 37
-1 bromo, hydroxy Chemical group 0.000 claims description 34
238000000034 method Methods 0.000 claims description 31
125000005605 benzo group Chemical group 0.000 claims description 28
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
125000003118 aryl group Chemical group 0.000 claims description 22
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 22
125000001931 aliphatic group Chemical group 0.000 claims description 21
125000001424 substituent group Chemical group 0.000 claims description 19
125000003545 alkoxy group Chemical group 0.000 claims description 16
JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 claims description 16
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
125000003277 amino group Chemical group 0.000 claims description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
230000007062 hydrolysis Effects 0.000 claims description 10
238000006460 hydrolysis reaction Methods 0.000 claims description 10
241001465754 Metazoa Species 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 8
125000000539 amino acid group Chemical group 0.000 claims description 7
229910052799 carbon Inorganic materials 0.000 claims description 7
150000002825 nitriles Chemical class 0.000 claims description 7
RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 claims description 6
108010020346 Polyglutamic Acid Proteins 0.000 claims description 6
229920002643 polyglutamic acid Polymers 0.000 claims description 6
230000009467 reduction Effects 0.000 claims description 5
201000011510 cancer Diseases 0.000 claims description 4
238000006356 dehydrogenation reaction Methods 0.000 claims description 4
125000000623 heterocyclic group Chemical group 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
239000002243 precursor Substances 0.000 claims description 4
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
125000004432 carbon atom Chemical group C* 0.000 claims description 3
238000006073 displacement reaction Methods 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
238000003780 insertion Methods 0.000 claims description 3
230000037431 insertion Effects 0.000 claims description 3
230000008569 process Effects 0.000 claims description 3
125000006239 protecting group Chemical group 0.000 claims description 3
DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 claims description 2
125000002947 alkylene group Chemical group 0.000 claims description 2
229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
230000026030 halogenation Effects 0.000 claims description 2
238000005658 halogenation reaction Methods 0.000 claims description 2
208000032839 leukemia Diseases 0.000 claims description 2
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 2
125000001302 tertiary amino group Chemical group 0.000 claims description 2
NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical group CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 claims 1
125000001475 halogen functional group Chemical group 0.000 abstract 3
239000000243 solution Substances 0.000 description 225
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 213
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 193
238000005481 NMR spectroscopy Methods 0.000 description 179
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 158
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 142
239000007787 solid Substances 0.000 description 141
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 136
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 135
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 129
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 129
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 128
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 127
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 125
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 92
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 87
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 81
239000000203 mixture Substances 0.000 description 74
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 68
239000000741 silica gel Substances 0.000 description 66
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238000010992 reflux Methods 0.000 description 60
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 57
239000011541 reaction mixture Substances 0.000 description 56
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 55
239000000725 suspension Substances 0.000 description 54
238000001819 mass spectrum Methods 0.000 description 50
238000004587 chromatography analysis Methods 0.000 description 45
229960000583 acetic acid Drugs 0.000 description 44
XIPFMBOWZXULIA-UHFFFAOYSA-N pivalamide Chemical compound CC(C)(C)C(N)=O XIPFMBOWZXULIA-UHFFFAOYSA-N 0.000 description 44
229940093499 ethyl acetate Drugs 0.000 description 42
235000019439 ethyl acetate Nutrition 0.000 description 42
239000000047 product Substances 0.000 description 42
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 35
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 32
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 27
239000002244 precipitate Substances 0.000 description 25
238000003756 stirring Methods 0.000 description 25
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 23
239000012299 nitrogen atmosphere Substances 0.000 description 23
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
238000001914 filtration Methods 0.000 description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 21
238000001816 cooling Methods 0.000 description 20
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 20
125000001246 bromo group Chemical group Br* 0.000 description 18
239000003921 oil Substances 0.000 description 18
235000019198 oils Nutrition 0.000 description 17
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 16
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 16
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 15
239000000706 filtrate Substances 0.000 description 15
238000000746 purification Methods 0.000 description 15
229920002554 vinyl polymer Polymers 0.000 description 15
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
229940124530 sulfonamide Drugs 0.000 description 14
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 14
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 12
238000004113 cell culture Methods 0.000 description 12
239000012043 crude product Substances 0.000 description 12
238000000921 elemental analysis Methods 0.000 description 12
239000008194 pharmaceutical composition Substances 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
238000009472 formulation Methods 0.000 description 11
239000000543 intermediate Substances 0.000 description 11
229910052943 magnesium sulfate Inorganic materials 0.000 description 11
239000002904 solvent Substances 0.000 description 11
235000011149 sulphuric acid Nutrition 0.000 description 11
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 10
239000005711 Benzoic acid Substances 0.000 description 10
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
239000002585 base Substances 0.000 description 10
235000010233 benzoic acid Nutrition 0.000 description 10
231100000135 cytotoxicity Toxicity 0.000 description 10
230000003013 cytotoxicity Effects 0.000 description 10
239000001117 sulphuric acid Substances 0.000 description 10
206010028980 Neoplasm Diseases 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
238000009835 boiling Methods 0.000 description 9
150000005690 diesters Chemical class 0.000 description 9
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 9
238000001035 drying Methods 0.000 description 9
239000012362 glacial acetic acid Substances 0.000 description 9
238000001556 precipitation Methods 0.000 description 9
239000011734 sodium Substances 0.000 description 9
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
239000002609 medium Substances 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
229910000027 potassium carbonate Inorganic materials 0.000 description 8
FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 8
210000004881 tumor cell Anatomy 0.000 description 8
238000005160 1H NMR spectroscopy Methods 0.000 description 7
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239000004480 active ingredient Substances 0.000 description 7
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
239000010410 layer Substances 0.000 description 7
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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
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
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PQIUGRLKNKSKTC-UHFFFAOYSA-N benzo[h]quinazoline Chemical compound N1=CN=C2C3=CC=CC=C3C=CC2=C1 PQIUGRLKNKSKTC-UHFFFAOYSA-N 0.000 description 4
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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
WSEQLMQNPBNMSL-FJXQXJEOSA-N diethyl (2s)-2-aminopentanedioate;hydron;chloride Chemical compound Cl.CCOC(=O)CC[C@H](N)C(=O)OCC WSEQLMQNPBNMSL-FJXQXJEOSA-N 0.000 description 4
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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)

APAP/P/1991/000283A 1990-06-19 1991-06-18 Benzoquinazole derivatives and pharmaceutical compounds thereof. AP218A (en)

Applications Claiming Priority (1)

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

Publications (2)

Publication Number	Publication Date
AP9100283A0 AP9100283A0 (en)	1991-07-31
AP218A true AP218A (en)	1992-09-27

Family

ID=10677828

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
APAP/P/1991/000283A AP218A (en)	1990-06-19	1991-06-18	Benzoquinazole derivatives and pharmaceutical compounds thereof.

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)

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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

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EP0296848A1 (en) *	1987-06-23	1988-12-28	Biomeasure, Inc.	Biological response modifiers, their production, and their use in therapy or in prophylaxis
EP0373891A2 (en) *	1988-12-15	1990-06-20	Imperial Chemical Industries Plc	Anti-tumour agents

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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

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EP0296848A1 (en) *	1987-06-23	1988-12-28	Biomeasure, Inc.	Biological response modifiers, their production, and their use in therapy or in prophylaxis
EP0373891A2 (en) *	1988-12-15	1990-06-20	Imperial Chemical Industries Plc	Anti-tumour agents

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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
CS186391A3 (en)	1992-04-15
DE69133371T2 (de)	2005-01-27
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
US5661155A (en)	1997-08-26	Treatment of cancer with pharmaceutically active benzoquinazoline compounds
US5932574A (en)	1999-08-03	Quinazoline derivatives
KR100221011B1 (ko)	1999-09-15	항-종양 화합물, 이의 제조 방법 및 이를 함유하는 약학 조성물
CA2592286C (en)	2012-05-29	Quinazoline derivatives for inhibiting cancer cell growth and method for the preparation thereof
CA2417897C (en)	2009-03-31	Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them
EP0823900B1 (en)	2000-12-27	Quinazoline derivatives
US6403580B1 (en)	2002-06-11	Quinazolines, pharmaceutical compositions containing these compounds, their use and processes for preparing them
CZ20021008A3 (cs)	2002-06-12	Deriváty chinazolinu, způsob jejich přípravy a farmaceutický prostředek, který je obsahuje
JPH10506633A (ja)	1998-06-30	キナゾリン誘導体
SK283952B6 (sk)	2004-06-08	Pyrido [2,3-D]pyrimidíny a farmaceutické kompozície na ich báze
WO1996033978A1 (en)	1996-10-31	Quinazoline derivative
SK288378B6 (sk)	2016-07-01	Použitie chinazolínových derivátov ako inhibítorov angiogenézy
CZ20024120A3 (cs)	2003-03-12	Substituované chinazolinové deriváty a jejich použití jako inhibitory
EP0318225A2 (en)	1989-05-31	6-Aryl aminomethyl quinoline derivatives and their use as anti-tumour agents
US6762188B1 (en)	2004-07-13	Pharmaceutically active benzoquinazoline compounds
US5405851A (en)	1995-04-11	Pharmaceutical compounds
CA2417955A1 (en)	2003-01-30	Quinazolines, pharmaceutical compositions containing these compounds, their use and processes for preparing them