SK3842002A3 - Quinazoline derivatives, process for the preparation thereof and pharmaceutical composition comprising the same - Google Patents

Quinazoline derivatives, process for the preparation thereof and pharmaceutical composition comprising the same Download PDF

Info

Publication number: SK3842002A3
Authority: SK; Slovakia
Prior art keywords: group; alkyl; carbon atoms; moiety; alkoxy
Prior art date: 1999-09-21

Application number

SK384-2002A

Other languages

English (en)

Slovak (sk)

Inventor

Andrew Austen Mortlock

Nicholas John Keen

Original Assignee

Astrazeneca Ab

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.)

1999-09-21

Filing date

2000-09-18

Publication date

2002-10-08

2000-09-18 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2002-10-08 Publication of SK3842002A3 publication Critical patent/SK3842002A3/sk

Links

238000000034 method Methods 0.000 title claims description 78
238000002360 preparation method Methods 0.000 title claims description 77
239000008194 pharmaceutical composition Substances 0.000 title claims description 6
125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 160
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 71
239000001257 hydrogen Substances 0.000 claims abstract description 71
229910052717 sulfur Inorganic materials 0.000 claims abstract description 43
229910052760 oxygen Inorganic materials 0.000 claims abstract description 38
108090000461 Aurora Kinase A Proteins 0.000 claims abstract description 36
102100032311 Aurora kinase A Human genes 0.000 claims abstract description 30
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 28
150000002148 esters Chemical class 0.000 claims abstract description 26
150000003839 salts Chemical class 0.000 claims abstract description 20
150000001408 amides Chemical class 0.000 claims abstract description 14
125000000217 alkyl group Chemical group 0.000 claims description 317
125000004432 carbon atom Chemical group C* 0.000 claims description 316
125000000623 heterocyclic group Chemical group 0.000 claims description 98
125000003545 alkoxy group Chemical group 0.000 claims description 97
-1 cyano, amino Chemical group 0.000 claims description 85
229910052757 nitrogen Inorganic materials 0.000 claims description 74
125000000524 functional group Chemical group 0.000 claims description 64
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 62
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 57
125000001424 substituent group Chemical group 0.000 claims description 56
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 47
229910052736 halogen Inorganic materials 0.000 claims description 46
150000002367 halogens Chemical class 0.000 claims description 45
125000003118 aryl group Chemical group 0.000 claims description 44
229910052799 carbon Inorganic materials 0.000 claims description 44
150000002431 hydrogen Chemical class 0.000 claims description 43
125000004122 cyclic group Chemical group 0.000 claims description 41
125000005842 heteroatom Chemical group 0.000 claims description 40
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 36
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 35
150000002430 hydrocarbons Chemical class 0.000 claims description 32
239000001301 oxygen Substances 0.000 claims description 32
125000000753 cycloalkyl group Chemical group 0.000 claims description 31
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 30
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 30
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 29
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 29
239000011593 sulfur Substances 0.000 claims description 29
125000004433 nitrogen atom Chemical group N* 0.000 claims description 27
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 27
125000004043 oxo group Chemical group O=* 0.000 claims description 25
125000004093 cyano group Chemical group *C#N 0.000 claims description 24
125000005843 halogen group Chemical group 0.000 claims description 24
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 21
125000003342 alkenyl group Chemical group 0.000 claims description 19
125000004103 aminoalkyl group Chemical group 0.000 claims description 16
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 16
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 16
229920006395 saturated elastomer Polymers 0.000 claims description 16
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 15
125000003282 alkyl amino group Chemical group 0.000 claims description 15
125000002947 alkylene group Chemical group 0.000 claims description 15
125000000304 alkynyl group Chemical group 0.000 claims description 15
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
125000003302 alkenyloxy group Chemical group 0.000 claims description 13
125000000392 cycloalkenyl group Chemical group 0.000 claims description 12
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 12
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 12
LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 11
239000000651 prodrug Substances 0.000 claims description 11
229940002612 prodrug Drugs 0.000 claims description 11
125000003418 alkyl amino alkoxy group Chemical group 0.000 claims description 10
125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 claims description 10
125000003277 amino group Chemical group 0.000 claims description 10
125000002431 aminoalkoxy group Chemical group 0.000 claims description 10
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
229910052731 fluorine Inorganic materials 0.000 claims description 9
239000011737 fluorine Chemical group 0.000 claims description 9
125000004430 oxygen atom Chemical group O* 0.000 claims description 9
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
125000006699 (C1-C3) hydroxyalkyl group Chemical group 0.000 claims description 8
125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 8
125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 8
125000004429 atom Chemical group 0.000 claims description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
229930195733 hydrocarbon Natural products 0.000 claims description 8
239000004215 Carbon black (E152) Substances 0.000 claims description 7
241001465754 Metazoa Species 0.000 claims description 7
125000003710 aryl alkyl group Chemical group 0.000 claims description 7
125000004966 cyanoalkyl group Chemical group 0.000 claims description 7
125000004434 sulfur atom Chemical group 0.000 claims description 7
125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims description 6
125000004423 acyloxy group Chemical group 0.000 claims description 6
150000001721 carbon Chemical group 0.000 claims description 6
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
239000002243 precursor Substances 0.000 claims description 6
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
125000004450 alkenylene group Chemical group 0.000 claims description 5
125000004419 alkynylene group Chemical group 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
230000002401 inhibitory effect Effects 0.000 claims description 5
125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 4
125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 4
125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 4
125000004104 aryloxy group Chemical group 0.000 claims description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
125000001589 carboacyl group Chemical group 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
239000000460 chlorine Chemical group 0.000 claims description 4
125000001072 heteroaryl group Chemical group 0.000 claims description 4
125000002632 imidazolidinyl group Chemical group 0.000 claims description 4
125000004193 piperazinyl group Chemical group 0.000 claims description 4
125000003386 piperidinyl group Chemical group 0.000 claims description 4
125000006413 ring segment Chemical group 0.000 claims description 4
125000005415 substituted alkoxy group Chemical group 0.000 claims description 4
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 3
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 3
125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
229910019142 PO4 Inorganic materials 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
125000005518 carboxamido group Chemical group 0.000 claims description 3
125000005553 heteroaryloxy group Chemical group 0.000 claims description 3
125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 3
125000005646 oximino group Chemical group 0.000 claims description 3
125000003072 pyrazolidinyl group Chemical group 0.000 claims description 3
125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 2
125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 2
125000005133 alkynyloxy group Chemical group 0.000 claims description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
125000004956 cyclohexylene group Chemical group 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
125000000466 oxiranyl group Chemical group 0.000 claims description 2
125000003107 substituted aryl group Chemical group 0.000 claims description 2
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
125000003396 thiol group Chemical class [H]S* 0.000 claims description 2
125000001183 hydrocarbyl group Chemical group 0.000 claims 15
125000004414 alkyl thio group Chemical group 0.000 claims 3
125000004070 6 membered heterocyclic group Chemical group 0.000 claims 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
239000010452 phosphate Substances 0.000 claims 1
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims 1
238000006467 substitution reaction Methods 0.000 claims 1
206010028980 Neoplasm Diseases 0.000 abstract description 16
201000011510 cancer Diseases 0.000 abstract description 9
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 2
239000003112 inhibitor Substances 0.000 abstract 1
125000000962 organic group Chemical group 0.000 abstract 1
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 224
239000007787 solid Substances 0.000 description 97
238000001819 mass spectrum Methods 0.000 description 93
238000005160 1H NMR spectroscopy Methods 0.000 description 71
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
239000000243 solution Substances 0.000 description 46
239000000203 mixture Substances 0.000 description 41
210000004027 cell Anatomy 0.000 description 39
239000011541 reaction mixture Substances 0.000 description 38
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
238000012360 testing method Methods 0.000 description 25
239000002904 solvent Substances 0.000 description 24
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 22
238000004128 high performance liquid chromatography Methods 0.000 description 18
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 18
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
239000004480 active ingredient Substances 0.000 description 15
239000002244 precipitate Substances 0.000 description 15
238000003828 vacuum filtration Methods 0.000 description 15
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 14
238000003556 assay Methods 0.000 description 13
108090000623 proteins and genes Proteins 0.000 description 13
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
238000001035 drying Methods 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 11
201000010099 disease Diseases 0.000 description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
230000000694 effects Effects 0.000 description 11
239000000725 suspension Substances 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
230000022131 cell cycle Effects 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 9
239000012298 atmosphere Substances 0.000 description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
238000001727 in vivo Methods 0.000 description 9
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
108091003079 Bovine Serum Albumin Proteins 0.000 description 8
108020004414 DNA Proteins 0.000 description 8
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
238000006243 chemical reaction Methods 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
239000000843 powder Substances 0.000 description 8
238000010992 reflux Methods 0.000 description 8
239000007858 starting material Substances 0.000 description 8
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 7
102000004190 Enzymes Human genes 0.000 description 7
108090000790 Enzymes Proteins 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 7
229930182816 L-glutamine Natural products 0.000 description 7
229930182555 Penicillin Natural products 0.000 description 7
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 7
238000009835 boiling Methods 0.000 description 7
239000012894 fetal calf serum Substances 0.000 description 7
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
229940049954 penicillin Drugs 0.000 description 7
102000004169 proteins and genes Human genes 0.000 description 7
229960005322 streptomycin Drugs 0.000 description 7
CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 6
WOVKYSAHUYNSMH-RRKCRQDMSA-N 5-bromodeoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(Br)=C1 WOVKYSAHUYNSMH-RRKCRQDMSA-N 0.000 description 6
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 6
108091000080 Phosphotransferase Proteins 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 6
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230000014509 gene expression Effects 0.000 description 6
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102000020233 phosphotransferase Human genes 0.000 description 6
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230000002062 proliferating effect Effects 0.000 description 6
239000003765 sweetening agent Substances 0.000 description 6
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 6
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 6
125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 5
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
LLLHRNQLGUOJHP-UHFFFAOYSA-N 4-chloro-6,7-dimethoxyquinazoline Chemical compound C1=NC(Cl)=C2C=C(OC)C(OC)=CC2=N1 LLLHRNQLGUOJHP-UHFFFAOYSA-N 0.000 description 5
239000005909 Kieselgur Substances 0.000 description 5
241000700605 Viruses Species 0.000 description 5
239000000872 buffer Substances 0.000 description 5
239000003085 diluting agent Substances 0.000 description 5
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239000006166 lysate Substances 0.000 description 5
RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 description 5
239000003921 oil Substances 0.000 description 5
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239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
229960002920 sorbitol Drugs 0.000 description 1
239000008347 soybean phospholipid Substances 0.000 description 1
230000020347 spindle assembly Effects 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229930101283 tetracycline Natural products 0.000 description 1
229960002180 tetracycline Drugs 0.000 description 1
235000019364 tetracycline Nutrition 0.000 description 1
150000003522 tetracyclines Chemical class 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
230000009466 transformation Effects 0.000 description 1
230000007704 transition Effects 0.000 description 1
238000013519 translation Methods 0.000 description 1
230000017105 transposition Effects 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
239000012588 trypsin Substances 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
239000011534 wash buffer Substances 0.000 description 1
239000003643 water by type Substances 0.000 description 1

Classifications

- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- 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
- C07D239/94—Nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical 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)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Catching Or Destruction (AREA)
Ropes Or Cables (AREA)
Earth Drilling (AREA)

SK384-2002A 1999-09-21 2000-09-18 Quinazoline derivatives, process for the preparation thereof and pharmaceutical composition comprising the same SK3842002A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9922173.1A GB9922173D0 (en)	1999-09-21	1999-09-21	Chemical compounds
PCT/GB2000/003562 WO2001021595A1 (en)	1999-09-21	2000-09-18	Quinazoline derivatives

Publications (1)

Publication Number	Publication Date
SK3842002A3 true SK3842002A3 (en)	2002-10-08

Family

ID=10861219

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK384-2002A SK3842002A3 (en)	1999-09-21	2000-09-18	Quinazoline derivatives, process for the preparation thereof and pharmaceutical composition comprising the same

Country Status (23)

Country	Link
US (1)	US7105669B1 (no)
EP (1)	EP1218357B1 (no)
JP (1)	JP2003509498A (no)
KR (1)	KR20020029136A (no)
CN (1)	CN1391560A (no)
AT (1)	ATE292628T1 (no)
AU (1)	AU7433000A (no)
BG (1)	BG106535A (no)
BR (1)	BR0014136A (no)
CA (1)	CA2384284A1 (no)
CZ (1)	CZ20021007A3 (no)
DE (1)	DE60019317T2 (no)
EE (1)	EE200200148A (no)
GB (1)	GB9922173D0 (no)
HK (1)	HK1046687A1 (no)
HU (1)	HUP0204226A3 (no)
IL (1)	IL148498A0 (no)
IS (1)	IS6309A (no)
NO (1)	NO20021395L (no)
PL (1)	PL354972A1 (no)
SK (1)	SK3842002A3 (no)
WO (1)	WO2001021595A1 (no)
ZA (1)	ZA200201831B (no)

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CN1627944A (zh)	2002-01-17	2005-06-15	神经能质公司	取代的喹唑啉－4－基胺类似物作为辣椒辣素调节剂
US6924285B2 (en)	2002-03-30	2005-08-02	Boehringer Ingelheim Pharma Gmbh & Co.	Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them
ES2400339T3 (es)	2002-07-15	2013-04-09	Symphony Evolution, Inc.	Compuestos, composiciones farmacéuticas de los mismos y su uso en el tratamiento del cáncer
US8309562B2 (en)	2003-07-03	2012-11-13	Myrexis, Inc.	Compounds and therapeutical use thereof
WO2005003100A2 (en)	2003-07-03	2005-01-13	Myriad Genetics, Inc.	4-arylamino-quinazolines as activators of caspases and inducers of apoptosis
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US7329664B2 (en)	2003-07-16	2008-02-12	Neurogen Corporation	Substituted (7-pyridyl-4-phenylamino-quinazolin-2-yl)-methanol analogues
GB0317665D0 (en)	2003-07-29	2003-09-03	Astrazeneca Ab	Qinazoline derivatives
DK1667991T3 (da)	2003-09-16	2008-08-18	Astrazeneca Ab	Quinazolinderivater som tyrosinkinaseinhibitorer
GB0326459D0 (en)	2003-11-13	2003-12-17	Astrazeneca Ab	Quinazoline derivatives
WO2005061519A1 (en)	2003-12-19	2005-07-07	Takeda San Diego, Inc.	Kinase inhibitors
WO2005072731A1 (en) *	2004-01-29	2005-08-11	X-Ceptor Therapeutics, Inc.	3-phenyl-n- ((1, 3, 4) thiadiazol-2-yl) -acrylamide derivatives and related compounds as modulators of estrogen-related receptors for the treatment of e.g. cancer, rheumatoid arthritis or neurological disorders
US7550598B2 (en)	2004-08-18	2009-06-23	Takeda Pharmaceutical Company Limited	Kinase inhibitors
US7285569B2 (en)	2004-09-24	2007-10-23	Hoff Hoffmann-La Roche Inc.	Tricycles, their manufacture and use as pharmaceutical agents
AR050948A1 (es)	2004-09-24	2006-12-06	Hoffmann La Roche	Derivados de ftalazinona; su obtencion y su utilizacion en la fabricacion de medicamentos para el tratamiento del cancer.
CA2581516C (en)	2004-10-12	2013-06-11	Astrazeneca Ab	Quinazoline derivatives
DE602005023333D1 (de)	2004-10-15	2010-10-14	Takeda Pharmaceutical	Kinaseinhibitoren
US8258145B2 (en)	2005-01-03	2012-09-04	Myrexis, Inc.	Method of treating brain cancer
EP1856053A1 (en) *	2005-01-14	2007-11-21	Millennium Pharmaceuticals, Inc.	Cinnamide and hydrocinnamide derivatives with raf-kinase inhibitory activity
KR20070113286A (ko)	2005-04-14	2007-11-28	에프. 호프만-라 로슈 아게	아미노피라졸 유도체, 이의 제조 및 약학 제제로서의 용도
ES2545382T3 (es)	2005-04-28	2015-09-10	Mitsubishi Tanabe Pharma Corporation	Derivado de cianopiridina y su uso como medicamento
GB0510963D0 (en) *	2005-05-28	2005-07-06	Astrazeneca Ab	Chemical compounds
US8119655B2 (en)	2005-10-07	2012-02-21	Takeda Pharmaceutical Company Limited	Kinase inhibitors
UY30183A1 (es)	2006-03-02	2007-10-31	Astrazeneca Ab	Derivados de quinolina
WO2007099323A2 (en) *	2006-03-02	2007-09-07	Astrazeneca Ab	Quinoline derivatives
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EP1921070A1 (de)	2006-11-10	2008-05-14	Boehringer Ingelheim Pharma GmbH & Co. KG	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstelllung
WO2008095847A1 (de)	2007-02-06	2008-08-14	Boehringer Ingelheim International Gmbh	Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung
US7863283B2 (en)	2008-01-17	2011-01-04	Bayer Schering Pharma Ag	Sulphoximine-substituted quinazoline derivatives as immuno-modulators, their preparation and use as medicaments
US8497369B2 (en)	2008-02-07	2013-07-30	Boehringer Ingelheim International Gmbh	Spirocyclic heterocycles medicaments containing said compounds, use thereof and method for their production
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EP2313397B1 (de)	2008-08-08	2016-04-20	Boehringer Ingelheim International GmbH	Cyclohexyloxy-substituierte heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung
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1999
- 1999-09-21 GB GBGB9922173.1A patent/GB9922173D0/en not_active Ceased
2000
- 2000-09-18 JP JP2001524974A patent/JP2003509498A/ja active Pending
- 2000-09-18 WO PCT/GB2000/003562 patent/WO2001021595A1/en not_active Ceased
- 2000-09-18 BR BR0014136-4A patent/BR0014136A/pt not_active IP Right Cessation
- 2000-09-18 US US10/088,852 patent/US7105669B1/en not_active Expired - Fee Related
- 2000-09-18 AU AU74330/00A patent/AU7433000A/en not_active Abandoned
- 2000-09-18 EP EP00962682A patent/EP1218357B1/en not_active Expired - Lifetime
- 2000-09-18 AT AT00962682T patent/ATE292628T1/de not_active IP Right Cessation
- 2000-09-18 PL PL00354972A patent/PL354972A1/xx not_active Application Discontinuation
- 2000-09-18 CZ CZ20021007A patent/CZ20021007A3/cs unknown
- 2000-09-18 IL IL14849800A patent/IL148498A0/xx unknown
- 2000-09-18 CA CA002384284A patent/CA2384284A1/en not_active Abandoned
- 2000-09-18 SK SK384-2002A patent/SK3842002A3/sk unknown
- 2000-09-18 HK HK02108373.8A patent/HK1046687A1/zh unknown
- 2000-09-18 DE DE60019317T patent/DE60019317T2/de not_active Expired - Fee Related
- 2000-09-18 CN CN00816000A patent/CN1391560A/zh active Pending
- 2000-09-18 KR KR1020027003679A patent/KR20020029136A/ko not_active Withdrawn
- 2000-09-18 EE EEP200200148A patent/EE200200148A/xx unknown
- 2000-09-18 HU HU0204226A patent/HUP0204226A3/hu unknown
2002
- 2002-03-05 ZA ZA200201831A patent/ZA200201831B/xx unknown
- 2002-03-19 IS IS6309A patent/IS6309A/is unknown
- 2002-03-20 BG BG106535A patent/BG106535A/bg unknown
- 2002-03-20 NO NO20021395A patent/NO20021395L/no unknown

Also Published As

Publication number	Publication date
HUP0204226A2 (en)	2003-05-28
HUP0204226A3 (en)	2003-07-28
NO20021395D0 (no)	2002-03-20
CZ20021007A3 (cs)	2002-06-12
DE60019317T2 (de)	2006-03-09
PL354972A1 (en)	2004-03-22
GB9922173D0 (en)	1999-11-17
US7105669B1 (en)	2006-09-12
BR0014136A (pt)	2002-05-21
HK1046687A1 (zh)	2003-01-24
DE60019317D1 (de)	2005-05-12
EP1218357B1 (en)	2005-04-06
CN1391560A (zh)	2003-01-15
KR20020029136A (ko)	2002-04-17
BG106535A (bg)	2002-12-29
ATE292628T1 (de)	2005-04-15
EE200200148A (et)	2003-04-15
CA2384284A1 (en)	2001-03-29
IL148498A0 (en)	2002-09-12
EP1218357A1 (en)	2002-07-03
AU7433000A (en)	2001-04-24
WO2001021595A1 (en)	2001-03-29
NO20021395L (no)	2002-05-15
IS6309A (is)	2002-03-19
JP2003509498A (ja)	2003-03-11
ZA200201831B (en)	2003-08-27

Publication	Publication Date	Title
CZ20021007A3 (cs)	2002-06-12	Deriváty chinazolinu, způsob jejich přípravy a farmaceutický prostředek, který je obsahuje
SK3822002A3 (en)	2002-10-08	Quinazoline derivatives, process for the preparation thereof and their use
SK3832002A3 (en)	2002-11-06	Quinazoline compounds and pharmaceutical compositions containing them
SK3872002A3 (en)	2002-12-03	Therapeutic quinazoline derivatives, method for the preparation thereof and pharmaceutical composition comprising same
EP1463506B1 (en)	2009-10-21	Substituted quinazoline derivatives as inhibitors of aurora kinases
BG107376A (bg)	2003-09-30	Заместени хиназолинови производни и тяхното използване като инхибитори
EP1294709A2 (en)	2003-03-26	Quinoline derivatives and their use as aurora 2 kinase inhibitors