ZA200403203B - Quinazoline derivatives as antitumor agents. - Google Patents
Quinazoline derivatives as antitumor agents. Download PDFInfo
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- ZA200403203B ZA200403203B ZA200403203A ZA200403203A ZA200403203B ZA 200403203 B ZA200403203 B ZA 200403203B ZA 200403203 A ZA200403203 A ZA 200403203A ZA 200403203 A ZA200403203 A ZA 200403203A ZA 200403203 B ZA200403203 B ZA 200403203B
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- ZA
- South Africa
- Prior art keywords
- alkyl
- group
- formula
- yloxy
- amino
- Prior art date
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- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title description 65
- 239000002246 antineoplastic agent Substances 0.000 title description 2
- -1 hydroxy, cyano, amino, carboxy, carbamoyl Chemical group 0.000 claims description 1246
- 125000000217 alkyl group Chemical group 0.000 claims description 966
- 239000001257 hydrogen Substances 0.000 claims description 241
- 229910052739 hydrogen Inorganic materials 0.000 claims description 241
- 150000001875 compounds Chemical class 0.000 claims description 211
- 125000001424 substituent group Chemical group 0.000 claims description 188
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 163
- 125000000623 heterocyclic group Chemical group 0.000 claims description 157
- 238000000034 method Methods 0.000 claims description 119
- 238000006243 chemical reaction Methods 0.000 claims description 108
- 125000003545 alkoxy group Chemical group 0.000 claims description 106
- 125000001153 fluoro group Chemical group F* 0.000 claims description 106
- 125000003282 alkyl amino group Chemical group 0.000 claims description 96
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 95
- 150000003839 salts Chemical class 0.000 claims description 89
- 125000005843 halogen group Chemical group 0.000 claims description 87
- 125000000304 alkynyl group Chemical group 0.000 claims description 86
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 84
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 82
- 230000008569 process Effects 0.000 claims description 79
- 229910052757 nitrogen Inorganic materials 0.000 claims description 78
- 125000003342 alkenyl group Chemical group 0.000 claims description 76
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 74
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 73
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 72
- 125000001589 carboacyl group Chemical group 0.000 claims description 68
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 67
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 66
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 65
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 61
- 229910052760 oxygen Inorganic materials 0.000 claims description 60
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 55
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 50
- 125000006239 protecting group Chemical group 0.000 claims description 48
- 125000004414 alkyl thio group Chemical group 0.000 claims description 47
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 45
- 125000001072 heteroaryl group Chemical group 0.000 claims description 45
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 44
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 44
- 125000003118 aryl group Chemical group 0.000 claims description 44
- 125000000524 functional group Chemical group 0.000 claims description 44
- 238000004519 manufacturing process Methods 0.000 claims description 44
- 206010028980 Neoplasm Diseases 0.000 claims description 43
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 39
- 238000011282 treatment Methods 0.000 claims description 39
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 38
- 125000004423 acyloxy group Chemical group 0.000 claims description 34
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 34
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 34
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 33
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 32
- 229910052717 sulfur Inorganic materials 0.000 claims description 32
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 30
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 29
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 27
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 26
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 26
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 26
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- 125000004518 1,2,5-thiadiazol-3-yl group Chemical group S1N=C(C=N1)* 0.000 claims description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 22
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 21
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 21
- 241001465754 Metazoa Species 0.000 claims description 19
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 19
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 18
- 241000282414 Homo sapiens Species 0.000 claims description 18
- 230000005764 inhibitory process Effects 0.000 claims description 18
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 18
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 17
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 17
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 17
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 17
- 125000004512 1,2,3-thiadiazol-4-yl group Chemical group S1N=NC(=C1)* 0.000 claims description 16
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 16
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 16
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 15
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 15
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 14
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 14
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 14
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 14
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 13
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 13
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 13
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 13
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 13
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 12
- 238000005859 coupling reaction Methods 0.000 claims description 12
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 12
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
- 102000001301 EGF receptor Human genes 0.000 claims description 11
- 108060006698 EGF receptor Proteins 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 239000003638 chemical reducing agent Substances 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 238000003780 insertion Methods 0.000 claims description 10
- 230000037431 insertion Effects 0.000 claims description 10
- 125000003386 piperidinyl group Chemical group 0.000 claims description 10
- 230000002265 prevention Effects 0.000 claims description 10
- 125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 claims description 9
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 9
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- 230000008878 coupling Effects 0.000 claims description 9
- 238000010168 coupling process Methods 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 8
- 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 claims description 7
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 7
- 125000002393 azetidinyl group Chemical group 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 238000003776 cleavage reaction Methods 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 6
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 6
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 5
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 230000029936 alkylation Effects 0.000 claims description 5
- 238000005804 alkylation reaction Methods 0.000 claims description 5
- 125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 5
- 230000007017 scission Effects 0.000 claims description 5
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 4
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 claims description 4
- 230000010933 acylation Effects 0.000 claims description 4
- 238000005917 acylation reaction Methods 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 4
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 230000003647 oxidation Effects 0.000 claims description 4
- 238000007254 oxidation reaction Methods 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 238000006268 reductive amination reaction Methods 0.000 claims description 4
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- DMEKUKDWAIXWSL-UHFFFAOYSA-N n,n-dimethyl-7-nitro-9h-fluoren-2-amine Chemical compound [O-][N+](=O)C1=CC=C2C3=CC=C(N(C)C)C=C3CC2=C1 DMEKUKDWAIXWSL-UHFFFAOYSA-N 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 claims description 2
- 125000004510 1,3,4-oxadiazol-5-yl group Chemical group O1C=NN=C1* 0.000 claims description 2
- LMSDCQDQSKEMTB-UHFFFAOYSA-N 2-[2-[2-chloro-4-[[5-(1-methylpiperidin-4-yl)oxyquinazolin-4-yl]amino]phenyl]sulfanylimidazol-1-yl]acetonitrile Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(SC=4N(C=CN=4)CC#N)=CC=3)=C12 LMSDCQDQSKEMTB-UHFFFAOYSA-N 0.000 claims description 2
- SEUIXENYEPZYRJ-UHFFFAOYSA-N 2-[[2-chloro-4-[[5-(1-methylpiperidin-4-yl)oxyquinazolin-4-yl]amino]phenoxy]methyl]benzonitrile Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4C(=CC=CC=4)C#N)=CC=3)=C12 SEUIXENYEPZYRJ-UHFFFAOYSA-N 0.000 claims description 2
- JTYRPYCCKFYWRC-UHFFFAOYSA-N 3,4,4a,5,6,7,8,8a-octahydro-2h-quinolin-1-yl-[2-ethynyl-4-[[5-(1-methylpiperidin-4-yl)oxyquinazolin-4-yl]amino]phenyl]methanone Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C(C(C(=O)N4C5CCCCC5CCC4)=CC=3)C#C)=C12 JTYRPYCCKFYWRC-UHFFFAOYSA-N 0.000 claims description 2
- XQCVZTVGBNNNGI-UHFFFAOYSA-N 4-[[2-chloro-4-[[5-(1-methylpiperidin-4-yl)oxyquinazolin-4-yl]amino]phenoxy]methyl]-1,3-thiazol-2-amine Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=C(N)SC=4)=CC=3)=C12 XQCVZTVGBNNNGI-UHFFFAOYSA-N 0.000 claims description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 2
- 150000001204 N-oxides Chemical class 0.000 claims description 2
- IBBKRHQKDWMGAK-UHFFFAOYSA-N [2-chloro-4-[[5-(1-methylpiperidin-4-yl)oxyquinazolin-4-yl]amino]phenyl]-thiophen-2-ylmethanone Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(C(=O)C=4SC=CC=4)=CC=3)=C12 IBBKRHQKDWMGAK-UHFFFAOYSA-N 0.000 claims description 2
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 claims description 2
- 150000002473 indoazoles Chemical class 0.000 claims description 2
- 125000000468 ketone group Chemical group 0.000 claims description 2
- JYQFMMYOKWXKHA-UHFFFAOYSA-N n-(1-benzylindol-5-yl)-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C4C=CN(CC=5C=CC=CC=5)C4=CC=3)=C12 JYQFMMYOKWXKHA-UHFFFAOYSA-N 0.000 claims description 2
- DTPHUOIKLOOWJX-UHFFFAOYSA-N n-(3-chloro-4-phenoxyphenyl)-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OC=4C=CC=CC=4)=CC=3)=C12 DTPHUOIKLOOWJX-UHFFFAOYSA-N 0.000 claims description 2
- RVGDTOSFHWDBLK-UHFFFAOYSA-N n-(3-methyl-4-phenylmethoxyphenyl)-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C(C)C(OCC=4C=CC=CC=4)=CC=3)=C12 RVGDTOSFHWDBLK-UHFFFAOYSA-N 0.000 claims description 2
- CXWMQFRBAIPPNS-UHFFFAOYSA-N n-[1-[(2,5-dimethylphenyl)methyl]indol-5-yl]-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C4C=CN(CC=5C(=CC=C(C)C=5)C)C4=CC=3)=C12 CXWMQFRBAIPPNS-UHFFFAOYSA-N 0.000 claims description 2
- LDPOMKGCIBEBEI-UHFFFAOYSA-N n-[1-[(2-chlorophenyl)methyl]indol-5-yl]-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C4C=CN(CC=5C(=CC=CC=5)Cl)C4=CC=3)=C12 LDPOMKGCIBEBEI-UHFFFAOYSA-N 0.000 claims description 2
- QCDFTBHCRSIZPQ-UHFFFAOYSA-N n-[1-[(2-fluorophenyl)methyl]indol-5-yl]-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C4C=CN(CC=5C(=CC=CC=5)F)C4=CC=3)=C12 QCDFTBHCRSIZPQ-UHFFFAOYSA-N 0.000 claims description 2
- BXHXRYYJSRYCFB-UHFFFAOYSA-N n-[1-[(2-methoxyphenyl)methyl]indol-5-yl]-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound COC1=CC=CC=C1CN1C2=CC=C(NC=3C4=C(OC5CCN(C)CC5)C=CC=C4N=CN=3)C=C2C=C1 BXHXRYYJSRYCFB-UHFFFAOYSA-N 0.000 claims description 2
- CFRKSCYTXXLRNQ-UHFFFAOYSA-N n-[1-[(3-fluorophenyl)methyl]indazol-5-yl]-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C4C=NN(CC=5C=C(F)C=CC=5)C4=CC=3)=C12 CFRKSCYTXXLRNQ-UHFFFAOYSA-N 0.000 claims description 2
- HBTRDSONVLGOKS-UHFFFAOYSA-N n-[3-chloro-4-(1,3-thiazol-4-ylmethoxy)phenyl]-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CSC=4)=CC=3)=C12 HBTRDSONVLGOKS-UHFFFAOYSA-N 0.000 claims description 2
- HHHOBSDBLSOFLQ-UHFFFAOYSA-N n-[3-chloro-4-(pyrazin-2-ylmethoxy)phenyl]-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=NC=4)=CC=3)=C12 HHHOBSDBLSOFLQ-UHFFFAOYSA-N 0.000 claims description 2
- MKNGJNHUZSCTJU-UHFFFAOYSA-N n-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 MKNGJNHUZSCTJU-UHFFFAOYSA-N 0.000 claims description 2
- ZIWNHMFNKNTHRU-UHFFFAOYSA-N n-[3-chloro-4-[(2,6-difluorophenyl)methoxy]phenyl]-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4C(=CC=CC=4F)F)=CC=3)=C12 ZIWNHMFNKNTHRU-UHFFFAOYSA-N 0.000 claims description 2
- AIWNFKKOWSWESK-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-5-(oxan-4-yloxy)quinazolin-4-amine Chemical compound FC1=CC=CC(COC=2C(=CC(NC=3C4=C(OC5CCOCC5)C=CC=C4N=CN=3)=CC=2)Cl)=C1 AIWNFKKOWSWESK-UHFFFAOYSA-N 0.000 claims description 2
- PKYOFSVQTJZERZ-UHFFFAOYSA-N n-[3-chloro-4-[(5-methyl-1,2-oxazol-3-yl)methoxy]phenyl]-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC4=NOC(C)=C4)=CC=3)=C12 PKYOFSVQTJZERZ-UHFFFAOYSA-N 0.000 claims description 2
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- UWYKJYMUNXTUKR-UHFFFAOYSA-N n-[3-chloro-4-(3-fluorophenoxy)phenyl]-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C1CN(C)CCC1OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OC=4C=C(F)C=CC=4)=CC=3)=C12 UWYKJYMUNXTUKR-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
- C07D239/94—Nitrogen atoms
-
- 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
-
- 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
- C07D401/14—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 three or more hetero rings
-
- 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
-
- 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
- C07D405/14—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 three or more hetero rings
-
- 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
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D417/14—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 three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Ceramic Engineering (AREA)
- Health & Medical Sciences (AREA)
- Manufacturing & Machinery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Structural Engineering (AREA)
- Materials Engineering (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
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GBGB0126433.2A GB0126433D0 (en) | 2001-11-03 | 2001-11-03 | Compounds |
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ZA200403200A ZA200403200B (en) | 2001-11-03 | 2004-04-28 | Quinazoline derivatives as antitumor agents. |
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CN (1) | CN1764651A (pt) |
AR (1) | AR037193A1 (pt) |
AT (1) | ATE421507T1 (pt) |
BR (1) | BR0213843A (pt) |
CA (1) | CA2465100A1 (pt) |
CO (1) | CO5580775A2 (pt) |
DE (1) | DE60230995D1 (pt) |
ES (1) | ES2319880T3 (pt) |
GB (1) | GB0126433D0 (pt) |
HK (1) | HK1065801A1 (pt) |
HU (1) | HUP0401994A2 (pt) |
IL (1) | IL161620A0 (pt) |
IS (1) | IS7241A (pt) |
MX (1) | MXPA04004220A (pt) |
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NZ (1) | NZ532523A (pt) |
PL (1) | PL369833A1 (pt) |
RU (1) | RU2004116908A (pt) |
TW (1) | TW200302221A (pt) |
WO (1) | WO2003040109A2 (pt) |
ZA (2) | ZA200403203B (pt) |
Families Citing this family (71)
Publication number | Priority date | Publication date | Assignee | Title |
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DE60211317T2 (de) * | 2001-03-23 | 2007-04-12 | Bayer Corp. | Rho-kinase inhibitoren |
DK1370552T3 (da) * | 2001-03-23 | 2007-05-07 | Bayer Pharmaceuticals Corp | Rho-kinase-inhibitorer |
RU2004116911A (ru) * | 2001-11-03 | 2005-11-10 | Астразенека Аб (Se) | Производные хиназолина в качестве противоопухолевых средств |
MXPA04007459A (es) * | 2002-02-01 | 2005-09-08 | Astrazeneca Ab | Compuestos de quinazolina. |
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 |
EP2277867B1 (en) | 2002-07-15 | 2012-12-05 | Symphony Evolution, Inc. | Compounds, pharmaceutical compositions thereof and their use in treating cancer |
GB0309009D0 (en) * | 2003-04-22 | 2003-05-28 | Astrazeneca Ab | Quinazoline derivatives |
GB0309850D0 (en) * | 2003-04-30 | 2003-06-04 | Astrazeneca Ab | Quinazoline derivatives |
US8309562B2 (en) | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | Compounds and therapeutical use thereof |
GB0317665D0 (en) | 2003-07-29 | 2003-09-03 | Astrazeneca Ab | Qinazoline derivatives |
SI1667991T1 (sl) * | 2003-09-16 | 2008-10-31 | Astrazeneca Ab | Kinazolinski derivati kot inhibitorji tirozin kinaze |
WO2005026151A1 (en) * | 2003-09-16 | 2005-03-24 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
WO2005026156A1 (en) * | 2003-09-16 | 2005-03-24 | Astrazeneca Ab | Quinazoline derivatives |
GB0321648D0 (en) * | 2003-09-16 | 2003-10-15 | Astrazeneca Ab | Quinazoline derivatives |
JP2007505871A (ja) * | 2003-09-16 | 2007-03-15 | アストラゼネカ アクチボラグ | キナゾリン誘導体 |
GB0322409D0 (en) * | 2003-09-25 | 2003-10-29 | Astrazeneca Ab | Quinazoline derivatives |
ES2371383T3 (es) | 2003-09-26 | 2011-12-30 | Exelixis, Inc. | N-[3-fluoro-4-({6-(metiloxi)-7-[(3-morfolin-4-ilpropil)oxi]quinolin-4-il}oxi)fenil]-n'-(4-fluorofenil)ciclopropan-1,1-dicarboxamida para el tratamiento del cáncer. |
DE10345875A1 (de) * | 2003-09-30 | 2005-04-21 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Vewendung und Verfahren zu ihrer Herstellung |
GB0326459D0 (en) * | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
EA011402B1 (ru) | 2004-01-23 | 2009-02-27 | Эмджен Инк. | Азотсодержащие гетероциклические производные и их фармацевтические применения |
AU2005207946A1 (en) | 2004-01-23 | 2005-08-11 | Amgen Inc. | Quinoline quinazoline pyridine and pyrimidine counds and their use in the treatment of inflammation angiogenesis and cancer |
ES2315834T3 (es) * | 2004-02-03 | 2009-04-01 | Astrazeneca Ab | Derivados de quinazolina. |
UA85706C2 (en) | 2004-05-06 | 2009-02-25 | Уорнер-Ламберт Компани Ллси | 4-phenylaminoquinazolin-6-yl amides |
CN1993349A (zh) * | 2004-06-04 | 2007-07-04 | 阿斯利康(瑞典)有限公司 | 作为erbb受体酪氨酸激酶的喹唑啉衍生物 |
JP4237242B2 (ja) | 2004-10-12 | 2009-03-11 | アストラゼネカ アクチボラグ | キナゾリン誘導体 |
AU2005312048B2 (en) | 2004-11-30 | 2012-08-02 | Amgen Inc. | Quinolines and quinazoline analogs and their use as medicaments for treating cancer |
EP1828152B1 (en) * | 2004-12-08 | 2008-08-20 | Bristol-Myers Squibb Company | Heterocyclic compounds as inhibitors of factor viia |
ATE501148T1 (de) * | 2004-12-14 | 2011-03-15 | Astrazeneca Ab | Pyrazolopyrimidinverbindungen als antitumormittel |
US8258145B2 (en) | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
EP1833482A4 (en) | 2005-01-03 | 2011-02-16 | Myriad Genetics Inc | COMPOUNDS AND ITS THERAPEUTIC USE |
GB0504475D0 (en) * | 2005-03-04 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
GB0504474D0 (en) * | 2005-03-04 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
JO2787B1 (en) | 2005-04-27 | 2014-03-15 | امجين إنك, | Alternative amide derivatives and methods of use |
GB0508715D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
GB0508717D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
CN101277939A (zh) * | 2005-09-09 | 2008-10-01 | 布里斯托尔-迈尔斯斯奎布公司 | 无环ikur抑制剂 |
US20090239861A1 (en) * | 2005-09-20 | 2009-09-24 | Robert Hugh Bradbury | Quinazoline derivatives as anticancer agents |
DE602006018331D1 (de) * | 2005-09-20 | 2010-12-30 | Astrazeneca Ab | 4-(1h-indazol-5-ylamino)chinazolinverbindungen als inhibitoren der erbb-rezeptortyrosinkinase zur behandlung von krebs |
ATE446294T1 (de) | 2005-11-15 | 2009-11-15 | Array Biopharma Inc | N4-phenyl-chinazolin-4-aminderivate und verwandte verbindungen als inhibitoren der erbb-typ-i- rezeptortyrosinkinase zur behandlung hyperproliferativer krankheiten |
JP2009517450A (ja) * | 2005-12-02 | 2009-04-30 | アストラゼネカ アクチボラグ | チロシンキナーゼ阻害薬としての4−アニリノ置換キナゾリン誘導体 |
US20090029968A1 (en) * | 2005-12-02 | 2009-01-29 | Bernard Christophe Barlaam | Quinazoline derivatives used as inhibitors of erbb tyrosine kinase |
US7482607B2 (en) * | 2006-02-28 | 2009-01-27 | Lawrenceville Plasma Physics, Inc. | Method and apparatus for producing x-rays, ion beams and nuclear fusion energy |
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-
2001
- 2001-11-03 GB GBGB0126433.2A patent/GB0126433D0/en not_active Ceased
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2002
- 2002-10-31 BR BR0213843-3A patent/BR0213843A/pt not_active IP Right Cessation
- 2002-10-31 US US10/494,388 patent/US20050054662A1/en not_active Abandoned
- 2002-10-31 EP EP02774961A patent/EP1444211B1/en not_active Expired - Lifetime
- 2002-10-31 MX MXPA04004220A patent/MXPA04004220A/es unknown
- 2002-10-31 RU RU2004116908/04A patent/RU2004116908A/ru not_active Application Discontinuation
- 2002-10-31 AT AT02774961T patent/ATE421507T1/de not_active IP Right Cessation
- 2002-10-31 JP JP2003542155A patent/JP2005511603A/ja not_active Ceased
- 2002-10-31 ES ES02774961T patent/ES2319880T3/es not_active Expired - Lifetime
- 2002-10-31 KR KR1020047006735A patent/KR20050042058A/ko not_active Application Discontinuation
- 2002-10-31 CN CNA028262824A patent/CN1764651A/zh active Pending
- 2002-10-31 WO PCT/GB2002/004932 patent/WO2003040109A2/en active Application Filing
- 2002-10-31 NZ NZ532523A patent/NZ532523A/en unknown
- 2002-10-31 DE DE60230995T patent/DE60230995D1/de not_active Expired - Lifetime
- 2002-10-31 HU HU0401994A patent/HUP0401994A2/hu unknown
- 2002-10-31 IL IL16162002A patent/IL161620A0/xx unknown
- 2002-10-31 PL PL02369833A patent/PL369833A1/xx not_active Application Discontinuation
- 2002-10-31 CA CA002465100A patent/CA2465100A1/en not_active Abandoned
- 2002-11-01 AR ARP020104182A patent/AR037193A1/es not_active Application Discontinuation
- 2002-11-01 TW TW091132368A patent/TW200302221A/zh unknown
-
2004
- 2004-04-28 ZA ZA200403203A patent/ZA200403203B/en unknown
- 2004-04-28 ZA ZA200403200A patent/ZA200403200B/en unknown
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- 2004-06-02 CO CO04051630A patent/CO5580775A2/es not_active Application Discontinuation
- 2004-06-03 NO NO20042288A patent/NO20042288L/no not_active Application Discontinuation
- 2004-11-08 HK HK04108771.4A patent/HK1065801A1/xx not_active IP Right Cessation
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HUP0401994A2 (hu) | 2005-01-28 |
JP2005511603A (ja) | 2005-04-28 |
MXPA04004220A (es) | 2004-09-10 |
AR037193A1 (es) | 2004-10-27 |
CA2465100A1 (en) | 2003-05-15 |
US20050054662A1 (en) | 2005-03-10 |
CN1764651A (zh) | 2006-04-26 |
PL369833A1 (en) | 2005-05-02 |
CO5580775A2 (es) | 2005-11-30 |
NZ532523A (en) | 2007-02-23 |
WO2003040109A2 (en) | 2003-05-15 |
ES2319880T3 (es) | 2009-05-14 |
HK1065801A1 (en) | 2005-03-04 |
TW200302221A (en) | 2003-08-01 |
EP1444211B1 (en) | 2009-01-21 |
IS7241A (is) | 2004-04-30 |
NO20042288L (no) | 2004-06-03 |
BR0213843A (pt) | 2004-08-31 |
US20070088044A1 (en) | 2007-04-19 |
ZA200403200B (en) | 2005-07-28 |
WO2003040109A3 (en) | 2003-06-26 |
DE60230995D1 (de) | 2009-03-12 |
EP1444211A2 (en) | 2004-08-11 |
KR20050042058A (ko) | 2005-05-04 |
ATE421507T1 (de) | 2009-02-15 |
RU2004116908A (ru) | 2005-11-10 |
IL161620A0 (en) | 2004-09-27 |
GB0126433D0 (en) | 2002-01-02 |
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