MXPA06002965A - Derivados de quinazolina como agentes antitumor. - Google Patents
Derivados de quinazolina como agentes antitumor.Info
- Publication number
- MXPA06002965A MXPA06002965A MXPA06002965A MXPA06002965A MXPA06002965A MX PA06002965 A MXPA06002965 A MX PA06002965A MX PA06002965 A MXPA06002965 A MX PA06002965A MX PA06002965 A MXPA06002965 A MX PA06002965A MX PA06002965 A MXPA06002965 A MX PA06002965A
- Authority
- MX
- Mexico
- Prior art keywords
- carbon atoms
- alkyl
- amino
- phenyl
- oxy
- Prior art date
Links
- 239000002246 antineoplastic agent Substances 0.000 title description 3
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title description 2
- 230000000694 effects Effects 0.000 claims abstract description 12
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 10
- 241001465754 Metazoa Species 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 230000001028 anti-proliverative effect Effects 0.000 claims abstract description 3
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims abstract 4
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims abstract 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 1782
- -1 hydroxy, cyano, amino, carboxy, carbamoyl Chemical group 0.000 claims description 1016
- 125000000217 alkyl group Chemical group 0.000 claims description 402
- 229910052799 carbon Inorganic materials 0.000 claims description 348
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 329
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 269
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 258
- 125000003545 alkoxy group Chemical group 0.000 claims description 242
- 125000001424 substituent group Chemical group 0.000 claims description 214
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 203
- 229910052739 hydrogen Inorganic materials 0.000 claims description 126
- 239000001257 hydrogen Substances 0.000 claims description 126
- 125000000623 heterocyclic group Chemical group 0.000 claims description 118
- 229910052757 nitrogen Inorganic materials 0.000 claims description 101
- 229910052736 halogen Inorganic materials 0.000 claims description 96
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 93
- 229910052760 oxygen Inorganic materials 0.000 claims description 83
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 82
- 125000004429 atom Chemical group 0.000 claims description 78
- 150000003246 quinazolines Chemical class 0.000 claims description 74
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 71
- 125000001153 fluoro group Chemical group F* 0.000 claims description 64
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 63
- 150000002367 halogens Chemical group 0.000 claims description 62
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 58
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 57
- 125000005843 halogen group Chemical group 0.000 claims description 56
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 54
- 125000003342 alkenyl group Chemical group 0.000 claims description 54
- 125000000304 alkynyl group Chemical group 0.000 claims description 54
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 54
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 49
- 229910052717 sulfur Inorganic materials 0.000 claims description 49
- 125000003282 alkyl amino group Chemical group 0.000 claims description 47
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 46
- 150000001875 compounds Chemical class 0.000 claims description 46
- 125000004423 acyloxy group Chemical group 0.000 claims description 44
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 44
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 42
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 41
- 125000004414 alkyl thio group Chemical group 0.000 claims description 41
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 40
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 40
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 39
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 38
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 38
- DRYRBWIFRVMRPV-UHFFFAOYSA-N quinazolin-4-amine Chemical compound C1=CC=C2C(N)=NC=NC2=C1 DRYRBWIFRVMRPV-UHFFFAOYSA-N 0.000 claims description 38
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 33
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 33
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 32
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 31
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 28
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 27
- 125000001188 haloalkyl group Chemical group 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 26
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 26
- 150000001721 carbon Chemical group 0.000 claims description 25
- 125000003386 piperidinyl group Chemical group 0.000 claims description 24
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 24
- 125000004043 oxo group Chemical group O=* 0.000 claims description 23
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 22
- 125000002757 morpholinyl group Chemical group 0.000 claims description 22
- 125000004193 piperazinyl group Chemical group 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 21
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 20
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 20
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 20
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 20
- 239000001301 oxygen Substances 0.000 claims description 20
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 19
- 229920006395 saturated elastomer Polymers 0.000 claims description 19
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 18
- 239000011593 sulfur Substances 0.000 claims description 18
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 17
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 17
- 125000000524 functional group Chemical group 0.000 claims description 17
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 17
- 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 claims description 17
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 17
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 17
- 125000004076 pyridyl group Chemical group 0.000 claims description 17
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 13
- 125000005242 carbamoyl alkyl group Chemical group 0.000 claims description 13
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000002950 monocyclic group Chemical group 0.000 claims description 11
- 241000156724 Antirhea Species 0.000 claims description 10
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 10
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 10
- 238000003780 insertion Methods 0.000 claims description 10
- 230000037431 insertion Effects 0.000 claims description 10
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 claims description 10
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 9
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 claims description 9
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 8
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 8
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 8
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 8
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 claims description 7
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 7
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 7
- 125000002393 azetidinyl group Chemical group 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
- 125000003551 oxepanyl group Chemical group 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 125000006319 alkynyl amino group Chemical group 0.000 claims description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 6
- 238000005859 coupling reaction Methods 0.000 claims description 6
- 230000005764 inhibitory process Effects 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 125000005724 cycloalkenylene group Chemical group 0.000 claims description 5
- YOXHCYXIAVIFCZ-UHFFFAOYSA-N cyclopropanol Chemical compound OC1CC1 YOXHCYXIAVIFCZ-UHFFFAOYSA-N 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 5
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 4
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 230000008878 coupling Effects 0.000 claims description 4
- 238000010168 coupling process Methods 0.000 claims description 4
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 4
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 3
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 3
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 3
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 2
- KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical group C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 claims description 2
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 2
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 claims description 2
- GELVZYOEQVJIRR-UHFFFAOYSA-N 2-chloropyrazine Chemical compound ClC1=CN=CC=N1 GELVZYOEQVJIRR-UHFFFAOYSA-N 0.000 claims description 2
- UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 claims description 2
- IBWYHNOFSKJKKY-UHFFFAOYSA-N 3-chloropyridazine Chemical compound ClC1=CC=CN=N1 IBWYHNOFSKJKKY-UHFFFAOYSA-N 0.000 claims description 2
- 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 2
- DBPKMSBWOKAKLA-UHFFFAOYSA-N 4-chloropyrimidine Chemical compound ClC1=CC=NC=N1 DBPKMSBWOKAKLA-UHFFFAOYSA-N 0.000 claims description 2
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 2
- 101100439664 Arabidopsis thaliana CHR8 gene Proteins 0.000 claims description 2
- FQKPEMCXVOITPC-SNVBAGLBSA-N COCC(=O)N1C[C@@H](CC1)OC1=NC2=CC=CC=C2C(=N1)N Chemical compound COCC(=O)N1C[C@@H](CC1)OC1=NC2=CC=CC=C2C(=N1)N FQKPEMCXVOITPC-SNVBAGLBSA-N 0.000 claims description 2
- 125000004273 azetidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 2
- 210000004369 blood Anatomy 0.000 claims description 2
- 239000008280 blood Substances 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- 125000004570 thiomorpholin-3-yl group Chemical group N1C(CSCC1)* 0.000 claims description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 24
- 125000001589 carboacyl group Chemical group 0.000 claims 11
- 150000002431 hydrogen Chemical group 0.000 claims 5
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims 2
- SNLRBQMQODFNMA-JOCHJYFZSA-N 1-[(2r)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]morpholin-4-yl]-2-(dimethylamino)ethanone Chemical compound C1N(C(=O)CN(C)C)CCO[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 SNLRBQMQODFNMA-JOCHJYFZSA-N 0.000 claims 1
- MOMRGTMRWDEZEU-IBGZPJMESA-N 1-[(2s)-2-[[4-[3-chloro-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound C1=NC(C)=CC=C1OC(C(=C1)Cl)=CC=C1NC1=NC=NC2=CC=CC(OC[C@H]3N(CCC3)C(=O)CO)=C12 MOMRGTMRWDEZEU-IBGZPJMESA-N 0.000 claims 1
- SNLRBQMQODFNMA-QFIPXVFZSA-N 1-[(2s)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]morpholin-4-yl]-2-(dimethylamino)ethanone Chemical compound C1N(C(=O)CN(C)C)CCO[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 SNLRBQMQODFNMA-QFIPXVFZSA-N 0.000 claims 1
- GSAYQUSXZRUHFJ-QFIPXVFZSA-N 2-hydroxy-1-[(2s)-2-[[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxymethyl]piperidin-1-yl]ethanone Chemical compound C1=NC(C)=CC=C1OC(C(=C1)C)=CC=C1NC1=NC=NC2=CC=CC(OC[C@H]3N(CCCC3)C(=O)CO)=C12 GSAYQUSXZRUHFJ-QFIPXVFZSA-N 0.000 claims 1
- BXIUCQLZRZVCKN-NRFANRHFSA-N 2-hydroxy-1-[(2s)-2-[[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]ethanone Chemical compound C1=NC(C)=CC=C1OC(C(=C1)C)=CC=C1NC1=NC=NC2=CC=CC(OC[C@H]3N(CCC3)C(=O)CO)=C12 BXIUCQLZRZVCKN-NRFANRHFSA-N 0.000 claims 1
- BSDGZUDFPKIYQG-UHFFFAOYSA-N 4-bromopyridine Chemical compound BrC1=CC=NC=C1 BSDGZUDFPKIYQG-UHFFFAOYSA-N 0.000 claims 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 1
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- 239000000956 alloy Substances 0.000 claims 1
- 229910045601 alloy Inorganic materials 0.000 claims 1
- FLKYBGKDCCEQQM-WYUVZMMLSA-M cefazolin sodium Chemical compound [Na+].S1C(C)=NN=C1SCC1=C(C([O-])=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 FLKYBGKDCCEQQM-WYUVZMMLSA-M 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
- OARGTCOLYMEKPB-UHFFFAOYSA-N n-ethenyl-n-methylethanamine Chemical group CCN(C)C=C OARGTCOLYMEKPB-UHFFFAOYSA-N 0.000 claims 1
- 125000004569 thiomorpholin-2-yl group Chemical group N1CC(SCC1)* 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 100
- 125000002252 acyl group Chemical group 0.000 description 38
- 229960005419 nitrogen Drugs 0.000 description 26
- 206010028980 Neoplasm Diseases 0.000 description 25
- RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 20
- 201000011510 cancer Diseases 0.000 description 17
- 102000005962 receptors Human genes 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 description 13
- 239000002253 acid Substances 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 11
- 229910052801 chlorine Inorganic materials 0.000 description 11
- 125000005113 hydroxyalkoxy group Chemical group 0.000 description 11
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 11
- 125000004980 cyclopropylene group Chemical group 0.000 description 10
- 125000005191 hydroxyalkylamino group Chemical group 0.000 description 10
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 8
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 8
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 8
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 108700020796 Oncogene Proteins 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 229910052727 yttrium Inorganic materials 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 102000001301 EGF receptor Human genes 0.000 description 6
- 108060006698 EGF receptor Proteins 0.000 description 6
- 241000282414 Homo sapiens Species 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 5
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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
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- 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
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- 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
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- 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
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- 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
- C07D403/14—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 three or more hetero rings
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- 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
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- 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)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
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- Structural Engineering (AREA)
- Inorganic Chemistry (AREA)
- Materials Engineering (AREA)
- Urology & Nephrology (AREA)
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- Hematology (AREA)
- Oncology (AREA)
- Dermatology (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0321648.8A GB0321648D0 (en) | 2003-09-16 | 2003-09-16 | Quinazoline derivatives |
| PCT/GB2004/003936 WO2005026152A1 (en) | 2003-09-16 | 2004-09-14 | Quinazoline derivatives as antitumor agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA06002965A true MXPA06002965A (es) | 2006-06-14 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA06002965A MXPA06002965A (es) | 2003-09-16 | 2004-09-14 | Derivados de quinazolina como agentes antitumor. |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US20070015743A1 (OSRAM) |
| EP (1) | EP1664029B1 (OSRAM) |
| JP (1) | JP2007505874A (OSRAM) |
| CN (1) | CN1882572A (OSRAM) |
| AR (1) | AR045752A1 (OSRAM) |
| AT (1) | ATE450528T1 (OSRAM) |
| AU (1) | AU2004272351A1 (OSRAM) |
| BR (1) | BRPI0414486A (OSRAM) |
| CA (1) | CA2539024A1 (OSRAM) |
| DE (1) | DE602004024420D1 (OSRAM) |
| GB (1) | GB0321648D0 (OSRAM) |
| IL (1) | IL174260A0 (OSRAM) |
| MX (1) | MXPA06002965A (OSRAM) |
| NO (1) | NO20061320L (OSRAM) |
| TW (1) | TW200526628A (OSRAM) |
| WO (1) | WO2005026152A1 (OSRAM) |
| ZA (1) | ZA200602189B (OSRAM) |
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| GB0126433D0 (en) * | 2001-11-03 | 2002-01-02 | Astrazeneca Ab | Compounds |
| ATE423104T1 (de) * | 2001-11-03 | 2009-03-15 | Astrazeneca Ab | Quinazolin derivate als antitumor-mittel |
| 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 |
| GB0309009D0 (en) * | 2003-04-22 | 2003-05-28 | Astrazeneca Ab | Quinazoline derivatives |
| GB0309850D0 (en) * | 2003-04-30 | 2003-06-04 | Astrazeneca Ab | Quinazoline derivatives |
| WO2005026151A1 (en) * | 2003-09-16 | 2005-03-24 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
| DK1667991T3 (da) * | 2003-09-16 | 2008-08-18 | Astrazeneca Ab | Quinazolinderivater som tyrosinkinaseinhibitorer |
| CA2539049A1 (en) * | 2003-09-16 | 2005-03-24 | Astrazeneca Ab | Quinazoline derivatives |
| EP1664030A1 (en) * | 2003-09-16 | 2006-06-07 | AstraZeneca AB | Quinazoline derivatives |
| GB0322409D0 (en) * | 2003-09-25 | 2003-10-29 | Astrazeneca Ab | Quinazoline derivatives |
| GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
| EP1713781B1 (en) | 2004-02-03 | 2008-11-05 | AstraZeneca AB | Quinazoline derivatives |
| CA2567832A1 (en) * | 2004-06-04 | 2005-12-15 | Astrazeneca Ab | Quinazoline derivatives as erbb receptor tyrosine kinases |
| DE602005026865D1 (de) * | 2004-12-14 | 2011-04-21 | Astrazeneca Ab | Pyrazolopyrimidinverbindungen als antitumormittel |
| GB0504474D0 (en) * | 2005-03-04 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
| GB0508717D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
| GB0508715D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
| NZ562109A (en) * | 2005-06-16 | 2011-03-31 | Myrexis Inc | Pharmaceutical compositions containing substituted (4-Phenyl)-methyl-(quinazolin-4-yl)-amine compounds, uses thereof, and methods of preparing the same |
| EP1940825A1 (en) * | 2005-09-20 | 2008-07-09 | Astra Zeneca AB | Quinazoline derivatives as anticancer agents |
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-
2003
- 2003-09-16 GB GBGB0321648.8A patent/GB0321648D0/en not_active Ceased
-
2004
- 2004-09-14 WO PCT/GB2004/003936 patent/WO2005026152A1/en not_active Ceased
- 2004-09-14 DE DE602004024420T patent/DE602004024420D1/de not_active Expired - Lifetime
- 2004-09-14 CA CA002539024A patent/CA2539024A1/en not_active Abandoned
- 2004-09-14 AU AU2004272351A patent/AU2004272351A1/en not_active Abandoned
- 2004-09-14 JP JP2006526685A patent/JP2007505874A/ja active Pending
- 2004-09-14 EP EP04768482A patent/EP1664029B1/en not_active Expired - Lifetime
- 2004-09-14 BR BRPI0414486-4A patent/BRPI0414486A/pt not_active Application Discontinuation
- 2004-09-14 AT AT04768482T patent/ATE450528T1/de not_active IP Right Cessation
- 2004-09-14 MX MXPA06002965A patent/MXPA06002965A/es unknown
- 2004-09-14 CN CNA2004800335283A patent/CN1882572A/zh active Pending
- 2004-09-14 US US10/572,262 patent/US20070015743A1/en not_active Abandoned
- 2004-09-16 AR ARP040103319A patent/AR045752A1/es unknown
- 2004-09-16 TW TW093128079A patent/TW200526628A/zh unknown
-
2006
- 2006-03-12 IL IL174260A patent/IL174260A0/en unknown
- 2006-03-15 ZA ZA200602189A patent/ZA200602189B/en unknown
- 2006-03-23 NO NO20061320A patent/NO20061320L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| ATE450528T1 (de) | 2009-12-15 |
| DE602004024420D1 (de) | 2010-01-14 |
| CN1882572A (zh) | 2006-12-20 |
| AU2004272351A1 (en) | 2005-03-24 |
| IL174260A0 (en) | 2006-08-01 |
| AR045752A1 (es) | 2005-11-09 |
| EP1664029B1 (en) | 2009-12-02 |
| BRPI0414486A (pt) | 2006-11-14 |
| ZA200602189B (en) | 2007-11-28 |
| WO2005026152A1 (en) | 2005-03-24 |
| CA2539024A1 (en) | 2005-03-24 |
| JP2007505874A (ja) | 2007-03-15 |
| EP1664029A1 (en) | 2006-06-07 |
| NO20061320L (no) | 2006-04-26 |
| TW200526628A (en) | 2005-08-16 |
| GB0321648D0 (en) | 2003-10-15 |
| US20070015743A1 (en) | 2007-01-18 |
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