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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- 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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- 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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- 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
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- 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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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA06002965A MXPA06002965A (es) | 2003-09-16 | 2004-09-14 | Derivados de quinazolina como agentes antitumor. |
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|---|---|
| US (1) | US20070015743A1 (enExample) |
| EP (1) | EP1664029B1 (enExample) |
| JP (1) | JP2007505874A (enExample) |
| CN (1) | CN1882572A (enExample) |
| AR (1) | AR045752A1 (enExample) |
| AT (1) | ATE450528T1 (enExample) |
| AU (1) | AU2004272351A1 (enExample) |
| BR (1) | BRPI0414486A (enExample) |
| CA (1) | CA2539024A1 (enExample) |
| DE (1) | DE602004024420D1 (enExample) |
| GB (1) | GB0321648D0 (enExample) |
| IL (1) | IL174260A0 (enExample) |
| MX (1) | MXPA06002965A (enExample) |
| NO (1) | NO20061320L (enExample) |
| TW (1) | TW200526628A (enExample) |
| WO (1) | WO2005026152A1 (enExample) |
| ZA (1) | ZA200602189B (enExample) |
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| JP2005515176A (ja) * | 2001-11-03 | 2005-05-26 | アストラゼネカ アクチボラグ | 抗腫瘍剤としてのキナゾリン誘導体 |
| 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 |
| BRPI0414488A (pt) * | 2003-09-16 | 2006-11-14 | Astrazeneca Ab | derivado de quinazolina, composição farmacêutica, uso de um derivado de quinazolina, métodos para produzir um efeito anti - proliferativo em um animal de sangue quente, para prevenção ou tratamento de tumores em um aminal de sangue quente, para fornecer um efeito inibidor da tirosina quinase de egfr seletivo em um animal de sangue quente e para tratar um cáncer em um animal de sangue quente e, processo para a preparação de um derivado de quinazolina |
| EP1664030A1 (en) * | 2003-09-16 | 2006-06-07 | AstraZeneca AB | Quinazoline derivatives |
| AU2004272350A1 (en) * | 2003-09-16 | 2005-03-24 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
| US7569577B2 (en) * | 2003-09-16 | 2009-08-04 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
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| GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
| ATE413389T1 (de) | 2004-02-03 | 2008-11-15 | Astrazeneca Ab | Chinazolinderivate |
| CA2567832A1 (en) * | 2004-06-04 | 2005-12-15 | Astrazeneca Ab | Quinazoline derivatives as erbb receptor tyrosine kinases |
| CN101124228B (zh) * | 2004-12-14 | 2011-06-15 | 阿斯利康(瑞典)有限公司 | 用作抗肿瘤药物的吡唑并嘧啶化合物 |
| GB0504474D0 (en) * | 2005-03-04 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
| GB0508717D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
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-
2003
- 2003-09-16 GB GBGB0321648.8A patent/GB0321648D0/en not_active Ceased
-
2004
- 2004-09-14 US US10/572,262 patent/US20070015743A1/en not_active Abandoned
- 2004-09-14 BR BRPI0414486-4A patent/BRPI0414486A/pt not_active Application Discontinuation
- 2004-09-14 CA CA002539024A patent/CA2539024A1/en not_active Abandoned
- 2004-09-14 JP JP2006526685A patent/JP2007505874A/ja active Pending
- 2004-09-14 AT AT04768482T patent/ATE450528T1/de not_active IP Right Cessation
- 2004-09-14 WO PCT/GB2004/003936 patent/WO2005026152A1/en not_active Ceased
- 2004-09-14 AU AU2004272351A patent/AU2004272351A1/en not_active Abandoned
- 2004-09-14 MX MXPA06002965A patent/MXPA06002965A/es unknown
- 2004-09-14 EP EP04768482A patent/EP1664029B1/en not_active Expired - Lifetime
- 2004-09-14 CN CNA2004800335283A patent/CN1882572A/zh active Pending
- 2004-09-14 DE DE602004024420T patent/DE602004024420D1/de not_active Expired - Lifetime
- 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 |
|---|---|
| EP1664029B1 (en) | 2009-12-02 |
| WO2005026152A1 (en) | 2005-03-24 |
| AR045752A1 (es) | 2005-11-09 |
| US20070015743A1 (en) | 2007-01-18 |
| IL174260A0 (en) | 2006-08-01 |
| NO20061320L (no) | 2006-04-26 |
| JP2007505874A (ja) | 2007-03-15 |
| CN1882572A (zh) | 2006-12-20 |
| BRPI0414486A (pt) | 2006-11-14 |
| ATE450528T1 (de) | 2009-12-15 |
| EP1664029A1 (en) | 2006-06-07 |
| AU2004272351A1 (en) | 2005-03-24 |
| GB0321648D0 (en) | 2003-10-15 |
| DE602004024420D1 (de) | 2010-01-14 |
| TW200526628A (en) | 2005-08-16 |
| CA2539024A1 (en) | 2005-03-24 |
| ZA200602189B (en) | 2007-11-28 |
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