ES2315834T3 - Derivados de quinazolina. - Google Patents
Derivados de quinazolina. Download PDFInfo
- Publication number
- ES2315834T3 ES2315834T3 ES05701999T ES05701999T ES2315834T3 ES 2315834 T3 ES2315834 T3 ES 2315834T3 ES 05701999 T ES05701999 T ES 05701999T ES 05701999 T ES05701999 T ES 05701999T ES 2315834 T3 ES2315834 T3 ES 2315834T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- group
- amino
- heterocyclyl
- hydrogen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- -1 amino- (C1-6) alkyl Chemical group 0.000 claims abstract description 1078
- 125000001424 substituent group Chemical group 0.000 claims abstract description 332
- 239000001257 hydrogen Substances 0.000 claims abstract description 315
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 315
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 276
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 263
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 259
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 226
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 201
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 158
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 122
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 104
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 100
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 96
- 150000001721 carbon Chemical group 0.000 claims abstract description 93
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 89
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 84
- 150000002367 halogens Chemical class 0.000 claims abstract description 83
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 80
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 74
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 71
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 62
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 60
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 57
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 54
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 claims abstract description 47
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 43
- 150000001335 aliphatic alkanes Chemical class 0.000 claims abstract description 39
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 34
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 32
- 125000003118 aryl group Chemical group 0.000 claims abstract description 32
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 29
- 238000003780 insertion Methods 0.000 claims abstract description 29
- 230000037431 insertion Effects 0.000 claims abstract description 29
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims abstract description 28
- 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 27
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 27
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims abstract description 26
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims abstract description 21
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims abstract description 19
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 18
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 18
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims abstract description 17
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims abstract description 16
- 125000000464 thioxo group Chemical group S=* 0.000 claims abstract description 16
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims abstract description 15
- 125000004966 cyanoalkyl group Chemical group 0.000 claims abstract description 15
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims abstract description 15
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 13
- 125000005133 alkynyloxy group Chemical group 0.000 claims abstract description 12
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 11
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 10
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims abstract description 7
- 125000003302 alkenyloxy group Chemical group 0.000 claims abstract description 6
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims abstract description 4
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 4
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 3
- 125000001589 carboacyl group Chemical group 0.000 claims abstract 28
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 149
- 150000001875 compounds Chemical class 0.000 claims description 123
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 121
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 118
- 238000006243 chemical reaction Methods 0.000 claims description 79
- 238000000034 method Methods 0.000 claims description 72
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 71
- 125000001153 fluoro group Chemical group F* 0.000 claims description 69
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 62
- 125000003342 alkenyl group Chemical group 0.000 claims description 58
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 53
- 150000003839 salts Chemical class 0.000 claims description 51
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 40
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 38
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 38
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 34
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 32
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 28
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 27
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 27
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 27
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 26
- 206010028980 Neoplasm Diseases 0.000 claims description 26
- 125000000524 functional group Chemical group 0.000 claims description 26
- 125000004429 atom Chemical group 0.000 claims description 25
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 25
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 25
- 239000001301 oxygen Substances 0.000 claims description 25
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 24
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 24
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 23
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 23
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 23
- 125000006239 protecting group Chemical group 0.000 claims description 23
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 22
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 22
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 21
- 230000008569 process Effects 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 18
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 18
- 201000011510 cancer Diseases 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 125000001246 bromo group Chemical group Br* 0.000 claims description 16
- 238000005859 coupling reaction Methods 0.000 claims description 16
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 15
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 15
- 230000000694 effects Effects 0.000 claims description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 10
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 9
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 9
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 9
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 8
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 8
- 230000008878 coupling Effects 0.000 claims description 8
- 238000010168 coupling process Methods 0.000 claims description 8
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 7
- 150000002576 ketones Chemical class 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 238000006268 reductive amination reaction Methods 0.000 claims description 5
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- BHVAKJBKJSVSDR-IBGZPJMESA-N (2S)-2-amino-3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]-2-methylpropanamide Chemical compound ClC=1C(=C(C=CC=1)NC1=NC=NC2=CC(=C(C=C12)C[C@@](N)(C)C(=O)N)OC)F BHVAKJBKJSVSDR-IBGZPJMESA-N 0.000 claims description 2
- IRCSMVSKUWTDJU-QFIPXVFZSA-N (2S)-3-[4-(3-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinazolin-6-yl]-2-methyl-2-(methylamino)propanamide Chemical compound ClC=1C(=C(C=CC=1)NC1=NC=NC2=CC(=C(C=C12)C[C@@](NC)(C)C(=O)N)OCCOC)F IRCSMVSKUWTDJU-QFIPXVFZSA-N 0.000 claims description 2
- NOUPFVBLDOHUPJ-NRFANRHFSA-N (2S)-3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]-2-(ethylamino)-2-methylpropanamide Chemical compound ClC=1C(=C(C=CC=1)NC1=NC=NC2=CC(=C(C=C12)C[C@@](NCC)(C)C(=O)N)OC)F NOUPFVBLDOHUPJ-NRFANRHFSA-N 0.000 claims description 2
- WBFNVNILPDYQMM-FQEVSTJZSA-N (2S)-3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]-2-methyl-2-(methylamino)propanamide Chemical compound ClC=1C(=C(C=CC=1)NC1=NC=NC2=CC(=C(C=C12)C[C@@](NC)(C)C(=O)N)OC)F WBFNVNILPDYQMM-FQEVSTJZSA-N 0.000 claims description 2
- DJUCIYJITXCSLS-FQEVSTJZSA-N (2S)-3-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]-2-methyl-2-(methylamino)propanamide Chemical compound ClC=1C=C(C=CC=1F)NC1=NC=NC2=CC(=C(C=C12)C[C@@](NC)(C)C(=O)N)OC DJUCIYJITXCSLS-FQEVSTJZSA-N 0.000 claims description 2
- NKMVJECLZMUMRO-PIJUOVFKSA-N (2r)-2-[1-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]ethyl-methylamino]propanamide Chemical compound C=12C=C(C(C)N(C)[C@H](C)C(N)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F NKMVJECLZMUMRO-PIJUOVFKSA-N 0.000 claims description 2
- LJNUYDJKKBIGJB-QGZVFWFLSA-N (2r)-2-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]methyl-methylamino]-3-methoxypropanamide Chemical compound N1=CN=C2C=C(OC)C(CN(C)[C@H](COC)C(N)=O)=CC2=C1NC1=CC=CC(Cl)=C1F LJNUYDJKKBIGJB-QGZVFWFLSA-N 0.000 claims description 2
- IKXPVMNZZLUFCI-UHFFFAOYSA-N 3-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]methyl-methylamino]-1-(2-methoxyethyl)azetidine-3-carboxamide Chemical compound C1N(CCOC)CC1(C(N)=O)N(C)CC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(Cl)=C1F IKXPVMNZZLUFCI-UHFFFAOYSA-N 0.000 claims description 2
- SGSZBDPHZWMJPU-UHFFFAOYSA-N 3-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]methyl-methylamino]-1-methylazetidine-3-carboxamide Chemical compound C=12C=C(CN(C)C3(CN(C)C3)C(N)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F SGSZBDPHZWMJPU-UHFFFAOYSA-N 0.000 claims description 2
- JLFUYZIWZMFTMH-UHFFFAOYSA-N 3-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]methyl-methylamino]-1-methylpiperidine-3-carboxamide Chemical compound C=12C=C(CN(C)C3(CN(C)CCC3)C(N)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F JLFUYZIWZMFTMH-UHFFFAOYSA-N 0.000 claims description 2
- VUWJAUDVPQZJHG-UHFFFAOYSA-N 3-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]methyl-methylamino]-1-propan-2-ylazetidine-3-carboxamide Chemical compound C=12C=C(CN(C)C3(CN(C3)C(C)C)C(N)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F VUWJAUDVPQZJHG-UHFFFAOYSA-N 0.000 claims description 2
- XRUQVQJWTQESAB-UHFFFAOYSA-N 4-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]methyl-methylamino]-1-methylpiperidine-4-carboxamide Chemical compound C=12C=C(CN(C)C3(CCN(C)CC3)C(N)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F XRUQVQJWTQESAB-UHFFFAOYSA-N 0.000 claims description 2
- OJXVSOYHWKXTRW-UHFFFAOYSA-N 4-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]methyl-methylamino]-n,1-dimethylpiperidine-4-carboxamide Chemical compound C=1C2=C(NC=3C(=C(Cl)C=CC=3)F)N=CN=C2C=C(OC)C=1CN(C)C1(C(=O)NC)CCN(C)CC1 OJXVSOYHWKXTRW-UHFFFAOYSA-N 0.000 claims description 2
- FXQBMHQIDXOJPW-UHFFFAOYSA-N N'-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]methyl]-N'-ethylcyclopropanecarbohydrazide Chemical compound C1(CC1)C(=O)NN(CC)CC=1C=C2C(=NC=NC2=CC1OC)NC1=C(C(=CC=C1)Cl)F FXQBMHQIDXOJPW-UHFFFAOYSA-N 0.000 claims description 2
- CVFXKZZCTHUDRF-UHFFFAOYSA-N N'-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]methyl]-N'-methylcyclopent-3-ene-1-carbohydrazide Chemical compound C1(CC=CC1)C(=O)NN(C)CC=1C=C2C(=NC=NC2=CC1OC)NC1=C(C(=CC=C1)Cl)F CVFXKZZCTHUDRF-UHFFFAOYSA-N 0.000 claims description 2
- PURZOLAIZPYHSS-UHFFFAOYSA-N N'-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]methyl]-N'-methylcyclopropanecarbohydrazide Chemical compound C1(CC1)C(=O)NN(C)CC=1C=C2C(=NC=NC2=CC=1OC)NC1=C(C(=CC=C1)Cl)F PURZOLAIZPYHSS-UHFFFAOYSA-N 0.000 claims description 2
- 229940124639 Selective inhibitor Drugs 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 230000001028 anti-proliverative effect Effects 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 150000003246 quinazolines Chemical class 0.000 claims 26
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 abstract description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 5
- 125000004415 heterocyclylalkyl group Chemical group 0.000 abstract description 5
- 125000004103 aminoalkyl group Chemical group 0.000 abstract description 4
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 abstract 1
- 125000001188 haloalkyl group Chemical group 0.000 abstract 1
- 150000002431 hydrogen Chemical class 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- OVSQVDMCBVZWGM-QSOFNFLRSA-N quercetin 3-O-beta-D-glucopyranoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C(C=2C=C(O)C(O)=CC=2)OC2=CC(O)=CC(O)=C2C1=O OVSQVDMCBVZWGM-QSOFNFLRSA-N 0.000 abstract 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 70
- 125000002252 acyl group Chemical group 0.000 description 63
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 49
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 38
- 229960005419 nitrogen Drugs 0.000 description 34
- 229920006395 saturated elastomer Polymers 0.000 description 34
- 239000002253 acid Substances 0.000 description 21
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 20
- 125000005842 heteroatom Chemical group 0.000 description 20
- 125000002950 monocyclic group Chemical group 0.000 description 20
- 239000011593 sulfur Chemical group 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000002585 base Substances 0.000 description 18
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 17
- 125000005843 halogen group Chemical group 0.000 description 17
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 17
- 239000000460 chlorine Substances 0.000 description 16
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 15
- 229910052801 chlorine Inorganic materials 0.000 description 15
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 14
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 13
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 13
- 125000003282 alkyl amino group Chemical group 0.000 description 13
- 239000003638 chemical reducing agent Substances 0.000 description 13
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 13
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP04290274 | 2004-02-03 | ||
| EP04290274 | 2004-02-03 |
Publications (1)
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|---|---|
| ES2315834T3 true ES2315834T3 (es) | 2009-04-01 |
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| AR (1) | AR047703A1 (https=) |
| AT (1) | ATE413389T1 (https=) |
| DE (1) | DE602005010824D1 (https=) |
| ES (1) | ES2315834T3 (https=) |
| TW (1) | TW200529851A (https=) |
| UY (1) | UY28736A1 (https=) |
| WO (1) | WO2005075439A1 (https=) |
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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 |
| GB0309009D0 (en) * | 2003-04-22 | 2003-05-28 | Astrazeneca Ab | Quinazoline derivatives |
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| GB0321648D0 (en) * | 2003-09-16 | 2003-10-15 | Astrazeneca Ab | Quinazoline derivatives |
| US20070032508A1 (en) * | 2003-09-16 | 2007-02-08 | Bradbury Robert H | Quinazoline derivatives as tyrosine kinase inhibitors |
| ES2305844T3 (es) * | 2003-09-16 | 2008-11-01 | Astrazeneca Ab | Derivados de quinazolina como inhibidores de tirosina cinasa. |
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| GB2418427A (en) | 2004-09-02 | 2006-03-29 | Univ Cambridge Tech | Ligands for G-protein coupled receptors |
| EP1838712B8 (en) * | 2004-12-14 | 2011-10-12 | AstraZeneca AB | Pyrazolopyrimidine compounds as antitumor agents |
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| WO2007034144A1 (en) * | 2005-09-20 | 2007-03-29 | Astrazeneca Ab | 4- (ih-indazol-s-yl-amino)-quinazoline compounds as erbb receptor tyrosine kinase inhibitors for the treatment of cancer |
| JP2009508917A (ja) * | 2005-09-20 | 2009-03-05 | アストラゼネカ アクチボラグ | 抗癌剤としてのキナゾリン誘導体 |
| 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 |
| JP2009517451A (ja) * | 2005-12-02 | 2009-04-30 | アストラゼネカ アクチボラグ | Ｅｒｂｂチロシンキナーゼの阻害剤として使用されるキナゾリン誘導体 |
| EP2216323A3 (en) | 2007-04-27 | 2010-12-29 | Paratek Pharmaceuticals, Inc. | Methods for synthesizing and purifying aminoalkyl tetracycline compounds |
| EP2176216B1 (en) * | 2007-07-06 | 2012-04-25 | Paratek Pharmaceuticals, Inc. | Methods for synthesizing 9-substituted minocycline |
| US7662967B2 (en) | 2007-08-02 | 2010-02-16 | Cambridge Enterprise Limited | Anti-inflammatory compounds and compositions |
| GB2452696B (en) | 2007-08-02 | 2009-09-23 | Cambridge Entpr Ltd | 3-(2',2'-dimethylpropanoylamino)-tetrahydropyridin-2-one and its use in pharmaceutical compositions |
| GB201604329D0 (en) * | 2016-03-14 | 2016-04-27 | Univ Strathclyde | Methods and systems for improving stability of a ship |
| CN111777620A (zh) * | 2019-04-04 | 2020-10-16 | 山东轩竹医药科技有限公司 | 酪氨酸激酶抑制剂的新用途 |
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| US4335127A (en) | 1979-01-08 | 1982-06-15 | Janssen Pharmaceutica, N.V. | Piperidinylalkyl quinazoline compounds, composition and method of use |
| KR910006138B1 (ko) | 1986-09-30 | 1991-08-16 | 에자이 가부시끼가이샤 | 환상아민 유도체 |
| US4921863A (en) | 1988-02-17 | 1990-05-01 | Eisai Co., Ltd. | Cyclic amine derivatives |
| US5721237A (en) | 1991-05-10 | 1998-02-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Protein tyrosine kinase aryl and heteroaryl quinazoline compounds having selective inhibition of HER-2 autophosphorylation properties |
| AU661533B2 (en) | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
| GB9510757D0 (en) | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
| MX9707453A (es) | 1995-03-30 | 1997-12-31 | Pfizer | Derivados de quinazolina. |
| GB9508535D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivative |
| GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
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| GB9508565D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quiazoline derivative |
| US5747498A (en) | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
| GB9514265D0 (en) | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
| BR9707495A (pt) | 1996-02-13 | 1999-07-27 | Zeneca Ltd | Derivado de quinazolina processo para a preparação do mesmo composição farmacêutica e processo para a produç o de um efeito antiangiogênico e/ou de redução de permeabilidade vascular em um animal de sangue quente |
| GB9603095D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
| HU228446B1 (en) | 1996-04-12 | 2013-03-28 | Warner Lambert Co | Kinazoline derivatives as irreversible inhibitors of protein-kinase, pharmaceutical compositions containing these compounds and use thereof |
| GB9607729D0 (en) | 1996-04-13 | 1996-06-19 | Zeneca Ltd | Quinazoline derivatives |
| ID19609A (id) | 1996-07-13 | 1998-07-23 | Glaxo Group Ltd | Senyawa-senyawa heterosiklik |
| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| EP0837063A1 (en) | 1996-10-17 | 1998-04-22 | Pfizer Inc. | 4-Aminoquinazoline derivatives |
| ZA986732B (en) | 1997-07-29 | 1999-02-02 | Warner Lambert Co | Irreversible inhibitiors of tyrosine kinases |
| GB9800575D0 (en) * | 1998-01-12 | 1998-03-11 | Glaxo Group Ltd | Heterocyclic compounds |
| WO2000009481A1 (en) | 1998-08-11 | 2000-02-24 | Takeda Chemical Industries, Ltd. | Cyclic amide compounds, process for producing the same, intermediates thereof and herbicides |
| US6297258B1 (en) | 1998-09-29 | 2001-10-02 | American Cyanamid Company | Substituted 3-cyanoquinolines |
| BR9914164A (pt) | 1998-09-29 | 2001-06-26 | American Cyanamid Co | Composto, método para o tratamento, inibição do crescimento de, ou erradiacação de um neoplasma, e de doença de rim policìstico, em um mamìfero em necessidade do mesmo, composição farmacêutica, e, processo para preparar um composto |
| ATE232205T1 (de) | 1998-10-01 | 2003-02-15 | Astrazeneca Ab | Chinolin- und chinazolin derivate und ihre verwendung als inhibitoren von krankheiten, bei denen cytokine beteiligt wird |
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-
2005
- 2005-01-31 JP JP2006551898A patent/JP5032851B2/ja not_active Expired - Fee Related
- 2005-01-31 DE DE602005010824T patent/DE602005010824D1/de not_active Expired - Lifetime
- 2005-01-31 CN CN2005800038578A patent/CN1914182B/zh not_active Expired - Fee Related
- 2005-01-31 EP EP05701999A patent/EP1713781B1/en not_active Expired - Lifetime
- 2005-01-31 US US10/586,965 patent/US7632840B2/en not_active Expired - Fee Related
- 2005-01-31 WO PCT/GB2005/000237 patent/WO2005075439A1/en not_active Ceased
- 2005-01-31 AT AT05701999T patent/ATE413389T1/de not_active IP Right Cessation
- 2005-01-31 ES ES05701999T patent/ES2315834T3/es not_active Expired - Lifetime
- 2005-02-02 UY UY28736A patent/UY28736A1/es unknown
- 2005-02-03 TW TW094103412A patent/TW200529851A/zh unknown
- 2005-02-03 AR ARP050100415A patent/AR047703A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TW200529851A (en) | 2005-09-16 |
| HK1095590A1 (en) | 2007-05-11 |
| CN1914182A (zh) | 2007-02-14 |
| WO2005075439A1 (en) | 2005-08-18 |
| UY28736A1 (es) | 2005-09-30 |
| JP2007523072A (ja) | 2007-08-16 |
| CN1914182B (zh) | 2011-09-07 |
| US7632840B2 (en) | 2009-12-15 |
| ATE413389T1 (de) | 2008-11-15 |
| DE602005010824D1 (de) | 2008-12-18 |
| US20070293490A1 (en) | 2007-12-20 |
| JP5032851B2 (ja) | 2012-09-26 |
| EP1713781A1 (en) | 2006-10-25 |
| AR047703A1 (es) | 2006-02-08 |
| EP1713781B1 (en) | 2008-11-05 |
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