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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (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)
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| 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 |
| 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 |
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| GB2418427A (en) | 2004-09-02 | 2006-03-29 | Univ Cambridge Tech | Ligands for G-protein coupled receptors |
| 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 |
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| US20090239861A1 (en) * | 2005-09-20 | 2009-09-24 | Robert Hugh Bradbury | Quinazoline derivatives as anticancer agents |
| ATE443053T1 (de) * | 2005-12-02 | 2009-10-15 | Astrazeneca Ab | Als inhibitoren von erbb-tyrosinkinase verwendete chinazoleinderivate |
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| WO2008134048A2 (en) | 2007-04-27 | 2008-11-06 | Paratek Pharmaceuticals, Inc. | Methods for synthesizing and purifying aminoalkyl tetracycline compounds |
| CN101784517A (zh) | 2007-07-06 | 2010-07-21 | 帕拉特克药品公司 | 合成取代的四环素化合物的方法 |
| GB2452696B (en) | 2007-08-02 | 2009-09-23 | Cambridge Entpr Ltd | 3-(2',2'-dimethylpropanoylamino)-tetrahydropyridin-2-one and its use in pharmaceutical compositions |
| US7662967B2 (en) | 2007-08-02 | 2010-02-16 | Cambridge Enterprise Limited | Anti-inflammatory compounds and 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 |
| GB9300059D0 (en) | 1992-01-20 | 1993-03-03 | Zeneca Ltd | Quinazoline derivatives |
| GB9510757D0 (en) | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
| DE69536015D1 (de) | 1995-03-30 | 2009-12-10 | Pfizer Prod Inc | Chinazolinone Derivate |
| GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
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| GB9508535D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivative |
| US5747498A (en) | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
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| GB9603095D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
| SK284073B6 (sk) | 1996-04-12 | 2004-09-08 | Warner-Lambert Company | Polycyklické zlúčeniny, ich použitie a farmaceutické kompozície na ich báze |
| GB9607729D0 (en) | 1996-04-13 | 1996-06-19 | Zeneca Ltd | Quinazoline derivatives |
| EP0912559B1 (en) | 1996-07-13 | 2002-11-06 | Glaxo Group Limited | Fused heterocyclic compounds as protein tyrosine kinase inhibitors |
| 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 |
| HU230728B1 (hu) | 1998-09-29 | 2017-12-28 | Wyeth Holdings Llc | Szubsztituált 3-cianokinolinok mint protein tirozin kinázok inhibitorai |
| BR9914162A (pt) | 1998-10-01 | 2001-06-26 | Astrazeneca Ab | Derivado de amida, processo para preparar um derivado de amida, ou um sal farmaceuticamente aceitável ou éster clivável in vivo do mesmo, composição farmacêutica e uso de um derivado de amida, ou um sal farmaceuticamente aceitável ou éster clivável in vivo do mesmo |
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-
2005
- 2005-01-31 AT AT05701999T patent/ATE413389T1/de not_active IP Right Cessation
- 2005-01-31 CN CN2005800038578A patent/CN1914182B/zh not_active Expired - Fee Related
- 2005-01-31 ES ES05701999T patent/ES2315834T3/es not_active Expired - Lifetime
- 2005-01-31 WO PCT/GB2005/000237 patent/WO2005075439A1/en not_active Ceased
- 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 DE DE602005010824T patent/DE602005010824D1/de not_active Expired - Lifetime
- 2005-01-31 JP JP2006551898A patent/JP5032851B2/ja not_active Expired - Fee Related
- 2005-02-02 UY UY28736A patent/UY28736A1/es unknown
- 2005-02-03 AR ARP050100415A patent/AR047703A1/es unknown
- 2005-02-03 TW TW094103412A patent/TW200529851A/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| UY28736A1 (es) | 2005-09-30 |
| AR047703A1 (es) | 2006-02-08 |
| JP2007523072A (ja) | 2007-08-16 |
| ATE413389T1 (de) | 2008-11-15 |
| TW200529851A (en) | 2005-09-16 |
| HK1095590A1 (en) | 2007-05-11 |
| CN1914182A (zh) | 2007-02-14 |
| CN1914182B (zh) | 2011-09-07 |
| EP1713781B1 (en) | 2008-11-05 |
| US7632840B2 (en) | 2009-12-15 |
| JP5032851B2 (ja) | 2012-09-26 |
| US20070293490A1 (en) | 2007-12-20 |
| EP1713781A1 (en) | 2006-10-25 |
| DE602005010824D1 (de) | 2008-12-18 |
| WO2005075439A1 (en) | 2005-08-18 |
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