CA2479642C - 4-anilino quinazoline derivatives as antiproliferative agents - Google Patents
4-anilino quinazoline derivatives as antiproliferative agents Download PDFInfo
- Publication number
- CA2479642C CA2479642C CA2479642A CA2479642A CA2479642C CA 2479642 C CA2479642 C CA 2479642C CA 2479642 A CA2479642 A CA 2479642A CA 2479642 A CA2479642 A CA 2479642A CA 2479642 C CA2479642 C CA 2479642C
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- CA
- Canada
- Prior art keywords
- alkyl
- group
- chloro
- alkanoyl
- fluoroanilino
- 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 - Fee Related
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- 230000001028 anti-proliverative effect Effects 0.000 title claims abstract description 18
- MTSNDBYBIZSILH-UHFFFAOYSA-N n-phenylquinazolin-4-amine Chemical class N=1C=NC2=CC=CC=C2C=1NC1=CC=CC=C1 MTSNDBYBIZSILH-UHFFFAOYSA-N 0.000 title description 5
- 238000000034 method Methods 0.000 claims abstract description 83
- 230000008569 process Effects 0.000 claims abstract description 53
- 238000011282 treatment Methods 0.000 claims abstract description 36
- 238000002360 preparation method Methods 0.000 claims abstract description 22
- 238000004519 manufacturing process Methods 0.000 claims abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- -1 nitro, carboxy Chemical group 0.000 claims description 1045
- 125000000217 alkyl group Chemical group 0.000 claims description 866
- 125000001424 substituent group Chemical group 0.000 claims description 448
- 125000001589 carboacyl group Chemical group 0.000 claims description 299
- 125000003545 alkoxy group Chemical group 0.000 claims description 191
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 168
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 165
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 152
- 150000001875 compounds Chemical class 0.000 claims description 150
- 229910052757 nitrogen Inorganic materials 0.000 claims description 150
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 130
- 125000005843 halogen group Chemical group 0.000 claims description 116
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 112
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 101
- 239000001257 hydrogen Substances 0.000 claims description 97
- 229910052739 hydrogen Inorganic materials 0.000 claims description 97
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 90
- 125000001153 fluoro group Chemical group F* 0.000 claims description 90
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 77
- 150000003246 quinazolines Chemical class 0.000 claims description 77
- 125000003342 alkenyl group Chemical group 0.000 claims description 72
- 150000003839 salts Chemical class 0.000 claims description 72
- 125000000304 alkynyl group Chemical group 0.000 claims description 68
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 67
- 125000002252 acyl group Chemical group 0.000 claims description 64
- 229910052799 carbon Inorganic materials 0.000 claims description 64
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 64
- 125000000623 heterocyclic group Chemical group 0.000 claims description 61
- 238000006243 chemical reaction Methods 0.000 claims description 58
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 58
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 55
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 52
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 52
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 50
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 50
- 125000003282 alkyl amino group Chemical group 0.000 claims description 45
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 45
- 125000004423 acyloxy group Chemical group 0.000 claims description 44
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 44
- 125000004043 oxo group Chemical group O=* 0.000 claims description 44
- 125000003386 piperidinyl group Chemical group 0.000 claims description 43
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 42
- 125000006239 protecting group Chemical group 0.000 claims description 40
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 38
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 38
- 229920006395 saturated elastomer Polymers 0.000 claims description 38
- 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 37
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 35
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 32
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 32
- 125000004414 alkyl thio group Chemical group 0.000 claims description 31
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 31
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 30
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 30
- 229910052717 sulfur Chemical group 0.000 claims description 30
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 29
- 125000005842 heteroatom Chemical group 0.000 claims description 28
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 27
- 239000011593 sulfur Chemical group 0.000 claims description 26
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 24
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 239000001301 oxygen Substances 0.000 claims description 24
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 23
- 125000000524 functional group Chemical group 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 18
- 241001465754 Metazoa Species 0.000 claims description 17
- 150000002431 hydrogen Chemical group 0.000 claims description 16
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 16
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 12
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000005137 alkenylsulfonyl group Chemical group 0.000 claims description 11
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 10
- 238000003776 cleavage reaction Methods 0.000 claims description 10
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000005136 alkenylsulfinyl group Chemical group 0.000 claims description 7
- 125000005108 alkenylthio group Chemical group 0.000 claims description 7
- 125000005134 alkynylsulfinyl group Chemical group 0.000 claims description 7
- 125000005139 alkynylsulfonyl group Chemical group 0.000 claims description 7
- 125000005109 alkynylthio group Chemical group 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 7
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 claims description 6
- 238000005859 coupling reaction Methods 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 230000029936 alkylation Effects 0.000 claims description 5
- 238000005804 alkylation reaction Methods 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 230000007017 scission Effects 0.000 claims description 5
- OQTRMOKXZGAHKG-SFHVURJKSA-N 1-[(2s)-2-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]pyrrolidin-1-yl]-2-(4-methylpiperazin-1-yl)ethanone Chemical compound C=12C=C(OC[C@H]3N(CCC3)C(=O)CN3CCN(C)CC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F OQTRMOKXZGAHKG-SFHVURJKSA-N 0.000 claims description 4
- QEBRMJTUPMNDKF-HNNXBMFYSA-N 1-[(3s)-3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound C=12C=C(O[C@@H]3CN(CCC3)C(=O)CN(C)C)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F QEBRMJTUPMNDKF-HNNXBMFYSA-N 0.000 claims description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 4
- RHHAVUPVXRAMLR-ZDUSSCGKSA-N n-(3-chloro-2-fluorophenyl)-7-methoxy-6-[(3s)-1-methylsulfonylpiperidin-3-yl]oxyquinazolin-4-amine Chemical compound C=12C=C(O[C@@H]3CN(CCC3)S(C)(=O)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F RHHAVUPVXRAMLR-ZDUSSCGKSA-N 0.000 claims description 3
- ANPMBHMDRDARRB-ACJLOTCBSA-N (2s,4r)-4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxy-n,n,1-trimethylpyrrolidine-2-carboxamide Chemical compound C=12C=C(O[C@H]3CN(C)[C@@H](C3)C(=O)N(C)C)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F ANPMBHMDRDARRB-ACJLOTCBSA-N 0.000 claims description 2
- HSZPIFWRDODQSY-SJCJKPOMSA-N (2s,4s)-4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxy-n,n-dimethylpyrrolidine-2-carboxamide Chemical compound C=12C=C(O[C@H]3C[C@H](NC3)C(=O)N(C)C)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F HSZPIFWRDODQSY-SJCJKPOMSA-N 0.000 claims description 2
- VERFDPCLRFVYAD-ZDUSSCGKSA-N (3s)-3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxy-n,n-dimethylpyrrolidine-1-sulfonamide Chemical compound C=12C=C(O[C@@H]3CN(CC3)S(=O)(=O)N(C)C)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F VERFDPCLRFVYAD-ZDUSSCGKSA-N 0.000 claims description 2
- KBIXTCZEFRUUAZ-CQSZACIVSA-N 1-[(2r)-2-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]pyrrolidin-1-yl]ethanone Chemical compound C=12C=C(OC[C@@H]3N(CCC3)C(C)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F KBIXTCZEFRUUAZ-CQSZACIVSA-N 0.000 claims description 2
- ALLCTPWIIGFMFC-HNNXBMFYSA-N 1-[(2s)-2-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]pyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound C=12C=C(OC[C@H]3N(CCC3)C(=O)CN(C)C)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F ALLCTPWIIGFMFC-HNNXBMFYSA-N 0.000 claims description 2
- WNCFXFFZDYNIPJ-AWEZNQCLSA-N 1-[(2s)-2-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxy-2-methylpropan-1-one Chemical compound C=12C=C(OC[C@H]3N(CCC3)C(=O)C(C)(C)O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F WNCFXFFZDYNIPJ-AWEZNQCLSA-N 0.000 claims description 2
- DABOZAKYWAXTGO-ZDUSSCGKSA-N 1-[(2s)-2-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound C=12C=C(OC[C@H]3N(CCC3)C(=O)CO)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F DABOZAKYWAXTGO-ZDUSSCGKSA-N 0.000 claims description 2
- KQJNSLFSIFNZDL-KRWDZBQOSA-N 1-[(2s)-2-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]pyrrolidin-1-yl]-2-morpholin-4-ylethanone Chemical compound C=12C=C(OC[C@H]3N(CCC3)C(=O)CN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F KQJNSLFSIFNZDL-KRWDZBQOSA-N 0.000 claims description 2
- KBIXTCZEFRUUAZ-AWEZNQCLSA-N 1-[(2s)-2-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]pyrrolidin-1-yl]ethanone Chemical compound C=12C=C(OC[C@H]3N(CCC3)C(C)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F KBIXTCZEFRUUAZ-AWEZNQCLSA-N 0.000 claims description 2
- QEBRMJTUPMNDKF-OAHLLOKOSA-N 1-[(3r)-3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound C=12C=C(O[C@H]3CN(CCC3)C(=O)CN(C)C)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F QEBRMJTUPMNDKF-OAHLLOKOSA-N 0.000 claims description 2
- JSBUNBCORFPCOC-GFCCVEGCSA-N 1-[(3r)-3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypyrrolidin-1-yl]-2-hydroxyethanone Chemical compound C=12C=C(O[C@H]3CN(CC3)C(=O)CO)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F JSBUNBCORFPCOC-GFCCVEGCSA-N 0.000 claims description 2
- SOFXNKBESSEJLC-CYBMUJFWSA-N 1-[(3r)-3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypyrrolidin-1-yl]ethanone Chemical compound C=12C=C(O[C@H]3CN(CC3)C(C)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F SOFXNKBESSEJLC-CYBMUJFWSA-N 0.000 claims description 2
- BGJVGJZKZPYAMV-KRWDZBQOSA-N 1-[(3s)-3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-pyrrolidin-1-ylethanone Chemical compound C=12C=C(O[C@@H]3CN(CCC3)C(=O)CN3CCCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F BGJVGJZKZPYAMV-KRWDZBQOSA-N 0.000 claims description 2
- VZFHDUMFRVSURN-UHFFFAOYSA-N 1-[3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-(3,3-difluoropyrrolidin-1-yl)ethanone Chemical compound C=12C=C(OC3CN(CCC3)C(=O)CN3CC(F)(F)CC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F VZFHDUMFRVSURN-UHFFFAOYSA-N 0.000 claims description 2
- UILHKOLRWSJNDW-TZHYSIJRSA-N 1-[3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-[(3r)-3-hydroxypyrrolidin-1-yl]ethanone Chemical compound C=12C=C(OC3CN(CCC3)C(=O)CN3C[C@H](O)CC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F UILHKOLRWSJNDW-TZHYSIJRSA-N 0.000 claims description 2
- SIKHQLKPCASMEL-UHFFFAOYSA-N 1-[3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-hydroxyethanone Chemical compound C=12C=C(OC3CN(CCC3)C(=O)CO)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F SIKHQLKPCASMEL-UHFFFAOYSA-N 0.000 claims description 2
- BGJVGJZKZPYAMV-UHFFFAOYSA-N 1-[3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-pyrrolidin-1-ylethanone Chemical compound C=12C=C(OC3CN(CCC3)C(=O)CN3CCCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F BGJVGJZKZPYAMV-UHFFFAOYSA-N 0.000 claims description 2
- FPPIVLMSIGJKPX-UHFFFAOYSA-N 1-[3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]ethanone Chemical compound C=12C=C(OC3CN(CCC3)C(C)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F FPPIVLMSIGJKPX-UHFFFAOYSA-N 0.000 claims description 2
- NOYQEMLFKXUGNZ-UHFFFAOYSA-N 1-[3-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]pyrrolidin-1-yl]ethanone Chemical compound C=12C=C(OCC3CN(CC3)C(C)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F NOYQEMLFKXUGNZ-UHFFFAOYSA-N 0.000 claims description 2
- APWGONAWSQJAFF-UHFFFAOYSA-N 1-[4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-morpholin-4-ylethanone Chemical compound C=12C=C(OC3CCN(CC3)C(=O)CN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F APWGONAWSQJAFF-UHFFFAOYSA-N 0.000 claims description 2
- FYUILKSGHOYVJD-UHFFFAOYSA-N 1-[4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-pyrrolidin-1-ylethanone Chemical compound C=12C=C(OC3CCN(CC3)C(=O)CN3CCCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F FYUILKSGHOYVJD-UHFFFAOYSA-N 0.000 claims description 2
- XLKMNDIRQXLLRJ-UHFFFAOYSA-N 1-[4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]ethanone Chemical compound C=12C=C(OC3CCN(CC3)C(C)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F XLKMNDIRQXLLRJ-UHFFFAOYSA-N 0.000 claims description 2
- FEGFNGQBRZUWHV-UHFFFAOYSA-N 2-(4-acetylpiperazin-1-yl)-1-[3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]ethanone Chemical compound C=12C=C(OC3CN(CCC3)C(=O)CN3CCN(CC3)C(C)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F FEGFNGQBRZUWHV-UHFFFAOYSA-N 0.000 claims description 2
- DUZUWJLVYVKTKY-UHFFFAOYSA-N 2-[3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-n,n-dimethylacetamide Chemical compound C=12C=C(OC3CN(CC(=O)N(C)C)CCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F DUZUWJLVYVKTKY-UHFFFAOYSA-N 0.000 claims description 2
- DIBGTMXGHUALIU-UHFFFAOYSA-N 2-[4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]acetamide Chemical compound C=12C=C(OC3CCN(CC(N)=O)CC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F DIBGTMXGHUALIU-UHFFFAOYSA-N 0.000 claims description 2
- FKIGKBRONDNFSA-UHFFFAOYSA-N 2-[4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]acetonitrile Chemical compound C=12C=C(OC3CCN(CC#N)CC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F FKIGKBRONDNFSA-UHFFFAOYSA-N 0.000 claims description 2
- SBAGQHZIOBAMDV-UHFFFAOYSA-N 4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxy-n,n-dimethylpiperidine-1-sulfonamide Chemical compound C=12C=C(OC3CCN(CC3)S(=O)(=O)N(C)C)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F SBAGQHZIOBAMDV-UHFFFAOYSA-N 0.000 claims description 2
- JOANRURMBNMJHR-UHFFFAOYSA-N 4-[[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxymethyl]piperidine-1-carbonitrile Chemical compound C=12C=C(OCC3CCN(CC3)C#N)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F JOANRURMBNMJHR-UHFFFAOYSA-N 0.000 claims description 2
- IIPZVWOEYKWBAM-IWPPFLRJSA-N [(4r)-4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxy-1-methylpyrrolidin-2-yl]-morpholin-4-ylmethanone Chemical compound C=12C=C(O[C@H]3CN(C)C(C3)C(=O)N3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F IIPZVWOEYKWBAM-IWPPFLRJSA-N 0.000 claims description 2
- PQNRFGOXGMDMSI-UHFFFAOYSA-N [2-[3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-2-oxoethyl] acetate Chemical compound C=12C=C(OC3CN(CCC3)C(=O)COC(C)=O)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F PQNRFGOXGMDMSI-UHFFFAOYSA-N 0.000 claims description 2
- QTMFEEDRXUIFDA-MRNPHLECSA-N [3-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidin-1-yl]-[(2s)-1-methylpyrrolidin-2-yl]methanone Chemical compound C=12C=C(OC3CN(CCC3)C(=O)[C@H]3N(CCC3)C)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F QTMFEEDRXUIFDA-MRNPHLECSA-N 0.000 claims description 2
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
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Classifications
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- 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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- A61P13/08—Drugs for disorders of the urinary system of the prostate
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
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| GB0301916A GB0301916D0 (en) | 2003-01-28 | 2003-01-28 | Compounds |
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| PCT/GB2003/001306 WO2003082831A1 (en) | 2002-03-28 | 2003-03-26 | 4-anilino quinazoline derivatives as antiproliferative agents |
Publications (2)
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| CA2479642A1 CA2479642A1 (en) | 2003-10-09 |
| CA2479642C true CA2479642C (en) | 2010-06-08 |
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| US7019012B2 (en) * | 2000-12-20 | 2006-03-28 | Boehringer Ingelheim International Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
| RU2004116911A (ru) * | 2001-11-03 | 2005-11-10 | Астразенека Аб (Se) | Производные хиназолина в качестве противоопухолевых средств |
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| KR101019131B1 (ko) * | 2001-11-19 | 2011-03-07 | 인터레우킨 제네틱스, 인코포레이티드 | 염증성 질환 및 감염성 질환에 대한 감수성 및 전사에영향을 미치는 인터루킨-1 좌의 기능적 다형성 |
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| 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 |
| NZ536114A (en) * | 2002-03-30 | 2007-11-30 | Boehringer Ingelheim Pharma | 4-(N-phenylamino)-quinazolines / quinolines as tyrosine kinase inhibitors |
| DE10214412A1 (de) * | 2002-03-30 | 2003-10-09 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| DE10221018A1 (de) * | 2002-05-11 | 2003-11-27 | Boehringer Ingelheim Pharma | Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie |
| EP1521747B1 (en) | 2002-07-15 | 2018-09-05 | Symphony Evolution, Inc. | Receptor-type kinase modulators and methods of use |
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| MXPA06002963A (es) * | 2003-09-16 | 2006-06-14 | Astrazeneca Ab | Derivados de quinazolina como inhibidores de cinasa de tirosina. |
| 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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| BRPI0414532B1 (pt) * | 2003-09-19 | 2018-06-05 | Astrazeneca Ab | Composto derivado de quinazolina, processo para preparar 0 mesmo, composição farmaceutica, e, uso de um composto derivado de quinazolina |
| DE602004004811T2 (de) * | 2003-09-19 | 2007-11-22 | Astrazeneca Ab | Chinazolinderivate |
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| WO2005044302A1 (en) * | 2003-11-06 | 2005-05-19 | Pfizer Products Inc. | Selective erbb2 inhibitor/anti-erbb antibody combinations in the treatment of cancer |
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| HRP20110958T1 (hr) | 2004-05-06 | 2012-01-31 | Warner-Lambert Company Llc | 4-fenilaminokinazolin-6-ilamidi |
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| ATE501148T1 (de) * | 2004-12-14 | 2011-03-15 | Astrazeneca Ab | Pyrazolopyrimidinverbindungen als antitumormittel |
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| GB0509227D0 (en) * | 2005-05-05 | 2005-06-15 | Chroma Therapeutics Ltd | Intracellular enzyme inhibitors |
| US20100234371A1 (en) * | 2005-08-22 | 2010-09-16 | Frank Himmelsbach | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, the use thereof and processes for the preparation thereof |
| ES2354457T3 (es) * | 2005-09-20 | 2011-03-15 | Astrazeneca Ab | Compuestos de 4-(1h-indazol-5-il-amino)-quinazolina como inhibidores del receptor erbb de la tirosina quinasa para el tratamiento del cáncer. |
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- 2003-03-19 TW TW096130334A patent/TW200813014A/zh unknown
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2010
- 2010-02-16 US US12/706,675 patent/US8399667B2/en not_active Expired - Fee Related
- 2010-09-09 CY CY20101100824T patent/CY1111039T1/el unknown
-
2012
- 2012-09-10 US US13/608,092 patent/US20130005727A1/en not_active Abandoned
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20180326 |