CA2545262A1 - Quinazoline derivatives - Google Patents
Quinazoline derivatives Download PDFInfo
- Publication number
- CA2545262A1 CA2545262A1 CA002545262A CA2545262A CA2545262A1 CA 2545262 A1 CA2545262 A1 CA 2545262A1 CA 002545262 A CA002545262 A CA 002545262A CA 2545262 A CA2545262 A CA 2545262A CA 2545262 A1 CA2545262 A1 CA 2545262A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- amino
- oxy
- quinazolin
- phenyl
- 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.)
- Abandoned
Links
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title abstract description 35
- 125000001424 substituent group Chemical group 0.000 claims abstract description 371
- 230000000694 effects Effects 0.000 claims abstract description 16
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 12
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims abstract description 7
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims abstract description 7
- 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
- 125000000217 alkyl group Chemical group 0.000 claims description 991
- -1 cyano, nitro, hydroxy, amino, carboxy, carbamoyl Chemical group 0.000 claims description 855
- 239000001257 hydrogen Substances 0.000 claims description 315
- 229910052739 hydrogen Inorganic materials 0.000 claims description 315
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 315
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 214
- 125000000623 heterocyclic group Chemical group 0.000 claims description 203
- 125000003545 alkoxy group Chemical group 0.000 claims description 188
- 125000005843 halogen group Chemical group 0.000 claims description 182
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 143
- 125000003342 alkenyl group Chemical group 0.000 claims description 123
- 150000001875 compounds Chemical class 0.000 claims description 121
- 125000000304 alkynyl group Chemical group 0.000 claims description 119
- 229910052760 oxygen Inorganic materials 0.000 claims description 119
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 110
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 104
- 125000003282 alkyl amino group Chemical group 0.000 claims description 101
- 229910052757 nitrogen Inorganic materials 0.000 claims description 100
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 94
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 88
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 82
- 238000006243 chemical reaction Methods 0.000 claims description 74
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 73
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 73
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 68
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 60
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 59
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 57
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 57
- 125000004414 alkyl thio group Chemical group 0.000 claims description 56
- 229910052717 sulfur Inorganic materials 0.000 claims description 55
- 125000004423 acyloxy group Chemical group 0.000 claims description 52
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 52
- 238000000034 method Methods 0.000 claims description 50
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 42
- 230000008569 process Effects 0.000 claims description 41
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 40
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 38
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 36
- 229910052799 carbon Inorganic materials 0.000 claims description 35
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 33
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 32
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 29
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 29
- 125000000524 functional group Chemical group 0.000 claims description 28
- 125000004076 pyridyl group Chemical group 0.000 claims description 27
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 27
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 26
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 26
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 125000005842 heteroatom Chemical group 0.000 claims description 24
- 239000001301 oxygen Substances 0.000 claims description 24
- 239000011593 sulfur Chemical group 0.000 claims description 24
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 23
- 229920006395 saturated elastomer Polymers 0.000 claims description 21
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 19
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 16
- 238000003780 insertion Methods 0.000 claims description 15
- 230000037431 insertion Effects 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 125000002947 alkylene group Chemical group 0.000 claims description 11
- 238000005859 coupling reaction Methods 0.000 claims description 11
- 125000002950 monocyclic group Chemical group 0.000 claims description 11
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 9
- 230000008878 coupling Effects 0.000 claims description 9
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 9
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 8
- 238000010168 coupling process Methods 0.000 claims description 8
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 6
- UXLZBZLBSUYMQQ-MRXNPFEDSA-N n-[(2r)-2-[4-[3-methyl-4-(1,3-thiazol-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropyl]acetamide Chemical compound C=12C(O[C@@H](CNC(C)=O)C)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OCC1=NC=CS1 UXLZBZLBSUYMQQ-MRXNPFEDSA-N 0.000 claims description 5
- RGCXZBHFAMZESU-FOIQADDNSA-N (2r)-n-[(2r)-1-[4-[3-chloro-4-(1,3-thiazol-4-ylmethoxy)anilino]quinazolin-5-yl]oxypropan-2-yl]-2,4-dihydroxybutanamide Chemical compound C=12C(OC[C@@H](C)NC(=O)[C@H](O)CCO)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CSC=N1 RGCXZBHFAMZESU-FOIQADDNSA-N 0.000 claims description 4
- HEHLJJFIAJUQJF-VGOFRKELSA-N (2r)-n-[(2r)-1-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropan-2-yl]-2,4-dihydroxybutanamide Chemical compound C=12C(OC[C@@H](C)NC(=O)[C@H](O)CCO)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 HEHLJJFIAJUQJF-VGOFRKELSA-N 0.000 claims description 4
- KDLYFRZQLPIQAE-LJQANCHMSA-N (2r)-n-[2-[4-[3-chloro-4-(1,3-thiazol-4-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-2,4-dihydroxybutanamide Chemical compound C=12C(OCCNC(=O)[C@H](O)CCO)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CSC=N1 KDLYFRZQLPIQAE-LJQANCHMSA-N 0.000 claims description 4
- BVOFMXJMDDDZLZ-OAQYLSRUSA-N (2r)-n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-2,4-dihydroxybutanamide Chemical compound C=12C(OCCNC(=O)[C@H](O)CCO)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 BVOFMXJMDDDZLZ-OAQYLSRUSA-N 0.000 claims description 4
- BVOFMXJMDDDZLZ-NRFANRHFSA-N (2s)-n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-2,4-dihydroxybutanamide Chemical compound C=12C(OCCNC(=O)[C@@H](O)CCO)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 BVOFMXJMDDDZLZ-NRFANRHFSA-N 0.000 claims description 4
- ZAKHJBQWEPRKMT-DEOSSOPVSA-N (2s)-n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-n,1-dimethylpyrrolidine-2-carboxamide Chemical compound O=C([C@H]1N(CCC1)C)N(C)CCOC(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZAKHJBQWEPRKMT-DEOSSOPVSA-N 0.000 claims description 4
- XMTAOKNQELBQQG-UHFFFAOYSA-N 2-hydroxy-n-[2-[4-[3-methyl-4-(1,3-thiazol-4-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]acetamide Chemical compound CC1=CC(NC=2C3=C(OCCNC(=O)CO)C=CC=C3N=CN=2)=CC=C1OCC1=CSC=N1 XMTAOKNQELBQQG-UHFFFAOYSA-N 0.000 claims description 4
- OKEMIUZADYEQMK-UHFFFAOYSA-N 2-hydroxy-n-methyl-n-[2-[4-[3-methyl-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]acetamide Chemical compound C=12C(OCCN(C)C(=O)CO)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OCC1=CC=CC=N1 OKEMIUZADYEQMK-UHFFFAOYSA-N 0.000 claims description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- ZQAVLJPAUJXLIX-OAHLLOKOSA-N n-[(2r)-1-[4-[3-chloro-4-(1,3-thiazol-4-ylmethoxy)anilino]quinazolin-5-yl]oxypropan-2-yl]-2-hydroxy-n-methylacetamide Chemical compound C=12C(OC[C@@H](C)N(C)C(=O)CO)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CSC=N1 ZQAVLJPAUJXLIX-OAHLLOKOSA-N 0.000 claims description 4
- AGYXOEHPGSPADW-QGZVFWFLSA-N n-[(2r)-1-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropan-2-yl]-n-methylacetamide Chemical compound C=12C(OC[C@@H](C)N(C)C(C)=O)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 AGYXOEHPGSPADW-QGZVFWFLSA-N 0.000 claims description 4
- PWDLHTPWJPPZSA-MRXNPFEDSA-N n-[(2r)-1-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropan-2-yl]acetamide Chemical compound C=12C(OC[C@@H](C)NC(C)=O)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 PWDLHTPWJPPZSA-MRXNPFEDSA-N 0.000 claims description 4
- ZUAGEVWCLRYTPM-QGZVFWFLSA-N n-[(2r)-2-[4-[3-chloro-4-[(2-fluorophenyl)methoxy]anilino]quinazolin-5-yl]oxypropyl]-n-methylacetamide Chemical compound C=12C(O[C@@H](CN(C)C(C)=O)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=C1F ZUAGEVWCLRYTPM-QGZVFWFLSA-N 0.000 claims description 4
- LXPPMOMDIWXDJD-QGZVFWFLSA-N n-[(2r)-2-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-5-yl]oxypropyl]-n-methylacetamide Chemical compound C=12C(O[C@@H](CN(C)C(C)=O)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC(F)=C1 LXPPMOMDIWXDJD-QGZVFWFLSA-N 0.000 claims description 4
- BREFKBNSGOBECV-GOSISDBHSA-N n-[(2r)-2-[4-[3-methyl-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropyl]acetamide Chemical compound C=12C(O[C@@H](CNC(C)=O)C)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OCC1=CC=CC=N1 BREFKBNSGOBECV-GOSISDBHSA-N 0.000 claims description 4
- ZHUAQXNXTUPMRX-SFHVURJKSA-N n-[(2s)-1-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropan-2-yl]-2-methoxy-n-methylacetamide Chemical compound C=12C(OC[C@H](C)N(C)C(=O)COC)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZHUAQXNXTUPMRX-SFHVURJKSA-N 0.000 claims description 4
- AGYXOEHPGSPADW-KRWDZBQOSA-N n-[(2s)-1-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropan-2-yl]-n-methylacetamide Chemical compound C=12C(OC[C@H](C)N(C)C(C)=O)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 AGYXOEHPGSPADW-KRWDZBQOSA-N 0.000 claims description 4
- PWDLHTPWJPPZSA-INIZCTEOSA-N n-[(2s)-1-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropan-2-yl]acetamide Chemical compound C=12C(OC[C@H](C)NC(C)=O)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 PWDLHTPWJPPZSA-INIZCTEOSA-N 0.000 claims description 4
- RYSILEDIQWYQBS-INIZCTEOSA-N n-[(2s)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropyl]acetamide Chemical compound C=12C(O[C@H](CNC(C)=O)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 RYSILEDIQWYQBS-INIZCTEOSA-N 0.000 claims description 4
- CSIZPMXNXKIGFQ-UHFFFAOYSA-N n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-2-hydroxy-n-(2-methoxyethyl)acetamide Chemical compound C=12C(OCCN(CCOC)C(=O)CO)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 CSIZPMXNXKIGFQ-UHFFFAOYSA-N 0.000 claims description 4
- PUUUPENHIRMZFW-UHFFFAOYSA-N n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-2-hydroxy-n-(oxan-4-yl)acetamide Chemical compound C1COCCC1N(C(=O)CO)CCOC(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 PUUUPENHIRMZFW-UHFFFAOYSA-N 0.000 claims description 4
- OIJXQVZPGHVADM-UHFFFAOYSA-N n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-2-hydroxy-n-methylpropanamide Chemical compound C=12C(OCCN(C)C(=O)C(O)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 OIJXQVZPGHVADM-UHFFFAOYSA-N 0.000 claims description 4
- FJRVTAFBUMIFKB-UHFFFAOYSA-N n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-2-hydroxy-n-prop-2-ynylacetamide Chemical compound C=12C(OCCN(C(=O)CO)CC#C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 FJRVTAFBUMIFKB-UHFFFAOYSA-N 0.000 claims description 4
- HWTLPRQUZNJVLY-UHFFFAOYSA-N n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-2-hydroxyacetamide Chemical compound C=12C(OCCNC(=O)CO)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 HWTLPRQUZNJVLY-UHFFFAOYSA-N 0.000 claims description 4
- WPVZQLCBCWRRPN-UHFFFAOYSA-N n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-2-methoxyacetamide Chemical compound C=12C(OCCNC(=O)COC)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 WPVZQLCBCWRRPN-UHFFFAOYSA-N 0.000 claims description 4
- IXSCLKPGPOGEFR-UHFFFAOYSA-N n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-3-hydroxy-n,2,2-trimethylpropanamide Chemical compound C=12C(OCCN(C)C(=O)C(C)(C)CO)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 IXSCLKPGPOGEFR-UHFFFAOYSA-N 0.000 claims description 4
- GQMZIGJBGLNSEM-UHFFFAOYSA-N n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-n-(1-methylpiperidin-4-yl)acetamide Chemical compound C1CN(C)CCC1N(C(C)=O)CCOC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 GQMZIGJBGLNSEM-UHFFFAOYSA-N 0.000 claims description 4
- DHTQPVZGPLQADO-UHFFFAOYSA-N n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-n-(2-hydroxyethyl)acetamide Chemical compound C=12C(OCCN(CCO)C(=O)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 DHTQPVZGPLQADO-UHFFFAOYSA-N 0.000 claims description 4
- BTZFEYUHUYLZSR-UHFFFAOYSA-N n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-n-cyclobutylacetamide Chemical compound C1CCC1N(C(=O)C)CCOC(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 BTZFEYUHUYLZSR-UHFFFAOYSA-N 0.000 claims description 4
- HONLRZUHJCHZQZ-UHFFFAOYSA-N n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-n-cyclopropyl-2-hydroxyacetamide Chemical compound C1CC1N(C(=O)CO)CCOC(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 HONLRZUHJCHZQZ-UHFFFAOYSA-N 0.000 claims description 4
- JTGFZPCQUAOLLV-UHFFFAOYSA-N n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-n-methylacetamide Chemical compound C=12C(OCCN(C)C(C)=O)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 JTGFZPCQUAOLLV-UHFFFAOYSA-N 0.000 claims description 4
- UVWKTXAUGZHLGF-UHFFFAOYSA-N n-[2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]-n-prop-2-ynylacetamide Chemical compound C=12C(OCCN(C(=O)C)CC#C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 UVWKTXAUGZHLGF-UHFFFAOYSA-N 0.000 claims description 4
- UGMLMRFRDGWJSC-HXUWFJFHSA-N tert-butyl n-[2-[[(2r)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropyl]amino]-2-oxoethyl]-n-methylcarbamate Chemical compound C=12C(O[C@@H](CNC(=O)CN(C)C(=O)OC(C)(C)C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 UGMLMRFRDGWJSC-HXUWFJFHSA-N 0.000 claims description 4
- KHYSEXYNSLDULJ-RTBURBONSA-N (2r)-n-[(2r)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropyl]-2-methoxy-n-methylpropanamide Chemical compound C=12C(O[C@H](C)CN(C)C(=O)[C@@H](C)OC)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 KHYSEXYNSLDULJ-RTBURBONSA-N 0.000 claims description 3
- MXIIFZGCKAYGMJ-HTAPYJJXSA-N (2r)-n-[(2s)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropyl]-2,4-dihydroxybutanamide Chemical compound C=12C(O[C@H](CNC(=O)[C@H](O)CCO)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 MXIIFZGCKAYGMJ-HTAPYJJXSA-N 0.000 claims description 3
- DEUFYWLAHJEEAI-XXBNENTESA-N (2s)-4-bromo-2-hydroxy-n-[(2r)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropyl]butanamide Chemical compound C=12C(O[C@@H](CNC(=O)[C@@H](O)CCBr)C)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 DEUFYWLAHJEEAI-XXBNENTESA-N 0.000 claims description 3
- HEHLJJFIAJUQJF-VGSWGCGISA-N (2s)-n-[(2r)-1-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropan-2-yl]-2,4-dihydroxybutanamide Chemical compound C=12C(OC[C@@H](C)NC(=O)[C@@H](O)CCO)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 HEHLJJFIAJUQJF-VGSWGCGISA-N 0.000 claims description 3
- MXIIFZGCKAYGMJ-VGSWGCGISA-N (2s)-n-[(2r)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropyl]-2,4-dihydroxybutanamide Chemical compound C=12C(O[C@@H](CNC(=O)[C@@H](O)CCO)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 MXIIFZGCKAYGMJ-VGSWGCGISA-N 0.000 claims description 3
- DCFPQVBAWLOOHB-MSOLQXFVSA-N (2s)-n-[(2r)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropyl]-2-hydroxy-n-methylpropanamide Chemical compound C=12C(O[C@@H](CN(C)C(=O)[C@H](C)O)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 DCFPQVBAWLOOHB-MSOLQXFVSA-N 0.000 claims description 3
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- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
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- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
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- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
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- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
Classifications
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms 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
- 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
- C07D417/02—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 two hetero rings
- C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Ceramic Engineering (AREA)
- Manufacturing & Machinery (AREA)
- Urology & Nephrology (AREA)
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- Vascular Medicine (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0326459.5A GB0326459D0 (en) | 2003-11-13 | 2003-11-13 | Quinazoline derivatives |
| GB0326459.5 | 2003-11-13 | ||
| PCT/GB2004/004761 WO2005051923A1 (en) | 2003-11-13 | 2004-11-11 | Quinazoline derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2545262A1 true CA2545262A1 (en) | 2005-06-09 |
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|---|---|---|---|
| CA002545262A Abandoned CA2545262A1 (en) | 2003-11-13 | 2004-11-11 | Quinazoline derivatives |
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| EP (1) | EP1685116A1 (enExample) |
| JP (1) | JP2007511491A (enExample) |
| KR (1) | KR20060127410A (enExample) |
| CN (2) | CN1906178A (enExample) |
| AR (1) | AR046452A1 (enExample) |
| AU (1) | AU2004293250A1 (enExample) |
| BR (1) | BRPI0416479A (enExample) |
| CA (1) | CA2545262A1 (enExample) |
| GB (1) | GB0326459D0 (enExample) |
| IL (1) | IL175421A0 (enExample) |
| NO (1) | NO20062353L (enExample) |
| TW (1) | TW200524903A (enExample) |
| UY (1) | UY28610A1 (enExample) |
| WO (1) | WO2005051923A1 (enExample) |
| ZA (1) | ZA200603817B (enExample) |
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| GB0126433D0 (en) * | 2001-11-03 | 2002-01-02 | Astrazeneca Ab | Compounds |
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| GB0309009D0 (en) * | 2003-04-22 | 2003-05-28 | Astrazeneca Ab | Quinazoline derivatives |
| GB0309850D0 (en) * | 2003-04-30 | 2003-06-04 | Astrazeneca Ab | Quinazoline derivatives |
| GB0321648D0 (en) * | 2003-09-16 | 2003-10-15 | Astrazeneca Ab | Quinazoline derivatives |
| WO2005026156A1 (en) * | 2003-09-16 | 2005-03-24 | Astrazeneca Ab | Quinazoline derivatives |
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| US7569577B2 (en) * | 2003-09-16 | 2009-08-04 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
| WO2005026157A1 (en) * | 2003-09-16 | 2005-03-24 | Astrazeneca Ab | Quinazoline derivatives |
| GB0322409D0 (en) * | 2003-09-25 | 2003-10-29 | Astrazeneca Ab | Quinazoline derivatives |
| EP1713781B1 (en) * | 2004-02-03 | 2008-11-05 | AstraZeneca AB | Quinazoline derivatives |
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| GB0504474D0 (en) * | 2005-03-04 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
| GB0508717D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
| GB0508715D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
| JP2009508918A (ja) * | 2005-09-20 | 2009-03-05 | アストラゼネカ アクチボラグ | 癌治療のためのerbB受容体チロシンキナーゼ阻害剤としての4−(1H−インダゾール−5−イル]アミノ)キナゾリン化合物 |
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| EP1957499A1 (en) * | 2005-12-02 | 2008-08-20 | AstraZeneca AB | 4-anilino-substituted quinazoline derivatives as tyrosine kinase inhibitors |
| WO2007063293A1 (en) * | 2005-12-02 | 2007-06-07 | Astrazeneca Ab | Quinazoleine derivatives used as inhibitors of erbb tyrosine kinase |
| KR101129868B1 (ko) | 2006-10-04 | 2012-04-12 | 화이자 프로덕츠 인코포레이티드 | 칼슘 수용체 길항제로서의 피리도[4,3-d]피리미딘-4(3H)-온 유도체 |
| CN101878203A (zh) | 2007-10-29 | 2010-11-03 | 纳科法尔马有限公司 | 作为抗癌剂的新的4-(四唑-5-基)喹唑啉衍生物 |
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| EP1957499A1 (en) | 2005-12-02 | 2008-08-20 | AstraZeneca AB | 4-anilino-substituted quinazoline derivatives as tyrosine kinase inhibitors |
| WO2007063293A1 (en) | 2005-12-02 | 2007-06-07 | Astrazeneca Ab | Quinazoleine derivatives used as inhibitors of erbb tyrosine kinase |
-
2003
- 2003-11-13 GB GBGB0326459.5A patent/GB0326459D0/en not_active Ceased
-
2004
- 2004-11-11 CA CA002545262A patent/CA2545262A1/en not_active Abandoned
- 2004-11-11 AU AU2004293250A patent/AU2004293250A1/en not_active Abandoned
- 2004-11-11 EP EP04798484A patent/EP1685116A1/en not_active Withdrawn
- 2004-11-11 WO PCT/GB2004/004761 patent/WO2005051923A1/en not_active Ceased
- 2004-11-11 CN CNA2004800404156A patent/CN1906178A/zh active Pending
- 2004-11-11 US US10/578,663 patent/US7625908B2/en not_active Expired - Fee Related
- 2004-11-11 CN CN201010119887A patent/CN101787019A/zh active Pending
- 2004-11-11 BR BRPI0416479-2A patent/BRPI0416479A/pt not_active Application Discontinuation
- 2004-11-11 JP JP2006538946A patent/JP2007511491A/ja active Pending
- 2004-11-11 KR KR1020067011553A patent/KR20060127410A/ko not_active Withdrawn
- 2004-11-11 UY UY28610A patent/UY28610A1/es not_active Application Discontinuation
- 2004-11-12 TW TW093134778A patent/TW200524903A/zh unknown
- 2004-11-12 AR ARP040104181A patent/AR046452A1/es unknown
-
2006
- 2006-05-04 IL IL175421A patent/IL175421A0/en unknown
- 2006-05-12 ZA ZA200603817A patent/ZA200603817B/en unknown
- 2006-05-23 NO NO20062353A patent/NO20062353L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| GB0326459D0 (en) | 2003-12-17 |
| CN1906178A (zh) | 2007-01-31 |
| BRPI0416479A (pt) | 2007-03-06 |
| KR20060127410A (ko) | 2006-12-12 |
| JP2007511491A (ja) | 2007-05-10 |
| UY28610A1 (es) | 2005-06-30 |
| US20070244136A1 (en) | 2007-10-18 |
| IL175421A0 (en) | 2006-09-05 |
| WO2005051923A1 (en) | 2005-06-09 |
| TW200524903A (en) | 2005-08-01 |
| AR046452A1 (es) | 2005-12-07 |
| AU2004293250A1 (en) | 2005-06-09 |
| NO20062353L (no) | 2006-08-09 |
| ZA200603817B (en) | 2007-10-31 |
| CN101787019A (zh) | 2010-07-28 |
| EP1685116A1 (en) | 2006-08-02 |
| US7625908B2 (en) | 2009-12-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |