CA2567832A1 - Quinazoline derivatives as erbb receptor tyrosine kinases - Google Patents

Info

Publication number

CA2567832A1

CA2567832A1 CA002567832A CA2567832A CA2567832A1 CA 2567832 A1 CA2567832 A1 CA 2567832A1 CA 002567832 A CA002567832 A CA 002567832A CA 2567832 A CA2567832 A CA 2567832A CA 2567832 A1 CA2567832 A1 CA 2567832A1

Authority

CA

Canada

Prior art keywords

oxy

alkyl

methyl

quinazolin

phenyl

Prior art date

2004-06-04

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

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title abstract description 118
• 102000001301 EGF receptor Human genes 0.000 title abstract description 14
• 108060006698 EGF receptor Proteins 0.000 title abstract description 14
• 238000000034 method Methods 0.000 claims abstract description 88
• 230000008569 process Effects 0.000 claims abstract description 70
• 238000004519 manufacturing process Methods 0.000 claims abstract description 7
• 230000001028 anti-proliverative effect Effects 0.000 claims abstract description 6
• 238000002360 preparation method Methods 0.000 claims abstract description 6
• 239000003814 drug Substances 0.000 claims abstract description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
• 125000000217 alkyl group Chemical group 0.000 claims description 787
• -1 cyano, nitro, hydroxy, amino, carboxy, carbamoyl Chemical group 0.000 claims description 710
• 125000001424 substituent group Chemical group 0.000 claims description 334
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 268
• 125000000623 heterocyclic group Chemical group 0.000 claims description 263
• 229910052757 nitrogen Inorganic materials 0.000 claims description 214
• 239000001257 hydrogen Substances 0.000 claims description 175
• 229910052739 hydrogen Inorganic materials 0.000 claims description 175
• 125000003545 alkoxy group Chemical group 0.000 claims description 160
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 140
• 125000005843 halogen group Chemical group 0.000 claims description 138
• 238000006243 chemical reaction Methods 0.000 claims description 99
• 125000000304 alkynyl group Chemical group 0.000 claims description 98
• 125000003342 alkenyl group Chemical group 0.000 claims description 96
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 92
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 91
• 125000003282 alkyl amino group Chemical group 0.000 claims description 90
• 150000001875 compounds Chemical class 0.000 claims description 77
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 72
• 229910052760 oxygen Inorganic materials 0.000 claims description 65
• 125000001589 carboacyl group Chemical group 0.000 claims description 62
• 150000003839 salts Chemical class 0.000 claims description 62
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 61
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 59
• 125000001153 fluoro group Chemical group F* 0.000 claims description 58
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 56
• 125000005842 heteroatom Chemical group 0.000 claims description 56
• 239000001301 oxygen Substances 0.000 claims description 55
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 54
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 51
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 48
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 47
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 47
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 46
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 44
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 40
• 125000004414 alkyl thio group Chemical group 0.000 claims description 40
• 125000004423 acyloxy group Chemical group 0.000 claims description 39
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 39
• 125000004043 oxo group Chemical group O=* 0.000 claims description 36
• 229910052717 sulfur Inorganic materials 0.000 claims description 36
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 35
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 34
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 31
• 125000000524 functional group Chemical group 0.000 claims description 30
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 30
• 125000004076 pyridyl group Chemical group 0.000 claims description 30
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 29
• 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 29
• 239000011593 sulfur Chemical group 0.000 claims description 28
• 229910052799 carbon Inorganic materials 0.000 claims description 25
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 24
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 24
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 23
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 23
• 230000000694 effects Effects 0.000 claims description 23
• 125000003396 thiol group Chemical class [H]S* 0.000 claims description 22
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 21
• 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 20
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 18
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 18
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 17
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 17
• 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 16
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 16
• 125000006239 protecting group Chemical group 0.000 claims description 16
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 16
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 15
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 15
• 125000003118 aryl group Chemical group 0.000 claims description 15
• 125000001072 heteroaryl group Chemical group 0.000 claims description 15
• 125000003386 piperidinyl group Chemical group 0.000 claims description 15
• 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 14
• 150000001412 amines Chemical class 0.000 claims description 14
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 14
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 14
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 14
• 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 14
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 13
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 13
• DRYRBWIFRVMRPV-UHFFFAOYSA-N quinazolin-4-amine Chemical compound C1=CC=C2C(N)=NC=NC2=C1 DRYRBWIFRVMRPV-UHFFFAOYSA-N 0.000 claims description 13
• 150000002431 hydrogen Chemical class 0.000 claims description 12
• 230000002401 inhibitory effect Effects 0.000 claims description 12
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
• 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 claims description 11
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 11
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 10
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 10
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 10
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 10
• 125000002393 azetidinyl group Chemical group 0.000 claims description 10
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 10
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 10
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 claims description 9
• 241001465754 Metazoa Species 0.000 claims description 9
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 9
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 9
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 9
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 9
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 9
• 229920002554 vinyl polymer Polymers 0.000 claims description 9
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 8
• 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 8
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 8
• 125000005133 alkynyloxy group Chemical group 0.000 claims description 8
• 125000001246 bromo group Chemical group Br* 0.000 claims description 8
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 claims description 8
• 125000004432 carbon atom Chemical group C* 0.000 claims description 8
• 125000001422 pyrrolinyl group Chemical group 0.000 claims description 8
• 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 7
• 239000007822 coupling agent Substances 0.000 claims description 6
• 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 6
• 125000005053 dihydropyrimidinyl group Chemical group N1(CN=CC=C1)* 0.000 claims description 6
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 6
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 6
• 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 6
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 6
• 230000003213 activating effect Effects 0.000 claims description 5
• 150000001408 amides Chemical class 0.000 claims description 5
• 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 5
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 5
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 5
• 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 5
• 125000006223 tetrahydrofuranylmethyl group Chemical group 0.000 claims description 5
• 125000006173 tetrahydropyranylmethyl group Chemical group 0.000 claims description 5
• 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 4
• 238000005859 coupling reaction Methods 0.000 claims description 4
• 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 4
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
• BTNBMGWBIOYPAU-FXAWDEMLSA-N (2s)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-1-[(3r)-3-hydroxypyrrolidin-1-yl]propan-1-one Chemical compound O([C@@H](C)C(=O)N1C[C@H](O)CC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 BTNBMGWBIOYPAU-FXAWDEMLSA-N 0.000 claims description 3
• BTNBMGWBIOYPAU-PXNSSMCTSA-N (2s)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-1-[(3s)-3-hydroxypyrrolidin-1-yl]propan-1-one Chemical compound O([C@@H](C)C(=O)N1C[C@@H](O)CC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 BTNBMGWBIOYPAU-PXNSSMCTSA-N 0.000 claims description 3
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 3
• 230000008878 coupling Effects 0.000 claims description 3
• 238000010168 coupling process Methods 0.000 claims description 3
• ZBYCKCQLRHBIOI-JOCHJYFZSA-N (2r)-1-(4-ethylpiperazin-1-yl)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropan-1-one Chemical compound C1CN(CC)CCN1C(=O)[C@@H](C)OC1=CC=CC2=NC=NC(NC=3C=C(C)C(OC=4C=NC(C)=CC=4)=CC=3)=C12 ZBYCKCQLRHBIOI-JOCHJYFZSA-N 0.000 claims description 2
• WHSWMMPWNOZHIK-IFMALSPDSA-N (2r)-1-[(2r)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropan-1-one Chemical compound O([C@H](C)C(=O)N1[C@H](CCC1)CO)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 WHSWMMPWNOZHIK-IFMALSPDSA-N 0.000 claims description 2
• WACRWIYZJJPTCG-TZIWHRDSSA-N (2r)-1-[(3r)-3-hydroxypiperidin-1-yl]-2-[4-[3-methoxy-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropan-1-one Chemical compound O=C([C@@H](C)OC=1C=CC=C2N=CN=C(C=12)NC=1C=C(C(=CC=1)OC=1C=NC(C)=CC=1)OC)N1CCC[C@@H](O)C1 WACRWIYZJJPTCG-TZIWHRDSSA-N 0.000 claims description 2
• HACPXTPHGGTGJL-IFMALSPDSA-N (2r)-1-[(3r)-3-hydroxypiperidin-1-yl]-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropan-1-one Chemical compound O([C@H](C)C(=O)N1C[C@H](O)CCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 HACPXTPHGGTGJL-IFMALSPDSA-N 0.000 claims description 2
• CUXVZRKCEYEHCD-TZIWHRDSSA-N (2r)-1-[(3r)-3-hydroxypyrrolidin-1-yl]-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropan-1-one Chemical compound O([C@H](C)C(=O)N1C[C@H](O)CC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 CUXVZRKCEYEHCD-TZIWHRDSSA-N 0.000 claims description 2
• DTKCUTKZQAYHLJ-DENIHFKCSA-N (2r)-1-[(3r)-3-hydroxypyrrolidin-1-yl]-2-[4-[3-methyl-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropan-1-one Chemical compound O([C@H](C)C(=O)N1C[C@H](O)CC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OCC1=CC=CC=N1 DTKCUTKZQAYHLJ-DENIHFKCSA-N 0.000 claims description 2
• BUVVFLDHQZDVQL-DUSLRRAJSA-N (2r)-2-[4-(3-chloro-4-pyridin-2-yloxyanilino)quinazolin-5-yl]oxy-1-(3-hydroxypiperidin-1-yl)propan-1-one Chemical compound O([C@H](C)C(=O)N1CC(O)CCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC1=CC=CC=N1 BUVVFLDHQZDVQL-DUSLRRAJSA-N 0.000 claims description 2
• FYBUGQUXSUURKW-QGZVFWFLSA-N (2r)-2-[4-(3-chloro-4-pyridin-2-yloxyanilino)quinazolin-5-yl]oxy-1-piperazin-1-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCNCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC1=CC=CC=N1 FYBUGQUXSUURKW-QGZVFWFLSA-N 0.000 claims description 2
• GQGOLYCZKGIRHT-OAHLLOKOSA-N (2r)-2-[4-(3-chloro-4-pyridin-2-yloxyanilino)quinazolin-5-yl]oxy-n,n-dimethylpropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC1=CC=CC=N1 GQGOLYCZKGIRHT-OAHLLOKOSA-N 0.000 claims description 2
• BSMOUWVKFROESP-MRXNPFEDSA-N (2r)-2-[4-(3-chloro-4-pyridin-2-yloxyanilino)quinazolin-5-yl]oxy-n-(2-hydroxyethyl)-n-methylpropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(C)CCO)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC1=CC=CC=N1 BSMOUWVKFROESP-MRXNPFEDSA-N 0.000 claims description 2
• ZMAHCPKWJSLWEH-QGZVFWFLSA-N (2r)-2-[4-(3-chloro-4-pyridin-2-yloxyanilino)quinazolin-5-yl]oxy-n-(2-methoxyethyl)-n-methylpropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(C)CCOC)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC1=CC=CC=N1 ZMAHCPKWJSLWEH-QGZVFWFLSA-N 0.000 claims description 2
• DXQMVGDBGQIEIK-QGZVFWFLSA-N (2r)-2-[4-(3-chloro-4-pyridin-2-yloxyanilino)quinazolin-5-yl]oxy-n-ethyl-n-(2-hydroxyethyl)propanamide Chemical compound C=12C(O[C@H](C)C(=O)N(CCO)CC)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC1=CC=CC=N1 DXQMVGDBGQIEIK-QGZVFWFLSA-N 0.000 claims description 2
• WEZZNWQATVXVDW-QGZVFWFLSA-N (2r)-2-[4-(3-fluoro-4-pyridin-3-yloxyanilino)quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCOCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1F)=CC=C1OC1=CC=CN=C1 WEZZNWQATVXVDW-QGZVFWFLSA-N 0.000 claims description 2
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• MBZYSNYQGXUZAF-LJQANCHMSA-N (2r)-2-[4-(3-methyl-4-pyridin-3-yloxyanilino)quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCOCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=CN=C1 MBZYSNYQGXUZAF-LJQANCHMSA-N 0.000 claims description 2
• WMDROLDZARJZNE-LJQANCHMSA-N (2r)-2-[4-(3-methyl-4-pyridin-4-yloxyanilino)quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCOCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=NC=C1 WMDROLDZARJZNE-LJQANCHMSA-N 0.000 claims description 2
• CQLYORSHVYBLMS-GOSISDBHSA-N (2r)-2-[4-(3-methyl-4-pyrimidin-5-yloxyanilino)quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCOCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CN=CN=C1 CQLYORSHVYBLMS-GOSISDBHSA-N 0.000 claims description 2
• TYPJWHGRDVHRRZ-OAHLLOKOSA-N (2r)-2-[4-[3-chloro-4-(1,3-thiazol-2-yloxy)anilino]quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCOCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC1=NC=CS1 TYPJWHGRDVHRRZ-OAHLLOKOSA-N 0.000 claims description 2
• QDHNOYPCQADHDW-OAHLLOKOSA-N (2r)-2-[4-[3-chloro-4-(1,3-thiazol-5-yloxy)anilino]quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCOCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC1=CN=CS1 QDHNOYPCQADHDW-OAHLLOKOSA-N 0.000 claims description 2
• BKUNUATYQBJKAW-MRXNPFEDSA-N (2r)-2-[4-[3-chloro-4-(1-methylpyrazol-4-yl)oxyanilino]quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCOCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC=1C=NN(C)C=1 BKUNUATYQBJKAW-MRXNPFEDSA-N 0.000 claims description 2
• DBJFVGIMTAWNDN-MRXNPFEDSA-N (2r)-2-[4-[3-chloro-4-(6-fluoropyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCOCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC1=CC=C(F)N=C1 DBJFVGIMTAWNDN-MRXNPFEDSA-N 0.000 claims description 2
• CTFGDXFXTZFJLD-GOSISDBHSA-N (2r)-2-[4-[3-chloro-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCOCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC1=CC=C(C)N=C1 CTFGDXFXTZFJLD-GOSISDBHSA-N 0.000 claims description 2
• DYOHMTPFQDFJSG-MRXNPFEDSA-N (2r)-2-[4-[3-chloro-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-n,n-dimethylpropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC1=CC=C(C)N=C1 DYOHMTPFQDFJSG-MRXNPFEDSA-N 0.000 claims description 2
• ZGBFXAWADCAOJE-QGZVFWFLSA-N (2r)-2-[4-[3-chloro-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-n-(2-hydroxyethyl)-n-methylpropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(C)CCO)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC1=CC=C(C)N=C1 ZGBFXAWADCAOJE-QGZVFWFLSA-N 0.000 claims description 2
• BTNBMGWBIOYPAU-YLJYHZDGSA-N (2r)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-1-[(3r)-3-hydroxypyrrolidin-1-yl]propan-1-one Chemical compound O([C@H](C)C(=O)N1C[C@H](O)CC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 BTNBMGWBIOYPAU-YLJYHZDGSA-N 0.000 claims description 2
• UTHNMKVUDJYYFU-GOSISDBHSA-N (2r)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-1-pyrrolidin-1-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 UTHNMKVUDJYYFU-GOSISDBHSA-N 0.000 claims description 2
• CBUHIHJVWPRZBD-RUZDIDTESA-N (2r)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-4-hydroxy-1-pyrrolidin-1-ylbutan-1-one Chemical compound O([C@H](CCO)C(=O)N1CCCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 CBUHIHJVWPRZBD-RUZDIDTESA-N 0.000 claims description 2
• UFOUYPHVNFLZQT-HSZRJFAPSA-N (2r)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-4-hydroxy-n,n-dimethylbutanamide Chemical compound C=12C(O[C@H](CCO)C(=O)N(C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 UFOUYPHVNFLZQT-HSZRJFAPSA-N 0.000 claims description 2
• QPPYSOHWFOUKPX-MRXNPFEDSA-N (2r)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-n,n-dimethylpropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 QPPYSOHWFOUKPX-MRXNPFEDSA-N 0.000 claims description 2
• QCTACFWJSRSNOJ-OAHLLOKOSA-N (2r)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-n-methylpropanamide Chemical compound C=12C(O[C@H](C)C(=O)NC)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 QCTACFWJSRSNOJ-OAHLLOKOSA-N 0.000 claims description 2
• DMWWQRAYTXZZJP-CQSZACIVSA-N (2r)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(N)=O)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 DMWWQRAYTXZZJP-CQSZACIVSA-N 0.000 claims description 2
• WZACCHHDKDZYQO-LJQANCHMSA-N (2r)-2-[4-[3-methoxy-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O=C([C@@H](C)OC=1C=CC=C2N=CN=C(C=12)NC=1C=C(C(=CC=1)OC=1C=NC(C)=CC=1)OC)N1CCOCC1 WZACCHHDKDZYQO-LJQANCHMSA-N 0.000 claims description 2
• AXAMEWIVQQBQPF-LJQANCHMSA-N (2r)-2-[4-[3-methoxy-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-1-piperazin-1-ylpropan-1-one Chemical compound O=C([C@@H](C)OC=1C=CC=C2N=CN=C(C=12)NC=1C=C(C(=CC=1)OC=1C=NC(C)=CC=1)OC)N1CCNCC1 AXAMEWIVQQBQPF-LJQANCHMSA-N 0.000 claims description 2
• ZIHGLKQTSBXMBZ-QGZVFWFLSA-N (2r)-2-[4-[3-methoxy-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-n,n-dimethylpropanamide Chemical compound COC1=CC(NC=2C3=C(O[C@H](C)C(=O)N(C)C)C=CC=C3N=CN=2)=CC=C1OC1=CC=C(C)N=C1 ZIHGLKQTSBXMBZ-QGZVFWFLSA-N 0.000 claims description 2
• CLVHWHRMEZJEAB-QGZVFWFLSA-N (2r)-2-[4-[3-methyl-4-(1,3-thiazol-2-yloxy)anilino]quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCOCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=NC=CS1 CLVHWHRMEZJEAB-QGZVFWFLSA-N 0.000 claims description 2
• AMBLTSYRYALCDZ-QGZVFWFLSA-N (2r)-2-[4-[3-methyl-4-(1,3-thiazol-5-yloxy)anilino]quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCOCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CN=CS1 AMBLTSYRYALCDZ-QGZVFWFLSA-N 0.000 claims description 2
• SHUGRJASNGVPQD-HXUWFJFHSA-N (2r)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCOCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 SHUGRJASNGVPQD-HXUWFJFHSA-N 0.000 claims description 2
• ZYLSCLXBHVKVII-HXUWFJFHSA-N (2r)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-1-piperazin-1-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCNCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 ZYLSCLXBHVKVII-HXUWFJFHSA-N 0.000 claims description 2
• YBLLSCVJZWJBBA-HXUWFJFHSA-N (2r)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-1-pyrrolidin-1-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 YBLLSCVJZWJBBA-HXUWFJFHSA-N 0.000 claims description 2
• UYBBJBMNZBJLRY-LJQANCHMSA-N (2r)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-n-(2-methylsulfanylethyl)propanamide Chemical compound C=12C(O[C@H](C)C(=O)NCCSC)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 UYBBJBMNZBJLRY-LJQANCHMSA-N 0.000 claims description 2
• ADLFECNKJJVXNF-XMMPIXPASA-N (2r)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-n-[3-(4-methylpiperazin-1-yl)propyl]propanamide Chemical compound O([C@H](C)C(=O)NCCCN1CCN(C)CC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 ADLFECNKJJVXNF-XMMPIXPASA-N 0.000 claims description 2
• KCYROHOXZDSAHS-MRXNPFEDSA-N (2r)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(N)=O)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 KCYROHOXZDSAHS-MRXNPFEDSA-N 0.000 claims description 2
• LJZISAWYNKRWIO-HXUWFJFHSA-N (2r)-2-[4-[3-methyl-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-1-pyrrolidin-1-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OCC1=CC=CC=N1 LJZISAWYNKRWIO-HXUWFJFHSA-N 0.000 claims description 2
• YJBCUEJJNJKFEU-LJQANCHMSA-N (2r)-2-[4-[4-(6-methoxypyridin-3-yl)oxy-3-methylanilino]quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound C1=NC(OC)=CC=C1OC(C(=C1)C)=CC=C1NC1=NC=NC2=CC=CC(O[C@H](C)C(=O)N3CCOCC3)=C12 YJBCUEJJNJKFEU-LJQANCHMSA-N 0.000 claims description 2
• GKIPTIQEDVKHHB-LJQANCHMSA-N (2r)-2-[4-[4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCOCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1)=CC=C1OC1=CC=C(C)N=C1 GKIPTIQEDVKHHB-LJQANCHMSA-N 0.000 claims description 2
• PCBSKIFMBDGJTQ-LJQANCHMSA-N (2r)-2-[4-[4-[6-(fluoromethyl)pyridin-3-yl]oxy-3-methylanilino]quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O([C@H](C)C(=O)N1CCOCC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(CF)N=C1 PCBSKIFMBDGJTQ-LJQANCHMSA-N 0.000 claims description 2
• UJYVEXAXJKPDHQ-HXUWFJFHSA-N (2r)-n,n-bis(2-hydroxyethyl)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(CCO)CCO)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 UJYVEXAXJKPDHQ-HXUWFJFHSA-N 0.000 claims description 2
• ZCASMWAAKLWYFO-JOCHJYFZSA-N (2r)-n,n-bis(2-methoxyethyl)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(CCOC)CCOC)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 ZCASMWAAKLWYFO-JOCHJYFZSA-N 0.000 claims description 2
• XNXUDGXKTVZKLB-GOSISDBHSA-N (2r)-n,n-dimethyl-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(C)C)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 XNXUDGXKTVZKLB-GOSISDBHSA-N 0.000 claims description 2
• RDQBRFGOAVGHTB-LJQANCHMSA-N (2r)-n-(2-acetamidoethyl)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)NCCNC(C)=O)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 RDQBRFGOAVGHTB-LJQANCHMSA-N 0.000 claims description 2
• FPHRUBHFWPHNIS-QGZVFWFLSA-N (2r)-n-(2-hydroxyethyl)-2-[4-(3-methyl-4-pyridin-2-yloxyanilino)quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)NCCO)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=CC=N1 FPHRUBHFWPHNIS-QGZVFWFLSA-N 0.000 claims description 2
• FRIZWTSUZGRCOM-GOSISDBHSA-N (2r)-n-(2-hydroxyethyl)-2-[4-[3-methoxy-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-n-methylpropanamide Chemical compound COC1=CC(NC=2C3=C(O[C@H](C)C(=O)N(C)CCO)C=CC=C3N=CN=2)=CC=C1OC1=CC=C(C)N=C1 FRIZWTSUZGRCOM-GOSISDBHSA-N 0.000 claims description 2
• STZSVNWFZKKZII-QGZVFWFLSA-N (2r)-n-(2-hydroxyethyl)-2-[4-[3-methoxy-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound COC1=CC(NC=2C3=C(O[C@H](C)C(=O)NCCO)C=CC=C3N=CN=2)=CC=C1OC1=CC=C(C)N=C1 STZSVNWFZKKZII-QGZVFWFLSA-N 0.000 claims description 2
• AEOJOWVJRRLUDH-GOSISDBHSA-N (2r)-n-(2-hydroxyethyl)-n-methyl-2-[4-(3-methyl-4-pyridin-2-yloxyanilino)quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(C)CCO)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=CC=N1 AEOJOWVJRRLUDH-GOSISDBHSA-N 0.000 claims description 2
• FALHGGCCRVONDY-LJQANCHMSA-N (2r)-n-(2-hydroxyethyl)-n-methyl-2-[4-[3-methyl-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(C)CCO)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OCC1=CC=CC=N1 FALHGGCCRVONDY-LJQANCHMSA-N 0.000 claims description 2
• ZEQVZRKILUBAEF-LJQANCHMSA-N (2r)-n-(2-methoxyethyl)-2-[4-[3-methoxy-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-n-methylpropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(C)CCOC)=CC=CC2=NC=NC=1NC(C=C1OC)=CC=C1OC1=CC=C(C)N=C1 ZEQVZRKILUBAEF-LJQANCHMSA-N 0.000 claims description 2
• HFBZFADLRHMTQV-LJQANCHMSA-N (2r)-n-(2-methoxyethyl)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)NCCOC)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 HFBZFADLRHMTQV-LJQANCHMSA-N 0.000 claims description 2
• IUTPYWIIYOGFJS-LJQANCHMSA-N (2r)-n-(2-methoxyethyl)-n-methyl-2-[4-(3-methyl-4-pyridin-2-yloxyanilino)quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(C)CCOC)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=CC=N1 IUTPYWIIYOGFJS-LJQANCHMSA-N 0.000 claims description 2
• SNIBNOLMGURVKM-HXUWFJFHSA-N (2r)-n-(2-methoxyethyl)-n-methyl-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(C)CCOC)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 SNIBNOLMGURVKM-HXUWFJFHSA-N 0.000 claims description 2
• UHNGQLQIXXAYRV-LJQANCHMSA-N (2r)-n-(3-hydroxypropyl)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)NCCCO)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 UHNGQLQIXXAYRV-LJQANCHMSA-N 0.000 claims description 2
• XOPDMYXFRHOXFS-HXUWFJFHSA-N (2r)-n-(3-hydroxypropyl)-n-methyl-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(C)CCCO)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 XOPDMYXFRHOXFS-HXUWFJFHSA-N 0.000 claims description 2
• BADAEIKKYQNVPB-HXUWFJFHSA-N (2r)-n-(3-methoxypropyl)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)NCCCOC)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 BADAEIKKYQNVPB-HXUWFJFHSA-N 0.000 claims description 2
• LXZSMFBLAYWXFB-RTBURBONSA-N (2r)-n-[(2r)-2-hydroxypropyl]-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)NC[C@H](O)C)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 LXZSMFBLAYWXFB-RTBURBONSA-N 0.000 claims description 2
• BJCWAEUSGICZGM-RBUKOAKNSA-N (2r)-n-[(2s)-1-hydroxypropan-2-yl]-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)N[C@H](CO)C)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 BJCWAEUSGICZGM-RBUKOAKNSA-N 0.000 claims description 2
• CPRJGTKAFRLWQC-QUCCMNQESA-N (2r)-n-[(2s)-2,3-dihydroxypropyl]-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)NC[C@H](O)CO)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 CPRJGTKAFRLWQC-QUCCMNQESA-N 0.000 claims description 2
• LXZSMFBLAYWXFB-RBUKOAKNSA-N (2r)-n-[(2s)-2-hydroxypropyl]-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)NC[C@@H](O)C)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 LXZSMFBLAYWXFB-RBUKOAKNSA-N 0.000 claims description 2
• JXMDJNJXXJPQER-JOCHJYFZSA-N (2r)-n-[2-(diethylamino)ethyl]-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)NCCN(CC)CC)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 JXMDJNJXXJPQER-JOCHJYFZSA-N 0.000 claims description 2
• JQULZZUKSJWYOE-HXUWFJFHSA-N (2r)-n-[2-(dimethylamino)ethyl]-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)NCCN(C)C)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 JQULZZUKSJWYOE-HXUWFJFHSA-N 0.000 claims description 2
• BIJPVPZNMWGQAV-GOSISDBHSA-N (2r)-n-cyclopropyl-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound O([C@H](C)C(=O)NC1CC1)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 BIJPVPZNMWGQAV-GOSISDBHSA-N 0.000 claims description 2
• KTZOLKJKQFNYEJ-QGZVFWFLSA-N (2r)-n-ethyl-2-[4-(3-methyl-4-pyridin-2-yloxyanilino)quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)NCC)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=CC=N1 KTZOLKJKQFNYEJ-QGZVFWFLSA-N 0.000 claims description 2
• JWMPFTSKSIICOQ-GOSISDBHSA-N (2r)-n-ethyl-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)NCC)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 JWMPFTSKSIICOQ-GOSISDBHSA-N 0.000 claims description 2
• WYJFOMKOPCUELS-HXUWFJFHSA-N (2r)-n-ethyl-n-(2-hydroxyethyl)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)N(CCO)CC)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 WYJFOMKOPCUELS-HXUWFJFHSA-N 0.000 claims description 2
• LJVILAHBLHROHD-QGZVFWFLSA-N (2r)-n-methyl-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@H](C)C(=O)NC)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 LJVILAHBLHROHD-QGZVFWFLSA-N 0.000 claims description 2
• QPPYSOHWFOUKPX-INIZCTEOSA-N (2s)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-n,n-dimethylpropanamide Chemical compound C=12C(O[C@@H](C)C(=O)N(C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 QPPYSOHWFOUKPX-INIZCTEOSA-N 0.000 claims description 2
• QCTACFWJSRSNOJ-HNNXBMFYSA-N (2s)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-n-methylpropanamide Chemical compound C=12C(O[C@@H](C)C(=O)NC)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 QCTACFWJSRSNOJ-HNNXBMFYSA-N 0.000 claims description 2
• DMWWQRAYTXZZJP-AWEZNQCLSA-N (2s)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@@H](C)C(N)=O)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 DMWWQRAYTXZZJP-AWEZNQCLSA-N 0.000 claims description 2
• RHKOFLSVENLYDP-IBGZPJMESA-N (2s)-n-(2-hydroxyethyl)-n-methyl-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C=12C(O[C@@H](C)C(=O)N(C)CCO)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 RHKOFLSVENLYDP-IBGZPJMESA-N 0.000 claims description 2
• IQNBHURYIWAEOA-UHFFFAOYSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-1-(4-methylpiperazin-1-yl)ethanone Chemical compound C1CN(C)CCN1C(=O)COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 IQNBHURYIWAEOA-UHFFFAOYSA-N 0.000 claims description 2
• ABIIALBXPJPBAM-HXUWFJFHSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-1-[(3r)-3-hydroxypyrrolidin-1-yl]-2-methylpropan-1-one Chemical compound C([C@H](O)CC1)N1C(=O)C(C)(C)OC(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ABIIALBXPJPBAM-HXUWFJFHSA-N 0.000 claims description 2
• IIDKWOQWPGRLIW-UHFFFAOYSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-1-morpholin-4-ylethanone Chemical compound C=1C=C(OCC=2N=CC=CC=2)C(Cl)=CC=1NC(C=12)=NC=NC2=CC=CC=1OCC(=O)N1CCOCC1 IIDKWOQWPGRLIW-UHFFFAOYSA-N 0.000 claims description 2
• IOSVSLOBJIGVKD-UHFFFAOYSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-1-piperazin-1-ylethanone Chemical compound C=1C=C(OCC=2N=CC=CC=2)C(Cl)=CC=1NC(C=12)=NC=NC2=CC=CC=1OCC(=O)N1CCNCC1 IOSVSLOBJIGVKD-UHFFFAOYSA-N 0.000 claims description 2
• ZTDGISKEIHFQJM-UHFFFAOYSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-2-methylpropanamide Chemical compound C=12C(OC(C)(C)C(N)=O)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZTDGISKEIHFQJM-UHFFFAOYSA-N 0.000 claims description 2
• UUJIQLYAPKAFLJ-UHFFFAOYSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-n,2-dimethylpropanamide Chemical compound C=12C(OC(C)(C)C(=O)NC)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 UUJIQLYAPKAFLJ-UHFFFAOYSA-N 0.000 claims description 2
• PMYRQDIKMXVAIG-UHFFFAOYSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-n-(1-hydroxy-2-methylpropan-2-yl)-2-methylpropanamide Chemical compound C=12C(OC(C)(C)C(=O)NC(C)(CO)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 PMYRQDIKMXVAIG-UHFFFAOYSA-N 0.000 claims description 2
• MLFLCYJMVUOBOR-UHFFFAOYSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-n-(2-hydroxyethyl)-2-methylpropanamide Chemical compound C=12C(OC(C)(C)C(=O)NCCO)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 MLFLCYJMVUOBOR-UHFFFAOYSA-N 0.000 claims description 2
• INQQFMUBAXLUJS-UHFFFAOYSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-n-(2-hydroxyethyl)-n,2-dimethylpropanamide Chemical compound C=12C(OC(C)(C)C(=O)N(CCO)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 INQQFMUBAXLUJS-UHFFFAOYSA-N 0.000 claims description 2
• DQSMJIPNCYLKDQ-UHFFFAOYSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-n-(2-hydroxyethyl)-n-methylacetamide Chemical compound C=12C(OCC(=O)N(CCO)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 DQSMJIPNCYLKDQ-UHFFFAOYSA-N 0.000 claims description 2
• GAIHXYHHTKIHDB-UHFFFAOYSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-n-(2-methoxyethyl)acetamide Chemical compound C=12C(OCC(=O)NCCOC)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 GAIHXYHHTKIHDB-UHFFFAOYSA-N 0.000 claims description 2
• HXVZBSLWEFSIDC-UHFFFAOYSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-n-(2-methylsulfonylethyl)acetamide Chemical compound C=12C(OCC(=O)NCCS(=O)(=O)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 HXVZBSLWEFSIDC-UHFFFAOYSA-N 0.000 claims description 2
• ZHJQWJWANKXJCA-UHFFFAOYSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-n-[2-(dimethylamino)ethyl]-n-methylacetamide Chemical compound C=12C(OCC(=O)N(C)CCN(C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZHJQWJWANKXJCA-UHFFFAOYSA-N 0.000 claims description 2
• HNILLTAIVGZWKT-UHFFFAOYSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-n-cyclobutylacetamide Chemical compound C=1C=C(OCC=2N=CC=CC=2)C(Cl)=CC=1NC(C=12)=NC=NC2=CC=CC=1OCC(=O)NC1CCC1 HNILLTAIVGZWKT-UHFFFAOYSA-N 0.000 claims description 2
• DHBDAUZNAMLHQZ-UHFFFAOYSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-n-ethyl-n-methylacetamide Chemical compound C=12C(OCC(=O)N(C)CC)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 DHBDAUZNAMLHQZ-UHFFFAOYSA-N 0.000 claims description 2
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• OAOJKRWXBFFKPW-UHFFFAOYSA-N 2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-n-methyl-n-(2-methylsulfonylethyl)acetamide Chemical compound C=12C(OCC(=O)N(CCS(C)(=O)=O)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 OAOJKRWXBFFKPW-UHFFFAOYSA-N 0.000 claims description 2
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• PBTDMULPNDZNOI-UHFFFAOYSA-N 2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-1-(4-methylpiperazin-1-yl)ethanone Chemical compound C1CN(C)CCN1C(=O)COC1=CC=CC2=NC=NC(NC=3C=C(C)C(OC=4C=NC(C)=CC=4)=CC=3)=C12 PBTDMULPNDZNOI-UHFFFAOYSA-N 0.000 claims description 2
• DBBOWDJNLYCSHP-UHFFFAOYSA-N 2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxy-1-piperazin-1-ylethanone Chemical compound C1=NC(C)=CC=C1OC(C(=C1)C)=CC=C1NC1=NC=NC2=CC=CC(OCC(=O)N3CCNCC3)=C12 DBBOWDJNLYCSHP-UHFFFAOYSA-N 0.000 claims description 2
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• CHACVFGFKLWKKP-UHFFFAOYSA-N n-(2-hydroxyethyl)-2-methyl-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanamide Chemical compound C1=NC(C)=CC=C1OC(C(=C1)C)=CC=C1NC1=NC=NC2=CC=CC(OC(C)(C)C(=O)NCCO)=C12 CHACVFGFKLWKKP-UHFFFAOYSA-N 0.000 claims description 2
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• OTPMITWGYZDQSV-HSZRJFAPSA-N tert-butyl 4-[(2r)-2-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxypropanoyl]piperazine-1-carboxylate Chemical compound O([C@H](C)C(=O)N1CCN(CC1)C(=O)OC(C)(C)C)C(C=12)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 OTPMITWGYZDQSV-HSZRJFAPSA-N 0.000 claims description 2
• 150000003246 quinazolines Chemical class 0.000 claims 29
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 8
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• BNZKRAMEZQEDKU-OAHLLOKOSA-N (2r)-2-[4-(3-chloro-4-pyridin-2-yloxyanilino)quinazolin-5-yl]oxy-n-(2-hydroxyethyl)propanamide Chemical compound C=12C(O[C@H](C)C(=O)NCCO)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OC1=CC=CC=N1 BNZKRAMEZQEDKU-OAHLLOKOSA-N 0.000 claims 1
• OAWKJLALCNLYTB-GOSISDBHSA-N (2r)-2-[4-(3-methoxy-4-pyridin-3-yloxyanilino)quinazolin-5-yl]oxy-1-morpholin-4-ylpropan-1-one Chemical compound O=C([C@@H](C)OC=1C=CC=C2N=CN=C(C=12)NC=1C=C(C(=CC=1)OC=1C=NC=CC=1)OC)N1CCOCC1 OAWKJLALCNLYTB-GOSISDBHSA-N 0.000 claims 1
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• FYQLSGTZXNFLBP-AREMUKBSSA-N (2r)-2-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxy-4-hydroxy-1-(4-methylpiperazin-1-yl)butan-1-one Chemical compound C1CN(C)CCN1C(=O)[C@@H](CCO)OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 FYQLSGTZXNFLBP-AREMUKBSSA-N 0.000 claims 1
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