CA2539024A1 - Quinazoline derivatives as antitumor agents - Google Patents

Info

Publication number

CA2539024A1

CA2539024A1 CA002539024A CA2539024A CA2539024A1 CA 2539024 A1 CA2539024 A1 CA 2539024A1 CA 002539024 A CA002539024 A CA 002539024A CA 2539024 A CA2539024 A CA 2539024A CA 2539024 A1 CA2539024 A1 CA 2539024A1

Authority

CA

Canada

Prior art keywords

alkyl

amino

phenyl

quinazolin

chloro

Prior art date

2003-09-16

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 3
• 239000002246 antineoplastic agent Substances 0.000 title description 3
• 125000001424 substituent group Chemical group 0.000 claims abstract description 219
• 230000000694 effects Effects 0.000 claims abstract description 31
• 241001465754 Metazoa Species 0.000 claims abstract description 28
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 27
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims abstract description 24
• 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims abstract description 24
• 238000004519 manufacturing process Methods 0.000 claims abstract description 20
• 230000001028 anti-proliverative effect Effects 0.000 claims abstract description 15
• -1 hydroxy, cyano, amino, carboxy, carbamoyl Chemical group 0.000 claims description 774
• 125000000217 alkyl group Chemical group 0.000 claims description 764
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 269
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 242
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 233
• 125000003545 alkoxy group Chemical group 0.000 claims description 182
• 229910052739 hydrogen Inorganic materials 0.000 claims description 128
• 239000001257 hydrogen Substances 0.000 claims description 127
• 150000001875 compounds Chemical class 0.000 claims description 123
• 125000000623 heterocyclic group Chemical group 0.000 claims description 121
• 125000005843 halogen group Chemical group 0.000 claims description 118
• 125000003282 alkyl amino group Chemical group 0.000 claims description 114
• 150000003246 quinazolines Chemical class 0.000 claims description 108
• 229910052760 oxygen Inorganic materials 0.000 claims description 82
• 238000000034 method Methods 0.000 claims description 80
• 150000003839 salts Chemical class 0.000 claims description 76
• 238000006243 chemical reaction Methods 0.000 claims description 70
• DRYRBWIFRVMRPV-UHFFFAOYSA-N quinazolin-4-amine Chemical compound C1=CC=C2C(N)=NC=NC2=C1 DRYRBWIFRVMRPV-UHFFFAOYSA-N 0.000 claims description 69
• 229910052757 nitrogen Inorganic materials 0.000 claims description 68
• 125000001153 fluoro group Chemical group F* 0.000 claims description 67
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 66
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 60
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 57
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 57
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 55
• 125000003342 alkenyl group Chemical group 0.000 claims description 54
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 52
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 51
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 50
• 229910052717 sulfur Inorganic materials 0.000 claims description 50
• 125000000304 alkynyl group Chemical group 0.000 claims description 49
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 49
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 48
• 229910052799 carbon Inorganic materials 0.000 claims description 48
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 46
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 46
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 45
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 43
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 42
• 125000004423 acyloxy group Chemical group 0.000 claims description 40
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 40
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 39
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 38
• 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 37
• 230000008569 process Effects 0.000 claims description 37
• 125000004414 alkyl thio group Chemical group 0.000 claims description 35
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 34
• 150000001721 carbon Chemical group 0.000 claims description 29
• 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 29
• 125000005842 heteroatom Chemical group 0.000 claims description 27
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 25
• 125000004043 oxo group Chemical group O=* 0.000 claims description 25
• 238000002360 preparation method Methods 0.000 claims description 25
• 125000003386 piperidinyl group Chemical group 0.000 claims description 24
• 125000000524 functional group Chemical group 0.000 claims description 23
• 125000002757 morpholinyl group Chemical group 0.000 claims description 23
• 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 claims description 23
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 23
• 125000004193 piperazinyl group Chemical group 0.000 claims description 22
• 125000006239 protecting group Chemical group 0.000 claims description 22
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 20
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 20
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 20
• 125000004432 carbon atom Chemical group C* 0.000 claims description 20
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 20
• 239000001301 oxygen Substances 0.000 claims description 20
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 18
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 18
• 239000011593 sulfur Chemical group 0.000 claims description 18
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 17
• 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 claims description 17
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 17
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 17
• 125000004076 pyridyl group Chemical group 0.000 claims description 17
• 229920006395 saturated elastomer Polymers 0.000 claims description 17
• 125000003396 thiol group Chemical class [H]S* 0.000 claims description 17
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
• 125000002950 monocyclic group Chemical group 0.000 claims description 13
• 125000003118 aryl group Chemical group 0.000 claims description 12
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 12
• 239000003814 drug Substances 0.000 claims description 12
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 11
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
• 125000001072 heteroaryl group Chemical group 0.000 claims description 11
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 11
• 239000003054 catalyst Substances 0.000 claims description 10
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 10
• 238000003780 insertion Methods 0.000 claims description 10
• 230000037431 insertion Effects 0.000 claims description 10
• 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 claims description 10
• 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 9
• JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 8
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 7
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 7
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 7
• 125000002947 alkylene group Chemical group 0.000 claims description 7
• 125000002393 azetidinyl group Chemical group 0.000 claims description 7
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 7
• 238000005859 coupling reaction Methods 0.000 claims description 7
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 7
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
• 125000003551 oxepanyl group Chemical group 0.000 claims description 7
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 7
• 125000005133 alkynyloxy group Chemical group 0.000 claims description 6
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
• 230000008878 coupling Effects 0.000 claims description 5
• 238000010168 coupling process Methods 0.000 claims description 5
• 125000005724 cycloalkenylene group Chemical group 0.000 claims description 5
• 125000002883 imidazolyl group Chemical group 0.000 claims description 5
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 5
• GRYACOOCWFNQOX-OAQYLSRUSA-N 1-[(2r)-2-[[4-[3-chloro-4-[(5-methyl-1,2-oxazol-3-yl)methoxy]anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound CN(C)CC(=O)N1CCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC4=NOC(C)=C4)=CC=3)=C12 GRYACOOCWFNQOX-OAQYLSRUSA-N 0.000 claims description 4
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 4
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 4
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 4
• AESKUPWTDDMLAL-HXUWFJFHSA-N 1-[(2r)-2-[[4-[3-chloro-4-(1,3-thiazol-4-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound CN(C)CC(=O)N1CCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CSC=4)=CC=3)=C12 AESKUPWTDDMLAL-HXUWFJFHSA-N 0.000 claims description 3
• COAXYQWUTMVSGV-GOSISDBHSA-N 1-[(2r)-2-[[4-[3-chloro-4-(1,3-thiazol-4-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CSC=4)=CC=3)=C12 COAXYQWUTMVSGV-GOSISDBHSA-N 0.000 claims description 3
• OZACVFLDNVJDRR-QGZVFWFLSA-N 1-[(2r)-2-[[4-[3-chloro-4-(1,3-thiazol-5-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4SC=NC=4)=CC=3)=C12 OZACVFLDNVJDRR-QGZVFWFLSA-N 0.000 claims description 3
• MXIWNBPAJCAGDV-HSZRJFAPSA-N 1-[(2r)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]piperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound CN(C)CC(=O)N1CCCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 MXIWNBPAJCAGDV-HSZRJFAPSA-N 0.000 claims description 3
• YANDZCHJZKYLGS-OAQYLSRUSA-N 1-[(2r)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-methoxyethanone Chemical compound COCC(=O)N1CCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 YANDZCHJZKYLGS-OAQYLSRUSA-N 0.000 claims description 3
• NDWYFHHXBYGFGR-RUZDIDTESA-N 1-[(2r)-2-[[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-pyrrolidin-1-ylethanone Chemical compound C1=NC(C)=CC=C1OC(C(=C1)C)=CC=C1NC1=NC=NC2=CC=CC(OC[C@@H]3N(CCC3)C(=O)CN3CCCC3)=C12 NDWYFHHXBYGFGR-RUZDIDTESA-N 0.000 claims description 3
• NXIRLXWPCIBZOF-UHFFFAOYSA-N 1-[4-[[4-[3-chloro-4-(1,3-thiazol-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]piperidin-1-yl]-2-hydroxyethanone Chemical compound C1CN(C(=O)CO)CCC1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4SC=CN=4)=CC=3)=C12 NXIRLXWPCIBZOF-UHFFFAOYSA-N 0.000 claims description 3
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 3
• IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 claims description 3
• 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 3
• GELVZYOEQVJIRR-UHFFFAOYSA-N 2-chloropyrazine Chemical compound ClC1=CN=CC=N1 GELVZYOEQVJIRR-UHFFFAOYSA-N 0.000 claims description 3
• UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 claims description 3
• 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 3
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 3
• XETYECRKJMCQOH-OAQYLSRUSA-N 2-hydroxy-1-[(2r)-2-[[4-[3-methyl-4-[(5-methyl-1,2-oxazol-3-yl)methoxy]anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]ethanone Chemical compound O1C(C)=CC(COC=2C(=CC(NC=3C4=C(OC[C@@H]5N(CCC5)C(=O)CO)C=CC=C4N=CN=3)=CC=2)C)=N1 XETYECRKJMCQOH-OAQYLSRUSA-N 0.000 claims description 3
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 3
• IBWYHNOFSKJKKY-UHFFFAOYSA-N 3-chloropyridazine Chemical compound ClC1=CC=CN=N1 IBWYHNOFSKJKKY-UHFFFAOYSA-N 0.000 claims description 3
• BSDGZUDFPKIYQG-UHFFFAOYSA-N 4-bromopyridine Chemical compound BrC1=CC=NC=C1 BSDGZUDFPKIYQG-UHFFFAOYSA-N 0.000 claims description 3
• DBPKMSBWOKAKLA-UHFFFAOYSA-N 4-chloropyrimidine Chemical compound ClC1=CC=NC=N1 DBPKMSBWOKAKLA-UHFFFAOYSA-N 0.000 claims description 3
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 3
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
• 125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
• 239000008194 pharmaceutical composition Substances 0.000 claims description 3
• 125000000464 thioxo group Chemical group S=* 0.000 claims description 3
• MOMRGTMRWDEZEU-LJQANCHMSA-N 1-[(2r)-2-[[4-[3-chloro-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound C1=NC(C)=CC=C1OC(C(=C1)Cl)=CC=C1NC1=NC=NC2=CC=CC(OC[C@@H]3N(CCC3)C(=O)CO)=C12 MOMRGTMRWDEZEU-LJQANCHMSA-N 0.000 claims description 2
• AJTYKPIFASHILD-OAQYLSRUSA-N 1-[(2r)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]-4-methylpiperazin-1-yl]-2-hydroxyethanone Chemical compound C1N(C)CCN(C(=O)CO)[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 AJTYKPIFASHILD-OAQYLSRUSA-N 0.000 claims description 2
• SNLRBQMQODFNMA-JOCHJYFZSA-N 1-[(2r)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]morpholin-4-yl]-2-(dimethylamino)ethanone Chemical compound C1N(C(=O)CN(C)C)CCO[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 SNLRBQMQODFNMA-JOCHJYFZSA-N 0.000 claims description 2
• MJBQFBQRZWOFCX-OAQYLSRUSA-N 1-[(2r)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxy-2-methylpropan-1-one Chemical compound CC(C)(O)C(=O)N1CCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 MJBQFBQRZWOFCX-OAQYLSRUSA-N 0.000 claims description 2
• REPSNCZQCJXPKQ-HXUWFJFHSA-N 1-[(3r)-3-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypyrrolidin-1-yl]-2-methoxyethanone Chemical compound C1N(C(=O)COC)CC[C@H]1OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 REPSNCZQCJXPKQ-HXUWFJFHSA-N 0.000 claims description 2
• AKHRXMOJLZKASL-LJQANCHMSA-N 1-[(3r)-3-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]piperidin-1-yl]-2-hydroxyethanone Chemical compound C1N(C(=O)CO)CCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 AKHRXMOJLZKASL-LJQANCHMSA-N 0.000 claims description 2
• FJXHIAXPPZRCTP-GOSISDBHSA-N 1-[(3r)-3-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound C1N(C(=O)CO)CC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 FJXHIAXPPZRCTP-GOSISDBHSA-N 0.000 claims description 2
• DLFWPOAZCQAEGU-GOSISDBHSA-N 1-[(3r)-3-[[4-[3-chloro-4-[(5-methyl-1,2-oxazol-3-yl)methoxy]anilino]quinazolin-5-yl]oxymethyl]piperidin-1-yl]-2-hydroxyethanone Chemical compound O1C(C)=CC(COC=2C(=CC(NC=3C4=C(OC[C@H]5CN(CCC5)C(=O)CO)C=CC=C4N=CN=3)=CC=2)Cl)=N1 DLFWPOAZCQAEGU-GOSISDBHSA-N 0.000 claims description 2
• YOVBTGYMPPDMHO-UHFFFAOYSA-N 1-[4-[[4-[3-chloro-4-(1,3-thiazol-4-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]piperidin-1-yl]-2-hydroxyethanone Chemical compound C1CN(C(=O)CO)CCC1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CSC=4)=CC=3)=C12 YOVBTGYMPPDMHO-UHFFFAOYSA-N 0.000 claims description 2
• 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 2
• WUWIAKWLBHOEOL-HXUWFJFHSA-N 2-hydroxy-1-[(2r)-2-[[4-[3-methyl-4-(1,3-thiazol-4-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]ethanone Chemical compound C=1C=C(OCC=2N=CSC=2)C(C)=CC=1NC(C=12)=NC=NC2=CC=CC=1OC[C@H]1CCCN1C(=O)CO WUWIAKWLBHOEOL-HXUWFJFHSA-N 0.000 claims description 2
• NNUJDACOPZZADK-OAQYLSRUSA-N [(2r)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-(1-hydroxycyclopropyl)methanone Chemical compound N1([C@H](CCC1)COC=1C2=C(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)N=CN=C2C=CC=1)C(=O)C1(O)CC1 NNUJDACOPZZADK-OAQYLSRUSA-N 0.000 claims description 2
• 125000004273 azetidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])C1([H])* 0.000 claims description 2
• 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 2
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 2
• 125000004569 thiomorpholin-2-yl group Chemical group N1CC(SCC1)* 0.000 claims description 2
• 125000001589 carboacyl group Chemical group 0.000 claims 10
• 150000002431 hydrogen Chemical group 0.000 claims 4
• NSANTJIAVWVLHA-WZONZLPQSA-N 1-[(2r)-2-[(1r)-1-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound O([C@H](C)[C@@H]1N(CCC1)C(=O)CO)C(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 NSANTJIAVWVLHA-WZONZLPQSA-N 0.000 claims 1
• NSANTJIAVWVLHA-FDDCHVKYSA-N 1-[(2r)-2-[(1s)-1-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxyethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound O([C@@H](C)[C@@H]1N(CCC1)C(=O)CO)C(C=12)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 NSANTJIAVWVLHA-FDDCHVKYSA-N 0.000 claims 1
• HWOCTTOWPSPEAG-GOSISDBHSA-N 1-[(2r)-2-[[4-(3-chloro-4-pyridin-3-yloxyanilino)quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OC=4C=NC=CC=4)=CC=3)=C12 HWOCTTOWPSPEAG-GOSISDBHSA-N 0.000 claims 1
• CAWSFQAXKDLSJL-LJQANCHMSA-N 1-[(2r)-2-[[4-[3-chloro-4-(1,3-thiazol-5-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound CN(C)CC(=O)N1CCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4SC=NC=4)=CC=3)=C12 CAWSFQAXKDLSJL-LJQANCHMSA-N 0.000 claims 1
• NTJPTMMEHGYIGG-OAQYLSRUSA-N 1-[(2r)-2-[[4-[3-chloro-4-(pyrazin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound CN(C)CC(=O)N1CCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=NC=4)=CC=3)=C12 NTJPTMMEHGYIGG-OAQYLSRUSA-N 0.000 claims 1
• XICURSSTRHKRMG-HXUWFJFHSA-N 1-[(2r)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]morpholin-4-yl]-2-hydroxyethanone Chemical compound C1N(C(=O)CO)CCO[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 XICURSSTRHKRMG-HXUWFJFHSA-N 0.000 claims 1
• HZIMDINNELHJCL-OAQYLSRUSA-N 1-[(2r)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]piperidin-1-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 HZIMDINNELHJCL-OAQYLSRUSA-N 0.000 claims 1
• VMXLBDNVEMGARR-JOCHJYFZSA-N 1-[(2r)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound CN(C)CC(=O)N1CCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 VMXLBDNVEMGARR-JOCHJYFZSA-N 0.000 claims 1
• OKMRYWPGNVTTAE-JOCHJYFZSA-N 1-[(2r)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-ethoxyethanone Chemical compound CCOCC(=O)N1CCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 OKMRYWPGNVTTAE-JOCHJYFZSA-N 0.000 claims 1
• FSHWIHXFSFIOAL-HXUWFJFHSA-N 1-[(2r)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 FSHWIHXFSFIOAL-HXUWFJFHSA-N 0.000 claims 1
• ZAESFTGXWHSEJW-XMMPIXPASA-N 1-[(2r)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-pyrrolidin-1-ylethanone Chemical compound C([C@@H]1COC=2C=CC=C3N=CN=C(C=23)NC=2C=C(C(=CC=2)OCC=2N=CC=CC=2)Cl)CCN1C(=O)CN1CCCC1 ZAESFTGXWHSEJW-XMMPIXPASA-N 0.000 claims 1
• WRSLJTGCVMSOMP-JOCHJYFZSA-N 1-[(2r)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-3-hydroxy-2,2-dimethylpropan-1-one Chemical compound OCC(C)(C)C(=O)N1CCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 WRSLJTGCVMSOMP-JOCHJYFZSA-N 0.000 claims 1
• ONDHFFYOEGIMFY-OAQYLSRUSA-N 1-[(2r)-2-[[4-[3-chloro-4-[(2-fluorophenyl)methoxy]anilino]quinazolin-5-yl]oxymethyl]piperidin-1-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4C(=CC=CC=4)F)=CC=3)=C12 ONDHFFYOEGIMFY-OAQYLSRUSA-N 0.000 claims 1
• CVELUWKBWXSBDT-JOCHJYFZSA-N 1-[(2r)-2-[[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-5-yl]oxymethyl]piperidin-1-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)=C12 CVELUWKBWXSBDT-JOCHJYFZSA-N 0.000 claims 1
• ZMALQXZDGDQVCT-LJQANCHMSA-N 1-[(2r)-2-[[4-[3-chloro-4-[(5-methyl-1,2-oxazol-3-yl)methoxy]anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound O1C(C)=CC(COC=2C(=CC(NC=3C4=C(OC[C@@H]5N(CCC5)C(=O)CO)C=CC=C4N=CN=3)=CC=2)Cl)=N1 ZMALQXZDGDQVCT-LJQANCHMSA-N 0.000 claims 1
• XEKHJZABXFJLNN-JOCHJYFZSA-N 1-[(2r)-2-[[4-[3-chloro-4-[(6-methylpyridin-2-yl)methoxy]anilino]quinazolin-5-yl]oxymethyl]piperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=CC=CC(COC=2C(=CC(NC=3C4=C(OC[C@@H]5N(CCCC5)C(=O)CO)C=CC=C4N=CN=3)=CC=2)Cl)=N1 XEKHJZABXFJLNN-JOCHJYFZSA-N 0.000 claims 1
• HWOCTTOWPSPEAG-SFHVURJKSA-N 1-[(2s)-2-[[4-(3-chloro-4-pyridin-3-yloxyanilino)quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OC=4C=NC=CC=4)=CC=3)=C12 HWOCTTOWPSPEAG-SFHVURJKSA-N 0.000 claims 1
• JFWUEJXMZHWXBE-NRFANRHFSA-N 1-[(2s)-2-[[4-[3-chloro-4-(1,3-thiazol-4-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]piperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound CN(C)CC(=O)N1CCCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CSC=4)=CC=3)=C12 JFWUEJXMZHWXBE-NRFANRHFSA-N 0.000 claims 1
• AESKUPWTDDMLAL-FQEVSTJZSA-N 1-[(2s)-2-[[4-[3-chloro-4-(1,3-thiazol-4-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound CN(C)CC(=O)N1CCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CSC=4)=CC=3)=C12 AESKUPWTDDMLAL-FQEVSTJZSA-N 0.000 claims 1
• COAXYQWUTMVSGV-SFHVURJKSA-N 1-[(2s)-2-[[4-[3-chloro-4-(1,3-thiazol-4-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CSC=4)=CC=3)=C12 COAXYQWUTMVSGV-SFHVURJKSA-N 0.000 claims 1
• NTJPTMMEHGYIGG-NRFANRHFSA-N 1-[(2s)-2-[[4-[3-chloro-4-(pyrazin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound CN(C)CC(=O)N1CCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=NC=4)=CC=3)=C12 NTJPTMMEHGYIGG-NRFANRHFSA-N 0.000 claims 1
• GEKBLFUVVXHHJO-IBGZPJMESA-N 1-[(2s)-2-[[4-[3-chloro-4-(pyrazin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=NC=4)=CC=3)=C12 GEKBLFUVVXHHJO-IBGZPJMESA-N 0.000 claims 1
• AJTYKPIFASHILD-NRFANRHFSA-N 1-[(2s)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]-4-methylpiperazin-1-yl]-2-hydroxyethanone Chemical compound C1N(C)CCN(C(=O)CO)[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 AJTYKPIFASHILD-NRFANRHFSA-N 0.000 claims 1
• SNLRBQMQODFNMA-QFIPXVFZSA-N 1-[(2s)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]morpholin-4-yl]-2-(dimethylamino)ethanone Chemical compound C1N(C(=O)CN(C)C)CCO[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 SNLRBQMQODFNMA-QFIPXVFZSA-N 0.000 claims 1
• MXIWNBPAJCAGDV-QHCPKHFHSA-N 1-[(2s)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]piperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound CN(C)CC(=O)N1CCCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 MXIWNBPAJCAGDV-QHCPKHFHSA-N 0.000 claims 1
• HZIMDINNELHJCL-NRFANRHFSA-N 1-[(2s)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]piperidin-1-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 HZIMDINNELHJCL-NRFANRHFSA-N 0.000 claims 1
• VMXLBDNVEMGARR-QFIPXVFZSA-N 1-[(2s)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound CN(C)CC(=O)N1CCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 VMXLBDNVEMGARR-QFIPXVFZSA-N 0.000 claims 1
• FSHWIHXFSFIOAL-FQEVSTJZSA-N 1-[(2s)-2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 FSHWIHXFSFIOAL-FQEVSTJZSA-N 0.000 claims 1
• ICATXXUQZRQGFA-QFIPXVFZSA-N 1-[(2s)-2-[[4-[3-chloro-4-[(2-fluorophenyl)methoxy]anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound CN(C)CC(=O)N1CCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4C(=CC=CC=4)F)=CC=3)=C12 ICATXXUQZRQGFA-QFIPXVFZSA-N 0.000 claims 1
• GUWNOERYOAKBRZ-FQEVSTJZSA-N 1-[(2s)-2-[[4-[3-chloro-4-[(2-fluorophenyl)methoxy]anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4C(=CC=CC=4)F)=CC=3)=C12 GUWNOERYOAKBRZ-FQEVSTJZSA-N 0.000 claims 1
• UXKYAIZQJBFWNB-QHCPKHFHSA-N 1-[(2s)-2-[[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound CN(C)CC(=O)N1CCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)=C12 UXKYAIZQJBFWNB-QHCPKHFHSA-N 0.000 claims 1
• XYKDYCHWPGJCGC-NRFANRHFSA-N 1-[(2s)-2-[[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)=C12 XYKDYCHWPGJCGC-NRFANRHFSA-N 0.000 claims 1
• TWLJJNZUTHNBDR-QHCPKHFHSA-N 1-[(2s)-2-[[4-[3-chloro-4-[(6-methylpyridin-2-yl)methoxy]anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound CN(C)CC(=O)N1CCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=C(C)C=CC=4)=CC=3)=C12 TWLJJNZUTHNBDR-QHCPKHFHSA-N 0.000 claims 1
• WCCQGLNOJNZQKU-NRFANRHFSA-N 1-[(2s)-2-[[4-[3-chloro-4-[(6-methylpyridin-2-yl)methoxy]anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound CC1=CC=CC(COC=2C(=CC(NC=3C4=C(OC[C@H]5N(CCC5)C(=O)CO)C=CC=C4N=CN=3)=CC=2)Cl)=N1 WCCQGLNOJNZQKU-NRFANRHFSA-N 0.000 claims 1
• HCAOXINOQOYUHQ-LJQANCHMSA-N 1-[(3r)-3-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypyrrolidin-1-yl]-2-hydroxyethanone Chemical compound C1N(C(=O)CO)CC[C@H]1OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 HCAOXINOQOYUHQ-LJQANCHMSA-N 0.000 claims 1
• MWAZWAHCSQYFGX-QGZVFWFLSA-N 1-[(3r)-3-[[4-[3-chloro-4-(1,3-thiazol-4-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]piperidin-1-yl]-2-hydroxyethanone Chemical compound C1N(C(=O)CO)CCC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CSC=4)=CC=3)=C12 MWAZWAHCSQYFGX-QGZVFWFLSA-N 0.000 claims 1
• BKUFSBCNMRDGHC-OAQYLSRUSA-N 1-[(3r)-3-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]-4-methylpiperazin-1-yl]-2-hydroxyethanone Chemical compound CN1CCN(C(=O)CO)C[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 BKUFSBCNMRDGHC-OAQYLSRUSA-N 0.000 claims 1
• VVMCEJKVUZSMIM-HXUWFJFHSA-N 1-[(3r)-3-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]morpholin-4-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCOC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 VVMCEJKVUZSMIM-HXUWFJFHSA-N 0.000 claims 1
• XRUPSFMUKJMDBV-HXUWFJFHSA-N 1-[(3r)-3-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound C1N(C(=O)CN(C)C)CC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 XRUPSFMUKJMDBV-HXUWFJFHSA-N 0.000 claims 1
• NJHOFVUAWDKRQT-LJQANCHMSA-N 1-[(3r)-3-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-methoxyethanone Chemical compound C1N(C(=O)COC)CC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 NJHOFVUAWDKRQT-LJQANCHMSA-N 0.000 claims 1
• SMHBUJOSMBKADR-NRFANRHFSA-N 1-[(3s)-3-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound C1N(C(=O)CN(C)C)CC[C@@H]1OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 SMHBUJOSMBKADR-NRFANRHFSA-N 0.000 claims 1
• HCAOXINOQOYUHQ-IBGZPJMESA-N 1-[(3s)-3-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxypyrrolidin-1-yl]-2-hydroxyethanone Chemical compound C1N(C(=O)CO)CC[C@@H]1OC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 HCAOXINOQOYUHQ-IBGZPJMESA-N 0.000 claims 1
• MWAZWAHCSQYFGX-KRWDZBQOSA-N 1-[(3s)-3-[[4-[3-chloro-4-(1,3-thiazol-4-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]piperidin-1-yl]-2-hydroxyethanone Chemical compound C1N(C(=O)CO)CCC[C@@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CSC=4)=CC=3)=C12 MWAZWAHCSQYFGX-KRWDZBQOSA-N 0.000 claims 1
• BKUFSBCNMRDGHC-NRFANRHFSA-N 1-[(3s)-3-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]-4-methylpiperazin-1-yl]-2-hydroxyethanone Chemical compound CN1CCN(C(=O)CO)C[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 BKUFSBCNMRDGHC-NRFANRHFSA-N 0.000 claims 1
• FTGJGRRUCPGLSO-QFIPXVFZSA-N 1-[(3s)-3-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]morpholin-4-yl]-2-(dimethylamino)ethanone Chemical compound CN(C)CC(=O)N1CCOC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 FTGJGRRUCPGLSO-QFIPXVFZSA-N 0.000 claims 1
• VVMCEJKVUZSMIM-FQEVSTJZSA-N 1-[(3s)-3-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-5-yl]oxymethyl]morpholin-4-yl]-2-hydroxyethanone Chemical compound OCC(=O)N1CCOC[C@H]1COC1=CC=CC2=NC=NC(NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)=C12 VVMCEJKVUZSMIM-FQEVSTJZSA-N 0.000 claims 1
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