TW200529851A - Quinazoline derivatives - Google Patents

Info

Publication number

TW200529851A

TW200529851A TW094103412A TW94103412A TW200529851A TW 200529851 A TW200529851 A TW 200529851A TW 094103412 A TW094103412 A TW 094103412A TW 94103412 A TW94103412 A TW 94103412A TW 200529851 A TW200529851 A TW 200529851A

Authority

TW

Taiwan

Prior art keywords

alkyl

group

formula

amino

hydrogen

Prior art date

2004-02-03

Links

• Espacenet
• Global Dossier
• Discuss

• 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title claims abstract description 18
• 238000000034 method Methods 0.000 claims abstract description 71
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 27
• 201000011510 cancer Diseases 0.000 claims abstract description 17
• 238000002360 preparation method Methods 0.000 claims abstract description 14
• 238000011282 treatment Methods 0.000 claims abstract description 11
• 239000003814 drug Substances 0.000 claims abstract description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
• -1 aminofluorenyl Chemical group 0.000 claims description 1047
• 125000000217 alkyl group Chemical group 0.000 claims description 856
• 125000001424 substituent group Chemical group 0.000 claims description 325
• 239000001257 hydrogen Substances 0.000 claims description 297
• 229910052739 hydrogen Inorganic materials 0.000 claims description 297
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 234
• 125000000623 heterocyclic group Chemical group 0.000 claims description 231
• 229910052757 nitrogen Inorganic materials 0.000 claims description 182
• 229910052799 carbon Inorganic materials 0.000 claims description 173
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 171
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 144
• 150000001875 compounds Chemical class 0.000 claims description 139
• 125000003545 alkoxy group Chemical group 0.000 claims description 133
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 118
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 97
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 82
• 150000001721 carbon Chemical group 0.000 claims description 78
• 125000001153 fluoro group Chemical group F* 0.000 claims description 78
• 238000006243 chemical reaction Methods 0.000 claims description 75
• 125000005843 halogen group Chemical group 0.000 claims description 71
• 125000003342 alkenyl group Chemical group 0.000 claims description 70
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 65
• 125000003282 alkyl amino group Chemical group 0.000 claims description 63
• 125000000304 alkynyl group Chemical group 0.000 claims description 61
• 150000001412 amines Chemical class 0.000 claims description 55
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 51
• 150000003839 salts Chemical class 0.000 claims description 50
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 47
• 125000004432 carbon atom Chemical group C* 0.000 claims description 47
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 45
• 125000000468 ketone group Chemical group 0.000 claims description 43
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 42
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 42
• 125000001072 heteroaryl group Chemical group 0.000 claims description 38
• 229910052717 sulfur Inorganic materials 0.000 claims description 35
• 125000003118 aryl group Chemical group 0.000 claims description 33
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 33
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 32
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 32
• 150000003246 quinazolines Chemical class 0.000 claims description 32
• 239000007789 gas Chemical group 0.000 claims description 31
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 30
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 28
• 229910052760 oxygen Inorganic materials 0.000 claims description 28
• 239000001301 oxygen Substances 0.000 claims description 28
• 125000000524 functional group Chemical group 0.000 claims description 27
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 26
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 25
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 25
• 125000002947 alkylene group Chemical group 0.000 claims description 24
• 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 24
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 23
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 23
• 125000004414 alkyl thio group Chemical group 0.000 claims description 22
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 22
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 22
• 125000006239 protecting group Chemical group 0.000 claims description 22
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 21
• 230000000694 effects Effects 0.000 claims description 21
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 21
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 19
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 19
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 18
• 125000001246 bromo group Chemical group Br* 0.000 claims description 17
• 229930194542 Keto Natural products 0.000 claims description 16
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 16
• 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 16
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 15
• XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical group NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 15
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 15
• YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 15
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 14
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 13
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 13
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
• 125000004429 atom Chemical group 0.000 claims description 12
• 238000005859 coupling reaction Methods 0.000 claims description 12
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 11
• 125000005133 alkynyloxy group Chemical group 0.000 claims description 11
• 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 10
• ROPLCSFPUPWHGJ-UHFFFAOYSA-N hydroxycyanamide Chemical compound ONC#N ROPLCSFPUPWHGJ-UHFFFAOYSA-N 0.000 claims description 10
• 230000005764 inhibitory process Effects 0.000 claims description 10
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 9
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 9
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 8
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
• 125000003504 2-oxazolinyl group Chemical class O1C(=NCC1)* 0.000 claims description 6
• 239000011737 fluorine Substances 0.000 claims description 6
• 229910052731 fluorine Inorganic materials 0.000 claims description 6
• 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• 239000000126 substance Substances 0.000 claims description 6
• 125000005323 thioketone group Chemical group 0.000 claims description 6
• UYRQABOKRLWBCR-UHFFFAOYSA-N 2,4-difluorobenzene-1,3-diamine Chemical compound NC1=CC=C(F)C(N)=C1F UYRQABOKRLWBCR-UHFFFAOYSA-N 0.000 claims description 5
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 5
• 230000008878 coupling Effects 0.000 claims description 5
• 238000010168 coupling process Methods 0.000 claims description 5
• 238000006467 substitution reaction Methods 0.000 claims description 5
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
• 241001465754 Metazoa Species 0.000 claims description 4
• 125000003368 amide group Chemical group 0.000 claims description 4
• LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 claims description 4
• 238000006268 reductive amination reaction Methods 0.000 claims description 4
• 241000282412 Homo Species 0.000 claims description 3
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
• 150000001924 cycloalkanes Chemical class 0.000 claims description 3
• AIMMVWOEOZMVMS-UHFFFAOYSA-N cyclopropanecarboxamide Chemical compound NC(=O)C1CC1 AIMMVWOEOZMVMS-UHFFFAOYSA-N 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• RNIXSZHNJLUJGC-UHFFFAOYSA-N hydroxy(nitro)cyanamide Chemical compound N#CN(O)[N+]([O-])=O RNIXSZHNJLUJGC-UHFFFAOYSA-N 0.000 claims description 3
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
• 125000003396 thiol group Chemical group [H]S* 0.000 claims description 3
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
• AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 claims description 2
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
• IVHRXFBIIZXYCI-UHFFFAOYSA-N 3-n-fluorobenzene-1,3-diamine Chemical compound NC1=CC=CC(NF)=C1 IVHRXFBIIZXYCI-UHFFFAOYSA-N 0.000 claims description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 2
• QRCJVAADFAROKA-UHFFFAOYSA-N amino 2-aminoacetate Chemical compound NCC(=O)ON QRCJVAADFAROKA-UHFFFAOYSA-N 0.000 claims description 2
• 230000001028 anti-proliverative effect Effects 0.000 claims description 2
• 229910052736 halogen Inorganic materials 0.000 claims description 2
• 150000002367 halogens Chemical class 0.000 claims description 2
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 5
• QNDFYLBDUWCFJO-UHFFFAOYSA-N 4-fluorobenzene-1,3-diamine Chemical compound NC1=CC=C(F)C(N)=C1 QNDFYLBDUWCFJO-UHFFFAOYSA-N 0.000 claims 1
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
• CHRMMMLUWHPZAH-UHFFFAOYSA-N 7-methoxyquinazoline Chemical compound C1=NC=NC2=CC(OC)=CC=C21 CHRMMMLUWHPZAH-UHFFFAOYSA-N 0.000 claims 1
• 101000589301 Homo sapiens Natural cytotoxicity triggering receptor 1 Proteins 0.000 claims 1
• BXDZOYLPNAIDOC-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide Chemical compound CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5C(=O)N(C6CCC(=O)NC6=O)C(=O)c45)CC3)s2)o1 BXDZOYLPNAIDOC-UHFFFAOYSA-N 0.000 claims 1
• 102100032870 Natural cytotoxicity triggering receptor 1 Human genes 0.000 claims 1
• 230000036983 biotransformation Effects 0.000 claims 1
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims 1
• 150000003857 carboxamides Chemical class 0.000 claims 1
• 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
• 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims 1
• GGHDAUPFEBTORZ-UHFFFAOYSA-N propane-1,1-diamine Chemical compound CCC(N)N GGHDAUPFEBTORZ-UHFFFAOYSA-N 0.000 claims 1
• 125000001567 quinoxalinyl group Chemical class N1=C(C=NC2=CC=CC=C12)* 0.000 claims 1
• 150000003342 selenium Chemical class 0.000 claims 1
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims 1
• 230000008569 process Effects 0.000 abstract description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
• 230000003463 hyperproliferative effect Effects 0.000 abstract 1
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 93
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 89
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 63
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 60
• 210000004027 cell Anatomy 0.000 description 46
• 229960005419 nitrogen Drugs 0.000 description 32
• 239000002585 base Substances 0.000 description 31
• 125000005842 heteroatom Chemical group 0.000 description 28
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 26
• 229920006395 saturated elastomer Polymers 0.000 description 25
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 24
• 125000002950 monocyclic group Chemical group 0.000 description 24
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 22
• 238000012360 testing method Methods 0.000 description 22
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 21
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 21
• 239000002953 phosphate buffered saline Substances 0.000 description 21
• 239000002253 acid Substances 0.000 description 20
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
• 125000003277 amino group Chemical group 0.000 description 18
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 18
• 239000011593 sulfur Substances 0.000 description 18
• 239000000243 solution Substances 0.000 description 16
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
• 125000001309 chloro group Chemical group Cl* 0.000 description 13
• 125000004122 cyclic group Chemical group 0.000 description 13
• 125000002757 morpholinyl group Chemical group 0.000 description 13
• 150000003254 radicals Chemical class 0.000 description 13
• 239000007858 starting material Substances 0.000 description 13
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical group C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 12
• 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 11
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 11
• 239000003638 chemical reducing agent Substances 0.000 description 11
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 10
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
• 108060006698 EGF receptor Proteins 0.000 description 10
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
• 239000012442 inert solvent Substances 0.000 description 10
• 230000002401 inhibitory effect Effects 0.000 description 10
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 10
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 10
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• 102000001301 EGF receptor Human genes 0.000 description 9
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 9
• 108091000080 Phosphotransferase Proteins 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 238000007796 conventional method Methods 0.000 description 9
• 235000019441 ethanol Nutrition 0.000 description 9
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 9
• 239000003960 organic solvent Substances 0.000 description 9
• 102000020233 phosphotransferase Human genes 0.000 description 9
• 108090000623 proteins and genes Proteins 0.000 description 9
• 230000009467 reduction Effects 0.000 description 9
• 238000006722 reduction reaction Methods 0.000 description 9
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
• 150000003973 alkyl amines Chemical class 0.000 description 8
• 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 description 8
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 8
• 102000004169 proteins and genes Human genes 0.000 description 8
• 229920002554 vinyl polymer Polymers 0.000 description 8
• 108700020796 Oncogene Proteins 0.000 description 7
• 125000002252 acyl group Chemical group 0.000 description 7
• 150000001409 amidines Chemical class 0.000 description 7
• 230000000903 blocking effect Effects 0.000 description 7
• 239000003054 catalyst Substances 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 7
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 7
• 239000003112 inhibitor Substances 0.000 description 7
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 7
• 230000026731 phosphorylation Effects 0.000 description 7
• 238000006366 phosphorylation reaction Methods 0.000 description 7
• 230000035755 proliferation Effects 0.000 description 7
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 7
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 7
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