RU2582610C2 - Производные хинолина и содержащие их ингибиторы melk - Google Patents
Производные хинолина и содержащие их ингибиторы melk Download PDFInfo
- Publication number
- RU2582610C2 RU2582610C2 RU2013108865/04A RU2013108865A RU2582610C2 RU 2582610 C2 RU2582610 C2 RU 2582610C2 RU 2013108865/04 A RU2013108865/04 A RU 2013108865/04A RU 2013108865 A RU2013108865 A RU 2013108865A RU 2582610 C2 RU2582610 C2 RU 2582610C2
- Authority
- RU
- Russia
- Prior art keywords
- compound
- quinolin
- cyclopropyl
- hydroxyphenyl
- chloro
- Prior art date
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- 229940124787 MELK inhibitor Drugs 0.000 title claims description 3
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title description 9
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 918
- -1 tiofenil Chemical group 0.000 claims abstract description 875
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 83
- 150000003839 salts Chemical class 0.000 claims abstract description 68
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 59
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 57
- 229910052736 halogen Chemical group 0.000 claims abstract description 52
- 150000002367 halogens Chemical group 0.000 claims abstract description 51
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract description 38
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 25
- 102100024299 Maternal embryonic leucine zipper kinase Human genes 0.000 claims abstract description 17
- 101710154611 Maternal embryonic leucine zipper kinase Proteins 0.000 claims abstract description 17
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 14
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 12
- 201000010099 disease Diseases 0.000 claims abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 11
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 230000002018 overexpression Effects 0.000 claims abstract description 7
- 125000000842 isoxazolyl group Chemical group 0.000 claims abstract description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 6
- 230000014509 gene expression Effects 0.000 claims abstract description 5
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 3
- 125000001424 substituent group Chemical group 0.000 claims description 242
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 198
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 141
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 108
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 94
- 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 78
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 42
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 34
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 32
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 24
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 21
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 claims description 17
- 239000004480 active ingredient Substances 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 13
- 125000003277 amino group Chemical group 0.000 claims description 12
- 125000004193 piperazinyl group Chemical group 0.000 claims description 12
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 11
- 201000011510 cancer Diseases 0.000 claims description 11
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 11
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 229910052805 deuterium Inorganic materials 0.000 claims description 9
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 9
- 238000011282 treatment Methods 0.000 claims description 9
- 206010006187 Breast cancer Diseases 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 8
- 230000000069 prophylactic effect Effects 0.000 claims description 8
- 230000001225 therapeutic effect Effects 0.000 claims description 8
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 7
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 7
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 5
- 125000005936 piperidyl group Chemical group 0.000 claims description 4
- UFJXIZSDRSWGHH-UHFFFAOYSA-N 1-[4-[[6-(3-aminopiperidin-1-yl)pyridin-3-yl]amino]-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-3-yl]ethanone Chemical compound CC(=O)C1=CN=C2C=CC(C=3C=C(Cl)C(O)=C(Cl)C=3)=CC2=C1NC(C=N1)=CC=C1N1CCCC(N)C1 UFJXIZSDRSWGHH-UHFFFAOYSA-N 0.000 claims description 3
- PEAZQTKOWOEYCZ-UKIBZPOASA-N C1C[C@@H](CN(C)C)CC[C@@H]1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 Chemical compound C1C[C@@H](CN(C)C)CC[C@@H]1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 PEAZQTKOWOEYCZ-UKIBZPOASA-N 0.000 claims description 3
- YFBRRBWSRJPOIT-RUCARUNLSA-N C1C[C@@H](CN(C)C)CC[C@@H]1NC1=C(C(C)=O)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 Chemical compound C1C[C@@H](CN(C)C)CC[C@@H]1NC1=C(C(C)=O)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 YFBRRBWSRJPOIT-RUCARUNLSA-N 0.000 claims description 3
- UYIMHVQEXCPIKN-RUCARUNLSA-N C1C[C@@H](CN(C)C)CC[C@@H]1NC1=C(C(C)=O)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(F)C=3)C=C12 Chemical compound C1C[C@@H](CN(C)C)CC[C@@H]1NC1=C(C(C)=O)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(F)C=3)C=C12 UYIMHVQEXCPIKN-RUCARUNLSA-N 0.000 claims description 3
- LCFDWDAPNUMZKM-UHFFFAOYSA-N [4-[[6-(3-aminopiperidin-1-yl)pyridin-3-yl]amino]-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-3-yl]-cyclopropylmethanone Chemical compound C1C(N)CCCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 LCFDWDAPNUMZKM-UHFFFAOYSA-N 0.000 claims description 3
- LCFDWDAPNUMZKM-LJQANCHMSA-N [4-[[6-[(3r)-3-aminopiperidin-1-yl]pyridin-3-yl]amino]-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-3-yl]-cyclopropylmethanone Chemical compound C1[C@H](N)CCCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 LCFDWDAPNUMZKM-LJQANCHMSA-N 0.000 claims description 3
- LCFDWDAPNUMZKM-IBGZPJMESA-N [4-[[6-[(3s)-3-aminopiperidin-1-yl]pyridin-3-yl]amino]-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-3-yl]-cyclopropylmethanone Chemical compound C1[C@@H](N)CCCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 LCFDWDAPNUMZKM-IBGZPJMESA-N 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- DKZYXHCYPUVGAF-UHFFFAOYSA-N 1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone Chemical compound CN(C)CC1CCC(CC1)Nc1c(cnc2ccc(nc12)-c1cc(Cl)c(O)c(Cl)c1)C(C)=O DKZYXHCYPUVGAF-UHFFFAOYSA-N 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 206010046766 uterine cancer Diseases 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims 7
- 125000005466 alkylenyl group Chemical group 0.000 claims 3
- 125000002757 morpholinyl group Chemical group 0.000 claims 3
- DLMHQUGZXIWVLQ-UHFFFAOYSA-N 1-[4-[[6-(3-aminopiperidin-1-yl)pyridin-3-yl]amino]-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-3-yl]propan-1-one Chemical compound CCC(=O)C1=CN=C2C=CC(C=3C=C(Cl)C(O)=C(Cl)C=3)=CC2=C1NC(C=N1)=CC=C1N1CCCC(N)C1 DLMHQUGZXIWVLQ-UHFFFAOYSA-N 0.000 claims 1
- 125000004431 deuterium atom Chemical group 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 4
- 239000003112 inhibitor Substances 0.000 abstract description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
- 125000000041 C6-C10 aryl group Chemical group 0.000 abstract 1
- 230000000259 anti-tumor effect Effects 0.000 abstract 1
- 239000000047 product Substances 0.000 description 246
- 239000007787 solid Substances 0.000 description 217
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 194
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 171
- 238000007429 general method Methods 0.000 description 161
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 150
- 239000011541 reaction mixture Substances 0.000 description 140
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 132
- 239000000243 solution Substances 0.000 description 104
- SKMHXQZCLNKWIE-UHFFFAOYSA-N (6-bromo-4-chloroquinolin-3-yl)-cyclopropylmethanone Chemical compound C1=NC2=CC=C(Br)C=C2C(Cl)=C1C(=O)C1CC1 SKMHXQZCLNKWIE-UHFFFAOYSA-N 0.000 description 72
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 65
- JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical compound O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 description 63
- 239000000203 mixture Substances 0.000 description 53
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 50
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 46
- 239000012044 organic layer Substances 0.000 description 45
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 43
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 39
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 39
- 238000005481 NMR spectroscopy Methods 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- ZVDDJPSHRNMSKV-UHFFFAOYSA-N acetaldehyde;hydrochloride Chemical compound Cl.CC=O ZVDDJPSHRNMSKV-UHFFFAOYSA-N 0.000 description 35
- 239000000725 suspension Substances 0.000 description 32
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 30
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 30
- 239000000741 silica gel Substances 0.000 description 30
- 229910002027 silica gel Inorganic materials 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- TZSUMDMNMCGUEP-UHFFFAOYSA-N 1-(6-bromo-4-chloroquinolin-3-yl)ethanone Chemical compound C1=CC(Br)=CC2=C(Cl)C(C(=O)C)=CN=C21 TZSUMDMNMCGUEP-UHFFFAOYSA-N 0.000 description 28
- 238000004440 column chromatography Methods 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 239000000460 chlorine Substances 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 20
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
- 239000000543 intermediate Substances 0.000 description 19
- 125000003107 substituted aryl group Chemical group 0.000 description 19
- 238000006722 reduction reaction Methods 0.000 description 18
- BXOBQDOEBJELFC-UHFFFAOYSA-N acetaldehyde;dihydrochloride Chemical compound Cl.Cl.CC=O BXOBQDOEBJELFC-UHFFFAOYSA-N 0.000 description 17
- 125000005236 alkanoylamino group Chemical group 0.000 description 17
- 238000000746 purification Methods 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- 239000010802 sludge Substances 0.000 description 16
- BAZVFQBTJPBRTJ-UHFFFAOYSA-N 2-chloro-5-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Cl)N=C1 BAZVFQBTJPBRTJ-UHFFFAOYSA-N 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- XTEOJPUYZWEXFI-UHFFFAOYSA-N butyl n-[3-[4-(imidazol-1-ylmethyl)phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate Chemical compound S1C(CC(C)C)=CC(C=2C=CC(CN3C=NC=C3)=CC=2)=C1S(=O)(=O)NC(=O)OCCCC XTEOJPUYZWEXFI-UHFFFAOYSA-N 0.000 description 13
- 238000003818 flash chromatography Methods 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- PCDHSSHKDZYLLI-UHFFFAOYSA-N butan-1-one Chemical compound CCC[C]=O PCDHSSHKDZYLLI-UHFFFAOYSA-N 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 12
- 125000004429 atom Chemical group 0.000 description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 10
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 10
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- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 description 9
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- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- OLOLNAQGBLYQRK-UHFFFAOYSA-N 1-(6-bromo-4-chloroquinolin-3-yl)propan-1-one Chemical compound C1=CC(Br)=CC2=C(Cl)C(C(=O)CC)=CN=C21 OLOLNAQGBLYQRK-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
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- 239000012458 free base Substances 0.000 description 8
- 125000004430 oxygen atom Chemical group O* 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 125000004434 sulfur atom Chemical group 0.000 description 8
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 150000001975 deuterium Chemical group 0.000 description 7
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 7
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 7
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 7
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- 206010028980 Neoplasm Diseases 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- XIUILXICGKBLQI-UHFFFAOYSA-N cyclopropanecarbaldehyde;hydrochloride Chemical compound Cl.O=CC1CC1 XIUILXICGKBLQI-UHFFFAOYSA-N 0.000 description 6
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- LPTMGLRSJZIYAE-UHFFFAOYSA-N 1-(6-bromo-4-chloroquinolin-3-yl)-2-methylpropan-1-one Chemical compound C1=CC(Br)=CC2=C(Cl)C(C(=O)C(C)C)=CN=C21 LPTMGLRSJZIYAE-UHFFFAOYSA-N 0.000 description 5
- RGCFVPSBPNJZAU-UHFFFAOYSA-N 1-(6-bromo-4-chloroquinolin-3-yl)butan-1-one Chemical compound C1=CC(Br)=CC2=C(Cl)C(C(=O)CCC)=CN=C21 RGCFVPSBPNJZAU-UHFFFAOYSA-N 0.000 description 5
- 125000005955 1H-indazolyl group Chemical group 0.000 description 5
- IAVSUBSFIDLDNW-UHFFFAOYSA-N 2,6-dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC(Cl)=C(O)C(Cl)=C1 IAVSUBSFIDLDNW-UHFFFAOYSA-N 0.000 description 5
- OFCBNMYNAHUDGE-UHFFFAOYSA-N 2-chloro-5-nitropyrimidine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1 OFCBNMYNAHUDGE-UHFFFAOYSA-N 0.000 description 5
- JDYWFZJIINVRGG-UHFFFAOYSA-N 4-[(dimethylamino)methyl]cyclohexan-1-amine Chemical compound CN(C)CC1CCC(N)CC1 JDYWFZJIINVRGG-UHFFFAOYSA-N 0.000 description 5
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 5
- DKLRMTJDWREBQA-UHFFFAOYSA-N 6-bromo-4-chloro-3-methylsulfonylquinoline Chemical compound C1=CC(Br)=CC2=C(Cl)C(S(=O)(=O)C)=CN=C21 DKLRMTJDWREBQA-UHFFFAOYSA-N 0.000 description 5
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 5
- 229930040373 Paraformaldehyde Natural products 0.000 description 5
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- VMFWIXUJCYEEQA-UHFFFAOYSA-N cyclopropyl-[4-[4-[1-(dimethylamino)ethyl]piperidin-1-yl]-6-(4-hydroxy-3-methoxyphenyl)quinolin-3-yl]methanone Chemical compound C1=C(O)C(OC)=CC(C=2C=C3C(N4CCC(CC4)C(C)N(C)C)=C(C(=O)C4CC4)C=NC3=CC=2)=C1 VMFWIXUJCYEEQA-UHFFFAOYSA-N 0.000 description 2
- MGSKUTGBRKLUAG-UHFFFAOYSA-N cyclopropyl-[4-[4-[1-(dimethylamino)ethyl]piperidin-1-yl]-7-fluoro-6-(4-hydroxy-3-methoxyphenyl)quinolin-3-yl]methanone Chemical compound C1=C(O)C(OC)=CC(C=2C(=CC3=NC=C(C(N4CCC(CC4)C(C)N(C)C)=C3C=2)C(=O)C2CC2)F)=C1 MGSKUTGBRKLUAG-UHFFFAOYSA-N 0.000 description 2
- KYJUNTYMASLDPG-UHFFFAOYSA-N cyclopropyl-[4-[[4-(diethylamino)cyclohexyl]amino]-6-(3,5-difluoro-4-hydroxyphenyl)quinolin-3-yl]methanone Chemical compound C1CC(N(CC)CC)CCC1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(F)C(O)=C(F)C=3)C=C12 KYJUNTYMASLDPG-UHFFFAOYSA-N 0.000 description 2
- PAYGDCKLJCPRJA-UHFFFAOYSA-N cyclopropyl-[4-[[4-(diethylamino)cyclohexyl]amino]-6-(4-hydroxy-3-methoxyphenyl)quinolin-3-yl]methanone Chemical compound C1CC(N(CC)CC)CCC1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(OC)C(O)=CC=3)C=C12 PAYGDCKLJCPRJA-UHFFFAOYSA-N 0.000 description 2
- TXOZSGUOHRWWLL-UHFFFAOYSA-N cyclopropyl-[4-[[4-(dimethylamino)cyclohexyl]amino]-6-(4-hydroxy-3-methoxyphenyl)quinolin-3-yl]methanone Chemical compound C1=C(O)C(OC)=CC(C=2C=C3C(NC4CCC(CC4)N(C)C)=C(C(=O)C4CC4)C=NC3=CC=2)=C1 TXOZSGUOHRWWLL-UHFFFAOYSA-N 0.000 description 2
- PVNZQGZWEUSTSQ-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-(4-piperidin-4-ylpiperidin-1-yl)quinolin-3-yl]methanone Chemical compound C1=C(Cl)C(O)=C(Cl)C=C1C1=CC=C(N=CC(C(=O)C2CC2)=C2N3CCC(CC3)C3CCNCC3)C2=C1 PVNZQGZWEUSTSQ-UHFFFAOYSA-N 0.000 description 2
- JEIDWBHFLNLBQE-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-(6-piperazin-1-ylpyridin-3-yl)quinolin-3-yl]methanone Chemical compound C1=C(Cl)C(O)=C(Cl)C=C1C1=CC=C(N=CC(C(=O)C2CC2)=C2C=3C=NC(=CC=3)N3CCNCC3)C2=C1 JEIDWBHFLNLBQE-UHFFFAOYSA-N 0.000 description 2
- XEMMNHUESNPJSG-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-(piperidin-4-ylamino)quinolin-3-yl]methanone Chemical compound C1=C(Cl)C(O)=C(Cl)C=C1C1=CC=C(N=CC(C(=O)C2CC2)=C2NC3CCNCC3)C2=C1 XEMMNHUESNPJSG-UHFFFAOYSA-N 0.000 description 2
- LYSQKZHZGMTPES-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-(piperidin-4-ylmethylamino)quinolin-3-yl]methanone Chemical compound C1=C(Cl)C(O)=C(Cl)C=C1C1=CC=C(N=CC(C(=O)C2CC2)=C2NCC3CCNCC3)C2=C1 LYSQKZHZGMTPES-UHFFFAOYSA-N 0.000 description 2
- VYOKTFDTHVLMML-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[(1-methylpiperidin-4-yl)amino]quinolin-3-yl]methanone Chemical compound C1CN(C)CCC1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 VYOKTFDTHVLMML-UHFFFAOYSA-N 0.000 description 2
- QMCHGINPCOHGAR-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[(1-piperidin-4-ylpyrazol-4-yl)amino]quinolin-3-yl]methanone Chemical compound C1=C(Cl)C(O)=C(Cl)C=C1C1=CC=C(N=CC(C(=O)C2CC2)=C2NC3=CN(N=C3)C3CCNCC3)C2=C1 QMCHGINPCOHGAR-UHFFFAOYSA-N 0.000 description 2
- IFXWBYJQKWQIIZ-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[(2-piperazin-1-ylpyrimidin-5-yl)amino]quinolin-3-yl]methanone Chemical compound C1=C(Cl)C(O)=C(Cl)C=C1C1=CC=C(N=CC(C(=O)C2CC2)=C2NC=3C=NC(=NC=3)N3CCNCC3)C2=C1 IFXWBYJQKWQIIZ-UHFFFAOYSA-N 0.000 description 2
- QPUTZCFAHFNHHW-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[(5-piperazin-1-ylpyridin-2-yl)amino]quinolin-3-yl]methanone Chemical compound C1=C(Cl)C(O)=C(Cl)C=C1C1=CC=C(N=CC(C(=O)C2CC2)=C2NC=3N=CC(=CC=3)N3CCNCC3)C2=C1 QPUTZCFAHFNHHW-UHFFFAOYSA-N 0.000 description 2
- TZBDQYWTTRFDED-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]quinolin-3-yl]methanone Chemical compound C1CN(C)CCN1C1=NC=C(C=2C3=CC(=CC=C3N=CC=2C(=O)C2CC2)C=2C=C(Cl)C(O)=C(Cl)C=2)C=N1 TZBDQYWTTRFDED-UHFFFAOYSA-N 0.000 description 2
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- CWZLFIGUABLARS-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[3-[(dimethylamino)methyl]anilino]quinolin-3-yl]methanone Chemical compound CN(C)CC1=CC=CC(NC=2C3=CC(=CC=C3N=CC=2C(=O)C2CC2)C=2C=C(Cl)C(O)=C(Cl)C=2)=C1 CWZLFIGUABLARS-UHFFFAOYSA-N 0.000 description 2
- KTUQWKGNYHMODK-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[3-[2-(4-methylpiperazin-1-yl)ethyl]anilino]quinolin-3-yl]methanone Chemical compound C1CN(C)CCN1CCC1=CC=CC(NC=2C3=CC(=CC=C3N=CC=2C(=O)C2CC2)C=2C=C(Cl)C(O)=C(Cl)C=2)=C1 KTUQWKGNYHMODK-UHFFFAOYSA-N 0.000 description 2
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- KBTDVRBJHQZXQD-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[4-(2-pyrrolidin-1-ylethyl)piperidin-1-yl]quinolin-3-yl]methanone Chemical compound C1=C(Cl)C(O)=C(Cl)C=C1C1=CC=C(N=CC(C(=O)C2CC2)=C2N3CCC(CCN4CCCC4)CC3)C2=C1 KBTDVRBJHQZXQD-UHFFFAOYSA-N 0.000 description 2
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- QZTSNGXWMSDEFN-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[4-[(dimethylamino)methyl]phenyl]quinolin-3-yl]methanone Chemical compound C1=CC(CN(C)C)=CC=C1C1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 QZTSNGXWMSDEFN-UHFFFAOYSA-N 0.000 description 2
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- CPYJCYCPESTRIX-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]amino]quinolin-3-yl]methanone Chemical compound C1CN(C)CCC1N1N=CC(NC=2C3=CC(=CC=C3N=CC=2C(=O)C2CC2)C=2C=C(Cl)C(O)=C(Cl)C=2)=C1 CPYJCYCPESTRIX-UHFFFAOYSA-N 0.000 description 2
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- YSVCSIFSQNVBBW-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[6-(2-hydroxyethylamino)pyridin-3-yl]amino]quinolin-3-yl]methanone Chemical compound C1=NC(NCCO)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 YSVCSIFSQNVBBW-UHFFFAOYSA-N 0.000 description 2
- NMDPMXWYBXKMAS-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[6-(3-hydroxypyrrolidin-1-yl)pyridin-3-yl]amino]quinolin-3-yl]methanone Chemical compound C1C(O)CCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 NMDPMXWYBXKMAS-UHFFFAOYSA-N 0.000 description 2
- XHQKBFOEOOBPPM-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino]-7-(trifluoromethyl)quinolin-3-yl]methanone Chemical compound C1CN(C)CCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC(C(F)(F)F)=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 XHQKBFOEOOBPPM-UHFFFAOYSA-N 0.000 description 2
- DWGBVIYEJLUOLC-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino]quinolin-3-yl]methanone Chemical compound C1CN(C)CCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 DWGBVIYEJLUOLC-UHFFFAOYSA-N 0.000 description 2
- LZMXVRGKSWCVKE-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[6-(piperidin-3-ylamino)pyridin-3-yl]amino]quinolin-3-yl]methanone Chemical compound C1=C(Cl)C(O)=C(Cl)C=C1C1=CC=C(N=CC(C(=O)C2CC2)=C2NC=3C=NC(NC4CNCCC4)=CC=3)C2=C1 LZMXVRGKSWCVKE-UHFFFAOYSA-N 0.000 description 2
- NPAAIXDDUBKEGW-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[6-(pyrrolidin-1-ylmethyl)pyridin-3-yl]amino]quinolin-3-yl]methanone Chemical compound C1=C(Cl)C(O)=C(Cl)C=C1C1=CC=C(N=CC(C(=O)C2CC2)=C2NC=3C=NC(CN4CCCC4)=CC=3)C2=C1 NPAAIXDDUBKEGW-UHFFFAOYSA-N 0.000 description 2
- DCWWKYJTBPXVQB-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[6-(pyrrolidin-3-ylamino)pyridin-3-yl]amino]quinolin-3-yl]methanone Chemical compound C1=C(Cl)C(O)=C(Cl)C=C1C1=CC=C(N=CC(C(=O)C2CC2)=C2NC=3C=NC(NC4CNCC4)=CC=3)C2=C1 DCWWKYJTBPXVQB-UHFFFAOYSA-N 0.000 description 2
- FTWBSPZGKJDTOW-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[6-[(4-methylpiperazin-1-yl)methyl]pyridin-3-yl]amino]quinolin-3-yl]methanone Chemical compound C1CN(C)CCN1CC(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 FTWBSPZGKJDTOW-UHFFFAOYSA-N 0.000 description 2
- CCAUXROLYAGTSK-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[6-[(dimethylamino)methyl]pyridin-3-yl]amino]quinolin-3-yl]methanone Chemical compound C1=NC(CN(C)C)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 CCAUXROLYAGTSK-UHFFFAOYSA-N 0.000 description 2
- KTWGYMJCZMKYCM-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[6-[2-(dimethylamino)ethoxy]pyridin-3-yl]amino]quinolin-3-yl]methanone Chemical compound C1=NC(OCCN(C)C)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 KTWGYMJCZMKYCM-UHFFFAOYSA-N 0.000 description 2
- ILTPXPCWECMALW-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[6-[2-(dimethylamino)ethylamino]pyridin-3-yl]amino]quinolin-3-yl]methanone Chemical compound C1=NC(NCCN(C)C)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 ILTPXPCWECMALW-UHFFFAOYSA-N 0.000 description 2
- UPICZACLFIHFBC-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[6-[2-(dimethylamino)ethylamino]pyridin-3-yl]amino]quinolin-3-yl]methanone;hydrochloride Chemical compound Cl.C1=NC(NCCN(C)C)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 UPICZACLFIHFBC-UHFFFAOYSA-N 0.000 description 2
- PMJOHZYXFPYBDN-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[6-[3-(dimethylamino)pyrrolidin-1-yl]pyridin-3-yl]amino]quinolin-3-yl]methanone Chemical compound C1C(N(C)C)CCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 PMJOHZYXFPYBDN-UHFFFAOYSA-N 0.000 description 2
- QRSQORZQFCDLOK-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[6-[3-(methylamino)pyrrolidin-1-yl]pyridin-3-yl]amino]quinolin-3-yl]methanone;trihydrochloride Chemical compound Cl.Cl.Cl.C1C(NC)CCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(Cl)C(O)=C(Cl)C=3)C=C12 QRSQORZQFCDLOK-UHFFFAOYSA-N 0.000 description 2
- UEKHQJCIOOAHBZ-UHFFFAOYSA-N cyclopropyl-[6-(3,5-dichloro-4-hydroxyphenyl)-7-fluoro-4-[(6-piperazin-1-ylpyridin-3-yl)amino]quinolin-3-yl]methanone Chemical compound C1=C(Cl)C(O)=C(Cl)C=C1C(C(=CC1=NC=C2C(=O)C3CC3)F)=CC1=C2NC1=CC=C(N2CCNCC2)N=C1 UEKHQJCIOOAHBZ-UHFFFAOYSA-N 0.000 description 2
- XRYHMCLHJGBCLV-UHFFFAOYSA-N cyclopropyl-[6-(3,5-difluoro-4-hydroxyphenyl)-4-(2-piperazin-1-ylethylamino)quinolin-3-yl]methanone Chemical compound C1=C(F)C(O)=C(F)C=C1C1=CC=C(N=CC(C(=O)C2CC2)=C2NCCN3CCNCC3)C2=C1 XRYHMCLHJGBCLV-UHFFFAOYSA-N 0.000 description 2
- HWZOXXKKUXXQRH-UHFFFAOYSA-N cyclopropyl-[6-(3,5-difluoro-4-hydroxyphenyl)-4-(piperidin-4-ylmethylamino)quinolin-3-yl]methanone Chemical compound C1=C(F)C(O)=C(F)C=C1C1=CC=C(N=CC(C(=O)C2CC2)=C2NCC3CCNCC3)C2=C1 HWZOXXKKUXXQRH-UHFFFAOYSA-N 0.000 description 2
- SXSPEFGXNXNDIS-UHFFFAOYSA-N cyclopropyl-[6-(3,5-difluoro-4-hydroxyphenyl)-4-[(1-methylpiperidin-4-yl)amino]quinolin-3-yl]methanone Chemical compound C1CN(C)CCC1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(F)C(O)=C(F)C=3)C=C12 SXSPEFGXNXNDIS-UHFFFAOYSA-N 0.000 description 2
- ZGRMDLLIRLILHM-UHFFFAOYSA-N cyclopropyl-[6-(3,5-difluoro-4-hydroxyphenyl)-4-[(1-methylpiperidin-4-yl)methylamino]quinolin-3-yl]methanone Chemical compound C1CN(C)CCC1CNC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(F)C(O)=C(F)C=3)C=C12 ZGRMDLLIRLILHM-UHFFFAOYSA-N 0.000 description 2
- RDIYIXMCUAEOLW-UHFFFAOYSA-N cyclopropyl-[6-(3,5-difluoro-4-hydroxyphenyl)-4-[3-[2-(dimethylamino)ethyl]anilino]quinolin-3-yl]methanone Chemical compound CN(C)CCC1=CC=CC(NC=2C3=CC(=CC=C3N=CC=2C(=O)C2CC2)C=2C=C(F)C(O)=C(F)C=2)=C1 RDIYIXMCUAEOLW-UHFFFAOYSA-N 0.000 description 2
- RSMFQMYLVTWHOU-UHFFFAOYSA-N cyclopropyl-[6-(3,5-difluoro-4-hydroxyphenyl)-4-[4-[1-(dimethylamino)ethyl]piperidin-1-yl]quinolin-3-yl]methanone Chemical compound C1CC(C(C)N(C)C)CCN1C1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(F)C(O)=C(F)C=3)C=C12 RSMFQMYLVTWHOU-UHFFFAOYSA-N 0.000 description 2
- UXRGWKIILXKLLI-UHFFFAOYSA-N cyclopropyl-[6-(3,5-difluoro-4-hydroxyphenyl)-4-[[6-(4-methylpiperazin-1-yl)pyridin-3-yl]amino]quinolin-3-yl]methanone Chemical compound C1CN(C)CCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=C(F)C(O)=C(F)C=3)C=C12 UXRGWKIILXKLLI-UHFFFAOYSA-N 0.000 description 2
- QRKKZHNOBHOINS-UHFFFAOYSA-N cyclopropyl-[6-(3,5-difluoro-4-hydroxyphenyl)-4-[[6-(pyrrolidin-1-ylmethyl)pyridin-3-yl]amino]quinolin-3-yl]methanone Chemical compound C1=C(F)C(O)=C(F)C=C1C1=CC=C(N=CC(C(=O)C2CC2)=C2NC=3C=NC(CN4CCCC4)=CC=3)C2=C1 QRKKZHNOBHOINS-UHFFFAOYSA-N 0.000 description 2
- RIECTTVLASNINJ-UHFFFAOYSA-N cyclopropyl-[6-(3-fluoro-4-hydroxy-5-methoxyphenyl)-4-[4-(pyrrolidin-1-ylmethyl)piperidin-1-yl]quinolin-3-yl]methanone Chemical compound FC1=C(O)C(OC)=CC(C=2C=C3C(N4CCC(CN5CCCC5)CC4)=C(C(=O)C4CC4)C=NC3=CC=2)=C1 RIECTTVLASNINJ-UHFFFAOYSA-N 0.000 description 2
- GAAGHMPWUDEJJW-UHFFFAOYSA-N cyclopropyl-[6-(4-hydroxy-3-methoxyphenyl)-4-(2-piperazin-1-ylethylamino)quinolin-3-yl]methanone Chemical compound C1=C(O)C(OC)=CC(C=2C=C3C(NCCN4CCNCC4)=C(C(=O)C4CC4)C=NC3=CC=2)=C1 GAAGHMPWUDEJJW-UHFFFAOYSA-N 0.000 description 2
- KIUVKHDUJLQWII-UHFFFAOYSA-N cyclopropyl-[6-(4-hydroxy-3-methoxyphenyl)-4-(piperidin-4-ylmethylamino)quinolin-3-yl]methanone Chemical compound C1=C(O)C(OC)=CC(C=2C=C3C(NCC4CCNCC4)=C(C(=O)C4CC4)C=NC3=CC=2)=C1 KIUVKHDUJLQWII-UHFFFAOYSA-N 0.000 description 2
- MMZBTRXUNVJXFU-UHFFFAOYSA-N cyclopropyl-[6-(4-hydroxy-3-methoxyphenyl)-4-[(1-methylpiperidin-4-yl)amino]quinolin-3-yl]methanone Chemical compound C1=C(O)C(OC)=CC(C=2C=C3C(NC4CCN(C)CC4)=C(C(=O)C4CC4)C=NC3=CC=2)=C1 MMZBTRXUNVJXFU-UHFFFAOYSA-N 0.000 description 2
- OASMUNXRYFKFHA-UHFFFAOYSA-N cyclopropyl-[6-(4-hydroxy-3-methoxyphenyl)-4-[(1-methylpiperidin-4-yl)methylamino]quinolin-3-yl]methanone Chemical compound C1=C(O)C(OC)=CC(C=2C=C3C(NCC4CCN(C)CC4)=C(C(=O)C4CC4)C=NC3=CC=2)=C1 OASMUNXRYFKFHA-UHFFFAOYSA-N 0.000 description 2
- JZDXZEVGELZBHL-UHFFFAOYSA-N cyclopropyl-[6-(4-hydroxy-3-methoxyphenyl)-4-[4-(pyrrolidin-1-ylmethyl)anilino]quinolin-3-yl]methanone Chemical compound C1=C(O)C(OC)=CC(C=2C=C3C(NC=4C=CC(CN5CCCC5)=CC=4)=C(C(=O)C4CC4)C=NC3=CC=2)=C1 JZDXZEVGELZBHL-UHFFFAOYSA-N 0.000 description 2
- CUEGGHUYFDTDMC-UHFFFAOYSA-N cyclopropyl-[6-(4-hydroxy-3-methoxyphenyl)-4-[4-[(4-methylpiperazin-1-yl)methyl]anilino]quinolin-3-yl]methanone Chemical compound C1=C(O)C(OC)=CC(C=2C=C3C(NC=4C=CC(CN5CCN(C)CC5)=CC=4)=C(C(=O)C4CC4)C=NC3=CC=2)=C1 CUEGGHUYFDTDMC-UHFFFAOYSA-N 0.000 description 2
- BPULTYBRXZNYHE-UHFFFAOYSA-N cyclopropyl-[6-[4-(difluoromethoxy)phenyl]-4-[4-[(dimethylamino)methyl]piperidin-1-yl]quinolin-3-yl]methanone Chemical compound C1CC(CN(C)C)CCN1C1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=CC(OC(F)F)=CC=3)C=C12 BPULTYBRXZNYHE-UHFFFAOYSA-N 0.000 description 2
- ZWLAHKTWIDOUMR-UHFFFAOYSA-N cyclopropyl-[6-[4-(difluoromethyl)phenyl]-4-[4-[(dimethylamino)methyl]piperidin-1-yl]quinolin-3-yl]methanone Chemical compound C1CC(CN(C)C)CCN1C1=C(C(=O)C2CC2)C=NC2=CC=C(C=3C=CC(=CC=3)C(F)F)C=C12 ZWLAHKTWIDOUMR-UHFFFAOYSA-N 0.000 description 2
- IBRGZAOFCIFXEB-UHFFFAOYSA-N cyclopropyl-[6-[4-hydroxy-3-(trifluoromethoxy)phenyl]-4-[4-(pyrrolidin-1-ylmethyl)piperidin-1-yl]quinolin-3-yl]methanone Chemical compound C1=C(OC(F)(F)F)C(O)=CC=C1C1=CC=C(N=CC(C(=O)C2CC2)=C2N3CCC(CN4CCCC4)CC3)C2=C1 IBRGZAOFCIFXEB-UHFFFAOYSA-N 0.000 description 2
- 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 201000004101 esophageal cancer Diseases 0.000 description 2
- MPUNXFHKIKBIFQ-UHFFFAOYSA-N ethyl 2-[(4-bromoanilino)methylidene]-3-oxohexanoate Chemical compound CCCC(=O)C(C(=O)OCC)=CNC1=CC=C(Br)C=C1 MPUNXFHKIKBIFQ-UHFFFAOYSA-N 0.000 description 2
- ODDCAKMSAKBYGM-UHFFFAOYSA-N ethyl 2-[(4-bromoanilino)methylidene]-3-oxopentanoate Chemical compound CCOC(=O)C(C(=O)CC)=CNC1=CC=C(Br)C=C1 ODDCAKMSAKBYGM-UHFFFAOYSA-N 0.000 description 2
- CACSRMCFCHYYIW-UHFFFAOYSA-N ethyl 2-[(4-bromoanilino)methylidene]-5-methyl-3-oxohexanoate Chemical compound CCOC(=O)C(C(=O)CC(C)C)=CNC1=CC=C(Br)C=C1 CACSRMCFCHYYIW-UHFFFAOYSA-N 0.000 description 2
- LFRYXOUTBZLMLJ-UHFFFAOYSA-N ethyl 3-(4-bromoanilino)-2-methylsulfonylprop-2-enoate Chemical compound CCOC(=O)C(S(C)(=O)=O)=CNC1=CC=C(Br)C=C1 LFRYXOUTBZLMLJ-UHFFFAOYSA-N 0.000 description 2
- HMSAMZHUOGHTLJ-UHFFFAOYSA-N ethyl 4-(3-aminopropylamino)-6-(4-hydroxyphenyl)quinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=C(O)C=C1 HMSAMZHUOGHTLJ-UHFFFAOYSA-N 0.000 description 2
- DGKQFOPGTRNCLU-UHFFFAOYSA-N ethyl 4-(3-aminopropylamino)-6-bromoquinoline-3-carboxylate Chemical compound C1=CC(Br)=CC2=C(NCCCN)C(C(=O)OCC)=CN=C21 DGKQFOPGTRNCLU-UHFFFAOYSA-N 0.000 description 2
- WGYJLPUCRUIFGM-UHFFFAOYSA-N ethyl 4-(4-acetamidoanilino)-6-bromoquinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1NC1=CC=C(NC(C)=O)C=C1 WGYJLPUCRUIFGM-UHFFFAOYSA-N 0.000 description 2
- MEJGQCALSGLJAG-UHFFFAOYSA-N ethyl 4-(4-acetamidoanilino)-6-chloroquinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Cl)=CC2=C1NC1=CC=C(NC(C)=O)C=C1 MEJGQCALSGLJAG-UHFFFAOYSA-N 0.000 description 2
- RILSCBLGXDGPRT-UHFFFAOYSA-N ethyl 4-(4-acetamidoanilino)-6-fluoroquinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(F)=CC2=C1NC1=CC=C(NC(C)=O)C=C1 RILSCBLGXDGPRT-UHFFFAOYSA-N 0.000 description 2
- ZVPJVAQYTADQPE-UHFFFAOYSA-N ethyl 4-(4-acetamidoanilino)-6-methoxyquinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(OC)=CC2=C1NC1=CC=C(NC(C)=O)C=C1 ZVPJVAQYTADQPE-UHFFFAOYSA-N 0.000 description 2
- BEGAILJMMRYWGX-UHFFFAOYSA-N ethyl 4-(4-acetamidoanilino)-6-methylquinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(C)=CC2=C1NC1=CC=C(NC(C)=O)C=C1 BEGAILJMMRYWGX-UHFFFAOYSA-N 0.000 description 2
- NAZMBTHXECFPGP-UHFFFAOYSA-N ethyl 4-(4-aminoanilino)-6-chloroquinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Cl)=CC2=C1NC1=CC=C(N)C=C1 NAZMBTHXECFPGP-UHFFFAOYSA-N 0.000 description 2
- YHIVYLGMTYHCNM-UHFFFAOYSA-N ethyl 4-(4-aminopiperidin-1-yl)-6-bromoquinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1N1CCC(N)CC1 YHIVYLGMTYHCNM-UHFFFAOYSA-N 0.000 description 2
- FVZAKASDTZXXOR-UHFFFAOYSA-N ethyl 4-[(1-ethylpyrrolidin-2-yl)methylamino]-6-(4-hydroxyphenyl)quinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(C=3C=CC(O)=CC=3)=CC2=C1NCC1CCCN1CC FVZAKASDTZXXOR-UHFFFAOYSA-N 0.000 description 2
- RDNGFALQJUXYHK-UHFFFAOYSA-N ethyl 4-[(3-acetamido-2-methylpropyl)amino]-6-bromoquinoline-3-carboxylate Chemical compound C1=CC(Br)=CC2=C(NCC(C)CNC(C)=O)C(C(=O)OCC)=CN=C21 RDNGFALQJUXYHK-UHFFFAOYSA-N 0.000 description 2
- GDNVPLHZYNZCSG-UHFFFAOYSA-N ethyl 4-[(3-aminocyclohexyl)amino]-6-bromoquinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1NC1CCCC(N)C1 GDNVPLHZYNZCSG-UHFFFAOYSA-N 0.000 description 2
- UGJSBMCZYFBUKW-UHFFFAOYSA-N ethyl 4-[(4-aminophenyl)methylamino]-6-bromoquinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1NCC1=CC=C(N)C=C1 UGJSBMCZYFBUKW-UHFFFAOYSA-N 0.000 description 2
- BXZFCYVUMXOKIH-UHFFFAOYSA-N ethyl 4-[2-(diethylamino)ethylamino]-6-(4-hydroxyphenyl)quinoline-3-carboxylate Chemical compound C=1C2=C(NCCN(CC)CC)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=C(O)C=C1 BXZFCYVUMXOKIH-UHFFFAOYSA-N 0.000 description 2
- JKZUYQWQNPXREP-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-(1h-indazol-5-yl)quinoline-3-carboxylate Chemical compound C1=C2NN=CC2=CC(C=2C=CC3=NC=C(C(=C3C=2)NCCCN(C)C)C(=O)OCC)=C1 JKZUYQWQNPXREP-UHFFFAOYSA-N 0.000 description 2
- XXEYQBZCAWCONR-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-(1h-pyrazol-4-yl)quinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C=1C=NNC=1 XXEYQBZCAWCONR-UHFFFAOYSA-N 0.000 description 2
- UOPGUFUVRUJYBU-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-(4-hydroxy-3-methoxyphenyl)quinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=C(O)C(OC)=C1 UOPGUFUVRUJYBU-UHFFFAOYSA-N 0.000 description 2
- YGSZDFHEWKHNAF-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-(4-hydroxyphenyl)quinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=C(O)C=C1 YGSZDFHEWKHNAF-UHFFFAOYSA-N 0.000 description 2
- LGWOQYCBBXBJSH-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-(4-methoxyphenyl)quinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=C(OC)C=C1 LGWOQYCBBXBJSH-UHFFFAOYSA-N 0.000 description 2
- USAZUNDHJPBZQQ-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-(4-sulfamoylphenyl)quinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=C(S(N)(=O)=O)C=C1 USAZUNDHJPBZQQ-UHFFFAOYSA-N 0.000 description 2
- UVBUFSSTEPTUBK-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-(trifluoromethoxy)quinoline-3-carboxylate Chemical compound C1=CC(OC(F)(F)F)=CC2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C21 UVBUFSSTEPTUBK-UHFFFAOYSA-N 0.000 description 2
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- FACMFBUGYFXBMJ-UHFFFAOYSA-N tert-butyl n-[1-[5-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]pyridin-2-yl]pyrrolidin-3-yl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 FACMFBUGYFXBMJ-UHFFFAOYSA-N 0.000 description 1
- OYSIVUNOMKSOCC-UHFFFAOYSA-N tert-butyl n-[1-[5-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]pyrimidin-2-yl]piperidin-3-yl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CCCN1C(N=C1)=NC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 OYSIVUNOMKSOCC-UHFFFAOYSA-N 0.000 description 1
- VRHQIMMGKZZFIK-UHFFFAOYSA-N tert-butyl n-[1-[5-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]pyrimidin-2-yl]piperidin-4-yl]carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCN1C(N=C1)=NC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 VRHQIMMGKZZFIK-UHFFFAOYSA-N 0.000 description 1
- DBRGYYIAWMCHLU-UHFFFAOYSA-N tert-butyl n-[1-[5-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]pyrimidin-2-yl]pyrrolidin-3-yl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CCN1C(N=C1)=NC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 DBRGYYIAWMCHLU-UHFFFAOYSA-N 0.000 description 1
- ZVPIEEDMVDQFKY-UHFFFAOYSA-N tert-butyl n-[2-[4-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]phenyl]propan-2-yl]carbamate Chemical compound C1=CC(C(C)(C)NC(=O)OC(C)(C)C)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 ZVPIEEDMVDQFKY-UHFFFAOYSA-N 0.000 description 1
- YKGOJBCBAUQJFY-UHFFFAOYSA-N tert-butyl n-[2-[5-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]pyridin-2-yl]oxyethyl]carbamate Chemical compound C1=NC(OCCNC(=O)OC(C)(C)C)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 YKGOJBCBAUQJFY-UHFFFAOYSA-N 0.000 description 1
- SSZKBGFWNFAXNC-UHFFFAOYSA-N tert-butyl n-[4-(2-aminoethyl)cyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(CCN)CC1 SSZKBGFWNFAXNC-UHFFFAOYSA-N 0.000 description 1
- NVQFOBONHIXDOC-UHFFFAOYSA-N tert-butyl n-[4-(aminomethyl)cyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(CN)CC1 NVQFOBONHIXDOC-UHFFFAOYSA-N 0.000 description 1
- SGNKPJPMWHKOJO-UHFFFAOYSA-N tert-butyl n-[4-(hydroxymethyl)cyclohexyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(CO)CC1 SGNKPJPMWHKOJO-UHFFFAOYSA-N 0.000 description 1
- KJFFKWZRBGVSOJ-UHFFFAOYSA-N tert-butyl n-[4-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]-1-adamantyl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)(CC2C3)CC3CC1C2NC(C1=CC(Br)=CC=C1N=C1)=C1C(=O)C1CC1 KJFFKWZRBGVSOJ-UHFFFAOYSA-N 0.000 description 1
- DIVXUHKRFRDNQR-UHFFFAOYSA-N tert-butyl n-[5-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]pyridin-2-yl]carbamate Chemical compound C1=NC(NC(=O)OC(C)(C)C)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 DIVXUHKRFRDNQR-UHFFFAOYSA-N 0.000 description 1
- SSJKTAJVXONZEY-UHFFFAOYSA-N tert-butyl n-[[4-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]cyclohexyl]methyl]carbamate Chemical compound C1CC(CNC(=O)OC(C)(C)C)CCC1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 SSJKTAJVXONZEY-UHFFFAOYSA-N 0.000 description 1
- KDLVVPMTCYKKCH-UHFFFAOYSA-N tert-butyl n-[[4-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]phenyl]methyl]carbamate Chemical compound C1=CC(CNC(=O)OC(C)(C)C)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 KDLVVPMTCYKKCH-UHFFFAOYSA-N 0.000 description 1
- RTXNDTNDOHQMTI-UHFFFAOYSA-N tert-butyl n-methyl-n-piperidin-3-ylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)C1CCCNC1 RTXNDTNDOHQMTI-UHFFFAOYSA-N 0.000 description 1
- XYKYUXYNQDXZTD-UHFFFAOYSA-N tert-butyl n-methyl-n-pyrrolidin-3-ylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)C1CCNC1 XYKYUXYNQDXZTD-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
- C07D215/46—Nitrogen atoms attached in position 4 with hydrocarbon radicals, substituted by nitrogen atoms, attached to said nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36951910P | 2010-07-30 | 2010-07-30 | |
| US61/369,519 | 2010-07-30 | ||
| PCT/US2011/045792 WO2012016082A1 (en) | 2010-07-30 | 2011-07-28 | Quinoline derivatives and melk inhibitors containing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2013108865A RU2013108865A (ru) | 2014-09-10 |
| RU2582610C2 true RU2582610C2 (ru) | 2016-04-27 |
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| Application Number | Title | Priority Date | Filing Date |
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| RU2013108865/04A RU2582610C2 (ru) | 2010-07-30 | 2011-07-28 | Производные хинолина и содержащие их ингибиторы melk |
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| TW (1) | TWI532483B (enExample) |
| WO (1) | WO2012016082A1 (enExample) |
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| US20130225524A1 (en) * | 2010-11-05 | 2013-08-29 | Deping Chai | Chemical Compounds |
| MX366983B (es) * | 2012-01-19 | 2019-08-01 | Oncotherapy Science Inc | Derivados de 1,5-naftiridina e inhibidores de cinasa de cremallallera de leucina embrionica materna que los contienen. |
| UY35464A (es) | 2013-03-15 | 2014-10-31 | Araxes Pharma Llc | Inhibidores covalentes de kras g12c. |
| WO2014143659A1 (en) | 2013-03-15 | 2014-09-18 | Araxes Pharma Llc | Irreversible covalent inhibitors of the gtpase k-ras g12c |
| TWI659021B (zh) | 2013-10-10 | 2019-05-11 | 亞瑞克西斯製藥公司 | Kras g12c之抑制劑 |
| US10254283B2 (en) | 2013-11-12 | 2019-04-09 | Dana-Farber Cancer Institute, Inc. | Biomarker for MELK activity and methods of using same |
| EP3085700B1 (en) * | 2013-12-20 | 2018-10-31 | Institute of Pharmacology and Toxicology Academy of Military Medical Sciences P.L.A. China | Novel piperidine carboxamide compound, preparation method, and usage thereof |
| JO3556B1 (ar) | 2014-09-18 | 2020-07-05 | Araxes Pharma Llc | علاجات مدمجة لمعالجة السرطان |
| US10011600B2 (en) | 2014-09-25 | 2018-07-03 | Araxes Pharma Llc | Methods and compositions for inhibition of Ras |
| EP3197870B1 (en) | 2014-09-25 | 2020-08-19 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
| KR20200091954A (ko) * | 2014-12-15 | 2020-07-31 | 더 리젠츠 오브 더 유니버시티 오브 미시간 | Egfr 및 pi3k의 소분자 억제제 |
| EP3265093A4 (en) | 2015-03-04 | 2018-11-07 | Dana-Farber Cancer Institute, Inc. | Tricyclic kinase inhibitors of melk and methods of use |
| EP3280708B1 (en) | 2015-04-10 | 2021-09-01 | Araxes Pharma LLC | Substituted quinazoline compounds and methods of use thereof |
| JP6789239B2 (ja) | 2015-04-15 | 2020-11-25 | アラクセス ファーマ エルエルシー | Krasの縮合三環系インヒビターおよびその使用の方法 |
| CA2993013A1 (en) * | 2015-07-22 | 2017-01-26 | Araxes Pharma Llc | Substituted quinazoline compounds and their use as inhibitors of g12c mutant kras, hras and/or nras proteins |
| US10144724B2 (en) | 2015-07-22 | 2018-12-04 | Araxes Pharma Llc | Substituted quinazoline compounds and methods of use thereof |
| CN108026046B (zh) * | 2015-07-22 | 2021-12-21 | 亚瑞克西斯制药公司 | 取代的喹唑啉化合物及其作为g12c突变体kras、hras和/或nras蛋白质的抑制剂的用途 |
| CN108137547B (zh) * | 2015-08-03 | 2021-11-12 | 百时美施贵宝公司 | 可用作TNFα调节剂的杂环化合物 |
| WO2017058915A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| WO2017058728A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| EP3356354A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
| WO2017058792A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| WO2017058768A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| EP3356339A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
| EP3356347A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
| EP3364977A4 (en) | 2015-10-19 | 2019-09-04 | Araxes Pharma LLC | PROCESS FOR SCREENING INHIBITORS OF RAS |
| EA038635B9 (ru) | 2015-11-16 | 2021-10-26 | Араксис Фарма Ллк | 2-замещенные соединения хиназолина, содержащие замещенную гетероциклическую группу, и способы их применения |
| WO2017100546A1 (en) | 2015-12-09 | 2017-06-15 | Araxes Pharma Llc | Methods for preparation of quinazoline derivatives |
| AU2016378579A1 (en) * | 2015-12-22 | 2018-06-14 | Vitae Pharmaceuticals, Inc. | Inhibitors of the menin-MLL interaction |
| US10822312B2 (en) | 2016-03-30 | 2020-11-03 | Araxes Pharma Llc | Substituted quinazoline compounds and methods of use |
| US10646488B2 (en) | 2016-07-13 | 2020-05-12 | Araxes Pharma Llc | Conjugates of cereblon binding compounds and G12C mutant KRAS, HRAS or NRAS protein modulating compounds and methods of use thereof |
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| BR112013002182B8 (pt) | 2023-02-28 |
| IL223871A (en) | 2016-11-30 |
| CA2806332C (en) | 2017-11-14 |
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