SG187633A1 - Quinoline derivatives and melk inhibitors containing the same - Google Patents
Quinoline derivatives and melk inhibitors containing the same Download PDFInfo
- Publication number
- SG187633A1 SG187633A1 SG2013006903A SG2013006903A SG187633A1 SG 187633 A1 SG187633 A1 SG 187633A1 SG 2013006903 A SG2013006903 A SG 2013006903A SG 2013006903 A SG2013006903 A SG 2013006903A SG 187633 A1 SG187633 A1 SG 187633A1
- Authority
- SG
- Singapore
- Prior art keywords
- quinolin
- compound
- chloro
- cyclopropyl
- methanone
- Prior art date
Links
- 229940124787 MELK inhibitor Drugs 0.000 title claims description 4
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title description 10
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 194
- -1 dimethylaminopropylaminocarbonyl Chemical group 0.000 claims description 1113
- 125000001424 substituent group Chemical group 0.000 claims description 250
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 236
- 125000000217 alkyl group Chemical group 0.000 claims description 230
- 125000005466 alkylenyl group Chemical group 0.000 claims description 147
- 125000001931 aliphatic group Chemical group 0.000 claims description 105
- 229910052792 caesium Inorganic materials 0.000 claims description 98
- 238000000034 method Methods 0.000 claims description 89
- 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 86
- 150000003839 salts Chemical class 0.000 claims description 73
- 125000000623 heterocyclic group Chemical group 0.000 claims description 66
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 64
- 229910052736 halogen Inorganic materials 0.000 claims description 58
- 150000002367 halogens Chemical class 0.000 claims description 58
- 229910052799 carbon Inorganic materials 0.000 claims description 49
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 46
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 42
- 125000003545 alkoxy group Chemical group 0.000 claims description 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 34
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 29
- 229910052757 nitrogen Inorganic materials 0.000 claims description 29
- 125000003107 substituted aryl group Chemical group 0.000 claims description 29
- 125000003282 alkyl amino group Chemical group 0.000 claims description 25
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
- 101710154611 Maternal embryonic leucine zipper kinase Proteins 0.000 claims description 21
- 102100024299 Maternal embryonic leucine zipper kinase Human genes 0.000 claims description 21
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 20
- 239000004480 active ingredient Substances 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 12
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 12
- 125000003277 amino group Chemical group 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 10
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 10
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 9
- 229910052805 deuterium Inorganic materials 0.000 claims description 9
- 230000002018 overexpression Effects 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 8
- 230000003449 preventive effect Effects 0.000 claims description 8
- 230000001225 therapeutic effect Effects 0.000 claims description 8
- 206010006187 Breast cancer Diseases 0.000 claims description 7
- 208000026310 Breast neoplasm Diseases 0.000 claims description 7
- 150000007945 N-acyl ureas Chemical class 0.000 claims description 7
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 7
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 7
- 229910052684 Cerium Inorganic materials 0.000 claims description 6
- 206010005003 Bladder cancer Diseases 0.000 claims description 5
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 5
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 5
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 5
- 125000005936 piperidyl group Chemical group 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 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
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- 201000011199 bladder lymphoma Diseases 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 206010046766 uterine cancer Diseases 0.000 claims description 2
- 125000004431 deuterium atom Chemical group 0.000 claims 1
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 description 648
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 366
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 286
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 172
- 239000000047 product Substances 0.000 description 134
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 114
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 113
- 239000007787 solid Substances 0.000 description 112
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 97
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 92
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 91
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 86
- 239000011541 reaction mixture Substances 0.000 description 85
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 75
- JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical compound O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 description 74
- 239000000460 chlorine Substances 0.000 description 68
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 67
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 62
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 description 58
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 53
- 241001024304 Mino Species 0.000 description 48
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 39
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- 229960003742 phenol Drugs 0.000 description 36
- ZVDDJPSHRNMSKV-UHFFFAOYSA-N acetaldehyde;hydrochloride Chemical compound Cl.CC=O ZVDDJPSHRNMSKV-UHFFFAOYSA-N 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 34
- 239000012044 organic layer Substances 0.000 description 34
- 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 32
- 239000000377 silicon dioxide Substances 0.000 description 31
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 30
- DJXNJVFEFSWHLY-UHFFFAOYSA-M quinoline-3-carboxylate Chemical compound C1=CC=CC2=CC(C(=O)[O-])=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-M 0.000 description 29
- 238000004440 column chromatography Methods 0.000 description 28
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 27
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 27
- 239000000725 suspension Substances 0.000 description 26
- 238000005481 NMR spectroscopy Methods 0.000 description 23
- 239000000203 mixture Substances 0.000 description 23
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 21
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 21
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- 239000000543 intermediate Substances 0.000 description 19
- 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 18
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
- 238000000746 purification Methods 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 17
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
- IIHQNAXFIODVDU-UHFFFAOYSA-N pyrimidine-2-carbonitrile Chemical compound N#CC1=NC=CC=N1 IIHQNAXFIODVDU-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 15
- BLTDCIWCFCUQCB-UHFFFAOYSA-N quinoline-3-carboxamide Chemical compound C1=CC=CC2=CC(C(=O)N)=CN=C21 BLTDCIWCFCUQCB-UHFFFAOYSA-N 0.000 description 15
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 14
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 13
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 13
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 13
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 13
- WTDFFADXONGQOM-UHFFFAOYSA-N formaldehyde;hydrochloride Chemical compound Cl.O=C WTDFFADXONGQOM-UHFFFAOYSA-N 0.000 description 13
- 125000006308 propyl amino group Chemical group 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 12
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 12
- PCDHSSHKDZYLLI-UHFFFAOYSA-N butan-1-one Chemical compound CCC[C]=O PCDHSSHKDZYLLI-UHFFFAOYSA-N 0.000 description 12
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 12
- 125000001245 hexylamino group Chemical group [H]N([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 12
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 12
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 12
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 11
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 11
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 11
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- 125000004429 atom Chemical group 0.000 description 10
- NDYMQOUYJJXCKJ-UHFFFAOYSA-N (4-fluorophenyl)-morpholin-4-ylmethanone Chemical compound C1=CC(F)=CC=C1C(=O)N1CCOCC1 NDYMQOUYJJXCKJ-UHFFFAOYSA-N 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 125000004076 pyridyl group Chemical group 0.000 description 9
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 150000007942 carboxylates Chemical class 0.000 description 8
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 8
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 125000004430 oxygen atom Chemical group O* 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 description 8
- 125000004434 sulfur atom Chemical group 0.000 description 8
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 8
- 125000001544 thienyl group Chemical group 0.000 description 8
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 7
- NMCMCSHJONWGMS-UHFFFAOYSA-N 4-(pyrrolidin-1-ylmethyl)piperidine Chemical compound C1CCCN1CC1CCNCC1 NMCMCSHJONWGMS-UHFFFAOYSA-N 0.000 description 7
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 7
- 150000001975 deuterium Chemical group 0.000 description 7
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 7
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- FEYLUKDSKVSMSZ-UHFFFAOYSA-N tert-butyl n-(4-aminocyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(N)CC1 FEYLUKDSKVSMSZ-UHFFFAOYSA-N 0.000 description 7
- FQYRLEXKXQRZDH-UHFFFAOYSA-N 4-aminoquinoline Chemical compound C1=CC=C2C(N)=CC=NC2=C1 FQYRLEXKXQRZDH-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 6
- 125000004193 piperazinyl group Chemical group 0.000 description 6
- 125000003226 pyrazolyl group Chemical group 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000012258 stirred mixture Substances 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 6
- 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
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 5
- JEOPNULJZZFNFK-SAZUREKKSA-N C1C[C@@H](COS(=O)(=O)C)CC[C@@H]1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 Chemical compound C1C[C@@H](COS(=O)(=O)C)CC[C@@H]1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 JEOPNULJZZFNFK-SAZUREKKSA-N 0.000 description 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 5
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 5
- 229910002091 carbon monoxide Inorganic materials 0.000 description 5
- 229960004132 diethyl ether Drugs 0.000 description 5
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 5
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 5
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- 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 1
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- 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 1
- 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 1
- 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 1
- IQURYDASUWQLME-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-methoxyquinoline-3-carboxylate Chemical compound C1=CC(OC)=CC2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C21 IQURYDASUWQLME-UHFFFAOYSA-N 0.000 description 1
- OABFDBDSRJQHQT-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-methylquinoline-3-carboxylate Chemical compound C1=CC(C)=CC2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C21 OABFDBDSRJQHQT-UHFFFAOYSA-N 0.000 description 1
- QZBNGVMWXLQUQW-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-pyridin-4-ylquinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=NC=C1 QZBNGVMWXLQUQW-UHFFFAOYSA-N 0.000 description 1
- VMTGQJIMLUYLLC-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]-6-thiophen-2-ylquinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=CS1 VMTGQJIMLUYLLC-UHFFFAOYSA-N 0.000 description 1
- ITZRBOCLNMKQQP-UHFFFAOYSA-N ethyl 4-[3-(dimethylamino)propylamino]quinoline-3-carboxylate Chemical compound C1=CC=CC2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C21 ITZRBOCLNMKQQP-UHFFFAOYSA-N 0.000 description 1
- SSMWAAZPTJIPOJ-UHFFFAOYSA-N ethyl 4-[[3-(aminomethyl)cyclohexyl]methylamino]-6-bromoquinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1NCC1CCCC(CN)C1 SSMWAAZPTJIPOJ-UHFFFAOYSA-N 0.000 description 1
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- FZHJPPKCGPWHSV-UHFFFAOYSA-N ethyl 6-(4-aminophenyl)-4-[3-(dimethylamino)propylamino]quinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=C(N)C=C1 FZHJPPKCGPWHSV-UHFFFAOYSA-N 0.000 description 1
- GYFXCSLTQVCEAM-UHFFFAOYSA-N ethyl 6-(4-carbamoylphenyl)-4-[3-(dimethylamino)propylamino]quinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=C(C(N)=O)C=C1 GYFXCSLTQVCEAM-UHFFFAOYSA-N 0.000 description 1
- KLZGCWXXLLIYAJ-UHFFFAOYSA-N ethyl 6-(4-cyanophenyl)-4-[3-(dimethylamino)propylamino]quinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=C(C#N)C=C1 KLZGCWXXLLIYAJ-UHFFFAOYSA-N 0.000 description 1
- YDSMAKMJNKUUAU-UHFFFAOYSA-N ethyl 6-(6-aminopyridin-3-yl)-4-[3-(dimethylamino)propylamino]quinoline-3-carboxylate Chemical compound C=1C2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C2C=CC=1C1=CC=C(N)N=C1 YDSMAKMJNKUUAU-UHFFFAOYSA-N 0.000 description 1
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- AWNWSRDLFOECAK-UHFFFAOYSA-N ethyl 6-bromo-4-(3-carbamoylpiperidin-1-yl)quinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1N1CCCC(C(N)=O)C1 AWNWSRDLFOECAK-UHFFFAOYSA-N 0.000 description 1
- BFNXREBOONZFTR-UHFFFAOYSA-N ethyl 6-bromo-4-(piperidin-4-ylmethylamino)quinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1NCC1CCNCC1 BFNXREBOONZFTR-UHFFFAOYSA-N 0.000 description 1
- OQGHFXOAFBNLLA-UHFFFAOYSA-N ethyl 6-bromo-4-(pyridin-4-ylmethylamino)quinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1NCC1=CC=NC=C1 OQGHFXOAFBNLLA-UHFFFAOYSA-N 0.000 description 1
- IAPHETGRBNQOOS-UHFFFAOYSA-N ethyl 6-bromo-4-[2-(diethylamino)ethylamino]quinoline-3-carboxylate Chemical compound C1=CC(Br)=CC2=C(NCCN(CC)CC)C(C(=O)OCC)=CN=C21 IAPHETGRBNQOOS-UHFFFAOYSA-N 0.000 description 1
- GCXYTARBKLKKKQ-UHFFFAOYSA-N ethyl 6-bromo-4-[3-(2-hydroxyethylamino)propylamino]quinoline-3-carboxylate Chemical compound C1=CC(Br)=CC2=C(NCCCNCCO)C(C(=O)OCC)=CN=C21 GCXYTARBKLKKKQ-UHFFFAOYSA-N 0.000 description 1
- NPMCACCUGBYQNL-UHFFFAOYSA-N ethyl 6-bromo-4-[3-(diethylamino)propylamino]quinoline-3-carboxylate Chemical compound C1=CC(Br)=CC2=C(NCCCN(CC)CC)C(C(=O)OCC)=CN=C21 NPMCACCUGBYQNL-UHFFFAOYSA-N 0.000 description 1
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- YSVWMQFJPRNKQS-UHFFFAOYSA-N ethyl 6-bromo-4-[4-(methylaminomethyl)piperidin-1-yl]quinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1N1CCC(CNC)CC1 YSVWMQFJPRNKQS-UHFFFAOYSA-N 0.000 description 1
- PVWKBCBLMHZXKZ-UHFFFAOYSA-N ethyl 6-bromo-4-[4-[(dimethylamino)methyl]anilino]quinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1NC1=CC=C(CN(C)C)C=C1 PVWKBCBLMHZXKZ-UHFFFAOYSA-N 0.000 description 1
- CVBAGPILGWGLKT-UHFFFAOYSA-N ethyl 6-bromo-4-[4-[(dimethylamino)methyl]piperidin-1-yl]quinoline-3-carboxylate Chemical compound CCOC(=O)C1=CN=C2C=CC(Br)=CC2=C1N1CCC(CN(C)C)CC1 CVBAGPILGWGLKT-UHFFFAOYSA-N 0.000 description 1
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- KMUSVINZSCTMHQ-UHFFFAOYSA-N ethyl 6-chloro-4-[3-(dimethylamino)propylamino]quinoline-3-carboxylate Chemical compound C1=CC(Cl)=CC2=C(NCCCN(C)C)C(C(=O)OCC)=CN=C21 KMUSVINZSCTMHQ-UHFFFAOYSA-N 0.000 description 1
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- 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 description 1
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- IYKBKCAGEIAKIG-UHFFFAOYSA-N tert-butyl n-[1-[5-[(3-acetyl-6-bromoquinolin-4-yl)amino]pyridin-2-yl]piperidin-3-yl]-n-methylcarbamate Chemical compound C1C(N(C)C(=O)OC(C)(C)C)CCCN1C(N=C1)=CC=C1NC1=C(C(C)=O)C=NC2=CC=C(Br)C=C12 IYKBKCAGEIAKIG-UHFFFAOYSA-N 0.000 description 1
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- VOLGCLSZKIEFHT-UHFFFAOYSA-N tert-butyl n-[1-[5-[[3-acetyl-6-(3,5-dichloro-4-hydroxyphenyl)quinolin-4-yl]amino]pyridin-2-yl]piperidin-3-yl]carbamate Chemical compound CC(=O)C1=CN=C2C=CC(C=3C=C(Cl)C(O)=C(Cl)C=3)=CC2=C1NC(C=N1)=CC=C1N1CCCC(NC(=O)OC(C)(C)C)C1 VOLGCLSZKIEFHT-UHFFFAOYSA-N 0.000 description 1
- OFGNMICBRGJFSM-UHFFFAOYSA-N tert-butyl n-[1-[5-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]pyridin-2-yl]piperidin-3-yl]-n-methylcarbamate Chemical compound C1C(N(C)C(=O)OC(C)(C)C)CCCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 OFGNMICBRGJFSM-UHFFFAOYSA-N 0.000 description 1
- BAFDCSZLGDNCQT-UHFFFAOYSA-N tert-butyl n-[1-[5-[[6-bromo-3-(cyclopropanecarbonyl)quinolin-4-yl]amino]pyridin-2-yl]pyrrolidin-3-yl]-n-methylcarbamate Chemical compound C1C(N(C)C(=O)OC(C)(C)C)CCN1C(N=C1)=CC=C1NC1=C(C(=O)C2CC2)C=NC2=CC=C(Br)C=C12 BAFDCSZLGDNCQT-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
- MSEQZQUQJNSYIK-UHFFFAOYSA-N tert-butyl n-[4-(pyrrolidin-1-ylmethyl)cyclohexyl]carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCC1CN1CCCC1 MSEQZQUQJNSYIK-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
- 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
- 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
- 125000003718 tetrahydrofuranyl group Chemical group 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
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- IAHBIMWHYUOIOH-UHFFFAOYSA-N vanadium hydrochloride Chemical compound Cl.[V] IAHBIMWHYUOIOH-UHFFFAOYSA-N 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
-
- 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
- C07D401/10—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
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- A—HUMAN NECESSITIES
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- 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
-
- 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
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (2)
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| US36951910P | 2010-07-30 | 2010-07-30 | |
| PCT/US2011/045792 WO2012016082A1 (en) | 2010-07-30 | 2011-07-28 | Quinoline derivatives and melk inhibitors containing the same |
Publications (1)
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| SG187633A1 true SG187633A1 (en) | 2013-03-28 |
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| EP2635279A4 (en) * | 2010-11-05 | 2014-10-29 | Glaxosmithkline Ip No 2 Ltd | CHEMICAL COMPOUNDS |
| AU2012366148B2 (en) * | 2012-01-19 | 2016-12-01 | Oncotherapy Science, Inc. | 1,5-naphthyridine derivatives and melk inhibitors containing the same |
| US9227978B2 (en) | 2013-03-15 | 2016-01-05 | Araxes Pharma Llc | Covalent inhibitors of Kras G12C |
| WO2014143659A1 (en) | 2013-03-15 | 2014-09-18 | Araxes Pharma Llc | Irreversible covalent inhibitors of the gtpase k-ras g12c |
| JO3805B1 (ar) | 2013-10-10 | 2021-01-31 | Araxes Pharma Llc | مثبطات كراس جي12سي |
| US10254283B2 (en) | 2013-11-12 | 2019-04-09 | Dana-Farber Cancer Institute, Inc. | Biomarker for MELK activity and methods of using same |
| JP6535007B2 (ja) * | 2013-12-20 | 2019-06-26 | インスティテュート オブ ファーマコロジー アンド トキシコロジー アカデミー オブ ミリタリー メディカル サイエンシズ ピー.エル.エー.チャイナ | 新規ピペリジンカルボキサミド化合物、その調製方法及び使用 |
| JO3556B1 (ar) | 2014-09-18 | 2020-07-05 | Araxes Pharma Llc | علاجات مدمجة لمعالجة السرطان |
| WO2016049568A1 (en) | 2014-09-25 | 2016-03-31 | Araxes Pharma Llc | Methods and compositions for inhibition of ras |
| US9862701B2 (en) | 2014-09-25 | 2018-01-09 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
| CA2969974C (en) * | 2014-12-15 | 2020-08-04 | The Regents Of The University Of Michigan | Small molecule inhibitors of egfr and pi3k |
| CA2975277A1 (en) | 2015-03-04 | 2016-09-09 | Dana-Farber Cancer Institute, Inc. | Tricyclic kinase inhibitors of melk and methods of use |
| JP2018513853A (ja) | 2015-04-10 | 2018-05-31 | アラクセス ファーマ エルエルシー | 置換キナゾリン化合物およびその使用方法 |
| ES2856880T3 (es) | 2015-04-15 | 2021-09-28 | Araxes Pharma Llc | Inhibidores tricíclicos condensados de KRAS y métodos de uso de los mismos |
| 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 |
| EP3325447A1 (en) * | 2015-07-22 | 2018-05-30 | 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 |
| UY36838A (es) * | 2015-08-03 | 2017-01-31 | Bristol Myers Squibb Company Una Corporación Del Estado De Delaware | Compuestos heterocíclicos moduladores de la señalización de tnf alfa y composiciones farmacéuticas que los contienen |
| US10858343B2 (en) | 2015-09-28 | 2020-12-08 | 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 |
| EP3356359B1 (en) | 2015-09-28 | 2021-10-20 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
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| WO2017058807A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| EP3356351A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
| US10730867B2 (en) | 2015-09-28 | 2020-08-04 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
| JP2018533939A (ja) | 2015-10-19 | 2018-11-22 | アラクセス ファーマ エルエルシー | Rasの阻害剤をスクリーニングするための方法 |
| CA3005089A1 (en) | 2015-11-16 | 2017-05-26 | Araxes Pharma Llc | 2-substituted quinazoline compounds comprising a substituted heterocyclic group and methods of use thereof |
| US9988357B2 (en) | 2015-12-09 | 2018-06-05 | Araxes Pharma Llc | Methods for preparation of quinazoline derivatives |
| MX2018007703A (es) * | 2015-12-22 | 2018-11-09 | Vitae Pharmaceuticals Inc | Inhibidores de la interaccion de menina-linaje leucemico mixto. |
| WO2017172979A1 (en) | 2016-03-30 | 2017-10-05 | 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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| US10736897B2 (en) | 2017-05-25 | 2020-08-11 | Araxes Pharma Llc | Compounds and methods of use thereof for treatment of cancer |
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| EP3658560A4 (en) | 2017-07-25 | 2021-01-06 | Crinetics Pharmaceuticals, Inc. | SOMATOSTAT IN MODULATORS AND USES THEREOF |
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