MX2007013276A - Derivados de quinolina y quinoxalina como inhibidores de actividad enzimatica de cinasa. - Google Patents

Info

Publication number

MX2007013276A

MX2007013276A MX2007013276A MX2007013276A MX2007013276A MX 2007013276 A MX2007013276 A MX 2007013276A MX 2007013276 A MX2007013276 A MX 2007013276A MX 2007013276 A MX2007013276 A MX 2007013276A MX 2007013276 A MX2007013276 A MX 2007013276A

Authority

MX

Mexico

Prior art keywords

methoxy

quinolin

yloxy

compound according

alkyl

Prior art date

2005-05-05

Links

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• Global Dossier
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• 239000003112 inhibitor Substances 0.000 title claims abstract description 14
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title description 10
• 108091000080 Phosphotransferase Proteins 0.000 title description 2
• 230000002255 enzymatic effect Effects 0.000 title description 2
• 102000020233 phosphotransferase Human genes 0.000 title description 2
• 125000001567 quinoxalinyl group Chemical class N1=C(C=NC2=CC=CC=C12)* 0.000 title description 2
• -1 cyano, cyclopropyl Chemical group 0.000 claims abstract description 398
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 280
• 150000001875 compounds Chemical class 0.000 claims abstract description 237
• 239000001257 hydrogen Chemical group 0.000 claims abstract description 61
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 36
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 25
• 125000003118 aryl group Chemical group 0.000 claims abstract description 24
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 21
• 102000003989 Aurora kinases Human genes 0.000 claims abstract description 20
• 230000000694 effects Effects 0.000 claims abstract description 20
• 108090000433 Aurora kinases Proteins 0.000 claims abstract description 19
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 19
• 125000006413 ring segment Chemical group 0.000 claims abstract description 18
• 125000002950 monocyclic group Chemical group 0.000 claims abstract description 14
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 13
• 108010051152 Carboxylesterase Proteins 0.000 claims abstract description 12
• 102000013392 Carboxylesterase Human genes 0.000 claims abstract description 12
• 125000002843 carboxylic acid group Chemical group 0.000 claims abstract description 9
• 125000004185 ester group Chemical group 0.000 claims abstract description 9
• 230000003834 intracellular effect Effects 0.000 claims abstract description 9
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 4
• 239000002253 acid Substances 0.000 claims description 102
• 239000000203 mixture Substances 0.000 claims description 90
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 80
• 150000003254 radicals Chemical class 0.000 claims description 55
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
• 125000000217 alkyl group Chemical group 0.000 claims description 29
• 210000004027 cell Anatomy 0.000 claims description 27
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
• 238000000034 method Methods 0.000 claims description 22
• 229910052757 nitrogen Inorganic materials 0.000 claims description 20
• 125000001424 substituent group Chemical group 0.000 claims description 20
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 19
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 17
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
• 125000001153 fluoro group Chemical group F* 0.000 claims description 16
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
• 238000002360 preparation method Methods 0.000 claims description 15
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
• 125000004076 pyridyl group Chemical group 0.000 claims description 12
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 11
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 11
• 101150101604 ACVR1B gene Proteins 0.000 claims description 10
• 206010028980 Neoplasm Diseases 0.000 claims description 10
• 201000010099 disease Diseases 0.000 claims description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
• 230000005764 inhibitory process Effects 0.000 claims description 10
• GPTFURBXHJWNHR-UHFFFAOYSA-N protopine Chemical compound C1=C2C(=O)CC3=CC=C4OCOC4=C3CN(C)CCC2=CC2=C1OCO2 GPTFURBXHJWNHR-UHFFFAOYSA-N 0.000 claims description 10
• 150000003839 salts Chemical class 0.000 claims description 10
• 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 claims description 9
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
• 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 9
• 210000002540 macrophage Anatomy 0.000 claims description 9
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
• 201000011510 cancer Diseases 0.000 claims description 8
• 125000004122 cyclic group Chemical group 0.000 claims description 8
• 125000005843 halogen group Chemical group 0.000 claims description 8
• 102000004190 Enzymes Human genes 0.000 claims description 7
• 108090000790 Enzymes Proteins 0.000 claims description 7
• 229910052799 carbon Inorganic materials 0.000 claims description 7
• 230000002401 inhibitory effect Effects 0.000 claims description 7
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
• 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 6
• 125000004450 alkenylene group Chemical group 0.000 claims description 6
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
• 125000003545 alkoxy group Chemical group 0.000 claims description 5
• 239000005441 aurora Substances 0.000 claims description 5
• 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 5
• 125000002837 carbocyclic group Chemical group 0.000 claims description 5
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
• 229910052717 sulfur Inorganic materials 0.000 claims description 5
• 150000003568 thioethers Chemical class 0.000 claims description 5
• DGVRQOFMFZGCJY-OAQYLSRUSA-N (2r)-2-amino-4-[4-(4-benzamidophenoxy)-6-methoxyquinolin-7-yl]oxybutanoic acid Chemical compound C1=CN=C2C=C(OCC[C@@H](N)C(O)=O)C(OC)=CC2=C1OC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1 DGVRQOFMFZGCJY-OAQYLSRUSA-N 0.000 claims description 4
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
• 150000001204 N-oxides Chemical class 0.000 claims description 4
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
• 239000012453 solvate Substances 0.000 claims description 4
• CVUARBOFEQLVSK-JOCHJYFZSA-N (2r)-2-amino-5-[4-(4-benzamidophenoxy)-6-methoxyquinolin-7-yl]oxypentanoic acid Chemical compound C1=CN=C2C=C(OCCC[C@@H](N)C(O)=O)C(OC)=CC2=C1OC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1 CVUARBOFEQLVSK-JOCHJYFZSA-N 0.000 claims description 3
• 208000023275 Autoimmune disease Diseases 0.000 claims description 3
• DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 3
• 125000002947 alkylene group Chemical group 0.000 claims description 3
• 125000004419 alkynylene group Chemical group 0.000 claims description 3
• 230000004663 cell proliferation Effects 0.000 claims description 3
• 238000001727 in vivo Methods 0.000 claims description 3
• HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims description 3
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 3
• 230000035755 proliferation Effects 0.000 claims description 3
• 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 3
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
• 101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 claims description 2
• 125000004429 atom Chemical group 0.000 claims description 2
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
• 229910052760 oxygen Inorganic materials 0.000 claims description 2
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
• 108020000002 NR3 subfamily Proteins 0.000 claims 3
• 239000008194 pharmaceutical composition Substances 0.000 claims 2
• VXVVXQYKXVYROC-FQEVSTJZSA-N (2s)-2-amino-4-[4-[2-fluoro-4-[[4-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-6-methoxyquinolin-7-yl]oxybutanoic acid Chemical compound C1=CN=C2C=C(OCC[C@H](N)C(O)=O)C(OC)=CC2=C1OC(C(=C1)F)=CC=C1NC(=O)NC1=CC=C(C(F)(F)F)C=C1 VXVVXQYKXVYROC-FQEVSTJZSA-N 0.000 claims 1
• 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 claims 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
• 108020004021 3-ketosteroid receptors Proteins 0.000 claims 1
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims 1
• 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 claims 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
• CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
• 239000000460 chlorine Substances 0.000 claims 1
• 229910052801 chlorine Inorganic materials 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
• 150000004677 hydrates Chemical class 0.000 claims 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims 1
• 210000001616 monocyte Anatomy 0.000 claims 1
• 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims 1
• 238000011200 topical administration Methods 0.000 claims 1
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
• 125000001475 halogen functional group Chemical group 0.000 abstract 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 262
• 238000005481 NMR spectroscopy Methods 0.000 description 221
• 238000006243 chemical reaction Methods 0.000 description 148
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 138
• 230000002829 reductive effect Effects 0.000 description 138
• 239000007787 solid Substances 0.000 description 130
• 239000000243 solution Substances 0.000 description 130
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
• 235000019439 ethyl acetate Nutrition 0.000 description 104
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 103
• 239000011541 reaction mixture Substances 0.000 description 101
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 98
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 82
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 77
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 76
• 239000012267 brine Substances 0.000 description 61
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 61
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
• 238000004440 column chromatography Methods 0.000 description 52
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 46
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
• 239000000047 product Substances 0.000 description 44
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 43
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 41
• 235000019341 magnesium sulphate Nutrition 0.000 description 41
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
• 238000000746 purification Methods 0.000 description 33
• 230000015572 biosynthetic process Effects 0.000 description 32
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 31
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
• 150000002148 esters Chemical class 0.000 description 30
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
• 238000003786 synthesis reaction Methods 0.000 description 30
• 101150041968 CDC13 gene Proteins 0.000 description 29
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 29
• 239000012044 organic layer Substances 0.000 description 28
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 28
• 239000003921 oil Substances 0.000 description 25
• 235000019198 oils Nutrition 0.000 description 25
• 229910000027 potassium carbonate Inorganic materials 0.000 description 25
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
• 235000019441 ethanol Nutrition 0.000 description 22
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
• 239000000284 extract Substances 0.000 description 21
• 235000011121 sodium hydroxide Nutrition 0.000 description 21
• 238000001914 filtration Methods 0.000 description 20
• 239000002244 precipitate Substances 0.000 description 19
• 229960000583 acetic acid Drugs 0.000 description 18
• 239000012299 nitrogen atmosphere Substances 0.000 description 18
• 239000002904 solvent Substances 0.000 description 18
• 239000010410 layer Substances 0.000 description 17
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 17
• 239000000706 filtrate Substances 0.000 description 16
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
• 229920006395 saturated elastomer Polymers 0.000 description 15
• 239000011734 sodium Substances 0.000 description 15
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
• HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 14
• MNLNTCJWJBWEJJ-LURJTMIESA-N (2s)-4-bromo-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CCBr MNLNTCJWJBWEJJ-LURJTMIESA-N 0.000 description 13
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
• 238000010992 reflux Methods 0.000 description 12
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 11
• 238000002953 preparative HPLC Methods 0.000 description 11
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
• 238000003756 stirring Methods 0.000 description 11
• 239000000725 suspension Substances 0.000 description 11
• DGVRQOFMFZGCJY-NRFANRHFSA-N (2s)-2-amino-4-[4-(4-benzamidophenoxy)-6-methoxyquinolin-7-yl]oxybutanoic acid Chemical compound C1=CN=C2C=C(OCC[C@H](N)C(O)=O)C(OC)=CC2=C1OC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1 DGVRQOFMFZGCJY-NRFANRHFSA-N 0.000 description 10
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
• 238000001704 evaporation Methods 0.000 description 10
• 230000008020 evaporation Effects 0.000 description 10
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• 239000007864 aqueous solution Substances 0.000 description 9
• 108090000371 Esterases Proteins 0.000 description 8
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
• 125000004432 carbon atom Chemical group C* 0.000 description 8
• 235000011181 potassium carbonates Nutrition 0.000 description 8
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
• 125000001544 thienyl group Chemical group 0.000 description 8
• SYKLZPMKNBDEOF-UHFFFAOYSA-N 4-chloro-6-methoxy-7-phenylmethoxyquinoline Chemical compound COC1=CC2=C(Cl)C=CN=C2C=C1OCC1=CC=CC=C1 SYKLZPMKNBDEOF-UHFFFAOYSA-N 0.000 description 7
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 7
• 238000003556 assay Methods 0.000 description 7
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 7
• CVPWYDXAVJCNAG-UHFFFAOYSA-N n-(4-hydroxyphenyl)benzamide Chemical compound C1=CC(O)=CC=C1NC(=O)C1=CC=CC=C1 CVPWYDXAVJCNAG-UHFFFAOYSA-N 0.000 description 7
• 235000015320 potassium carbonate Nutrition 0.000 description 7
• 239000000843 powder Substances 0.000 description 7
• 235000017557 sodium bicarbonate Nutrition 0.000 description 7
• PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 6
• 108010033040 Histones Proteins 0.000 description 6
• 102000006947 Histones Human genes 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• 239000012298 atmosphere Substances 0.000 description 6
• 239000003054 catalyst Substances 0.000 description 6
• 229940079593 drug Drugs 0.000 description 6
• 239000003814 drug Substances 0.000 description 6
• 238000003818 flash chromatography Methods 0.000 description 6
• 230000004048 modification Effects 0.000 description 6
• 238000012986 modification Methods 0.000 description 6
• 229910052763 palladium Inorganic materials 0.000 description 6
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
• 229910014455 Ca-Cb Inorganic materials 0.000 description 5
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