JP5906253B2 - 抗ウイルス性化合物 - Google Patents

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Publication number

JP5906253B2

JP5906253B2 JP2013544826A JP2013544826A JP5906253B2 JP 5906253 B2 JP5906253 B2 JP 5906253B2 JP 2013544826 A JP2013544826 A JP 2013544826A JP 2013544826 A JP2013544826 A JP 2013544826A JP 5906253 B2 JP5906253 B2 JP 5906253B2

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JP

Japan

Prior art keywords

optionally substituted

independently

membered

alkyl

occurrence

Prior art date

2010-12-16

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

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• 150000001875 compounds Chemical class 0.000 title claims description 305
• 230000000840 anti-viral effect Effects 0.000 title 1
• -1 selected phosphonoxy Chemical group 0.000 claims description 1149
• 125000000623 heterocyclic group Chemical group 0.000 claims description 342
• 229910052736 halogen Inorganic materials 0.000 claims description 300
• 150000002367 halogens Chemical class 0.000 claims description 243
• 125000001424 substituent group Chemical group 0.000 claims description 222
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 206
• 125000004043 oxo group Chemical group O=* 0.000 claims description 198
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 194
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 170
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 160
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 159
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 139
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 118
• 125000004429 atom Chemical group 0.000 claims description 102
• 125000006643 (C2-C6) haloalkenyl group Chemical group 0.000 claims description 82
• 229910052739 hydrogen Inorganic materials 0.000 claims description 73
• 239000001257 hydrogen Substances 0.000 claims description 73
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 60
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 56
• 150000003839 salts Chemical class 0.000 claims description 54
• 125000002837 carbocyclic group Chemical group 0.000 claims description 52
• 229910052757 nitrogen Inorganic materials 0.000 claims description 40
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
• 229910052717 sulfur Inorganic materials 0.000 claims description 27
• 229910052760 oxygen Inorganic materials 0.000 claims description 26
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 25
• 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 25
• 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims description 25
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 25
• 125000000217 alkyl group Chemical group 0.000 claims description 25
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 24
• AZHCBEAXMJJJIQ-UHFFFAOYSA-N carbamoyl 2-carbamoyloxy-3-methylbutanoate Chemical compound C(N)(OC(C(=O)OC(N)=O)C(C)C)=O AZHCBEAXMJJJIQ-UHFFFAOYSA-N 0.000 claims description 20
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
• 125000000464 thioxo group Chemical group S=* 0.000 claims description 7
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 6
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 5
• 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 5
• 125000004450 alkenylene group Chemical group 0.000 claims description 4
• WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Natural products O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 3
• 239000003795 chemical substances by application Substances 0.000 claims description 2
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical group [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims 2
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 166
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 138
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 112
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 110
• 239000000203 mixture Substances 0.000 description 96
• 125000005843 halogen group Chemical group 0.000 description 90
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 80
• 239000000243 solution Substances 0.000 description 76
• 125000001153 fluoro group Chemical group F* 0.000 description 75
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 66
• 125000002619 bicyclic group Chemical group 0.000 description 65
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 64
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 61
• 125000004008 6 membered carbocyclic group Chemical group 0.000 description 60
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 57
• 238000000034 method Methods 0.000 description 56
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 52
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 51
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
• 238000006243 chemical reaction Methods 0.000 description 43
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
• 125000001309 chloro group Chemical group Cl* 0.000 description 41
• 235000019439 ethyl acetate Nutrition 0.000 description 41
• 125000004076 pyridyl group Chemical group 0.000 description 40
• 239000007787 solid Substances 0.000 description 40
• 239000000543 intermediate Substances 0.000 description 39
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 36
• 239000000047 product Substances 0.000 description 34
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 30
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
• 239000011734 sodium Substances 0.000 description 27
• 125000000335 thiazolyl group Chemical group 0.000 description 26
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 26
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
• 125000004435 hydrogen atom Chemical class [H]* 0.000 description 25
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 23
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
• 229910052799 carbon Inorganic materials 0.000 description 21
• 239000000741 silica gel Substances 0.000 description 21
• 229910002027 silica gel Inorganic materials 0.000 description 21
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 20
• 239000002904 solvent Substances 0.000 description 19
• 239000000126 substance Substances 0.000 description 19
• 239000002253 acid Substances 0.000 description 18
• 239000012267 brine Substances 0.000 description 18
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 17
• 230000000670 limiting effect Effects 0.000 description 17
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 16
• 125000003118 aryl group Chemical group 0.000 description 16
• 239000003921 oil Substances 0.000 description 16
• 235000019198 oils Nutrition 0.000 description 16
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
• 239000002585 base Substances 0.000 description 15
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 15
• 238000006467 substitution reaction Methods 0.000 description 15
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 14
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 13
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 13
• 125000005873 benzo[d]thiazolyl group Chemical group 0.000 description 13
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 13
• 125000000714 pyrimidinyl group Chemical group 0.000 description 13
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 12
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
• 125000000753 cycloalkyl group Chemical group 0.000 description 12
• 150000002148 esters Chemical class 0.000 description 12
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
• 125000003386 piperidinyl group Chemical group 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 12
• 239000011541 reaction mixture Substances 0.000 description 12
• 125000001054 5 membered carbocyclic group Chemical group 0.000 description 11
• 238000006069 Suzuki reaction reaction Methods 0.000 description 11
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 11
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 11
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 11
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
• 125000002393 azetidinyl group Chemical group 0.000 description 10
• 238000001914 filtration Methods 0.000 description 10
• 125000000262 haloalkenyl group Chemical group 0.000 description 10
• 239000000651 prodrug Substances 0.000 description 10
• 229940002612 prodrug Drugs 0.000 description 10
• 238000003756 stirring Methods 0.000 description 10
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 9
• 239000000284 extract Substances 0.000 description 9
• 125000000232 haloalkynyl group Chemical group 0.000 description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 9
• 125000006239 protecting group Chemical group 0.000 description 9
• 125000006413 ring segment Chemical group 0.000 description 9
• 238000003786 synthesis reaction Methods 0.000 description 9
• NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 9
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 8
• 125000001246 bromo group Chemical group Br* 0.000 description 8
• 125000004452 carbocyclyl group Chemical group 0.000 description 8
• 238000004587 chromatography analysis Methods 0.000 description 8
• 125000001188 haloalkyl group Chemical group 0.000 description 8
• 125000001183 hydrocarbyl group Chemical group 0.000 description 8
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 8
• 239000012074 organic phase Substances 0.000 description 8
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 8
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 7
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 7
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 7
• 239000007821 HATU Substances 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 150000001336 alkenes Chemical class 0.000 description 7
• 125000003342 alkenyl group Chemical group 0.000 description 7
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
• 239000000706 filtrate Substances 0.000 description 7
• 125000002950 monocyclic group Chemical group 0.000 description 7
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 7
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 6
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 6
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
• 239000005909 Kieselgur Substances 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 229960000583 acetic acid Drugs 0.000 description 6
• 150000001412 amines Chemical class 0.000 description 6
• 239000003054 catalyst Substances 0.000 description 6
• 239000012043 crude product Substances 0.000 description 6
• 125000000392 cycloalkenyl group Chemical group 0.000 description 6
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 6
• 150000004985 diamines Chemical class 0.000 description 6
• 238000000605 extraction Methods 0.000 description 6
• LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 6
• 208000015181 infectious disease Diseases 0.000 description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 description 6
• 125000002971 oxazolyl group Chemical group 0.000 description 6
• 229910000027 potassium carbonate Inorganic materials 0.000 description 6
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 6
• 239000012453 solvate Substances 0.000 description 6
• 125000003003 spiro group Chemical group 0.000 description 6
• CEFVHPDFGLDQKU-YFKPBYRVSA-N (2s)-2-(methoxycarbonylamino)-3-methylbutanoic acid Chemical compound COC(=O)N[C@@H](C(C)C)C(O)=O CEFVHPDFGLDQKU-YFKPBYRVSA-N 0.000 description 5
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 5
• 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 5
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 5
• 241000700605 Viruses Species 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 125000004432 carbon atom Chemical group C* 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• 238000010168 coupling process Methods 0.000 description 5
• 239000003814 drug Substances 0.000 description 5
• 238000003818 flash chromatography Methods 0.000 description 5
• 238000010438 heat treatment Methods 0.000 description 5
• 125000001072 heteroaryl group Chemical group 0.000 description 5
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 5
• 239000003960 organic solvent Substances 0.000 description 5
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 230000002829 reductive effect Effects 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 5
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 4
• OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 4
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
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