TWI485150B - 三唑并吡啶化合物及其作為脯胺醯基羥化酶抑制劑或紅血球生成素生產誘導劑之作用 - Google Patents

Info

Publication number

TWI485150B

TWI485150B TW099123410A TW99123410A TWI485150B TW I485150 B TWI485150 B TW I485150B TW 099123410 A TW099123410 A TW 099123410A TW 99123410 A TW99123410 A TW 99123410A TW I485150 B TWI485150 B TW I485150B

Authority

TW

Taiwan

Prior art keywords

compound

group

pharmaceutically acceptable

acceptable salt

alkyl

Prior art date

2009-07-17

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• 238000004519 manufacturing process Methods 0.000 title claims description 114
• 102000003951 Erythropoietin Human genes 0.000 title claims description 37
• 108090000394 Erythropoietin Proteins 0.000 title claims description 37
• 229940105423 erythropoietin Drugs 0.000 title claims description 37
• OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 title claims description 37
• 239000003795 chemical substances by application Substances 0.000 title claims description 22
• 230000001939 inductive effect Effects 0.000 title claims description 18
• -1 Triazolopyridine compound Chemical class 0.000 title description 174
• 229940078467 Prolyl hydroxylase inhibitor Drugs 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 516
• 150000003839 salts Chemical class 0.000 claims description 121
• 125000001424 substituent group Chemical group 0.000 claims description 101
• 125000000217 alkyl group Chemical group 0.000 claims description 80
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 62
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 52
• 208000007502 anemia Diseases 0.000 claims description 49
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
• 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 30
• 125000005843 halogen group Chemical group 0.000 claims description 30
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 26
• 125000003118 aryl group Chemical group 0.000 claims description 22
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
• 239000003814 drug Substances 0.000 claims description 21
• 125000001072 heteroaryl group Chemical group 0.000 claims description 18
• 229910052799 carbon Inorganic materials 0.000 claims description 16
• 125000006621 (C3-C8) cycloalkyl-(C1-C6) alkyl group Chemical group 0.000 claims description 14
• 206010058116 Nephrogenic anaemia Diseases 0.000 claims description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims description 14
• SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 claims description 13
• 230000036961 partial effect Effects 0.000 claims description 13
• 229910052757 nitrogen Inorganic materials 0.000 claims description 12
• 229940124597 therapeutic agent Drugs 0.000 claims description 10
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
• 125000005842 heteroatom Chemical group 0.000 claims description 9
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 8
• 125000006553 (C3-C8) cycloalkenyl group Chemical group 0.000 claims description 8
• 125000004434 sulfur atom Chemical group 0.000 claims description 8
• 229910052717 sulfur Inorganic materials 0.000 claims description 7
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 6
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
• 229940122439 Hydroxylase inhibitor Drugs 0.000 claims description 4
• 125000004432 carbon atom Chemical group C* 0.000 claims description 4
• 210000003734 kidney Anatomy 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 3
• 238000006467 substitution reaction Methods 0.000 claims description 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 192
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 168
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 135
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 132
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 116
• 239000000203 mixture Substances 0.000 description 110
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 96
• 238000005160 1H NMR spectroscopy Methods 0.000 description 82
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 79
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 76
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 74
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 66
• 235000019439 ethyl acetate Nutrition 0.000 description 66
• 239000012453 solvate Substances 0.000 description 61
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 60
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 56
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 56
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 47
• 150000001335 aliphatic alkanes Chemical class 0.000 description 40
• 230000002829 reductive effect Effects 0.000 description 40
• 239000007787 solid Substances 0.000 description 40
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 39
• 239000012046 mixed solvent Substances 0.000 description 37
• 239000011541 reaction mixture Substances 0.000 description 37
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 35
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 34
• 239000012044 organic layer Substances 0.000 description 33
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
• 238000001914 filtration Methods 0.000 description 32
• 238000010438 heat treatment Methods 0.000 description 31
• 238000006243 chemical reaction Methods 0.000 description 28
• 229910052801 chlorine Inorganic materials 0.000 description 28
• 125000001309 chloro group Chemical group Cl* 0.000 description 28
• 239000000243 solution Substances 0.000 description 28
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• 238000001816 cooling Methods 0.000 description 26
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
• 238000002360 preparation method Methods 0.000 description 26
• 238000003756 stirring Methods 0.000 description 26
• DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 24
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
• 238000007796 conventional method Methods 0.000 description 24
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 23
• 239000002585 base Substances 0.000 description 22
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
• 230000002401 inhibitory effect Effects 0.000 description 21
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 20
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 20
• 125000006239 protecting group Chemical group 0.000 description 20
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 18
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 18
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 18
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 18
• 201000010099 disease Diseases 0.000 description 18
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 18
• 238000000034 method Methods 0.000 description 18
• 229920006395 saturated elastomer Polymers 0.000 description 17
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
• 235000017557 sodium bicarbonate Nutrition 0.000 description 17
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 16
• 238000004440 column chromatography Methods 0.000 description 16
• 229910052731 fluorine Inorganic materials 0.000 description 16
• 125000001153 fluoro group Chemical group F* 0.000 description 16
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 16
• 101000987586 Homo sapiens Eosinophil peroxidase Proteins 0.000 description 15
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
• 238000005576 amination reaction Methods 0.000 description 15
• 239000003480 eluent Substances 0.000 description 15
• 102000044890 human EPO Human genes 0.000 description 15
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 15
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 14
• 239000000706 filtrate Substances 0.000 description 14
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 14
• 229910000027 potassium carbonate Inorganic materials 0.000 description 13
• 235000011181 potassium carbonates Nutrition 0.000 description 13
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 12
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 12
• 235000011054 acetic acid Nutrition 0.000 description 12
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 12
• 239000011734 sodium Substances 0.000 description 12
• 229910052708 sodium Inorganic materials 0.000 description 12
• 239000002253 acid Substances 0.000 description 11
• 238000010511 deprotection reaction Methods 0.000 description 11
• 230000000694 effects Effects 0.000 description 11
• 229910052763 palladium Inorganic materials 0.000 description 11
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 11
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 10
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• 101000730368 Homo sapiens Phosducin Proteins 0.000 description 10
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 10
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 10
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 10
• WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 10
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
• 239000012043 crude product Substances 0.000 description 10
• 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 10
• 229910052740 iodine Inorganic materials 0.000 description 10
• 229940098779 methanesulfonic acid Drugs 0.000 description 10
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
• 102000008109 Mixed Function Oxygenases Human genes 0.000 description 9
• 108010074633 Mixed Function Oxygenases Proteins 0.000 description 9
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 9
• 235000011089 carbon dioxide Nutrition 0.000 description 9
• 210000004027 cell Anatomy 0.000 description 9
• 229940079593 drug Drugs 0.000 description 9
• 150000002332 glycine derivatives Chemical class 0.000 description 9
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 9
• 239000002904 solvent Substances 0.000 description 9
• 238000012360 testing method Methods 0.000 description 9
• PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 9
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 8
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
• 101000881648 Homo sapiens Egl nine homolog 1 Proteins 0.000 description 8
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 8
• 102000053692 human EGLN1 Human genes 0.000 description 8
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
• 239000002243 precursor Substances 0.000 description 8
• 238000010992 reflux Methods 0.000 description 8
• 229910052938 sodium sulfate Inorganic materials 0.000 description 8
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 8
• 235000011152 sodium sulphate Nutrition 0.000 description 8
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 7
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
• 239000001768 carboxy methyl cellulose Substances 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 7
• 210000003743 erythrocyte Anatomy 0.000 description 7
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 7
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 7
• 229910052744 lithium Inorganic materials 0.000 description 7
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 7
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 6
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 6
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
• 102000002508 Peptide Elongation Factors Human genes 0.000 description 6
• 108010068204 Peptide Elongation Factors Proteins 0.000 description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• 239000007864 aqueous solution Substances 0.000 description 6
• 150000001721 carbon Chemical group 0.000 description 6
• 239000003054 catalyst Substances 0.000 description 6
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 6
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 6
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 6
• 239000010410 layer Substances 0.000 description 6
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 6
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
• 239000011591 potassium Substances 0.000 description 6
• 229960003975 potassium Drugs 0.000 description 6
• 229910052700 potassium Inorganic materials 0.000 description 6
• NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 6
• 239000012312 sodium hydride Substances 0.000 description 6
• 229910000104 sodium hydride Inorganic materials 0.000 description 6
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 6
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