ES2389737T3 - Análogos de ácidos nucleicos bicíclicos modificados en 5' - Google Patents

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Publication number

ES2389737T3

ES2389737T3 ES07797414T ES07797414T ES2389737T3 ES 2389737 T3 ES2389737 T3 ES 2389737T3 ES 07797414 T ES07797414 T ES 07797414T ES 07797414 T ES07797414 T ES 07797414T ES 2389737 T3 ES2389737 T3 ES 2389737T3

Authority

ES

Spain

Prior art keywords

substituted

compound

oligomeric compound

group

compound according

Prior art date

2006-05-11

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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• -1 modified bicyclic nucleic acid Chemical class 0.000 title claims abstract description 166
• 102000039446 nucleic acids Human genes 0.000 title claims description 38
• 108020004707 nucleic acids Proteins 0.000 title claims description 38
• 239000002777 nucleoside Substances 0.000 claims abstract description 124
• 125000001424 substituent group Chemical group 0.000 claims abstract description 46
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 38
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 35
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 30
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 27
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 27
• 125000006239 protecting group Chemical group 0.000 claims abstract description 18
• 150000008300 phosphoramidites Chemical class 0.000 claims abstract description 17
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 14
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 14
• 125000002252 acyl group Chemical group 0.000 claims abstract description 13
• 125000002743 phosphorus functional group Chemical group 0.000 claims abstract description 12
• 229910052698 phosphorus Inorganic materials 0.000 claims abstract description 10
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
• 150000002367 halogens Chemical class 0.000 claims abstract description 8
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims abstract description 7
• 239000011574 phosphorus Substances 0.000 claims abstract description 7
• 229910019142 PO4 Inorganic materials 0.000 claims abstract description 6
• 239000010452 phosphate Substances 0.000 claims abstract description 3
• 150000001875 compounds Chemical class 0.000 claims description 281
• 108091034117 Oligonucleotide Proteins 0.000 claims description 70
• 125000003835 nucleoside group Chemical group 0.000 claims description 67
• 238000000034 method Methods 0.000 claims description 63
• 230000027455 binding Effects 0.000 claims description 37
• 230000014509 gene expression Effects 0.000 claims description 34
• 150000007523 nucleic acids Chemical class 0.000 claims description 34
• 150000003833 nucleoside derivatives Chemical class 0.000 claims description 27
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
• 125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 17
• 239000002773 nucleotide Substances 0.000 claims description 16
• 125000003729 nucleotide group Chemical group 0.000 claims description 16
• 239000000178 monomer Substances 0.000 claims description 15
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 14
• 150000004713 phosphodiesters Chemical class 0.000 claims description 13
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 9
• 238000001727 in vivo Methods 0.000 claims description 9
• 125000000304 alkynyl group Chemical group 0.000 claims description 8
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 8
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
• 229920000642 polymer Polymers 0.000 claims description 7
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 6
• LVUCQZQLDPFLBJ-UHFFFAOYSA-N (2-cyano-3-methyl-2-propan-2-ylbutyl)peroxyphosphonamidous acid Chemical group CC(C)C(C(C)C)(C#N)COOP(N)O LVUCQZQLDPFLBJ-UHFFFAOYSA-N 0.000 claims description 4
• 241001465754 Metazoa Species 0.000 claims description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
• 238000000338 in vitro Methods 0.000 claims description 4
• 230000002401 inhibitory effect Effects 0.000 claims description 4
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
• 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims description 4
• 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 claims description 3
• 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
• 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 3
• FAQJJMHZNSSFSM-UHFFFAOYSA-N phenylglyoxylic acid Chemical compound OC(=O)C(=O)C1=CC=CC=C1 FAQJJMHZNSSFSM-UHFFFAOYSA-N 0.000 claims description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
• UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 claims description 2
• YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 claims description 2
• 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 claims description 2
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 2
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 2
• FGIVSGPRGVABAB-UHFFFAOYSA-N fluoren-9-ylmethyl hydrogen carbonate Chemical compound C1=CC=C2C(COC(=O)O)C3=CC=CC=C3C2=C1 FGIVSGPRGVABAB-UHFFFAOYSA-N 0.000 claims 1
• 125000006728 (C1-C6) alkynyl group Chemical group 0.000 abstract 1
• 230000001681 protective effect Effects 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 174
• 238000006243 chemical reaction Methods 0.000 description 132
• 238000002360 preparation method Methods 0.000 description 110
• 235000019439 ethyl acetate Nutrition 0.000 description 87
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 86
• 239000000243 solution Substances 0.000 description 85
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 80
• 238000003756 stirring Methods 0.000 description 64
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
• 239000012267 brine Substances 0.000 description 62
• 238000000746 purification Methods 0.000 description 62
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 62
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
• 239000007832 Na2SO4 Substances 0.000 description 55
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 55
• 229910052938 sodium sulfate Inorganic materials 0.000 description 55
• 235000011152 sodium sulphate Nutrition 0.000 description 55
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 48
• 239000000203 mixture Substances 0.000 description 47
• 210000004027 cell Anatomy 0.000 description 46
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
• 239000012044 organic layer Substances 0.000 description 38
• 229910052681 coesite Inorganic materials 0.000 description 37
• 229910052906 cristobalite Inorganic materials 0.000 description 37
• 239000000377 silicon dioxide Substances 0.000 description 37
• 235000012239 silicon dioxide Nutrition 0.000 description 37
• 229910052682 stishovite Inorganic materials 0.000 description 37
• 229910052905 tridymite Inorganic materials 0.000 description 37
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 36
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
• 238000004440 column chromatography Methods 0.000 description 36
• 239000007787 solid Substances 0.000 description 35
• 108090000623 proteins and genes Proteins 0.000 description 32
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 30
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 29
• 235000000346 sugar Nutrition 0.000 description 28
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
• 239000000523 sample Substances 0.000 description 26
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
• 229920002477 rna polymer Polymers 0.000 description 24
• 238000011282 treatment Methods 0.000 description 23
• 125000004432 carbon atom Chemical group C* 0.000 description 22
• 101150006308 botA gene Proteins 0.000 description 21
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
• 125000000217 alkyl group Chemical group 0.000 description 18
• 230000015572 biosynthetic process Effects 0.000 description 18
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 18
• 238000003786 synthesis reaction Methods 0.000 description 18
• 238000004458 analytical method Methods 0.000 description 17
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• 229910052757 nitrogen Inorganic materials 0.000 description 17
• 239000002243 precursor Substances 0.000 description 17
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 16
• 230000000692 anti-sense effect Effects 0.000 description 16
• 238000003752 polymerase chain reaction Methods 0.000 description 16
• 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 14
• 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 14
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
• 125000003118 aryl group Chemical group 0.000 description 14
• 125000005842 heteroatom Chemical group 0.000 description 14
• 108020004999 messenger RNA Proteins 0.000 description 14
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• 229910052799 carbon Inorganic materials 0.000 description 13
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• 125000001072 heteroaryl group Chemical group 0.000 description 13
• 102000004169 proteins and genes Human genes 0.000 description 13
• 230000002829 reductive effect Effects 0.000 description 13
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
• 108020004414 DNA Proteins 0.000 description 12
• 102000053602 DNA Human genes 0.000 description 12
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 12
• 125000001931 aliphatic group Chemical group 0.000 description 12
• 239000000725 suspension Substances 0.000 description 12
• 238000005160 1H NMR spectroscopy Methods 0.000 description 11
• 125000000524 functional group Chemical group 0.000 description 11
• 229910052739 hydrogen Inorganic materials 0.000 description 11
• 150000008163 sugars Chemical class 0.000 description 11
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
• 241000699670 Mus sp. Species 0.000 description 10
• LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 10
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• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
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• 125000004122 cyclic group Chemical group 0.000 description 9
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• 125000003342 alkenyl group Chemical group 0.000 description 8
• 125000003710 aryl alkyl group Chemical group 0.000 description 8
• 238000001514 detection method Methods 0.000 description 8
• WGABOZPQOOZAOI-UHFFFAOYSA-N 2-[4-[[(3,5-dimethoxy-4-methylbenzoyl)-(3-phenylpropyl)amino]methyl]phenyl]acetic acid Chemical compound COC1=C(C)C(OC)=CC(C(=O)N(CCCC=2C=CC=CC=2)CC=2C=CC(CC(O)=O)=CC=2)=C1 WGABOZPQOOZAOI-UHFFFAOYSA-N 0.000 description 7
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• 238000012360 testing method Methods 0.000 description 7
• 210000001519 tissue Anatomy 0.000 description 7
• DPRJPRMZJGWLHY-HNGSOEQISA-N (e,3r,5s)-7-[5-(4-fluorophenyl)-3-propan-2-yl-1-pyrazin-2-ylpyrazol-4-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound OC(=O)C[C@H](O)C[C@H](O)/C=C/C=1C(C(C)C)=NN(C=2N=CC=NC=2)C=1C1=CC=C(F)C=C1 DPRJPRMZJGWLHY-HNGSOEQISA-N 0.000 description 6
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 6
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