IL228707A - Tetrahydroquinoline history used as bromodomain inhibitors - Google Patents

Info

Publication number

IL228707A

IL228707A IL228707A IL22870713A IL228707A IL 228707 A IL228707 A IL 228707A IL 228707 A IL228707 A IL 228707A IL 22870713 A IL22870713 A IL 22870713A IL 228707 A IL228707 A IL 228707A

Authority

IL

Israel

Prior art keywords

methyl

mmol

compound

amino

acetyl

Prior art date

2011-04-21

Links

• Espacenet
• Global Dossier
• Discuss

• 102000001805 Bromodomains Human genes 0.000 title description 36
• 108050009021 Bromodomains Proteins 0.000 title description 34
• 239000003112 inhibitor Substances 0.000 title description 17
• 125000000147 tetrahydroquinolinyl group Chemical class N1(CCCC2=CC=CC=C12)* 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims description 154
• 150000003839 salts Chemical class 0.000 claims description 91
• -1 5-cyanopyridin-2-yl Chemical group 0.000 claims description 46
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 29
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 11
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 11
• 235000001968 nicotinic acid Nutrition 0.000 claims description 10
• 239000011664 nicotinic acid Substances 0.000 claims description 10
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
• 229910052736 halogen Inorganic materials 0.000 claims description 6
• 150000002367 halogens Chemical class 0.000 claims description 6
• 125000001424 substituent group Chemical group 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• 125000000623 heterocyclic group Chemical group 0.000 claims description 3
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 5
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
• 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
• 239000000203 mixture Substances 0.000 description 121
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 86
• 235000002639 sodium chloride Nutrition 0.000 description 84
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
• 239000000243 solution Substances 0.000 description 60
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 57
• 239000000543 intermediate Substances 0.000 description 57
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
• 238000000034 method Methods 0.000 description 49
• 235000019439 ethyl acetate Nutrition 0.000 description 46
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 46
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 44
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
• 238000002360 preparation method Methods 0.000 description 41
• 239000002904 solvent Substances 0.000 description 39
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 38
• 239000007787 solid Substances 0.000 description 35
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 28
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 27
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• 239000010410 layer Substances 0.000 description 27
• 239000008194 pharmaceutical composition Substances 0.000 description 27
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 25
• 239000011541 reaction mixture Substances 0.000 description 25
• 238000011282 treatment Methods 0.000 description 25
• 230000002829 reductive effect Effects 0.000 description 23
• 229910052757 nitrogen Inorganic materials 0.000 description 22
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 22
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 21
• 239000012267 brine Substances 0.000 description 20
• 238000001819 mass spectrum Methods 0.000 description 20
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
• 210000004027 cell Anatomy 0.000 description 18
• 201000010099 disease Diseases 0.000 description 18
• 239000012044 organic layer Substances 0.000 description 18
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
• 239000000725 suspension Substances 0.000 description 18
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
• 239000002253 acid Substances 0.000 description 16
• 229940125763 bromodomain inhibitor Drugs 0.000 description 16
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 239000003814 drug Substances 0.000 description 15
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
• 239000003921 oil Substances 0.000 description 15
• 238000012856 packing Methods 0.000 description 15
• 239000000843 powder Substances 0.000 description 15
• 108090000623 proteins and genes Proteins 0.000 description 15
• 235000019198 oils Nutrition 0.000 description 14
• 108010033040 Histones Proteins 0.000 description 13
• 239000002585 base Substances 0.000 description 13
• 239000012530 fluid Substances 0.000 description 13
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
• 238000006243 chemical reaction Methods 0.000 description 12
• 239000006260 foam Substances 0.000 description 12
• 235000019253 formic acid Nutrition 0.000 description 12
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
• 229910000027 potassium carbonate Inorganic materials 0.000 description 12
• 239000003643 water by type Substances 0.000 description 12
• 239000000047 product Substances 0.000 description 11
• GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 10
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 10
• 102100033641 Bromodomain-containing protein 2 Human genes 0.000 description 10
• 101000871850 Homo sapiens Bromodomain-containing protein 2 Proteins 0.000 description 10
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
• 239000008346 aqueous phase Substances 0.000 description 10
• 238000009472 formulation Methods 0.000 description 10
• 238000004128 high performance liquid chromatography Methods 0.000 description 10
• 102000004169 proteins and genes Human genes 0.000 description 10
• 238000000746 purification Methods 0.000 description 10
• 239000003826 tablet Substances 0.000 description 10
• 238000012360 testing method Methods 0.000 description 10
• 102100029895 Bromodomain-containing protein 4 Human genes 0.000 description 9
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
• UXRDAJMOOGEIAQ-CKOZHMEPSA-N [(8r,9s,10r,13s,14s,17r)-17-acetyl-10,13-dimethyl-16-methylidene-3-oxo-1,2,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1=CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(=C)[C@](OC(=O)C)(C(C)=O)[C@@]1(C)CC2 UXRDAJMOOGEIAQ-CKOZHMEPSA-N 0.000 description 9
• 235000011054 acetic acid Nutrition 0.000 description 9
• 238000010828 elution Methods 0.000 description 9
• 230000008569 process Effects 0.000 description 9
• 235000011121 sodium hydroxide Nutrition 0.000 description 9
• 238000000825 ultraviolet detection Methods 0.000 description 9
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 8
• 108091005625 BRD4 Proteins 0.000 description 8
• 102100033642 Bromodomain-containing protein 3 Human genes 0.000 description 8
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 8
• 101000871851 Homo sapiens Bromodomain-containing protein 3 Proteins 0.000 description 8
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
• 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 230000001154 acute effect Effects 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• 108090000765 processed proteins & peptides Proteins 0.000 description 8
• 239000012453 solvate Substances 0.000 description 8
• 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 8
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 8
• 239000013543 active substance Substances 0.000 description 7
• 238000003556 assay Methods 0.000 description 7
• 239000000872 buffer Substances 0.000 description 7
• 238000004587 chromatography analysis Methods 0.000 description 7
• 239000012074 organic phase Substances 0.000 description 7
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].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.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 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 7
• 239000000546 pharmaceutical excipient Substances 0.000 description 7
• 239000003981 vehicle Substances 0.000 description 7
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 6
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
• 239000007995 HEPES buffer Substances 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• 239000000443 aerosol Substances 0.000 description 6
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 210000003483 chromatin Anatomy 0.000 description 6
• 239000003085 diluting agent Substances 0.000 description 6
• 239000000499 gel Substances 0.000 description 6
• 235000011167 hydrochloric acid Nutrition 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 239000003446 ligand Substances 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
• 239000000377 silicon dioxide Substances 0.000 description 6
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
• 229940124597 therapeutic agent Drugs 0.000 description 6
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
• ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 5
• 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 5
• 108010077544 Chromatin Proteins 0.000 description 5
• 102000006947 Histones Human genes 0.000 description 5
• 241001465754 Metazoa Species 0.000 description 5
• 206010028980 Neoplasm Diseases 0.000 description 5
• 206010040047 Sepsis Diseases 0.000 description 5
• 229920002472 Starch Polymers 0.000 description 5
• 235000012538 ammonium bicarbonate Nutrition 0.000 description 5
• 239000001099 ammonium carbonate Substances 0.000 description 5
• 239000011230 binding agent Substances 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
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• 238000000576 coating method Methods 0.000 description 5
• 239000006071 cream Substances 0.000 description 5
• 239000002552 dosage form Substances 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• 238000003818 flash chromatography Methods 0.000 description 5
• 238000000198 fluorescence anisotropy Methods 0.000 description 5
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 5
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
• 239000003607 modifier Substances 0.000 description 5
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• 229920006395 saturated elastomer Chemical group 0.000 description 5
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• 235000019698 starch Nutrition 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• 208000011580 syndromic disease Diseases 0.000 description 5
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
• 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 4
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
• UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 4
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
• 108010010803 Gelatin Proteins 0.000 description 4
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
• 206010033645 Pancreatitis Diseases 0.000 description 4
• 206010040070 Septic Shock Diseases 0.000 description 4
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
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• 150000001412 amines Chemical class 0.000 description 4
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• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
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• 239000005711 Benzoic acid Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
• 208000037487 Endotoxemia Diseases 0.000 description 3
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
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• 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 3
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
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