ES2968881T3 - Derivados de ácidos biliares fluorados - Google Patents

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Publication number

ES2968881T3

ES2968881T3 ES19748933T ES19748933T ES2968881T3 ES 2968881 T3 ES2968881 T3 ES 2968881T3 ES 19748933 T ES19748933 T ES 19748933T ES 19748933 T ES19748933 T ES 19748933T ES 2968881 T3 ES2968881 T3 ES 2968881T3

Authority

ES

Spain

Prior art keywords

compound

ethyl

cholan

fluoro

general formula

Prior art date

2018-07-30

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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• 239000003613 bile acid Substances 0.000 title description 16
• 150000001875 compounds Chemical class 0.000 claims abstract description 255
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims abstract description 43
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims abstract description 32
• 238000011282 treatment Methods 0.000 claims abstract description 28
• 206010016654 Fibrosis Diseases 0.000 claims abstract description 21
• 230000004761 fibrosis Effects 0.000 claims abstract description 20
• 208000022309 Alcoholic Liver disease Diseases 0.000 claims abstract description 8
• 208000005176 Hepatitis C Diseases 0.000 claims abstract description 8
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims abstract description 7
• 208000033222 Biliary cirrhosis primary Diseases 0.000 claims abstract description 7
• 208000012654 Primary biliary cholangitis Diseases 0.000 claims abstract description 7
• 206010008609 Cholangitis sclerosing Diseases 0.000 claims abstract description 6
• 206010008635 Cholestasis Diseases 0.000 claims abstract description 6
• 206010010317 Congenital absence of bile ducts Diseases 0.000 claims abstract description 6
• 206010067125 Liver injury Diseases 0.000 claims abstract description 6
• 201000005271 biliary atresia Diseases 0.000 claims abstract description 6
• 231100000234 hepatic damage Toxicity 0.000 claims abstract description 6
• 208000010710 hepatitis C virus infection Diseases 0.000 claims abstract description 6
• 230000008818 liver damage Effects 0.000 claims abstract description 6
• 201000000742 primary sclerosing cholangitis Diseases 0.000 claims abstract description 6
• 208000010157 sclerosing cholangitis Diseases 0.000 claims abstract description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 65
• 238000000034 method Methods 0.000 claims description 49
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 24
• 125000000217 alkyl group Chemical group 0.000 claims description 20
• GHDLZGOOOLEJKI-UHFFFAOYSA-N benzenesulfonylurea Chemical compound NC(=O)NS(=O)(=O)C1=CC=CC=C1 GHDLZGOOOLEJKI-UHFFFAOYSA-N 0.000 claims description 20
• 229940125782 compound 2 Drugs 0.000 claims description 20
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 claims description 19
• 229940126543 compound 14 Drugs 0.000 claims description 19
• 125000001424 substituent group Chemical group 0.000 claims description 18
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
• 229940124530 sulfonamide Drugs 0.000 claims description 15
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 14
• 125000002947 alkylene group Chemical group 0.000 claims description 13
• 210000004185 liver Anatomy 0.000 claims description 13
• 150000003456 sulfonamides Chemical class 0.000 claims description 13
• 150000003839 salts Chemical class 0.000 claims description 12
• 239000013543 active substance Substances 0.000 claims description 10
• 125000003118 aryl group Chemical group 0.000 claims description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• 201000010099 disease Diseases 0.000 claims description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
• 125000004450 alkenylene group Chemical group 0.000 claims description 8
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 8
• 125000001188 haloalkyl group Chemical group 0.000 claims description 8
• 125000005843 halogen group Chemical group 0.000 claims description 8
• 125000005647 linker group Chemical group 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 125000001072 heteroaryl group Chemical group 0.000 claims description 7
• 229910052739 hydrogen Inorganic materials 0.000 claims description 7
• 229910052757 nitrogen Inorganic materials 0.000 claims description 7
• 229910052731 fluorine Inorganic materials 0.000 claims description 6
• 125000001153 fluoro group Chemical group F* 0.000 claims description 6
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 6
• 230000000155 isotopic effect Effects 0.000 claims description 6
• 238000002360 preparation method Methods 0.000 claims description 6
• 210000000936 intestine Anatomy 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• 230000002265 prevention Effects 0.000 claims description 5
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 claims description 4
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims description 4
• UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 claims description 4
• LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 claims description 4
• 239000003054 catalyst Substances 0.000 claims description 4
• 229940125904 compound 1 Drugs 0.000 claims description 4
• 229940125797 compound 12 Drugs 0.000 claims description 4
• 229940126214 compound 3 Drugs 0.000 claims description 4
• 229940125898 compound 5 Drugs 0.000 claims description 4
• 210000003734 kidney Anatomy 0.000 claims description 4
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 claims description 3
• WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 claims description 3
• IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 claims description 3
• ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 claims description 3
• 229940126657 Compound 17 Drugs 0.000 claims description 3
• 208000001145 Metabolic Syndrome Diseases 0.000 claims description 3
• OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 claims description 3
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 3
• 229940125773 compound 10 Drugs 0.000 claims description 3
• 229940125758 compound 15 Drugs 0.000 claims description 3
• 229940126142 compound 16 Drugs 0.000 claims description 3
• 229940125810 compound 20 Drugs 0.000 claims description 3
• 229940126086 compound 21 Drugs 0.000 claims description 3
• 229940126208 compound 22 Drugs 0.000 claims description 3
• 230000006378 damage Effects 0.000 claims description 3
• 229940079593 drug Drugs 0.000 claims description 3
• 208000028774 intestinal disease Diseases 0.000 claims description 3
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims description 3
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 claims description 3
• YKFCISHFRZHKHY-NGQGLHOPSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;trihydrate Chemical compound O.O.O.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 YKFCISHFRZHKHY-NGQGLHOPSA-N 0.000 claims description 2
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
• 206010053684 Cerebrohepatorenal syndrome Diseases 0.000 claims description 2
• 206010010356 Congenital anomaly Diseases 0.000 claims description 2
• 208000027205 Congenital disease Diseases 0.000 claims description 2
• 208000029767 Congenital, Hereditary, and Neonatal Diseases and Abnormalities Diseases 0.000 claims description 2
• 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 2
• 208000015872 Gaucher disease Diseases 0.000 claims description 2
• 208000022461 Glomerular disease Diseases 0.000 claims description 2
• 206010018364 Glomerulonephritis Diseases 0.000 claims description 2
• 208000018565 Hemochromatosis Diseases 0.000 claims description 2
• 208000002972 Hepatolenticular Degeneration Diseases 0.000 claims description 2
• 206010020772 Hypertension Diseases 0.000 claims description 2
• 206010072877 Intestinal fibrosis Diseases 0.000 claims description 2
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
• 208000030601 Parasitic Liver disease Diseases 0.000 claims description 2
• JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 claims description 2
• 208000018839 Wilson disease Diseases 0.000 claims description 2
• 201000004525 Zellweger Syndrome Diseases 0.000 claims description 2
• 208000036813 Zellweger spectrum disease Diseases 0.000 claims description 2
• 229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 claims description 2
• ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 claims description 2
• 229960001076 chlorpromazine Drugs 0.000 claims description 2
• 239000007822 coupling agent Substances 0.000 claims description 2
• 208000033679 diabetic kidney disease Diseases 0.000 claims description 2
• 208000007345 glycogen storage disease Diseases 0.000 claims description 2
• 208000006454 hepatitis Diseases 0.000 claims description 2
• 231100000283 hepatitis Toxicity 0.000 claims description 2
• 208000002672 hepatitis B Diseases 0.000 claims description 2
• 230000001631 hypertensive effect Effects 0.000 claims description 2
• 208000015181 infectious disease Diseases 0.000 claims description 2
• 201000006334 interstitial nephritis Diseases 0.000 claims description 2
• 229960003350 isoniazid Drugs 0.000 claims description 2
• QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 claims description 2
• 229960000485 methotrexate Drugs 0.000 claims description 2
• 201000009925 nephrosclerosis Diseases 0.000 claims description 2
• 208000030761 polycystic kidney disease Diseases 0.000 claims description 2
• 229960005371 tolbutamide Drugs 0.000 claims description 2
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 claims 1
• JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 claims 1
• 102100038495 Bile acid receptor Human genes 0.000 abstract description 57
• 101000603876 Homo sapiens Bile acid receptor Proteins 0.000 abstract description 57
• 239000000556 agonist Substances 0.000 abstract description 15
• 230000006806 disease prevention Effects 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
• 238000006243 chemical reaction Methods 0.000 description 72
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 66
• 238000005160 1H NMR spectroscopy Methods 0.000 description 58
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
• 239000000243 solution Substances 0.000 description 56
• 238000004293 19F NMR spectroscopy Methods 0.000 description 46
• 235000019439 ethyl acetate Nutrition 0.000 description 46
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 44
• 239000012074 organic phase Substances 0.000 description 40
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
• 210000004027 cell Anatomy 0.000 description 39
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• ZXERDUOLZKYMJM-ZWECCWDJSA-N obeticholic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)CCC(O)=O)CC[C@H]21 ZXERDUOLZKYMJM-ZWECCWDJSA-N 0.000 description 31
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• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
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• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
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• -1 3,3-difluorocholan-24-oic acid Chemical compound 0.000 description 18
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• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 18
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 18
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
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