CA2712750A1 - Aldh-2 inhibitors in the treatment of addiction - Google Patents

Info

Publication number

CA2712750A1

CA2712750A1 CA2712750A CA2712750A CA2712750A1 CA 2712750 A1 CA2712750 A1 CA 2712750A1 CA 2712750 A CA2712750 A CA 2712750A CA 2712750 A CA2712750 A CA 2712750A CA 2712750 A1 CA2712750 A1 CA 2712750A1

Authority

CA

Canada

Prior art keywords

phenyl

chromen

hydroxyphenyl

compound

methoxy

Prior art date

2008-01-24

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 206010012335 Dependence Diseases 0.000 title claims abstract description 18
• 239000003112 inhibitor Substances 0.000 title abstract description 10
• 238000011282 treatment Methods 0.000 title description 22
• -1 amphetamines Chemical compound 0.000 claims abstract description 126
• ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims abstract description 76
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 68
• 229960003920 cocaine Drugs 0.000 claims abstract description 38
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims abstract description 23
• 229960002715 nicotine Drugs 0.000 claims abstract description 23
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims abstract description 23
• 239000003795 chemical substances by application Substances 0.000 claims abstract description 17
• 241000124008 Mammalia Species 0.000 claims abstract description 7
• 150000001875 compounds Chemical class 0.000 claims description 303
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 100
• 125000000217 alkyl group Chemical group 0.000 claims description 94
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 66
• 125000001072 heteroaryl group Chemical group 0.000 claims description 64
• 239000001257 hydrogen Substances 0.000 claims description 63
• 229910052739 hydrogen Inorganic materials 0.000 claims description 63
• 125000001424 substituent group Chemical group 0.000 claims description 58
• 125000003118 aryl group Chemical group 0.000 claims description 57
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 56
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 48
• 229910052760 oxygen Inorganic materials 0.000 claims description 41
• 238000000034 method Methods 0.000 claims description 40
• 125000003545 alkoxy group Chemical group 0.000 claims description 39
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 39
• 239000001301 oxygen Substances 0.000 claims description 39
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 38
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 33
• 125000000623 heterocyclic group Chemical group 0.000 claims description 31
• 229910052736 halogen Inorganic materials 0.000 claims description 27
• 150000002367 halogens Chemical group 0.000 claims description 27
• 125000002947 alkylene group Chemical group 0.000 claims description 25
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
• 125000003342 alkenyl group Chemical group 0.000 claims description 23
• 125000000304 alkynyl group Chemical group 0.000 claims description 20
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
• YYOOFJZTRCPVFD-UHFFFAOYSA-N 3-[[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]oxymethyl]benzoic acid Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(O)=O)=CC=C2C1=O YYOOFJZTRCPVFD-UHFFFAOYSA-N 0.000 claims description 13
• 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 6
• 125000004193 piperazinyl group Chemical group 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• 239000011593 sulfur Chemical group 0.000 claims description 6
• NSJKIAFITKUSDQ-UHFFFAOYSA-N 2-morpholin-4-ylethyl 3-[[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=COC2=CC(OCC=3C=C(C=CC=3)C(=O)OCCN3CCOCC3)=CC=C2C1=O NSJKIAFITKUSDQ-UHFFFAOYSA-N 0.000 claims description 5
• 101100240527 Caenorhabditis elegans nhr-22 gene Proteins 0.000 claims description 4
• ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 229940127240 opiate Drugs 0.000 claims description 4
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
• 229910007161 Si(CH3)3 Inorganic materials 0.000 claims description 3
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims description 3
• PWLLITGVGRJVJF-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)ethyl 3-[[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound C1CN(C)CCN1CCOC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(NS(C)(=O)=O)=CC=4)=CO3)=O)=CC=2)=C1 PWLLITGVGRJVJF-UHFFFAOYSA-N 0.000 claims description 2
• DSXLGECROFSXMB-UHFFFAOYSA-N 2-(dimethylamino)ethyl 3-[[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound CN(C)CCOC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(NS(C)(=O)=O)=CC=4)=CO3)=O)=CC=2)=C1 DSXLGECROFSXMB-UHFFFAOYSA-N 0.000 claims description 2
• VFKSORDIMAUFFL-UHFFFAOYSA-N 4-(oxathian-3-yl)morpholine Chemical compound O1SC(CCC1)N1CCOCC1 VFKSORDIMAUFFL-UHFFFAOYSA-N 0.000 claims description 2
• LRNIOOQOHZTKJY-UHFFFAOYSA-N ethyl 3-[[3-[4-(methanesulfonamido)phenyl]-4-oxochromen-7-yl]oxymethyl]benzoate Chemical compound CCOC(=O)C1=CC=CC(COC=2C=C3C(C(C(C=4C=CC(NS(C)(=O)=O)=CC=4)=CO3)=O)=CC=2)=C1 LRNIOOQOHZTKJY-UHFFFAOYSA-N 0.000 claims description 2
• 125000003386 piperidinyl group Chemical group 0.000 claims description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 claims description 2
• 125000005505 thiomorpholino group Chemical group 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims 9
• 150000002431 hydrogen Chemical group 0.000 claims 7
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 3
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 3
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
• HTFFABIIOAKIBH-UHFFFAOYSA-N diazinane Chemical compound C1CCNNC1 HTFFABIIOAKIBH-UHFFFAOYSA-N 0.000 claims 1
• 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 claims 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
• 125000002632 imidazolidinyl group Chemical group 0.000 claims 1
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
• 125000002950 monocyclic group Chemical group 0.000 claims 1
• 125000005310 triazolidinyl group Chemical group N1(NNCC1)* 0.000 claims 1
• 239000003814 drug Substances 0.000 abstract description 18
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 abstract description 14
• 229940079593 drug Drugs 0.000 abstract description 14
• 229960003638 dopamine Drugs 0.000 abstract description 7
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 abstract description 4
• 150000002515 isoflavone derivatives Chemical class 0.000 abstract description 3
• 229960005181 morphine Drugs 0.000 abstract description 2
• 229930012930 isoflavone derivative Natural products 0.000 abstract 1
• 230000005764 inhibitory process Effects 0.000 description 202
• 239000000203 mixture Substances 0.000 description 141
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 135
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 100
• 238000006243 chemical reaction Methods 0.000 description 97
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 80
• 238000002360 preparation method Methods 0.000 description 76
• 229910001868 water Inorganic materials 0.000 description 73
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 70
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 61
• 239000002904 solvent Substances 0.000 description 59
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 58
• 239000000243 solution Substances 0.000 description 57
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 56
• OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical compound C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 description 55
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 52
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 51
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
• 235000019439 ethyl acetate Nutrition 0.000 description 49
• 230000002829 reductive effect Effects 0.000 description 46
• 239000000725 suspension Substances 0.000 description 37
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 32
• 239000000741 silica gel Substances 0.000 description 31
• 229910002027 silica gel Inorganic materials 0.000 description 31
• 229960001866 silicon dioxide Drugs 0.000 description 31
• 241000700159 Rattus Species 0.000 description 30
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 30
• ZQSIJRDFPHDXIC-UHFFFAOYSA-N daidzein Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(O)=CC=C2C1=O ZQSIJRDFPHDXIC-UHFFFAOYSA-N 0.000 description 30
• 239000000047 product Substances 0.000 description 30
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 29
• 239000011541 reaction mixture Substances 0.000 description 28
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 27
• 239000004480 active ingredient Substances 0.000 description 27
• 239000007787 solid Substances 0.000 description 26
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
• 150000001412 amines Chemical class 0.000 description 22
• 125000004181 carboxyalkyl group Chemical group 0.000 description 22
• 229910052938 sodium sulfate Inorganic materials 0.000 description 22
• 235000011152 sodium sulphate Nutrition 0.000 description 22
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 21
• 239000000843 powder Substances 0.000 description 21
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 20
• 125000004432 carbon atom Chemical group C* 0.000 description 20
• 238000003756 stirring Methods 0.000 description 20
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
• 239000003826 tablet Substances 0.000 description 19
• 230000000694 effects Effects 0.000 description 18
• 239000004615 ingredient Substances 0.000 description 18
• 238000012360 testing method Methods 0.000 description 18
• 102000005369 Aldehyde Dehydrogenase Human genes 0.000 description 17
• 108020002663 Aldehyde Dehydrogenase Proteins 0.000 description 17
• 238000005481 NMR spectroscopy Methods 0.000 description 17
• 239000012267 brine Substances 0.000 description 17
• 125000000392 cycloalkenyl group Chemical group 0.000 description 17
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
• 239000012442 inert solvent Substances 0.000 description 16
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
• 241001465754 Metazoa Species 0.000 description 15
• 235000013305 food Nutrition 0.000 description 15
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 15
• 238000005160 1H NMR spectroscopy Methods 0.000 description 14
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 14
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
• 239000002585 base Substances 0.000 description 14
• 239000012043 crude product Substances 0.000 description 14
• 239000000706 filtrate Substances 0.000 description 14
• 238000001914 filtration Methods 0.000 description 14
• 125000005843 halogen group Chemical group 0.000 description 14
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 13
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 13
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 13
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 13
• 239000012044 organic layer Substances 0.000 description 13
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
• 150000003839 salts Chemical class 0.000 description 12
• 239000005711 Benzoic acid Substances 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 11
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
• 238000003818 flash chromatography Methods 0.000 description 11
• 229910052757 nitrogen Inorganic materials 0.000 description 11
• 239000007858 starting material Substances 0.000 description 11
• 125000000547 substituted alkyl group Chemical group 0.000 description 11
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
• 125000004414 alkyl thio group Chemical group 0.000 description 10
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 10
• 238000004440 column chromatography Methods 0.000 description 10
• 239000007924 injection Substances 0.000 description 10
• 238000002347 injection Methods 0.000 description 10
• 238000012549 training Methods 0.000 description 10
• 229930194542 Keto Natural products 0.000 description 9
• 125000002252 acyl group Chemical group 0.000 description 9
• 125000004442 acylamino group Chemical group 0.000 description 9
• 125000004423 acyloxy group Chemical group 0.000 description 9
• 125000005110 aryl thio group Chemical group 0.000 description 9
• 125000004104 aryloxy group Chemical group 0.000 description 9
• 235000007240 daidzein Nutrition 0.000 description 9
• 125000005553 heteroaryloxy group Chemical group 0.000 description 9
• 125000000468 ketone group Chemical group 0.000 description 9
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 9
• 150000003573 thiols Chemical class 0.000 description 9
• 239000007832 Na2SO4 Substances 0.000 description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 125000000033 alkoxyamino group Chemical group 0.000 description 8
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 8
• 125000006598 aminocarbonylamino group Chemical group 0.000 description 8
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 8
• 239000007864 aqueous solution Substances 0.000 description 8
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• 229910052681 coesite Inorganic materials 0.000 description 8
• 229910052906 cristobalite Inorganic materials 0.000 description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
• 238000001035 drying Methods 0.000 description 8
• 239000011521 glass Substances 0.000 description 8
• 125000005368 heteroarylthio group Chemical group 0.000 description 8
• 125000004470 heterocyclooxy group Chemical group 0.000 description 8
• 125000004468 heterocyclylthio group Chemical group 0.000 description 8
• 238000004128 high performance liquid chromatography Methods 0.000 description 8
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 8
• 125000004464 hydroxyphenyl group Chemical group 0.000 description 8
• 239000000546 pharmaceutical excipient Substances 0.000 description 8
• 229910000027 potassium carbonate Inorganic materials 0.000 description 8
• 238000001953 recrystallisation Methods 0.000 description 8
• 230000002787 reinforcement Effects 0.000 description 8
• 229910052682 stishovite Inorganic materials 0.000 description 8
• 229910052905 tridymite Inorganic materials 0.000 description 8
• GMTUGPYJRUMVTC-UHFFFAOYSA-N Daidzin Natural products OC(COc1ccc2C(=O)C(=COc2c1)c3ccc(O)cc3)C(O)C(O)C(O)C=O GMTUGPYJRUMVTC-UHFFFAOYSA-N 0.000 description 7
• KYQZWONCHDNPDP-UHFFFAOYSA-N Daidzoside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 KYQZWONCHDNPDP-UHFFFAOYSA-N 0.000 description 7
• 102000010909 Monoamine Oxidase Human genes 0.000 description 7
• 125000004429 atom Chemical group 0.000 description 7
• KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 7
• 230000008033 biological extinction Effects 0.000 description 7
• 238000004587 chromatography analysis Methods 0.000 description 7
• 239000012230 colorless oil Substances 0.000 description 7
• KYQZWONCHDNPDP-QNDFHXLGSA-N daidzein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 KYQZWONCHDNPDP-QNDFHXLGSA-N 0.000 description 7
• 201000010099 disease Diseases 0.000 description 7
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• 238000001802 infusion Methods 0.000 description 7
• 235000011181 potassium carbonates Nutrition 0.000 description 7
• 238000010898 silica gel chromatography Methods 0.000 description 7
• 239000000377 silicon dioxide Substances 0.000 description 7
• 235000012239 silicon dioxide Nutrition 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 238000012384 transportation and delivery Methods 0.000 description 7
• 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 7
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 6
• GEOFIVBSXPVRPE-UHFFFAOYSA-N 3-[3-[[3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxymethyl]-1,2,4-oxadiazol-5-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2ON=C(COC=3C=C4C(C(C(C=5C=CC(O)=CC=5)=CO4)=O)=CC=3)N=2)=C1 GEOFIVBSXPVRPE-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• 229920002472 Starch Polymers 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• 150000002430 hydrocarbons Chemical group 0.000 description 6
• 235000019359 magnesium stearate Nutrition 0.000 description 6
• 239000002609 medium Substances 0.000 description 6
• 239000008188 pellet Substances 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
• 238000012746 preparative thin layer chromatography Methods 0.000 description 6
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