HU199476B

HU199476B - Process for producing benzopyrano /and -thiopyrano/ pyridines and pharmaceutical compositions comprising such compounds

Process for producing benzopyrano /and -thiopyrano/ pyridines and pharmaceutical compositions comprising such compounds Download PDF

Info

Publication number: HU199476B
Authority: HU; Hungary
Prior art keywords: formula; alkyl; compound; ring; hydroxy
Prior art date: 1984-05-10

Application number

HU851751A

Other languages

English (en)

Hungarian (hu)

Other versions

HUT37939A (en

Inventor

Alan J Hutchison

Original Assignee

Ciba Geigy Ag

Priority date

1984-05-10

Filing date

1985-05-09

Publication date

1990-02-28

1985-05-09 Application filed by Ciba Geigy Ag filed Critical Ciba Geigy Ag

1986-03-28 Publication of HUT37939A publication Critical patent/HUT37939A/hu

1990-02-28 Publication of HU199476B publication Critical patent/HU199476B/hu

Links

150000001875 compounds Chemical class 0.000 title claims description 193
238000000034 method Methods 0.000 title claims description 64
230000008569 process Effects 0.000 title claims description 40
239000008194 pharmaceutical composition Substances 0.000 title claims description 9
150000003222 pyridines Chemical class 0.000 title 1
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 45
125000004423 acyloxy group Chemical group 0.000 claims abstract description 21
229910052760 oxygen Inorganic materials 0.000 claims abstract description 19
239000001301 oxygen Substances 0.000 claims abstract description 17
150000002367 halogens Chemical class 0.000 claims abstract description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 13
229910052736 halogen Inorganic materials 0.000 claims abstract description 10
150000003839 salts Chemical class 0.000 claims description 59
239000000243 solution Substances 0.000 claims description 53
-1 hydroxy, hydroxy Chemical group 0.000 claims description 46
239000000203 mixture Substances 0.000 claims description 46
125000001424 substituent group Chemical group 0.000 claims description 43
125000000217 alkyl group Chemical group 0.000 claims description 41
229910052739 hydrogen Inorganic materials 0.000 claims description 41
239000001257 hydrogen Substances 0.000 claims description 41
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 30
238000002360 preparation method Methods 0.000 claims description 29
239000007858 starting material Substances 0.000 claims description 29
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 24
150000002431 hydrogen Chemical class 0.000 claims description 23
238000006243 chemical reaction Methods 0.000 claims description 20
239000003638 chemical reducing agent Substances 0.000 claims description 20
230000002829 reductive effect Effects 0.000 claims description 20
125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 18
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 15
125000003545 alkoxy group Chemical group 0.000 claims description 14
229910052717 sulfur Chemical group 0.000 claims description 14
125000004043 oxo group Chemical group O=* 0.000 claims description 12
239000011593 sulfur Chemical group 0.000 claims description 12
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 10
125000000524 functional group Chemical group 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 8
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
125000005843 halogen group Chemical group 0.000 claims description 7
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
230000003287 optical effect Effects 0.000 claims description 7
239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 6
230000000701 neuroleptic effect Effects 0.000 claims description 6
239000002775 capsule Substances 0.000 claims description 5
239000003153 chemical reaction reagent Substances 0.000 claims description 5
239000003795 chemical substances by application Substances 0.000 claims description 5
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 5
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
239000003176 neuroleptic agent Substances 0.000 claims description 5
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
230000001430 anti-depressive effect Effects 0.000 claims description 4
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
150000002148 esters Chemical class 0.000 claims description 4
230000002452 interceptive effect Effects 0.000 claims description 4
229910052740 iodine Inorganic materials 0.000 claims description 4
239000011230 binding agent Substances 0.000 claims description 3
125000001589 carboacyl group Chemical group 0.000 claims description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
239000012948 isocyanate Substances 0.000 claims description 3
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
230000009257 reactivity Effects 0.000 claims description 3
239000000829 suppository Substances 0.000 claims description 3
BJMSUUATNLDQQZ-DGCLKSJQSA-N (4as,10br)-4-propyl-1,2,3,4a,5,10b-hexahydrochromeno[3,4-b]pyridin-7-ol Chemical compound C1=CC=C2[C@H]3CCCN(CCC)[C@@H]3COC2=C1O BJMSUUATNLDQQZ-DGCLKSJQSA-N 0.000 claims description 2
HBVFKJAKZKTZOB-BXKDBHETSA-N (4as,10br)-8-bromo-7-methoxy-4-methyl-1,2,3,4a,5,10b-hexahydrochromeno[3,4-b]pyridine Chemical compound C([C@@H]12)CCN(C)[C@@H]1COC1=C2C=CC(Br)=C1OC HBVFKJAKZKTZOB-BXKDBHETSA-N 0.000 claims description 2
125000002252 acyl group Chemical group 0.000 claims description 2
230000008030 elimination Effects 0.000 claims description 2
238000003379 elimination reaction Methods 0.000 claims description 2
230000026030 halogenation Effects 0.000 claims description 2
238000005658 halogenation reaction Methods 0.000 claims description 2
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
229920006395 saturated elastomer Polymers 0.000 claims description 2
238000009738 saturating Methods 0.000 claims description 2
125000003302 alkenyloxy group Chemical group 0.000 claims 2
238000005661 deetherification reaction Methods 0.000 claims 2
238000010511 deprotection reaction Methods 0.000 claims 2
239000003937 drug carrier Substances 0.000 claims 2
238000002347 injection Methods 0.000 claims 2
239000007924 injection Substances 0.000 claims 2
239000000314 lubricant Substances 0.000 claims 2
239000006187 pill Substances 0.000 claims 2
230000002195 synergetic effect Effects 0.000 claims 2
239000003826 tablet Substances 0.000 claims 2
HVJVYKLJJCMEFE-TZMCWYRMSA-N (4aS,10bR)-7-ethoxy-4,8-dimethyl-1,2,3,4a,5,10b-hexahydrochromeno[3,4-b]pyridine Chemical compound C(C)OC1=C(C=CC2=C1OC[C@H]1N(CCC[C@@H]12)C)C HVJVYKLJJCMEFE-TZMCWYRMSA-N 0.000 claims 1
RVISITFMLATVSR-DGCLKSJQSA-N (4aS,10bR)-7-methoxy-4,8-dimethyl-1,2,3,4a,5,10b-hexahydrochromeno[3,4-b]pyridine Chemical compound C([C@@H]12)CCN(C)[C@@H]1COC1=C2C=CC(C)=C1OC RVISITFMLATVSR-DGCLKSJQSA-N 0.000 claims 1
OOTZGPWBIFXGSV-TZMCWYRMSA-N (4aS,10bR)-8-ethyl-7-methoxy-4-methyl-1,2,3,4a,5,10b-hexahydrochromeno[3,4-b]pyridine Chemical compound C(C)C1=C(C2=C(C=C1)[C@@H]1[C@H](N(CCC1)C)CO2)OC OOTZGPWBIFXGSV-TZMCWYRMSA-N 0.000 claims 1
UKQPRJSOSVDGII-NWDGAFQWSA-N (4as,10br)-4-propyl-1,2,3,4a,5,10b-hexahydrochromeno[3,4-b]pyridin-10-ol Chemical compound C1=CC(O)=C2[C@H]3CCCN(CCC)[C@@H]3COC2=C1 UKQPRJSOSVDGII-NWDGAFQWSA-N 0.000 claims 1
239000002168 alkylating agent Substances 0.000 claims 1
229940100198 alkylating agent Drugs 0.000 claims 1
230000002152 alkylating effect Effects 0.000 claims 1
238000007075 allylic rearrangement reaction Methods 0.000 claims 1
125000004429 atom Chemical group 0.000 claims 1
239000000796 flavoring agent Substances 0.000 claims 1
235000013355 food flavoring agent Nutrition 0.000 claims 1
238000009472 formulation Methods 0.000 claims 1
230000003301 hydrolyzing effect Effects 0.000 claims 1
150000002513 isocyanates Chemical class 0.000 claims 1
125000006701 (C1-C7) alkyl group Chemical group 0.000 abstract description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 4
125000004442 acylamino group Chemical group 0.000 abstract 2
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 abstract 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 78
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 73
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
239000002904 solvent Substances 0.000 description 45
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
239000011541 reaction mixture Substances 0.000 description 42
239000000047 product Substances 0.000 description 35
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 26
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
238000007710 freezing Methods 0.000 description 21
230000008014 freezing Effects 0.000 description 21
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridine hydrochloride Substances [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 21
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
238000001035 drying Methods 0.000 description 18
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 18
229910000041 hydrogen chloride Inorganic materials 0.000 description 18
235000019439 ethyl acetate Nutrition 0.000 description 15
229910052943 magnesium sulfate Inorganic materials 0.000 description 15
235000019341 magnesium sulphate Nutrition 0.000 description 15
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
239000002585 base Substances 0.000 description 14
230000000694 effects Effects 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
238000010992 reflux Methods 0.000 description 13
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
230000009467 reduction Effects 0.000 description 12
238000006722 reduction reaction Methods 0.000 description 12
125000006239 protecting group Chemical group 0.000 description 11
238000003756 stirring Methods 0.000 description 11
239000002253 acid Substances 0.000 description 10
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 10
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 10
230000003518 presynaptic effect Effects 0.000 description 10
239000000725 suspension Substances 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
108050004812 Dopamine receptor Proteins 0.000 description 8
102000015554 Dopamine receptor Human genes 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
239000004480 active ingredient Substances 0.000 description 8
238000010790 dilution Methods 0.000 description 8
239000012895 dilution Substances 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
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 7
238000010438 heat treatment Methods 0.000 description 7
239000012280 lithium aluminium hydride Substances 0.000 description 7
238000012360 testing method Methods 0.000 description 7
102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 6
108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
241000124008 Mammalia Species 0.000 description 6
229920002472 Starch Polymers 0.000 description 6
239000000556 agonist Substances 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
239000012458 free base Substances 0.000 description 6
238000005984 hydrogenation reaction Methods 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
239000008107 starch Substances 0.000 description 6
235000019698 starch Nutrition 0.000 description 6
229940086542 triethylamine Drugs 0.000 description 6
SHHLMGCHMMCOOS-UHFFFAOYSA-N 4h-chromen-3-one Chemical class C1=CC=C2CC(=O)COC2=C1 SHHLMGCHMMCOOS-UHFFFAOYSA-N 0.000 description 5
KLYMTKVJYHTFIA-UHFFFAOYSA-N 4h-thiochromen-3-one Chemical class C1=CC=C2CC(=O)CSC2=C1 KLYMTKVJYHTFIA-UHFFFAOYSA-N 0.000 description 5
208000028017 Psychotic disease Diseases 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
230000001270 agonistic effect Effects 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
238000009833 condensation Methods 0.000 description 5
230000005494 condensation Effects 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
239000003085 diluting agent Substances 0.000 description 5
229960003638 dopamine Drugs 0.000 description 5
239000000284 extract Substances 0.000 description 5
238000000338 in vitro Methods 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
239000012442 inert solvent Substances 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
239000002798 polar solvent Substances 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 4
KUNSCSSLJIBBFD-UHFFFAOYSA-N 6-methoxy-4h-chromen-3-one Chemical compound O1CC(=O)CC2=CC(OC)=CC=C21 KUNSCSSLJIBBFD-UHFFFAOYSA-N 0.000 description 4
MNFVMLMDLUSEBS-UHFFFAOYSA-N 9-methoxy-4-propyl-2,3,4a,5-tetrahydrochromeno[3,4-b]pyridine Chemical compound C1=C(OC)C=C2C3=CCCN(CCC)C3COC2=C1 MNFVMLMDLUSEBS-UHFFFAOYSA-N 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 4
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical class NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 4
210000003169 central nervous system Anatomy 0.000 description 4
238000001816 cooling Methods 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
229960001760 dimethyl sulfoxide Drugs 0.000 description 4
239000003136 dopamine receptor stimulating agent Substances 0.000 description 4
239000003480 eluent Substances 0.000 description 4
238000001914 filtration Methods 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
229940057948 magnesium stearate Drugs 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
230000020477 pH reduction Effects 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
238000000159 protein binding assay Methods 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
ZELHQPRBSCZNHW-QMDUSEKHSA-N (4aS,10bR)-7-methoxy-4-propyl-1,2,3,4a,5,10b-hexahydrochromeno[3,4-b]pyridine hydrochloride Chemical compound Cl.C1=CC=C2[C@H]3CCCN(CCC)[C@@H]3COC2=C1OC ZELHQPRBSCZNHW-QMDUSEKHSA-N 0.000 description 3
CEVXGMUELSDOPY-LOCPCMAASA-N (4as,10br)-4-propyl-1,2,3,4a,5,10b-hexahydrochromeno[3,4-b]pyridin-7-ol;hydrochloride Chemical compound Cl.C1=CC=C2[C@H]3CCCN(CCC)[C@@H]3COC2=C1O CEVXGMUELSDOPY-LOCPCMAASA-N 0.000 description 3
JFSZKRWNAVLJHH-QMDUSEKHSA-N (4as,10br)-4-propyl-1,2,3,4a,5,10b-hexahydrochromeno[3,4-b]pyridin-9-ol;hydrochloride Chemical compound Cl.C1=C(O)C=C2[C@H]3CCCN(CCC)[C@@H]3COC2=C1 JFSZKRWNAVLJHH-QMDUSEKHSA-N 0.000 description 3
JBWLMIOJPWLYPQ-IAGOWNOFSA-N (4as,10br)-9-methoxy-10b-methyl-4-propyl-4a,5-dihydro-3h-chromeno[3,4-b]pyridine Chemical compound C1=C(OC)C=C2[C@@]3(C)C=CCN(CCC)[C@@H]3COC2=C1 JBWLMIOJPWLYPQ-IAGOWNOFSA-N 0.000 description 3
ASXGAOFCKGHGMF-UHFFFAOYSA-N 6-amino-5,6,7,8-tetrahydronaphthalene-2,3-diol Chemical compound OC1=C(O)C=C2CC(N)CCC2=C1 ASXGAOFCKGHGMF-UHFFFAOYSA-N 0.000 description 3
HHEBBHNRCWBWFR-UHFFFAOYSA-N 8-methoxy-4h-chromen-3-one Chemical compound C1C(=O)COC2=C1C=CC=C2OC HHEBBHNRCWBWFR-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 3
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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