DD249480A5 - 3-amino-dihydro-(1)-benzopyrane und benzothiopyrane - Google Patents

3-amino-dihydro-(1)-benzopyrane und benzothiopyrane Download PDF

Info

Publication number: DD249480A5
Authority: DD; German Democratic Republic
Prior art keywords: formula; compound; hydroxy; pharmaceutically acceptable; hydrogen
Prior art date: 1985-09-03

Application number

DD86294093A

Other languages

German (de)

English (en)

Inventor

Alan J Hutchison

Original Assignee

��`��@��k��

Priority date (The priority date 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 date listed.)

1985-09-03

Filing date

1986-09-02

Publication date

1987-09-09

1986-09-02 Application filed by ��`��@��k�� filed Critical ��`��@��k��

1987-09-09 Publication of DD249480A5 publication Critical patent/DD249480A5/de

Links

ONJRTQUWKRDCTA-UHFFFAOYSA-N 2h-thiochromene Chemical compound C1=CC=C2C=CCSC2=C1 ONJRTQUWKRDCTA-UHFFFAOYSA-N 0.000 title description 10
SVWDNDQOXZHBRM-UHFFFAOYSA-N 3,4-dihydro-2h-chromen-3-amine Chemical compound C1=CC=C2CC(N)COC2=C1 SVWDNDQOXZHBRM-UHFFFAOYSA-N 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 144
150000003839 salts Chemical class 0.000 claims abstract description 52
125000000217 alkyl group Chemical group 0.000 claims abstract description 49
239000001257 hydrogen Substances 0.000 claims abstract description 38
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 38
125000003545 alkoxy group Chemical group 0.000 claims abstract description 33
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 31
229910052717 sulfur Inorganic materials 0.000 claims abstract description 31
239000011593 sulfur Substances 0.000 claims abstract description 31
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 30
229910052760 oxygen Inorganic materials 0.000 claims abstract description 30
239000001301 oxygen Substances 0.000 claims abstract description 30
125000004423 acyloxy group Chemical group 0.000 claims abstract description 15
229910052736 halogen Inorganic materials 0.000 claims abstract description 12
150000002367 halogens Chemical class 0.000 claims abstract description 12
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 10
125000004104 aryloxy group Chemical group 0.000 claims abstract description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 7
238000000034 method Methods 0.000 claims description 72
238000002360 preparation method Methods 0.000 claims description 40
230000008569 process Effects 0.000 claims description 39
239000000203 mixture Substances 0.000 claims description 35
239000007858 starting material Substances 0.000 claims description 35
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 27
150000002431 hydrogen Chemical group 0.000 claims description 26
229910052757 nitrogen Inorganic materials 0.000 claims description 22
150000002148 esters Chemical class 0.000 claims description 19
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 11
125000000524 functional group Chemical group 0.000 claims description 8
230000010933 acylation Effects 0.000 claims description 6
238000005917 acylation reaction Methods 0.000 claims description 6
238000003776 cleavage reaction Methods 0.000 claims description 6
230000009467 reduction Effects 0.000 claims description 5
230000007017 scission Effects 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
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 4
230000003287 optical effect Effects 0.000 claims description 4
125000002947 alkylene group Chemical group 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
238000006266 etherification reaction Methods 0.000 claims description 3
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
SFLCTKUTPODWQY-UHFFFAOYSA-N 3-(dipropylamino)-3,4-dihydro-2h-thiochromen-5-ol Chemical compound C1=CC(O)=C2CC(N(CCC)CCC)CSC2=C1 SFLCTKUTPODWQY-UHFFFAOYSA-N 0.000 claims description 2
VIKRKVIGFPSDLR-UHFFFAOYSA-N [3-(dipropylamino)-3,4-dihydro-2h-thiochromen-5-yl] 2,2-dimethylpropanoate Chemical compound C1=CC(OC(=O)C(C)(C)C)=C2CC(N(CCC)CCC)CSC2=C1 VIKRKVIGFPSDLR-UHFFFAOYSA-N 0.000 claims description 2
230000029936 alkylation Effects 0.000 claims description 2
238000005804 alkylation reaction Methods 0.000 claims description 2
238000006482 condensation reaction Methods 0.000 claims description 2
125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 15
VAEQDEJISQYQNF-UHFFFAOYSA-N 5-ethoxy-n,n-dipropyl-3,4-dihydro-2h-chromen-3-amine Chemical compound C1=CC(OCC)=C2CC(N(CCC)CCC)COC2=C1 VAEQDEJISQYQNF-UHFFFAOYSA-N 0.000 claims 1
FJXLQMYTYYEJOW-UHFFFAOYSA-N 5-methoxy-n,n-dipropyl-3,4-dihydro-2h-thiochromen-3-amine Chemical compound C1=CC(OC)=C2CC(N(CCC)CCC)CSC2=C1 FJXLQMYTYYEJOW-UHFFFAOYSA-N 0.000 claims 1
BXUSAIRVHMRQAU-UHFFFAOYSA-N 5-propoxy-n,n-dipropyl-3,4-dihydro-2h-thiochromen-3-amine Chemical compound S1CC(N(CCC)CCC)CC2=C1C=CC=C2OCCC BXUSAIRVHMRQAU-UHFFFAOYSA-N 0.000 claims 1
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
-1 Arylniederalkoxy Chemical group 0.000 abstract description 42
125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 33
210000003169 central nervous system Anatomy 0.000 abstract description 6
102000005962 receptors Human genes 0.000 abstract description 6
108020003175 receptors Proteins 0.000 abstract description 6
208000015114 central nervous system disease Diseases 0.000 abstract description 2
229940121356 serotonin receptor antagonist Drugs 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 97
239000000243 solution Substances 0.000 description 61
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 49
239000002904 solvent Substances 0.000 description 40
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
238000006243 chemical reaction Methods 0.000 description 29
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
239000002253 acid Substances 0.000 description 20
229910052943 magnesium sulfate Inorganic materials 0.000 description 19
235000019341 magnesium sulphate Nutrition 0.000 description 19
239000011541 reaction mixture Substances 0.000 description 19
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
238000010992 reflux Methods 0.000 description 14
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
238000001035 drying Methods 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 11
239000004480 active ingredient Substances 0.000 description 10
239000002585 base Substances 0.000 description 10
239000000543 intermediate Substances 0.000 description 10
KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 9
241000124008 Mammalia Species 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000012074 organic phase Substances 0.000 description 9
230000035484 reaction time Effects 0.000 description 9
229940076279 serotonin Drugs 0.000 description 9
239000000725 suspension Substances 0.000 description 9
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
125000003118 aryl group Chemical group 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
230000003518 presynaptic effect Effects 0.000 description 8
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 8
229920002472 Starch Polymers 0.000 description 7
239000003814 drug Substances 0.000 description 7
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
229910000041 hydrogen chloride Inorganic materials 0.000 description 7
125000006239 protecting group Chemical group 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
235000019698 starch Nutrition 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
208000019901 Anxiety disease Diseases 0.000 description 6
102000015554 Dopamine receptor Human genes 0.000 description 6
108050004812 Dopamine receptor Proteins 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
238000000338 in vitro Methods 0.000 description 6
238000001727 in vivo Methods 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000008194 pharmaceutical composition Substances 0.000 description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
239000008107 starch Substances 0.000 description 6
KLYMTKVJYHTFIA-UHFFFAOYSA-N 4h-thiochromen-3-one Chemical class C1=CC=C2CC(=O)CSC2=C1 KLYMTKVJYHTFIA-UHFFFAOYSA-N 0.000 description 5
102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 5
108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 5
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 5
238000007126 N-alkylation reaction Methods 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
230000036506 anxiety Effects 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
229940079593 drug Drugs 0.000 description 5
239000008101 lactose Substances 0.000 description 5
230000020477 pH reduction Effects 0.000 description 5
239000012071 phase Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
SHHLMGCHMMCOOS-UHFFFAOYSA-N 4h-chromen-3-one Chemical class C1=CC=C2CC(=O)COC2=C1 SHHLMGCHMMCOOS-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
230000001270 agonistic effect Effects 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
239000002249 anxiolytic agent Substances 0.000 description 4
230000000949 anxiolytic effect Effects 0.000 description 4
239000003638 chemical reducing agent Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 4
208000035475 disorder Diseases 0.000 description 4
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
239000003136 dopamine receptor stimulating agent Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
239000010410 layer Substances 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
230000002582 psychostimulating effect Effects 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
230000004936 stimulating effect Effects 0.000 description 4
230000000638 stimulation Effects 0.000 description 4
125000001424 substituent group Chemical group 0.000 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 description 4
UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 4
YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 3
VORYRUKJTFFASM-UHFFFAOYSA-N 5-methoxy-3,4-dihydro-2h-thiochromen-3-amine Chemical compound S1CC(N)CC2=C1C=CC=C2OC VORYRUKJTFFASM-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
208000020401 Depressive disease Diseases 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
125000001931 aliphatic group Chemical group 0.000 description 3
235000011114 ammonium hydroxide Nutrition 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
239000002775 capsule Substances 0.000 description 3
125000001589 carboacyl group Chemical group 0.000 description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
239000012876 carrier material Substances 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000001816 cooling Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
239000007789 gas Substances 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
150000004678 hydrides Chemical class 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
229910052744 lithium Inorganic materials 0.000 description 3
239000000463 material Substances 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
238000000159 protein binding assay Methods 0.000 description 3
238000006722 reduction reaction Methods 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
238000003797 solvolysis reaction Methods 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
MQEYWTXIDOHHMO-LDWIPMOCSA-N (3r,4r)-3-bromo-5-methoxy-3,4-dihydro-2h-chromen-4-ol Chemical compound O1C[C@@H](Br)[C@H](O)C2=C1C=CC=C2OC MQEYWTXIDOHHMO-LDWIPMOCSA-N 0.000 description 2
RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 2
NOOYFQLPKUQDNE-UHFFFAOYSA-N 2-(bromomethyl)prop-2-enoic acid Chemical compound OC(=O)C(=C)CBr NOOYFQLPKUQDNE-UHFFFAOYSA-N 0.000 description 2
BTHJVPKYGFOXFA-UHFFFAOYSA-N 5-ethoxy-n,n-dipropyl-3,4-dihydro-2h-thiochromen-3-amine;hydrochloride Chemical compound Cl.C1=CC(OCC)=C2CC(N(CCC)CCC)CSC2=C1 BTHJVPKYGFOXFA-UHFFFAOYSA-N 0.000 description 2
LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 description 2
229940000681 5-hydroxytryptophan Drugs 0.000 description 2
GGVRQHBZJLDTNZ-UHFFFAOYSA-N 5-methoxy-n,n-dipropyl-3,4-dihydro-2h-thiochromen-3-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=C2CC(N(CCC)CCC)CSC2=C1 GGVRQHBZJLDTNZ-UHFFFAOYSA-N 0.000 description 2
UPBSICACNAVTFQ-UHFFFAOYSA-N 8-methoxy-4h-thiochromen-3-one Chemical compound C1C(=O)CSC2=C1C=CC=C2OC UPBSICACNAVTFQ-UHFFFAOYSA-N 0.000 description 2
XVHFGNFNNYLIGU-UHFFFAOYSA-N 8-methoxy-n,n-dipropyl-3,4-dihydro-2h-thiochromen-3-amine;hydrochloride Chemical compound Cl.C1=CC=C(OC)C2=C1CC(N(CCC)CCC)CS2 XVHFGNFNNYLIGU-UHFFFAOYSA-N 0.000 description 2
208000024827 Alzheimer disease Diseases 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
208000015879 Cerebellar disease Diseases 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
208000027089 Parkinsonian disease Diseases 0.000 description 2
206010034010 Parkinsonism Diseases 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
208000028017 Psychotic disease Diseases 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
206010039966 Senile dementia Diseases 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
239000000556 agonist Substances 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
229940005530 anxiolytics Drugs 0.000 description 2
239000002830 appetite depressant Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
125000005333 aroyloxy group Chemical group 0.000 description 2
239000004305 biphenyl Substances 0.000 description 2
235000010290 biphenyl Nutrition 0.000 description 2
238000009835 boiling Methods 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
244000309464 bull Species 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
210000003710 cerebral cortex Anatomy 0.000 description 2
LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 2
208000010877 cognitive disease Diseases 0.000 description 2
238000009833 condensation Methods 0.000 description 2
230000005494 condensation Effects 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
238000005661 deetherification reaction Methods 0.000 description 2
238000006731 degradation reaction Methods 0.000 description 2
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 2
JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 2
229960003638 dopamine Drugs 0.000 description 2
239000003480 eluent Substances 0.000 description 2
230000002255 enzymatic effect Effects 0.000 description 2
230000032050 esterification Effects 0.000 description 2
238000005886 esterification reaction Methods 0.000 description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
239000000284 extract Substances 0.000 description 2
238000001640 fractional crystallisation Methods 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
229910000043 hydrogen iodide Inorganic materials 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
239000007788 liquid Substances 0.000 description 2
239000012528 membrane Substances 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
239000011707 mineral Substances 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
239000002808 molecular sieve Substances 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
230000000701 neuroleptic effect Effects 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
LDCYZAJDBXYCGN-UHFFFAOYSA-N oxitriptan Natural products C1=C(O)C=C2C(CC(N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-UHFFFAOYSA-N 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
108090000765 processed proteins & peptides Proteins 0.000 description 2
239000000651 prodrug Substances 0.000 description 2
229940002612 prodrug Drugs 0.000 description 2
LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
238000006268 reductive amination reaction Methods 0.000 description 2
239000000952 serotonin receptor agonist Substances 0.000 description 2
238000007086 side reaction Methods 0.000 description 2
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
238000003756 stirring Methods 0.000 description 2
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 2
ZMZFEEBOYDRFCQ-UHFFFAOYSA-N tert-butyl n-(5-methoxy-3,4-dihydro-2h-thiochromen-3-yl)carbamate Chemical compound S1CC(NC(=O)OC(C)(C)C)CC2=C1C=CC=C2OC ZMZFEEBOYDRFCQ-UHFFFAOYSA-N 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
VRHHGFQAXXIRJW-UHFFFAOYSA-N 10h-thiochromeno[3,2-b]pyridine Chemical class C1=CN=C2CC3=CC=CC=C3SC2=C1 VRHHGFQAXXIRJW-UHFFFAOYSA-N 0.000 description 1
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
POEXKURDQFJBLF-UHFFFAOYSA-N 2-(phenylsulfanylmethyl)prop-2-enoic acid Chemical compound OC(=O)C(=C)CSC1=CC=CC=C1 POEXKURDQFJBLF-UHFFFAOYSA-N 0.000 description 1
DSCJETUEDFKYGN-UHFFFAOYSA-N 2-Methoxybenzenethiol Chemical compound COC1=CC=CC=C1S DSCJETUEDFKYGN-UHFFFAOYSA-N 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
FYGBLYHZMDOVAE-UHFFFAOYSA-N 2-[(3-methoxythiophen-2-yl)methyl]prop-2-enoic acid Chemical compound COC1=C(SC=C1)CC(C(=O)O)=C FYGBLYHZMDOVAE-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
KSDMMCFWQWBVBW-UHFFFAOYSA-N 2-sulfanylbenzaldehyde Chemical compound SC1=CC=CC=C1C=O KSDMMCFWQWBVBW-UHFFFAOYSA-N 0.000 description 1
LZNNMMKMGKFYLL-UHFFFAOYSA-N 2h-pyran-3-carboxylic acid Chemical compound OC(=O)C1=CC=COC1 LZNNMMKMGKFYLL-UHFFFAOYSA-N 0.000 description 1
OOBGBZQAHJBVEW-UHFFFAOYSA-N 2h-thiochromen-3-amine Chemical compound C1=CC=C2SCC(N)=CC2=C1 OOBGBZQAHJBVEW-UHFFFAOYSA-N 0.000 description 1
HMJPRXLPAGOYFX-UHFFFAOYSA-N 3,4-dihydro-2h-thiochromen-3-amine Chemical class C1=CC=C2CC(N)CSC2=C1 HMJPRXLPAGOYFX-UHFFFAOYSA-N 0.000 description 1
FYCYMUIHNGDOBW-UHFFFAOYSA-N 3-(dipropylamino)-3,4-dihydro-2h-chromen-5-ol;hydrochloride Chemical compound Cl.C1=CC(O)=C2CC(N(CCC)CCC)COC2=C1 FYCYMUIHNGDOBW-UHFFFAOYSA-N 0.000 description 1
PXSSMALRVSYAFM-UHFFFAOYSA-N 3-(dipropylamino)-3,4-dihydro-2h-chromen-8-ol Chemical compound C1=CC=C2CC(N(CCC)CCC)COC2=C1O PXSSMALRVSYAFM-UHFFFAOYSA-N 0.000 description 1
RVBCYWRUNOUAJD-UHFFFAOYSA-N 3-(dipropylamino)-3,4-dihydro-2h-thiochromen-5-ol;hydrochloride Chemical compound Cl.C1=CC(O)=C2CC(N(CCC)CCC)CSC2=C1 RVBCYWRUNOUAJD-UHFFFAOYSA-N 0.000 description 1
RUJXBUPXDYWFSB-UHFFFAOYSA-N 3-(dipropylamino)-3,4-dihydro-2h-thiochromen-6-ol;hydrochloride Chemical compound Cl.C1=C(O)C=C2CC(N(CCC)CCC)CSC2=C1 RUJXBUPXDYWFSB-UHFFFAOYSA-N 0.000 description 1
CNPWAJWACHEYRY-UHFFFAOYSA-N 3-(dipropylamino)-3,4-dihydro-2h-thiochromen-7-ol;hydrochloride Chemical compound Cl.OC1=CC=C2CC(N(CCC)CCC)CSC2=C1 CNPWAJWACHEYRY-UHFFFAOYSA-N 0.000 description 1
OFKWWALNMPEOSZ-UHFFFAOYSA-N 3-(hydrazinylmethyl)phenol Chemical compound NNCC1=CC=CC(O)=C1 OFKWWALNMPEOSZ-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
QMVAZEHZOPDGHA-UHFFFAOYSA-N 3-methoxybenzenethiol Chemical compound COC1=CC=CC(S)=C1 QMVAZEHZOPDGHA-UHFFFAOYSA-N 0.000 description 1
PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
125000005274 4-hydroxybenzoic acid group Chemical group 0.000 description 1
YDTKSRQDBPMRCP-UHFFFAOYSA-N 5-ethoxy-4h-thiochromen-3-one Chemical compound S1CC(=O)CC2=C1C=CC=C2OCC YDTKSRQDBPMRCP-UHFFFAOYSA-N 0.000 description 1
KYTDQPMVBIJULI-UHFFFAOYSA-N 5-ethoxy-n,n-diethyl-3,4-dihydro-2h-chromen-3-amine;hydrochloride Chemical compound Cl.O1CC(N(CC)CC)CC2=C1C=CC=C2OCC KYTDQPMVBIJULI-UHFFFAOYSA-N 0.000 description 1
ROOHLBWNKFJZHJ-UHFFFAOYSA-N 5-methoxy-2h-chromene Chemical compound O1CC=CC2=C1C=CC=C2OC ROOHLBWNKFJZHJ-UHFFFAOYSA-N 0.000 description 1
QROOOJOYXVKIJE-UHFFFAOYSA-N 5-methoxy-3,4-dihydro-2h-thiochromene-3-carboxylic acid Chemical compound S1CC(C(O)=O)CC2=C1C=CC=C2OC QROOOJOYXVKIJE-UHFFFAOYSA-N 0.000 description 1
LXLFVZLZBQOFAA-UHFFFAOYSA-N 5-methoxy-4h-chromen-3-one Chemical compound O1CC(=O)CC2=C1C=CC=C2OC LXLFVZLZBQOFAA-UHFFFAOYSA-N 0.000 description 1
FCBPOLKAMDMPOC-UHFFFAOYSA-N 5-methoxy-4h-thiochromen-3-one Chemical compound S1CC(=O)CC2=C1C=CC=C2OC FCBPOLKAMDMPOC-UHFFFAOYSA-N 0.000 description 1
RSTRABDDRIHFNA-UHFFFAOYSA-N 5-phenylmethoxy-n,n-dipropyl-3,4-dihydro-2h-chromen-3-amine;hydrochloride Chemical compound Cl.C=12CC(N(CCC)CCC)COC2=CC=CC=1OCC1=CC=CC=C1 RSTRABDDRIHFNA-UHFFFAOYSA-N 0.000 description 1
XTSUHDWHLFLEQD-UHFFFAOYSA-N 5-phenylmethoxy-n,n-dipropyl-3,4-dihydro-2h-thiochromen-3-amine;hydrochloride Chemical compound Cl.C=12CC(N(CCC)CCC)CSC2=CC=CC=1OCC1=CC=CC=C1 XTSUHDWHLFLEQD-UHFFFAOYSA-N 0.000 description 1
LITHGADQYVVATL-UHFFFAOYSA-N 5-propoxy-n,n-dipropyl-3,4-dihydro-2h-chromen-3-amine;hydrochloride Chemical compound Cl.O1CC(N(CCC)CCC)CC2=C1C=CC=C2OCCC LITHGADQYVVATL-UHFFFAOYSA-N 0.000 description 1
DUSOEUPHZZTNAH-UHFFFAOYSA-N 5-propoxy-n,n-dipropyl-3,4-dihydro-2h-thiochromen-3-amine;hydrochloride Chemical compound Cl.S1CC(N(CCC)CCC)CC2=C1C=CC=C2OCCC DUSOEUPHZZTNAH-UHFFFAOYSA-N 0.000 description 1
FNYGDLUDLGUSSO-UHFFFAOYSA-N 7-methoxy-3,4-dihydro-2h-thiochromene-3-carboxylic acid Chemical compound C1C(C(O)=O)CSC2=CC(OC)=CC=C21 FNYGDLUDLGUSSO-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
HHEBBHNRCWBWFR-UHFFFAOYSA-N 8-methoxy-4h-chromen-3-one Chemical compound C1C(=O)COC2=C1C=CC=C2OC HHEBBHNRCWBWFR-UHFFFAOYSA-N 0.000 description 1
CMOPFQKLYWMREO-UHFFFAOYSA-N 8-methoxy-n,n-dimethyl-3,4-dihydro-2h-thiochromen-3-amine;hydrochloride Chemical compound Cl.C1C(N(C)C)CSC2=C1C=CC=C2OC CMOPFQKLYWMREO-UHFFFAOYSA-N 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
229910015900 BF3 Inorganic materials 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
GTNLQUGDCPGCJE-UHFFFAOYSA-N C(C)OC(CC1=C(C=CC=C1O)CSC(=O)OCC)=O Chemical compound C(C)OC(CC1=C(C=CC=C1O)CSC(=O)OCC)=O GTNLQUGDCPGCJE-UHFFFAOYSA-N 0.000 description 1
JKICAMNFTJJEDO-UHFFFAOYSA-N C(C)OC1=CC=CC=C1C(C(=O)OCC)SCCC(=O)OCC Chemical compound C(C)OC1=CC=CC=C1C(C(=O)OCC)SCCC(=O)OCC JKICAMNFTJJEDO-UHFFFAOYSA-N 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
229930186147 Cephalosporin Natural products 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
235000001258 Cinchona calisaya Nutrition 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
229940081615 DOPA decarboxylase inhibitor Drugs 0.000 description 1
208000012661 Dyskinesia Diseases 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000001828 Gelatine Substances 0.000 description 1
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 1
239000004471 Glycine Substances 0.000 description 1
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 1
WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
208000016285 Movement disease Diseases 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
QILLQPDBHCSSQP-UHFFFAOYSA-N O1CC(=O)CC2=C1C=CC=C2OC.O1CC(=O)CC2=C1C=CC=C2OC Chemical compound O1CC(=O)CC2=C1C=CC=C2OC.O1CC(=O)CC2=C1C=CC=C2OC QILLQPDBHCSSQP-UHFFFAOYSA-N 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
241000220304 Prunus dulcis Species 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
JVVXZOOGOGPDRZ-SLFFLAALSA-N [(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 JVVXZOOGOGPDRZ-SLFFLAALSA-N 0.000 description 1
PNCIISXITKPDRO-UHFFFAOYSA-N [3-(dipropylamino)-3,4-dihydro-2h-chromen-5-yl] benzoate Chemical compound C=12CC(N(CCC)CCC)COC2=CC=CC=1OC(=O)C1=CC=CC=C1 PNCIISXITKPDRO-UHFFFAOYSA-N 0.000 description 1
AGUJNMVTXLGAQH-UHFFFAOYSA-N [3-(dipropylamino)-3,4-dihydro-2h-chromen-5-yl] n,n-dimethylcarbamate Chemical compound C1=CC(OC(=O)N(C)C)=C2CC(N(CCC)CCC)COC2=C1 AGUJNMVTXLGAQH-UHFFFAOYSA-N 0.000 description 1
YWVWJXINRDFDGJ-UHFFFAOYSA-N [3-(dipropylamino)-3,4-dihydro-2h-chromen-8-yl] 2,2-dimethylpropanoate;hydrochloride Chemical compound Cl.C1=CC=C(OC(=O)C(C)(C)C)C2=C1CC(N(CCC)CCC)CO2 YWVWJXINRDFDGJ-UHFFFAOYSA-N 0.000 description 1
FQMSLOIUIWEFRS-UHFFFAOYSA-N [3-(dipropylamino)-3,4-dihydro-2h-thiochromen-8-yl] benzoate Chemical compound C1C(N(CCC)CCC)CSC2=C1C=CC=C2OC(=O)C1=CC=CC=C1 FQMSLOIUIWEFRS-UHFFFAOYSA-N 0.000 description 1
239000002250 absorbent Substances 0.000 description 1
230000002745 absorbent Effects 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
230000009471 action Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
239000012790 adhesive layer Substances 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
230000001800 adrenalinergic effect Effects 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
150000001447 alkali salts Chemical class 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
150000005215 alkyl ethers Chemical class 0.000 description 1
150000001351 alkyl iodides Chemical class 0.000 description 1
235000020224 almond Nutrition 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
229940040526 anhydrous sodium acetate Drugs 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
230000000561 anti-psychotic effect Effects 0.000 description 1
125000003435 aroyl group Chemical group 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
NUECKNGJZRYMCT-UHFFFAOYSA-N benzoic acid;3-(dipropylamino)-3,4-dihydro-2h-thiochromen-8-ol Chemical compound OC(=O)C1=CC=CC=C1.C1=CC=C2CC(N(CCC)CCC)CSC2=C1O NUECKNGJZRYMCT-UHFFFAOYSA-N 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000037396 body weight Effects 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 1
RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 1
239000000872 buffer Substances 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
244000309466 calf Species 0.000 description 1
150000004657 carbamic acid derivatives Chemical class 0.000 description 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000005018 casein Substances 0.000 description 1
BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
235000021240 caseins Nutrition 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
229940124587 cephalosporin Drugs 0.000 description 1
150000001780 cephalosporins Chemical class 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 1
KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 1
238000000576 coating method Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
229940099112 cornstarch Drugs 0.000 description 1
KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000018044 dehydration Effects 0.000 description 1
238000006297 dehydration reaction Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 1
229960005215 dichloroacetic acid Drugs 0.000 description 1
DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
229940008406 diethyl sulfate Drugs 0.000 description 1
MHUWZNTUIIFHAS-CLFAGFIQSA-N dioleoyl phosphatidic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC MHUWZNTUIIFHAS-CLFAGFIQSA-N 0.000 description 1
WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000000534 dopa decarboxylase inhibitor Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
125000001240 enamine group Chemical group 0.000 description 1
150000002081 enamines Chemical class 0.000 description 1
229960002179 ephedrine Drugs 0.000 description 1
150000002168 ethanoic acid esters Chemical class 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
NJOHKZHRCFGWBD-UHFFFAOYSA-N ethyl 2-[2-acetyloxy-6-(2-ethoxy-2-oxoethyl)sulfanylphenyl]acetate Chemical compound CCOC(=O)CSC1=CC=CC(OC(C)=O)=C1CC(=O)OCC NJOHKZHRCFGWBD-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000000605 extraction Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
238000005187 foaming Methods 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
TUHMQDODLHWPCC-UHFFFAOYSA-N formyl cyanide Chemical compound O=CC#N TUHMQDODLHWPCC-UHFFFAOYSA-N 0.000 description 1
238000004508 fractional distillation Methods 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
150000002366 halogen compounds Chemical class 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
230000002140 halogenating effect Effects 0.000 description 1
125000001072 heteroaryl group Chemical group 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
229910000039 hydrogen halide Inorganic materials 0.000 description 1
239000012433 hydrogen halide Substances 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000002452 interceptive effect Effects 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
239000011630 iodine Substances 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
239000000644 isotonic solution Substances 0.000 description 1
229960004502 levodopa Drugs 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
125000005905 mesyloxy group Chemical group 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
150000004692 metal hydroxides Chemical class 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
150000005217 methyl ethers Chemical class 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
VBTQNRFWXBXZQR-UHFFFAOYSA-N n-bromoacetamide Chemical compound CC(=O)NBr VBTQNRFWXBXZQR-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
GLQSVCODIQCKBM-UHFFFAOYSA-N n-ethyl-5-methoxy-7-methyl-3,4-dihydro-2h-thiochromen-3-amine;hydrochloride Chemical compound Cl.CC1=CC(OC)=C2CC(NCC)CSC2=C1 GLQSVCODIQCKBM-UHFFFAOYSA-N 0.000 description 1
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
210000000653 nervous system Anatomy 0.000 description 1
239000003176 neuroleptic agent Substances 0.000 description 1
239000003076 neurotropic agent Substances 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
210000002445 nipple Anatomy 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000006072 paste Substances 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical class OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
125000000864 peroxy group Chemical group O(O*)* 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
239000011505 plaster Substances 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
239000011241 protective layer Substances 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
229960001404 quinidine Drugs 0.000 description 1
229960000948 quinine Drugs 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
239000000018 receptor agonist Substances 0.000 description 1
229940044601 receptor agonist Drugs 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
241000894007 species Species 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical class O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
VYHUPEVKUKGKDO-UHFFFAOYSA-N tert-butyl n-(7-methoxy-3,4-dihydro-2h-thiochromen-3-yl)carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CSC2=CC(OC)=CC=C21 VYHUPEVKUKGKDO-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
CWERGRDVMFNCDR-UHFFFAOYSA-M thioglycolate(1-) Chemical compound [O-]C(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-M 0.000 description 1
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical class SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 1
125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
230000007279 water homeostasis Effects 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/74—Benzo[b]pyrans, hydrogenated in the carbocyclic ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
- C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Biomedical Technology (AREA)
Public Health (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Anesthesiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Pyrane Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
Dental Preparations (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

DD86294093A 1985-09-03 1986-09-02 3-amino-dihydro-(1)-benzopyrane und benzothiopyrane DD249480A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US77206885A	1985-09-03	1985-09-03

Publications (1)

Publication Number	Publication Date
DD249480A5 true DD249480A5 (de)	1987-09-09

Family

ID=25093804

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD86294093A DD249480A5 (de)	1985-09-03	1986-09-02	3-amino-dihydro-(1)-benzopyrane und benzothiopyrane

Country Status (18)

Country	Link
EP (1)	EP0222996B1 (es)
JP (1)	JPS6259273A (es)
KR (1)	KR900003883B1 (es)
AT (1)	ATE63744T1 (es)
AU (1)	AU596113B2 (es)
DD (1)	DD249480A5 (es)
DE (1)	DE3679378D1 (es)
DK (1)	DK418486A (es)
ES (1)	ES2001923A6 (es)
FI (1)	FI86720C (es)
GR (1)	GR862239B (es)
HU (1)	HU202853B (es)
IL (1)	IL79920A (es)
NO (1)	NO863507L (es)
NZ (1)	NZ217432A (es)
PH (1)	PH22522A (es)
PT (1)	PT83300B (es)
ZA (1)	ZA866685B (es)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4957928A (en) *	1986-06-26	1990-09-18	Ciba-Geigy Corporation	Hydrogenated 1-benzooxacycloalkylpyridinecarboxylic acid compounds
US4801605A (en) *	1986-08-29	1989-01-31	Ciba-Geigy Corporation	3-amino-dihydro-[1]-benzopyrans and benzothiopyrans
SE8605504D0 (sv) *	1986-12-19	1986-12-19	Astra Laekemedel Ab	Novel chroman derivatives
EP0322361A3 (de) *	1987-12-23	1990-01-24	Ciba-Geigy Ag	Weitere hydrierte 1-Benzooxacycloalkylpyridincarbonsäureverbindungen
NZ231969A (en) *	1988-12-23	1992-09-25	Beecham Group Plc	Benzopyran derivatives, analogues, precursors, and medicaments
CA2047236C (en) *	1989-04-27	1997-07-22	Bengt Ronny Andersson	Substituted 3-amino chromans
SE8904127D0 (sv) *	1989-12-07	1989-12-07	Astra Ab	New biocyclic amino-substituted compounds
US5420151A (en) *	1989-12-22	1995-05-30	Aktiebolaget Astra	Chroman derivatives
SE8904361D0 (sv)	1989-12-22	1989-12-22	Astra Ab	New chroman and thiochroman derivatives
US5616610A (en) *	1989-12-22	1997-04-01	Astra Aktiebolag	(R)-5-carbamoyl-8-fluoro-3-N,N-disubstituted-amino-3,4-dihydro-2H-1-benzopyrans
US5273994A (en) *	1990-04-09	1993-12-28	Adir Et Compagnie	3-aminochroman compounds
FR2660657B1 (fr) *	1990-04-09	1993-05-07	Adir	Nouveaux derives du 3-aminochromane, leur procede de preparation et les compositions pharmaceutiques qui les contiennent.
FR2678617B1 (fr) *	1991-07-01	1995-01-20	Adir	Nouveau procede de synthese d'enantiomeres de derives du 3-amino chromane.
FR2681325B1 (fr) *	1991-09-16	1993-12-17	Fabre Medicament Pierre	Derives de l'aminomethyl-4 piperidine, leur preparation et leur application en therapeutique.
HRP920935A2 (en) *	1991-10-08	1995-08-31	Astra Ab	New therapeutically active compound
FR2689509B1 (fr) *	1992-04-01	1994-06-03	Adir	Nouveaux derives spiraniques du 3-amino chromane, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent.
CZ282172B6 (cs) *	1992-11-30	1997-05-14	Smithkline Beecham Plc	Benzpyranové analogy pro léčení úzkosti, mánie, deprese nebo symptomů po přerušení podávání drog nebo léčiv, způsob přípravy těchto sloučenin, jejich použití a farmaceutický prostředek obsahující tyto sloučeniny
US7125904B2 (en)	2002-10-11	2006-10-24	Portela & C.A., S.A.	Peripherally-selective inhibitors of dopamine-β-hydroxylase and method of their preparation

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3629289A (en) *	1969-04-24	1971-12-21	Parke Davis & Co	Chromanamines
US3607886A (en) *	1969-04-24	1971-09-21	Parke Davis & Co	Chromanamines
US4203895A (en) *	1978-04-14	1980-05-20	Warner-Lambert Company	Process for the preparation of cis-(±)-3,4-dihydro-N,N,2-trimethyl-2H-1-benzopyran-3-amine and intermediates produced thereby

1986
- 1986-09-01 AT AT86112104T patent/ATE63744T1/de not_active IP Right Cessation
- 1986-09-01 EP EP86112104A patent/EP0222996B1/de not_active Expired - Lifetime
- 1986-09-01 GR GR862239A patent/GR862239B/el unknown
- 1986-09-01 PH PH34204A patent/PH22522A/en unknown
- 1986-09-01 DE DE8686112104T patent/DE3679378D1/de not_active Expired - Lifetime
- 1986-09-02 NO NO863507A patent/NO863507L/no unknown
- 1986-09-02 IL IL79920A patent/IL79920A/xx unknown
- 1986-09-02 ES ES8601568A patent/ES2001923A6/es not_active Expired
- 1986-09-02 DD DD86294093A patent/DD249480A5/de not_active IP Right Cessation
- 1986-09-02 NZ NZ217432A patent/NZ217432A/xx unknown
- 1986-09-02 ZA ZA866685A patent/ZA866685B/xx unknown
- 1986-09-02 HU HU863786A patent/HU202853B/hu not_active IP Right Cessation
- 1986-09-02 DK DK418486A patent/DK418486A/da unknown
- 1986-09-03 JP JP61206047A patent/JPS6259273A/ja active Pending
- 1986-09-03 FI FI863558A patent/FI86720C/fi not_active IP Right Cessation
- 1986-09-03 PT PT83300A patent/PT83300B/pt not_active IP Right Cessation
- 1986-09-03 AU AU62317/86A patent/AU596113B2/en not_active Ceased
- 1986-09-03 KR KR1019860007357A patent/KR900003883B1/ko not_active Expired

Also Published As

Publication number	Publication date
ES2001923A6 (es)	1988-07-01
NO863507L (no)	1987-03-04
FI863558A0 (fi)	1986-09-03
FI86720C (fi)	1992-10-12
ZA866685B (en)	1987-04-29
PT83300B (pt)	1989-05-12
EP0222996A2 (de)	1987-05-27
JPS6259273A (ja)	1987-03-14
HU202853B (en)	1991-04-29
PH22522A (en)	1988-10-17
DK418486D0 (da)	1986-09-02
DE3679378D1 (de)	1991-06-27
AU6231786A (en)	1987-03-05
EP0222996A3 (en)	1987-12-02
IL79920A (en)	1991-07-18
KR900003883B1 (ko)	1990-06-04
FI863558A7 (fi)	1987-03-04
ATE63744T1 (de)	1991-06-15
KR870003088A (ko)	1987-04-15
EP0222996B1 (de)	1991-05-22
NO863507D0 (no)	1986-09-02
HUT44771A (en)	1988-04-28
AU596113B2 (en)	1990-04-26
NZ217432A (en)	1990-03-27
PT83300A (en)	1986-10-01
GR862239B (en)	1986-12-31
FI86720B (fi)	1992-06-30
DK418486A (da)	1987-03-04
IL79920A0 (en)	1986-12-31

Legal Events

Date	Code	Title	Description
1995-06-22	ENJ	Ceased due to non-payment of renewal fee

Publication	Publication Date	Title
DD249480A5 (de)	1987-09-09	3-amino-dihydro-(1)-benzopyrane und benzothiopyrane
EP0280269B1 (de)	1992-02-12	3-Amino-dihydro-[1]-benzopyrane und Benzothiopyrane
EP1487834B1 (de)	2007-04-25	Aza-bicyclische n-biarylamide mit affinität zum alpha7 nikotinischen acetylcholin-rezeptor
DE60102581T2 (de)	2005-02-03	Azabizyklische carbamate und ihre anwendung als antagonisten des alpha-7 nikotinischen acetylcholin rezeptors
DE69426327T2 (de)	2001-04-12	Bicyclische amid-derivate und ihre verwendung als muskel entspannende verbindungen
DE69715865T2 (de)	2003-08-07	Muscarin-antagonisten
EP0026848A1 (de)	1981-04-15	Tetralinderivate, ihre Herstellung und Heilmittel, welche diese Verbindungen enthalten
EP0271795A2 (de)	1988-06-22	Octahydro-10-oxo-6H-pyridazo [1,2-a] [1,2] diazepin-Derivate, Zwischenprodukte und Verfahren zu deren Herstellung sowie diese enthaltende Arzneimittel
EP0161218B1 (de)	1991-06-26	Benzo-(pyrano und thiopyrano)-pyridine
DE3882679T2 (de)	1993-11-04	Kardiovaskulaer aktive verbindungen.
EP0149840A1 (de)	1985-07-31	Substituierte 5,11-Dihydro-6H-dibenz(b,e)azepin-6-one, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
DE69617700T2 (de)	2002-07-18	Neue kondensierten isochinoline als dopamin-rezeptor-liganden
DE69402463T2 (de)	1997-11-27	(7S)-7-(2R)-2-(3-Chlorophenyl)-2-Hydoxyethylamino-5,6,7,8-Tetrahydronaphtalen-2-yloxy Essigsäure, ihre pharmazeutisch akzeptablen Salze, mit Beta-3-adrenergischer agonistischer Aktivität und diese enthaltende pharmazeutische Zusammensetzungen
EP0000395B1 (de)	1981-01-07	2-Piperazinotetraline, ihre Herstellung und Verwendung als Arzneimittel
DD143613A5 (de)	1980-09-03	Verfahren zur herstellung von 4-amino-2-piperidino-chinazolin-derivaten
DE69611303T2 (de)	2001-07-05	Benzolsulfonamidderivate, ihre herstellung und ihre therapeutische verwendung
EP0298919A2 (de)	1989-01-11	4-Amino-substituierte 1,2-Dihydroxynaphthalin-Derivate
EP1335720A1 (de)	2003-08-20	Sulfonamiden zur behandlung von erkrankungen des zentralen nervensystems
EP0455596B1 (de)	1994-11-02	Substituierte Indole
EP0389425B1 (de)	1995-04-26	Neue Benzothiopyranylamine
EP0298921B1 (de)	1992-12-23	1,2-Benzisoxazole und 1,2-Benzisothiazole
DE68905363T2 (de)	1993-08-05	Heterotetracyclische laktamderivate, verfahren zu ihrer herstellung und pharmazeutische zubereitungen, die sie enthalten.
DE60112917T2 (de)	2006-06-08	Neue polyzyklische indanylimidazole mit alpha2 adrenergik aktivität
DE2207430C3 (de)	1982-05-13	1,2,4,5-Tetrahydro-3H-3-benzazepin, ein Verfahren zu ihrer Herstellung und diese enthaltendes pharmazeutisches Mittel
EP0037990A1 (de)	1981-10-21	Phenyl-chinolizidine, entsprechende pharmazeutische Präparate, die Herstellung der Wirkstoffe sowie entsprechende Ausgangsverbindungen