CY1544A - Oxysalicylamido derivatives - Google Patents

Oxysalicylamido derivatives Download PDF

Info

Publication number: CY1544A
Authority: CY; Cyprus
Prior art keywords: compound; formula; group; lower alkyl; ethyl
Prior art date: 1984-01-31

Application number

CY1544A

Other languages

English (en)

Original Assignee

Astra Laekemedel Ab

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.)

1984-01-31

Filing date

1991-03-22

Publication date

1991-03-22

1991-03-22 Application filed by Astra Laekemedel Ab filed Critical Astra Laekemedel Ab

1991-03-22 Publication of CY1544A publication Critical patent/CY1544A/en

Links

150000001875 compounds Chemical class 0.000 claims abstract description 149
238000000034 method Methods 0.000 claims abstract description 65
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 52
125000000217 alkyl group Chemical group 0.000 claims abstract description 43
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 37
-1 methylenedioxy Chemical group 0.000 claims abstract description 36
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
150000003839 salts Chemical class 0.000 claims abstract description 25
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 23
229910052736 halogen Inorganic materials 0.000 claims abstract description 22
150000002367 halogens Chemical class 0.000 claims abstract description 21
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 20
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 20
239000001257 hydrogen Substances 0.000 claims abstract description 19
238000002360 preparation method Methods 0.000 claims abstract description 17
125000004950 trifluoroalkyl group Chemical group 0.000 claims abstract description 13
125000002252 acyl group Chemical group 0.000 claims abstract description 12
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 12
125000001246 bromo group Chemical group Br* 0.000 claims abstract description 11
125000003342 alkenyl group Chemical group 0.000 claims abstract description 10
125000000304 alkynyl group Chemical group 0.000 claims abstract description 10
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 10
125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 9
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 9
239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 9
125000005117 dialkylcarbamoyl group Chemical group 0.000 claims abstract description 8
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims abstract description 8
230000003287 optical effect Effects 0.000 claims abstract description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 39
230000008569 process Effects 0.000 claims description 22
101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 claims description 13
229910052794 bromium Inorganic materials 0.000 claims description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
239000005864 Sulphur Substances 0.000 claims description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
229910052740 iodine Inorganic materials 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
239000001301 oxygen Substances 0.000 claims description 5
230000015572 biosynthetic process Effects 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
239000004480 active ingredient Substances 0.000 claims description 3
201000010099 disease Diseases 0.000 claims description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
229940079593 drug Drugs 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
150000001408 amides Chemical group 0.000 claims description 2
125000003277 amino group Chemical group 0.000 claims description 2
239000012736 aqueous medium Substances 0.000 claims description 2
239000003795 chemical substances by application Substances 0.000 claims description 2
230000002140 halogenating effect Effects 0.000 claims description 2
150000002431 hydrogen Chemical group 0.000 claims 10
125000005277 alkyl imino group Chemical group 0.000 claims 2
125000001841 imino group Chemical group [H]N=* 0.000 claims 2
101100295738 Gallus gallus COR3 gene Proteins 0.000 claims 1
229940125773 compound 10 Drugs 0.000 claims 1
230000003291 dopaminomimetic effect Effects 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
230000004064 dysfunction Effects 0.000 claims 1
239000004615 ingredient Substances 0.000 claims 1
ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 8
230000001225 therapeutic effect Effects 0.000 abstract description 4
239000002184 metal Substances 0.000 abstract 1
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 60
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
239000000203 mixture Substances 0.000 description 39
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
239000000243 solution Substances 0.000 description 33
239000002904 solvent Substances 0.000 description 33
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 28
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 27
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
239000013543 active substance Substances 0.000 description 23
229940022682 acetone Drugs 0.000 description 20
238000005481 NMR spectroscopy Methods 0.000 description 18
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
229960003638 dopamine Drugs 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 17
238000001704 evaporation Methods 0.000 description 17
230000008020 evaporation Effects 0.000 description 17
238000005160 1H NMR spectroscopy Methods 0.000 description 16
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 16
239000003921 oil Substances 0.000 description 16
235000019198 oils Nutrition 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 14
229910052757 nitrogen Inorganic materials 0.000 description 13
125000003118 aryl group Chemical group 0.000 description 12
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
239000000047 product Substances 0.000 description 12
239000003826 tablet Substances 0.000 description 12
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 11
229960004046 apomorphine Drugs 0.000 description 11
239000002775 capsule Substances 0.000 description 11
238000004817 gas chromatography Methods 0.000 description 11
238000001035 drying Methods 0.000 description 10
229910000069 nitrogen hydride Inorganic materials 0.000 description 10
102000005962 receptors Human genes 0.000 description 10
108020003175 receptors Proteins 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
238000012360 testing method Methods 0.000 description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
239000001828 Gelatine Substances 0.000 description 9
241000700159 Rattus Species 0.000 description 9
239000002253 acid Substances 0.000 description 9
229920000159 gelatin Polymers 0.000 description 9
235000019322 gelatine Nutrition 0.000 description 9
210000004556 brain Anatomy 0.000 description 8
230000000694 effects Effects 0.000 description 8
238000009472 formulation Methods 0.000 description 8
239000010410 layer Substances 0.000 description 8
238000001819 mass spectrum Methods 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
229910052799 carbon Inorganic materials 0.000 description 7
238000000605 extraction Methods 0.000 description 7
239000012044 organic layer Substances 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
206010042008 Stereotypy Diseases 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
150000002430 hydrocarbons Chemical group 0.000 description 6
208000013403 hyperactivity Diseases 0.000 description 6
235000019359 magnesium stearate Nutrition 0.000 description 6
230000014759 maintenance of location Effects 0.000 description 6
238000003756 stirring Methods 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
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 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
241001465754 Metazoa Species 0.000 description 5
UNRBEYYLYRXYCG-ZETCQYMHSA-N [(2s)-1-ethylpyrrolidin-2-yl]methanamine Chemical compound CCN1CCC[C@H]1CN UNRBEYYLYRXYCG-ZETCQYMHSA-N 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
125000005843 halogen group Chemical group 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
239000008101 lactose Substances 0.000 description 5
230000003389 potentiating effect Effects 0.000 description 5
230000009467 reduction Effects 0.000 description 5
229950001675 spiperone Drugs 0.000 description 5
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
230000000561 anti-psychotic effect Effects 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
229960001760 dimethyl sulfoxide Drugs 0.000 description 4
239000003480 eluent Substances 0.000 description 4
238000001914 filtration Methods 0.000 description 4
239000007903 gelatin capsule Substances 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
239000003176 neuroleptic agent Substances 0.000 description 4
229920001592 potato starch Polymers 0.000 description 4
239000007858 starting material Substances 0.000 description 4
229910021653 sulphate ion Inorganic materials 0.000 description 4
239000000725 suspension Substances 0.000 description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
229920002554 vinyl polymer Polymers 0.000 description 4
238000005303 weighing Methods 0.000 description 4
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical group [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 3
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
239000002841 Lewis acid Substances 0.000 description 3
229910019142 PO4 Inorganic materials 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
238000007171 acid catalysis Methods 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
230000004913 activation Effects 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
150000008064 anhydrides Chemical class 0.000 description 3
239000000164 antipsychotic agent Substances 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
230000006399 behavior Effects 0.000 description 3
KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 3
230000027455 binding Effects 0.000 description 3
238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
238000001816 cooling Methods 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
239000012458 free base Substances 0.000 description 3
150000007517 lewis acids Chemical class 0.000 description 3
239000007788 liquid Substances 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
150000002829 nitrogen Chemical class 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
239000010452 phosphate Substances 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
238000010992 reflux Methods 0.000 description 3
238000000926 separation method Methods 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
239000007787 solid Substances 0.000 description 3
DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
230000002739 subcortical effect Effects 0.000 description 3
208000011580 syndromic disease Diseases 0.000 description 3
CFGDUGSIBUXRMR-UHFFFAOYSA-N 1,2-dihydropyrrol-2-ide Chemical class C=1C=[C-]NC=1 CFGDUGSIBUXRMR-UHFFFAOYSA-N 0.000 description 2
NSKSXYUOXAQHCH-UHFFFAOYSA-N 2,3,6-trimethoxybenzoic acid Chemical compound COC1=CC=C(OC)C(C(O)=O)=C1OC NSKSXYUOXAQHCH-UHFFFAOYSA-N 0.000 description 2
OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 description 2
AQUBASBAVWBYPD-JTQLQIEISA-N 3-amino-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-6-hydroxy-2-methoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(O)C=CC(N)=C1OC AQUBASBAVWBYPD-JTQLQIEISA-N 0.000 description 2
NMMPPJMYVSIOJE-UHFFFAOYSA-N 3-bromo-2,5,6-trimethoxybenzoyl chloride Chemical compound COC1=CC(Br)=C(OC)C(C(Cl)=O)=C1OC NMMPPJMYVSIOJE-UHFFFAOYSA-N 0.000 description 2
GUJRSXAPGDDABA-NSHDSACASA-N 3-bromo-N-[[(2S)-1-ethyl-2-pyrrolidinyl]methyl]-2,6-dimethoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(OC)C=CC(Br)=C1OC GUJRSXAPGDDABA-NSHDSACASA-N 0.000 description 2
OQOZGNFSDYSQCV-NSHDSACASA-N 3-bromo-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2,5,6-trimethoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(OC)C(Br)=CC(OC)=C1OC OQOZGNFSDYSQCV-NSHDSACASA-N 0.000 description 2
QIGDYWLSMVXJAY-UHFFFAOYSA-N 3-chloro-2,5,6-trimethoxybenzoic acid Chemical compound COC1=CC(Cl)=C(OC)C(C(O)=O)=C1OC QIGDYWLSMVXJAY-UHFFFAOYSA-N 0.000 description 2
CNYFTYULLUBARK-AWEZNQCLSA-N 3-ethyl-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2,5,6-trimethoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(OC)C(CC)=CC(OC)=C1OC CNYFTYULLUBARK-AWEZNQCLSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
229920000945 Amylopectin Polymers 0.000 description 2
208000019901 Anxiety disease Diseases 0.000 description 2
229910015845 BBr3 Inorganic materials 0.000 description 2
239000007848 Bronsted acid Substances 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
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 2
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 2
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 2
208000020401 Depressive disease Diseases 0.000 description 2
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
102000015554 Dopamine receptor Human genes 0.000 description 2
108050004812 Dopamine receptor Proteins 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
235000019483 Peanut oil Nutrition 0.000 description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
208000035755 Psychosomatic disease Diseases 0.000 description 2
208000028017 Psychotic disease Diseases 0.000 description 2
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
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 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
206010047700 Vomiting Diseases 0.000 description 2
239000003377 acid catalyst Substances 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
230000001090 anti-dopaminergic effect Effects 0.000 description 2
JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
230000005540 biological transmission Effects 0.000 description 2
230000031709 bromination Effects 0.000 description 2
238000005893 bromination reaction Methods 0.000 description 2
239000000872 buffer Substances 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
230000001055 chewing effect Effects 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
208000004209 confusion Diseases 0.000 description 2
230000001054 cortical effect Effects 0.000 description 2
239000012043 crude product Substances 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
235000013681 dietary sucrose Nutrition 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000003818 flash chromatography Methods 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000013355 food flavoring agent Nutrition 0.000 description 2
238000011534 incubation Methods 0.000 description 2
SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 description 2
239000012948 isocyanate Substances 0.000 description 2
150000002513 isocyanates Chemical class 0.000 description 2
230000033001 locomotion Effects 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
239000012528 membrane Substances 0.000 description 2
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
XQWBYOCDKGECKG-LBPRGKRZSA-N n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2,3,6-trimethoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(OC)C=CC(OC)=C1OC XQWBYOCDKGECKG-LBPRGKRZSA-N 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
239000012434 nucleophilic reagent Substances 0.000 description 2
239000000312 peanut oil Substances 0.000 description 2
150000002989 phenols Chemical class 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000000843 powder Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
229960003448 remoxipride Drugs 0.000 description 2
230000004044 response Effects 0.000 description 2
201000000980 schizophrenia Diseases 0.000 description 2
208000019116 sleep disease Diseases 0.000 description 2
208000022925 sleep disturbance Diseases 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
239000000126 substance Substances 0.000 description 2
229960004793 sucrose Drugs 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
229940095064 tartrate Drugs 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
235000015112 vegetable and seed oil Nutrition 0.000 description 2
239000008158 vegetable oil Substances 0.000 description 2
ZZJYIKPMDIWRSN-TZBSWOFLSA-N (+)-butaclamol Chemical compound C12=CC=CC=C2CCC2=CC=CC3=C2[C@@H]1CN1CC[C@@](C(C)(C)C)(O)C[C@@H]13 ZZJYIKPMDIWRSN-TZBSWOFLSA-N 0.000 description 1
SKYZYDSNJIOXRL-BTQNPOSSSA-N (6ar)-6-methyl-5,6,6a,7-tetrahydro-4h-dibenzo[de,g]quinoline-10,11-diol;hydrochloride Chemical compound Cl.C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 SKYZYDSNJIOXRL-BTQNPOSSSA-N 0.000 description 1
GAZNVVBKELWTBC-UHFFFAOYSA-N 2,3,4-trimethoxybenzoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C(OC)=C1OC GAZNVVBKELWTBC-UHFFFAOYSA-N 0.000 description 1
IATCWONKKGHXNJ-UHFFFAOYSA-N 2,3,6-trimethoxy-5-propylbenzoic acid Chemical compound CCCC1=CC(OC)=C(OC)C(C(O)=O)=C1OC IATCWONKKGHXNJ-UHFFFAOYSA-N 0.000 description 1
HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 1
SEYURSMOEWBZSA-QMMMGPOBSA-N 2-[(2s)-1-ethylpyrrolidin-2-yl]ethanamine Chemical compound CCN1CCC[C@H]1CCN SEYURSMOEWBZSA-QMMMGPOBSA-N 0.000 description 1
PWMFKTQXTCPHKY-UHFFFAOYSA-N 2-amino-3-bromo-5,6-dimethoxybenzoic acid Chemical compound COC1=CC(Br)=C(N)C(C(O)=O)=C1OC PWMFKTQXTCPHKY-UHFFFAOYSA-N 0.000 description 1
JVZAYLSEXNKOFB-JTQLQIEISA-N 2-amino-3-bromo-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-5,6-dimethoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(N)C(Br)=CC(OC)=C1OC JVZAYLSEXNKOFB-JTQLQIEISA-N 0.000 description 1
XOJHLTLVNGPNPT-UHFFFAOYSA-N 2-methoxy-3,6-bis(phenylmethoxy)benzoic acid Chemical compound C1=CC(OCC=2C=CC=CC=2)=C(C(O)=O)C(OC)=C1OCC1=CC=CC=C1 XOJHLTLVNGPNPT-UHFFFAOYSA-N 0.000 description 1
BOHSCHORFQOYMV-UHFFFAOYSA-N 3,5-dibromo-2,6-dimethoxybenzoic acid Chemical compound COC1=C(Br)C=C(Br)C(OC)=C1C(O)=O BOHSCHORFQOYMV-UHFFFAOYSA-N 0.000 description 1
HMFAZNJRBIZQSC-JTQLQIEISA-N 3-amino-5-bromo-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2,6-dimethoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(OC)C(N)=CC(Br)=C1OC HMFAZNJRBIZQSC-JTQLQIEISA-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
YHDRAWVCUZZYCU-UHFFFAOYSA-N 3-bromo-2,5,6-trimethoxybenzoic acid Chemical compound COC1=CC(Br)=C(OC)C(C(O)=O)=C1OC YHDRAWVCUZZYCU-UHFFFAOYSA-N 0.000 description 1
AVPORVRTSFQDRF-UHFFFAOYSA-N 3-bromo-5-hydroxy-2,6-dimethoxybenzoic acid Chemical compound COC1=C(O)C=C(Br)C(OC)=C1C(O)=O AVPORVRTSFQDRF-UHFFFAOYSA-N 0.000 description 1
QCJVKEMZGGNURL-JTQLQIEISA-N 3-bromo-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2,6-dimethoxy-5-nitrobenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(OC)C(Br)=CC([N+]([O-])=O)=C1OC QCJVKEMZGGNURL-JTQLQIEISA-N 0.000 description 1
ZGACYDUTNBUCGP-VWLOTQADSA-N 3-bromo-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2-hexadecanoyl-5,6-dimethoxybenzamide Chemical compound CCCCCCCCCCCCCCCC(=O)C1=C(Br)C=C(OC)C(OC)=C1C(=O)NC[C@H]1N(CC)CCC1 ZGACYDUTNBUCGP-VWLOTQADSA-N 0.000 description 1
NLIPZVMIMUCCIK-JTQLQIEISA-N 3-bromo-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-5-hydroxy-2,6-dimethoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(OC)C(O)=CC(Br)=C1OC NLIPZVMIMUCCIK-JTQLQIEISA-N 0.000 description 1
MPKKCEUANNGJTC-NSHDSACASA-N 3-chloro-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2,5,6-trimethoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(OC)C(Cl)=CC(OC)=C1OC MPKKCEUANNGJTC-NSHDSACASA-N 0.000 description 1
SGXUYOXSIBSRTB-LBPRGKRZSA-N 3-ethyl-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2,5-dihydroxy-6-methoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(O)C(CC)=CC(O)=C1OC SGXUYOXSIBSRTB-LBPRGKRZSA-N 0.000 description 1
NHGHSSSIIOPHJZ-ZDUSSCGKSA-N 3-ethyl-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2-hydroxy-5,6-dimethoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(O)C(CC)=CC(OC)=C1OC NHGHSSSIIOPHJZ-ZDUSSCGKSA-N 0.000 description 1
VXEGSRKPIUDPQT-UHFFFAOYSA-N 4-[4-(4-methoxyphenyl)piperazin-1-yl]aniline Chemical compound C1=CC(OC)=CC=C1N1CCN(C=2C=CC(N)=CC=2)CC1 VXEGSRKPIUDPQT-UHFFFAOYSA-N 0.000 description 1
PVYFJVBTMPNPEN-DEOSSOPVSA-N 4-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2-methoxy-3,6-bis(phenylmethoxy)benzamide Chemical compound CCN1CCC[C@H]1CC1=CC(OCC=2C=CC=CC=2)=C(C(N)=O)C(OC)=C1OCC1=CC=CC=C1 PVYFJVBTMPNPEN-DEOSSOPVSA-N 0.000 description 1
PJNKQCUVRYAQNE-JTQLQIEISA-N 4-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-3,6-dihydroxy-2-methoxybenzamide Chemical compound CCN1CCC[C@H]1CC1=CC(O)=C(C(N)=O)C(OC)=C1O PJNKQCUVRYAQNE-JTQLQIEISA-N 0.000 description 1
XYNBEIZBNVFDJT-PPHPATTJSA-N 4-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-3,6-dihydroxy-2-methoxybenzamide;hydrochloride Chemical compound Cl.CCN1CCC[C@H]1CC1=CC(O)=C(C(N)=O)C(OC)=C1O XYNBEIZBNVFDJT-PPHPATTJSA-N 0.000 description 1
IWMSWYCDJJWHFO-LBPRGKRZSA-N 5-amino-3-ethyl-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2-hydroxy-6-methoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(O)C(CC)=CC(N)=C1OC IWMSWYCDJJWHFO-LBPRGKRZSA-N 0.000 description 1
AXNQEJWWGGMBFH-LBPRGKRZSA-N 5-bromo-2,3-diethoxy-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-6-hydroxybenzamide Chemical compound CCOC1=CC(Br)=C(O)C(C(=O)NC[C@H]2N(CCC2)CC)=C1OCC AXNQEJWWGGMBFH-LBPRGKRZSA-N 0.000 description 1
RJMFJSBUCRXRGR-VIFPVBQESA-N 5-bromo-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2,3-dihydroxy-6-methoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(O)C(O)=CC(Br)=C1OC RJMFJSBUCRXRGR-VIFPVBQESA-N 0.000 description 1
PVTGDSOBBMPZMQ-JTQLQIEISA-N 5-chloro-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2-hydroxy-3,6-dimethoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(O)C(OC)=CC(Cl)=C1OC PVTGDSOBBMPZMQ-JTQLQIEISA-N 0.000 description 1
WTKIGCPVTZEDQY-ZDUSSCGKSA-N 5-ethyl-n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2-hydroxy-3,6-dimethoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(O)C(OC)=CC(CC)=C1OC WTKIGCPVTZEDQY-ZDUSSCGKSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
229910002012 Aerosil® Inorganic materials 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
101100097467 Arabidopsis thaliana SYD gene Proteins 0.000 description 1
YLMXBNACRIGGFX-UHFFFAOYSA-N C=1[C-]=NNN=1 Chemical compound C=1[C-]=NNN=1 YLMXBNACRIGGFX-UHFFFAOYSA-N 0.000 description 1
125000006519 CCH3 Chemical group 0.000 description 1
101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical class ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 1
239000004150 EU approved colour Substances 0.000 description 1
244000165918 Eucalyptus papuana Species 0.000 description 1
208000027776 Extrapyramidal disease Diseases 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
WPPONCHFOIIFIJ-UHFFFAOYSA-N N1N=NN=[C-]1 Chemical compound N1N=NN=[C-]1 WPPONCHFOIIFIJ-UHFFFAOYSA-N 0.000 description 1
239000005662 Paraffin oil Substances 0.000 description 1
DPWPWRLQFGFJFI-UHFFFAOYSA-N Pargyline Chemical compound C#CCN(C)CC1=CC=CC=C1 DPWPWRLQFGFJFI-UHFFFAOYSA-N 0.000 description 1
229920005439 Perspex® Polymers 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical class NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 description 1
101100495925 Schizosaccharomyces pombe (strain 972 / ATCC 24843) chr3 gene Proteins 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
208000007107 Stomach Ulcer Diseases 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
230000009471 action Effects 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
239000000556 agonist Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000005215 alkyl ethers Chemical class 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
239000004411 aluminium Substances 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
125000003368 amide group Chemical group 0.000 description 1
239000000538 analytical sample Substances 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000002973 anti-dopamine Effects 0.000 description 1
229960003990 apomorphine hydrochloride Drugs 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
230000003542 behavioural effect Effects 0.000 description 1
150000003936 benzamides Chemical class 0.000 description 1
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 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
NBLAIKHFQBOVPV-UHFFFAOYSA-N bis(ethoxycarbonyl)azaniumylideneazanide Chemical compound CCOC(=O)[N+](=[N-])C(=O)OCC NBLAIKHFQBOVPV-UHFFFAOYSA-N 0.000 description 1
238000009835 boiling Methods 0.000 description 1
229910052796 boron Inorganic materials 0.000 description 1
239000012267 brine Substances 0.000 description 1
FNXLCIKXHOPCKH-UHFFFAOYSA-N bromamine Chemical class BrN FNXLCIKXHOPCKH-UHFFFAOYSA-N 0.000 description 1
GSQACUNMFGRAKY-UHFFFAOYSA-N bromine;1,4-dioxane Chemical compound [Br].C1COCCO1 GSQACUNMFGRAKY-UHFFFAOYSA-N 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 1
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
235000013539 calcium stearate Nutrition 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
239000004203 carnauba wax Substances 0.000 description 1
235000013869 carnauba wax Nutrition 0.000 description 1
239000000969 carrier Substances 0.000 description 1
150000003943 catecholamines Chemical class 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
230000008859 change Effects 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
238000005660 chlorination reaction Methods 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
238000000576 coating method Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
235000005687 corn oil Nutrition 0.000 description 1
239000002285 corn oil Substances 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
239000007822 coupling agent Substances 0.000 description 1
239000013058 crude material Substances 0.000 description 1
230000020335 dealkylation Effects 0.000 description 1
238000006900 dealkylation reaction Methods 0.000 description 1
239000003405 delayed action preparation Substances 0.000 description 1
230000017858 demethylation Effects 0.000 description 1
238000010520 demethylation reaction Methods 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
KUMNEOGIHFCNQW-UHFFFAOYSA-N diphenyl phosphite Chemical compound C=1C=CC=CC=1OP([O-])OC1=CC=CC=C1 KUMNEOGIHFCNQW-UHFFFAOYSA-N 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
208000000718 duodenal ulcer Diseases 0.000 description 1
GCFHZZWXZLABBL-UHFFFAOYSA-N ethanol;hexane Chemical compound CCO.CCCCCC GCFHZZWXZLABBL-UHFFFAOYSA-N 0.000 description 1
HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000007789 gas Substances 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
201000005917 gastric ulcer Diseases 0.000 description 1
239000000499 gel Substances 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
ARBOVOVUTSQWSS-UHFFFAOYSA-N hexadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCC(Cl)=O ARBOVOVUTSQWSS-UHFFFAOYSA-N 0.000 description 1
QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
150000002440 hydroxy compounds Chemical class 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
CUILPNURFADTPE-UHFFFAOYSA-N hypobromous acid Chemical compound BrO CUILPNURFADTPE-UHFFFAOYSA-N 0.000 description 1
JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
150000003949 imides Chemical class 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000002540 isothiocyanates Chemical class 0.000 description 1
239000004922 lacquer Substances 0.000 description 1
239000003446 ligand Substances 0.000 description 1
230000002197 limbic effect Effects 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
RHMQNXNXUZLEIY-UHFFFAOYSA-N methanol;2-propan-2-yloxypropane Chemical compound OC.CC(C)OC(C)C RHMQNXNXUZLEIY-UHFFFAOYSA-N 0.000 description 1
NSPJNIDYTSSIIY-UHFFFAOYSA-N methoxy(methoxymethoxy)methane Chemical compound COCOCOC NSPJNIDYTSSIIY-UHFFFAOYSA-N 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
CMKFMAOMSNBJHX-MRXNPFEDSA-N n-[[(2r)-1-benzylpyrrolidin-2-yl]methyl]-3-bromo-2,5,6-trimethoxybenzamide Chemical compound COC1=CC(Br)=C(OC)C(C(=O)NC[C@@H]2N(CCC2)CC=2C=CC=CC=2)=C1OC CMKFMAOMSNBJHX-MRXNPFEDSA-N 0.000 description 1
PQQXQOJIDLXQOC-HNNXBMFYSA-N n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2,3,6-trimethoxy-5-propylbenzamide Chemical compound CCCC1=CC(OC)=C(OC)C(C(=O)NC[C@H]2N(CCC2)CC)=C1OC PQQXQOJIDLXQOC-HNNXBMFYSA-N 0.000 description 1
UQUSHEDVYVRCJT-LBPRGKRZSA-N n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2-hydroxy-5,6-dimethoxy-3-methylbenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(O)C(C)=CC(OC)=C1OC UQUSHEDVYVRCJT-LBPRGKRZSA-N 0.000 description 1
UCSPRWCFKNGDEC-DEOSSOPVSA-N n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-2-methoxy-3,6-bis(phenylmethoxy)benzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C(C(=C(OCC=1C=CC=CC=1)C=C1)OC)=C1OCC1=CC=CC=C1 UCSPRWCFKNGDEC-DEOSSOPVSA-N 0.000 description 1
ZQMWIMXUDSTEFT-NSHDSACASA-N n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-3-hydroxy-2,6-dimethoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(OC)C=CC(O)=C1OC ZQMWIMXUDSTEFT-NSHDSACASA-N 0.000 description 1
DQDAHRKHWVTGOB-NSHDSACASA-N n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-6-hydroxy-2,3-dimethoxybenzamide Chemical compound CCN1CCC[C@H]1CNC(=O)C1=C(O)C=CC(OC)=C1OC DQDAHRKHWVTGOB-NSHDSACASA-N 0.000 description 1
PVJRHMUARAWGGE-MERQFXBCSA-N n-[[(2s)-1-ethylpyrrolidin-2-yl]methyl]-6-hydroxy-2,3-dimethoxybenzamide;hydrochloride Chemical compound Cl.CCN1CCC[C@H]1CNC(=O)C1=C(O)C=CC(OC)=C1OC PVJRHMUARAWGGE-MERQFXBCSA-N 0.000 description 1
XVDBWWRIXBMVJV-UHFFFAOYSA-N n-[bis(dimethylamino)phosphanyl]-n-methylmethanamine Chemical compound CN(C)P(N(C)C)N(C)C XVDBWWRIXBMVJV-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
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000001537 neural effect Effects 0.000 description 1
230000000701 neuroleptic effect Effects 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
210000001009 nucleus accumben Anatomy 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
229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
229960001779 pargyline Drugs 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000012071 phase Substances 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
XIPFMBOWZXULIA-UHFFFAOYSA-N pivalamide Chemical compound CC(C)(C)C(N)=O XIPFMBOWZXULIA-UHFFFAOYSA-N 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000004926 polymethyl methacrylate Substances 0.000 description 1
230000001242 postsynaptic effect Effects 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
229960004063 propylene glycol Drugs 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
AUKXFNABVHIUAC-UHFFFAOYSA-N pyrrolidin-2-ylmethylamine Chemical class NCC1CCCN1 AUKXFNABVHIUAC-UHFFFAOYSA-N 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000003252 repetitive effect Effects 0.000 description 1
QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
229910052814 silicon oxide Inorganic materials 0.000 description 1
239000005049 silicon tetrachloride Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 1
OMJKKNSEIURJRF-UHFFFAOYSA-M sodium;phenylmethaneselenolate Chemical compound [Na+].[Se-]CC1=CC=CC=C1 OMJKKNSEIURJRF-UHFFFAOYSA-M 0.000 description 1
241000894007 species Species 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000008227 sterile water for injection Substances 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000007939 sustained release tablet Substances 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000004149 thio group Chemical group *S* 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
229940086542 triethylamine Drugs 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000007306 turnover Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000001993 wax Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- 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
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/21—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Neurology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Biomedical Technology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Neurosurgery (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Psychiatry (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyrrole Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

CY1544A 1984-01-31 1991-03-22 Oxysalicylamido derivatives CY1544A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
SE8400478A SE8400478D0 (sv)	1984-01-31	1984-01-31	Oxysalicylamido derivatives

Publications (1)

Publication Number	Publication Date
CY1544A true CY1544A (en)	1991-03-22

Family

ID=20354529

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CY1544A CY1544A (en)	1984-01-31	1991-03-22	Oxysalicylamido derivatives

Country Status (25)

Country	Link
EP (1)	EP0156776B1 (da)
JP (1)	JPH07103097B2 (da)
AT (1)	ATE41770T1 (da)
AU (1)	AU575113B2 (da)
CA (1)	CA1253869A (da)
CY (1)	CY1544A (da)
DD (1)	DD231349A5 (da)
DE (1)	DE3569111D1 (da)
DK (1)	DK38685A (da)
ES (3)	ES8609239A1 (da)
FI (1)	FI83771C (da)
GB (1)	GB2153354B (da)
GR (1)	GR850268B (da)
HK (1)	HK53090A (da)
HU (1)	HU198684B (da)
IE (1)	IE57888B1 (da)
IS (1)	IS1442B6 (da)
MY (1)	MY102377A (da)
NO (1)	NO171363C (da)
NZ (1)	NZ210939A (da)
PH (2)	PH22430A (da)
PT (1)	PT79900B (da)
SE (1)	SE8400478D0 (da)
SG (1)	SG35290G (da)
ZA (1)	ZA85158B (da)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5446147A (en) *	1992-04-03	1995-08-29	Trustees Of The University Of Pennsylvania	Fluorinated and iodinated dopamine agents

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5822110B2 (ja) *	1977-08-08	1983-05-06	塩野義製薬株式会社	ベンズアミド誘導体の合成法
FR2440946A2 (fr) *	1978-01-20	1980-06-06	Ile De France	Nouveaux benzamides heterocycliques substitues, leurs procedes de preparation et leur application comme modificateurs du comportement
SE411118B (sv) *	1978-03-23	1979-12-03	Astra Laekemedel Ab	Ett forfarande for framstellning av 2,6-dialkoxibensamider med terapentiska egenskaper
JPS55130957A (en) *	1979-03-30	1980-10-11	Kyowa Hakko Kogyo Co Ltd	Production of benzamide derivative
SE8101536L (sv) *	1981-03-11	1982-09-12	Astra Laekemedel Ab	Bensamid-derivat
SE8205135D0 (sv) *	1982-09-09	1982-09-09	Astra Laekemedel Ab	Benzamido-derivatives

1984
- 1984-01-31 SE SE8400478A patent/SE8400478D0/xx unknown
1985
- 1985-01-07 ZA ZA85158A patent/ZA85158B/xx unknown
- 1985-01-21 DE DE8585850022T patent/DE3569111D1/de not_active Expired
- 1985-01-21 NO NO850244A patent/NO171363C/no unknown
- 1985-01-21 EP EP85850022A patent/EP0156776B1/en not_active Expired
- 1985-01-21 AT AT85850022T patent/ATE41770T1/de not_active IP Right Cessation
- 1985-01-23 CA CA000472638A patent/CA1253869A/en not_active Expired
- 1985-01-25 AU AU38088/85A patent/AU575113B2/en not_active Ceased
- 1985-01-25 NZ NZ210939A patent/NZ210939A/xx unknown
- 1985-01-28 GB GB08502095A patent/GB2153354B/en not_active Expired
- 1985-01-28 PH PH31786A patent/PH22430A/en unknown
- 1985-01-29 DD DD85272829A patent/DD231349A5/de not_active IP Right Cessation
- 1985-01-29 DK DK38685A patent/DK38685A/da not_active Application Discontinuation
- 1985-01-30 HU HU85343A patent/HU198684B/hu not_active IP Right Cessation
- 1985-01-30 IE IE220/85A patent/IE57888B1/en not_active IP Right Cessation
- 1985-01-30 FI FI850398A patent/FI83771C/fi not_active IP Right Cessation
- 1985-01-30 PT PT79900A patent/PT79900B/pt not_active IP Right Cessation
- 1985-01-30 ES ES539955A patent/ES8609239A1/es not_active Expired
- 1985-01-30 JP JP60014622A patent/JPH07103097B2/ja not_active Expired - Lifetime
- 1985-01-30 GR GR850268A patent/GR850268B/el unknown
- 1985-01-31 IS IS2974A patent/IS1442B6/is unknown
1986
- 1986-01-13 ES ES550826A patent/ES8801199A1/es not_active Expired
- 1986-01-13 ES ES550825A patent/ES8707712A1/es not_active Expired
1987
- 1987-09-29 MY MYPI87002193A patent/MY102377A/en unknown
1988
- 1988-02-29 PH PH36568A patent/PH24046A/en unknown
1990
- 1990-05-18 SG SG352/90A patent/SG35290G/en unknown
- 1990-07-12 HK HK530/90A patent/HK53090A/xx not_active IP Right Cessation
1991
- 1991-03-22 CY CY1544A patent/CY1544A/en unknown

Also Published As

Publication number	Publication date
NO171363B (no)	1992-11-23
SE8400478D0 (sv)	1984-01-31
IE850220L (en)	1985-07-31
JPH07103097B2 (ja)	1995-11-08
FI83771C (fi)	1991-08-26
ATE41770T1 (de)	1989-04-15
ES539955A0 (es)	1986-09-01
PT79900A (en)	1985-02-01
NO171363C (no)	1993-03-03
AU3808885A (en)	1985-08-08
HU198684B (en)	1989-11-28
IS1442B6 (is)	1990-12-14
JPS60178859A (ja)	1985-09-12
HUT37750A (en)	1986-02-28
ES8609239A1 (es)	1986-09-01
SG35290G (en)	1990-07-13
EP0156776A1 (en)	1985-10-02
ES550825A0 (es)	1987-08-16
NO850244L (no)	1985-08-01
EP0156776B1 (en)	1989-03-29
GR850268B (da)	1985-05-28
DK38685D0 (da)	1985-01-29
FI850398L (fi)	1985-08-01
HK53090A (en)	1990-07-20
FI850398A0 (fi)	1985-01-30
GB2153354A (en)	1985-08-21
DD231349A5 (de)	1985-12-24
ES8707712A1 (es)	1987-08-16
PH22430A (en)	1988-09-12
FI83771B (fi)	1991-05-15
ES8801199A1 (es)	1987-12-16
MY102377A (en)	1992-06-17
IE57888B1 (en)	1993-05-05
AU575113B2 (en)	1988-07-21
PT79900B (en)	1987-02-03
GB2153354B (en)	1987-10-21
DK38685A (da)	1985-08-01
NZ210939A (en)	1988-10-28
CA1253869A (en)	1989-05-09
GB8502095D0 (en)	1985-02-27
IS2974A7 (is)	1985-08-01
PH24046A (en)	1990-03-05
DE3569111D1 (en)	1989-05-03
ES550826A0 (es)	1987-12-16
ZA85158B (en)	1985-09-25

Publication	Publication Date	Title
KR890001375B1 (ko)	1989-05-02	벤즈아미도 유도체의 제조 방법
GB2176785A (en)	1987-01-07	Annellated benzamide derivatives
US4937260A (en)	1990-06-26	Benzamido-derivatives
DK154137B (da)	1988-10-17	Analogifremgangsmaade til fremstilling af meta-sulfonamido-benzamidderivater
TWI360540B (en)	2012-03-21	Tetrahydroisoquinolylsulphonamide derivatives, the
US5498628A (en)	1996-03-12	Naphthamide derivatives
US6063964A (en)	2000-05-16	5-hydroxymethyl-2-aminotetralins as cardiovascular agents
CY1544A (en)	1991-03-22	Oxysalicylamido derivatives
US5240957A (en)	1993-08-31	Oxysalicylamido derivatives
EP0207913B1 (en)	1990-10-31	Catechol carboxamides, process for their preparation, intermediates and a pharmaceutical preparation
EP2438050B9 (en)	2014-04-23	Novel derivatives of aryl-{4-halogeno-4-[aminomethyl]-piperidin-1-yl}-methanone, their method of preparation and their use as medicinal products
Clarke et al.	1978	A series of hexahydro [1, 4] oxazino [3, 4-a] isoquinolines as potential neuroleptics
FI89796C (fi)	1993-11-25	Oxisalicylamidoderivaters mellanprodukter
KR19980703590A (ko)	1998-11-05	5-ｈｔ1ａ 수용체에 대한 높은 친화도를 갖는 페녹시에틸아민유도체, 그의 제조, 그의 약물로서의 용도 및 상기 유도체를 함유하는 제약 조성물
NO863924L (no)	1982-09-13	Mellomprodukter for bruk ved fremstilling av terapeutisk virksomme benzamidderivater.
CZ304599A3 (cs)	2000-02-16	5-hydroxymethyl-2-aminotetraliny