CA1055945A - Produit pharmaceutique et methode pour la production d'un compose antipsychotique, ne provoquant pas de symptomes extrapyramidaux - Google Patents

Produit pharmaceutique et methode pour la production d'un compose antipsychotique, ne provoquant pas de symptomes extrapyramidaux

Info

Publication number: CA1055945A
Authority: CA; Canada
Prior art keywords: chloro; hydrogen; methyl; formula; mol
Prior art date: 1974-11-06
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA238,781A

Other languages

English (en)

Other versions

CA238781S (en

Inventor

Charles L. Zirkle

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

GlaxoSmithKline Inc

Original Assignee

Smith Kline and French Canada Ltd

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.)

1974-11-06

Filing date

1975-10-31

Publication date

1979-06-05

1975-10-31 Application filed by Smith Kline and French Canada Ltd filed Critical Smith Kline and French Canada Ltd

1979-06-05 Application granted granted Critical

1979-06-05 Publication of CA1055945A publication Critical patent/CA1055945A/fr

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 32
230000000561 anti-psychotic effect Effects 0.000 title abstract description 13
239000008194 pharmaceutical composition Substances 0.000 title abstract description 4
208000027776 Extrapyramidal disease Diseases 0.000 title description 6
-1 piperidylidene Chemical class 0.000 claims abstract description 29
150000001875 compounds Chemical class 0.000 claims abstract description 18
231100000252 nontoxic Toxicity 0.000 claims abstract description 10
230000003000 nontoxic effect Effects 0.000 claims abstract description 10
238000006243 chemical reaction Methods 0.000 claims abstract description 9
JNELGWHKGNBSMD-UHFFFAOYSA-N xanthone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3OC2=C1 JNELGWHKGNBSMD-UHFFFAOYSA-N 0.000 claims abstract description 7
YRHRIQCWCFGUEQ-UHFFFAOYSA-N thioxanthen-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3SC2=C1 YRHRIQCWCFGUEQ-UHFFFAOYSA-N 0.000 claims abstract description 4
239000001257 hydrogen Substances 0.000 claims description 35
229910052739 hydrogen Inorganic materials 0.000 claims description 35
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 24
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 21
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 17
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
239000001301 oxygen Substances 0.000 claims description 16
229910052760 oxygen Inorganic materials 0.000 claims description 16
238000010992 reflux Methods 0.000 claims description 13
235000019260 propionic acid Nutrition 0.000 claims description 12
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 12
239000002904 solvent Substances 0.000 claims description 12
NCYNKWQXFADUOZ-UHFFFAOYSA-N 1,1-dioxo-2,1$l^{6}-benzoxathiol-3-one Chemical compound C1=CC=C2C(=O)OS(=O)(=O)C2=C1 NCYNKWQXFADUOZ-UHFFFAOYSA-N 0.000 claims description 11
239000002253 acid Substances 0.000 claims description 11
150000001408 amides Chemical class 0.000 claims description 10
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
229940098779 methanesulfonic acid Drugs 0.000 claims description 8
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 6
238000010438 heat treatment Methods 0.000 claims description 6
150000002431 hydrogen Chemical group 0.000 claims description 6
QUXRAOQDUJFWIA-UHFFFAOYSA-N 4-(2-chloroxanthen-9-ylidene)-1-methylpiperidine Chemical compound C1CN(C)CCC1=C1C2=CC(Cl)=CC=C2OC2=CC=CC=C21 QUXRAOQDUJFWIA-UHFFFAOYSA-N 0.000 claims description 5
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
229910052717 sulfur Inorganic materials 0.000 claims description 5
239000011593 sulfur Substances 0.000 claims description 5
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 4
XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 3
VKOJCXWEBUNAGY-UHFFFAOYSA-N 2-chloro-9-(1-methylpiperidin-4-yl)xanthen-9-ol Chemical compound C1CN(C)CCC1C1(O)C2=CC(Cl)=CC=C2OC2=CC=CC=C21 VKOJCXWEBUNAGY-UHFFFAOYSA-N 0.000 claims description 2
PRWJZNITVOUZBU-UHFFFAOYSA-N 2-chloroxanthen-9-one Chemical compound C1=CC=C2C(=O)C3=CC(Cl)=CC=C3OC2=C1 PRWJZNITVOUZBU-UHFFFAOYSA-N 0.000 claims description 2
150000001347 alkyl bromides Chemical class 0.000 claims description 2
YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 claims description 2
239000003960 organic solvent Substances 0.000 claims description 2
235000013350 formula milk Nutrition 0.000 claims 11
238000002360 preparation method Methods 0.000 claims 2
150000001263 acyl chlorides Chemical class 0.000 claims 1
229960002337 magnesium chloride Drugs 0.000 claims 1
TWRXJAOTZQYOKJ-UHFFFAOYSA-L magnesium chloride Substances [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims 1
229910001629 magnesium chloride Inorganic materials 0.000 claims 1
235000011147 magnesium chloride Nutrition 0.000 claims 1
239000004480 active ingredient Substances 0.000 abstract description 9
241001465754 Metazoa Species 0.000 abstract description 5
208000024891 symptom Diseases 0.000 abstract description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 116
239000000243 solution Substances 0.000 description 69
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 57
239000000203 mixture Substances 0.000 description 55
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
239000011541 reaction mixture Substances 0.000 description 26
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
239000000284 extract Substances 0.000 description 20
229940076134 benzene Drugs 0.000 description 19
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
239000007818 Grignard reagent Substances 0.000 description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 10
150000004795 grignard reagents Chemical class 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
239000007787 solid Substances 0.000 description 10
MYGXGCCFTPKWIH-UHFFFAOYSA-N 4-chloro-1-methylpiperidine Chemical compound CN1CCC(Cl)CC1 MYGXGCCFTPKWIH-UHFFFAOYSA-N 0.000 description 9
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
239000003921 oil Substances 0.000 description 9
235000019198 oils Nutrition 0.000 description 9
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
238000003756 stirring Methods 0.000 description 9
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 7
239000007864 aqueous solution Substances 0.000 description 7
239000003814 drug Substances 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
239000000047 product Substances 0.000 description 7
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
229940079593 drug Drugs 0.000 description 6
239000012280 lithium aluminium hydride Substances 0.000 description 6
239000011777 magnesium Substances 0.000 description 6
QTOOYVGXYKLUNG-UHFFFAOYSA-N 4-(2-chloroxanthen-9-ylidene)piperidine Chemical compound C12=CC(Cl)=CC=C2OC2=CC=CC=C2C1=C1CCNCC1 QTOOYVGXYKLUNG-UHFFFAOYSA-N 0.000 description 5
102000015554 Dopamine receptor Human genes 0.000 description 5
108050004812 Dopamine receptor Proteins 0.000 description 5
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
235000011054 acetic acid Nutrition 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
239000000164 antipsychotic agent Substances 0.000 description 5
239000012458 free base Substances 0.000 description 5
239000005457 ice water Substances 0.000 description 5
229910052749 magnesium Inorganic materials 0.000 description 5
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 5
239000008096 xylene Substances 0.000 description 5
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
239000005711 Benzoic acid Substances 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
235000019270 ammonium chloride Nutrition 0.000 description 4
235000010233 benzoic acid Nutrition 0.000 description 4
229960004365 benzoic acid Drugs 0.000 description 4
239000003937 drug carrier Substances 0.000 description 4
229940093499 ethyl acetate Drugs 0.000 description 4
235000019439 ethyl acetate Nutrition 0.000 description 4
230000003902 lesion Effects 0.000 description 4
229940032330 sulfuric acid Drugs 0.000 description 4
238000010626 work up procedure Methods 0.000 description 4
JFRMYMMIJXLMBB-UHFFFAOYSA-N xanthydrol Chemical compound C1=CC=C2C(O)C3=CC=CC=C3OC2=C1 JFRMYMMIJXLMBB-UHFFFAOYSA-N 0.000 description 4
FQLSBXCEUFTIHI-UHFFFAOYSA-N 4-(2-chlorothioxanthen-9-ylidene)piperidine Chemical compound C12=CC(Cl)=CC=C2SC2=CC=CC=C2C1=C1CCNCC1 FQLSBXCEUFTIHI-UHFFFAOYSA-N 0.000 description 3
IWNPWQRBFNOGHM-UHFFFAOYSA-N 9h-thioxanthen-9-ol Chemical compound C1=CC=C2C(O)C3=CC=CC=C3SC2=C1 IWNPWQRBFNOGHM-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
229910021591 Copper(I) chloride Inorganic materials 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
229940005529 antipsychotics Drugs 0.000 description 3
239000002775 capsule Substances 0.000 description 3
KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 3
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 3
229940045803 cuprous chloride Drugs 0.000 description 3
229960003638 dopamine Drugs 0.000 description 3
230000003291 dopaminomimetic effect Effects 0.000 description 3
239000003480 eluent Substances 0.000 description 3
239000012259 ether extract Substances 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
238000000605 extraction Methods 0.000 description 3
150000004678 hydrides Chemical class 0.000 description 3
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
229910000041 hydrogen chloride Inorganic materials 0.000 description 3
239000011976 maleic acid Substances 0.000 description 3
150000002688 maleic acid derivatives Chemical class 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
239000000725 suspension Substances 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
BQDNFXRLGVGWRP-UHFFFAOYSA-N 2,6-difluorothioxanthen-9-one Chemical compound C1=C(F)C=C2C(=O)C3=CC=C(F)C=C3SC2=C1 BQDNFXRLGVGWRP-UHFFFAOYSA-N 0.000 description 2
WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 2
IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
YESXXPJHOUAICR-UHFFFAOYSA-N 3-fluorothioxanthen-9-one Chemical compound C1=CC=C2C(=O)C3=CC=C(F)C=C3SC2=C1 YESXXPJHOUAICR-UHFFFAOYSA-N 0.000 description 2
UHGZJXZINNENOT-UHFFFAOYSA-N 4-(2-bromothioxanthen-9-ylidene)-1-methylpiperidine Chemical compound C1CN(C)CCC1=C1C2=CC(Br)=CC=C2SC2=CC=CC=C21 UHGZJXZINNENOT-UHFFFAOYSA-N 0.000 description 2
WTZPERAJKMXMSC-UHFFFAOYSA-N 4-(2-bromoxanthen-9-ylidene)piperidine Chemical compound C12=CC(Br)=CC=C2OC2=CC=CC=C2C1=C1CCNCC1 WTZPERAJKMXMSC-UHFFFAOYSA-N 0.000 description 2
LNGGMSPZRSOIPB-UHFFFAOYSA-N 4-(2-chloroxanthen-9-ylidene)-1-(cyclobutylmethyl)piperidine Chemical compound C12=CC(Cl)=CC=C2OC2=CC=CC=C2C1=C(CC1)CCN1CC1CCC1 LNGGMSPZRSOIPB-UHFFFAOYSA-N 0.000 description 2
QDOJNWFOCOWAPO-UHFFFAOYSA-N 4-chloro-1-methylpiperidine;hydron;chloride Chemical compound Cl.CN1CCC(Cl)CC1 QDOJNWFOCOWAPO-UHFFFAOYSA-N 0.000 description 2
VAVKIJNEVUPNQP-UHFFFAOYSA-N 9-(1-methylpiperidin-4-ylidene)xanthene-2-carbonitrile Chemical compound C1CN(C)CCC1=C1C2=CC(C#N)=CC=C2OC2=CC=CC=C21 VAVKIJNEVUPNQP-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
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 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
229940025084 amphetamine Drugs 0.000 description 2
239000003708 ampul Substances 0.000 description 2
239000012223 aqueous fraction Substances 0.000 description 2
230000006399 behavior Effects 0.000 description 2
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 2
239000003610 charcoal Substances 0.000 description 2
ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 2
229960001076 chlorpromazine Drugs 0.000 description 2
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
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238000001665 trituration Methods 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
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
- C07D311/82—Xanthenes
- C07D311/84—Xanthenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 9
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- 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
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- 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
- C07C65/24—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 polycyclic

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Biomedical Technology (AREA)
Psychiatry (AREA)
Epidemiology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CA238,781A 1974-11-06 1975-10-31 Produit pharmaceutique et methode pour la production d'un compose antipsychotique, ne provoquant pas de symptomes extrapyramidaux Expired CA1055945A (fr)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US52121674A	1974-11-06	1974-11-06

Publications (1)

Publication Number	Publication Date
CA1055945A true CA1055945A (fr)	1979-06-05

Family

ID=24075868

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA238,781A Expired CA1055945A (fr)	1974-11-06	1975-10-31	Produit pharmaceutique et methode pour la production d'un compose antipsychotique, ne provoquant pas de symptomes extrapyramidaux

Country Status (17)

Country	Link
JP (1)	JPS5826754B2 (fr)
AU (1)	AU498298B2 (fr)
BE (1)	BE835224A (fr)
CA (1)	CA1055945A (fr)
CH (1)	CH624403A5 (fr)
DE (1)	DE2549841A1 (fr)
DK (1)	DK139429B (fr)
ES (1)	ES442357A1 (fr)
FR (1)	FR2290202A1 (fr)
HU (1)	HU174639B (fr)
IE (1)	IE42137B1 (fr)
IL (1)	IL48400A (fr)
LU (1)	LU73714A1 (fr)
NL (1)	NL7512974A (fr)
NZ (1)	NZ179139A (fr)
PH (1)	PH12158A (fr)
ZA (1)	ZA756550B (fr)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2357251A1 (fr) *	1976-07-09	1978-02-03	Merck & Co Inc	1-methyl-4-(2-carboxy-1-thioxanthan-9-ylidene)-piperidine
US4073912A (en) *	1976-10-12	1978-02-14	Smithkline Corporation	Piperidylidene derivatives of benzo-fused xanthenes, thioxanthenes and dibenzoxepins and antipsychotic use thereof
US4089961A (en) *	1976-11-08	1978-05-16	Smithkline Corporation	Antipsychotically useful quinolizidylidene derivatives of xanthenes, thioxanthenes and dibenzoxepins
NZ189108A (en) *	1977-12-29	1982-02-23	Kefalas As	2-methylthio-6-fluoro-9-(1-methyl-4-piperidylidene)-thioxanthene and pharmaceutical compositions intermediate 2-methylthio-6-fluoro-9-(1-methyl-4-piperidyl)-thioxanthen-9-ol
US4777177A (en) *	1984-10-19	1988-10-11	Ciba-Geigy Corporation	Pesticidal thioxanthen-9-ylidenepiperidines
US5250681A (en) *	1988-06-02	1993-10-05	Ajinomoto Co., Inc.	Piperidine derivatives and hypotensives containing the same
CA2004211A1 (fr) *	1988-11-30	1990-05-31	Masataka Syoji	Derives de piperidine et hypotenseurs les contenant
EP1306376A1 (fr) *	2001-10-25	2003-05-02	Biofrontera Pharmaceuticals AG	Dérives de 4-(thio- or selenoxanthene-9-ylidene)-piperidine ou acridine et leur application comme antagonistes selectives de 5-HT2B
US7060711B2 (en)	2001-10-25	2006-06-13	Biofrontera Bioscience Gmbh	Derivatives of 4-(thio- or selenoxanthene-9-ylidene)-piperidine or acridine and its use as a selective 5-HT2B receptor antagonist
US7589103B2 (en)	2003-06-27	2009-09-15	Janssen Pharmaceutica N.V.	Tricyclic-bridged piperidinylidene derivatives as 8-opioid modulators
CA2574768A1 (fr)	2004-08-05	2006-02-05	Janssen Pharmaceutica N.V.	Modulateurs tricycliques du recepteur opioide delta
EP1836196A1 (fr) *	2004-12-22	2007-09-26	Janssen Pharmaceutica N.V.	Modulateurs des recepteurs opioides delta tricycliques
MX2007007626A (es)	2004-12-22	2008-01-28	Johnson & Johnson	Moduladores delta-opioides triciclicos.
CN101119992A (zh)	2004-12-22	2008-02-06	詹森药业有限公司	三环δ阿片样物质调节剂
US7432257B2 (en)	2005-01-06	2008-10-07	Janssen Pharmaceutica N.V.	Piperdinyl-phenoxazine and phenothiazine derivatives as δ-opioid modulators
CA2612491A1 (fr)	2005-06-16	2006-12-28	Janssen Pharmaceutica N.V.	Modulateurs d'opioides tricycliques
US8222419B2 (en)	2006-09-29	2012-07-17	Nippon Zoki Pharmaceutical Co., Ltd.	Oxepin derivative

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NL260070A (fr) *	1960-02-25
NL283292A (fr) *	1961-09-29
DE1670118A1 (de) *	1966-07-22	1970-11-05	Boehringer Mannheim Gmbh	Verfahren zur Herstellung neuer Derivate des 6,11-Dihydro-dibenz[b,e]oxepins und ihrer Salze
US3470188A (en) *	1967-01-05	1969-09-30	Smithkline Corp	9-cycloalkyl-lower alkyl-piperidylidene derivatives of xanthenes and thioxanthenes
JPS5018478A (fr) *	1973-05-17	1975-02-26

1975
- 1975-10-16 ZA ZA00756550A patent/ZA756550B/xx unknown
- 1975-10-31 AU AU86247/75A patent/AU498298B2/en not_active Expired
- 1975-10-31 CA CA238,781A patent/CA1055945A/fr not_active Expired
- 1975-11-02 IL IL48400A patent/IL48400A/xx unknown
- 1975-11-03 NZ NZ179139A patent/NZ179139A/xx unknown
- 1975-11-03 HU HU75SI1494A patent/HU174639B/hu not_active IP Right Cessation
- 1975-11-03 PH PH17733A patent/PH12158A/en unknown
- 1975-11-04 FR FR7533631A patent/FR2290202A1/fr active Granted
- 1975-11-04 LU LU73714A patent/LU73714A1/xx unknown
- 1975-11-04 DK DK495775AA patent/DK139429B/da not_active IP Right Cessation
- 1975-11-04 IE IE2398/75A patent/IE42137B1/en unknown
- 1975-11-04 BE BE161500A patent/BE835224A/fr not_active IP Right Cessation
- 1975-11-05 NL NL7512974A patent/NL7512974A/xx not_active Application Discontinuation
- 1975-11-05 CH CH1432175A patent/CH624403A5/de not_active IP Right Cessation
- 1975-11-05 JP JP50133564A patent/JPS5826754B2/ja not_active Expired
- 1975-11-05 ES ES442357A patent/ES442357A1/es not_active Expired
- 1975-11-06 DE DE19752549841 patent/DE2549841A1/de active Granted

Also Published As

Publication number	Publication date
DK139429B (da)	1979-02-19
AU498298B2 (en)	1979-03-01
FR2290202A1 (fr)	1976-06-04
IL48400A0 (en)	1976-01-30
HU174639B (hu)	1980-02-28
LU73714A1 (fr)	1976-06-11
NZ179139A (en)	1978-04-28
DK495775A (fr)	1976-05-07
DE2549841A1 (de)	1976-05-13
CH624403A5 (en)	1981-07-31
DE2549841C2 (fr)	1988-07-07
AU8624775A (en)	1977-05-05
BE835224A (fr)	1976-05-04
IE42137B1 (en)	1980-06-04
ZA756550B (en)	1976-09-29
DK139429C (fr)	1979-08-06
JPS5170768A (fr)	1976-06-18
PH12158A (en)	1978-11-10
JPS5826754B2 (ja)	1983-06-04
IL48400A (en)	1979-01-31
IE42137L (en)	1976-05-06
NL7512974A (nl)	1976-05-10
ES442357A1 (es)	1977-04-01
FR2290202B1 (fr)	1980-05-23

Publication	Publication Date	Title
US4086350A (en)	1978-04-25	Pharmaceutical compositions and method of producing anti-psychotic activity without extrapyramidal symptoms
US3014911A (en)	1961-12-26	Derivatives of dibenzo[a, e]cycloheptatriene
US5294619A (en)	1994-03-15	Arylpiperidine derivatives
IE44055B1 (en)	1981-07-29	Phthalanes
US2684965A (en)	1954-07-27	Aminoalkylpiperidines
US4013668A (en)	1977-03-22	5-(1,1-diphenyl-3-(5- or 6-hydroxy-2-azabicyclo(2.2.2)oct-2-yl)propyl)-2-alkyl-1,3,4-oxadiazoles and related compounds
US3470188A (en)	1969-09-30	9-cycloalkyl-lower alkyl-piperidylidene derivatives of xanthenes and thioxanthenes
NO147029B (no)	1982-10-11	Analogifremgangsmaate ved fremstilling av terapeutisk virksomme trisubstituerte 1-fenyl-2,3,4,5-tetrahydro-1h-3-benzazepinforbindelser
NO122814B (fr)	1971-08-16
IE42137B1 (en)	1980-06-04	Compositions containing piperidyl xanthenes,thioxanthenes and dibenzozepins
US4309545A (en)	1982-01-05	Oximino-1-hydroxyoctahydrobenzo[c]quinolines and derivatives thereof
CA2146923A1 (fr)	1994-04-28	Derives d'acide benzoique avec condensation heterocyclique, antagonistes du recepteur 5-ht4
US2976291A (en)	1961-03-21	Ethers of z
CA1102807A (fr)	1981-06-09	Traduction non-disponible
JPS6036436B2 (ja)	1985-08-20	１０‐〔ω‐（ベンゾイルピペリジニル）アルキル〕フエノチアジアジンおよびその酸付加塩ならびにそれらの製造法
Kaiser et al.	1974	Analogs of phenothiazines. 5. Synthesis and neuropharmacological activity of some piperidylidene derivatives of thioxanthenes, xanthenes, dibenzoxepins, and acridans
US4042695A (en)	1977-08-16	Thiaxanthene derivatives, compositions thereof and methods of treating therewith
US3316272A (en)	1967-04-25	Heterocyclic derivatives of triphenyl-ethylenes, triphenylethanes and triphenylethanols
IE67871B1 (en)	1996-05-01	Novel benzothiopyranylamines
US2941999A (en)	1960-06-21	Phenthiazine derivatives
US4032640A (en)	1977-06-28	4H-Benzo[4,5]cyclohepta[1,2-b]thiophenes
CA1090334A (fr)	1980-11-25	Alkylthio-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro- 1h-3-benzazepines a action dopaminergique
US3140284A (en)	1964-07-07	New phenothiazine derivatives and a process for the production thereof
NO138806B (no)	1978-08-07	Analogifremgangsmaate for fremstilling av neuroleptisk aktive 6-fluor-substituert tiaxanten-derivater
US3094526A (en)	1963-06-18	10-[(3-and 4-hydroxy-1-piperidyl) loweralkyl phenothiazines