JPS5942370A - イソキノリン誘導体及びその製造方法、並びに該誘導体を含有する医薬 - Google Patents

イソキノリン誘導体及びその製造方法、並びに該誘導体を含有する医薬

Info

Publication number: JPS5942370A
Authority: JP; Japan
Prior art keywords: general formula; lower alkyl; alkyl group; methyl; reaction
Prior art date: 1982-06-04
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.): Pending

Application number

JP58098139A

Other languages

English (en)

Japanese (ja)

Inventor

ギユラ・デイ−ク

エルツエベト・ザラ

ラヨス・ギヨルギイ

マルトン・フエケテ

マルジト・ドダ

アンドラス・セレジ

ベラ・カニイスカ

エルツエベト・トト

マリア・ホルバト

サンドル・マンヤイ

フリギエス・ギヨルジエニイ

ギヨルギイ・バスゾビクス

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.)

Egyt Gyogyszervegyeszeti Gyar

Original Assignee

Egyt Gyogyszervegyeszeti Gyar

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.)

1982-06-04

Filing date

1983-06-03

Publication date

1984-03-08

1983-06-03 Application filed by Egyt Gyogyszervegyeszeti Gyar filed Critical Egyt Gyogyszervegyeszeti Gyar

1984-03-08 Publication of JPS5942370A publication Critical patent/JPS5942370A/ja

Status Pending legal-status Critical Current

Links

239000003814 drug Substances 0.000 title claims description 9
238000004519 manufacturing process Methods 0.000 title claims description 5
125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 title 1
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 129
150000001875 compounds Chemical class 0.000 claims description 110
239000002253 acid Substances 0.000 claims description 50
150000003839 salts Chemical class 0.000 claims description 43
238000000034 method Methods 0.000 claims description 39
238000006243 chemical reaction Methods 0.000 claims description 36
125000000217 alkyl group Chemical group 0.000 claims description 32
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 30
239000007858 starting material Substances 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 16
239000003054 catalyst Substances 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 15
-1 8-(n-butylamino-acetylamino)-4-(p-chloro-phenyl)-2-methyl- 1,2,3,4-tetrahydro-isoquinoline Chemical compound 0.000 claims description 13
239000003960 organic solvent Substances 0.000 claims description 12
125000000623 heterocyclic group Chemical group 0.000 claims description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
229910052801 chlorine Inorganic materials 0.000 claims description 8
230000002378 acidificating effect Effects 0.000 claims description 7
239000012429 reaction media Substances 0.000 claims description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
229910052500 inorganic mineral Inorganic materials 0.000 claims description 6
239000011707 mineral Substances 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
238000007363 ring formation reaction Methods 0.000 claims description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
239000000460 chlorine Substances 0.000 claims description 5
239000002904 solvent Substances 0.000 claims description 5
229910052717 sulfur Inorganic materials 0.000 claims description 5
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 4
239000011230 binding agent Substances 0.000 claims description 4
239000004020 conductor Substances 0.000 claims description 4
229930195733 hydrocarbon Natural products 0.000 claims description 4
150000002430 hydrocarbons Chemical class 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
229920006395 saturated elastomer Polymers 0.000 claims description 4
125000004434 sulfur atom Chemical group 0.000 claims description 4
239000004215 Carbon black (E152) Substances 0.000 claims description 3
125000004429 atom Chemical group 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
229910052757 nitrogen Inorganic materials 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 2
239000004480 active ingredient Substances 0.000 claims description 2
150000001412 amines Chemical class 0.000 claims description 2
229940079593 drug Drugs 0.000 claims description 2
239000012948 isocyanate Substances 0.000 claims description 2
150000002513 isocyanates Chemical class 0.000 claims description 2
150000002431 hydrogen Chemical group 0.000 claims 7
125000001309 chloro group Chemical group Cl* 0.000 claims 3
239000002841 Lewis acid Substances 0.000 claims 2
229910052736 halogen Inorganic materials 0.000 claims 2
150000002367 halogens Chemical class 0.000 claims 2
150000007517 lewis acids Chemical class 0.000 claims 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
231100000252 nontoxic Toxicity 0.000 claims 2
230000003000 nontoxic effect Effects 0.000 claims 2
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 claims 1
239000003377 acid catalyst Substances 0.000 claims 1
229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 claims 1
235000009508 confectionery Nutrition 0.000 claims 1
125000005843 halogen group Chemical group 0.000 claims 1
125000001841 imino group Chemical group [H]N=* 0.000 claims 1
125000004430 oxygen atom Chemical group O* 0.000 claims 1
150000003248 quinolines Chemical class 0.000 claims 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 225
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 169
239000000243 solution Substances 0.000 description 70
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
239000000047 product Substances 0.000 description 49
238000002844 melting Methods 0.000 description 44
230000008018 melting Effects 0.000 description 44
239000011541 reaction mixture Substances 0.000 description 44
238000004458 analytical method Methods 0.000 description 35
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
239000000203 mixture Substances 0.000 description 32
229910001868 water Inorganic materials 0.000 description 28
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
238000001816 cooling Methods 0.000 description 26
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 25
239000000843 powder Substances 0.000 description 24
238000003756 stirring Methods 0.000 description 24
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 20
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 20
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 18
239000011976 maleic acid Substances 0.000 description 18
239000013078 crystal Substances 0.000 description 17
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
239000002585 base Substances 0.000 description 13
230000000694 effects Effects 0.000 description 11
238000005259 measurement Methods 0.000 description 11
239000000284 extract Substances 0.000 description 10
XXPANQJNYNUNES-UHFFFAOYSA-N nomifensine Chemical compound C12=CC=CC(N)=C2CN(C)CC1C1=CC=CC=C1 XXPANQJNYNUNES-UHFFFAOYSA-N 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
239000008346 aqueous phase Substances 0.000 description 9
239000007864 aqueous solution Substances 0.000 description 9
239000012071 phase Substances 0.000 description 9
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 8
150000007513 acids Chemical class 0.000 description 8
238000004364 calculation method Methods 0.000 description 8
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
238000001953 recrystallisation Methods 0.000 description 8
241000699670 Mus sp. Species 0.000 description 7
238000000354 decomposition reaction Methods 0.000 description 7
229960001073 nomifensine Drugs 0.000 description 7
239000003208 petroleum Substances 0.000 description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
239000000935 antidepressant agent Substances 0.000 description 6
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 6
230000001430 anti-depressive effect Effects 0.000 description 5
229940005513 antidepressants Drugs 0.000 description 5
238000009835 boiling Methods 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
239000007787 solid Substances 0.000 description 5
238000007920 subcutaneous administration Methods 0.000 description 5
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
230000007423 decrease Effects 0.000 description 4
239000012458 free base Substances 0.000 description 4
235000010755 mineral Nutrition 0.000 description 4
229960005333 tetrabenazine Drugs 0.000 description 4
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
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RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
239000000908 ammonium hydroxide Substances 0.000 description 3
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
239000002026 chloroform extract Substances 0.000 description 3
239000012259 ether extract Substances 0.000 description 3
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
238000000855 fermentation Methods 0.000 description 3
230000004151 fermentation Effects 0.000 description 3
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
239000010931 gold Substances 0.000 description 3
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150000004820 halides Chemical class 0.000 description 3
229910000041 hydrogen chloride Inorganic materials 0.000 description 3
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
230000006742 locomotor activity Effects 0.000 description 3
HNHVTXYLRVGMHD-UHFFFAOYSA-N n-butyl isocyanate Chemical compound CCCCN=C=O HNHVTXYLRVGMHD-UHFFFAOYSA-N 0.000 description 3
229920000137 polyphosphoric acid Chemical class 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
238000010992 reflux Methods 0.000 description 3
230000004936 stimulating effect Effects 0.000 description 3
239000008096 xylene Substances 0.000 description 3
ZJTJFKNUUGFHRB-UVTDQMKNSA-N (Z)-2-(8-amino-2-methyl-4-phenyl-3,4-dihydro-1H-isoquinolin-1-yl)but-2-enedioic acid Chemical compound C12=CC=CC(N)=C2C(\C(=C\C(O)=O)C(O)=O)N(C)CC1C1=CC=CC=C1 ZJTJFKNUUGFHRB-UVTDQMKNSA-N 0.000 description 2
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
229910015900 BF3 Inorganic materials 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
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241000282326 Felis catus Species 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
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125000001931 aliphatic group Chemical group 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 2
235000005583 doda Nutrition 0.000 description 2
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
238000000605 extraction Methods 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
229960003878 haloperidol Drugs 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000010410 layer Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000000463 material Substances 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
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230000000144 pharmacologic effect Effects 0.000 description 2
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BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
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230000001225 therapeutic effect Effects 0.000 description 2
231100001274 therapeutic index Toxicity 0.000 description 2
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
239000011592 zinc chloride Substances 0.000 description 2
235000005074 zinc chloride Nutrition 0.000 description 2
DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
HLYSUDKSAQOMSL-UHFFFAOYSA-N 1,1-dichlorohexadecane Chemical compound CCCCCCCCCCCCCCCC(Cl)Cl HLYSUDKSAQOMSL-UHFFFAOYSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
DVGIYWMJXYCEFJ-UHFFFAOYSA-N 2-[(2-aminophenyl)methyl-methylamino]-1-phenylethanol Chemical compound C=1C=CC=C(N)C=1CN(C)CC(O)C1=CC=CC=C1 DVGIYWMJXYCEFJ-UHFFFAOYSA-N 0.000 description 1
NNVATDBGKYTMIL-UHFFFAOYSA-N 2-methyl-4-phenyl-3,4-dihydro-1h-isoquinoline Chemical compound C12=CC=CC=C2CN(C)CC1C1=CC=CC=C1 NNVATDBGKYTMIL-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
102220643922 ADP-ribosylhydrolase ARH3_C26F_mutation Human genes 0.000 description 1
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
DJGSPLZLOQXJEK-UHFFFAOYSA-N Cl.ClCC(=O)C=1C=CC=C2C(CN(C(C12)N)C)C1=CC=C(C=C1)Cl Chemical compound Cl.ClCC(=O)C=1C=CC=C2C(CN(C(C12)N)C)C1=CC=C(C=C1)Cl DJGSPLZLOQXJEK-UHFFFAOYSA-N 0.000 description 1
229940126062 Compound A Drugs 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
241000257465 Echinoidea Species 0.000 description 1
206010015995 Eyelid ptosis Diseases 0.000 description 1
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
102000003946 Prolactin Human genes 0.000 description 1
108010057464 Prolactin Proteins 0.000 description 1
LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
230000007059 acute toxicity Effects 0.000 description 1
231100000403 acute toxicity Toxicity 0.000 description 1
231100000369 acute toxicity data Toxicity 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
230000002973 anti-dopamine Effects 0.000 description 1
230000000648 anti-parkinson Effects 0.000 description 1
230000000891 anti-reserpine Effects 0.000 description 1
239000000939 antiparkinson agent Substances 0.000 description 1
239000006286 aqueous extract Substances 0.000 description 1
239000013040 bath agent Substances 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000004397 blinking Effects 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
NRDQFWXVTPZZAZ-UHFFFAOYSA-N butyl carbonochloridate Chemical compound CCCCOC(Cl)=O NRDQFWXVTPZZAZ-UHFFFAOYSA-N 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
235000010216 calcium carbonate Nutrition 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000000969 carrier Substances 0.000 description 1
238000010276 construction Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
238000007865 diluting Methods 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
229960003638 dopamine Drugs 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
230000003325 follicular Effects 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
239000005457 ice water Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
IYRMNDOLPONSCJ-UHFFFAOYSA-N isoquinolin-2-ium;chloride Chemical compound Cl.C1=NC=CC2=CC=CC=C21 IYRMNDOLPONSCJ-UHFFFAOYSA-N 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
230000003902 lesion Effects 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
235000014380 magnesium carbonate Nutrition 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000003607 modifier Substances 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
238000000465 moulding Methods 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
150000007530 organic bases Chemical group 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
239000006187 pill Substances 0.000 description 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
229940097325 prolactin Drugs 0.000 description 1
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
201000003004 ptosis Diseases 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
239000002994 raw material Substances 0.000 description 1
229960003147 reserpine Drugs 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
239000013049 sediment Substances 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000009495 sugar coating Methods 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
235000013548 tempeh Nutrition 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000005505 thiomorpholino group Chemical group 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1
230000021542 voluntary musculoskeletal movement Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
- 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
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Neurology (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Other In-Based Heterocyclic Compounds (AREA)

JP58098139A 1982-06-04 1983-06-03 イソキノリン誘導体及びその製造方法、並びに該誘導体を含有する医薬 Pending JPS5942370A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
HU1798/82		1982-06-04
HU821797A HU186518B (en)	1982-06-04	1982-06-04	Process for producing 8-bracket-amino-acyl-amino-bracket closed-4-aryl-2-methyl-1,2,3,4-tetrahydro-isoquinoline derivatives
HU1797/82		1982-06-04

Publications (1)

Publication Number	Publication Date
JPS5942370A true JPS5942370A (ja)	1984-03-08

Family

ID=10956238

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP58098139A Pending JPS5942370A (ja)	1982-06-04	1983-06-03	イソキノリン誘導体及びその製造方法、並びに該誘導体を含有する医薬

Country Status (3)

Country	Link
JP (1)	JPS5942370A (fr)
BE (1)	BE896927A (fr)
HU (1)	HU186518B (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH03148222A (ja) *	1989-11-01	1991-06-25	Tanabe Seiyaku Co Ltd	パーキンソニズム予防・治療剤

Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1164192A (en) *	1966-05-05	1969-09-17	Hoechst Ag	Tetrahydroisoquinolines and process for preparing them

1982
- 1982-06-04 HU HU821797A patent/HU186518B/hu not_active IP Right Cessation
1983
- 1983-06-02 BE BE1/10798A patent/BE896927A/fr not_active IP Right Cessation
- 1983-06-03 JP JP58098139A patent/JPS5942370A/ja active Pending

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1164192A (en) *	1966-05-05	1969-09-17	Hoechst Ag	Tetrahydroisoquinolines and process for preparing them

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH03148222A (ja) *	1989-11-01	1991-06-25	Tanabe Seiyaku Co Ltd	パーキンソニズム予防・治療剤

Also Published As

Publication number	Publication date
BE896927A (fr)	1983-12-02
HU186518B (en)	1985-08-28

Publication	Publication Date	Title
RU2156239C2 (ru)	2000-09-20	Замещенные 4-(1,2,3,4-тетрагидро-1-нафталинил)-1н-имидазолы и 4-(2,3-дигидро-1н-инден-1-ил)-1н-имидазолы, способы их получения и фармацевтическая композиция на их основе
JPH054983A (ja)	1993-01-14	イソキノリノン誘導体、その製造方法およびその誘導体を有効成分として含有する５−ｈｔ３レセプター拮抗剤
JP2002504484A (ja)	2002-02-12	新規化合物
JPS6332072B2 (fr)	1988-06-28
EA006237B1 (ru)	2005-10-27	Производные аминоалкилбензоилбензофурана, способ их получения и содержащие их композиции
US4153789A (en)	1979-05-08	Phenylindolines
EP1246817B1 (fr)	2004-06-23	Derives de 4-phenyle-1-piperazinyle, -piperidinyle et -tetrahydropyridyle
US4314943A (en)	1982-02-09	Heterocyclic substituted aryloxy 3-indolyl-tertiary butylaminopropanols
US4243666A (en)	1981-01-06	4-Amino-2-piperidino-quinazolines
US4021552A (en)	1977-05-03	10-[ω-(BENZOYLPIPERIDINYL)ALKYL]PHENOTHIAZINES
JPH08502057A (ja)	1996-03-05	カルモジュリン拮抗特性を有する複素環式アミン
US3931222A (en)	1976-01-06	Tetrahydro-carbazole derivates
US3935214A (en)	1976-01-27	2-or 3 keto-3-or-2-phenyl-1,4-disubstituted piperazines
JPS5942370A (ja)	1984-03-08	イソキノリン誘導体及びその製造方法、並びに該誘導体を含有する医薬
US3953448A (en)	1976-04-27	Piperazino-anilido compounds
US4537975A (en)	1985-08-27	1-Phenylindazol-3-one compounds
US4537895A (en)	1985-08-27	Isoquinoline derivatives
JPS5942369A (ja)	1984-03-08	イソキノリン誘導体及びその製造方法、並びに該誘導体を含有する医薬
CA2166470C (fr)	2001-12-18	Enantiomeres possedant des proprietes pharmacologiques
US3721675A (en)	1973-03-20	Oxazolidin-2-one derivatives
US4104398A (en)	1978-08-01	3-Lower alkoxycyproheptadines as serotonin inhibitors
US4495352A (en)	1985-01-22	Heterocyclic substituted aryloxy 3-indolyl-tertiary butylaminopropanols
JP2001512491A (ja)	2001-08-21	１−（イソキノリン−１−イル）−４−（１−フェニメチル）ピペラジン；ドーパミン受容体サブタイプ特異的リガンド
SU1480771A3 (ru)	1989-05-15	Способ получени 9-амино-5,6,6 @ ,7-тетрагидро-4Н-бензо @ , @ тиазоло @ 4,5- @ хинолинов или их кислотно-аддитивных солей в виде рацемата, энантиомеров или смеси энантиомеров
JPS62190156A (ja)	1987-08-20	ベンゼン融合β−ジケトシクロアルキレンの対称性Ｏ−置換ジオキシム、それらの調製方法およびそれらの薬物への適用

JPS5942370A - イソキノリン誘導体及びその製造方法、並びに該誘導体を含有する医薬 - Google Patents

Info

Links

Classifications

Landscapes

Applications Claiming Priority (3)

Publications (1)

Family

ID=10956238

Family Applications (1)

Country Status (3)

Cited By (1)

Citations (1)

Patent Citations (1)

Cited By (1)

Also Published As

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