CA1153380A - Sels de tetrahydroisoquinolinium, agents de blocage neuromusculaire - Google Patents

Sels de tetrahydroisoquinolinium, agents de blocage neuromusculaire

Info

Publication number: CA1153380A
Authority: CA; Canada
Prior art keywords: trans; methyl; salt; pharmaceutically acceptable; propyl
Prior art date: 1979-10-19
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

CA000362668A

Other languages

English (en)

Inventor

Hassan A. El-Sayad

Roy A. Swaringen, Jr.

David A. Yeowell

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.)

Wellcome Foundation Ltd

Original Assignee

Wellcome Foundation 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.)

1979-10-19

Filing date

1979-10-19

Publication date

1983-09-06

1979-10-19 Application filed by Wellcome Foundation Ltd filed Critical Wellcome Foundation Ltd

1983-09-06 Application granted granted Critical

1983-09-06 Publication of CA1153380A publication Critical patent/CA1153380A/fr

Status Expired legal-status Critical Current

Links

230000000903 blocking effect Effects 0.000 title description 6
230000002232 neuromuscular Effects 0.000 title description 6
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical class C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 title description 3
238000000034 method Methods 0.000 claims abstract description 99
150000001875 compounds Chemical class 0.000 claims abstract description 54
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 51
150000001450 anions Chemical class 0.000 claims abstract description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 11
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 9
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims abstract description 8
125000000217 alkyl group Chemical group 0.000 claims abstract description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 4
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 4
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 4
150000003839 salts Chemical class 0.000 claims description 91
230000008569 process Effects 0.000 claims description 77
239000000203 mixture Substances 0.000 claims description 61
AWJUIBRHMBBTKR-UHFFFAOYSA-O isoquinolin-2-ium Chemical compound C1=[NH+]C=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-O 0.000 claims description 42
238000000926 separation method Methods 0.000 claims description 27
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 26
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 26
DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 claims description 25
238000002360 preparation method Methods 0.000 claims description 20
DIVRAHZSTAIUNB-UHFFFAOYSA-N 3-[3-(2-carboxyethyl)phenyl]propanoic acid Chemical compound OC(=O)CCC1=CC=CC(CCC(O)=O)=C1 DIVRAHZSTAIUNB-UHFFFAOYSA-N 0.000 claims description 7
-1 propyl 1,4-phenylenedipropionate Chemical compound 0.000 claims description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
229910019142 PO4 Inorganic materials 0.000 claims description 3
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 claims description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 3
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 3
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 3
PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 claims description 3
239000010452 phosphate Substances 0.000 claims description 3
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 3
229910021653 sulphate ion Inorganic materials 0.000 claims description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 3
239000000126 substance Substances 0.000 claims 27
NBTGEURICRTMGL-WHFBIAKZSA-N Ala-Gly-Ser Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O NBTGEURICRTMGL-WHFBIAKZSA-N 0.000 claims 19
230000000875 corresponding effect Effects 0.000 claims 18
XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 claims 18
YLCILCNDLBSOIO-UHFFFAOYSA-N (3-prop-2-enoyloxyphenyl) prop-2-enoate Chemical compound C=CC(=O)OC1=CC=CC(OC(=O)C=C)=C1 YLCILCNDLBSOIO-UHFFFAOYSA-N 0.000 claims 8
JMMVHMOAIMOMOF-UHFFFAOYSA-N (4-prop-2-enoyloxyphenyl) prop-2-enoate Chemical compound C=CC(=O)OC1=CC=C(OC(=O)C=C)C=C1 JMMVHMOAIMOMOF-UHFFFAOYSA-N 0.000 claims 8
HGXJNYNUTHMEOS-UHFFFAOYSA-N (4-propanoyloxyphenyl) propanoate Chemical compound CCC(=O)OC1=CC=C(OC(=O)CC)C=C1 HGXJNYNUTHMEOS-UHFFFAOYSA-N 0.000 claims 6
DFOCUWFSRVQSNI-UHFFFAOYSA-N 3-[4-(2-carboxyethyl)phenyl]propanoic acid Chemical compound OC(=O)CCC1=CC=C(CCC(O)=O)C=C1 DFOCUWFSRVQSNI-UHFFFAOYSA-N 0.000 claims 1
241001239379 Calophysus macropterus Species 0.000 claims 1
239000000842 neuromuscular blocking agent Substances 0.000 abstract description 10
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 abstract description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 2
239000008194 pharmaceutical composition Substances 0.000 abstract description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 34
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 34
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
238000004128 high performance liquid chromatography Methods 0.000 description 23
230000002999 depolarising effect Effects 0.000 description 22
239000000243 solution Substances 0.000 description 19
239000003795 chemical substances by application Substances 0.000 description 18
230000000694 effects Effects 0.000 description 17
239000002904 solvent Substances 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
230000009471 action Effects 0.000 description 14
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 10
239000007787 solid Substances 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 9
238000011084 recovery Methods 0.000 description 8
238000010992 reflux Methods 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
230000036515 potency Effects 0.000 description 7
239000000047 product Substances 0.000 description 7
238000001953 recrystallisation Methods 0.000 description 7
PMDCZENCAXMSOU-UHFFFAOYSA-N N-ethylacetamide Chemical compound CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
YRYCIFUZSUMAAY-UHFFFAOYSA-N (RS)-1-benzyl-1,2,3,4-tetrahydroisoquinoline Chemical class N1CCC2=CC=CC=C2C1CC1=CC=CC=C1 YRYCIFUZSUMAAY-UHFFFAOYSA-N 0.000 description 5
CQVWOJSAGPFDQL-UHFFFAOYSA-N 3-iodopropan-1-ol Chemical group OCCCI CQVWOJSAGPFDQL-UHFFFAOYSA-N 0.000 description 5
241000282693 Cercopithecidae Species 0.000 description 5
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
150000004694 iodide salts Chemical class 0.000 description 5
238000001356 surgical procedure Methods 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
206010002091 Anaesthesia Diseases 0.000 description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
241000124008 Mammalia Species 0.000 description 4
206010029315 Neuromuscular blockade Diseases 0.000 description 4
239000002253 acid Substances 0.000 description 4
230000037005 anaesthesia Effects 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
229960001760 dimethyl sulfoxide Drugs 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
238000009472 formulation Methods 0.000 description 4
229920001467 poly(styrenesulfonates) Polymers 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
QAVRVPRGXUDLHV-UHFFFAOYSA-N 3-[4-(3-chloro-3-oxopropyl)phenyl]propanoyl chloride Chemical compound ClC(=O)CCC1=CC=C(CCC(Cl)=O)C=C1 QAVRVPRGXUDLHV-UHFFFAOYSA-N 0.000 description 3
206010021118 Hypotonia Diseases 0.000 description 3
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
208000001871 Tachycardia Diseases 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
MUQUYTSLDVKIOF-CHJKCJHBSA-N alcuronium Chemical compound C/1([C@@H]23)=C\N([C@H]4\5)C6=CC=CC=C6[C@]4(CC[N@@+]4(CC=C)C\C6=C\CO)[C@@H]4C[C@@H]6C/5=C/N3C3=CC=CC=C3[C@@]22CC[N@@+]3(CC=C)C/C(=C/CO)[C@@H]\1C[C@H]32 MUQUYTSLDVKIOF-CHJKCJHBSA-N 0.000 description 3
229960004322 alcuronium Drugs 0.000 description 3
238000001949 anaesthesia Methods 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
238000005349 anion exchange Methods 0.000 description 3
150000001805 chlorine compounds Chemical class 0.000 description 3
239000000544 cholinesterase inhibitor Substances 0.000 description 3
239000012043 crude product Substances 0.000 description 3
150000004683 dihydrates Chemical class 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000003814 drug Substances 0.000 description 3
238000001640 fractional crystallisation Methods 0.000 description 3
ICLWTJIMXVISSR-UHFFFAOYSA-N gallamine Chemical compound CCN(CC)CCOC1=CC=CC(OCCN(CC)CC)=C1OCCN(CC)CC ICLWTJIMXVISSR-UHFFFAOYSA-N 0.000 description 3
229960003054 gallamine Drugs 0.000 description 3
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
239000007788 liquid Substances 0.000 description 3
238000005649 metathesis reaction Methods 0.000 description 3
230000036640 muscle relaxation Effects 0.000 description 3
MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 description 3
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 3
GVEAYVLWDAFXET-XGHATYIMSA-N pancuronium Chemical compound C[N+]1([C@@H]2[C@@H](OC(C)=O)C[C@@H]3CC[C@H]4[C@@H]5C[C@@H]([C@@H]([C@]5(CC[C@@H]4[C@@]3(C)C2)C)OC(=O)C)[N+]2(C)CCCCC2)CCCCC1 GVEAYVLWDAFXET-XGHATYIMSA-N 0.000 description 3
229960005457 pancuronium Drugs 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
AXOIZCJOOAYSMI-UHFFFAOYSA-N succinylcholine Chemical compound C[N+](C)(C)CCOC(=O)CCC(=O)OCC[N+](C)(C)C AXOIZCJOOAYSMI-UHFFFAOYSA-N 0.000 description 3
229940032712 succinylcholine Drugs 0.000 description 3
230000006794 tachycardia Effects 0.000 description 3
150000004685 tetrahydrates Chemical class 0.000 description 3
239000008096 xylene Substances 0.000 description 3
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
FEWLNYSYJNLUOO-UHFFFAOYSA-N 1-Piperidinecarboxaldehyde Chemical compound O=CN1CCCCC1 FEWLNYSYJNLUOO-UHFFFAOYSA-N 0.000 description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
RQFUZUMFPRMVDX-UHFFFAOYSA-N 3-Bromo-1-propanol Chemical group OCCCBr RQFUZUMFPRMVDX-UHFFFAOYSA-N 0.000 description 2
KRXUBZPHAPGHPE-UHFFFAOYSA-N 3-[3-(2-carboxyethenyl)phenyl]prop-2-enoic acid Chemical compound OC(=O)C=CC1=CC=CC(C=CC(O)=O)=C1 KRXUBZPHAPGHPE-UHFFFAOYSA-N 0.000 description 2
IRTZDBMSONMPDZ-UHFFFAOYSA-N 3-[3-(3-chloro-3-oxopropyl)phenyl]propanoyl chloride Chemical compound ClC(=O)CCC1=CC=CC(CCC(Cl)=O)=C1 IRTZDBMSONMPDZ-UHFFFAOYSA-N 0.000 description 2
LAMUXTNQCICZQX-UHFFFAOYSA-N 3-chloropropan-1-ol Chemical compound OCCCCl LAMUXTNQCICZQX-UHFFFAOYSA-N 0.000 description 2
229940126062 Compound A Drugs 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
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 2
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
208000001953 Hypotension Diseases 0.000 description 2
ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
230000036592 analgesia Effects 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
239000002981 blocking agent Substances 0.000 description 2
230000037396 body weight Effects 0.000 description 2
239000003610 charcoal Substances 0.000 description 2
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
230000036461 convulsion Effects 0.000 description 2
239000013078 crystal Substances 0.000 description 2
229950000405 decamethonium Drugs 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
238000001914 filtration Methods 0.000 description 2
238000005187 foaming Methods 0.000 description 2
239000007789 gas Substances 0.000 description 2
WUAXWQRULBZETB-UHFFFAOYSA-N homoveratric acid Chemical compound COC1=CC=C(CC(O)=O)C=C1OC WUAXWQRULBZETB-UHFFFAOYSA-N 0.000 description 2
230000036571 hydration Effects 0.000 description 2
238000006703 hydration reaction Methods 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
230000036543 hypotension Effects 0.000 description 2
238000001802 infusion Methods 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
RHCSKNNOAZULRK-UHFFFAOYSA-N mescaline Chemical compound COC1=CC(CCN)=CC(OC)=C1OC RHCSKNNOAZULRK-UHFFFAOYSA-N 0.000 description 2
239000002808 molecular sieve Substances 0.000 description 2
LCEDQNDDFOCWGG-UHFFFAOYSA-N morpholine-4-carbaldehyde Chemical compound O=CN1CCOCC1 LCEDQNDDFOCWGG-UHFFFAOYSA-N 0.000 description 2
230000003387 muscular Effects 0.000 description 2
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
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KGPAYJZAMGEDIQ-UHFFFAOYSA-N laudanosine Natural products C1=C(OC)C(OC)=CC=C1CC1C2=CC(OC)=C(OC)C=C2CCN1C KGPAYJZAMGEDIQ-UHFFFAOYSA-N 0.000 description 1
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210000003205 muscle Anatomy 0.000 description 1
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239000003158 myorelaxant agent Substances 0.000 description 1
229960002362 neostigmine Drugs 0.000 description 1
LULNWZDBKTWDGK-UHFFFAOYSA-M neostigmine bromide Chemical compound [Br-].CN(C)C(=O)OC1=CC=CC([N+](C)(C)C)=C1 LULNWZDBKTWDGK-UHFFFAOYSA-M 0.000 description 1
125000004971 nitroalkyl group Chemical group 0.000 description 1
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239000001301 oxygen Substances 0.000 description 1
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238000000053 physical method Methods 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
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239000000843 powder Substances 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
239000002510 pyrogen Substances 0.000 description 1
150000003248 quinolines Chemical class 0.000 description 1
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229920005989 resin Polymers 0.000 description 1
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239000011833 salt mixture Substances 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229910052709 silver Inorganic materials 0.000 description 1
239000004332 silver Substances 0.000 description 1
ADZWSOLPGZMUMY-UHFFFAOYSA-M silver bromide Chemical compound [Ag]Br ADZWSOLPGZMUMY-UHFFFAOYSA-M 0.000 description 1
229940045105 silver iodide Drugs 0.000 description 1
HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
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210000002460 smooth muscle Anatomy 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
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KUCOHFSKRZZVRO-UHFFFAOYSA-N terephthalaldehyde Chemical compound O=CC1=CC=C(C=O)C=C1 KUCOHFSKRZZVRO-UHFFFAOYSA-N 0.000 description 1
238000012360 testing method Methods 0.000 description 1
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229960003279 thiopental Drugs 0.000 description 1
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238000010792 warming Methods 0.000 description 1
238000002424 x-ray crystallography Methods 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
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/18—Aralkyl radicals
- C07D217/20—Aralkyl radicals with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000362668A 1979-10-19 1979-10-19 Sels de tetrahydroisoquinolinium, agents de blocage neuromusculaire Expired CA1153380A (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US8653079A	1979-10-19	1979-10-19
US086530		1979-10-19

Publications (1)

Publication Number	Publication Date
CA1153380A true CA1153380A (fr)	1983-09-06

Family

ID=22199190

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000362668A Expired CA1153380A (fr)	1979-10-19	1979-10-19	Sels de tetrahydroisoquinolinium, agents de blocage neuromusculaire

Country Status (3)

Country	Link
CA (1)	CA1153380A (fr)
DE (1)	DE3039304A1 (fr)
GB (1)	GB2061929B (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8418303D0 (en) *	1984-07-18	1984-08-22	Wellcome Found	Compounds
BG41897A1 (en) *	1985-07-19	1987-09-15	Ivanov	Dichlormethylate of n, n'- 4, 10- dioxa- 3, 11- bis- tetrahydropapaverine and method for its preparation

1979
- 1979-10-19 CA CA000362668A patent/CA1153380A/fr not_active Expired
1980
- 1980-10-15 GB GB8033219A patent/GB2061929B/en not_active Expired
- 1980-10-17 DE DE19803039304 patent/DE3039304A1/de not_active Withdrawn

Also Published As

Publication number	Publication date
GB2061929B (en)	1983-06-22
GB2061929A (en)	1981-05-20
DE3039304A1 (de)	1981-05-27

Legal Events

Date	Code	Title	Description
2000-09-06	MKEX	Expiry

Publication	Publication Date	Title
US4491665A (en)	1985-01-01	Method of preparing isomers of bis isoquinolinium compounds
EP0971898B1 (fr)	2005-05-11	Isoquinoleines substituees en tant qu'inhibiteurs neuromusculaires exercant une action extremement courte
EP0181055B1 (fr)	1991-02-06	Sels de bis-diméthoxyméthyl(triméthoxybenzyl)isoquinoléine, leur préparation et compositions pharmaceutiques les contenant
US5556978A (en)	1996-09-17	Neuromuscular blocking agents
JP2823356B2 (ja)	1998-11-11	神経筋遮断剤
US4701460A (en)	1987-10-20	Long duration neuromuscular blocking agents
US4192877A (en)	1980-03-11	Neuromuscular blocking agents
CA1113096A (fr)	1981-11-24	Agents de blocage neuromusculaire
CA1153380A (fr)	1983-09-06	Sels de tetrahydroisoquinolinium, agents de blocage neuromusculaire
US4235906A (en)	1980-11-25	Bis-isoquinolinium compounds, compositions and methods of use
CA1125287A (fr)	1982-06-08	Modes d'emploi de substances a base de bis-isoquinolinium
ES et al.	0	SUBSTITUIERTE ISOCHINOLINE ALS ULTRA KURZ WIRKENDE NEUROMUSKULÄRE BLOCKER ISOQUINOLEINES SUBSTITUEES EN TANT QU’INHIBITEURS NEUROMUSCULAIRES EXERCANT UNE ACTION EXTREMEMENT COURTE
EP0080682A1 (fr)	1983-06-08	Composés de bis-isoquinolinium, compositions pharmaceutiques et synthèse
HK1077570A (en)	2006-02-17	Substituted isoquinolines as ultra short acting neuromuscular blockers
JPH053868B2 (fr)	1993-01-18
HK1065530A (en)	2005-02-25	Isoquinolines and preparation thereof
HK1023342B (en)	2004-07-30	Substituted isoquinolines as ultra short acting neuromuscular blockers