CA1074320A - 1'-hydroxy-5-alkoxy inferieur-2-alkyl inferieur-7,8-cyclopentano (h)-1,2,3,4-tetrahydroisoquinoline - Google Patents

1'-hydroxy-5-alkoxy inferieur-2-alkyl inferieur-7,8-cyclopentano (h)-1,2,3,4-tetrahydroisoquinoline

Info

Publication number: CA1074320A
Authority: CA; Canada
Prior art keywords: cyclopentano; tetrahydroisoquinoline; hydroxy; methyl; acid
Prior art date: 1974-03-28
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

CA321,344A

Other languages

English (en)

Inventor

Ian W. Mathison

Raymond H. Jones

William E. Solomons

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.)

Marion Laboratories Inc

Original Assignee

Marion Laboratories Inc

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.)

1974-03-28

Filing date

1979-02-13

Publication date

1980-03-25

1974-03-28 Priority claimed from US05/455,672 external-priority patent/US3947454A/en

1979-02-13 Application filed by Marion Laboratories Inc filed Critical Marion Laboratories Inc

1979-02-13 Priority to CA321,344A priority Critical patent/CA1074320A/fr

1980-03-25 Application granted granted Critical

1980-03-25 Publication of CA1074320A publication Critical patent/CA1074320A/fr

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 claims abstract description 13
150000001875 compounds Chemical class 0.000 abstract description 20
238000002360 preparation method Methods 0.000 abstract description 8
150000003526 tetrahydroisoquinolines Chemical class 0.000 abstract description 5
241001465754 Metazoa Species 0.000 abstract description 4
239000000543 intermediate Substances 0.000 abstract description 4
230000000694 effects Effects 0.000 abstract description 2
230000000144 pharmacologic effect Effects 0.000 abstract description 2
230000015572 biosynthetic process Effects 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
239000000243 solution Substances 0.000 description 12
239000002253 acid Substances 0.000 description 11
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000000047 product Substances 0.000 description 9
238000007792 addition Methods 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
-1 lithium aluminum hydride Chemical compound 0.000 description 6
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 5
235000019260 propionic acid Nutrition 0.000 description 5
239000007858 starting material Substances 0.000 description 5
239000003826 tablet Substances 0.000 description 5
QZNNVYOVQUKYSC-JEDNCBNOSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanoic acid;hydron;chloride Chemical compound Cl.OC(=O)[C@@H](N)CC1=CN=CN1 QZNNVYOVQUKYSC-JEDNCBNOSA-N 0.000 description 4
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
125000000217 alkyl group Chemical group 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 4
229920000137 polyphosphoric acid Polymers 0.000 description 4
150000003839 salts Chemical class 0.000 description 4
239000000725 suspension Substances 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
239000013543 active substance Substances 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
239000001110 calcium chloride Substances 0.000 description 3
229960002713 calcium chloride Drugs 0.000 description 3
229910001628 calcium chloride Inorganic materials 0.000 description 3
235000011148 calcium chloride Nutrition 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
239000012043 crude product Substances 0.000 description 3
238000001035 drying Methods 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
238000001914 filtration Methods 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000000843 powder Substances 0.000 description 3
150000003242 quaternary ammonium salts Chemical class 0.000 description 3
238000010992 reflux Methods 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
239000002904 solvent Substances 0.000 description 3
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
KRLDCRSPHOQRDO-UHFFFAOYSA-N 5-methoxy-2-methyl-3,4-dihydro-1h-isoquinoline Chemical compound C1N(C)CCC2=C1C=CC=C2OC KRLDCRSPHOQRDO-UHFFFAOYSA-N 0.000 description 2
WBMJEALSBAAGCE-UHFFFAOYSA-N 5-methoxy-2-methyl-3,4-dihydro-1h-isoquinoline-8-carbaldehyde Chemical compound C1N(C)CCC2=C1C(C=O)=CC=C2OC WBMJEALSBAAGCE-UHFFFAOYSA-N 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-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
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
235000015165 citric acid Nutrition 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
230000032050 esterification Effects 0.000 description 2
238000005886 esterification reaction Methods 0.000 description 2
125000001033 ether group Chemical group 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
238000002955 isolation Methods 0.000 description 2
239000012280 lithium aluminium hydride 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
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
239000012429 reaction media Substances 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000003765 sweetening agent Substances 0.000 description 2
150000003512 tertiary amines Chemical class 0.000 description 2
229910052719 titanium Inorganic materials 0.000 description 2
239000010936 titanium Substances 0.000 description 2
QYAPHLRPFNSDNH-MRFRVZCGSA-N (4s,4as,5as,6s,12ar)-7-chloro-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O QYAPHLRPFNSDNH-MRFRVZCGSA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-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
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 1
CZNJCCVKDVCRKF-UHFFFAOYSA-N Benzyl sulfate Chemical compound OS(=O)(=O)OCC1=CC=CC=C1 CZNJCCVKDVCRKF-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 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
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
238000005727 Friedel-Crafts reaction Methods 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
239000005909 Kieselgur Substances 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
241000700159 Rattus Species 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-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
235000011054 acetic acid Nutrition 0.000 description 1
230000002730 additional effect Effects 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
150000008051 alkyl sulfates Chemical class 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
230000003276 anti-hypertensive effect Effects 0.000 description 1
239000011260 aqueous acid Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
229940073608 benzyl chloride Drugs 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
GRTGGSXWHGKRSB-UHFFFAOYSA-N dichloromethyl methyl ether Chemical compound COC(Cl)Cl GRTGGSXWHGKRSB-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
230000001631 hypertensive effect Effects 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008297 liquid dosage form Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
239000000203 mixture Substances 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000002895 organic esters Chemical class 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
239000002304 perfume Substances 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
230000007017 scission Effects 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000035488 systolic blood pressure Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000003799 water insoluble solvent Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)

CA321,344A 1974-03-28 1979-02-13 1'-hydroxy-5-alkoxy inferieur-2-alkyl inferieur-7,8-cyclopentano (h)-1,2,3,4-tetrahydroisoquinoline Expired CA1074320A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA321,344A CA1074320A (fr)	1974-03-28	1979-02-13	1'-hydroxy-5-alkoxy inferieur-2-alkyl inferieur-7,8-cyclopentano (h)-1,2,3,4-tetrahydroisoquinoline

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US05/455,672 US3947454A (en)	1974-03-28	1974-03-28	5 or 1'-Hydroxy-2-alkyl-7,8-cyclopentano[h]-1,2,3,4-tetrahydroisoquinolines and esters
CA223,274A CA1063118A (fr)	1974-03-28	1975-03-27	5 ou l'-hydroxy-2-alkyl-7,8-cyclopentano(h)-1,2,3,4-tetrahydroisoquinolines et esters derives
CA321,344A CA1074320A (fr)	1974-03-28	1979-02-13	1'-hydroxy-5-alkoxy inferieur-2-alkyl inferieur-7,8-cyclopentano (h)-1,2,3,4-tetrahydroisoquinoline

Publications (1)

Publication Number	Publication Date
CA1074320A true CA1074320A (fr)	1980-03-25

Family

ID=27163880

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA321,344A Expired CA1074320A (fr)	1974-03-28	1979-02-13	1'-hydroxy-5-alkoxy inferieur-2-alkyl inferieur-7,8-cyclopentano (h)-1,2,3,4-tetrahydroisoquinoline

Country Status (1)

Country	Link
CA (1)	CA1074320A (fr)

1979
- 1979-02-13 CA CA321,344A patent/CA1074320A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1997-03-25	MKEX	Expiry

Publication	Publication Date	Title
US3666763A (en)	1972-05-30	4-phenyl isoquinolines and process for preparing same
IE42216B1 (en)	1980-07-02	Benzomorphane derivatives
NO753062L (fr)	1976-03-10
CA1250582A (fr)	1989-02-28	Derives de tetrahydrocorynantheine et preparation
DE2254298A1 (de)	1974-05-16	Neue (heteroarylmethyl)-normorphine, deren saeureadditionssalze, verfahren zu deren herstellung sowie deren verwendung als arzneimittel
US4059586A (en)	1977-11-22	5-Alkoxy-2-alkyl-1,2,3,4-tetrahydroisoquinolene-8-carboxaldehyde and derivatives
FR2495470A1 (fr)	1982-06-11	Nouveaux medicaments a base de derives de (quinolyl-4)-1 (piperidyl-4)-2 ethanol ou (quinolyl-4)-1 (piperidyl-4)-3 propanol
US3947454A (en)	1976-03-30	5 or 1'-Hydroxy-2-alkyl-7,8-cyclopentano[h]-1,2,3,4-tetrahydroisoquinolines and esters
US3810899A (en)	1974-05-14	2-hydroxy-n-substituted-morphinan derivatives
US3978067A (en)	1976-08-31	7,8-Cyclopentano[H]-1,2,3,4-tetrahydroisoquinoline-1'-ones
US3953458A (en)	1976-04-27	1-Substituted amino-2-alkyl-5-hydroxy-7,8-cyclopentano[h]-1,2,3,4-tetrahydroisoquinolines
US4194044A (en)	1980-03-18	Process for preparing 3-phenoxy morphinans
US4163853A (en)	1979-08-07	1-(P-phenoxy)benzyl-1,2,3,4,5,6,7,8-octahydroisoquinolines
US3796715A (en)	1974-03-12	8-alkoxy-3,4-dihydroisoquinolines
US3311633A (en)	1967-03-28	Behydro-emehnes
CA1041526A (fr)	1978-10-31	Benzopyrannes cyclopenta substitues de groupements alkyles
US3047571A (en)	1962-07-31	Derivatives of oxopiperidinyl phenthiazines
EP0043729B1 (fr)	1984-02-01	Isoquinoléines à activité dopaminergique
US3962254A (en)	1976-06-08	N-substituted-5,6-dihydroxycyclopentano[h]-1,2,3,4-tetrahydroisoquinolines and ethers and esters thereof
US3954774A (en)	1976-05-04	N-substituted-7,8-dihydroxycyclopentano[f]-1,2,3,4-tetrahydroisoquinolines and ethers and esters thereof
KR810000801B1 (ko)	1981-07-08	2-테트라 하이드로 푸르푸릴-6,7-벤조모르판류의 제조방법
CA1088935A (fr)	1980-11-04	Derives levogyres de 3-phenoxymorphinane
US3840522A (en)	1974-10-08	Hexahydrobenzazocines
US3450704A (en)	1969-06-17	Substituted 2 - (3 - aryl - 3 - keto (or 3-hydroxy)-propyl) - 1,2,3,4 - tetrahydroisoquinolines
CA1063117A (fr)	1979-09-25	Cyclopentano (h) ou (f) 1,2,3,4-tetrahydroisoquinolines