CA1098035A - Traduction non-disponible - Google Patents

Traduction non-disponible

Info

Publication number: CA1098035A
Authority: CA; Canada
Prior art keywords: glaucine; active compound; composition according; hydrobromide; dosage unit
Prior art date: 1977-04-18
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

CA301,259A

Other languages

English (en)

Inventor

Alfred G. Maasbol

Alexander K. Sim

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.)

Karl O Helm AG

Original Assignee

Karl O Helm AG

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.)

1977-04-18

Filing date

1978-04-17

Publication date

1981-03-24

1977-04-18 Priority claimed from DE2717062A external-priority patent/DE2717062C2/de

1977-04-18 Priority claimed from DE2717001A external-priority patent/DE2717001C2/de

1978-04-17 Application filed by Karl O Helm AG filed Critical Karl O Helm AG

1981-03-24 Application granted granted Critical

1981-03-24 Publication of CA1098035A publication Critical patent/CA1098035A/fr

Status Expired legal-status Critical Current

Links

239000000203 mixture Substances 0.000 title claims abstract description 38
230000000954 anitussive effect Effects 0.000 title claims abstract description 12
230000002785 anti-thrombosis Effects 0.000 title abstract description 12
239000003146 anticoagulant agent Substances 0.000 title abstract description 10
229940124584 antitussives Drugs 0.000 title abstract description 7
RUZIUYOSRDWYQF-OAHLLOKOSA-N (6ar)-1,2,9,10-tetramethoxy-6-methyl-5,6,6a,7-tetrahydro-4h-dibenzo[de,g]quinoline Chemical compound CN1CCC2=CC(OC)=C(OC)C3=C2[C@H]1CC1=C3C=C(OC)C(OC)=C1 RUZIUYOSRDWYQF-OAHLLOKOSA-N 0.000 title description 79
JVNHJTPLXAMENH-UHFFFAOYSA-N 6-methyl-5,6,6a,7-tetrahydro-4h-dibenzo[de,g]quinoline-1,2,3,4-tetrol Chemical compound C12=CC=CC=C2CC2N(C)CC(O)C3=C(O)C(O)=C(O)C1=C32 JVNHJTPLXAMENH-UHFFFAOYSA-N 0.000 title description 4
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 title 1
RUZIUYOSRDWYQF-HNNXBMFYSA-N (S)-glaucine Chemical compound CN1CCC2=CC(OC)=C(OC)C3=C2[C@@H]1CC1=C3C=C(OC)C(OC)=C1 RUZIUYOSRDWYQF-HNNXBMFYSA-N 0.000 claims abstract description 43
DABPOQZSGVNAAS-UHFFFAOYSA-N Glaucocalactone Natural products O=CC12C3C(C4)OC(=O)C2C(C)(C)CCC1OC(=O)C13CC4C(=C)C1OC(=O)C DABPOQZSGVNAAS-UHFFFAOYSA-N 0.000 claims abstract description 42
150000001875 compounds Chemical class 0.000 claims abstract description 42
229940113086 glaucine Drugs 0.000 claims abstract description 32
229930004041 glaucine Natural products 0.000 claims abstract description 28
150000003839 salts Chemical class 0.000 claims abstract description 12
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
RMMKCAKVLLJONG-UHFFFAOYSA-N 6-methyl-5,6,6a,7-tetrahydro-4h-dibenzo[de,g]quinoline-1,2,9,10-tetrol Chemical compound C12=CC(O)=C(O)C=C2CC2N(C)CCC3=CC(O)=C(O)C1=C32 RMMKCAKVLLJONG-UHFFFAOYSA-N 0.000 claims abstract description 4
239000000243 solution Substances 0.000 claims description 33
239000002775 capsule Substances 0.000 claims description 13
239000003826 tablet Substances 0.000 claims description 13
229950005627 embonate Drugs 0.000 claims description 12
238000004220 aggregation Methods 0.000 claims description 9
210000001772 blood platelet Anatomy 0.000 claims description 9
239000008298 dragée Substances 0.000 claims description 9
239000006187 pill Substances 0.000 claims description 9
230000002776 aggregation Effects 0.000 claims description 8
239000007787 solid Substances 0.000 claims description 6
230000002401 inhibitory effect Effects 0.000 claims description 5
239000006188 syrup Substances 0.000 claims description 3
235000020357 syrup Nutrition 0.000 claims description 3
238000002347 injection Methods 0.000 claims description 2
239000007924 injection Substances 0.000 claims description 2
239000007788 liquid Substances 0.000 claims 5
PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 abstract description 5
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical group C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 31
230000000694 effects Effects 0.000 description 27
206010011224 Cough Diseases 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
239000013543 active substance Substances 0.000 description 25
238000012360 testing method Methods 0.000 description 25
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 24
238000002844 melting Methods 0.000 description 24
230000008018 melting Effects 0.000 description 24
DKSZLDSPXIWGFO-BLOJGBSASA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.OP(O)(O)=O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC DKSZLDSPXIWGFO-BLOJGBSASA-N 0.000 description 22
229960004415 codeine phosphate Drugs 0.000 description 22
DFFLCVRJWUOGPN-RSAXXLAASA-N (6as)-1,2,9,10-tetramethoxy-6-methyl-5,6,6a,7-tetrahydro-4h-dibenzo[de,g]quinoline-6-ium;bromide Chemical compound Br.CN1CCC2=CC(OC)=C(OC)C3=C2[C@@H]1CC1=C3C=C(OC)C(OC)=C1 DFFLCVRJWUOGPN-RSAXXLAASA-N 0.000 description 21
241001465754 Metazoa Species 0.000 description 19
239000000047 product Substances 0.000 description 17
OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 16
229960004126 codeine Drugs 0.000 description 15
XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 15
235000019441 ethanol Nutrition 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
230000000052 comparative effect Effects 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
229960001789 papaverine Drugs 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
229930008281 A03AD01 - Papaverine Natural products 0.000 description 7
239000000443 aerosol Substances 0.000 description 7
230000037396 body weight Effects 0.000 description 7
230000001965 increasing effect Effects 0.000 description 7
238000000034 method Methods 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
241000700198 Cavia Species 0.000 description 6
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
230000008602 contraction Effects 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
230000011514 reflex Effects 0.000 description 6
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
229920002472 Starch Polymers 0.000 description 5
208000007536 Thrombosis Diseases 0.000 description 5
-1 dimethylaminoethyl group Chemical group 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
210000000936 intestine Anatomy 0.000 description 5
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 5
239000008107 starch Substances 0.000 description 5
235000019698 starch Nutrition 0.000 description 5
XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 4
HNZPJEARRSZDST-UHFFFAOYSA-N 6-methyl-5,6,6a,7-tetrahydro-4h-dibenzo[de,g]quinoline-1,2,3,4-tetrol;hydrochloride Chemical compound Cl.C12=CC=CC=C2CC2N(C)CC(O)C3=C(O)C(O)=C(O)C1=C32 HNZPJEARRSZDST-UHFFFAOYSA-N 0.000 description 4
XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 4
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
KGPAYJZAMGEDIQ-KRWDZBQOSA-N Laudanosine Chemical compound C1=C(OC)C(OC)=CC=C1C[C@H]1C2=CC(OC)=C(OC)C=C2CCN1C KGPAYJZAMGEDIQ-KRWDZBQOSA-N 0.000 description 4
VHRSWCTVFBWHKE-UHFFFAOYSA-N Laudanosoline Chemical compound CN1CCC2=CC(O)=C(O)C=C2C1CC1=CC=C(O)C(O)=C1 VHRSWCTVFBWHKE-UHFFFAOYSA-N 0.000 description 4
208000005392 Spasm Diseases 0.000 description 4
229930006000 Sucrose Natural products 0.000 description 4
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
239000003814 drug Substances 0.000 description 4
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 4
235000019359 magnesium stearate Nutrition 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
239000000546 pharmaceutical excipient Substances 0.000 description 4
239000002904 solvent Substances 0.000 description 4
230000008925 spontaneous activity Effects 0.000 description 4
239000000126 substance Substances 0.000 description 4
229960004793 sucrose Drugs 0.000 description 4
239000000454 talc Substances 0.000 description 4
235000012222 talc Nutrition 0.000 description 4
229910052623 talc Inorganic materials 0.000 description 4
UOTMYNBWXDUBNX-UHFFFAOYSA-N 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxyisoquinolin-2-ium;chloride Chemical compound Cl.C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 UOTMYNBWXDUBNX-UHFFFAOYSA-N 0.000 description 3
241000700199 Cavia porcellus Species 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
208000007101 Muscle Cramp Diseases 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
235000021355 Stearic acid Nutrition 0.000 description 3
230000009471 action Effects 0.000 description 3
239000006227 byproduct Substances 0.000 description 3
AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 3
229960004484 carbachol Drugs 0.000 description 3
239000013078 crystal Substances 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
239000012153 distilled water Substances 0.000 description 3
231100000673 dose–response relationship Toxicity 0.000 description 3
229940079593 drug Drugs 0.000 description 3
238000001035 drying Methods 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
238000001914 filtration Methods 0.000 description 3
229960001340 histamine Drugs 0.000 description 3
230000000968 intestinal effect Effects 0.000 description 3
230000008991 intestinal motility Effects 0.000 description 3
239000008101 lactose Substances 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
238000005259 measurement Methods 0.000 description 3
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
229960003207 papaverine hydrochloride Drugs 0.000 description 3
239000000523 sample Substances 0.000 description 3
238000000926 separation method Methods 0.000 description 3
239000008117 stearic acid Substances 0.000 description 3
230000000638 stimulation Effects 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
230000001629 suppression Effects 0.000 description 3
229940095064 tartrate Drugs 0.000 description 3
SANXPMGEBDLSJX-FERBBOLQSA-M (1s)-1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-2,2-dimethyl-3,4-dihydro-1h-isoquinolin-2-ium;iodide Chemical compound [I-].C1=C(OC)C(OC)=CC=C1C[C@@H]1[N+](C)(C)CCC2=CC(OC)=C(OC)C=C21 SANXPMGEBDLSJX-FERBBOLQSA-M 0.000 description 2
UMVRVVIYKLBXAF-UHFFFAOYSA-N 1-[(3,4-dihydroxyphenyl)methyl]-2-methyl-3,4-dihydro-1h-isoquinoline-6,7-diol;hydrobromide Chemical compound Br.CN1CCC2=CC(O)=C(O)C=C2C1CC1=CC=C(O)C(O)=C1 UMVRVVIYKLBXAF-UHFFFAOYSA-N 0.000 description 2
244000215068 Acacia senegal Species 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
241000699800 Cricetinae Species 0.000 description 2
229920000084 Gum arabic Polymers 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
240000001090 Papaver somniferum Species 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 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
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
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 2
239000000205 acacia gum Substances 0.000 description 2
235000010489 acacia gum Nutrition 0.000 description 2
229930013930 alkaloid Natural products 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
238000001816 cooling Methods 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
230000002496 gastric effect Effects 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
230000011987 methylation Effects 0.000 description 2
238000007069 methylation reaction Methods 0.000 description 2
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
238000010992 reflux Methods 0.000 description 2
230000029058 respiratory gaseous exchange Effects 0.000 description 2
210000002784 stomach Anatomy 0.000 description 2
229960001367 tartaric acid Drugs 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
230000001732 thrombotic effect Effects 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
LZJRNLRASBVRRX-ZDUSSCGKSA-N (+)-Boldine Natural products CN1CCC2=CC(O)=C(OC)C3=C2[C@@H]1CC1=C3C=C(OC)C(O)=C1 LZJRNLRASBVRRX-ZDUSSCGKSA-N 0.000 description 1
ONMKCYMMGBIVPT-UHFFFAOYSA-N 1-methoxyphenanthrene Chemical compound C1=CC2=CC=CC=C2C2=C1C(OC)=CC=C2 ONMKCYMMGBIVPT-UHFFFAOYSA-N 0.000 description 1
SDEBYHVDMCQKNZ-UHFFFAOYSA-N 4-methoxy-6-piperazin-1-ylpyrimidine;hydrochloride Chemical compound Cl.C1=NC(OC)=CC(N2CCNCC2)=N1 SDEBYHVDMCQKNZ-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
235000005976 Citrus sinensis Nutrition 0.000 description 1
240000002319 Citrus sinensis Species 0.000 description 1
206010010774 Constipation Diseases 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
229920000742 Cotton Polymers 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
206010017999 Gastrointestinal pain Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000001828 Gelatine Substances 0.000 description 1
229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
241000699673 Mesocricetus auratus Species 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
235000008753 Papaver somniferum Nutrition 0.000 description 1
229920005439 Perspex® Polymers 0.000 description 1
201000005702 Pertussis Diseases 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
241000557172 Stylophorum diphyllum Species 0.000 description 1
239000002253 acid Substances 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
150000003797 alkaloid derivatives Chemical class 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 1
230000001407 anti-thrombic effect Effects 0.000 description 1
239000003434 antitussive agent Substances 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
238000003287 bathing Methods 0.000 description 1
239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
238000012505 colouration Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
229960001270 d- tartaric acid Drugs 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
238000010586 diagram Methods 0.000 description 1
235000013681 dietary sucrose Nutrition 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
230000006872 improvement Effects 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
230000002427 irreversible effect Effects 0.000 description 1
230000007794 irritation Effects 0.000 description 1
210000003801 laryngeal nerve Anatomy 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
230000005923 long-lasting effect Effects 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
201000005202 lung cancer Diseases 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
239000012528 membrane Substances 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
229940102396 methyl bromide Drugs 0.000 description 1
230000004089 microcirculation Effects 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
229960005181 morphine Drugs 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
235000006502 papoula Nutrition 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
229960001412 pentobarbital Drugs 0.000 description 1
238000003359 percent control normalization Methods 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
210000002381 plasma Anatomy 0.000 description 1
239000004926 polymethyl methacrylate Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical class [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000008569 process Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
238000000611 regression analysis Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
230000000630 rising effect Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229960001866 silicon dioxide Drugs 0.000 description 1
238000010583 slow cooling Methods 0.000 description 1
239000002002 slurry Substances 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
NKAAEMMYHLFEFN-ZVGUSBNCSA-M sodium;(2r,3r)-2,3,4-trihydroxy-4-oxobutanoate Chemical compound [Na+].OC(=O)[C@H](O)[C@@H](O)C([O-])=O NKAAEMMYHLFEFN-ZVGUSBNCSA-M 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
230000003033 spasmogenic effect Effects 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000002885 thrombogenetic effect Effects 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
201000008827 tuberculosis Diseases 0.000 description 1
238000002211 ultraviolet spectrum Methods 0.000 description 1
230000002792 vascular Effects 0.000 description 1
210000000264 venule Anatomy 0.000 description 1
238000010792 warming Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
229940045860 white wax Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/235—Saturated compounds containing more than one carboxyl group
- C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
- C07C59/255—Tartaric acid
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/18—Ring systems of four or more rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/22—Ortho- or ortho- and peri-condensed systems containing three rings containing only six-membered rings
- C07C2603/26—Phenanthrenes; Hydrogenated phenanthrenes

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Hematology (AREA)
Diabetes (AREA)
Pulmonology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicinal Preparation (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Other In-Based Heterocyclic Compounds (AREA)

CA301,259A 1977-04-18 1978-04-17 Traduction non-disponible Expired CA1098035A (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
DE2717062A DE2717062C2 (de)	1977-04-18	1977-04-18	Arzneimittel mit antitussiver Wirkung
DE2717001A DE2717001C2 (de)	1977-04-18	1977-04-18	Arzneimittel mit antithrombotischer Wirkung
DEP2717001.0		1977-04-18
DEP2717062.3		1977-04-18

Publications (1)

Publication Number	Publication Date
CA1098035A true CA1098035A (fr)	1981-03-24

Family

ID=25771874

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA301,259A Expired CA1098035A (fr)	1977-04-18	1978-04-17	Traduction non-disponible

Country Status (7)

Country	Link
JP (1)	JPS53130437A (fr)
AU (1)	AU520608B2 (fr)
CA (1)	CA1098035A (fr)
FR (1)	FR2387652A1 (fr)
GB (1)	GB1587378A (fr)
IT (1)	IT1104846B (fr)
NL (1)	NL7803601A (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5645459A (en) *	1979-09-20	1981-04-25	Otsuka Pharmaceut Co Ltd	Cyclic amine
FR2843963B1 (fr) *	2002-08-30	2004-10-22	Sederma Sa	Nouvelles molecules derivees de la noraporphine

1978
- 1978-04-04 NL NL7803601A patent/NL7803601A/xx not_active Application Discontinuation
- 1978-04-13 GB GB14623/78A patent/GB1587378A/en not_active Expired
- 1978-04-17 FR FR7811244A patent/FR2387652A1/fr active Granted
- 1978-04-17 CA CA301,259A patent/CA1098035A/fr not_active Expired
- 1978-04-17 IT IT48932/78A patent/IT1104846B/it active
- 1978-04-18 AU AU35198/78A patent/AU520608B2/en not_active Expired
- 1978-04-18 JP JP4621578A patent/JPS53130437A/ja active Pending

Also Published As

Publication number	Publication date
IT7848932A0 (it)	1978-04-17
NL7803601A (nl)	1978-10-20
GB1587378A (en)	1981-04-01
AU3519878A (en)	1979-10-25
JPS53130437A (en)	1978-11-14
FR2387652B1 (fr)	1982-04-23
AU520608B2 (en)	1982-02-11
FR2387652A1 (fr)	1978-11-17
IT1104846B (it)	1985-10-28

Publication	Publication Date	Title
US5223541A (en)	1993-06-29	Tramadol n-oxide material, enantiomers and compositions thereof, and their use
KR0172596B1 (ko)	1999-02-01	진해제로서의 엔도에테노/엔도에타노-에폭시모르피난 유도체의 (+)-이성질체
JP6091426B2 (ja)	2017-03-08	鎮痛剤として有用な新規モルフィナン類
RU2409365C2 (ru)	2011-01-20	ПРИМЕНЕНИЕ 3,11b-ЦИС-ДИГИДРОТЕТРАБЕНАЗИНА ДЛЯ ЛЕЧЕНИЯ СИМПТОМОВ БОЛЕЗНИ ГЕНТИНГТОНА
WO1988002254A1 (fr)	1988-04-07	Nouvel agent psychostimulant
US4528289A (en)	1985-07-09	Corynantheine derivates, processes for their preparation, and their use
CA1098035A (fr)	1981-03-24	Traduction non-disponible
JP2906339B2 (ja)	1999-06-21	活性成分としてデヒドロエボジアミン−ＨＣｌを含有する記憶増強および抗痴呆剤
US4279914A (en)	1981-07-21	Thrombocyte aggregation inhibiting composition and methods
JPH05500822A (ja)	1993-02-18	経口的に活性な非中毒性鎮痛薬
WO1995021827A1 (fr)	1995-08-17	Nouveau compose du type aconitine, agent antipyretique, analgesique et anti-inflammatoire
US4370331A (en)	1983-01-25	L-Glaucine containing composition for cough relief
US5804589A (en)	1998-09-08	Use of N-cyclohexyl benzamides for treating bowel disorders
GB2201676A (en)	1988-09-07	Piperazinecarboxylic acid, its preparation and pharmaceutical compositions containing it
JPS63275583A (ja)	1988-11-14	新規なアコニチン系化合物およびそれらを有効成分とする鎮痛・抗炎症剤
US3248292A (en)	1966-04-26	Pharmaceutically active dimethoxyquinazolines
IE47223B1 (en)	1984-01-25	Anti-tussic or anti-thrombotic pharmaceutical compositions and their preparation
US7629355B2 (en)	2009-12-08	Treatment of chemical dependency with substantially nonaddicting normorphine and norcodeine derivatives
US4183939A (en)	1980-01-15	Glaucine analgesic method
DE69619156T2 (de)	2002-08-14	Verwendung von alpha-Aminomethyl-3,4-dichlorbenzylthioaceamiden zur Herstellung eines dopaminwiederergreifungshemmenden Medikaments sowie Verbindungen zur Verwendung derselben
CA1331994C (fr)	1994-09-13	(+)-1-((3,4,5-trimethoxy)-benzyloxymethyl)-1-phenyl-n,n- propylamine, procede d'obtention et son utilisation et son utilisation en therapeutique
FI68812C (fi)	1985-11-11	Foerfarande foer framstaellning av terapeutiskt effektiva 1- och d,1-glausinlactatsalter
CA1220200A (fr)	1987-04-07	Procede de preparation d'halomethylates de levallorphan et composes pharmaceutiques les contenant et ayant une action inhibitrice des opiaces
US4265912A (en)	1981-05-05	Glaucine lactate salts
CA1337424C (fr)	1995-10-24	Composes anitumeur extraits d'une eponge marine du genre dercitus

Legal Events

Date	Code	Title	Description
1998-03-24	MKEX	Expiry