PL91808B1 - - Google Patents
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- PL91808B1 PL91808B1 PL1973174973A PL17497373A PL91808B1 PL 91808 B1 PL91808 B1 PL 91808B1 PL 1973174973 A PL1973174973 A PL 1973174973A PL 17497373 A PL17497373 A PL 17497373A PL 91808 B1 PL91808 B1 PL 91808B1
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- 150000001875 compounds Chemical class 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 230000021736 acetylation Effects 0.000 claims description 3
- 238000006640 acetylation reaction Methods 0.000 claims description 3
- 230000011987 methylation Effects 0.000 claims description 3
- 238000007069 methylation reaction Methods 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910052717 sulfur Chemical group 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- 239000003791 organic solvent mixture Substances 0.000 claims 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 229950006134 normorphine Drugs 0.000 claims 1
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-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
- -1 acetyl chloride Chemical class 0.000 description 5
- 229950004392 norcodeine Drugs 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 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 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 239000008896 Opium Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound 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 2
- 229960004126 codeine Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- 229960001027 opium Drugs 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- YIUIVFFUEVPRIU-UHFFFAOYSA-N 8-chlorotheophylline Chemical compound O=C1N(C)C(=O)N(C)C2=NC(Cl)=N[C]21 YIUIVFFUEVPRIU-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 244000248349 Citrus limon Species 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- ONBWJWYUHXVEJS-ZTYRTETDSA-N Normorphine Chemical class C([C@@H](NCC1)[C@@H]2C=C[C@@H]3O)C4=CC=C(O)C5=C4[C@@]21[C@H]3O5 ONBWJWYUHXVEJS-ZTYRTETDSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000000729 antidote Substances 0.000 description 1
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 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
- 239000002775 capsule Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 238000005661 deetherification reaction Methods 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 229950003851 desomorphine Drugs 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- MKFVFIFKKBWIBD-UHFFFAOYSA-N lithium;methane Chemical compound [Li].C MKFVFIFKKBWIBD-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 230000001035 methylating effect Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- HKOIXWVRNLGFOR-KOFBORESSA-N norcodeine Chemical compound O[C@H]([C@@H]1O2)C=C[C@H]3[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4 HKOIXWVRNLGFOR-KOFBORESSA-N 0.000 description 1
- HKOIXWVRNLGFOR-UHFFFAOYSA-N norcodeine Natural products O1C2C(O)C=CC3C4CC5=CC=C(OC)C1=C5C23CCN4 HKOIXWVRNLGFOR-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Emergency Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Networks Using Active Elements (AREA)
Description
Przedmiotem wynalazku jest sposób wytwarzania nowych N-(heteroarylometylo)-dezoksy-normorfin i -norkodein, scislej N-(heteroarylometylo)-zl7-dezok- sy-normorfin i -norkodein oraz odpowiednich dwu- hydrozwiazków o wzorze ogólnym 1, w którym R oznacza grupe metylowa lub acetylowa, R' ozna¬ cza wodór lub grupe metylowa, a X oznacza tlen lub siarke i ich soli addycyjnych z kwasami. No¬ we zwiazki wykazuja wartosciowe wlasciwosci te¬ rapeutyczne.Wedlug wynalazku nowe zwiazki wytwarza sie przez metylowanie lub acetylowanie zwiazków o wzorze ogólnym 1, w którym R oznacza wodór.Acetylowanie prowadzi sie przez reakcje z akty¬ wowana pochodna kwasu octowego, np. halogen¬ kiem acetylu, korzystnie chlorkiem acetylu lub bezwodnikiem octowym. Metylowanie prowadzi sie za pomoca srodków metylujacych, takich jak siar¬ czan dwumetylowy, jodek metylu lub dwuazome- tan. Produkty reakcji znanymi metodami wyodreb¬ nia sie, oczyszcza i krystalizuje i ewentualnie prze¬ prowadza w odpowiednie zwiazki addycyjne.Wytwarzanie zwiazku wyjsciowego przeprowadza sie przez alkilowanie zwiazków o wzorze ogólnym 2 zwiazkami o wzorze 3, w którym R' i X maja wyzej podane znaczenie, a Y oznacza latwo amo¬ nowo odszczepialna grupe, np. chlorowiec, zwlasz¬ cza chlor, brom lub jod lub grupe arylosulfony- loksylowa, aralkilosulfonyloksylowa lub alkilosul- fonyloksylowa.Reakcje zwiazku nor o wzorze ogólnym 2 pro¬ wadzi sie z obliczona iloscia lub malym nadmia¬ rem srodka alkilujacego o wzorze ogólnym 3, sku- tecznie w obecnosci srodka wiazacego kwas. Jako srodek wiazacy kwas stosuje sie aminy, jak np. trójetyloamine, dwucyklcheksylcetyloamine lub weglany metali, np. weglan sodowy lub potasowy lub wodoroweglany metali, zwlaszcza wodoroweg¬ lan sodowy lub wodorotlenki metali, lub tlenki metali. Reakcje prowadzi sie korzystnie w obo¬ jetnym rozpuszczalniku lub w mieszaninie roz¬ puszczalników, np. w tetrahydrcfuranie, dioksanie, chlorku metylenu, dwumetylofcrmamidzie, sulfo- tlenku dwumetylu. Korzystnie stosuje sie miesza¬ niny z tetrahydrofuranu i dwumetyloformamidu.Temperatura reakcji waha sie w szerokich gra¬ nicach, szczególnie stosuje sie temperatury od 0°C do temperatury wrzenia stosowanego rozpuszczal¬ nika wzglednie mieszaniny rozpuszczalników. Po zakonczeniu reakcji, produkty reakcji znanymi me¬ todami wyodrebnia sie i ewentualnie przeprowa¬ dza w odpowiednie zwiazki addycyjne.Zwiazki wyjsciowe o wzorze 2 sa znane. Do¬ tychczas nie znane zwiazki nor mozna znanymi metodami wytwarzac. Mozna, np. tozylowac ko¬ deine i nastepnie za pomoca wodorku litowogli- nowego przeprowadzic w zl7-dezoksy-kodeine. Na¬ stepnie odmetylowanie, np. za pomoca rozkladu bromkiem cyjanu daje zl7-dezoksy-norkodeine, któ¬ ra przeksztalca sie przez uwodornienie podwójnego 9180891808 wiazania w odpowiednia dwuhydrodezoksy-norko- deine. Za pomoca eterowego rozszczepienia Zl7-de- zoksy-norkodeiny wzglednie dwuhydro-dezoksy- -norkodeiny otrzymuje sie odpowiednie pochodne normorfiny.Otrzymywane sposobem wedlug wynalazku zwia¬ zki o wzorze ogólnym 1 sa zasadami i mozna je w znany sposób przeprowadzic w ich fizjologicz¬ nie dopuszczalne sole addycyjne z kwasami. Od¬ powiednimi do tworzenia soli kwasami sa kwasy mineralne, takie jak kwas solny, bromowodorowy, jodowodorowy, fluorowodorowy, siarkowy, fosforo¬ wy, azotowy lub kwasy organiczne, takie jak kwas octowy, propioniow^, maslowy, walerianowy, pi- walinowy, kapronowy, szczawiowy, malonowy, bur¬ sztynowy maleinowy, fumarowy, mlekowy, wino¬ wy, cytrynowy, jablkowy, benzoesowy, p-amino- benzoesowy, p-hydroksybenzoesowy, ftalowy, teref- talowy, cynamonowy, salicylowy, askorbinowy, 8- -chloroteofilina, kwas metanosulfonowy, benzeno- sulfonowy, etanofosfonowy itp.Otrzymywane sposobem wedlug wynalazku de- zoksy-normorfiny i -norkodeiny o wzorze ogól¬ nym 1 oraz ich sole addycyjne z kwasami wy¬ wieraja terapeutycznie pozyteczny wplyw na cen¬ tralny uklad nerwowy. Wykazuja one wybitny antagonizm wobec morfiny, badany na myszach i mozna je stosowac przeto jako antidotum przy zatruciach lekami zawierajacymi opium i do zwal¬ czania nalogu morfinizowania. Ponadto zwiazki o wzorze ogólnym 1 i ich sole addycyjne z kwa¬ sami posiadaja dzialanie analgetyczne i przeciw- kaszlowe.Otrzymywane sposobem wedlug wynalazku zwia¬ zki o wzorze ogólnym 1 i ich sole addycyjne z kwasami mozna stosowac doustnie i pozajeli¬ towe. Dawka wynosi przy stosowaniu doustnym —300,. zwlaszcza 50—150 mg. Zwiazki o wzorze 1 wzglednie ich sole addycyjne z kwasami mozna stosowac równiez jako dodatek do leków zawie¬ rajacych opium lub równiez laczyc z innymi usmierzajacymi ból substancjami czynnymi, takimi jak srodki znieczulajace, uspokajajace, nasenne.Odpowiednimi galenowymi postaciami uzytkowy¬ mi sa, np. tabletki, kapsulki, czopki, roztwory, zawiesiny lub proszki, do wytwarzania których stosuje sie zwykle uzywane galenowe srodki po¬ mocnicze, nosniki, srodki rozkruszajace lub posliz¬ gowe lub substancje powodujace przedluzone dzia¬ lanie. Tego rodzaju formy uzytkowe wytwarza sie znanymi metodami. 39 40 45 50 Przyklad. N-[2-metylo-furylo-(3)]-0-acetylo- -nordezoksymorfina Przez reakcje N-[2-metylo-furylometylo-(3)]-nor- dezomorfiny z bezwodnikiem kwasu 'octowego w pirydynie otrzymuje sie tytulowy zwiazek, któ¬ rego chlorowodorek topnieje w temperaturze 185— —187°C.Wyzej opisanym sposobem wytwarza sie naste¬ pujace zwiazki: R -CE. wzór 6 -CH3 -CH3 -CH3 -CH3 A. Pochodne N-pod- stawnik wzór 4 wzór 7 wzór 7 wzór 8 wzór 9 wzór 10 dwuhydrodezoksy Zasada sól wzór 5 wzór 5 HCl HCl HCl HCl Temperatura topnienia °C 180—182 128—131 233—235 (rozklad) 225—228 220—223 207—209 (rozklad) B. Pochodne dezoksy 1 R -CH3 -CH3 -CH3 ' -CH3 N-pod- stawnik wzór 11 wzór 8 wzór 10 wzór 12 Zasada sól HCl HCl HCl zasada Temperatura topnienia °C 221—223 232—234 213—214 (rozklad) 140—141 | PL
Claims (2)
- Zastrzezenia patentowe 1. Sposób wytwarzania nowych N-(heteroarylo- metylo)-dezoksynormorfin i -norkodein, scislej N- -(heteroarylometylo)-Zl7-dezoksy-normorfin i -nor¬ kodein i odpowiednich dwuhydrozwiazków o wzo¬ rze ogólnym 1, w którym R oznacza grupe metylowa lub acetylowa, R' oznacza wodór lub grupe mety¬ lowa, a X oznacza tlen lub siarke, oraz ich soli addycyjnych z kwasami, znamienny tym, ze zwiaz¬ ki o wzorze ogólnym 1, w którym R oznacza wo¬ dór, poddaje sie acetylowaniu lub metylowaniu i otrzymany zwiazek o wzorze 1 ewentualnie prze¬ prowadza sie w ich sole addycyjne z kwasami.
- 2. Sposób wedlug zastrz. 1, znamienny tym, ze reakcje prowadzi sie w obecnosci organicznego rozpuszczalnika lub mieszaniny rozpuszczalników.91808 N-CK R' VX^ WZdR 1 mo tr WZdR2 Y-CK l-R" WZÓR3 H2C- *0' W2dR 4 HOOC-CH HC-COOH WZÓR 591808 O .n -C-CH3 -H2C O' WZdR 6 WZdR 7 -KCT-fc -H2CT WZdR 8 WZÓR 9 H3C- O /3 WZÓR 10 WZdR 11 -H3CTr CH3 WZ(3R 12 RSW Zakl. Graf. W-wa, Srebrna 16 z. 603-77/O —105 + 20 egz. Cena 10 zl PL
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2245141A DE2245141A1 (de) | 1972-09-14 | 1972-09-14 | Neue n-(heteroarylmethyl)-desoxynormorphine und -norcodeine, deren saeureadditionssalze, verfahren zu deren herstellung sowie deren verwendung als arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PL91808B1 true PL91808B1 (pl) | 1977-03-31 |
Family
ID=5856355
Family Applications (8)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL1973174972A PL91807B1 (pl) | 1972-09-14 | 1973-09-13 | |
| PL1973174974A PL91809B1 (pl) | 1972-09-14 | 1973-09-13 | |
| PL1973165187A PL87721B1 (pl) | 1972-09-14 | 1973-09-13 | |
| PL1973174969A PL91837B1 (pl) | 1972-09-14 | 1973-09-13 | |
| PL1973174970A PL91836B1 (pl) | 1972-09-14 | 1973-09-13 | |
| PL1973174971A PL91829B1 (pl) | 1972-09-14 | 1973-09-13 | |
| PL1973174973A PL91808B1 (pl) | 1972-09-14 | 1973-09-13 | |
| PL1973174968A PL90720B1 (pl) | 1972-09-14 | 1973-09-13 |
Family Applications Before (6)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL1973174972A PL91807B1 (pl) | 1972-09-14 | 1973-09-13 | |
| PL1973174974A PL91809B1 (pl) | 1972-09-14 | 1973-09-13 | |
| PL1973165187A PL87721B1 (pl) | 1972-09-14 | 1973-09-13 | |
| PL1973174969A PL91837B1 (pl) | 1972-09-14 | 1973-09-13 | |
| PL1973174970A PL91836B1 (pl) | 1972-09-14 | 1973-09-13 | |
| PL1973174971A PL91829B1 (pl) | 1972-09-14 | 1973-09-13 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL1973174968A PL90720B1 (pl) | 1972-09-14 | 1973-09-13 |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US3928359A (pl) |
| JP (1) | JPS4966700A (pl) |
| AT (1) | AT326281B (pl) |
| BE (1) | BE804836A (pl) |
| BG (8) | BG21227A3 (pl) |
| CH (7) | CH589090A5 (pl) |
| CS (8) | CS168680B2 (pl) |
| DD (1) | DD109384A5 (pl) |
| DE (1) | DE2245141A1 (pl) |
| ES (8) | ES418563A1 (pl) |
| FI (1) | FI55512C (pl) |
| FR (1) | FR2199982B1 (pl) |
| GB (1) | GB1449222A (pl) |
| HU (1) | HU166367B (pl) |
| IE (1) | IE38320B1 (pl) |
| IL (1) | IL43216A (pl) |
| NL (1) | NL7312621A (pl) |
| NO (1) | NO139482C (pl) |
| PL (8) | PL91807B1 (pl) |
| RO (2) | RO63003A (pl) |
| SE (1) | SE413510B (pl) |
| SU (8) | SU498911A3 (pl) |
| YU (2) | YU243973A (pl) |
| ZA (1) | ZA737289B (pl) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4236008A (en) * | 1978-09-19 | 1980-11-25 | E. I. Du Pont De Nemours And Company | Fluorination of precursors for fluorine analogs of hydrocodone and oxycodone |
| US4241065A (en) * | 1979-07-02 | 1980-12-23 | E. I. Du Pont De Nemours And Company | Fluoro analogs of hydrocodone and oxycodone useful as analgesics, narcotic antagonists or both |
| WO1999038869A1 (en) * | 1998-01-29 | 1999-08-05 | Monash University | Therapeutic compounds |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2107989A1 (de) * | 1971-02-19 | 1972-09-07 | Boehringer Sohn Ingelheim | N-(Furyl-methy])-morphinane, deren Säureadditionssalze sowie Verfahren zu deren Herstellung |
-
1972
- 1972-09-14 DE DE2245141A patent/DE2245141A1/de active Pending
-
1973
- 1973-09-03 AT AT761673A patent/AT326281B/de not_active IP Right Cessation
- 1973-09-07 ES ES418563A patent/ES418563A1/es not_active Expired
- 1973-09-11 CH CH207177A patent/CH589090A5/xx not_active IP Right Cessation
- 1973-09-11 CH CH198077A patent/CH589088A5/xx not_active IP Right Cessation
- 1973-09-11 CH CH207377A patent/CH591491A5/xx not_active IP Right Cessation
- 1973-09-11 CH CH207077A patent/CH591490A5/xx not_active IP Right Cessation
- 1973-09-11 CH CH198177A patent/CH589089A5/xx not_active IP Right Cessation
- 1973-09-11 CH CH1298673A patent/CH590287A5/xx not_active IP Right Cessation
- 1973-09-11 CH CH207277A patent/CH605958A5/xx not_active IP Right Cessation
- 1973-09-11 US US396171A patent/US3928359A/en not_active Expired - Lifetime
- 1973-09-12 BG BG025616A patent/BG21227A3/xx unknown
- 1973-09-12 CS CS288*[A patent/CS168680B2/cs unknown
- 1973-09-12 CS CS286*[A patent/CS168678B2/cs unknown
- 1973-09-12 CS CS285*[A patent/CS168677B2/cs unknown
- 1973-09-12 CS CS282*[A patent/CS168674B2/cs unknown
- 1973-09-12 BG BG025619A patent/BG21230A3/xx unknown
- 1973-09-12 DD DD173479A patent/DD109384A5/xx unknown
- 1973-09-12 BG BG025618A patent/BG21229A3/xx unknown
- 1973-09-12 CS CS284*[A patent/CS168676B2/cs unknown
- 1973-09-12 CS CS287*[A patent/CS168679B2/cs unknown
- 1973-09-12 BG BG25617A patent/BG21228A3/xx unknown
- 1973-09-12 CS CS283*[A patent/CS168675B2/cs unknown
- 1973-09-12 HU HUBO1463A patent/HU166367B/hu unknown
- 1973-09-12 BG BG025614A patent/BG21225A3/xx unknown
- 1973-09-12 SU SU1962620A patent/SU498911A3/ru active
- 1973-09-12 IE IE1630/73A patent/IE38320B1/xx unknown
- 1973-09-12 CS CS6322A patent/CS168673B2/cs unknown
- 1973-09-12 BG BG24524A patent/BG21412A3/xx unknown
- 1973-09-12 BG BG025613A patent/BG21224A3/xx unknown
- 1973-09-13 PL PL1973174972A patent/PL91807B1/pl unknown
- 1973-09-13 PL PL1973174974A patent/PL91809B1/pl unknown
- 1973-09-13 IL IL43216A patent/IL43216A/en unknown
- 1973-09-13 PL PL1973165187A patent/PL87721B1/pl unknown
- 1973-09-13 PL PL1973174969A patent/PL91837B1/pl unknown
- 1973-09-13 NL NL7312621A patent/NL7312621A/xx not_active Application Discontinuation
- 1973-09-13 BE BE135636A patent/BE804836A/xx unknown
- 1973-09-13 PL PL1973174970A patent/PL91836B1/pl unknown
- 1973-09-13 JP JP48103716A patent/JPS4966700A/ja active Pending
- 1973-09-13 PL PL1973174971A patent/PL91829B1/pl unknown
- 1973-09-13 ZA ZA00737289A patent/ZA737289B/xx unknown
- 1973-09-13 PL PL1973174973A patent/PL91808B1/pl unknown
- 1973-09-13 RO RO7300076068A patent/RO63003A/ro unknown
- 1973-09-13 PL PL1973174968A patent/PL90720B1/pl unknown
- 1973-09-13 FI FI2853/73A patent/FI55512C/fi active
- 1973-09-13 YU YU02439/73A patent/YU243973A/xx unknown
- 1973-09-13 RO RO7382817A patent/RO70193A/ro unknown
- 1973-09-13 NO NO3588/73A patent/NO139482C/no unknown
- 1973-09-13 GB GB4314673A patent/GB1449222A/en not_active Expired
- 1973-09-14 SE SE7312583A patent/SE413510B/xx unknown
- 1973-09-14 FR FR7333092A patent/FR2199982B1/fr not_active Expired
-
1974
- 1974-01-28 BG BG025615A patent/BG21226A3/bg unknown
- 1974-09-19 ES ES430201A patent/ES430201A1/es not_active Expired
- 1974-09-19 ES ES430197A patent/ES430197A1/es not_active Expired
- 1974-09-19 ES ES430199A patent/ES430199A1/es not_active Expired
- 1974-09-19 ES ES430200A patent/ES430200A1/es not_active Expired
- 1974-09-19 ES ES430202A patent/ES430202A1/es not_active Expired
- 1974-09-19 ES ES430203A patent/ES430203A1/es not_active Expired
- 1974-09-19 ES ES430198A patent/ES430198A1/es not_active Expired
- 1974-09-30 SU SU2063985A patent/SU503523A3/ru active
- 1974-09-30 SU SU2063982A patent/SU528878A3/ru active
- 1974-09-30 SU SU2063983A patent/SU509239A3/ru active
- 1974-09-30 SU SU2063380A patent/SU503524A3/ru active
- 1974-09-30 SU SU2063987A patent/SU506299A3/ru active
- 1974-09-30 SU SU2063986A patent/SU505366A3/ru active
- 1974-09-30 SU SU2063984A patent/SU520049A3/ru active
-
1979
- 1979-10-19 YU YU02548/79A patent/YU254879A/xx unknown
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