PL91407B1 - - Google Patents
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- PL91407B1 PL91407B1 PL1972173621A PL17362172A PL91407B1 PL 91407 B1 PL91407 B1 PL 91407B1 PL 1972173621 A PL1972173621 A PL 1972173621A PL 17362172 A PL17362172 A PL 17362172A PL 91407 B1 PL91407 B1 PL 91407B1
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims 1
- 206010030113 Oedema Diseases 0.000 description 13
- 241000700159 Rattus Species 0.000 description 10
- 239000000126 substance Substances 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 208000025865 Ulcer Diseases 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 239000005995 Aluminium silicate Substances 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 235000012211 aluminium silicate Nutrition 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 229940113118 carrageenan Drugs 0.000 description 4
- 235000010418 carrageenan Nutrition 0.000 description 4
- 229920001525 carrageenan Polymers 0.000 description 4
- 239000000679 carrageenan Substances 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 4
- 230000008961 swelling Effects 0.000 description 4
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 4
- -1 4-biphenylyl Chemical group 0.000 description 3
- 229960002895 phenylbutazone Drugs 0.000 description 3
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- YLGXILFCIXHCMC-JHGZEJCSSA-N methyl cellulose Chemical compound COC1C(OC)C(OC)C(COC)O[C@H]1O[C@H]1C(OC)C(OC)C(OC)OC1COC YLGXILFCIXHCMC-JHGZEJCSSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000002322 anti-exudative effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 230000001562 ulcerogenic effect Effects 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/09—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis
- C07C29/10—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis of ethers, including cyclic ethers, e.g. oxiranes
- C07C29/103—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis of ethers, including cyclic ethers, e.g. oxiranes of cyclic ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/147—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof
- C07C29/149—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of carboxylic acids or derivatives thereof with hydrogen or hydrogen-containing gases
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/17—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrogenation of carbon-to-carbon double or triple bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/60—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by elimination of -OH groups, e.g. by dehydration
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/18—Monohydroxylic alcohols containing only six-membered aromatic rings as cyclic part
- C07C33/24—Monohydroxylic alcohols containing only six-membered aromatic rings as cyclic part polycyclic without condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/26—Polyhydroxylic alcohols containing only six-membered aromatic rings as cyclic part
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pain & Pain Management (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Rheumatology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
Przedmiotem wynalazku jest sposób wytwarza¬ nia nowego 4-(4-bifenylilo)-butanohi-l o wzorze 1.Nowy zwiazek wytwarza sie przez reakcje zwiazku Grignarda o wzorze ogólnym 2, w któ¬ rym Hal oznacza atom chloru, bromu lub jodu, z tlenkiem etylenu. Reakcje prowadzi sie w roz¬ puszczalniku, takim jak eter, tetrahydrofuran, ben¬ zen lub ich mieszaniny, w temperaturze od —40°C do +70°C, zwlaszcza w temperaturze 0°C do —40°C. Korzystnie reakcje prowadzi sie, stosujac gaz ochronny, jak azot.Zwiazki wyjsciowe o wzorze 2 sa znanymi zwiazkami lub mozna je wytwarzac w znany spo¬ sób.Nowe zwiazki wykazuja wartosciowe wlasciwos¬ ci farmakologiczne, w szczególnosci posiadaja one dobre dzialanie przeciwzapaleniowe. 4-(4-bifenylilo)-buitanol-l badano pod wzgledem jego czynnosci przeciwzapaleniowej i zdolnosci znaszania go przez zywe organizmy. Substancje te badano, porównujac z fenylobutazonem na jej dzialanie przeeiwwysiejkowe wobec obrzeku spowo¬ dowanego kaolinem i karagenem na tylnych la¬ pach szczurów oraz na jej dzialanie wrzodotwór- cze i ostra toksycznosc po podawaniu doustnym szczurom doswiadczalnym. a) Obrzek kaolinowy na tylnej laptie szczura: Wyzwolenie obrzeku przeprowadzano wedlug wskazówek Hillabrechta (Arzneimittel-Forsch. 4, <507 (1954) przez podpodeszwowe wstrzykniecie 0,05 ml 10% zawiesiny kaolinu w 0,85% roztworze NaCl.Pomiar grubosci lapy szczura przeprowadzono metoda Deop£ner'a i Cerletti'ego (Int. Arch. Aller- gy Imunol. 12, 89 (1958)).Samce szczurów FW 49 o ciezarze 120—150 % otrzymaly poddawana badaniu substancje na 30 minut przed wywolaniem obrzeku, za pomoca zglebnika przelykowo-zoladkowego. Po 5 godzi¬ nach od spowodowania obrzeku otrzymane wartos¬ ci obrzmienia u zwierzat zraktowanych badana substancja porównywano z wartosciami, otrzyma¬ nymi u zwierzat kontrolnych. Przez graficzna eks¬ trapolacje procentowych wartosci zahamowania obrzeku, okreslonych z róznych dawek, oznaczono dawke, która prowadzi do 315% zmniejszenia obrze¬ ku (BD35). b) Obrzek karagenowy na tylnej lapiie szczura.Wyzwolenie obrzeku wywolanego karagenem przeprowadzano metoda Wintera i inn. (Proc. Soc. exp. Biol. Med. 111, 544 (1962), po podpodeszwo- wym wstrzyknieciu 0,05 mi 1% roztworu karage- nu w 85% roztwonze NaCl. Badana substancje wprowadzono na 60 minut przed wywolaniem obrzeku. Dla oceny dzialania hamugacego obrzek oznaczono wartosci pomiarowe, otrzymane po 3 go¬ dzinach od wywolania obrzeku. Pozostale szczegó¬ ly p®tejpówania byly analogiczne do opisanych przy obrzeku wywolanym kaolinem. c) Dzialanie wrzodotwórcze. 91 407mm Badanie na dzialanie wrzodotwórcze prowadzono na szczurach FW 49 obu plci (1:1), o ciezarze 130—150 g. Zwierzeta oftrzymaly badana substancje raz dziennie w ciagu 3 kolejnych dni, w postaci mieszaniny roztartej z tyloza, za pomoca zglebni¬ ka przelyfcowo-zoladkowego. W 4 godziny po ostat¬ nim zaaplikowaniu, zwierzeta zabito i zbadano slu¬ zówke zoladka i dwunastnicy na owrzodzenie. Ze skladu procentowego zwierzat, które po róznych dawkach wykazaly co najmniej jeden wrzód, obli¬ czono wartosc ED50 metoda Litchfield'a i Wil- coxon'a (J. Pnarmacól. exp. Therap. 96, 99 (1954). d) Óstfst tdksycznosc Ostra toksycznosc LD50 oznaczono po doustnym podawaniu samcom i samicom (1:1) szczurów FW 49 o przecietnym ciezarze 135 g. Substancje poda¬ wano roztarta w tylozie. Obliczenia LD60, o ile to bylo mozliwe, przeprowadzano wedlug Litchfield'a i WilcoKonte z procenttdlwego skladu zwierzat, któ¬ re po róznych dawkach padly w ciagu 14 dni. e) Wskaznik terapeutyczny Wskaznik terapeutyczny jak« rtfiifrrMite zakfetiu terapeutycznego oblicza sie przez iitav©raemie ilo¬ razu z wartosci ED50 oznaczonej Sl£ dzialania wrzodortiwórczega wzglednie z wartosci LD50 (do- usimie), oznaczonej na szczurach oraz wartosci EB35 oznaczonej w badaniu dzialania przeciwwy- siekowegó (test na obrzek kaolLliOwy i fefcrageno- wy).Wyniki otrzymanie w tych badaniach podane sa w tablicy 1 i 2.Nowa substancja przewyzsza znany fenylobuta- zon pod wzgledem dzialania przeciiwzapalenacKwego.Toksycznosc i czynnosc wrzddtttjwófcza nowej substancji nie zwieksza sie W takim1 stopniu, ja¬ kiego nalezaloby sie spodziewac, sadzac ze wzrostu czynnosci przeciwzapaleniowej. Uzyskano dzieki temu znacznie korzystniejsze wskazniki terapeu¬ tyczne dla nowego zwiazku, które swiadcza o jego korzystniejszym zakresie terapeutycznym od za¬ kresu znanego dla fenylobutazomu.Tablica 1 Substancja Fenylobu- tazon 4-/4-btfe- hytilMfc fcateroia Obrzek fcaaliino- wy EDjs iper os mg/hg 58 9* i Obrzek mowy EDss per os mm 69 9,B Ostra (toksycznosc na sztó^tfaitih Ld50 P&r os rng/kg 864 %ZQ granica to¬ lerancji przy 950/0 podobien- stwtie 793—942 703—974 Czynnosc wlrzodo- twóroza na szczurach ED50 per os mg/kg 102 48,3 granica tolerancji przy 950/0 :pm^do- podobien- sitwie 82—138 42,2^55,3 1 f a b 1 i c a Z Sutafctameja 1 ^mytomMizan '4-/4M&iteiyiilC/- ¦ -tefcanol-1 Czynnosc {r2e*rW- wjrfsi^fcdwfcl. mg/kg* «M 9*7 Owfcra tok- . sywmoLc LD50 m£/kg «64 830 Czynnosc Wzodo- twórcza ED|o mg/kg im 48*3 W*tófcftft& lers^ltye^if StoSuIlelk toksycznej do pnze- •ciwwysie- fcowej EDso/EDss IM 86,5 StóiatMelt t^ymmdsiei ttw6rc®Gjj do ipnzecfilw- wysiejkiciw^j ED50/ED35 [ W | 4,99 | * smlmia aryitmertyiesma iw&iiwsci ED35 ALa obrzeku kaollinawiego i wartosci 8D35 dla obrzeku karagenowego.Bla stosówdnia farmakologicznego sporzadza sie z nowego zwiazku ó wzorze 1, ewentualnie z inny¬ mi substancjami czynnymi, znane postacie prepa¬ ratów f^rmaóeUtycznyoh. Oawka jednostkowa wy- nfc&i ib—:2fot) mg, korzystnie 30—150 mg, a dawka dzienna wynosi 50—500 mg, korzystnie 7ft—3t*0 mg.Nastepujacy przyklad wyjasnia blizej wynalazek, nie ograniczajac jego zaltresu. 60 Przyklad. 4-i(4ibiLfenyllilo)Hbutanol-l.Ik roztworu zwiazku Grignarda z 16,C g (0,061 mola) bromku 2n(4-toiifenyliilo -etyiki, (temperatura topienia 3&—4t)óC) i i,5 g (0,062 gramoatómu) wiór¬ ków magnezowych w lSO ml absolutnego eteru, wkraipla sie w temperaturze okolo 0*C oziebiony roztwór z 4,0 g (t) 0&1 mola) tlenku et^ltenu w &0 ml914%1 absolutnego eteru, podczas energicznego mieszania.Miesza sie w temperaturze 0°—10°C dalej, pozosta¬ wia przez noc, ogrzewa do wrzenia mieszanine przez 30 minut pod chlodnica zwrotna i po oziebie¬ niu poddaje znanej obróbce dodajac 2n kwas solny.Przemyty do odczynu obojetnego roztwór eterowy suszy sie i zateza. Pozostalosc destyluje sie w wy¬ sokiej prózni (temperatura wrzenia: 148—149°C (0,1 mm Hg) i przekrystalizowuje z eteru nafto¬ wego. Otrzymuje sie przy tym 4^(4Hbifenylilo)-bu- tanol-1, o temperaturze topnienia: 75—76°C. Wy¬ dajnosc: (54% wydajnosci teoretycznej). PL
Claims (2)
- Zastrzezenia patentowe 1. Sposób wytwarzania nowego 4^(4^bifenylilo)- bu/tanolu-1 o wzorze 1, znamienny tym, ze zwia¬ zek Grigmarda o wzorze ogólnymi 2, w którym Hal oznacza atom chloru, bromu lub jodu, poddaje sie reakcji z tlenkiem etylenu, w obecnosci rozpusz¬ czalnika.
- 2. Sposób wedlug zaistrz. 1, znamienny tym, ze jako rozpuszczalnik stosuje sie eter etylowy, tetra- hydrofuran, dwumetoksyetan, benzeia lub miesza¬ nine tych rozpuszczalników. CH2-CHrCH2-CH2-0H WZÓR 1 CH2-CH2-Mg-Hal WZÓR 2 PL
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2151312A DE2151312C3 (de) | 1971-10-15 | 1971-10-15 | 4- (4-Biphen ylyl) -l-butanol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PL91407B1 true PL91407B1 (pl) | 1977-02-28 |
Family
ID=5822378
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL1972173621A PL91407B1 (pl) | 1971-10-15 | 1972-10-13 | |
| PL1972173619A PL91408B1 (pl) | 1971-10-15 | 1972-10-13 | |
| PL1972173620A PL91409B1 (pl) | 1971-10-15 | 1972-10-13 | |
| PL1972158243A PL83601B1 (pl) | 1971-10-15 | 1972-10-13 |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL1972173619A PL91408B1 (pl) | 1971-10-15 | 1972-10-13 | |
| PL1972173620A PL91409B1 (pl) | 1971-10-15 | 1972-10-13 | |
| PL1972158243A PL83601B1 (pl) | 1971-10-15 | 1972-10-13 |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US3801654A (pl) |
| JP (3) | JPS5320031B2 (pl) |
| AT (7) | AT315823B (pl) |
| AU (1) | AU469279B2 (pl) |
| BE (1) | BE790086A (pl) |
| BG (5) | BG20332A3 (pl) |
| CA (1) | CA993897A (pl) |
| CH (4) | CH575358A5 (pl) |
| CS (7) | CS160615B2 (pl) |
| DD (1) | DD103233A5 (pl) |
| DE (1) | DE2151312C3 (pl) |
| DK (1) | DK129573B (pl) |
| ES (5) | ES407583A1 (pl) |
| FI (1) | FI55984C (pl) |
| FR (1) | FR2157860B1 (pl) |
| GB (1) | GB1361574A (pl) |
| HU (1) | HU164696B (pl) |
| IE (1) | IE36775B1 (pl) |
| IL (1) | IL40571A (pl) |
| NL (1) | NL7213927A (pl) |
| NO (1) | NO136092C (pl) |
| PH (1) | PH13645A (pl) |
| PL (4) | PL91407B1 (pl) |
| RO (8) | RO71307A (pl) |
| SE (2) | SE399417B (pl) |
| SU (7) | SU453823A3 (pl) |
| YU (5) | YU255972A (pl) |
| ZA (1) | ZA727320B (pl) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4053639A (en) * | 1964-01-24 | 1977-10-11 | The Boots Company Limited | Therapeutically active phenylalkane derivatives |
| BE790085A (fr) * | 1971-10-15 | 1973-04-13 | Thomae Gmbh Dr K | Nouveaux 4-(4-biphenylyl)-butanols |
| DE2240440A1 (de) * | 1972-08-17 | 1974-02-28 | Thomae Gmbh Dr K | Neue (4-biphenylyl)-alkohole und verfahren zu ihrer herstellung |
| DE2240438A1 (de) * | 1972-08-17 | 1974-02-28 | Thomae Gmbh Dr K | Neue 2-(4-biphenylyl)-tetrahydrofurane und verfahren zu ihrer herstellung |
| DE2341506A1 (de) * | 1973-08-16 | 1975-02-27 | Thomae Gmbh Dr K | Neue biphenylderivate und verfahren zu ihrer herstellung |
| DE2528958A1 (de) * | 1975-06-28 | 1977-01-13 | Merck Patent Gmbh | Araliphatische dihalogenverbindungen und verfahren zu ihrer herstellung |
| DE2708520A1 (de) * | 1977-02-26 | 1978-08-31 | Thomae Gmbh Dr K | Neue arzneimittelkombinationen und verfahren zu ihrer herstellung |
| DE3001303A1 (de) * | 1980-01-16 | 1981-07-23 | Basf Ag, 6700 Ludwigshafen | Optisch aktive phenylpropan-derivate, ihre herstellung und verwendung |
| AT399471B (de) * | 1993-06-04 | 1995-05-26 | Ifw Manfred Otte Ges M B H & C | Spritzgiessform |
-
0
- BE BE790086D patent/BE790086A/xx not_active IP Right Cessation
-
1971
- 1971-10-15 DE DE2151312A patent/DE2151312C3/de not_active Expired
-
1972
- 1972-09-22 SE SE7212263A patent/SE399417B/xx unknown
- 1972-10-04 US US00294940A patent/US3801654A/en not_active Expired - Lifetime
- 1972-10-05 AT AT852372A patent/AT315823B/de not_active IP Right Cessation
- 1972-10-05 AT AT573673A patent/AT321897B/de not_active IP Right Cessation
- 1972-10-05 AT AT573773A patent/AT321900B/de not_active IP Right Cessation
- 1972-10-05 AT AT573373A patent/AT321901B/de not_active IP Right Cessation
- 1972-10-05 AT AT573473A patent/AT321899B/de not_active IP Right Cessation
- 1972-10-05 AT AT573573A patent/AT321898B/de not_active IP Right Cessation
- 1972-10-05 AT AT573873*7A patent/AT327177B/de not_active IP Right Cessation
- 1972-10-06 PH PH13983A patent/PH13645A/en unknown
- 1972-10-11 DD DD166149A patent/DD103233A5/xx unknown
- 1972-10-12 SU SU1839112A patent/SU453823A3/ru active
- 1972-10-12 SU SU1955028A patent/SU471710A3/ru active
- 1972-10-12 SU SU1955026A patent/SU464105A3/ru active
- 1972-10-12 YU YU02559/72A patent/YU255972A/xx unknown
- 1972-10-12 SU SU1957826A patent/SU474968A3/ru active
- 1972-10-12 SU SU1955030A patent/SU464106A3/ru active
- 1972-10-13 PL PL1972173621A patent/PL91407B1/pl unknown
- 1972-10-13 CS CS5231*[A patent/CS160615B2/cs unknown
- 1972-10-13 GB GB4744272A patent/GB1361574A/en not_active Expired
- 1972-10-13 BG BG023544A patent/BG20332A3/xx unknown
- 1972-10-13 CH CH1500072A patent/CH575358A5/xx not_active IP Right Cessation
- 1972-10-13 FR FR7236362A patent/FR2157860B1/fr not_active Expired
- 1972-10-13 CS CS5230*[A patent/CS160614B2/cs unknown
- 1972-10-13 ZA ZA727320A patent/ZA727320B/xx unknown
- 1972-10-13 CA CA153,847A patent/CA993897A/en not_active Expired
- 1972-10-13 ES ES407583A patent/ES407583A1/es not_active Expired
- 1972-10-13 AU AU47748/72A patent/AU469279B2/en not_active Expired
- 1972-10-13 BG BG023545A patent/BG20333A3/xx unknown
- 1972-10-13 BG BG023543A patent/BG19586A3/xx unknown
- 1972-10-13 DK DK506872AA patent/DK129573B/da not_active IP Right Cessation
- 1972-10-13 CS CS5229*[A patent/CS160613B2/cs unknown
- 1972-10-13 BG BG021617A patent/BG20560A3/xx unknown
- 1972-10-13 JP JP10314872A patent/JPS5320031B2/ja not_active Expired
- 1972-10-13 PL PL1972173619A patent/PL91408B1/pl unknown
- 1972-10-13 BG BG023546A patent/BG20777A3/xx unknown
- 1972-10-13 IE IE1394/72A patent/IE36775B1/xx unknown
- 1972-10-13 NL NL7213927A patent/NL7213927A/xx not_active Application Discontinuation
- 1972-10-13 NO NO3683/72A patent/NO136092C/no unknown
- 1972-10-13 CS CS5226*[A patent/CS160610B2/cs unknown
- 1972-10-13 FI FI2841/72A patent/FI55984C/fi active
- 1972-10-13 CH CH72676A patent/CH590185A5/xx not_active IP Right Cessation
- 1972-10-13 PL PL1972173620A patent/PL91409B1/pl unknown
- 1972-10-13 CS CS6922A patent/CS160609B2/cs unknown
- 1972-10-13 CS CS5227*[A patent/CS160611B2/cs unknown
- 1972-10-13 CS CS5228*[A patent/CS160612B2/cs unknown
- 1972-10-13 PL PL1972158243A patent/PL83601B1/pl unknown
- 1972-10-13 CH CH63676A patent/CH589575A5/xx not_active IP Right Cessation
- 1972-10-13 HU HUTO891A patent/HU164696B/hu unknown
- 1972-10-13 IL IL40571A patent/IL40571A/xx unknown
- 1972-10-15 RO RO7283160A patent/RO71307A/ro unknown
- 1972-10-15 RO RO7283157A patent/RO70060A/ro unknown
- 1972-10-15 RO RO7283156A patent/RO69378A/ro unknown
- 1972-10-15 RO RO7283159A patent/RO71306A/ro unknown
- 1972-10-15 RO RO7283155A patent/RO70567A/ro unknown
- 1972-10-15 RO RO7283154A patent/RO70059A/ro unknown
- 1972-10-16 RO RO7283153A patent/RO70058A/ro unknown
- 1972-10-16 RO RO7272524A patent/RO71244A/ro unknown
-
1973
- 1973-05-26 ES ES415243A patent/ES415243A1/es not_active Expired
- 1973-05-26 ES ES415242A patent/ES415242A1/es not_active Expired
- 1973-05-26 ES ES415244A patent/ES415244A1/es not_active Expired
- 1973-05-26 ES ES415241A patent/ES415241A1/es not_active Expired
- 1973-08-23 SU SU1955029A patent/SU496714A3/ru active
- 1973-08-23 SU SU1955347A patent/SU496713A3/ru active
-
1976
- 1976-01-26 SE SE7600800A patent/SE7600800L/xx unknown
- 1976-04-29 CH CH206977A patent/CH599082A5/xx not_active IP Right Cessation
-
1977
- 1977-09-09 JP JP10868477A patent/JPS5387342A/ja active Granted
- 1977-09-09 JP JP10868377A patent/JPS5387341A/ja active Granted
-
1979
- 1979-08-13 YU YU01971/79A patent/YU197179A/xx unknown
- 1979-08-13 YU YU01972/79A patent/YU197279A/xx unknown
- 1979-08-13 YU YU01974/79A patent/YU197479A/xx unknown
- 1979-08-13 YU YU01973/79A patent/YU197379A/xx unknown
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